INFECTIUOS DISEASESEXANTHEMATOUS FEVERS

1. Exanthem, meaning to bloom or to break out, refers to an eruption or rash that is associated with fever and implies that the eruption is infectious in origin

2. Exanthems may be caused by viruses, bacteria, Rickettsia, Mycoplasma, and fungi. Moreover, certain allergic and immune-complex diseases such as childhood arthritis can mimic infectious exanthems

3. Common in children. Clinical ranged from nonspecific viral infections to classic viralexanthems, bacterial infection or drug allergy.

4. Severity varies from self-limited viral diseases to potentially life threatening severe bacterial diseases.

5. Fever with rashInfectious: Bacterial

-Scarlet fever -Staphylococcal Scalded Skin Syndrome-Toxic shock syndrome-Meningococcemia-Leptospirosis

Classic viral exanthems-Measles-Rubella-Roseola-Infectious mononucleosis-Fifth disease

DISEASE CHARACTER OF RASHEnterovirus infection Maculopapular; generalized to most of body; discreteExanthem subitum

(roseola)Maculopapular and discrete; begins on trunk and spreads to face and usually

spares the limbs

Erythema infectiosum(fifth disease)

Red and flushed cheeks with circumoral pallor; subsequent proximal maculopapular rash on extremities (lacelike)

Slapped-cheek appearance in otherwise healthy childRubella

(German measles)Pink, maculopapular, discrete; begins on face and spreads to

trunk and extremities

MumpsMaculopapular, discrete, concentrated on trunk; may have urticaria; may be 1st

sign of illness

Infectious mononucleosis Macular or maculopapular and discrete; when associated with ampicillin administration, is confluent (morbilliform) and more intense

Rubeola (measles)

Red to brown macular rash that spreads from face and neck to trunk and extremities; confluent (morbilliform), particularly on face; begins after onset of

fever and fades after 6-7 days with temporary staining of skinKoplik spots

Scarlet feverErythematous papular eruption sometimes associated with generalized

erythema; concentrated on trunk and proximal extremities; feels similar to fine sandpaper

Kawasaki diseaseRash ranges from maculopapular to scarlatiniform to urticaria; marked erythema

of palms and soles

ENTERIC FEVER

Etiology:1. Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi), a gram-negative

bacterium. 2. A very similar but often less severe disease is caused by S. Paratyphi A and rarely by S.

Paratyphi B (Schotmulleri) and S. Paratyphi C (Hirschfeldii). 3. The ratio of disease caused by S. Typhi to that caused by S. Paratyphi is about 10 to 1.

Epidemiology:1. The age-specific incidence of typhoid may be highest in children <5 yr of age, with

comparatively higher rates of complications and hospitalization2. many strains of S. Typhi have developed plasmid-mediated multidrug resistance to all 3 of

the primary antimicrobials: ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole.

Transmission:1. Direct or indirect contact with an infected person (sick or chronic carrier) is a prerequisite

for infection. 2. Ingestion of foods or water contaminated with S. Typhi from human feces is the most

common mode of transmission, although water-borne outbreaks due to poor sanitation or contamination can occur in developing countries.

3. Oysters and other shellfish cultivated in water contaminated by sewage or the use of night soil as fertilizer may also cause infection.

Pathogenesis:1. Incubation period ranges from 4 to 14 days2. Organisms invade the body through the gut mucosa in the terminal ileum; then enter the

mesenteric lymphoid system, and then pass into the bloodstream via the lymphatics. 3. Patients who are infected with HIV and with Helicobacter pylori infection have an

increased risk for acquiring typhoid fever.Clinical features:

1. The clinical presentation varies from a mild illness to a severe clinical picture 2. Children <5 yr of age have comparatively higher rates of complications and

hospitalization. 3. Diarrhea, toxicity, and complications such as disseminated intravascular complications

are also more common in infancy, with higher case fatality rates. 4. Complications of typhoid fever seen in adults, such as relative bradycardia, neurologic

manifestations, and gastrointestinal bleeding, are rare.5. Typhoid fever usually presents with high-grade fever with a wide variety of associated

features such as generalized myalgia, abdominal pain, hepatosplenomegaly, abdominal pain, and anorexia.

6. In children, diarrhea may be present in the earlier stages of the illness and may be followed by constipation.

7. The fever may rise gradually, but the classic stepladder rise of fever is relatively rare. 8. In about 25% of cases, a macular or maculopapular rash (rose spots) may be visible

around the 7th–10th day of the illness

9. If no complications occur, the symptoms and physical findings gradually resolve within 2–4 wk; however, the illness may be associated with malnutrition in a number of affected children.

Complications:1. Clinically significant hepatitis and cholecystitis are relatively rare and may be associated

with higher rates of adverse outcome. 2. Intestinal hemorrhage (<1%) and perforation (0.5–1%) is infrequent among children. 3. Rare complications include toxic myocarditis, which may manifest by arrhythmias,

sinoatrial block, or cardiogenic shock. 4. Neurologic complications are also relatively uncommon among children and may include

delirium, psychosis, increased intracranial pressure, acute cerebellar ataxia, chorea, deafness, and Guillain-Barré syndrome.

5. Other reported complications include fatal bone marrow necrosis, disseminated intravascular coagulation (DIC), hemolytic uremic syndrome, pyelonephritis, nephrotic syndrome, meningitis, endocarditis, parotitis, orchitis, and suppurative lymphadenitis.

Diagnosis:1. blood cultures are positive in 40–60% of the patients seen early in the course of the

disease, and stool and urine cultures become positive after the 1st wk. 2. While blood leukocyte counts are low and in younger children leukocytosis is a common 3. Thrombocytopenia may be a marker of severe illness and accompany DIC. 4. The classic Widal test measures antibodies against O and H antigens of S. Typhi but lacks

sensitivity and specificity in endemic areas. Because many false-positive and false-negative results occur, diagnosis of typhoid fever by Widal test alone is prone to error.

5. A nested PCR is a promising means of making a rapid diagnosis. D.D:

1. The early stages of enteric fever may be confused with alternative conditions such as acute gastroenteritis, bronchitis, or bronchopneumonia.

2. The differential diagnosis also includes malaria; tuberculosis, brucellosis, tularemia, leptospirosis, and rickettsial diseases; and viral infections such as Dengue fever, acute hepatitis, and infectious mononucleosis.

Treatment:1. Adequate rest and hydration 2. Antipyretic therapy: acetaminophen 15 mg/kg mg every 4–6 hr PO 3. A soft, easily digestible diet 4. Thearpy with chloramphenicol or amoxicillin is associated with relapses, whereas the

quinolones and 3rd generation cephalosporins are associated with higher cure rates.

SUSCEPTIBILITY Antibiotic Daily Dose (mg/kg/day) Days

Fully sensitive Chloramphenicol 50–75 14–21

Amoxicillin 75–100 14

Multidrug resistant Fluoroquinolone or 15 5–7

cefixime 15–20 7–14

Quinolone resistant Azithromycin or 8–10 7

SUSCEPTIBILITY Antibiotic Daily Dose (mg/kg/day) Days

ceftriaxone 75 10–14

5. Relapse with all antibiotics may occur in 15% of previously treated patients.6. Although additional treatment with dexamethasone (3 mg/kg for the initial dose, followed

by 1 mg/kg every 6 hr for 48 hr) has been recommended among severely ill patients with shock.

Prognosis:1. Infants and children with underlying malnutrition and those infected with multidrug-

resistant isolates are at higher risk for adverse outcomes.2. Despite appropriate therapy, 2–4% of infected children may relapse after initial clinical

response to treatment. Prevention:

1. During outbreaks, therefore, a combination of central chlorination as well as domestic water purification is important.

2. In endemic situations, consumption of street foods, especially ice cream and cut fruit has been recognized as an important risk factor.

3. The human-to-human spread by chronic carriers is preventable by proper handwashing. 4. Vaccine:

1. An oral, live-attenuated preparation of the Ty21a strain of S. Typhi has been shown to have good efficacy (67–82%) for up to 5 years. Significant adverse effects are rare.

2. The Vi capsular polysaccharide can be used in people ≥2 yr of age. It is given as a single intramuscular dose, with a booster every 2 yr and has a protective efficacy of 70–80%.

FEVER OF UNCERTAIN ORIGIN (FUO)

1. Definition: Petersdorf and Beeson (1961):1. Fever higher than 38.3oC on several occasions recorded by health personnel 2. Duration of fever – 3 weeks as outpatient3. One week of study in hospital (as inpatient)

2. New Definition: Durack and Street in 1987 1. 3 outpatient visits, or 3 days in hospital.

3. Expanded definitions:1. Classical PUO: When temperature > 38ºC (101ºF) recorded on several occasions

occurring for more than three weeks in spite of investigations on three OPD visits or three days of stay in hospital or one week of invasive ambulatory investigations is called classic FUO

2. Nosocomial PUO: Three days of investigations including at least two days incubtion of cultures, is the minimum requirement for this diagnosis.

3. Neutropenic PUO: This diagnosis should be considered when investigation including at least two days of incubation of cultures.

4. HIV-Associated PUO: This diagnosis is considered if appropriate investigations over three days including two day of incubation of cultures reveals no source.

4. Fever without a focus:

Acute onset of fever, present for less than a week without localizing symptoms and signs and with no apparent infectious or noninfectious causes.

5. Hyperpyrexia: temperature more than 41˚C:6. Clues for FUO evaluation:

i. Age:1. <6years: respiratory, genitourinary tract infection, osteomyelitis, JRA, rarely

leukemia2. Adolescents: tuberculosis, inflammatory bowel disease, autoimmune disease,

lymphomasii. Exposure:

1. Wild or domestic animals: Zoonosis, leptospirosis2. Pica: Toxocara, Toxoplasma3. Visit to endemic area: malaria4. Eye drops: atropine fever

iii. Genetic disorder in family: Nephrogenic Diabetes Incipitus; Reiley Dey etciv. Absence of sweating:

1. Nephrogenic diabetes insipitus2. Unhydrotic ectodermal dysplasia3. Familial dysautonomia(Reily Dey)

v. Red weeping eyes: polyarteritis nodosavi. Palpebral conjunctivitis:

1. Measles2. Cocksackie3. TB4. Infectious mononucleosis

vii. Bulbar conjunctivitis:1. Kawaski2. Leptospirosis

viii. Conjunctival hemorrhage: infective endocarditisix. Uveitis:

1. Sarcoidosis2. JRA3. SLE

x. Chorioretinitis:1. CMV2. Toxoplasma

xi. Proptosis: orbital cellulitisxii. Lack of tears:

1. Familial dysautonomia(Reily Dey)2. Sjogren syndrome: ("Sicca syndrome") is an autoimmune disorder in which

immune cells attack and destroy the exocrine glands that produce tears and saliva. The hallmark symptoms of the disorder are dry mouth and dry eyes

xiii. Sinus tenderness: sinusitisxiv. Fever blisters: rules out enteric fever; staph infectionxv. Conjested pharynx:

1. Infectious mononucleosis2. Kawaski

xvi. Bone pain and tenderness: Osteomyelitis Leukemia

xvii. Referred pain over trapezium: subdiaphramatic abscessxviii. Tenderness per rectum: pelvic abscess

7. Lab:i. CBC:

1. Poly < 5000: i. no bacterial etiology

ii. enteric fever2. Poly>10000 and > bands : bacterial sepsis

ii. ESR:1. > 30 mm: infallamatory conditions2. >100 mm:

i. Autoimmuneii. TB

iii. Kawasakiiii. Blood culture: aerobic, anerobic, enteric and AFBiv. Urine culture: mid stream of suprapubic

1. Mantoux: positive primary TB; Negative in sarcoidosis2. Xray : Chest, sinus and mastoid3. Bone marrow: Leukemia and MP4. Lyumphnode: biopsy or FNAC: TB and lymphoma

8. Ultimate causes as reported in various studies:

Infections 30 - 40 %

Malignancies 20 – 25 %

Collagen Vascular Disease 10 – 20 %

Miscellaneous 15 – 20 %

Undiagnosed 10 – 15 %

9. Treatment:1. Avoid empirical trials; it obscures diagnosis of infective endocarditis , meningitis etc2. ATT if the child is critically ill and TB is suspected

10. Prognosis:1. Children with FUO has better prognosis than adults2. More often FUO is due to atypical presentation of a common illness3. In 25% cases the diagnosis remains unclear

MALARIA

1. Definition:Malaria is an acute and chronic illness characterized by paroxysms of fever, chills, sweats, fatigue, anemia and splenomegaly.

2. Etiology:Caused by intracellular parasite plasmodium protozoa; 4 species:

1. Falciparum2. Malariae3. Ovale4. Vivax

3. Transmitted by:1. Female anopheles mosquitoes2. Blood transfusion3. Contaminated needles4. Trans placental to fetus5. Organ transplant

4. Epidemiology:1. Occurs in > 100 countries2. P. Falcifarum and p.malariae are found in most places3. P. Vivax is the predominant type in india

5. Pathogenesis:1. The exoerythrocytic phase begins with inoculation of sporozoites by female anopheles

mosquitoes 2. Schizonts develop in hepatocytes and released into blood stream as merozoites (1-2

weeks).3. P.falciparum and p.malaiae have only one phase in hepatocytes.4. P.ovale and p.vivax release merozoites after 6-9 days; hepatic phase persists up to 5

years to cause relapse.5. Merozoites enter RBCs to develop into ring forms and then to trophozoites6. Trophozoites multiply and released as merozoites by rupturing RBCs.7. Some trophozoites in RBC develop into gametocytes to enter sexual cycle in mosquitos.

6. Pathologic process:1. Fever during release of merozoites from RBC 2. Anemia due to:

1. Haemolysis2. Sequestration of RBCs in spleen3. Bone marrow suppression

7. Immunopathology:1. Intracellular parasites killed by macrophages, RES (spleen); extracellular

parasites killed by antibody mediated immunity2. Immunity is not complete; does not eradicate or prevent reinfection; prevents

only severity of disease.3. Immune mediated disorders:

1. No sufficient immunity after infection and hence re infections can occur

2. Hb F resist p.falciparum; hence newborn shows resistance to malaria

3. Severe disease in pregnancy and infancy8. Resistance to malaria:

b. Hb s resists malarial infection in generalc. Lack of blood group duffy resists p.vivaxd. Hb.F and ovalocytes resist p.falciparume. Newborn is resistant due to HB.F and maternal antibodies.f. 3 m to 5 yrs: lack of immunity and develop severe diseaseg. Severe disease in pregnancy

9. Clinical features:i. Incubation:

1. P.falciparum 9-14 days2. P.vivax 12-17 days may go up to 12 months or more. 3. Hypnozoites are responsible for long incubation and late relapses in these two

species of malaria.i. P.ovale 16-18 days

ii. P.malariae 6-12 monthsii. Prodrome:

i. 2-3 daysii. Headache

iii. Fatigueiv. Anorexiav. Myalgia

vi. Mild fevervii. Pain chest and abdomen and joints

iii. Illness:i. Paroxysms of fever alternate with wellness

ii. Fever coincides with rupture of RBCs and release of merozoitesiii. Chills, swaets, headache, myalgia, nausea, vomiting, diarrhea, pallor,

and jaundice.iv. Periodicity:

1. P.vivax and ovale every 48 hrs2. P.malairae every 72 hrs3. P.falciparum less periodicity4. Mixed infections less periodicity

iv. Children:i. High fever

ii. Drowsinessiii. Lethargyiv. Cyanosisv. Hepatoslenomegaly

vi. Convulsionsvii. Hypoglycaemia

viii. Hyperkalemiaix. Acidosis x. Dehydration

v. Recrudescence: relapse of fever due to dormant parasitesa. From liver: p. Vivax and p.ovaleb. From RBC: p.malariae

vi. P.falciparum features:a. Intense parasitemia > 60% (others only 2%) due to invasion of both mature

and immature RBCs; b. High fatality

vii. P.vivale:a. Can cause death due to splenic ruptureb. Relapse from hepatic phase from 6 m to 5 yrs

viii. P.malariae:a. Low parasitemiab. Infects only mature RBCsc. Mildest form of malariad. Chronic infectione. Recrudescence even after 30 yrs

ix. P.ovale:a. Least commonb. Acute and chronicc. Can occur in conjunction with P.falciparum

10. Congenital malaria:1. Abortion2. Still birth3. Prematurity and IUGR4. Neonatal death5. Affected NB may show fever, pallor, jaundice, and hepatosplenomegaly.

