Leptospirosis - DR Yuli PPT PDF

LEPTOSPIROSIS Anak Agung Ayu Yuli Gayatri Division of Tropical and Infectious Disease Department of Internal Medicine Medicine Faculty Udayana University – RS Ngoerah Block Infectious Diseases 2024 1 2 Background  Leptospirosis is one o...

LEPTOSPIROSIS Anak Agung Ayu Yuli Gayatri Division of Tropical and Infectious Disease Department of Internal Medicine Medicine Faculty Udayana University – RS Ngoerah Block Infectious Diseases 2024 1 2 Background  Leptospirosis is one of the most common zoonotic diseases worldwide  The disease is found mainly where humans come into contact with the urine of infected animals or a urine-polluted environment  Affect>1 million persons annually, causing 56.000 death It is estimated that leptospirosis is under-reported in many countries due to the difficulties of clinical diagnosis and unavailability of diagnostic laboratory services. 3  Global estimate of Morbidity and Mortality 4 Definition  Leptospirosis is a zoonosis disease cause by Leptospira interogans and/or it’s serotypes.  Its also known as: mud fever, slime fever, swamp fever, autumnal fever, infectious jaundice, field fever. 5 MODES OF TRANSMISSION  Rodents have traditionally been considered as the main reservoir of Leptospira spp.,although several other animals (such as cattle, buffaloes, dogs, pigs, goats and cats) can act as reservoirs.  Direct transmission occurs through contact with an infected animal.  Indirect transmission occurs through contact with contaminated urine, water or soil or drinking of water or ingestion of food contaminated with urine 6 of infected animals. ETIOLOGY  Ordo spirochaetales, family leptospiraceae, genus leptospira included 2 species; L. interrogans (pathogen) & L. biflexa (non pathogen)  The most infect human is L. icterohaemorrhagica. 7 Leptospira 8 Modes of Transmission  Contact transmission:Through cuts and abrasions of the skin, or through the mucous membranes of the eyes, nose and mouth with water contaminated with the urine of infected animals  Vehicle-borne transmission:Leptospirosis can occasionally also be transmitted through the drinking of water or ingestion of food contaminated with urine of infected animals  Sexual transmission:Human-to-human transmission occurs only very rarely during sexual intercourse  Congenital transmission:Trans-placentally from the mother to the foetus and via breast milk to a child 9 10 Clinical Description  The usual presentation is an acute febrile illness with headache, muscle pain (particularly calf muscle) and fatigue associated with any of the following symptoms/signs: red eyes, no or less urination, jaundice, cough, coughing blood and breathlessness, haemorrhages (from the intestines; lung bleeding is notorious in some areas), meningeal irritation, cardiac arrhythmia or failure, skin rash.  Other common symptoms include nausea, vomiting, abdominal pain, diarrhea and joint pain. 11 Incubation period and period of infectiousness  Incubation periodtypically, between 5 to 14 days (range of 2—30 days)  Period of infectiousness (the time interval during which an infected person can transmit the infection to other susceptible persons)first seven to ten days of illness. 12 Risk factors Occupational hazard Recreational hazard  Farm and agricultural  People engaging in workers. recreational water sports  Pet shop workers. (e.g, rafting, swimming,  Miners. wading, kayaking).  Campers  Veterinarians.  Sewer workers.  Abattoir workers.  Meat handlers.  Military personnel. 13 Pathogenesis  Contaminated water  leptospira enter into the body via skin abration- mucose membran (conjungtiva, oropharings, nasopharings)  blood stream (leptospiremia)  multiple organs vasculitis: leptospira adhesion with membran cells & cellular toxycity plasma leakage, extravasation & bleeding.  Multiplication in the blood & tissue leptospira may isolated from blood & cerebrospinal fluid (4-10 days of the first of 14 illness). Pathogenesis of Organ damage  Kidney: leptospira migrasion into interstitium and tubulus renalis nefritis interstitialis & nekrosis tubulus (leptospiuria 1- 4 weeks) renal failure.  