Epidemiology• Distributed worldwide but mostly in the tropic• mostly affect populations in rural settings and semi-urban slums• Global annual incidence of endemic human leptospirosis: 5 cases per 100 000 population• Limited studies have suggested that the median annual incidence: per 100 000 population – African Region 95.5 – Western Pacific 66.4 – Americas 12.5 – South-East Asia 4.8 – Europe 0.5• 5 to 30% of mortality
Number of Leptospirosis cases 2004 - 2010 YEAR CASE DEATH 2004 263 20 2005 378 20 2006 527 22 2007 949 22 2008 1263 47 2009 1418 62 2010 1976 69Source: Report of Morbidity & Mortality for Inpatient for the year 2004-2010 ( PER-PD206); Health Informatics Centre, MOH
Outbreak• Examples of outbreak:- athletes competing in the Eco-Challenge-Sabah 2000 in Malaysia; 44% of those who reported feeling ill met the case definition of leptospirosis. Significant risk factors included kayaking and swimming in and swallowing water from the Segama River-Recreational area in Maran, Pahang in June 2010 - 83 people involved in a search mission after one person went missing (drowned) -22 suspected with leptospirosis. 8 personsdied
Outbreak in Sarawak 2011• 148 cases of leptospirosis were recorded from Jan 1 to Dec 15 (2011), a significant increase considering that only 49 cases were recorded for the whole of 2010. -1st outbreak happened at SMK Bandar Baru Bintangor. 114 students were inflicted with mild flu- like illness. - 2nd outbreak involved 5 army recruits after they had attended a training exercise in LunduRead more: http://www.theborneopost.com/2011/12/27/13-die-of-leptospirosis-in-sarawak-this-year/#ixzz1rylzqZih
• Epidemics are typically seen during flooding, and changing environmental trends• Underreported – misdiagnosed/ undiagnosed• Age-more in 20-30 years old, rare in young children and infant- due to low exposure.• Children are particularly vulnerable to serious forms of the disease.• Sex- male > female-greater occupational exposure to infected animals and contaminated environment
Introduction• A notifiable disease in Malaysia• Caused by pathogenic spirochete of the genus leptospira • L.interrogans • L.biflexa. • Others• Leptospira strains have been divided into 23 sub groups• Pathogenic or saprophytic leptospires.• Each sub-group consists of several strains designated as serovars.• More than 260 serovars identified. 37 serovars in M’sia.
Leptospira interrogans• A species of genus Leptospira• Gram negative obligate aerobe spirochete• Finely coiled, thin, motile• Periplasmic flagellum for mobility• 2 important pathogenic serovars from this species are Canicola and Icterohaemorrhagiae.• reside in alkaline water, alkaline soil- survive in these area for months or years• also could be found in urine
Mode of transmission• Leptospira bacteria have been found in dogs, rats, livestock, mice, rabbits, frogs, fish, snakes, and certain birds and insects.• Transmission- direct contact with urine - contact with soil, water, or plants that have been contaminated by animal urine.• Leptospira bacteria can enter the body through cuts or skin damage areas or through mucous membranes.
Pathophysiology• Gains entry via intact skin or mucosa.• Multiplies in blood and tissue.• Spread to any part of the body but particularly affects the liver and kidney.• Kidney- migrates to the interstitium, renal tubules, and tubular lumen, causing interstitial nephritis and tubular necrosis.• Renal failure- Usually due to tubular damage – hypovolemia from dehydration & altered capillary permeability• Liver –Centrilobular necrosis with proliferation of Kupffer cells. Jaundice due to hepatocellular dysfunction.• Skeletal muscle- causing edema, vacuolization of myofibrils, and focal necrosis.
