LeptospirosisLeptospirosis prepared byprepared by

Dr. Abdulaziz SuleimanDr. Abdulaziz SuleimanDepartment of MedicineDepartment of MedicineMedical Collage / DuhokMedical Collage / Duhok

Leptospirosis is one of the most Leptospirosis is one of the most common zoonotic diseases, favoured common zoonotic diseases, favoured by a tropical climateby a tropical climate

Spirochetal diseaseSpirochetal disease Systemic infection manifested as widespread Systemic infection manifested as widespread

vasculitisvasculitis Leptospira interrogansLeptospira interrogans is pathogenic is pathogenic

for humans.for humans.

Microbiology and epidemiology

The most frequent hosts are The most frequent hosts are rodentsrodents L. ictero-haemorrhagiaeL. ictero-haemorrhagiae is the is the

classical parasite of rats.classical parasite of rats. The organisms persist indefinitely in The organisms persist indefinitely in

the convoluted tubules of the kidney the convoluted tubules of the kidney and are shed into the urine in massive and are shed into the urine in massive numbers, but infection is numbers, but infection is asymptomatic in the host. asymptomatic in the host.

Microbiology and epidemiology

Reservoires of InfectionReservoires of Infection

RatsRats DogsDogs Rodents including rabbitsRodents including rabbits Wild animalsWild animals CatsCats

Leptospires can enter their human Leptospires can enter their human hosts through hosts through intact skinintact skin or or mucous mucous membranesmembranes, but entry is facilitated by , but entry is facilitated by cuts and abrasions. cuts and abrasions.

Prolonged immersion in Prolonged immersion in contaminated water will also favour contaminated water will also favour invasion, as the spirochaete can invasion, as the spirochaete can survive in water for months. survive in water for months.

epidemiology

Sources of Human InfectionsSources of Human Infections

Contaminated Water or soil from Contaminated Water or soil from infected urineinfected urine

Direct animal contactsDirect animal contacts Occupational exposure : farmers, Occupational exposure : farmers,

vets, abattoire workersvets, abattoire workers

PathogenesisPathogenesis

Entry sitesEntry sites : : skin woundsskin wounds or or abrasionsabrasions in hand in hand and feet and and feet and mucous membranesmucous membranes, conjunctiva, , conjunctiva, nasal, oralnasal, oral

BacteremiaBacteremia involving the entire body including involving the entire body including eye, CSFeye, CSF

Systemic effectSystemic effect and vasculitis due to endotoxin and vasculitis due to endotoxin (hyaluronidase) (hyaluronidase)

Hemorrhagic necrosisHemorrhagic necrosis esp. in liver, lung, and esp. in liver, lung, and kidneys kidneys jaundice, ARF, hemorrhages jaundice, ARF, hemorrhages

Clinical featuresClinical features

After a relatively brief bacteraemia, invading After a relatively brief bacteraemia, invading organisms are distributed throughout the body, organisms are distributed throughout the body, mainly in mainly in kidneys, liver, meninges and kidneys, liver, meninges and brain. brain.

The incubation period averages The incubation period averages 1-2 weeks1-2 weeks. . Four main clinical syndromes can be discerned Four main clinical syndromes can be discerned

Bacteraemic leptospirosisBacteraemic leptospirosis

Following incubation period of 7-14 daysFollowing incubation period of 7-14 days High spiking fever, headaches, myalgia, High spiking fever, headaches, myalgia,

arthralgias, vomiting and diarroheaarthralgias, vomiting and diarrohea Lasting 4 – 7 daysLasting 4 – 7 days Proteinuria and increased creatinnineProteinuria and increased creatinnine Conjunctival congestion is the only Conjunctival congestion is the only

notable physical sign.notable physical sign. Organism detectable but serologic diagnosis not Organism detectable but serologic diagnosis not

possiblepossible

Aseptic meningitisAseptic meningitis

Caused by Caused by L. canicolaL. canicola infection, infection, very difficult to distinguish from viral very difficult to distinguish from viral

meningitis. meningitis.

