Bab 2 Demam Pada Anak Soal (1-10)

Mohd Nazshua bin Mohd Irwan Serigar

1. Bagaimana pembagian demam berdasarkan lama, suhu tubuh dan polanya?

Berdasarkan suhu tubuh:-

Berdasarkan pola:-

Continuous fever: Temperature remains above normal throughout the day and does not fluctuate more than 1 °C in 24 hours, e.g. lobar pneumonia, typhoid, urinary tract infection, brucellosis, or typhus. Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau. (Drops due to fever-reducing drugs are excluded.)

Intermittent fever: The temperature elevation is present only for a certain period, later cycling back to normal, e.g. malaria, kala-azar, pyaemia, or septicemia. Following are its types

o Quotidian fever, with a periodicity of 24 hours, typical of Malariao Tertian fever (48 hour periodicity), typical of Malariao Quartan fever (72 hour periodicity), typical of Plasmodium malariae).

Remittent fever: Temperature remains above normal throughout the day and fluctuates more than 1 °C in 24 hours, e.g., infective endocarditis.

Pel-Ebstein fever: A specific kind of fever associated with Hodgkin's lymphoma, being high for one week and low for the next week and so on. However, there is some debate as to whether this pattern truly exists.

A neutropenic fever, also called febrile neutropenia, is a fever in the absence of normal immune system function. Because of the lack of infection-fighting neutrophils, a bacterial infection can spread rapidly; this fever is, therefore, usually considered to require urgent medical attention. This kind of fever is more commonly seen in people receiving immune-suppressing chemotherapy than in apparently healthy people.

Febricula is an old term for a low-grade fever, especially if the cause is unknown, no other symptoms are present, and the patient recovers fully in less than a week.

Berdasarkan lama:-

a. Fever less than 7 days-also known as Fever of short duration or fever with localizing signs

- a diagnosis can be established by clinical history and physical examination

-ex: Dengue, Otitis Media

b. Fever lasting longer than 7 days

- also known as Fever without localizing signs (without a focus)

- a history and physical examination fail to establish a cause, although a diagnosis of occult bacteremia may be suggested by laboratory studies

-ex:Malaria, Infective Endocarditis, Rheumatic Fever

c. Fever of Unknown Origin

-defined as temperature greater than 100.4°F (38°C) lasting for more than 14 days with no obvious cause despite a complete history, physical examination, and routine screening laboratory evaluation.

2. Bagaimana menentukan perjalanan demam pada anak?

A. History taking :

-Characteristic of fever : onset, duration, pattern-Associated symptoms-Assessment of risk factors : Host, Agent, Environment(animal-contact, recent travel, raw

meat consumption (tularemia), vaccination etc.)

B. Physical Examination:

-HR increase ~ 15 BPM/1ºC � - Metabolic �Rate 10-12%/1ºC � -Insensible water loss : 300-500 ml/m2/day- Electrolyte & nutritional consequence-Other specific signs & symptoms according to their diseases

3. Gejala atau keluhan apa saja yang dapat menyertai demam?

Stiff neck Skin rash : haemorrhagic (petechiae), maculopapular Skin sepsis Discharge from ear Severe palmar pallor Local tenderness Fast breathing Local tenderness Severe malnutrition Dehydration Headache Pain on passing urine Ear pain Sweating Cough

4. Kelainan atau penyakit apa saja yang dapat menyebabkan demam?

A. Endogenous Cause- Infection & Inflammation- Malignancy- CNT Disease – Tissue injury- Hereditary : FMF, Ectodermic dysplasia- Metabolic Diseases- Kawasaki- Endocrine- CNS (thermoregulatory center)- granulomatous

B. Exogenous cause- Drug : cocaine, amphotericin, ATB- Vaccine- Biologic agent : GM-CSF, IL, IFN- Factitious fever

5. Bagaimana pola demam yang khas untuk penyakit-penyakit demam tifioid, malaria, morbili, varisela dan demam denggi?

a. demam TifoidA slowly progressive fever as high as 40 °C (104 °F). The fever usually rises in the afternoon up to the first and second week. It shows a step-ladder pattern.