11. Diagnosis of Malarial Fever:a. P.falciparum: ring forms with double chromatic dots; RBC with more than one parasitesb. Microscopy:

Thick smear:1. Make thick smear by joining the 3 drops of blood and spreading it with corner of

another slide. Correct thickness is attained when newsprint is barely legible through the smear.

2. It should be 10 mm diameter; 10 mm away from the edge of the slide; contains 10 layers of RBCs and 10 wbcs should be visible per oil immersion field of microscope.

Thin smear1. With the edge of the slide spread a new drop of blood to the surface of the first

slide. Air dry, allowing 10 minutes for the thin smear.2. It is uniformly spread over the slide. It is tongue shaped. Thin enough so that

newsprint can be read through the smear. Consists of a single layer of RBCs.3. After drying, only thin smear is fixed by dipping thin smear into methanol for 5

seconds.

Staining:1. Giemza staining:

Dry; fix thin smear with methanol and not thick smear; add 3% giemza stain; allow 30-45 mts; wash with water; dry.

2. JSB stain: After dehemoglobinisation by treating with distilled water for 10 mts, dip the thick smear in jsb ii stain two to three times. Wash it by dipping in buffer water two to three times. Then keep the thick film dipped in jsb i stain for 40-60 seconds. Wash it with buffer water. Drain, dry and examine.

13.Rapid diagnostic tests:1. Immunochromatographic tests:

Are based on the capture of the parasite antigens from the peripheral blood using specific antibodies. If the target antigen is present in the blood, a labelled antigen/antibody complex is formed and permits visualization as coloured lines.

2. Quantitative buffy coat (qbc) test: QBC test is a new method for identifying the malarial parasite in the peripheral blood. It involves staining of the centrifuged and compressed red cell layer (buffy coat) with acridine orange and its examination under uv light source.

14. Treatment: 1. Uncomplicated malaria:

Drugs Dose

Tab. ChloroquineDay 0: (first day of treatment) 10 mg/ kg of bw single doseDay 1: 10 mg/ kg of bw single doseDay 2: 5 mg/ kg of bw single dose

Primaquin Single dose of 0.25 mg/ kg body weight daily for 14 days2. Chloroquin resistant malaria:

ACT (artesunate combination treatment)

4 mg/ kg bw of artesunate daily for 3 days plus 25 mg/ kg bw of sulphadoxine + 1.25 mg/ kg bw of pyrimethamin on the first day (or)Oral quinine 10 mg/ kg bw daily for 3 days with tab doxycline (100 mg) (or)Tab. Mefloquin (25 mg/ kg bw, but total dose does not exceed 1000 mg) (and)Tab. Primaquin in single dose of 0.75 mg/ kg bw

15. Treatment of complications:1. Corticosteroids are contraindicated as they cause prolonged coma and increased mortality.2. Anemia is treated with RBC packed cells 10 ml/kg with frusemide3. Shock is treated with normal saline

16. CEREBRAL MALARIA:

1. Pathophysiology:a. Cerebral malaria is the most important complication of falciparum malaria.

b. The basic underlying defect seems to be clogging of the cerebral circulation by the parasitized red cells.

c. This results in sequestration of the parasites in deeper blood vessels. d. Obstruction to the cerebral microcirculation results in hypoxia and increased lactate

production due to anaerobic glycolysis. e. White retina is characteristic of malarial retinopathy.

2. Clinical features:i. High-grade fever and failure to eat and drink.

ii. Vomiting and cough are common. iii. Coma persists more than 30 minutes after a convulsion iv. Deep breathing due to acidosis v. Cold, clammy skin due to shock

vi. Opisthotonus posture, mimicking either tetanus or meningitis.vii. Neurological signs:

a. Symmetrical upper motor neuron and brain stem disturbances b. Diconjugate gaze, decerebrate and decorticate postures.c. Unarosable comad. Corneal reflex and 'doll's eye' movements may be absent.e. Retinal haemorrhages and exudates are rarer than in adults.f. CSF examination in cerebral malaria is usually normal; Increase in

pressure, protein level and cell-count (mostly lymphocytes, 50cells/ml) may be seen.

3. Other features: i. Severe anaemia ii. Acute renal failure

iii. Pulmonary oedema or adult respiratory distress syndrome (ards).iv. Hypoglycaemia v. Circulatory collapse, shock, hypotension

vi. Spontaneous bleeding/disseminated intravascular coagulation.vii. Jaundice

4. Treatment of Severe and complicated malaria and cerebral malaria:

Iv quinine

Quinine salt 20 mg/ kg bw on admission (iv infusion or divided im injection) followed by maintenance dose of 10 mg/ kg bw 8 hourly; infusion rate should not exceed 5 mg/ kg bw per hour.The parenteral treatment should be given for minimum of 48 hours and once the patient tolerates oral therapy, quinine 10 mg/ kg bw three times a day with doxyclycline 100 mg once a day or clindamycin in pregnant women and children under 8 years of age, shouldbe given to complete 7 days of treatment in patient treated with parenteral quinine. Or

ArtemisininDerivatives

(b) artesunate: 2.4 mg/ kg body weight iv or im given on admission, then at 12 hours and 24 hours, then once a day for 7 days; Or(c) artemether: 3.2 mg/ kg body weight im given on admission then 1.6 mg/ kg body weight per Day for 7 days;

Or(d) arteether: 150 mg daily im for 3 days in adults only (not recommended for children);Followed by full course of act to patients completed treatment with artemisinin derivatives (b, c and d).

17. BLACKWATER FEVER:

1. Black water fever (BWF) is a severe clinical syndrome and complication of falciparum malaria characterized by intra vascular haemolysis, haemoglobinuria and kidney failure.

2. Black water fever is caused by heavy parasitization of red blood cells with plasmodium falciparum. When the red blood cells burst, hemoglobin leaks into the blood plasma.

3. This free hemoglobin damages the glomerulus in the kidney, and begins to leak into the urine where it causes further damage to the tubules of the kidney.

4. Within a few days of onset there are chills, with rigor, high fever, jaundice, vomiting, rapidly progressive anemia and the passage of dark red or black urine.

5. The cause of hemolytic crises in this disease is unknown. There is rapid and massive destruction of red blood cells with the production of hemoglobinemia, hemoglobinuria, intense jaundice, anuria (passage of less than 50 milliliter of urine in a day), and finally death in the majority of cases.

6. The most probable explanation for blackwater fever is an autoimmune reaction.7. Blackwater fever is much less common today than it was before 1950. It may be that

quinine plays a role in triggering the condition, and this drug is no longer commonly used for malaria prophylaxis.

8. The treatment is antimalarial chemotherapy, intravenous fluid and sometimes supportive care such as intensive care and dialysis.

MEASLES (Rubeola)

Aetiology: • Single stranded RNA with lipid envelope; Genus: morbilivirus; Family: paramyxoviridae • Human are the only host

Epidemiology• Most infectious viruses known to man. • Rarely will an un-immunized child escape. • Responsible for approximately 6 million deaths • Responsible for more deaths than any other single agent. • Median case fatality ratio of 3.7%, range 0 to 23.9%.• Vaccine from 1963 changed the epidemiology.

Transmission & Pathology• By droplets through respiratory mucosa and rarely conjunctiva.• Infective period: 3 days before and 5 days after rashes appear.• Necrosis of respiratory epithelium• Lymphocytic infiltration• Small vessel vasculitis of skin and mucosa• giant cells (up to 26 nuclei)

• Fused cells with more than 100 nuclei called Warthin-Finkaldey giant cellsPathogenesis: 4 phases

1. Incubation: Infection of mucosaà lympadenopathy à viremeia à RES à secondary viremia à reach body surface to form exanthema

2. Prodrome: It is charecterized by mild fever, conjunctivitis, coryza, cough and photophobia. Transverse linear injection of the lower lid margins, called a Stimson line, is present before the more generalized conjunctival inflammation obscures it.

3. Enanthem: Koplick spots is the pathagnamonic sign1. Koplick spots 1-4 days before exanthem; 2. Inner cheek between premolars3. Also rarely on conjunctiva and vaginal mucosa

4. Exanthem:1. Symptoms abate as rash appears2. Rash:

1. Maculopapular2. First seen around hairline and behind ears3. Spreads downwards to trunk and limbs4. Finally confluence and fade over 7 days5. Leaves brawny desquamation of skin

3. Febrile seizures may occur in children predisposed to them. Types of measles:

1. Subclinical measles:a) Occurs in vaccinated or those who received passsive antibodies like or recipients of

blood products b) The rash may be indistinct, brief, or, rarely, entirely absent. c) Persons with inapparent or subclinical measles do not shed measles virus and do

not transmit infection to household contacts.2. Atypical Measles:

a) Atypical measles occurs in individuals who had previously received killed measles vaccines

b) They have high fever, abdominal pain, cough, vomiting, and pleuritic chest pain c) Conjunctivitis and koplik spots are rarely presentd) Rash begins in limbs with little involvement of the face and upper part of the trunk. e) Pneumonia, hilar adenopathy, and pleural effusions are common. f) Recovery from atypical measles may take 2 weeks or longer.

3. Black measles: a) Severe hemorrhagic measles, or black measles, is most common in infants in

developing countries with high mortalityb) Sudden onset of high fever accompanied by seizures or altered mental status. c) Pneumonia, a hemorrhagic exanthem and enanthem, bleeding from the mouth,

nose, and gastrointestinal tract, and probable disseminated intravascular coagulation follow

4. Modified Measles:

a) Modified measles occur in individuals who have received immune globulin after exposure to measles.

b) The clinical manifestations are milder c) The incubation period is prolonged from 14 to 20 days. d) Complications are rare

Lab tests for measles: 1. Reduction in the total white blood cell count, with lymphocytes decreased more than

neutrophils. 2. Absolute neutropenia may occur3. In measles not complicated by bacterial infection, the erythrocyte sedimentation rate

and c-reactive protein levels are normal.Diagnosis:

1. Koplick spot with typical rash gives a definitive clinical diagnosis2. Ig M antibody appears 1–2 days after the onset of the rash and remains detectable for

about 1 mo 3. A 4-fold rise in Ig G antibodies in acute and convalescent specimens taken 2–4 wk later. 4. Viral isolation from blood, urine, or respiratory secretions can be doen in viral labs 5. Molecular detection by polymerase chain reaction is possible

Differential diagnosis: 1. Rubella, 2. Scarlet fever, 3. Drug rashes 4. Serum sickness, 5. Roseola infantum, 6. Infectious mononucleosis, 7. Erythema infectiosum and 8. Echovirus and 9. Coxsackievirus infections and 10. Kawasaki syndrome

Complications:1. Mortality more in

1. <5 and > 20 yrs.2. Vit.A def. and malnutrition.3. Immune def.4. Malignancy

2. Measles precipitates Vit.A def with blinding malnutrition3. Respiratory complications:

1. Otitis media, 2. Pneumonia:

i. Interstitial pneumonia may be caused by the measles virus (giant cell pneumonia).Also known as Hecht's pneumonia; this is a deadly but fortunately rare complication of measles.

ii. Bacterial: pneumococcus, group A Streptococcus, Staphylococcus aureus, and Haemophilus influenzae type b are common

3. Laryngitis, tracheitis, and bronchitis and bronchiolitis are common and may be due to the virus alone.

4. Sinusitis and mastoiditis.5. Retropharyngeal abscess6. Measles may exacerbate underlying Mycobacterium tuberculosis infection.

There may also be a temporary loss of hypersensitivity reaction to tuberculin skin testing.

7. Bronchiolitis obliterans: rare and life-threatening form of non-reversible obstructive lung disease in which the bronchioles are plugged with granulation tissue. Causes death.

4. Gastro enteritis and dehydration5. Appendicitis due to lymphoid hyperplasia6. Febrile seizures in 3%7. Encephalitis 1 in 10008. Black measles: black measles, a rare, severe, often fatal, form of measles in which

hemorrhage into the skin lesions and mucous membranes is associated with a sudden rise in temperature, convulsions, delirium, stupor, coma, and marked respiratory distress. Called also hemorrhagic measles.

9. Myocarditis10. Prgnancy: leads to fetal death, and neonatal mortality11. Subute sclerosing pan encephalitis (SSPE)

1. Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection of immune resistant measles virus (which can be a result of a mutation of the virus itself). 1 in 100,000 people infected with measles develop SSPE.

2. Clinically: Insiduos onset, suble changes in behaviour, school failure3. Three stages:

i. Irritability; Reduced attention span; Temper outburstsii. Massive myoclonus; no loss of consciousness

iii. Disappearance of myoclonus ; Choreo athetosis; Immobility; Dystonia; Lead pipe rigidity; dementia; stupor; coma; death.

4. Diagnosis:1. Clinical; myoclonus and consciousness2. Measles antibody in CSF3. EEG : Characteristic periodic activity (Rademecker complex)4. Brain biopsy: eosinophilicinclusion bodies in the cytoplasm nuclei of neurons

and glial cells5. Treatment:

Combinations of treatment for SSPE include:a) Oral inosine pranobex (oral isoprinosine) combined with intrathecal

(injection through a lumbar puncture into the spinal fluid) or intraventricular interferon alpha.

b) Oral inosine pranobex (oral isoprinosine) combined with interferon beta.

c) Intrathecal interferon alpha combined with intravenous ribavirin.6. Prognosis: death in 3 years

Treatment of Measles:1. No antiviral drugs are effective2. Hydration, antipyretics, O23. Ventilator support for severe respiratory involvement4. Vit A 1-2 L units to prevent blinding malnutrition5. IV ribaverin tried in immune def.

Prognosis: death 1 in 1000; 15 % in immune def.Prevention:

1. Measles 9 month2. MMR in 15 months

Post exposure prophylaxis:1. Measles vaccine within 72 hrs2. IM/IV IgG within 6 days

CHICKENPOX

Varicella-Zoster Virus (VZV)ETIOLOGY.

1. VZV is a neurotropic human herpesvirus with similarities to herpes simplex virus, which is also α-herpesvirus.

2. These viruses are enveloped with double-stranded DNA genomes that encode more than 70 proteins, including proteins that are targets of cellular and humoral immunity.

EPIDEMIOLOGY. 1. It is a more serious disease with higher rates of complications and deaths among infants,

adults, and immunocompromised persons. 2. Within households, transmission of VZV to susceptible individuals occurs at a rate of 65–

86%; 3. More casual contact, such as occurs in a school class room, is associated with lower attack

rates among susceptible children. PATHOGENESIS.

1. VZV is transmitted in respiratory secretions and in the fluid of skin lesions either by airborne spread or through direct contact.

2. Primary infection (varicella) results from inoculation of the virus onto the mucosa of the upper respiratory tract and tonsillar lymphoid tissue.

3. Widespread cutaneous lesions occur during a 2nd viremic phase that lasts 3–7 days. 4. Peripheral blood mononuclear cells carry infectious virus, generating new crops of vesicles

during this period of viremia. 5. VZV is also transported back to upper respiratory mucosal sites during the late incubation

period, permitting spread to susceptible contacts before the appearance of rash. 6. In the immunocompromised child, it results in disseminated infection with resultant

complications in the lungs, liver, brain, and other organs. 7. Subsequent reactivation of latent virus causes herpes zoster, a vesicular rash that usually is

dermatomal in distribution 8. The skin lesions of varicella and herpes zoster have identical histopathology, and infectious

VZV is present in both.

9. Varicella elicits humoral and cell-mediated immunity that is highly protective against symptomatic reinfection. Suppression of cell-mediated immunity to VZV correlates with an increased risk for VZV reactivation as herpes zoster.

CLINICAL MANIFESTATIONS. 1. It has variable severity but is usually self-limited. 2. It may be associated with severe complications, including bacterial superinfection,

pneumonia, encephalitis, bleeding disorders, congenital infection, and life-threatening perinatal infection.