Laboratory findingsLaboratory findings include a include a neutrophil leucocytosis, neutrophil leucocytosis, abnormal LFTsabnormal LFTs presence of albumin and casts in the presence of albumin and casts in the

urine. urine.

Weil’s DiseaseWeil’s Disease Icteric leptospirosisIcteric leptospirosis

Less common but severe formLess common but severe form characterised by fever, haemorrhages, characterised by fever, haemorrhages,

jaundice and renal impairment. jaundice and renal impairment. Conjunctival hyperaemia is a frequent Conjunctival hyperaemia is a frequent

feature. feature. transient macular erythematous rash, but transient macular erythematous rash, but

the characteristic skin changes are purpura the characteristic skin changes are purpura and large areas of bruising.and large areas of bruising.

In severe cases there may be epistaxis, In severe cases there may be epistaxis, haematemesis and melaena, or bleeding into haematemesis and melaena, or bleeding into the pleural, pericardial or subarachnoid the pleural, pericardial or subarachnoid spaces.spaces.

Weil's disease may also be associated with Weil's disease may also be associated with myocarditis,myocarditis, encephalitisencephalitis and and aseptic aseptic meningitismeningitis

Oliguric renal failureOliguric renal failure and and Liver dysfunctionLiver dysfunction dominate the dominate the clinical pictureclinical picture

Conjunctival hemorrhage Conjunctival hemorrhage in leptospirosisin leptospirosis

Pulmonary syndromePulmonary syndrome

This syndrome has long been This syndrome has long been recognised in the Far East. recognised in the Far East.

It is characterised by haemoptysis, It is characterised by haemoptysis, patchy lung infiltrates on chest X-ray, patchy lung infiltrates on chest X-ray, and respiratory failure. and respiratory failure.

A polymorphonuclear leucocytosis , A polymorphonuclear leucocytosis , thrombocytopenia and elevated creatine thrombocytopenia and elevated creatine kinase. kinase.

In jaundiced patients there is mild In jaundiced patients there is mild hepatitis and the prothrombin time may hepatitis and the prothrombin time may be a little prolonged. be a little prolonged.

The CSF in leptospiral meningitis shows The CSF in leptospiral meningitis shows a variable cellular response, a a variable cellular response, a moderately elevated protein land normal moderately elevated protein land normal glucose.glucose.

Diagnosis

Diagnosis

Blood culturesBlood cultures are positive if taken are positive if taken before the 10th day of illness. before the 10th day of illness.

Leptospires appear in the urine during Leptospires appear in the urine during the 2nd week of illness, the 2nd week of illness,

Serological testsSerological tests are diagnostic if are diagnostic if seroconversion or a fourfold increase in seroconversion or a fourfold increase in titre is demonstrated. titre is demonstrated.

Detection of leptospiral DNA by Detection of leptospiral DNA by PCR PCR is is possible in blood in early symptomatic possible in blood in early symptomatic disease, and in urine from the 8th day of disease, and in urine from the 8th day of illness and for many months thereafter. illness and for many months thereafter.

Differential DiagnosisDifferential Diagnosis

VH feverVH fever Rickettsial disease : Scrub typhus, Rickettsial disease : Scrub typhus,

murine typhusmurine typhus Acute viral hepatitisAcute viral hepatitis SepsisSepsis InfluenzaInfluenza Aseptic MeningitisAseptic Meningitis

TreatmentTreatment

Early anti-microbial therapy is Early anti-microbial therapy is importantimportantshorten the course and prevent shorten the course and prevent carrier statecarrier state

oral oral doxycycline doxycycline (100 mg 12-hourly for 1 (100 mg 12-hourly for 1 week) week)

intravenous intravenous penicillinpenicillin (900 mg 6-hourly for 1 (900 mg 6-hourly for 1 week) is effective but may not prevent the week) is effective but may not prevent the development of renal failure.development of renal failure.