• Muscular microcirculation is impaired and capillary permeability is increased, with resultant fluid leakage and circulatory hypovolemia• Disseminated vasculitic syndrome may result from damage to the capillary endothelium.• Invade aqueous humor of the eye, may persist for many months, occ lead to chronic or recurrent uveitis.• The disease is most often self-limited and nonfatal.• Systemic immune response may eliminate the organism from the body but may also lead to a symptomatic inflammatory reaction that can produce secondary end- organ injury
Clinical Features• incubation period -2 - 30 days (average 10 days)• 2phases: (< 50% of cases) • Begins with flu-like symptoms then briefly asymptomatic until the second phase begins.• First phase(1 week ): Septicaemic/ Leptospiremia phase • Organism may be isolated from blood cultures, cerebrospinal fluid (CSF), and most tissues. • High, remittent fever(38-40oC) • Retroorbital headache, chills and rigors • Myalgia : paraspinal, calf, abdominal muscle • Conjuctival suffusion • Maculopapular/ purpuric skin rashes • Vomitting
• Second stage - immune or leptospiruric stage – Bodys immunologic response to infection – Circulating antibodies may be detected – Organism may be isolated from urine – It may not be recoverable from blood or CSF. – Lasts 4-30 days – Disease referable to specific organs is seen. – These organs include the meninges, liver, eyes, and kidney.• Nonspecific symptoms, i.e fever and myalgia, less severe than in the first stage and last a few days to a few weeks.• Aseptic meningitis is the most important clinical syndrome observed in the immune anicteric stage. -lasts a few days but occasionally lasts 1-2 weeks.• Meningeal symptoms develop in 50% of patients.• Mild delirium may also be seen.• Weil’s disease
Anicteric leptospirosis•milder form of the disease.•Almost 90% of patients have this type of illness.• Patients have fever, myalgia but do not have jaundice. remittent fever with chills - Calf, abdominal & lumbosacral muscles are verypainful & severely tender.• May have conjunctival suffusion- usually bilateral, mostmarked on palpebral conjunctiva, it may be associatedwith unilateral or bilateral conjunctival haemorrhage.
Other manifestations•Usually intense headache, sometimes throbbing, commonlyin frontal region, often not relieved by analgesics.•Renal- usually asymptomatic urinary abnormality i.e mildproteinuria with few casts & cells in the urine.•Pulmonary- cough & chest pain and in few cases byhaemoptysis.•Hemorrhagic tendencies are also present in some patients•All the clinical features either decrease or disappear within 2to 3 days and then they reappear.•DDX: malaria, dengue hemorrhagic fever, viral hepatitis etc.•In endemic area all cases of fever with myalgia andconjunctival suffusion should be considered as suspectedcases of leptospirosis.
Icteric leptospirosis•It is the severe form of the disease.• It is characterized by jaundice and is usuallyassociated with involvement of other organs.• About 5-10% of patients have these type ofmanifestations. • profound jaundice • renal dysfunction • hepatic necrosis • pulmonary dysfunction • hemorrhagic diathesis
SSX• General - rash, fever, bleeding, signs of hypovolemia/cardiogenic shock• Icteric - Jaundice, hepatomegaly, abdominal tenderness• Pulmonary - Cough, hemoptysis, dyspnea, respiratory distress• Neurologic - Cranial nerve palsies, confusion, changes in consciousness, delirium, other signs of meningitis• Ocular - Subconjunctival hemorrhage, uveitis, signs of iridocyclitis or chorioretinitis• Hematologic - Bleeding, petechiae, purpura, ecchymosis, splenomegaly• Cardiac - Signs of congestive heart failure, pericarditis
Investigations• WBC increased - 3-26/microL; Thrombocytopenia uncommon.• CK elevated markly• UFEME: proteinuria, pyuria, granular casts and occasionally microscopic hematuria• LFT: deranged ALT,AST in 40%, usually < 200IU/L, jaundice in weil’s syndrome• BUSE: Hyponatremia, hypokalemia• CSF - neutrophilic or lymphocytic pleocytosis with minimal to moderately elevated protein and normal glucose.• CXR- show small nodular densities, which can progress to confluent consolidation or a ground glass appearance – alveolar hemorrhage, ARDS, or pulmonary edema
Diagnosis• Culture from clinical specimen – Blood- within 10 days – CSF Within 5 - 10 days – Urine within 10-30 days• Serology-Rapid test, MAT(gold standard ), ELISA – 4X rise in titres between acute and convalescent-phase – A single titer of >1:800 is strong evidence of current or recent infection with leptospira – rapid tests, the microplate IgM ELISA and an IgM dot-ELISA dipstick test• polymerase chain reaction (PCR)
CASE CLASSIFICATIONLeptospirosis is difficult to distinguish from a number of other diseases on clinicalgrounds alone. History of possible exposure is paramount to aid clinical diagnosis.Clinical caseA case that is compatible with the following clinical description:Acute febrile illness with history of exposure to water and/or environmentpossibly contaminated with infected animal urine with ANY of the followingsymptoms:• Headache• Myalgia particularly associated with the calf muscles and lumbar region• Arthralgia• Conjunctival suffusion• Meningeal irritation• Anuria or oliguria and/or proteinuria• Jaundice• Hemorrhages (from the intestines and lungs)• Cardiac arrhythmia or failure• Skin rash• GI symptoms such as nausea, vomiting, abdominal pain, diarrhea
CASE CLASSIFICATIONProbable CaseA clinical case AND positive ELISA/other Rapid tests.Confirmed case:A confirmed case of leptospirosis is a suspected OR probable case with anyone of the following laboratory tests:• Microscopic Agglutination Test (MAT), – For single serum specimen - titre 1:400 – For paired sera - four fold or greater rise in titre• Positive PCR• Positive culture for pathogenic leptospires• Demonstration of leptospires in tissues using immunohistochemical staining• In places where the laboratory capacity is not well established, a case can beconsidered as confirmed if the result is positive by two (2) different rapiddiagnostic tests.