3. The illness usually begins 14–16 days after exposure, although the incubation period can range from 10 to 21 days.

4. Subclinical varicella is rare; almost all exposed, susceptible persons experience a rash. 5. Prodromal symptoms may be present, particularly in older children and adults. Fever,

malaise, anorexia, headache, and occasionally mild abdominal pain may occur 24–48 hr before the rash appears. Temperature elevation is usually moderate, usually from 100 to 102°F but may be as high as 106°F; fever and other systemic symptoms persist during the 1st 2–4 days after the onset of the rash.

6. Exanthem:a. Varicella lesions often appear first on the scalp, face, or trunk. b. The initial exanthem consists of intensely pruritic erythematous macules that evolve

through the papular stage to form clear, fluid-filled vesicles. c. Clouding and umbilication of the lesions begin in 24–48 hr. d. While the initial lesions are crusting, new crops form on the trunk and then the

extremities; the simultaneous presence of lesions in various stages of evolution is characteristic of varicella.

e. The distribution of the rash is predominantly central or centripetal, in contrast to smallpox, where the rash is more prominent on the face and distal extremities.

f. Ulcerative lesions involving the mucosa of oropharynx and vagina are also common; many children have vesicular lesions on the eyelids and conjunctivae, but corneal involvement and serious ocular disease is rare.

g. The average number of varicella lesions is about 300, but healthy children may have fewer than 10 to more than 1,500 lesions.

The differential diagnosis of varicella:1. includes vesicular rashes caused by other infectious agents, such as herpes simplex virus,

enterovirus, monkey pox, rickettsial pox, or S. aureus; drug reactions; contact dermatitis; and insect bites.

2. Severe varicella was the most common illness confused with smallpox before the eradication of smallpox.

Varicella in Vaccinated Individuals (“Breakthrough Varicella”). 1. Vaccine is >95% effective in preventing severe varicella and during epidemic vaccinated

children may develop breakthrough varicella. 2. The rash in breakthrough disease is frequently atypical, predominantly maculopapular,

vesicles are seen less commonly, and the illness is most commonly mild with <50 lesions and little or no fever.

3. Breakthrough cases are less contagious than wild-type infections within household settings. Progressive Varicella.

1. Progressive varicella, with visceral organ involvement, coagulopathy, severe hemorrhage, and continued vesicular lesion development, is a dreaded complication of primary VZV infection.

2. Can occur in:a. immunocompromised children, b. pregnant women, and c. newborns, d. those with malignancy, particularly if chemotherapy was e. varicella-related deaths usually occur within 3 days after the diagnosis of varicella

pneumonia. f. Continued new lesion formation for weeks or months, have been described in

children with HIV infection. Neonatal Chickenpox.

1. Newborns have particularly high mortality in the circumstances of a susceptible mother contracting varicella around the time of delivery.

2. Infants whose mothers develop varicella in the period from 5 days prior to delivery to 2 days afterward are at high risk for severe varicella.

3. The infant acquires the infection transplacentally as a result of maternal viremia, which may occur up to 48 hr prior to the maternal rash.

4. Management:a. Newborns whose mothers develop varicella 5 days before to 2 days after delivery

should receive human varicella-zoster immune globulin (VariZIG) b. Although neonatal varicella may occur in about half of these infants despite

administration of VariZIG, it is usually mild. c. Because perinatally acquired varicella may be life threatening, the infant should be

treated with acyclovir (10 mg/kg every 8 hr IV) when lesions develop. DIAGNOSIS of varicella.

1. Leukopenia is typical during the 1st 72 hr; it is followed by a relative and absolute lymphocytosis.

2. VZV can be identified quickly by direct fluorescence assay of cells from cutaneous lesions, and by PCR amplification testing.

3. Although multinucleated giant cells can be detected with nonspecific stains (Tzanck smear), they have poor sensitivity and do not differentiate VZV from herpes simplex virus infections.

4. VZV IgG antibodies can be detected by several methods and a 4-fold rise in IgG antibodies is also confirmatory of acute infection.

5. Testing for VZV IgM antibodies is not useful for clinical diagnosis because commercially available methods are unreliable and the kinetics of the IgM response are not well defined.

TREATMENT. 1. Oral therapy with acyclovir (20 mg/kg/dose, maximum 800 mg/dose) given as 4 doses/day

for 5 days should be used to treat uncomplicated varicella. 2. Any patient who has signs of disseminated VZV, including pneumonia, severe hepatitis,

thrombocytopenia, or encephalitis, should receive intravenous acyclovir (500 mg/m2 every 8 hr IV) therapy initiated within 72 hr of development of initial symptoms.

3. Treatment is continued for 7 days or until no new lesions have appeared for 48 hr. COMPLICATIONS.

1. Varicella hepatitis is relatively common but rarely clinically symptomatic. 2. Mild thrombocytopenia occurs in 1–2% of children 3. Purpura, hemorrhagic vesicles, hematuria, and gastrointestinal bleeding are rare 4. Cerebellar ataxia occurs in 1 in every 4,000 cases. 5. Other complications: Encephalitis, pneumonia, nephritis, nephrotic syndrome, hemolytic-

uremic syndrome, arthritis, myocarditis, pericarditis, pancreatitis, and orchitis.6. Bacterial Infections:

1. Secondary infections due to group A streptococci and S. aureus, may occur in up to 5% of children with varicella. These range from superficial impetigo to cellulitis, lymphadenitis, and subcutaneous abscesses.

2. Serious invasive infections caused by group A streptococcus, can have a fatal outcome. 3. Bacterial toxin-mediated diseases (toxic shock syndrome) also may complicate varicella.

7. Encephalitis and Cerebellar Ataxia. 1. Encephalitis (1/50,000 cases of varicella) and acute cerebellar ataxia (¼,000 cases of

varicella) are well-described neurologic complications of varicella; morbidity from CNS complications is highest among patients younger than 5 yr or older than 20 yr. Nuchal rigidity, altered consciousness, and seizures characterize meningoencephalitis.

2. Patients with cerebellar ataxia have a gradual onset of gait disturbance, nystagmus, and slurred speech. Neurologic symptoms usually begin 2–6 days after the onset of the rash but may occur during the incubation period or after resolution of the rash. Clinical recovery is typically rapid, occurring within 24–72 hr, and is usually complete.

8. Pneumonia. 1. Varicella pneumonia is a severe complication that accounts for most of the increased

morbidity and mortality in adults and other high-risk populations, but pneumonia may also complicate varicella in young children.

2. Smoking has been described as a risk factor for severe pneumonia complicating varicella. PROGNOSIS.

1. Primary varicella has a mortality rate of 2–3 per 100,000 cases with the lowest case fatality rates among children 1–9 yr of age (-1 death per 100,000 cases).

2. Compared with these age groups, infants have a 4 times greater risk of dying and adults have a 25 times greater high risk of dying.

3. Neuritis with herpes zoster should be managed with appropriate analgesics. Postherpetic neuralgia can be a severe problem in adults and may persist for months, requiring care by a specialist in pain management.

PREVENTION. 1. Vaccine.

1. Varicella is a vaccine-preventable disease. Live virus varicella vaccine is available as a monovalent vaccine and is also available in combination with measles, mumps, and rubella (MMRV) vaccines. Administration of varicella vaccine within 4 wk of MMR vaccine has been associated with a higher risk for breakthrough disease; therefore, it is recommended that the vaccines either be administered simultaneously at different sites or be given at least 4 wk apart.

2. Varicella vaccine is recommended for routine administration to children at 12–18 mo and at 4–6 yr of age.

3. Catch-up vaccination with the second dose is recommended for children and adolescents who received only 1 dose.

4. Varicella vaccine is contraindicated in children with cell-mediated immune deficiencies, and the vaccine may be considered for HIV-infected children with a CD4 count greater than 15%.

Postexposure Prophylaxis. 1. Vaccine given to normal children within 3–5 days after exposure (as soon as possible is

preferred) is effective in preventing or modifying varicella, especially in a household setting where exposure is very likely to result in infection.

2. High-titer anti-VZV immune globulin as postexposure prophylaxis is recommended for immunocompromised children, pregnant women, and newborns exposed to maternal varicella. The recommended dose is 1 vial (125 units) for each 10 kg increment (maximum 625 units) given intramuscularly as soon as possible but within 96 hr after exposure.

HERPES ZOSTER

1. Herpes zoster:a. Reactivation of the latent infection of VZV causes herpes zoster (shingles). b. Because it is due to the reactivation of latent VZV, is uncommon in childhood and shows

no seasonal variation in incidence. c. The lifetime risk for herpes zoster for individuals with a history of varicella is 10–15%,

with 75% of cases occurring after 45 yr of age. d. Herpes zoster is very rare in healthy children <10 yr of age except for infants who were

infected in utero or in the 1st year of life; herpes zoster in children tends to be milder than disease in adults and is less frequently associated with postherpetic neuralgia. However, herpes zoster occurs more frequently, occasionally multiple times, and may be severe in children receiving immunosuppressive therapy for malignancy or other diseases and in those who have HIV infection.

Clinical fatures: 1. Herpes zoster manifests as vesicular lesions clustered within 1 or less commonly 2 adjacent

dermatomes. 2. In the elderly, herpes zoster typically begins with burning pain, with clusters of skin lesions in

a dermatomal pattern. 3. Almost half of the elderly with herpes zoster develop complications; the most frequent

complication is postherpetic neuralgia, a painful condition that affects the nerves despite resolution of the shingles skin lesions.

4. In children, the rash is mild, with new lesions appearing for a few days; symptoms of acute neuritis are minimal; and complete resolution usually occurs within 1–2 wk.

5. In contrast to adults, postherpetic neuralgia is very unusual in children. 6. Immunocompromised children may have more severe herpes zoster, which is similar to that

in adults, including postherpetic neuralgia. Managemnt:

1. Antiviral drugs are effective for treatment of herpes zoster. In healthy adults, acyclovir (800 mg 5 times a day PO for 5 days), famciclovir (500 mg tid PO for 7 days), and valacyclovir (1,000 mg tid PO for 7 days) reduce the duration of the illness and the risk for developing postherpetic neuralgia;

2. Concomitant corticosteroid usage improves the quality of life in the elderly.3. In otherwise healthy children, herpes zoster is a less severe disease, and postherpetic

neuralgia is rare. Therefore, treatment of uncomplicated herpes zoster in the child with an antiviral agent may not always be necessary, although some experts would treat with oral acyclovir (20 mg/kg/dose, maximum 800 mg/dose) to shorten the duration of the illness. Use of corticosteroids for herpes zoster in otherwise healthy children is not recommended.

4. Patients at high risk for disseminated disease should receive acyclovir (500 mg/m2 or 10 mg/kg every 8 hr IV). Oral acyclovir, famciclovir, or valacyclovir are options for immunocompromised patients with uncomplicated herpes zoster and who are considered at low risk for visceral dissemination.

Prevention:A new VZV vaccine formulation was licensed in 2006 for use as a single immunization of individuals >60 yr of age for prevention of herpes zoster reactivation and to decrease the frequency of postherpetic neuralgia. It is not indicated for the treatment of zoster or postherpetic neuralgia

MUMPS

Etiology:• Single stranded RNA; Family Para myxoviridae; Genus Rubula virus• Human beings are the only host

Epidemiology:1. Age: 5-9 yrs; epidemic at 4 yrs ; significant reduction after vaccination2. Infectivity: 7 days before and 7 after parotid swelling appears3. Pathology4. Can involve Salivary glands; CNS; Testes; Thyroid; Ovaries; Heart; Kidneys; Liver; Joints.5. Infection à epithelium àlymphnode àviremia àtarget tissues ànecrosis with

lymphocytic infiltration à focal ischemia à healingClinical features

1. Incubation 12-25 days2. Asymptomatic in some3. Non specific symptoms in others4. Typical illness :

– Prodrome: 1- 2 days of fever; headache and vomiting; – Unilateral or bilateral (70%) swelling of parotids; tenderness; ear pain

Parotid swelling:– Angle of lower jaw obscured– Ear lobe lifted up and out– Stensen duct opening red and swollen– Sub mandibular glands can be involved– Lymphatic obstruction leads to edema over sternum

– Fever resolves in 3 days swelling in 7 daysDiagnosis

• Increase in serum amylase• Leucopenia• Relative lymphocytosis• Viral isolation

• PCR• Paired serology: rise in titre of acute and convalescent sera of IgG by

– Compliment fixation– Hemagglutination– Enzyme immuno assay and ELIZA

• Ig M by EIA demonstrates recent infectionD.D

• Parotid swelling occurs in influenza; CMV; E.B virus; HIV; staph infection(poly increased)• Sialidinitis due to calculus• Sjogren syndrome: autoimmune disorder in which immune cells attack and destroy the

exocrine glands that produce tears and saliva. The hallmark symptoms of the disorder are dry mouth and dry eyes (part of what are known as sicca symptoms).

• SLE: a chronic autoimmune connective tissue disease that can affect any part of the body.SLE is one of several diseases known as "the great imitators" because it often mimics or is mistaken for other illnesses.

• Parotid tumourComplications

1. Meningitis; Encephalitis2. Gonadal atrophy; 30% gonadal involvement; sterility if bilateral; oopheritis can mimic

appendicitis3. Nerve deafness4. Thrombocytopenia5. Transverse myelitis6. Pregnancy: fetal loss 7. Pancreatitis à diabetes8. Myocarditis9. Thyroiditis à myxaedema10. Rare: optic neuritis; nephritis

Treatment: Non specific; pain killers and restPrognosis: good rarely death due to encephalitisPrevention: MMR at 15 m and 5 yrs; contra indicated in egg and neomycin allergy, pregnancy

and HIV DIPHTHERIA

1. Definition:i. Acute toxic infection caused by corynebacterium diphtheriae

ii. Diphtheria in Greek means a piece of leatheriii. I st infection in history conquered by the principles of bacteriology, immunology and

public health.2. Etiology:

i. corynebacterium diphtheriae are aerobic, nonencapsulated, non-spore forming, non motile, pleomorphic, gram positive bacilli

ii. Mitis, intermedius and gravis, belfanti are serotypes.iii. Produce exotoxin after encoded by a bacteriophage iv. C.ulcreans less commonly produces similar disease.