b. Malaria

The classic symptom of malaria is cyclical occurrence of sudden coldness followed by rigor and then fever and sweating lasting four to six hours, occurring every two days in P. vivax and P. ovale infections, while every three days for P. malariae. P. falciparum can have recurrent fever every 36–48 hours or a less pronounced and almost continuous fever.

c. MorbiliHistory of fever of at least three days, with at least one of the three C's (cough, coryza, conjunctivitis).

d. VariselaMild fever. The fever varies between 101º F to 105º F and returns to normal when the blisters have disappeared.

e. demam DenggiSudden-onset high fever, often over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days

6. Dapatkah anda menentukan perjalanan demam untuk penyakit-penyakit di atas?

a. demam TifoidFirst stage: Signs and symptoms often appear one to three weeks after exposure to the bacterium, S. typhi. In some cases, symptoms may take up to two months to appear. individuals may not become sick for as long as two months after exposure. The incubation period for paratyphoid fever is shorter, usually one to 10 days under normal circumstances. Once signs and symptoms do appear, individuals will likely experience: fever, often as high as 103-104 degrees Fahrenheit headache; weakness and fatigue; a sore throat; abdominal pain; and diarrhea or constipation. Children are more likely to have diarrhea whereas adults may become severely constipated. During the second week, individuals may develop a rash of small, flat, rose-colored spots on the lower chest or upper abdomen. The rash is temporary, and usually disappears in three or four days.

Second stage: If the individual does not receive treatment for typhoid fever, they may enter a second stage during which the individual becomes very ill. The fever will remain high, and the individual may develop either diarrhea that has the color and consistency of pea soup or severe constipation. They may lose considerable weight during this phase, and the abdomen may become extremely distended.

Third stage or the typhoid state: By the third week, the individual may become delirious, lying motionless and exhausted with their eyes half-closed in what is known as the typhoid state. Life-threatening complications often develop at this time, such as pneumonia.

Improvement stage: Improvement may come slowly during the fourth week. A fever is likely to decrease gradually until the temperature returns to normal in another week to 10 days. Signs and symptoms can return up to two weeks after the fever has subsided.

Paratyphoid fever causes signs and symptoms similar to those of typhoid fever, but in a milder form. Complications are not as severe, and individuals generally recover more quickly.

b. MalariaSymptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia (caused by hemolysis), hemoglobinuria, retinal damage, and convulsions. The classic symptom of malaria is cyclical occurrence of sudden coldness followed by rigor and then fever and sweating lasting four to six hours, occurring every two days in P. vivax and P. ovale infections, while every three days for P. malariae. P. falciparum can have recurrent fever every 36–48 hours or a less pronounced and almost continuous fever. For reasons that are poorly understood, but that may be related to high intracranial pressure, children with malaria frequently exhibit abnormal posturing, a sign indicating severe brain damage. Malaria has been found to cause cognitive impairments, especially in children. It causes widespread anemia during a period of rapid brain development and also direct brain damage. This neurologic damage results from cerebral malaria to which children are more vulnerable. Cerebral malaria is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever.

Severe malaria is almost exclusively caused by P. falciparum infection, and usually arises 6–14 days after infection. Consequences of severe malaria include coma and death if untreated—young children and pregnant women are especially vulnerable. Splenomegaly (enlarged spleen), severe headache, cerebral ischemia, hepatomegaly (enlarged liver), hypoglycemia, and hemoglobinuria with renal failure may occur. Renal failure is a feature of blackwater fever, where hemoglobin from lysed red blood cells leaks into the urine. Severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease, fatality rates can exceed 20%, even with intensive care and treatment. In endemic areas, treatment is often less satisfactory and the overall fatality rate for all cases of malaria can be as high as one in ten. Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.