Treatment• Majority of the infection are self limiting• Antibiotic – Shorter duration of illness/ hospital stay, prevent urinary shedding, rapid resolution of organ impairment• General supportive care• Treatment of complication
Antibiotic• Mild/ outpatientDoxycycline 100mg BD X 1/52 (2mg/kg/day) OrAmpicillin 500-750mg 6hourly X 1/52 OrAmoxicillin 500mg 6hrly X 1/52• Severe Disease:IV penicillin G 1.5MU 6hourly X 1/52 OrIV Ceftriaxone 1g OD X 1/52 OrIV Cefotaxime 1g 6 hourly
penicillin allergy:-• azithromycin (10 mg/kg on D1; max dose 500 mg/day, followed by 5 mg/kg/day OD ; max dose 250 mg/day)Or• clarithromycin (15 mg/kg/day divided in two equal doses; max dose 1 g/day).Jarisch-Herxheimer reaction• Rare complication of treatment• release of endotoxin-like substances when large numbers of spirocete are killed by antibiotics• It is manifested by fever, chills, rigor, hypotension, headache, tachycardia, hyperventilation, vasodilation with flushing, myalgia.• It should be treated supportively
Supportive care• Patients with renal failure may require dialysis; renal function is restored in most.• Those with Weil syndrome may need transfusions of whole blood, platelets, or both.• Supportive therapy and careful management of renal, hepatic, hematologic, and CNS complications are important.
Notification• All probable and confirmed cases must be notified to the nearest Health District Office within 1 week of the date of diagnosis.• Notification of cases can be done using Rev/ 2010 form• All notified cases must be investigated using the Investigation Form
Prevention• Vaccination of domestic animals against leptospirosis provides substantial protection, but is not effective in 100 percent of animals.• Vaccine for human not widely avaiable. Vaccines commercially available – icterohaemorrhagiae, hardjo, pomona.• The major control measure available for humans – to avoid potential sources of infection such as stagnant water, water derived from run off from animal farms – rodent control – protection of food from animal contamination.
ProphylaxisPre-exposure Prophylaxis• May be considered for people at high risk of exposure to potentially contaminated sources e.g. soldiers going into jungles, rescue team• Dose:Doxycycline 200mg stat dose then weekly throughout the stayORAzithromycin 500mg stat dose then weekly throughout the stay (For pregnant women and those who are allergic to Doxycycline)• However the benefit of pre-exposure prophylaxis remains controversial where possible benefits need to be balanced with potential side effects (e.g. doxycycline induced photosensitivity, nausea, etc.)
ProphylaxisPost-Exposure• In an outbreak, there may be a role for post exposure prophylaxis for those exposed to a common source as the index case.Dose:• Doxycycline 200mg stat dose then followed by 100mg BD for 5 – 7 days for those symptomatic with the first onset of fever.OR• Azithromycin 1gm on Day-1, followed by Azithromycin 500mg daily for 2 days(For pregnant women and those who are allergic to Doxycycline)
Reference• Guideline for the diagnosis, management, prevention and Control of leptospirosis in Malaysia. Disease Control Division, Department of Public Health, MOH Malaysia. 2011 1st edition• www.uptodate.com• Guidelines for prevention and control of Leptospirosis, zoonosis division, National institute of communicable disease, Delhi 2006• Soo, Lau, Chew, Hu. Sarawak Handbook of Medical Emergencies, 3rd edition, CE publication, 2011.• http://www.who.int/topics/leptospirosis/en