3. Pathogenesis:

i. Transmission by droplets sometimes by contact with skin lesionii. Asymptomatic carriers also spread the disease

iii. Children under 15 are susceptible iv. Remain in superficial layers of respiratory mucosa and multiplyv. Induce cell necrosis by toxin

4. Psuedomembrane: i. Cell necrosis, fibrin, leukocytes, epithelial cells , RBCs and bacilli together form a dense

membraneii. Adherent to underlying tissues

iii. Bleeds on peelingiv. Usually seen on tonsil and posterior fornix.v. Nasal , laryngeal , conjunctival and cutaneous lesions possible

vi. Cervical glands enlarge to form bull neckvii. Exotoxin affects heart, kidneys and CNS

5. Clinical featuresi. Incubation 2-5 days

ii. Nasal:• Membrane in nares and upper lip

iii. Faucial:• Membrane on tonsils, fornix, palate, pharynx and uvula• Cervical nodes enlarge

iv. Laryngeal:• Membrane on larynx and can spread to trachea and bronchi• Hoarseness, stridor and croup

6. Other sites:i. Cutaneous:

• Non healing ulcers with grey brown membrane• Spreads to others• Provides immunity to host

ii. Eye:• Ulcerative conjunctivitis

iii. Vulvo vaginitis iv. Otitis externa

7. Diagnosis:i. Culture from lesions

ii. Smear to identify organismsiii. Toxigenicity to be determined ( Elek test)iv. PCR for toxin gene

8. Complications:i. Cardiomyopathy (10-24%)

• 2nd week• Tachycardia• Prolonged P-R interwal • ST-T changes• Heart blocks

• CCFii. Neuropathy

• Occurs after 2-3 weeks• Palatal palsy• Occulomotor

• Strabismus• ciliary paralysis

• Blurred vision• Loss of accommodation

• Peripheral neuritis• muscle weakness• Diaphragmatic paralysis

9. DDi. Infectious mononucleosus

ii. Vincents anginaiii. Streptococcal pharyngitisiv. herpes

10. Treatment :i. Antidiphtheritic serum after sensitivity tests

• Nasal: 10 to 20000 U IM• Faucial: 15 to 25000 U IM/IV• Laryngeal 20 to 40000 IM/IV• Severe forms: 40 to 100 000 U half IM ; half IV

ii. Drugs:• Crystalline penicillin 25 to 50 000 U /kg IV in 3 doses for 14 days• Erythromycin is an alternative

iii. Tracheostomy iv. ECG monitoringv. Nutrition and hydration

11. Prognosis :i. Mortality 30-50% reduced to 5-10% by effective management

ii. ADS within 72 hrs reduce mortalityiii. Mortality high in facial and laryngeal diphtheria

12. Prevention:i. Antibiotic prophylaxis to carries

ii. Diphtheria vaccine 5 doses before 5 yrsiii. Adult vaccine by 11-12 yrs

PERTUSIS

1. Etiology:– Bordetella pertusis: epidemic and sporadic causes– Bordetella parapertusis: sporadic cases– B.bronchiseptica: animal pathogen

2. Epidemiology:– World over 60 million cases and 500,000 deaths

– Vaccine caused >99% reduction in incidence– 1-6 yr more susceptible– More cases in older children

3. Pathogenesis– Gram negative coccobacilli – Droplet infection– Colonize only ciliated epithelium– Local epithelial damage– Pertusis toxin – mechanism unclear; inhibits immune functions of host

4. Clinical manifestations– Incubation 3-12 days– Catarrhal:

• 1-2 weeks; fever; rhinorrhea; lacrimation and conjunctival suffusion– Paroxysmal:

• 2-6 weeks• Initial dry intermittent cough • Machine – gun burst of uninterrupted cough• Loud whoop• Vomiting• Clutches a comforting adult

– convalescent stage :• 2 weeks• Symptoms regress

5. Infants:a. No stagesb. No typical cough or whoopc. After a trigger may develop signs of choking, cyanosis and apnea.d. Paroxysm may continue intermittently for a longer period

SIDS6. Immunized children and adults:

a. No distinct stages– Whoop not apparent– Uninterrupted cough– Post tussive emesis– Lasts for 3 weeks

7. Physical findingsa. Uninformative in manyb. Secondary infection may show signs of pneumoniac. Conjunctival hemorrhage and petechiae on the faced. Swollen eye lids

8. Diagnosis a. Cough with whoopb. Absence of fever and lung signsc. Lymphocytosis d. Normal CXR

e. Pharyngeal swap culture:i. Bordet Gengou medium

ii. Colonies like mercury dropletsf. PCR from throat swapsg. Serum for agglutinins

9. Treatment :a. Azithromycin 10 mg/kg od for 5 daysb. Erythromycin for > 1 m infants (causes pyloric stenosis In NB )c. Air way maintenanced. Quiet environmente. Mist inhalationf. Small frequent feeding

10. Isolation: up to 5 days of treatment11. Complications:

a. Apneab. Secondary infectionsc. Otitis mediad. CNS hemorrhagee. Herniaf. Laceration of lingual frenulum g. SIDSh. Pertusis encephalopathy

12. Prevention:a. DPT (DTwP)b. Acellular pertusis vaccine (DTaP)c. Tdap for adolescents

POLIOMYELITIS

1. Virus:1. Single stranded RNA; Family: Picarnoviridae; genus:Enterovirus2. Type 1,2,3 are antigenically different3. Humans are the only host4. PV1 is highly localized to regions in India, Pakistan, Afghanistan, and Egypt, West and

Central Africa. Wild poliovirus type 2 has probably been eradicated; it was last detected in October 1999 in Uttar Pradesh, India. Wild PV3 is found in parts of only five countries (Nigeria, Niger, Pakistan, India, and Sudan).

2. Transmission:1. Excreted from GIT and transmitted by feco oral method and disease occurs in CNS

3. Epidemiology:1. 90-95% subclinical or abortive2. 5 % non paralytic illness3. 1in 1000 paralytic polio in infants; 1 in 100 in adolescents.4. Poor sanitation and overcrowding predisposes transmission5. Infectivity: 2 weeks before and several weeks after the onset of illness.

4. Pathogenesis:

1. Enter cells with specific polio receptors in GIT epithelium à regional lymphadenopathy à pimary viremia à RES & CNS through nerve endings à spinal motor neurons à multiplyà Release by cell death

2. Vaccine virus similar course but no replication in CNS3. Vaccine virus after acquiring neurovirulance can produce similar illness (VAPP)

5. Pathology:1. Motor neurons of spinal cord invaded; poly and lymphocytic infiltration and

inflammation; edema; more neuronal loss due to inflammatory edema.2. Anterior horn cell, internuncial neurons and dorsal ganglion can be invoveld;3. Vermis of cerebellum, substantia nigra, red nucleus of pons, thalamus,

hypothalamus, pallidum and motor cortex can be involved to variable extent.6. Immunity:

1. Infants 0-4 months have transplacental Ig.G 2. Type specific immunity by natural and vaccine virus through IgG3. GIT gets IgA for surface immunity.

7. Incubation:1. 8-12 days or longer.

8. Clinical Types:1. Abortive:

Mild influenza like illness; fever, malice, head ache and anorexia.Recovery in 2-3 days.

2. Non Paralytic:1.Minor illness: as above2.Major illness:

1. Neck stiffness 2. Stiffness of muscles of trunk and limbs- spinal rigidity3. Fleeting bladder paralysis4. Constipation5. Loss of head control6. Depressed tendon reflexes7. Loss of abdominal and cremastric reflexes8. No sensory disturbances

3. Paralytic Polio: 1 in 100 cases1. Spinal2. Bulbar3. Spino bulbar4. Polio encephalitis

4. Spinal:1.Phase I: Similar to abortive polio2.Phase II:

1. Apparent recovery from phase I followed by2. Fever, head ache, muscle pain, paresthesias, muscle spasm3. Asymmetrical and spotty paralysis4. Proximal more than distal muscle groups5. Diaphragm and intercostals paralysis

6. Reduced DTR7. Bladder and bowel dysfunction8. Provocation paralysis following IM inj.9. Sensation is intact10. Recovery 6-12 months

5. Bulbar:1. May occur alone2. Nasal voice due to palatal palsy3. Pooling of saliva4. Irregular respiration5. Diminished cough reflex6. Deviation of uvula 7. Increase in BP8. Hyperpyrexia9. Cardiac arrhythmias10. Skin mottling due to vasomotor instability11. Aphonia due to vocal cord paralysis12. Weakness of hyoid muscle and rope sign by pulling hyoid backwards13. Cranial nerve palsies

6. Polio encephalitis:1. Irrritabilty2. drowsiness3. Coma4. Tremors 5. Seizures

9. Ventilatory insufficiency: due to1. Pharyngeal and laryngeal weakness2. Intercostal and diaphragmatic paralysis3. Dysfunction of respiratory centres4. Early diagnosis:

1.Anxious expression2.Working of ala nasii3.Week cough reflexes4.Paradoxical abdominal movements5. Deltoid weakness as the area is adjacent to phrenic nerve in spinal cord

10. Diagnosis:1. Fever, asymmetry and spotty paralysis without sensory involvement.2. 2 Stool specimens in 24-48 hrs apart for viral solation3. DNA sequence for wild, vaccine and non polio viruses4. CSF: early polymorphic leukocytosis; later lymphocytosis5. Paired serology for increasing titre.

11. DD:1. VAPP Vaccine associated paralytic polio)2. AFP:

1. Guillain Barre Syndrome: symmetric; ascending with sensory involvement

2.Transverse myelitis3.Traumatic paralysis

12. Treatment:1. Symptomatic2. Pain killers3. Bed rest4. No Im inj and surgery; tonsillectomy can lead to bulbar polio5. Hot tub baths6. Splinting in neutral positions7. Phsiotherapy after pain subsides8. Air way maintenance9. Tracheostomy10. Ventilatory support

13. Prevention:1. The first inactivated virus vaccine was developed in 1952 by Jonas Salk, and

announced to the world on April 12, 1955. The Salk vaccine, or inactivated poliovirus vaccine (IPV), is based on poliovirus grown in a type of monkey kidney tissue culture (Vero cellline), which is chemically inactivated with formalin. After two doses of IPV (given by injection), 90% or more of individuals develop protective antibody to all three serotypes of poliovirus, and at least 99% are immune to poliovirus following three doses.

2. Subsequently, Albert Sabin developed another live, oral polio vaccine (OPV). It was produced by the repeated passage of the virus through non-human cells at sub-physiological temperatures.Three doses of live-attenuated OPV produce protective antibody to all three poliovirus types in more than 95% of recipients.

14. Eradication:1. High infant immunization coverage with four doses of oral polio vaccine (OPV) in the first

year of life in developing and endemic countries, and routine immunization with OPV and/or IPV elsewhere.

2. Organization of “National immunization days” to provide supplementary doses of oral polio vaccine to all children less than five years of age.

3. Active surveillance for wild poliovirus through reporting and laboratory testing of all cases of acute flaccid paralysis among children less than fifteen years of age.

4. Targeted "mop-up" campaigns once wild poliovirus transmission is limited to a specific focal area.

5. Pulse Polio is an immunization campaign established by the government of India in 1994 to eradicate poliomyelitis (polio) in India by vaccinating annually all children under age five against poliovirus.

Every child receives a dose of Oral Polio Vaccine (OPV), a live, attenuated virus which colonises the gastrointestinal tract. This virus competitively inhibits the wild, disease-causing poliovirus. Not only does this prevent pernicious infection in the host, it precludes transmission of the wild poliovirus to other hosts. Since poliovirus cannot survive outside a host for more than two weeks, theoretically it would be eradicated, resulting in the eradication of poliomyelitis.

ACUTE FLACCID PARALYSIS

Definition of Acute Flaccid Paralysis 1. Flaccid paralys is one occurring over hours or few days with hypotonia, hyporeflexia, loss of

power and wasting if persists for longer period. It involves lower motor neuron complexWHO definition of AFP:

1. Flaccid paralysis of less than 4 weeks duration in children less than 15 years of age will be considered as a case of AFPAcute: rapid progression of paralysis from onset to maximum paralysis (hours to days)Flaccid: loss of muscle tone, “floppy” – as opposed to spastic or rigidParalysis: weakness, loss of voluntary movement

Differentail diagnoses of AFP 1. Anterrior horn cell:

1. Viral: poliomyelitis (1) 2. Immune mediated: acute transverse myelitis (4)

2. Nerve trunk: 1. Immune mediated: Guillain-Barre (2) 2. Toxin: Diphtheria; porphyria 3. Traumatic: IM injections (3)

3. Neuromuscular junction: 1. Tick toxin 2. Botulinum

4. Muscles: 1. Myositis

5. Metabolic: 1. Familial periodic paralysis: autosomal recessive; abnormal K levels; episodic

paralysis

AFP SURVEILLANCE:

WHO definition for polio surveillance:Flaccid paralysis of less than 4 weeks duration in children less than 15 years of age will be considered as a case of AFP and should be investigated for isolation of polio virus and confirmation of diagnosis. This is the joint responsibility of PHC/Deputy Director of HS/SMO (Surveillance MO)

Background rate 1. At least one case of AFP (excluding polio) occurs annually for every 100,000 children less

than 15 years of age. This is referred to as the “background” rate of AFP among children. 2. The non-polio causes of AFP including (but not limited to):

1. Guillian-Barré Syndrome (GBS), 2. Transverse Myelitis and 3. Traumatic Neuritis account

3. Sensitive surveillance for AFP must be able to detect a minimum of 1 case per 100,000 children less than 15 years of age.

The Purpose of AFP Surveillance

1. AFP surveillance helps to detect reliably areas where poliovirus transmission is occurring.2. AFP surveillance helps us to identify areas of priority for focusing immunisation activities. 3. It is the most reliable tool to measure the quality and impact of polio immunisation

activities. 4. It is necessary for polio free certification from WHO

AFP CASE INVESTIGATION 1. Case Notification: all health facilities, clinicians and other practitioners are required to notify

AFP cases immediately to the District Immunization Officer (DIO), by the fastest available means

2. Case Investigation: 1. All cases should be verified and investigated within 48 hours of notification2. Collect two stool samples from the child at a minimum interval of 24 hours

within 14 days; from late-reported cases for up to 60 days3. Outbreak Response Immunization: is organized in the community and performed as soon as

possible.4. Search: The investigation team searches for additional AFP cases in the community called

“hot cases”5. Stool sample: the specimens to arrive at the laboratory within 72 hours of dispatch in cold

chain6. Lab report: isolation result is reported to the surveillance program no more than 28 days

from the time the specimen by lab7. Sixty day follow-up: is done between the 60th and 90th day in certain categories of AFP cases

to determine the presence/ absence of residual paralysis8. Within 90 days of paralysis onset, all cases should undergo final classification as confirmed

polio, non- polio AFP or compatible with poliomyelitis.1. An AFP case is “confirmed” as polio only by the isolation of wild poliovirus from any

stool specimen.2. An AFP case is classified as “non-polio AFP” if wild poliovirus is not isolated from

adequate stool specimens.3. 60 day followup examination reveals persistent weakness or paralysis, or the child

has died or is lost to follow-up, the final classification of the case is one as “compatible”

4. All other cases are discarded as non polio AFPTETANUS

Definition:Tetanus is an acute, spastic paralytic illness caused by the neurotoxin of Clostridium tetaniBacteriology:

Clostridium tetani is a motile, gram positive, spore-forming, obligate anaerobe; drum stick appearance in microscopy.

Ubiquitous and found in soil, dust, alimentary tract of animals. Produce a single toxin tetanospasmin Does not invade tissues and no inflammation

Epidemiology:

1. Ubiquitous; found in 90 developing countries; causes neonatal and maternal mortality.

Causes of infection:1. Penetrating injury by dirty nail, splinter, glass piece etc.2. IM injection by drug abusers3. Contaminated surgical instruments4. Animal bites-dog, bats etc 5. Abscess including dental abscess6. Chronic middle ear infection7. Burns8. Chronic ulcers9. Compound fractures10. Frost bite11. Gangrene12. Intestinal surgery13. Ritual scarification-circumcision, female genital mutilation14. Insect bites15. Septic abortion16. Unclean delivery17. No obvious cause

Pathogenesis:Tetanus occurs after introduction of spores which germinate and multiply without tissue invasion; release toxin after cell lysis; toxin binds at the neuromuscular junction; enters motor nerves; retrograde axonal transport; enters the a-motor neuron; passes on to adjacent inhibitory interneuron; prevents the release of g-amino butyric acid (GABA)leading to sustained muscle contraction without relaxation.

Mechanism:Tetanospamin is a Zinc containing enzyme protein; it inactivates synaptobrevin that helps fusion of synaptic vesicles with terminal cell membrane

Clinical features: Incubation: 2-14 days or even more. Generalized and localized tetanus:

Features of Generalized tetanus:1. Trismus or lock jaw due to masseter spasm.2. Headache, restlessness, irritability.3. Stiffness, difficulty in chewing and swallowing4. Neck muscle spam5. Facial muscle spasm leading to risus sardonicus (Origin: L. Risus= laughter + Sardinia =

herb fr, ref. to effects of Strychnos nux-vomica) 6. Opisthotonus (body arches in such a way only heel and occiput touch the surface due to

total contraction of opposing muscles acquiring an equilibrium position.7. Laryngeal and respiratory muscle spasm leading to asphyxia8. Consciousness is intact; pain is preserved; anxious look.9. Tetanic seizures characterized by sudden severe tonic contractions of the muscles with

fists clinching, flexion, and adduction of the arms and hyperextension of legs. The spasm progresses in severity and duration. The spasms are triggered by light, sound and touch.