c. MorbiliThe classical symptoms of measles include four-day fevers and the three Cs—cough, coryza (runny nose) and conjunctivitis (red eyes). The fever may reach up to 40 °C (104 °F). Koplik's spots seen inside the mouth are pathognomonic (diagnostic) for measles, but are not often seen, even in real cases of measles, because they are transient and may disappear within a day of arising.The characteristic measles rash is classically described as a generalized, maculopapular, erythematous rash that begins several days after the fever starts. It starts on the head before spreading to cover most of the body, often causing itching. The rash is said to "stain", changing color from red to dark brown, before disappearing. The measles rash appears two to four days after initial symptoms, and lasts for up to eight days.

d. VariselaThe incubation period of chickenpox is between 10 and 20 days.Before the typical rash appears, patients often develop a fever, headache, swollen glands and other flu like symptoms. Skin vesicles contain the virus but are not the primary sources. Scabs are not infectious. Patients are contagious from 2 days before onset of the rash until all lesions have crusted.

e. demam DenggiTypically, people infected with dengue virus are asymptomatic (80%) or only have mild symptoms such as an uncomplicated fever. Others have more severe illness (5%), and in a small proportion it is life-threatening. The incubation period (time between exposure and onset of symptoms) ranges from 3–14 days, but most often it is 4–7 days. Therefore, travelers returning from endemic areas are unlikely to have dengue if fever or other symptoms start more than 14 days after arriving home. Children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea), but are more susceptible to the severe complications.

The characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. The alternative name for dengue, "break-bone fever", comes from the associated muscle and joint pains. The course of infection is divided into three phases: febrile, critical, and recovery.

The febrile phase involves high fever, often over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days. At this stage, a rash occurs in approximately 50–80% of those with symptoms. It occurs in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4–7), as a measles-like rash. Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point, as may some mild bleeding from the mucous membranes of the mouth and nose. The fever itself is classically biphasic in nature, breaking and then returning for one or two days, although there is wide variation in how often this pattern actually happens.

In some people, the disease proceeds to a critical phase, which follows the resolution of the high fever and typically lasts one to two days. During this phase there may be significant fluid accumulation in the chest and abdominal cavity due to increased capillary permeability and leakage. This leads to depletion of fluid from the circulation and decreased blood supply to vital organs. During this phase, organ dysfunction and severe bleeding, typically from the gastrointestinal tract, may occur. Shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue, however those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk

The recovery phase occurs next, with resorption of the leaked fluid into the bloodstream. This usually lasts two to three days. The improvement is often striking, but there may be severe itching and a slow heart rate. During this stage, a fluid overload state may occur; if it affects the brain, it may cause a reduced level of consciousness or seizures.

7. Dapatkah anda menjelaskan patofisiologi penyakit-penyakit di atas?

a. demam Tifoid

b. MalariaMalaria develops via two phases: an exoerythrocytic and an erythrocytic phase. The exoerythrocytic phase involves infection of the hepatic system, or liver, whereas the erythrocytic phase involves infection of the erythrocytes, or red blood cells. When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver. Within minutes of being introduced into the human host, the sporozoites infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days. Once in the liver, these organisms differentiate to yield thousands of merozoites, which, following rupture of their host cells, escape into the blood and infect red blood cells, thus beginning the erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.

Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their hosts to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.

Some P. vivax and P. ovale sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant for periods ranging from several months (6–12 months is typical) to as long as three years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in these two species of malaria.

The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria. High endothelial venules (the smallest branches of the circulatory system) can be blocked by the attachment of masses of these infected red blood cells. The blockage of these vessels causes symptoms such as in placental and cerebral malaria. In cerebral malaria the sequestrated red blood cells can breach the blood brain barrier possibly leading to coma.