May cause “ May cause “ Jarish-HuxheimerJarish-Huxheimer type type reaction”reaction”

Parenteral Parenteral ceftriaxoneceftriaxone (1 g daily) is as (1 g daily) is as effective as penicillin. effective as penicillin.

PreventionPrevention

Vaccination of domestic animalsVaccination of domestic animals Rodent controlRodent control Protective gloves and bootsProtective gloves and boots Avoid swimming in contaminated Avoid swimming in contaminated

waterswaters Vaccination in endemic regionVaccination in endemic region

Question 1. The following infections may be acquired by the following means

tetanus-respiratory droplets or dust listeriosis-eating contaminated cheese legionellosis-water aerosols schistosomiasis-via penetration of the

skin leptospirosis-via rat urine

Question 2 Recognised features of brucellosis include

a characteristically rapid response to penicillins

fever, night sweats and back pain splenomegaly oligoarthritis and spondylitis thrombocytopenia

Relapsing feverRelapsing fever

Relapsing feverRelapsing fever

two distinct types of relapsing fever two distinct types of relapsing fever due to systemic infection by borrelial due to systemic infection by borrelial spirochaetesspirochaetes::

LouseLouse--borne relapsing fever borne relapsing fever TickTick--borne relapsing feverborne relapsing fever

Louse-borne relapsing feverLouse-borne relapsing fever

The human body louse, The human body louse, Pediculus humanusPediculus humanus, , causes itching. causes itching.

Borreliae Borreliae ((B. recurrentisB. recurrentis)) are liberated from are liberated from the infected lice when they are crushed during the infected lice when they are crushed during scratching, which also inoculates the borreliae scratching, which also inoculates the borreliae into the skin. into the skin.

The borreliae multiply in the blood, where they The borreliae multiply in the blood, where they are abundant in the febrile phases, and invade are abundant in the febrile phases, and invade most tissues.most tissues.

Onset is sudden with high fever. Onset is sudden with high fever. injected conjunctivae, a petechial rash, injected conjunctivae, a petechial rash,

epistaxis and herpes labialis. epistaxis and herpes labialis. jaundice is commonjaundice is common tender and palpable spleen and livertender and palpable spleen and liver severe serosal and intestinal haemorrhagesevere serosal and intestinal haemorrhage mental confusion and meningism. mental confusion and meningism. The fever ends in crisis between the 4th and The fever ends in crisis between the 4th and

10th days, often associated with profuse 10th days, often associated with profuse sweating, hypotension, and circulatory failure. sweating, hypotension, and circulatory failure.

there are one or more relapsesthere are one or more relapses

Clinical features

Investigations and managementInvestigations and management

The organisms are demonstrated in the blood The organisms are demonstrated in the blood during fever either by during fever either by dark ground microscopydark ground microscopy of a wet film or by of a wet film or by staining thick and thin staining thick and thin films. films.

The safest treatment is The safest treatment is procaine penicillinprocaine penicillin 300 300 mg i.m., followed the next day by 0.5 g mg i.m., followed the next day by 0.5 g tetracycline.tetracycline.

DoxycyclineDoxycycline 200 mg once by mouth has the 200 mg once by mouth has the advantage of also being curative for typhusadvantage of also being curative for typhus

The patient, clothing and all contacts must be The patient, clothing and all contacts must be freed from lice. freed from lice.

Tick-borne relapsing feverTick-borne relapsing fever

Soft ticks Soft ticks transmit transmit B. duttoniB. duttoni through saliva while through saliva while feeding on their host. feeding on their host.

Those sleeping in Those sleeping in mud housesmud houses are at risk, as the tick are at risk, as the tick hides in crevices during the day and feeds on humans hides in crevices during the day and feeds on humans during the night. during the night.