10. Urinary retention due to bladder sphincter spasm.11. Autonomic disturbances like tachycardia, dysarrythmias, labile hypertension, sweating

and cutaneous vasoconstriction.12. Severe progression of symptoms in the first week, stabilization in 2nd week,

amelioration in 3rd week. Neonatal Tetanus (Tetanus Neonatorum):

1. Spores contaminate umbilical stump due to unclean instrument or applicants like cow dung.

2. Manifests in 3-12 days3. Progressive difficulty in feeding4. Diminished movements, stiffness and rigitity.5. Progressive spasms6. opisthotonus

Localized tetanus:1. Results in painful spasms of muscles adjacent to the wound2. May precede generalized tetanus3. Cephalic tetanus, a rare form involves bulbar musculature due to contaminated wound

on head, nose or otitis media. It is characterized by retracted eyelids, deviated gaze, trismus, risus sardonicus, spastic tongue, and pharyngeal spasm.

Diagnosis:1. One disease in Medicine that allows confirmation by clinical features. Typical spasm with

normal sensorium.2. Leukocytosis 3. Normal CSF4. Normal EEG and EMG.5. Smear for C.tetani is usually negative.6. In 1/3 cases isolation of organism is possible.

D.D:1. Unmistaken diagnosis is possible2. Trismus is seen in pharyngeal abscess and brain stem encephalitis.3. Rabies has typical hydrophobia.4. Strychnine poisoning has spasm but no Trismus.5. Hypocalcaemia has laryngeal and carpopedal spasm but no Trismus6. Epilepsy may mimic tetanus but normal sensorium in later condition.

Treatment:1. Wound debridement and cleaning to clear tetanus bacilli and anaerobic conditions.2. Human tetanus immunoglobin 3000-6000 units as IM; infiltration around wound not

considered necessary now. Intra thecal not effective.3. Intravenous immunoglobin as an alternative if TIG is not available.4. Another alternative is tetanus antitoxin; 50,000 to 100 000 U half IM and half IV. After

sensitivity tests.5. Penicillin G100000 U/kg in 4 divided IV doses for 10-14 days.6. IV metronidazole 500 mg 8 hrly for adults.7. Erythromycin and tetracycline for allergic patients.8. Diazepam 0.1 to 0.2 mg/kg IV every 3-4 hrs later titrated to need.

9. Intra thecal baclofen in intensive care settings.10. Vecuronium and pancuronium followed by ventilation improves ultimate survival.11. Autonomic instability is treated by b-blockers and morphine.

Supportive care:1. Dark and secluded settings protected from sound, light and touch.2. Suction of secretions3. Maintenance of nutrition and hydration with electrolytes.4. Avoid infection, ulceration and constipation.

Complications:1. Aspiration pneumonia2. Intramuscular haematomas.3. Bone fractures4. Renal failure due to myoglobinuria.5. Hyperpyrexia6. Cardiac arrhythmias7. Venous thrombosis

Prognosis:1. Synapses regenerate in spinal cord and recovers slowly.2. No antibodies are formed and hence TT immunization is necessary.3. High mortality in younger age groups.4. Better prognosis in long incubation and localized tetanus.5. Cephalic tetanus has poor prognosis6. Long term sequelae include cerebral palsy, mental retardation.7. Mortality: Generalized tetanus=5to 35%; neonatal tetanus=10-75%

Prevention:1. DTP vaccination in early childhood2. Boosters every 10yrs3. Antenatal TT4. TT and TIG 250 IU in tetanus prone wounds5. Wound cleaning after injury.

CHILDHOOD (PRIMARY) TUBERCULOSIS

1. EPIDEMIOLOGY2. world

1. 95% in developing countries2. 1/3 of world population affected3. 8 % MDR TB4. HIV co epidemic

1. India1. 3.8 million cases2. 4,400 die every day3. 0.8 % among U54. MDR 3%

2. Transmission:a. airborne droplet from an adult with TB cavity and forceful cough

b. no transmission by children because:1.paucibacillary2.less cough3.less tussive force

3. Clinical types:1. Primary TB:

• Latent tuberculosis• Primary complex• Progressive primary complex• Disseminated tuberculosis• Reactivation tuberculosis

2. Secondary TB: adult type4. Difference between primary and secondary TB:

No Primary TB Adult TB1 No prior immune sensitization Very strong existing immunity2 Disease spreads to regional gland and

further disseminates to different organs

Localization of the disease to the affected organ

3 Delayed hypersensitivity develops during the course of disease hence less tissue destruction

More tissue destruction due to delayed hypersensitivity

4 Sub pleural focus develops anywhere in the lung- Ghon focus

Apical region commonly affected due to more Oxygen availability- simon focus

5 Casseation and cavitation less common

Casseation and cavitatation more pronounced

6 Lesions leal by calcification Healing by fibrosis5. Pathogenesis:

1. An adult with tuberculous cavity coughs with enough tussive force 2. Child gets the infection; portal of entry is lung;3. incubation 4-8 weeks; 4. Bacteria settle in a well ventilated sub pleural lung for eg. Rt middle or lower lobe

and this is called Ghon Focus5. bacteria multiply in alveoli 6. Neutrophils try to eliminate bacilli but are not able to eliminate the bacteria due to

resistant bacterial wall7. Monocytes enter the scene and engulf the bacteria but not able to do intra cellular

killing due to tough bacterial wall8. Monocytes form special giant cells called Langhan type of giant cells and epithelioid

cells (macrophages) 9. Lymphocytes invade the area and get sensitized; CD4 cells secrete specific

lymphokines which activate CD8 cells which lyse bacilli loaded monocytes and macrophages kill the bacteria. Delayed hypersensitivity is developed by CD4 cells and Mantoux becomes positive by the end of 4-6 weeks.

10. Delayed hypersensitivity is responsible for tissue destruction such as casseation and cavitation and also allergic reactions like phlectanular keratoconjunctivitis and erythema nodosum.

6. Clinical Types:1. Latent Tuberculosis

i. Asymptomaticii. Mx + ve

iii. CXR normaliv. No clinical signsv. 40 % develop symptomatic TB

vi. Maximum progression in first 2 yrsvii. Reactivation during adolescence

2. Primary complex: i. The basic pathology is primary focus in some part lung and lymphangitis and

regional adenitis; all three constitute primar or ghon complexii. More than 50% of infants and children with radiographically moderate to severe

PC have no physical findings and are discovered only by contact tracing. iii. Nonproductive cough and mild dyspnea are the most common symptoms.

3. Progressive PC:i. The primary focus enlarges steadily and develops a large caseous center.

Liquefaction may cause formation of a primary cavity associated with large numbers of tubercle bacilli.

ii. The enlarging focus may slough necrotic debris into the adjacent bronchus, leading to further intrapulmonary dissemination.

iii. Significant signs or symptoms are frequent in locally progressive disease in children. High fever, severe cough with sputum production, weight loss, and night sweats are common.

4. Disseminated TB:i. Tubercle bacilli are disseminated to distant sites, including liver, spleen, skin, and

lung apices, in all cases of tuberculosis infection. ii. Multiple organ involvement is common, leading to hepatomegaly, splenomegaly,

lymphadenitis in superficial or deep nodes, and papulonecrotic tuberculids appearing on the skin.

iii. Bones and joints or kidneys also may become involved. iv. Meningitis occurs only late in the course of the disease.iv. Miliary TB:

i. The most clinically significant form of disseminated tuberculosis is aemolyt disease, which occurs when massive numbers of tubercle bacilli are released into the bloodstream, causing disease in two or more organs.

ii. Miliary tuberculosis usually complicates the primary infection, occurring within 2-6 mo of the initial infection. Although this form of disease is most common in infants and young children, it is also found in adolescents and older adults, resulting from the breakdown of a previously healed primary pulmonary lesion.

v. Because this form of tuberculosis is most common in infants and malnourished or immunosuppressed patients, the host’s immune incompetency probably also plays a role in pathogenesis.

5. Reactivation Tuberculosis:i. Older children and adolescents with reactivation tuberculosis are more likely to

experience fever, anorexia, malaise, weight loss, night sweats, productive cough, hemoptysis, and chest pain than children with primary pulmonary tuberculosis

ii. Tuberculous pleural effusions, which can be local or general, originate in the discharge of bacilli into the pleural space from a subpleural pulmonary focus or caseated lymph node.

iii. Asymptomatic local pleural effusion is so frequent in primary tuberculosis that it is basically a component of the primary complex. Larger and clinically significant effusions occur months to years after the primary infection.

iv. Tuberculous pleural effusion is infrequent in children <6 yr of age and rare in children <2 yr of age

6. CVS TB:i. The most common form of cardiac tuberculosis is pericarditis. Pericarditis usually

arises from direct invasion or lymphatic drainage from subcarinal lymph nodes. 7. Time line

9. Immunity

1. Mainly Cell mediated immunity; Humeral immunity less role2. Bacilli land on well ventilated subpleural area of lung3. Neutrophils migarate first but could not fight due to resistant bacterial cell wall4. Monocytes come for second line defense engulf the bacteria but could not kill ; form

epithelioid cells- multinucelate giant cells5. Third comes T lymphocytes; CD4 get sensitized and release cytokines 6. CD4 release cytokines which activate CD8 cytotoxic cells7. CD8 lyse monocyte and release bacteria8. Activated macrophages ultimately kill the bacteria9. After sensizitization of T lymphocytes, granuloma formation occurs to prevent spread of

infection

10. TB granuloma: Cntral area of casseation surrounded my epitheloid cells, Langhan type of giant cells and lymphocytes with bacilli in caseous material.

10. External markers1. Wasting2. Lanugo hair3. Long eye lashes4. Phlectenular conjunctivitis5. Scrofuloderma 6. Sinus ulcers7. Lupus vulgares 8. Tuberculids9. Skin TB10. Scrfuloderma11. Veruka and lupus vulgares

11. TB in Prgnancy1. Prematurity2. IUGR3. Increased peri natal mortality4. Congenital TB in NB is rare

12. Investications1. Mantoux:2. Bacterial isolation and culture:

1. Gastric aspirate- 3 consecutive morning samples2. Bronchoscopy and aspirate3. Negative culture and smear do not rule out TB4. AFB staining:

Ziehl-Neelsen stain1. Heat fix2. Smear with carbol fuchsin 3. Steam – 5 mts 4. Rinse5. Add 3% acid – alcohol - 5 minutes6. Rinse7. Methylene blue-1 mt 8. Rinse9. Dry

10. Bright red purple bacilli5. Auramine-rhodamine florescent stain.

1. Requires a fluorescent microscope. 2. The fluorochrome dyes used 3. The fluorescing mycobacteria are seen as bright yellow-orange bacilli

against a dark background.6. Culture:

Lowenstein-Jensen medium:1. Egg medium

2. glycerol enhances the growth of M.tuberculosis3. also used in drug susceptibility testing 4. > 3 weeks for growth5. > 4 weeks for sensitivity6. rough, tough and buff colonies

3.CXR• Primary focus• Miliary TB• Calcified hilar adenitis etc

4.Other tests• Interferon release by T cells towards MT antigens

• Quantiferon TB c-gold• T Spot- TB

• Elispot (elliza identifies T cells specific for TB) 13. TB & HIV :

a. 30% more in HIVb. Mx – ve c. Rapid progressiond. Lymphocytosis favours viral replication-vicious cyclee. Rifampicin toxicity increased by ART

14: Treatment of Primary TB:1. Pulmonary: 2HRZ/4HR

a. INH, Rifampicin and pyrazinamide for 2 monthsb. INH, Rifampicin for next 4 months

2. MDR TB:a. Add ehtambutol and SM

3. DOTS: “Directly Observed Therapy, Short-course“a. 2 months drugs under direct observation by health workerb. Intermittent course

i. Basis for Intermittent ChemotherapyIn vitro experiments have shown that after a culture of M. tuberculosis has been exposed to certain drugs for sometimes, it takes several days (the “lag period”), before multiplication starts again

ii. Higher dosing in intermittent treatment increase peek plasma levels

4. Indications for Corticosteroids:a. TBMb. Tuberculomac. Endobronchial TBd. Pericarditise. Miliary TB

15. Prevention :BCG:

i. Live attenuated vaccine prepared from mycobacterium bovis - Bacillus Calmette – Guérin

ii. Heat and light sensitive vaccineiii. Add 1 cc NaCl to vial; 0.05 ml intradermal; left arm; no spirit for cleaningiv. Time: Within 14 days after birthv. Reaction:

a. 2 to 3 weeks - papuleb. 5 weeks - 4-8 mm in diameterc. 6-12 weeks - shallow ulcer covered with a crust. d. Healing with round scar 2-10 mm in diameter.e. Scar not a must

vi. Complications:1. BCG Abcess2. Keloid3. Adenitis4. Spread of tubercular disease

vii. Contraindications:1. symptomatic HIV2. Immunocompromised child3. Mx + ve child

viii. Prevents serious forms of TB in infancyix. 50% effective in Primary TBx. 80% protective in CNS TB

xi. No protection for adults as effect wanes after 5 years12. Also used for diagnosis as accelerated BCG reaction

16. NB & TB MotherNeonate:

• INH for 3 months• Isolation for MDR TB

Pregnancy:• Pyrazinamide teratogenic • Isoniacid, Rifampicin and ethambutol

INTERPRETATION OF TUBERCULIN TEST (MANTOUX)

1. Mantoux skin test:1. Basis: Delayed cellular hypersensitivity2. 0.1 ml intradermal of 5 TU of PPD Tween 803. Read after 48-72 hrs4. Early reaction is not positive5. Delayed reaction also is positive

2. False positive:1. Nontuberculous mycobacteria 2. Earlier BCG vaccination ( positive for Mx up to 5 yrs; usually <10 mm in size)

3. False Negative:1. Anergy

2. Infant3. Malnutrition4. Suppressed immunity5. Vaccine: Measles; MMR6. Measles infection7. Miliary TB8. Technical error

4. Mantoux reading : positive reaction:

1. Contact history ; Symptoms of PC }2. HIV }3. Immuno supression } > 5 mm4. High prevalence area >10 mm5. Low prevalence area > 15 mm6. Recent Mx conversion >10 mm7. Serial Mantoux in a patient: becomes positive

PEDIATRIC HIV

1. Etiology1. Family: Retroviridae2. Genus: Lentivirus3. HIV I: contains 2 copies of single stranded RNA4. HIV II: common among monkeys; rare in Ped.HIV difficult to identify with HIV I tests;

specific antibody test or III generation ELIZA should be used for testing2. Epdemiology:

1. Affects sexually promiscuous people2. Others:

a. Mother to child transmission to neonateb. Sex victimsc. Hospital and lab personneld. IV drug userse. Blood receipients

3. Infection 1. HIV 1: Gp 120 carries a binding site to CD4 molecule with co recptors like CC5 of T

Cell and gain entry into cell ;2. Viral RNA enters into cell cytoplasm3. Viral RNA transcribes viral DNA copies using reverse transcriptase4. DNA copies enters chromosomal DNA to form provirus5. Proviral DNA encodes production of viral RNAà viral proteins à assembly à buds

out of cell as new HIV 1 virus6. Virus attacks young CD4 cells7. Viral release by CD4 cell lysis 8. Gradual decrease in CD4 population

4. HIV transmission 1. Penetrating sex with infected partner2. Virtually vertical (MTCT) in pediatric population

3. Rarely through:1. blood products, clotting factors- 3-6%2. Homosexual contacts in adolescent boys3. Heterosexual contact in adolescent girls 4. IV drug use

4. Transmission by household contacts is nonexistent 4. Risk factors for MTCT

1. Preterm < 34 weeks2. Low CD4 count in mother3. Birt weight < 2500 gms 4. Rupture of membranes for > 4 hours5. Mother’s viral load > 1000 copies/mL 6. Vaginal delivery7. Instrumental delivery8. Caserian + ART to infant decrease transmission by 87 %

6. Mother To Child Transmission 1. Transmission rate is 12-30 %2. Intra uterine: 30-40 %3. Intrapartum: 60-70 %4. Breastfeeding:

7. Transplacental 1. PCR is positive in fetal tissue by 10 weeks of gestation2. In situ hybridization and immuno cytochemistry identify virus in fetal tissue in 1st

trimester3. Viral detection soon after birth

8. Intrapartum 1. Infected blood, cervico vaginal secretions in birth canal à conjunctiva, skin

abrasions, gastric mucosa2. Infected infant negative for viral detection in first week of life3. First born twin 3 times more infected