Although the red blood cell surface adhesive proteins (called PfEMP1, for Plasmodium falciparum erythrocyte membrane protein 1) are exposed to the immune system, they do not serve as good immune targets, because of their extreme diversity; there are at least 60 variations of the protein within a single parasite and effectively limitless versions within parasite populations. The parasite switches between a broad repertoire of PfEMP1 surface proteins, thus staying one step ahead of the pursuing immune system.

Some merozoites turn into male and female gametocytes. Since the gametocytes are formed in the blood of the vertebrate host, the vertebrate host is the definitive host of the disease. If a mosquito pierces the skin of an infected person, it potentially picks up gametocytes within the blood. Fertilization and sexual recombination of the parasite occurs in the mosquito's gut. New

sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially attractive to the mosquitoes, and malaria in pregnant women is an important cause of stillbirths, infant mortality and low birth weight, particularly in P. falciparum infection, but also in other species infection, such as P. vivax.

c. Morbili/Measles

Measles first gains access to the body via the upper respiratory tract or the conjunctiva. The virus quickly spreads to the immediate lymph nodes. Destruction of the lymphoid tissues leads to a profound leucopenia. A primary viraemia ensues which is responsible for spreading the virus throughout the rest of the R-E system and the respiratory system. A secondary viraemia follows whereby the virus is further spread to involve the skin, the viscera, kidney and bladder. The Koplik's spots and the rash in measles are thought to result from a delayed hypersensitivity reaction, the virus antigen being absent from the lesion itself.

1. Acute measles panencephalitis - It is likely that CNS involvement, even in uncomplicated measles, is common. Transient EEG abnormalities are detected in 50% of patients. Measles virus is rarely isolated from the brain of a patient with acute measles panencephalitis. Therefore, current theories favour an autoimmune reaction as the possible cause of CNS damage.

2. Subacute measles encephalitis - arise only in patients with severe immune disorder. Therefore it is not usually accompanied by the formation of antibodies in the CSF. Infectious virus has not been isolated by conventional methods, suggesting defects in replication. Recently biological studies on brain tissue from a case of SME revealed that the envelope proteins were missing from the brain tissue and only the N and the P protein were consistently detected.

3. SSPE - in SSPE, the virus is first thought to gain entry to the CNS during the viraemia. Once there, it establishes a low-grade persistent infection. It is not known whether viral replication itself, or immunopathological mechanisms are responsible for the development of lesions. In SSPE, free infectious virus particles have never been isolated from the brain or the CSF, although some viral antigens may be found. Giant cells which are characteristic of acute measles infection are also absent. However, viral nucleocapsids are present in the cytoplasm. Therefore, some defect must exist in the virus replication process that prevents maturation. In the absence of free infectious particles, the infection may spread slowly by infectious nucleocapsids from cell to cell.

Antibodies in the CSF are oligoclonal as opposed to the polyclonal response seen in the sera. This suggests that antibody in the CSF is made locally by a much smaller population of lymphocytes which have invaded this compartment. The M-protein is not recognized by the antibodies present in the CSF. SSPE brain lesions have M, N and P proteins present in infected cells whereas the envelope proteins are missing. The measles mRNAs isolated from SSPE patients showed a high rate of mutations, the highest rate of mutation in the M gene, followed by the F, H, P and N genes. In some cases, infectious MV particles may be recovered if the brain cells are co-cultured with tissue culture cells susceptible to measles virus. In other cases though, the block is only partially overcome and the agent remains cell associated. In this case, although MV envelope mRNAs are present, the envelope proteins are not synthesized. Another hallmark

of SSPE is the hyperimmune response to measles antigens that include neutralizing antibodies in the serum and the CSF. In spite of this, the infection cannot be controlled. CMI is much more important than the humoral response in clearing measles virus infection. There is no evidence to suggest that the CMI is impaired in patients who develop SSPE.