RodentsRodents are the reservoir in all parts of the world are the reservoir in all parts of the world except East Africa, where humans are the reservoir. except East Africa, where humans are the reservoir.

Clinical manifestationsClinical manifestations are similar to the are similar to the louse-borne disease but spirochaetes are louse-borne disease but spirochaetes are detected in fewer patients on dark field detected in fewer patients on dark field microscopy.microscopy.

A 7-day course of treatment with either A 7-day course of treatment with either tetracyclinetetracycline (500 mg 6-hourly) or (500 mg 6-hourly) or erythromycinerythromycin (500 mg 6-hourly) is needed. (500 mg 6-hourly) is needed.

Question 3. The typical features of leptospirosis include

incubation period of 1-3 months exposure risk in abattoirs, farms and inland

waterways fever, severe myalgia, headache and

conjunctival suffusion meningitis in Leptospira icterohaemorrhagiae

rather than L. canicola infection possible diagnosis by examination of the urine

PlaguePlague

PlaguePlague

is caused by is caused by Yersinia pestisYersinia pestis, a small , a small Gram-negative bacillusGram-negative bacillus that is spread that is spread between between rodents by their fleasrodents by their fleas. .

If domestic rats become infected, infected If domestic rats become infected, infected fleas may bite humans. fleas may bite humans.

Epidemics of plague, such as the Epidemics of plague, such as the 'Black 'Black Death',Death', have occurred since ancient have occurred since ancient times. times.

It is often said that the first sign of plague It is often said that the first sign of plague is the is the appearance of dead rats. appearance of dead rats.

Bubonic plagueBubonic plague

most common form of the disease,most common form of the disease, onset is usually suddenonset is usually sudden rigor, high fever, dry skin and severe headache. rigor, high fever, dry skin and severe headache. pain and swelling at the site of the affected lymph pain and swelling at the site of the affected lymph

nodes begin. nodes begin. The groin is the most common site of this The groin is the most common site of this 'bubo','bubo',

swollen lymph nodes and surrounding tissue swollen lymph nodes and surrounding tissue in the majority of patients toxaemia quickly in the majority of patients toxaemia quickly

increases with a rapid pulse, hypotension and increases with a rapid pulse, hypotension and mental confusionmental confusion. .

The spleen is usually palpableThe spleen is usually palpable. .

Septicaemic plagueSepticaemic plague

Those not exhibiting a bubo usually Those not exhibiting a bubo usually deteriorate rapidly and have a high deteriorate rapidly and have a high mortality. mortality.

a rapid pulse, hypotension and a rapid pulse, hypotension and mental confusionmental confusion..

The elderly are more prone to this form The elderly are more prone to this form of illness. of illness.

Pneumonic plaguePneumonic plague

primary infection in the lung, primary infection in the lung, the onset of disease is very sudden, with the onset of disease is very sudden, with

cough and dyspnoea and massive cough and dyspnoea and massive hemoptysis, highly infective sputum. hemoptysis, highly infective sputum.

Developed cyanosed and dies. Developed cyanosed and dies.

InvestigationsInvestigations

The organism may be The organism may be cultured cultured from from blood, sputum and bubo aspirates. blood, sputum and bubo aspirates.

The diagnosis may be confirmed by The diagnosis may be confirmed by seroconversion seroconversion or a or a single high titresingle high titre (> 128) of (> 128) of anti-F1 antibodiesanti-F1 antibodies in serum in serum

ManagementManagement

treatment must be started as soon as treatment must be started as soon as samples have been collected for laboratory samples have been collected for laboratory diagnosis. diagnosis.

StreptomycinStreptomycin (1 g 12-hourly) or (1 g 12-hourly) or

gentamicingentamicin (1 mg/kg 8-hourly) is the (1 mg/kg 8-hourly) is the drug of choice. drug of choice.