9. Breast feeding 1. Both virus and viral laden cells are present breast milk 2. Mother infected before pregnancy: 14 % 3. Mother infected postnatally: 29 %4. Benefit of breastfeeding outweighs the risk of HIV in developing countries5. WHO: breastfeed first 6 months and rapid weaning thereafter

10. Pathogenesis1. Virus enters via mucosal breaks2. Virus infects T helper (CD4) cells, monocytes and macrophages3. CD 4 receptors are also present in: Microglia, Astrocytes, oligodentroglia, Placent.

villus cells4. Co receptor CXCR 4 and CCR 5 are also necessary for viral attachmnt 5. Persons who lack CCR5 are highly protected from HIV 7. Lymphocyte proliferation against viral antigen produce generalized

lymphadenopathy

8. Younger the CD4 cells the more they are invaded9. HIV is peculiar that it uses CD4 cells meant for eliminating them as host cells10. CD4 cell count decreases and viraemia increases in 3-6 weeks producing flulike

illness11. Then by 2-4 months body mounts up cellular and humoral immune defense to

reduce viraemia12. Now there is a symptom free period only for a short period to be followed by

gradual reduction CD4 cells and appearance of symptom complex 11. Course of illness

1. Rapid course and death in 6-9 months- 15-25 %; in transplacental transmission and is due to underdeveloped immune system in fetus

2. Slow progression with survival up to 6 years; 60-80% ; occurs in intra partum infection

3. Long term survivors: < 5%; occurs in good immune system and attenuated virus4. CD4 < 1500 / mmᵌ is equivalent < 200 / mmᵌ in adults as infants normally have

lymphocytosis15. Clinical manifestations: Clinical categories

Category N: asymptomaticCategory A:

Any 2 of the following:1. Lymphadenoapthy2. Parotitis3. Hepatomegaly4. Splenomegaly5. Dermatitis6. Recurrent sinusitis7. Otitis

Category B1. Lymphocytic interstitial pneumonia2. Oropharngeal thrush > 2 mo3. Chronic diarrhea4. Fever > 1 mo5. Hepatitis6. Herpes simplex7. Pneumonitis8. Varicella 9. Cardiomegaly10. neuropathy

Category C1. With 2 serious bacterial infections: sepsis, meningitis, pneumonia in 2 years2. Esophageal candidasis3. Cryptococcoal infection4. Encephalopathy5. Malignancies6. Disseminated TB

7. Pneumocystis pneumonia8. Cerebral toxoplasmosis9. Severe wasting

16. Immunologic category -CD 4 counts / μL:Immunity < 12 yr 1-5 yr 6-12 yr1.No suppression >1500 >1000 >500 2.Moderate suppression 750-1500 500-1000 200-5003. Severe suppression < 750 < 500 < 200

17. Combined categorization: A1; A2; A3 etc18. Oppurtunitic infections:

1. Pneumocysti carinii pneumonia- PCP1. Most common OI in Ped. HIV ; Common in 3-6 mo of age2. It accounts for 57% of AIDS-defining conditions 3. High Mortality at 1 yr4. Fever, tacypnaea, hypoxemia5. CXR: interstitial infiltrates6. Diagnosis: staining of bronchial aspirtae for PC7. Treatment:

1. IV TMP-SMZ; IV corticosteroids; Oral maintenance for 21 days2. Pentamidine: 4 mg/kg/day, single dose IV for 21 deays

8. Prophylaxis: TMP-SMZ1. Age (Year) CD4 Count (Absolute Count/Micro-Litre)2. 1-5 <500 3. 6-12 <200

2. Non-tuberculosis mycobacterial infections: 1. Mycobacterium avium complex, M. kansasii, M. chelonei & M. fortuitum 2. Slowly progressive. High-grade fever, weight loss, abdominal pain and

anemia are common. 3. Night sweats, diarrhea, malaise, hepatomegaly, osteomyelitis, meningo

encephalitis and intra abdominal and soft tissue abscesses also occur with this infection.

4. Treatment: Clarithromycin or Azithromycin with Ethambutol and/or Rifabutin

3. Tuberculosis: 1. Most common HIV-related OI; 2. High incidence of drug-resistant tuberculosis 3. Depletion and dysfunction of CD4 cells with defects in the function of

macrophages and monocytes 4. Miliary TB, hepatosplenomegaly, lymphadenopathy, TBM, and genito-

urinary tuberculosis may occur.5. Mx is usually negative; positive if the induration is 5 mm 6. PCR test has high sensitivity and specificity. 4-drug regimen of Isoniazid,

Rifampin, Pyrazinamide and Ethambutol.7. Duration of treatment is for 6-12 months for pulmonary, 12 months for

extra-pulmonary disease.

8. ART & ATT : 1. In a patient with CD4 count less than 200, ART to be started two

weeks to two months after starting of tuberculosis therapy.2. If CD4 count is higher, ART after induction phase of tuberculosis is

complete 4. VIRAL INFECTIONS

HERPES SIMPLEX 1 & 2:1. Recurrent self-limited cluster of orolabial ulcers with severe stomatitis and

cutaneous dissemination2. Oral Acyclovir 80 mg/kg/day in 3-4 divided doses for 10 days

VARICELLA ZOSTER VIRUS (VZV):1. Persistent lesions for more than one month after onset 2. pneumonia, hepatitis and encephalitis3. IV Acyclovir 1500 mg/m2/day in 3 divided doses for 7-10 days; 4. Oral therapy 80 mg/kg/day in 4 divided

CYTOMEGALOVIRUS (CMV):1. CMV infection is an AIDS defining condition. 2. More than 90% of HIV-infected pregnant women are CMV-infected; mother

infects child pre or post natally 3. Chorioretinitis à visual loss and retinal detachment4. diarrhoea, abdominal pain5. Pneumonitis 6. Encephalitis: It manifests as sub-acute dementia complex.7. Ganciclovir 10 mg/kg/day in 2 divided doses, intra-venously, over 1-2 hours

for 14-21 days8. Life-long prophylaxis with Ganciclovir (5 mg/kg/d IV 5 days per week)

4. TOXOPLASMA GONDII INFECTION 1. Women transmits toxoplasma to the foetus2. Low-birth weight, microcephaly hydrocephalus, hepatosplenomegaly and

chorioretinitis.3. CNS: headache, fever, changes in the mental status, seizures; hemiparesis, ataxia

and cranial nerve palsies.4. Multiple ring-enhancing lesions-granulomas is seen on the mri or the ct scan of the

brain.5. The drugs used are sulfadiazine & pyrimethamine.6. Folinic acid for prevention of drug-induced suppression of the bone marrow.

5. CANDIDA INFECTIONS 1. Oral thrush and diaper dermatitis are common2. Esophageal candidiasis present with substernal or abdominal pain, dysphagia and

weight loss. 3. Disseminated infection may manifest as sepsis and shock.4. Nystatin, Amphotericin B and Azoles.5. For esophageal candidiasis, Fluconazole is the drug of choice. Amphotericin for

treating for resistant cases6. DIARRHEA

1. Diarrhoea may persist for several days leading to wasting and cachexia.2. Cryptosporidium: Paramomycin 3. Isospora: Oral TMP-SMX 4. Cyclospora: Oral TMP-SMX5. Microsporidium : Albendazole 400 mg twice a day6. Entamoeba Histolytica: Metronidazole 7. Giardia Lamblia: Metronidazole Furazolidone Tinidazole

19. Differences in pediatric and adult hivinfection:1. Progression of disease is more rapid 2. Immune system is more immature with higher CD 4 counts3. Recurrent invasive bacterial infections are more common4. Disseminated CMV, Candida, Herpes Simplex and Varicella Zoster are more common5. LIP occur almost exclusively in children6. CNS infections are common7. Peripheral neuropathy, myopathy are rare in children

20. Skin manifestations in hiv-infected children:Infectious Disorders and Lesions Non-Infectious Disorders and Lesions

Viral Infections:Herpes simplex, Herpes zoster,Molluscum contagiosum, Warts

Atopic dermatitis; Seborrheic dermatitis, Generalized dermatitis, NutritionalDeficiency

Fungal Infections:Candida, Tinea, Onchomycosis

Eczema, Psoriasis, Drug eruptions

Bacterial:Impetigo Vasculitis

Other: Scabies Alopecia

21. Hematological abnormalities:

Abnormality Mechanism

Anemia Auto-immune; Suppression of the bone marrow by drugs Nutritional deficiency (folic acid, Vitamin B12, micronutrients)

Thrombocytopenia Immune-mediated, Nutritional deficiency (Vitamin B12 deficiency)

Neutropenia Immune-mediated destruction

Lymphopenia Bone marrow suppression due to altered cytokine production, CD4+ apoptosis induced by HIV replication

Eosinophilia Shifting of immune response from Th1 to Th2 cytokine profile

22. Other manifestations:1. Cardiac: Myopathy 2. CNS: HIV Encephalopathy; peripheral neuropathy3. Nephropathy: due to virus, immune complex mediated vasculitis, or opportunistic

infections

4. Respiratory: Lymphoid Interstitial Pneumonitis (LIP)1. Cough and Tachypnea 2. Diffuse bilateral reticulondular or interstitial infiltrates on chest

radiograph5. Malignancy:

1. Non-Hodgkin’s lymphoma, leiomyomas and leiomyosarcomas and leukemia

2. Kaposi’s sarcoma is rare23. Diagnosis

1. Viral Culture: 100% specific; costly and needs sophisticated laboratory set up2. Polymerase Chain Reaction (PCR) RNA/DNA:

1. Two PCRs have to be positive, done beyond one month and at least one of them after age of 3 months.

2. Detect nearly 100% of infected newborns3. Enzyme Linked Immunosorbent Assay (ELISA)

1. I Generation ELISA: antigen from crude viral lysate 2. II generation: part of virus3. III Generation ELISA: synthetic peptides as the antigen4. Rapid tests

ELIZA1. Current kids are 100% sensitive and specific.2. Detection of anti-HIV antibodies in patient’s sera. 3. The ELISA is performed by the use of purified antigen, bound to a plate containing small

wells.4. The latest ELISA is the Rapid Test with results in 10 mts5. Eliza test should be confirmed by Western Blot or repeated Eliza with different antigens

ELIZA : method1. HIV antigens pre-coated onto an ELISA plate2. HIV antibodies of patient will bind to the HIV antigens on the plate. 3. Anti-human immunoglobulin is coupled to an enzyme is now added which binds to

human HIV antibodies4. Chromogen or substrate is then added which changes color when cleaved by the enzyme

attached to the second antibodyWestern Blot Analysis (WBA)

1. Plasma electrophoresis on a strip pre-impregnated with various HIV antigens (i.e. p24, p28, gp41, gp120, gp160,).

2. show bands of all these antibodies depending on their presence in the samples3. In India, it is not mandatory to do WBA

24. Management Care immediately after birth1. Cord clamped soon; no milking; 2. Early baby bathing3. Single dose NVP to mother during labour and to the baby within 72 hours after birth.4. Exclusive replacement feeding is afass — acceptable, feasible, affordable, sustainable

and safe5. Quick weaning at 6 mo

6. CTX prophylaxis from age of 4–6 weeks; 5 mg/kg/day 7. Growth monitoring8. Screen for infections

25. When to start ART in children, guided by CD4 1. < 11 month infants : if CD4 < 1500 cells/mm3 2. 12–35 months : if CD4 < 750 cells/mm3 3. 36–59 months : if CD4 <350 cells/mm3 4. > 5 years old : < 350 cells/mm3 especially if symptomatic; or 5. Before CD4 drops below 200 cells/mm3.

26. ARV regimens 1. Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine NVP 2. Stavudine (D4T) + Lamivudine (3TC) + Nevirapine (NVP)3. Vaccine:

1. if the HIV-infected child is asymptomatic or mildly symptomatic – vaccinations should be given.

2. Withold vaccine (live vaccines) for HIV-infected children who are symptomatic and severely immuno-compromised.

27. Prevention 1. Transmission from the mother to child is likely to be about 15-45%.2. There is 16.2% greater risk of mother-to-infant transmission of HIV when children are

breast-fed as opposed to formula-fed. 3. Single dose NVP 200mg given at the onset of labour and 4. single dose of syrup NVP 2mg/kg weight to the baby within 72 hours decreases risk of

transmission by 13.1% (breast feeding)..5. Transmission of the HIV virus occurs most commonly during the first few months after

birth6. Avoid manipulations like amniocentesis and external cephalic version increase the risk

of transmission of HIV.7. Long duration of rupture of membranes increase the transmission risk. It has been

estimated that with every hour, the risk of transmission increases by 2%. 8. Placental disruption and infections also adversely affect transmission. 9. Invasive fetal monitoring should be avoided, as should all invasive obstetric procedures.10. Where facilities are available, elective LSCS should be offered. 11. If instrumental delivery is necessary, then forceps are a better option than vacuum

suction cup delivery. 12. Emergency LSCS is associated with high transmission13. In India – normal delivery is recommended unless the woman has obstetric reasons 14. When replacement feeding (infant formula) is acceptable, feasible, affordable,

sustainable and clean water is available, HIV-infected mothers should avoid breastfeeding completely.

15. Otherwise, exclusive breastfeeding is recommended during the first months of life, with early abrupt weaning at 3-4 months or 6 months of age

HIV – AIDS DEFINING PULMONARY INFECTIONS:

1. The Centers for Disease Control and Prevention (CDC) defines an HIV+ person with a CD4 cell count of 200 or less as having AIDS. The CDC has also developed a list of more than 20 opportunistic infections (OIs) that are considered AIDS-defining conditions (see below). If a child with HIV has one or more of these OIs, it gives the diagnosis of AIDS.

2. Aids defining pulmonary infections are:1. Candidiasis of bronchi, trachea, or lungs2. Mycobacterium avium complex or M. Kansasii, disseminated or extrapulmonary 3. Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium,

other species or unidentified species, disseminated or extrapulmonary 4. Pneumocystis carinii pneumonia 5. Pneumonia, recurrent 6. Histoplasmosis, disseminated or extrapulmonary

GUILLAIN-BARRE’ SYNDROME

1. It is a postinfectious polyneuropathy involving mainly motor and sometimes sensory and autonomic nerves.

2. Progressive symmetric ascending muscle paralysisPathophysiology

1. Resemblance of the pathogens to antigens on peripheral nerves (molecular mimicry) leads to an overzealous autoimmune response mounted by T-lymphocytes and macrophages

2. Autoimmune process leads to:1. Demyelination2. Axonal degenerataion

Etiological agents1. Symptoms start about 10 days after a nonspecific viral infection. 2. Usual infections are:

1. GIT: camphylobacter jejuni, Helicobacter, 2. R.S: Mycoplasma pneumonia 3. Vaccines: Rabies, influenza, oral polio and meningococcal and H1N1 vaccines.