d. VariselaThe incubation period of varicella is generally 14 to 16 days, with a range of 11 to 20 days after contact. Primary infection with VZV results in chickenpox. Prodromal symptoms of fever, malaise, and anorexia may precede the rash by 1 day. The characteristic rash appears initially as small red papules that rapidly progress to nonumbilicated, oval, "teardrop" vesicles on an erythematous base. The fluid progresses from clear to cloudy, and the vesicles ulcerate, crust, and heal. New crops appear for 3 to 4 days, usually beginning on the trunk followed by the head, the face, and, less commonly, the extremities. There may be a total of 100 to 500 lesions, with all forms of lesions being present at the same time. Pruritus is universal and marked. Lesions also may be present on mucous membranes. Lymphadenopathy may be generalized. The severity of the rash varies, as do systemic signs and fever, which generally abate after 3 to 4 days.

The pre-eruption phase of zoster includes intense localized pain and tenderness along a dermatome, accompanied by malaise and fever. In adults, the pain of acute neuritis in the affected dermatomes is characteristically intense and constant. In several days, the eruption of papules, which quickly vesiculate, occurs in the dermatome or in two adjacent dermatomes. Groups of lesions occur for 1 to 7 days, then progress to crusts and healing. The typical areas involved are dorsal and lumbar, although cephalic and sacral lesions may develop. Lesions generally are unilateral and are accompanied by regional lymphadenopathy. In one third of patients, a few vesicles occur outside the primary dermatome. Any branch of cranial nerve V may be involved, which also may cause corneal and intraoral lesions. Involvement of cranial nerve VII may result in facial paralysis and ear canal vesicles (Ramsay Hunt syndrome). Ophthalmic zoster may be associated with ipsilateral cerebral angiitis and stroke. Immunocompromised persons may have unusually severe, painful herpes zoster that involves cutaneous and, rarely, visceral dissemination (to liver, lungs, and CNS). Postherpetic neuralgia is pain persisting longer than 1 month and is uncommon in children.

Pathologic changes in fatal measles usually represent the compound effect of viral and secondary bacterial infection. Pneumonia is almost invariably present, most frequently interstitial. More representative are changes of the uncomplicated viral diseases within the tonsillar, nasopharyngeal, and appendiceal tissue removed during the prodrome. These changes consist of round cell infiltration and the presence of multinucleated giant cells. 

Simultaneous with the onset of rash, measles-specific antibodies are detectable in serum. Leukopenia (an abnormally low number of leukocytes in the circulating blood) is observed on the first day of rash mainly due to a decrease in lymphocytes; subsequently, granulocytopenia

(an acute blood disorder) ensues as well.

Cell-mediated immunity is impaired during measles. There is transient suppression of the tuberculin reaction, evident with the measles vaccine.  In severe disease, the magnitude of depression of the total lymphocytes has been positively correlated with a lessened chance of recovery.The measles virus infects monocytes by binding to the CD46 surface protein, which in turn is utilized as the measles-specific entry mediator.  When measles bind to CD46, there is a down-regulation of IL-12 production.  Decreased IL-12 released favors a predominance of a Th2-like response because IL-12 is a necessary stimulus for Th1 clonal expansion.  IL-12 stimulates resting and activated T cells, inducing the production of IFN-gamma by T cells, activates NK cells, and inhibits IL-4 production. Decreasing the IL-12 production could impair the acquisition of adaptive immunity to measles and facilitate a generalized immunosuppression because IL-12 normally promotes the rapid induction of Ag-specific T cells in the naive host.

e. demam Denggi

Dengue infection is caused by 1 of 4 related, but antigenically distinct, viral serotypes: dengue virus 1 (DENV-1), dengue virus 2 (DENV-2), dengue virus 3 (DENV-3), and dengue virus 4 (DENV-4). Genetic studies of sylvatic strains suggest that the 4 viruses evolved from a common ancestor in primate populations approximately 1000 years ago and that all 4 viruses separately emerged into a human urban transmission cycle 500 years ago in either Asia or Africa. Albert Sabin speciated these viruses in 1944. Each serotype is known to have several different genotypes.