Tetracycline Tetracycline (500 mg 6-hourly) and (500 mg 6-hourly) and

chloramphenicolchloramphenicol (12.5 mg/kg 6-hourly) (12.5 mg/kg 6-hourly) are alternatives. are alternatives.

Question 4. In patients with rubella infection

the RNA virus spreads by the faecal-oral route

a prolonged fever is typical infectivity is present for 7 days before and

after the rash sub-occipital lymphadenopathy is typical the risk of serious fetal damage is < 5%

after the 16th week of pregnancy

Tularaemia Tularaemia

It is caused by a highly infectious It is caused by a highly infectious Gram-negative bacillus, Gram-negative bacillus, Francisella Francisella tularensis.tularensis...

Wild rabbits, rodents, and Wild rabbits, rodents, and domestic dogs or cats are some of domestic dogs or cats are some of the many potential reservoirs, and the many potential reservoirs, and ticks, mosquitoes or other biting ticks, mosquitoes or other biting flies are the vectors.flies are the vectors.

TularaemiaTularaemia

Infection is introduced either through Infection is introduced either through • an arthropod or animal bite or an arthropod or animal bite or • via contact with infected animals, via contact with infected animals, soil or water through skin abrasions. soil or water through skin abrasions.

Clinical presentationClinical presentation

'ulceroglandular''ulceroglandular' most common variety of most common variety of the disease (70-80%), characterised by the disease (70-80%), characterised by skin ulceration with regional skin ulceration with regional lymphadenopathy.lymphadenopathy.

pulmonary tularaemiapulmonary tularaemia result from result from inhalation of the infected aerosols, inhalation of the infected aerosols, presenting as pneumonia. presenting as pneumonia.

OculoglandularOculoglandular

Investigations and managementInvestigations and management

Demonstration of a single high titre (≥ Demonstration of a single high titre (≥ 1:160) or a fourfold rise in 2-3 weeks in 1:160) or a fourfold rise in 2-3 weeks in the tularaemia tube agglutination test the tularaemia tube agglutination test confirms the diagnosis. confirms the diagnosis.

Treatment Treatment consists of a 7-10-day course of consists of a 7-10-day course of parenteral aminoglycosides, parenteral aminoglycosides,

streptomycinstreptomycin (7.5-10 mg/kg 12-hourly) or (7.5-10 mg/kg 12-hourly) or

gentamicingentamicin (1.7 mg/kg 8-hourly). (1.7 mg/kg 8-hourly).

NocardiosisNocardiosis

Nocardiosis is an uncommon Gram-Nocardiosis is an uncommon Gram-positive bacterial infection caused by positive bacterial infection caused by aerobic actinomycetes of the genus aerobic actinomycetes of the genus NocardiaNocardia. .

They can cause localised or systemic They can cause localised or systemic suppurative disease in suppurative disease in immunocompromised humans, immunocompromised humans, especially especially lung and brain lung and brain abscesses. abscesses.

TreatmentsTreatments

Co-trimoxazoleCo-trimoxazole is the treatment of choice is the treatment of choice third-generation cephalosporins and third-generation cephalosporins and

carbapenems have also been used carbapenems have also been used successfully. successfully.

For severe infections an aminoglycoside For severe infections an aminoglycoside such as such as amikacinamikacin is usually added. is usually added.

Oral treatment is usually continued for a Oral treatment is usually continued for a year if there is CNS involvement.year if there is CNS involvement.

Surgical drainage of large abscesses may Surgical drainage of large abscesses may be necessary. be necessary.

Actinomyces israeliiActinomyces israelii

Actinomyces israeliiActinomyces israelii can cause deep can cause deep infection in the head and neck, and infection in the head and neck, and also suppurating disease in the pelvis also suppurating disease in the pelvis associated with intrauterine associated with intrauterine contraceptive devices (IUCDs). contraceptive devices (IUCDs).

Treatment is usually with Treatment is usually with penicillin or penicillin or doxycycline. doxycycline.