Liver: sentrilobuler necrosis & proliferasion of kuppfer cells.  Lung: cause by bleeding (not due to Inflammation).  Invasion to ke skeletal tissue: oedema, vacuolisasi myofibril, & focal necrosis.  Severe leptospirosis microsirkulasion damage &increase of capillary permeabilityplasma leakage & hypovolemia.  Risk of Jarisch-Herxheimer reaction after antibiotic treatment 15 Typical course of Leptospirosis 16  Clinical syndromes MILD SEVERE  anicteric leptospirosis 85-90%  Icteric leptospirosis 10-15%  Flu like or acute undifferentiated  Weil’s disease fever after around one week  High mortality rate 5-40% fever stops but then comes back  Meningitis/meningo-encephalitis for a second phase.  Pulmonary haemorrhage with  Additional symptoms can be respiratory failure gastrointestinal pain, rash, redness of the conjunctiva.  Jaundice, bleeding tendency, renal failure haemorrhage and  Most cases are misdiagnosed infection of the heart muscle with as other febrile illness arrhythmias (historically called  This category is often self- Weil’s syndrome) are major limited Patient may not seek indicators for severity medical attention 17 Clinical Progression of Leptospiraosis 18 Groups at increased risk of severe illness (most vulnerable)  Health status (Pregnant women, people with renal disease, cancer, chronic lung or liver disease and diabetes.)  Age Mortality increases particularly in patients older than 60 years of age.  Host genetic polymorphism, immunologypeople with weakened immune systems such as those receiving chemotherapy, steroids, transplant recipients or HIV carriers  Nutrition malnutrition  Genotype of serovar of strains involved  Late definitive and supportive treatment 19 Clinical Diagnosis Anicteric “Mild” Leptospirosis  Difficult Clinical diagnosis  Mild, atypical, anicteric leptospirosis cases are often confused with other acute febrile illnesses misdiagnosed  Anicteric leptospirosis should be included in the differential diagnosis of every patient with acute fever  Risk factors associated with leptospirosis should be identified as high index of suspicion for diagnosis 20 Anicteric “ Mild” leptospirosis Differential diagnosis Influenza, Dengue Infection, Hanta virus infection, Typhoid fever, Meningitis, Uncomplicated malaria, HIV seroconversion illness, Ricketsiosis/ Murine typhus, Infectous mononucleosis, other viral infections 21 Clinical Diagnosis (2) Severe Leptospirosis  Diagnosis of severe leptospirosis is easy to recognized especially in endemic area  Most hospitalized Leptospirosis patients in the Tropic are severe icteric leptospirosis  Multi-organ involvement are common Multiorgan disfunctions  A fatal leptospirosis fatality rate 5-40%, despite in hospital treatment  Should be included in the DD of other potentially fatal infectious diseases 22 Case Definition of Leptospirosis A ‘confirmed case’ requires definitive laboratory evidence of leptospirosis infection by one of the following: 1. Isolation of pathogenic Leptospira species 2. A fourfold or greater rise in Leptospira MAT titre between acute and convalescent-phase sera obtained at least two weeks apart, and preferably conducted at the same laboratory 3. A single Leptospira MAT titre ≥400, supported by a positive ELISA IgM result 23 Diagnosis Laboratorium 24 Pulmonary involvement Pulmonary hemorrhage has been increasingly reported Lepto patients with PH highest mortality rates (50-70%) Most cases are clinically unrecognized (underdiagnosis) Clinical signs vary : sudden increase of RR to impending RF ARDS, chest pain, low Hb/Ht, hemoptysis not always found Histopathology (autopsy): diffuse intra-alveolar hemorrhage with or without alveolar damage Possible causes of death in severe leptospirosis Severe sepsis  Septic shock “irreversible” Pulmonary hemorrhage  ARDS, respiratory failure “Myocarditis”  Cardiac arrhythmias, heart failure Acute kidney injury  