Infection with one dengue serotype confers lifelong homotypic immunity and a very brief period of partial heterotypic immunity, but each individual can eventually be infected by all 4 serotypes. Several serotypes can be in circulation during an epidemic.

Dengue viruses are transmitted by the bite of an infected Aedes (subgenus Stegomyia) mosquito. Globally, A aegypti is the predominant highly efficient mosquito vector for dengue infection, but A albopictus and other Aedes species can also transmit dengue with varying degrees of efficiency.

Aedes mosquito species have adapted well to human habitation, often breeding around dwellings in small amounts of stagnant water found in old tires or other small containers discarded by humans. Female Aedes mosquitoes are daytime feeders. They inflict an innocuous bite and are easily disturbed during a blood meal, causing them to move on to finish a meal on another individual, making them efficient vectors. Entire families who develop infection within a 24- to 36-hour period, presumably from the bites of a single infected vector, are not unusual.

Humans serve as the primary reservoir for dengue; however, certain nonhuman primates in Africa and Asia also serve as hosts but do not develop dengue hemorrhagic fever. Mosquitoes

acquire the virus when they feed on a carrier of the virus. The mosquito can transmit dengue if it immediately bites another host. In addition, transmission occurs after 8-12 days of viral replication in the mosquito's salivary glands (extrinsic incubation period). The mosquito remains infected for the remainder of its 15- to 65-day lifespan. Vertical transmission of dengue virus in mosquitoes has been documented. The eggs of Aedes mosquitoes withstand long periods of desiccation, reportedly as long as 1 year, but are killed by temperatures of less than 10°C.

Once inoculated into a human host, dengue has an incubation period of 3-14 days (average 4-7 d) while viral replication takes place in target dendritic cells. Infection of target cells, primarily those of the reticuloendothelial system, such as dendritic cells, hepatocytes, and endothelial cells, result in the production of immune mediators that serve to shape the quantity, type, and duration of cellular and humoral immune response to both the initial and subsequent virus infections.

Following incubation, a 5- to 7-day acute febrile illness ensues. Recovery is usually complete by 7-10 days.

Dengue hemorrhagic fever or dengue shock syndrome usually develops around the third to seventh day of illness, approximately at the time of defervescence. The major pathophysiological abnormalities caused by dengue hemorrhagic fever and dengue shock syndrome include the rapid onset of plasma leakage, altered hemostasis, and damage to the liver, resulting in severe fluid losses and bleeding. Plasma leakage is caused by increased capillary permeability and may manifest as hemoconcentration, as well as pleural effusion and ascites. Bleeding is caused by capillary fragility and thrombocytopenia and may manifest in various forms, ranging from petechial skin hemorrhages to life-threatening gastrointestinal bleeding. Liver damage manifests as increases in levels of alanine aminotransferase and aspartate aminotransferase, low albumin levels, and deranged coagulationparameters(PT,PTT).

In persons with fatal dengue hepatitis, infection was demonstrated in more than 90% of hepatocytes and Kupffer cells with minimal cytokine response (tumor necrosis factor [TNF]–alpha, interleukin [IL]–2). This is similar to that seen with fatal yellow fever and Ebola infections.

Most patients who develop dengue hemorrhagic fever or dengue shock syndrome have had prior infection with one or more dengue serotypes. In individuals with low levels of neutralizing antibodies, nonneutralizing antibodies to one dengue serotype, when bound by macrophage and monocyte Fc receptors, have been proposed to result in increased viral entry and replication and increased cytokine production and complement activation. This phenomenon is called antibody-dependent enhancement.

Some researchers suggest T-cell immunopathology may play a role, with increased T-cell activation and apoptosis. Increased concentrations of interferon have been recorded 1-2 days following fever onset during symptomatic secondary dengue infections. The activation of cytokines, including TNF-alpha, TNF receptors, soluble CD8, and soluble IL-2 receptors, has been correlated with disease severity. Cuban studies have shown that stored serum sample analysis demonstrated progressive loss of cross-reactive neutralizing antibodies to DENV-2 as the interval since DENV-1 infection increased. In addition, certain dengue strains, particularly

those of DENV-2, have been proposed to be more virulent, in part because more epidemics of dengue hemorrhagic fever have been associated with DENV-2 than with the other serotypes.