Clinical 1. Paralysis starts from lower limbs and progress upward to involve respiratory and bulbar

muscles (Landry ascending paralysis) 2. Weakness is symmetrical and progress over days to weeks 3. Muscle pain is common in early phase4. Paresthesia 5. Flaccid quadriplegia occurs in severe cases 6. Dysphagia and facial weakness indicate impending respiratory failure 7. Bulbar involvement occurs in 50% of cases 8. Aspiration is a risk leading to pneumonias 9. Papilledema can occur in some children 10. Urinary incontinence or retention of urine is a complication in about 20% of cases but is usually transient.11. Extraoccular muscles involvement is rare but more common in a variant of this syndrome

called Miller-Fischer syndrome: External optholmoplegia

Ataxia Areflexia

Signs: 1. Absent tendon reflexes 2. ANS: labile BP, bradycardia, hypotension

Congenital Guillain-Barre’ Syndrome has been reported Laboratory Findings and Diagnosis

CSF:1. The CSF protein is elevated to more than twice the upper limit of normal, 2. glucose level is normal, and3. There is no pleocytosis. Fewer than 10 white blood cells/mm3 are found. 4. The results of bacterial cultures are negative, and viral cultures rarely isolate specific

viruses. 5. The dissociation between high CSF protein and a lack of cellular response is diagnostic of

Guillain-Barré syndrome. ENMG

1. Motor nerve conduction velocities are greatly reduced, and sensory nerve conduction time is often slow.

2. An electromyogram shows evidence of acute denervation of muscle. Serology

1. Serum creatine phosphokinase (CK) level may be mildly elevated or normal. 2. Antiganglioside antibodies, mainly against GM1 and GD1, are sometimes

Muscle biopsy1. Muscle biopsy is not usually required for diagnosis; specimens appear normal in early

stages and show evidence of denervation atrophy in chronic stages. Nerve biopsy

Sural nerve biopsy tissue shows segmental demyelination, focal inflammation, and wallerian degeneration; usually not required for diagnosis

Evidence for infection1. Serologic testing for Campylobacter infection helps establish the cause if results are

positive but does not alter the course of treatment. 2. Antibodies for Helicobacter, Mycoplasma etc can be demonstrated

Treatment of GBS 1. Hospitalization 2. IV gamma globulin 400 mg/kg/day for 5 days 3. Interferon is also effective in combination with IVIG 4. Plasma exchange transfusion helps in removing antigen autoantibody complexes 5. Steroids tried but less effective- high dose methyl prednisolone IV 6. Gabapentin or carbamzepine for neuropathic pain 7. No need for antibiotics

Prognosis 1. The clinical course is usually benign, and spontaneous recovery begins within 2-3 wk.2. Improvement usually follows a gradient inverse to the direction of involvement, with

recovery of bulbar function first and lowers extremity weakness resolving last.

3. Bulbar and respiratory muscle involvement may lead to death if the syndrome is not recognized and treated.

4. three clinical features are predictive of poor outcome with sequelae: 1. Cranial nerve involvement, intubation, and maximum disability at the time of

presentation.

DENGUE FEVER AND DENGUE HEMORRHAGIC FEVER

ETIOLOGY:1. There are at least 4 distinct antigenic types of dengue virus, members of the family

Flaviviridae. EPIDEMIOLOGY:

1. Dengue viruses are transmitted by mosquitoes of the Stegomyia family. Aedes aegypti, a daytime biting mosquito is the principal vector and is highly urbanized, breeding in water stored for drinking or bathing and in rainwater collected in any container.

PATHOGENESIS:1. It is usually associated with 2nd infections with dengue types 1–4. 2. Circulation of infection-enhancing antibodies at the time of infection is the strongest risk

factor for development of severe disease. 3. Mild degree of disseminated intravascular coagulation, liver damage, and

thrombocytopenia may operate synergistically. 4. Capillary damage allows fluid, electrolytes, small proteins, and, in some instances, red cells

to leak into extravascular spaces. 5. This results in hemoconcentration, hypovolemia, increased cardiac work, tissue hypoxia,

metabolic acidosis, and hyponatremia.6. Minimal to moderate hemorrhages are seen in the upper gastrointestinal tract, and

petechial hemorrhages are common in the interventricular septum of the heart, on the pericardium, and on the subserosal surfaces of major viscera. Focal hemorrhages are occasionally seen in the lungs, liver, adrenals, and subarachnoid space.

7. The liver is usually enlarged, often with fatty changes. Yellow, watery, and at times blood-tinged effusions are present in serous cavities in about 3/4 of patients.

CLINICAL MANIFESTATIONS:1. The incubation period is 1–7 days. The clinical manifestations are variable and are influenced

by the age of the patient. 2. In infants and young children, the disease may be undifferentiated or characterized by fever

for 1–5 days, pharyngeal inflammation, rhinitis, and mild cough. A majority of infected older children and adults experience sudden onset of fever, with temperature rapidly increasing to 39.4–41.1°C , usually accompanied by frontal or retro-orbital pain, particularly when pressure is applied to the eyes.

3. Occasionally, severe back pain precedes the fever (back-break fever). 4. A transient, macular, generalized rash that blanches under pressure may be seen during the

1st 24–48 hr of fever. 5. The pulse rate may be slow relative to the degree of fever. 6. Myalgia and arthralgia occur soon after the onset and increase in severity. 7. From the 2nd to 6th days of fever, nausea and vomiting and pronounced anorexia may

develop.

8. About 1–2 days after defervescence, a generalized, morbilliform, maculopapular rash appears that spares the palms and soles. It disappears in 1–5 days; desquamation may occur. Rarely there is edema of the palms and soles.

9. About the time this 2nd rash appears, the body temperature, which has previously decreased to normal, may become slightly elevated and demonstrate the characteristic biphasic temperature pattern.

Dengue Hemorrhagic Fever:1. Differentiation between dengue fever and dengue hemorrhagic fever is difficult early in the

course of illness. A relatively mild 1st phase is followed after 2–5 days by rapid clinical deterioration and collapse. In this 2nd phase, the patient usually has cold, clammy extremities, a warm trunk, flushed face, diaphoresis, restlessness, irritability, and mid-epigastric pain.

2. Frequently, there are scattered petechiae on the forehead and extremities; spontaneous ecchymoses are common.

3. Approximately 20–30% of cases of dengue hemorrhagic fever are complicated by dengue shock syndrome.

4. After a 24–36 hr period of crisis, convalescence is fairly rapid in the children who recover. The temperature may return to normal before or during the stage of shock. Bradycardia and ventricular extrasystoles are common during convalescence.

DIAGNOSIS:1. The World Health Organization criteria for dengue hemorrhagic fever are:

a. Fever,b. Minor or major hemorrhagic manifestations, c. Thrombocytopenia (≤100,000/mm3), and d. Objective evidence of increased capillary permeability (hematocrit increased by

≥20%), serosal effusion (by chest radiography or ultrasonography), or hypoalbuminemia.

e. Dengue shock syndrome criteria include those for dengue hemorrhagic fever as well as hypotension or narrow pulse pressure (≤20 mm hg).

2. The tourniquet test result may be positive. The test is performed by inflating a blood pressure cuff halfway between the systolic and diastolic blood pressures for approximately 5 minutes. After release, the number of petechiae in a 2.5 x 2.5 cm patch is counted. Greater than 20 petechiae indicate a positive test.

3. Virologic diagnosis can be established by serologic tests or by isolation of the virus from blood leukocytes or serum.

4. In both primary and secondary dengue infections, there is a relatively transient appearance of antidengue immunoglobulin M (IgM) antibodies. These disappear after 6–12 wk, which can be used to time a dengue infection.

5. In 2nd primary dengue infections, most antibodies are of the IgG class. 6. Serologic diagnosis depends on a 4-fold or greater increase in IgG antibody titer in paired

sera by hemagglutination inhibition, complement fixation, enzyme immunoassay, or neutralization test.

7. Viral RNA can be detected in blood or tissues by specific complementary RNA probes or amplified first by the polymerase chain reaction (PCR) or by real-time PCR.

Other tests:

1. Other abnormalities include moderate elevations of the serum transaminase levels, consumption of complement, mild metabolic acidosis with hyponatremia, occasionally hypochloremia, slight elevation of serum urea nitrogen, and hypoalbuminemia.

2. Roentgenograms of the chest reveal pleural effusions (left > right) in nearly all patients with dengue shock syndrome.

DIFFERENTIAL DIAGNOSIS:1. The differential diagnosis of dengue fever includes viral respiratory and influenza-like

diseases, the early stages of malaria, mild yellow fever, scrub typhus, viral hepatitis, meningococcemia and leptospirosis.

TREATMENT:1. Uncomplicated dengue fever:

a. It is mainly supportive. Bed rest is advised during the febrile period. Antipyretics should be used to keep body temperature <40°C (104°F). Analgesics or mild sedation may be required to control pain.

b. Aspirin is contraindicated and should not be used because of its effects on hemostasis.

c. Fluid and electrolyte replacement is required for deficits caused by sweating, fasting, thirsting, vomiting, and diarrhea.

2. Dengue Hemorrhagic Fever: a. Patients who are cyanotic or have labored breathing should be given oxygen. b. Rapid intravenous replacement of fluids and electrolytes can frequently sustain

patients until spontaneous recovery occurs. Normal saline is more effective in treating shock than the more expensive Ringer lactated saline. When pulse pressure is ≤10 mm Hg, or when elevation of the hematocrit persists after replacement of fluids, plasma or colloid preparations are indicated.

c. Care must be taken to avoid overhydration, which may contribute to cardiac failure.d. Transfusions of fresh blood or platelets suspended in plasma may be required to

control bleeding; e. Disseminated intravascular coagulation may require treatment. f. Corticosteroids do not shorten the duration of disease or improve prognosis in

children receiving careful supportive therapy.g. Hypervolemia during the fluid reabsorptive phase may be life threatening and is

heralded by a decrease in hematocrit with wide pulse pressure. Diuretics and digitalization may be necessary.

COMPLICATIONS:1. Fluid and electrolyte losses, hyperpyrexia, and febrile convulsions are the most frequent

complications in infants and young children. 2. Epistaxis, petechiae, and purpuric lesions are uncommon but may occur at any stage. 3. Infrequently, after the febrile stage, prolonged asthenia, mental depression, bradycardia,

and ventricular extrasystoles may occur in children.PROGNOSIS:

1. Death has occurred in 40–50% of patients with shock, but with adequate intensive care deaths should occur in <1% of cases.

PREVENTION:

1. Prophylaxis consists of avoiding mosquito bites by use of insecticides, repellents, body covering with clothing, screening of houses, and destruction of A. aegypti breeding sites.

2. The possibility exists that dengue vaccination may sensitize a recipient so that ensuing dengue infection could result in hemorrhagic fever.

TOXIC SHOCK SYNDROME

TSS is an acute multisystem disease characterized by high fever, hypotension, vomiting, diarrhea, myalgias, nonfocal neurologic abnormalities, conjunctival hyperemia, strawberry tongue, and an erythematous rash with subsequent desquamation on the hands and feet.ETIOLOGY:

TSS is caused by TSST-1-producing strains of S. aureus, which may colonize the vagina or cause focal sites of staphylococcal infection.

EPIDEMIOLOGY:1. Menstrual TSS:

a. Many cases occur in menstruating women who is 15–25 yr of age and who use tampons or other vaginal devices (diaphragm, contraceptive sponge).

2. Nonmenstrual TSS:a. S. aureus infection of nasal packing b. Wound infections, sinusitis, tracheitis, pneumonia, empyema, abscesses, burns,

osteomyelitis, and primary bacteremia. 3. During mass vaccination with multi dose measles vaccine; Staph.aureus contamination is

possible due to lack of specific preservative and TSS has been reported in India as a complication of measles vaccine

PATHOGENESIS:S. aureus strains produce a number of extracellular toxins, which causes massive loss of fluid from the intravascular space directly or after production of interleukin 1 and tumor necrosis factor CLINICAL MANIFESTATIONS:

1. The diagnosis of TSS is based on clinical manifestations. The onset is abrupt, with high fever, vomiting, and diarrhea, and is accompanied by sore throat, headache, and myalgias.

2. A diffuse erythematous macular rash (sunburn-like or scarlatiniform) appears within 24 hr and may be associated with hyperemia of pharyngeal, conjunctival, and vaginal mucous membranes.

3. A strawberry tongue is common. 4. Symptoms often include alterations in the level of consciousness, oliguria, and hypotension,

which in severe cases may progress to shock and disseminated intravascular coagulation. 5. Complications, including acute respiratory distress syndrome, myocardial dysfunction, and

renal failure, are commensurate with the degree of shock. 6. Recovery occurs within 7–10 days and is associated with desquamation, particularly of palms

and soles; hair and nail loss have also been observed after 1–2 mo. DIAGNOSIS:

1. There is no specific laboratory test; appropriate selective tests for hepatic, renal, muscular, gastrointestinal, cardiopulmonary, and central nervous systems involvement.

2. Bacterial cultures of the associated focus (vagina, abscess) before administration of antibiotics

Differential Diagnosis:1. Group A streptococcus can cause a similar TSS-like illness from focal streptococcal infection

such as cellulitis or pneumonia.2. Kawasaki disease closely resembles TSS clinically but is usually not as severe or rapidly

progressive. Kawasaki disease typically occurs in children younger than 5 yr. 3. Scarlet fever, Rocky Mountain spotted fever, leptospirosis, toxic epidermal necrolysis, sepsis,

and measles must also be considered in the differential diagnosis.TREATMENT:

1. Parenteral administration of a β-lactamase-resistant antistaphylococcal antibiotic (nafcillin or a 1st generation cephalosporin) or

2. Vancomycin or3. Clindamycin 4. Removal of any retained tampons 5. Drainage of focally infected sites 6. Fluid replacement 7. Inotropic agents 8. Corticosteroids and intravenous immunoglobulin may be helpful in severe cases.

PREVENTION:1. Using tampons intermittently during each menstrual period. 2. Discard measles vaccine on the same day of vaccine session

H1N1 INFLUENZA (SWINE FLU)

INTRODUCTION1. Influenza A viruses have a complex epidemiology involving avian and mammalian hosts that

serve as reservoirs with the potential for infecting the human population. 2. The segmented nature of the influenza genome allows reassortment to occur between an

animal virus and a human virus when co-infection occurs. 3. Minor changes within a serotype are termed antigenic drift; major changes in serotype are

termed antigenic shift. TRANSMISSION

1. Human-to-human transmission of swine flu can also occur. 2. Disease spreads very quickly among the population especially in crowded places.3. Cold and dry weather enables the virus to survive and epidemics appear in winter.4. People may become infected by touching/handling something contaminated with flu viruses

on it and then touching their mouth or nose. SYMPTOMS

1. fever, lethargy, lack of appetite and cough. 2. runny nose, sore throat, nausea, vomiting and diarrhoea.

DIAGNOSIS OF SWINE FLU1. Preferred respiratory samples : nasopharyngeal swab and throat swab2. Available Laboratory tests:

a. Rapid Antigen Tests: not as sensitive as other available tests.b. RT-PCRc. Virus isolationd. Virus Genome Sequencing

e. Four-fold rise in swine influenza A (H1N1) virus specific neutralizing antibodies.3. Infectious period: The infectious period for a confirmed case of swine influenza A (H1N1)

virus infection is defined as 1 day prior to the onset of illness to 7 days after onset4. ANTIVIRAL TREATMENT

a. Oseltamivir is the recommended drug both for prophylaxis and treatment.b. Supportive therapy includes:

1. IV Fluids.2. Parentral nutrition.3. Oxygen therapy 4. Antibiotics for secondary infection.5. Vasopressors for shock.6. Paracetamol or ibuprofen is prescribed for fever, myalgia and headache. 7. Patient is advised to drink plenty of fluids.8. Smokers should avoid smoking. 9. Salicylate / aspirin is strictly contra-indicated

5. ANTIVIRAL CHEMOPROPHYLAXISa. Prophylaxis: Oseltamivir is given to all close contacts of suspected and health care

personnel coming in contact with suspected, probable or confirmed casesb. Prophylaxis should be provided till 10 days after last exposure (maximum period of

6 weeks) infants 20 mg OD older children 30-40 mg OD6. Close Contacts of suspected, probable and confirmed cases should be advised to remain at

home (voluntary home quarantine) for at least 7 days after the last contact with the case. 7. Adult patients should be discharged 7 days after symptoms have subsided.8. Children should be discharged 14 days after symptoms have subsided.

AVIAN INFLUENZA (BIRD FLU)

Introduction:Highly pathogenic avian influenza A(H5N1) virus has increased the risk of human exposure to the virus since 2003; The largest number of cases has occurred in Vietnam, particularly during the third, ongoing wave, and the first human death was recently reported in Indonesia.

Transmission:For human influenza A (H5N1) infections, evidence is consistent with bird-to-human and limited, nonsustained human-to-human transmission to date.

Incubation: most cases occurred within two to four days after exposure; recent reports indicate similar intervals but with ranges of up to eight days.

Initial Symptomsa. Most patients have initial symptoms of high fever and an influenza-like illness with lower

respiratory tract symptoms.b. Diarrhea, vomiting, abdominal pain, pleuritic pain, and bleeding from the nose and

gums have also been reported early in the course of illness in some patients. Clinical Course

a. Respiratory distress, tachypnea, and inspiratory crackles are common. b. Sputum production is variable and sometimes bloody.

c. Almost all patients have clinically apparent pneumonia; Radiology:

a. Radiographic changes include diffuse, multifocal, or patchy infiltrates; interstitial infiltrates; and segmental or lobular consolidation with air bronchograms.

b. Pleural effusions are uncommon. Micrbiology:

a. Limited microbiologic data indicate that this process is a primary viral pneumonia, usually without bacterial suprainfection at the time of hospitalization.

Progression:b. Progression to respiratory failure has been associated acute respiratory distress

syndrome (ARDS). c. Multiorgan failure with signs of renal dysfunction and sometimes cardiac compromise,

including cardiac dilatation and supraventricular tachyarrhythmias, has been common.d. Other complications have included pulmonary hemorrhage, pneumothorax,

pancytopenia, Reye's syndrome, and sepsis syndrome without documented bacteremiaCase Fatality:

The case fatality rate was 89 percent among those younger than 15 years of age in Thailand. Laboratory Findings

a. Common laboratory findings have been leukopenia, particularly lymphopenia; mild-to-moderate thrombocytopenia; and slightly or moderately elevated aminotransferase levels.

Virologic Diagnosisa. Viral isolationb. The detection of H5-specific RNA c. Commercial rapid antigen tests are less sensitive

Managementa. Ventilatory support b. Intensive care for multiorgan failure and sometimes hypotension. c. Empirical treatment with broad-spectrum antibiotics, antiviral agents, alone or with

corticosteroids, d. Isolation for clinical monitoring, appropriate diagnostic testing, and antiviral therapy.

Antiviral Agentsa. Patients with suspected influenza A (H5N1) should promptly receive a neuraminidase

inhibitor pending the results of diagnostic laboratory testing. b. These viruses are susceptible in vitro to oseltamivir and zanamivir. Oral oseltamivir and

topical zanamivir are active in animal models of influenza A (H5N1). Prevention

ImmunizationNo influenza A (H5) vaccines are currently commercially available for humans. Earlier H5 vaccines were poorly immunogenic and required two doses of high hemagglutinin antigen content or the addition of MF59 adjuvant to generate neutralizing antibody responses

Hospital-Infection Controla. Influenza is a well-recognized nosocomial pathogen. Current recommendations are

based on efforts to reduce transmission to health care workers and other patients in a nonpandemic situation and on the interventions used to contain SARS.

b. The efficiency of surgical masks, even multiple ones, is much less than that of N-95 masks, but they could be used if the latter are not available.

c. Chemoprophylaxis with 75 mg of oseltamivir once daily for 7 to 10 days is warranted for persons who have had a possible unprotected exposure

CHILDHOOD IMMUNIZATION

VPD - vaccine-preventable diseaseDefinition of VPD:

1. An infectious disease for which an effective preventive vaccine exists. 2. If a person dies from it, the death is considered a vaccine-preventable death.3. 1.4 million U5 deaths were from vaccine-preventable diseases. 4. With 100% immunization, one out of seven deaths could be prevented5. The 8 targeted VPDs in India are:

1. Diphtheria,2. Hepatitis B, 3. Measles, 4. Pertusis,5. Poliomyelitis, 6. Tetanus,7. Tuberculosis,8. JE

6. Six killer diseases:1. Polio, 2. Diphtheria, 3. Tuberculosis, 4. Pertusis (whooping cough),5. Measles and6. Tetanus.

7. Fully immunized child: A child who received1. One dose of BCG, 2. Three doses of DPT and OPV 3. One dose of measles before one year of age

4. This gives a child the best chance for survival BCG:

1. Live attenuated vaccine prepared from mycobacterium bovis - Bacillus Calmette – Guérin Danish 1331strain subcultured every 3 weeks for 13 years

2. Heat and light sensitive vaccine3. Add 1 cc NaCl to vial; 0.05 ml intradermal; left arm; no spirit for cleaning4. Within 14 days after birth5. 2 to 3 weeks - papule

1. 5 weeks - 4-8 mm in diameter2. 6-12 weeks - shallow ulcer covered with a crust. 3. Healing with round scar 2-10 mm in diameter.4. Scar not a must5. Prevents serious forms of TB in infancy6. complications

1. Abcess2. Keloid3. Adenitis4. Spread of tubercular disease

7. Contraindication:1. HIV2. Immunocompromised child3. Mx + ve child

OPV:1. Live attenuated whole virus vaccine2. Trivalent- types I, II & III3. Light and heat sensitive4. From NB Up to 5 years of age5. 4 doses at 6,10,14 weeks and 16-24 months6. Pulse polio for U5 children as and when planned7. Neurovirulance – vaccine associated poliomyelitis8. Contraindications: > 5 years; severe immune deficiency; severe diarrhea

DPT:1. Diphteria and tetanus: toxoid2. Pertusis: whole cellular inactivated bacteria3. 6,10,14 and 16-24 months4. Should not freeze5. Intramuscular vaccine- preferably antero lateral thigh6. Site of injection7. DPT-Vaccine reactions8. Local redness and swelling, induration, 9. Fever 10. Prolonged crying 11. Febrile convulsions 12. Hypotonic–hyporesponsive episodes 13. Pertusis contrindicated in:

1. Incessant crying for more than 3 hours2. Fever more than 40.5c

3. Hypotonic–hyporesponsive episodes 4. Progressive neurological disease5. > 6 years of age

Double antigen-DT :1. Diphtheria and tetanus toxoid2. 4 ½ to 5 years age3. No specific contraindications4. Pain swelling and fever can occur

TT:1. 6,10,14, 1 ½ years, 4-5 years, 10, 16 years and later every ten years2. Antenatal – 2 doses at 1 month interval 3. Pain, eryythema, tenderness and induration 4. No specific contraindications5. No need for TT in trivial injuries

Measles:1. Live attenuated virus2. 0.5 ml subcutaneous3. After completion of 9 months4. Mild fever and cold few days later5. Toxic shock syndrome is an important adverse reaction due to contamination of

staph.aureus.6. contraindications:

1. Neomycin and egg allergy2. Immune compromised children

Optional vaccines:Mumps, measles and rubella vaccine (MMR):

1. Mumps can cause sterility, myocarditis and encephalitis2. Rubella can cause fetal malformation- Congenital rubella syndrome with CHD

and mental retardation3. MMR is given at 15 completed months4. Adverse effects and contraindications similar to measles5. ? autism

Hepatitis B vaccination:1. Sexual and perinatal, needle stick transmission2. Severe acute & chronic active hepatitis, hepatic carcinoma3. HbB positive mother, NB to receive:

3. HbB vaccine at birth4. HbB immune globulin 100 IU within 2-3 days

4. Normal schedule: 0,1,6 months or 6,10,14 weeks along with DPT5. Child dose .5 ml; adult dose 1 ml IM, no boosters6. May have Pain and fever

Haemophilus influenza Type B:1. Produce otitis media, pneumonia and meningitis in children2. Capsular polysaccharide vaccine3. < 6 months:6,10,14 weeks combined with DPT

4. > 6 months: 2 doses at 1 month interwal 5. >15 months: 1 dose6. Booster at 18 months7. > 5 years: No need for vaccine8. IM ; safe vaccine ; mild fever and pain

COLD CHAIN SYSTEM:

1. Cold chain definition:1. Vaccines are sensitive to heat and freezing and must be kept at the correct temperature

from the time they are manufactured until they are used. i. The system used for keeping and distributing vaccines in good condition is called

the cold chain. ii. The cold chain consists of a series of storage and transport links, all designed to

keep vaccines within an acceptable range until it reaches the user.2. Maintenance of the cold chain requires vaccines and diluents to be:

i. Collected from the manufacturer or an airport as soon as they are available;ii. Transported between 2ºc and 8ºc from the airport and from one store to

another;iii. Stored at the correct temperature in primary/central and intermediate

3. Vaccine stores and in health facilities;i. Transported between 2ºc and 8ºc to outreach sites and during mobile sessions;

ii. Kept between 2ºc and 8ºc range during immunization sessions; andiii. Kept between 2ºc and 8ºc during return to health facilities from outreach sites.

4. After vaccines reach the health facility:i. Keep them between 2ºC and 8ºC in health facility refrigerator (ILR).

ii. Carry them to the immunization session in a vaccine carrier with frozen ice packs or ice.

iii. Keep the vaccines cool using a foam pad in the vaccine carrier while Health worker immunizes the children.

5. Cold chain equipments:i. Primary vaccine stores need cold or freezer rooms, freezers, refrigerators, cold

boxes, and sometimes refrigerator trucks for transportation.ii. Intermediate vaccine stores, depending on their size/capacity, need cold and

freezer rooms, and/or freezers, refrigerators, and cold boxes.iii. Health facilities need refrigerators with freezing compartments, cold boxes and

vaccine carriers.6. Vaccine vial monitors:

i. A vaccine vial monitor (VVM) is a label that changes colour when the vaccine vial has been exposed to heat over a period of time.

ii. Before opening a vial, the status of the VVM must be checked to see whether the vaccine has been damaged by heat.

iii. Use only vials with inner squares that are lighter in colour than the outside circle

National imuunization ScheduleFor Pregnant Women:

TT-1 Early in pregnancy 0.5 ml Intra-muscular Upper ArmTT-2 4 weeks after TT-1* 0.5 ml Intra-muscular Upper ArmTT- Booster If received 2 TT doses in a pregnancy within the last 3 yrs 0.5 ml Intra-

muscular Upper ArmFor Infants:

BCG At birth or as early as possible till one year of age (0.05ml until 1 month age) Intra-dermal Left Upper Arm

Hepatitis B At birth or as early as possible within 24 hours 0.5 ml Intra-muscular Antero-lateral side of mid-thigh

OPV-0 At birth or as early as possible within the first 15 days 2 drops Oral OPV 1,2 & 3 At 6 weeks, 10 weeks & 14 weeks 2 drops Oral DPT1,2 & 3 At 6 weeks, 10 weeks & 14 weeks 0.5 ml Intra-muscular Antero-lateral

side of mid thighHepatitis B 1,2 & 3 At 6 weeks, 10 weeks & 14 weeks 0.5 ml Intra-muscular Antero-lateral side

of mid-thighMeasles 9 completed months-12 months.(give up to 5 years if not received at 9-12

months age) 0.5 ml Sub-cutaneous Right upper ArmVitamin A(1stdose) At 9 months with measles 1 ml ( 1 lakh IU) Oral

For Children:DPT booster 16-24 months 0.5 ml Intra-muscular Antero-lateral side of mid-thighOPV Booster 16-24 months 2 drops Oral JapaneseEncephalitis 16-24 months with DPT/OPV booster 0.5 ml Sub-cutaneous Left Upper ArmVitamin A(2nd to 9th dose) 16 months with DPT/OPV booster Then, one dose every 6 months up to the

age of 5 years. 2 ml (2 lakh IU) Oral DT Booster 5-6 years 0.5 ml. Intra-muscular Upper ArmTT 10 years & 16 years 0.5 ml Intra-muscular Upper Arm

Proposed Changes in the National Immunization Schedule: 2009-101. DT Booster to be replaced by DPT Booster at 5-6 years of age.2. In select well-performing states, MR to be given with DPT Booster at 16-24months (Dose: 0.5 ml;

Route: Sub-cutaneous; Site: Right Upper Arm)3. DPT and HepB vaccines at 6, 10 and 14 weeks to be replaced by DPT-HepBHib (Pentavalent)

vaccine.

NEWER VACCINES:1. Conventional vaccines contained the whole of organism or the toxin whereas the immunogenic

protein component is not separated 2. Second-Generation or new vaccines

1. Conjugate Vaccines :a. Pneumococci and H.Influenza produce serious diseases in childrenb. They are capsulated organisms with polysaccaride in the capsule preventing

immune reaction c. The patient can not produce antibody

d. This antigen is combined with a protein from another organism and this is called conjugate vaccine

2. Subunit Vaccines (polypeptide vaccines) 1. Vaccines are developed from antigenic fragments2. They are able to evoke an immune response,3. They have fewer side effects than a vaccine made from the whole organism. 4. Subunit vaccines can be made from a part the actual microbe, or in the

laboratory using genetic engineering techniques. 5. Eg:

• Viral subunit : HBsAg • Bacterial subunit : Acellular pertussis • Against pneumonia caused by streptococcus pneumoniae

3. Recombinant subunit vaccine a. The recombinant vaccine is made by inserting a tiny portion of the virus’

genetic material into common baker’s yeast. b. This process induces the yeast to produce an antigen, which is then purified. c. The purified antigen, when combined with an adjuvant, a substance that

stimulates the immune system, results in a safe and very effective vaccine.d. Eg. Hepatitis B vaccine

4. Recombinant Vector Vaccines a. A weakened virus or bacterium is made as a vector or carrierb. Genetic material from the disease-causing organism is made antigenic but

not pathogenic is inserted into the vectorc. Eg. d. Vaccinia virus acts as vector in which several genes from HIV are inserted to

produce a vaccinee. Weakened bacterium—salmonella—carry portions of the hepatitis B virus

to produce HB vaccine5. DNA vaccines

1. DNA sequence used as a vaccine.2. This DNA sequence code for antigenic protein of a pathogen.3. As this DNA Inserted into cells (plasmids) it is translated to form antigenic

protein. 4. Immune response raised against this protein.5. In this way , DNA vaccine provide immunity against that pathogen.6. Eg: Human papilloma virus vaccine; herpes vaccine and this technology is

also used to prepare vaccine against certain cancers 6. VIROSOMES

1. virosomes represent reconstituted empty influenza virus envelopes2. Antigens can be incorporated into virosomes 3. Virosomes are small vesicles containing viral membrane proteins 4. Virosomes fuse with cells of the immune system and thus deliver their

contents - the specific antigens – directly to their target cells, eliciting a specific first-class immune response

5. Eg. Hep A and Influenza vaccines

3. Some new vaccines:i. Inactivated polio vaccine: IPV

a. Dose .5 ml IMb. Schedule: 6,10,14 weeks and at 18 mo ( in addition to OPV)c. Use: 1. immune compromised children; 2. for eradication of polio where

polio virus is circulating even after many pulse polio sessionsii. Rota virus vaccine:

a. Oral vaccine 1 ml/doseb. 1st dose: 6 weeks; 2nd dose 10 weeks of lifec. Protects against rota virus gastroenteritisd. RV5 (RotaTeq) is a live oral vaccine contains five re assortant rotaviruses

developed from human and bovine parent rotavirus strains e. RV1 (Rotarix) contains one strain of live attenuated human rotavirusf. Any rotavirus gatroenteritis - 74%-87% effectiveg. Routine vaccination of all infants without a contraindicationh. Intussusception was a suspected complication in older vaccines

iii. Human papilloma virus vaccine:a. To protect women against cervical cancerb. Two vaccines available:

i. Quadrivalent: mixture of L1 protein and sero types 16,18,6 & 11ii. Bivalent vaccine: mixture of L1 protein and sero types 16&18

c. Age: 9-26 yearsd. Dose: .5 ml IMe. Schedule: 0,2,6 months

VACCINES FOR ADOLESCENTS- IAP

Tdap/Td 10 years

TT Booster at 10 and 16 years

Rubella As part of MMR vaccine or (Monovalent) 1 dose to girls at 12-13 years of age, if not given earlier

MMR 1 dose at 12-13 years of age. (if not given earlier)

Hepatitis B 3 Doses (0, 1 and 6 m) if not given earlier

Typhoid TA, Vi or Oral typhoid vaccine every 3 years

Varicella* 1 dose upto 12-13 years and 2 doses after 13 years of age. (if not given earlier)

Hepatitis A* 2 doses (0 and 6 months) if not given earlier

Human Pappiloma Virus vaccineFor Girls only

Studies show a rapid rise in ano-genital HPV infections by –15 yrs age hence ensure immunization completed prior to it.11-12 yrs endorsed by the Society for Adolescent Medicine (SAM), 9-10 yrs left to the discretion of the care provider.3 doses of HPV given at 0, 2 and 6 months in the Deltoid.