8. Dapatkah anda membedakan demam pada penyakit infeksi (viral, bakteria) ataupun oleh sebab penyakit non infeksi?

The Society of Critical Care Medicine defines a fever as a temperature greater than 38.3 °C. Most infectious causes of fever follow a diurnal pattern. There are many causes of noninfectious fever. With the exception of drug fever and transfusion reaction, noninfectious fever usually does not lead to a fever greater than 39.8°C.

Routine laboratory tests, such as a complete blood count to look for evidence of bleeding, leukocytosis, and eosinophilia; a liver panel and an amylase and lipase test; ECG with cardiac enzymes; and a check of lactic acid level can help to quickly rule in or rule out many of the most common causes of noninfectious fever.

Imaging studies such as a chest radiograph; computed tomography of the head, chest, abdomen, and pelvis; right upper quadrant ultrasound; and lower extremity venous duplex may also be necessary to complete the workup.

Drug withdrawal fever should always be considered in a patient with a history of substance abuse. In many cases this abuse history may not be known to the clinician, so clinical suspicion should be high.

Drugs are a commonly considered etiology of fever; in reality very few cases are cited in the literature. Drugs commonly associated with drug fever are the Beta-lactam antibiotics, procainamide, and diphenylhydantoin.

A. Penyebab Infeksi

v      Parasit v      Bakteri v      Virus v      Jamur v      dll.

B. Penyebab Non Infeksi

v      Neoplasma v      Nekrosis Jaringan v      Kelainan Kolagen Vaskular

v      Emboli Paru / Trombosis vena dalam v      Obat , metabolism, dll.

9. Gejala dan tanda apa saja selain demam pada penyakit infeksi (viral, bakteria) ataupun oleh sebab penyakit non infeksi?

Since there are many symptoms, only drug fever as the causative agent of non infectious and typhoid fever as the causative agent of infectious are used as examples.

Non infectious: Drug feveru Some 3-7% of fevers on an inpatient medical service are drug reactionsu History of atopy is a risk factoru Patient may have been on the “sensitizing medication” for days to yearsu On physical patient looks “inappropriately well” for degree of fever :

- fever usually 102º to 104º - relative bradycardia - 5-10% have rash

u Lab tests show - leukocytosis with left shift- eosinophils on peripheral smear (common)- eosinophilia (low-grade)- elevated ESR- mildly elevated AP, AST, ALT

Infectious: Thyphoid fever- fever, often as high as 103-104 degrees Fahrenheit- headache;- weakness and fatigue;- a sore throat;- abdominal pain;- diarrhea or constipation

10. Pemeriksaan apa saja yang diperlukan untuk menentukan diagnosis, setelah anda menentukan diagnosis banding demam?

Laboratory diagnosis of infection includes examination of bacterial morphology using Gram stain, various culture techniques, molecular microbiologic methods such as polymerase chain reaction (PCR), and assessment of the immune response with antibody titers or skin testing (e.g., tuberculosis). The acute phase response is the nonspecific metabolic and inflammatory response to infection, trauma, autoimmune disease, and some malignancies. Acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are commonly elevated during an infection, but are not specific for infection and do not identify any specific infection. These tests are often useful to show response to therapy (e.g., osteomyelitis).

The complete blood count frequently is obtained to identify evidence of bone marrow response to infection. The initial response to infection, especially in children, is usually a leukocytosis, which is an increase in the number of circulating leukocytes, with a neutrophilic response to bacterial and viral infections. With most viral infections, the initial neutrophilic response is transient and is followed quickly by the characteristic mononuclear response. In general, bacterial infections are associated with greater neutrophilia than are viral infections. A shift to the left is an increase in the numbers of circulating immature cells of the neutrophil series, including band forms, metamyelocytes, and myelocytes. A shift to the left indicates the rapid release of cells from the bone marrow and characteristically is seen in the early stages of infection and with bacterial infections. Transient lymphopenia at the beginning of illness and lasting 24 to 48 hours has been described with many viral infections. Atypical lymphocytes are mature T lymphocytes with larger, eccentrically placed, and indented nuclei that classically are seen with infectious mononucleosis caused by Epstein-Barr virus (EBV). Other infections associated with atypical lymphocytosis include cytomegalovirus (CMV) infection, toxoplasmosis, viral hepatitis, rubella, roseola, mumps, and some drug reactions. Eosinophilia is characteristic of tissue-invasive multicellular parasites, such as the migration of the larval stages of the parasite through skin, connective tissue, and viscera. High-grade eosinophilia (>30% eosinophils, or a total eosinophil count >3000/μL) frequently occurs during the muscle invasion phase of trichinellosis, the pulmonary phases of ascariasis and hookworm infection (eosinophilic pneumonia), and the hepatic and CNS phases of visceral larva migrans. Other common screening tests include urinalysis for urinary tract infections (UTIs),

transaminases for liver function, and lumbar puncture for evaluation of the CSF if there is concern for meningitis or encephalitis. A grouping of various tests may help distinguish viral versus bacterial infection, but definitive diagnosis requires culture or PCR.

Cultures are the mainstay of diagnosis. Blood cultures are sensitive and specific for bacteremia that may be primary or secondary to a focus (osteomyelitis, gastroenteritis, urinary tract, endocarditis). Urine cultures confirm UTI, which may be occult in young infants. CSF cultures should be obtained with any lumbar puncture. Other cultures are determined by the presence of fluid collections or masses that are suspected to be infectious. Tissue culture techniques help identify viruses and intracellular pathogens. Rapid tests are useful for preliminary diagnosis and are included in numerous bacterial, viral, fungal, and parasitic antigen detection tests. Serologic tests, using enzyme-linked immunosorbent assay (ELISA) or Western blotting, showing an IgM response, high IgG, or seroconversion between acute and convalescent sera can be used for diagnosis. Molecular detection methods, such as PCR for DNA or RNA, offer the specificity of culture, high sensitivity, and rapid results. When an unusual infection is suspected, the laboratory must be notified before the sample is obtained.

The choice of diagnostic imaging mode should be based on the location of the findings. In the absence of localizing signs and an acute infection, imaging of the entire body is rarely productive. There is often more than one suitable approach to diagnostic imaging of suspected infections. Plain x-rays are useful for the middle and lower respiratory tract, but they have been superseded by cross-sectional imaging techniques. Ultrasonography is a noninvasive, nonirradiating technique well suited to infants and children for solid organs, such as the kidneys, liver, pancreas, and spleen. It also is useful to identify soft tissue abscesses with lymphadenitis and to diagnose suppurative arthritis of the hip. CT (with contrast enhancement) and MRI (with gadolinium enhancement) allow characterization of lesions and precise anatomic localization and are the modalities of choice for the brain. CT shows greater bone detail, and MRI shows greater tissue detail. High-resolution CT is useful for complicated chest infections. Contrast studies (upper gastrointestinal series, barium enema) are used to identify mucosal lesions of the gastrointestinal tract, with CT or MRI for evaluation of appendicitis and intra-abdominal masses. A voiding cystourethrogram (VCUG) is used to evaluate for ureteral reflux, which is a predisposing factor for upper UTIs. MRI is especially useful for diagnosis of osteomyelitis, myositis, and necrotizing fasciitis. Radionuclide scans, such as technetium-99m for osteomyelitis and dimercaptosuccinic acid (DMSA) for acute pyelonephritis or chronic renal scarring, are often informative.