electrolytes disturbances, acidosis (uremic syndrome) GI bleeding hypovolemic (post-hemorrhagic) shock Intracerebral bleeding Note: Multiple causes of death may occur in one patient Icteric Leptospirosis Differential diagnosis  Severe falciparum Malaria  Severe complicated Typhoid fever  Haemorrhagic fevers with renal failure (HFRF)– Hantavirus type Dobrava  Other severe viral haemorrhagic fevers 27 Complications  Renal Failure  DIC  ARDS  myokarditis 28 Diagnosis  clinicaly  Laboratorium test: diagnostic: The disease is usually diagnosed in the laboratory by detecting antibodies, (serodiagnosis including :MAT (microscopic agglutination test), ELISA, Haemaglutination) by culturing the bacteria from blood, urine or tissues, or by demonstrating the presence of leptospira in tissues using antibodies labelled with fluorescent markers 29 Common diagnostic test for Leptospirosis 30 FAINE CRITERIA (WHO) Part A jumlah: 33 A+B > 25 Presumptive Leptospirosis 31 The WHO-SEA guidelines of Leptospirosis diagnostic 32 Appropriate specimen testing WHO/FAO/OIE Collaborating Center for Reference and Research on Leptospirosis. Coopers Plains, 2019 33 Diagnosis Other laboratory tests:  hematology: leukositosis/ normal/leucopenia, netrophylia & ESR increase, trombositopenia  urinalysis: proteinuria, lekosuria or torak/cast  Liver test: high bilirubin direct without inceasing of transaminase.  Renal Function test: increasing BUN, ureum & creatinin on patient with renal complication  Other lab test to excluded differential diagnosis banding Radiologis 34 Possible investigation findings in Leptospirosis 35 AJGP VOL. 47, NO. 3, MARCH 2018 Management  Depend on severity and stage of illness. Supportive treatment required on the severe Leptospirosis and/ or with complications.  No isolation is needed because there is almost no human to human ytransmission  Leptospirosis treated with antibiotics that should be given as early in the course of illness as possible. Usually its effective for 4- 7 days. 36 MANAGEMENT  Case treatment: Clinicians should commence empiric treatment if leptospirosis is clinically suspected. Do not wait for laboratory results  Exposure investigation: A history of possible exposure should be Sought: An accupational history, Recreational exposure, A history of contact with common host animales, Travel history)  Education; informed about the nature of the infection and the mode of transmission  Isolation and restriction: not requiredit is rarely transmissible from person to person 37  Treatment and Chemoprophylaxis 38  Leptospirosis 1. Suspect Case  Acute fever with or without headache, with:  Mascle ache  Malaise with /or without  Conjuctival suffusion and  History of contact with everything contaminated by Leptospira  For example contact history  Berjalan di daerah banjir atau genangan air.  Bertempat tinggal di daerah rawan banjir.  Higiene perseorangan kurang (tidak cuci tangan, tanpa APD dsb).  Luka terbuka / tidak diobati (termasuk kulit pecah2).  Banyak tikus dirumah atau lingkungan tempat tinggal/bekerja.  Rekreasi dalam air, olah raga air, lomba tri juang/triathlon).  Kontak dg tanah di daerah endemik spt berkebun, bertani dll.  Pekerjaan sebagai faktor risiko terpajan Leptospira. 2. Probable case Leptospirosis Unit Pelayanan Kesehatan (tanpa fasilitas Lab) Kasus Suspect disertai minimal dua dari gejala dibawah ini: - nyeri betis - batuk dengan/tanpa batuk darah - sesak nafas - ikterus - manifestasi perdarahan (ptekie, mimisan, hematemesis dll) - iritasi meningeal - anuria-oliguria dan/atau proteinuria - aritmia jantung Catatan: Kasus probable yang mengarah ke klinis berat segera dirujuk ke RS (ada dr.SpPD, plus fasilitas perawatan dialisis & ICU) Ikterus, gagal ginjal, perdarahan adalah indikator klinis Leptospirosis berat 2. Probable case Leptospirosis Unit Pelayanan Kesehatan (dengan fasilitas Lab) Kasus Suspect dg IgM positif (RDT) dengan / atau Minimal 3 dari kriteria laboratorium dibawah ini: 1. proteinuria, piuria, hematuria 2. lekositosis dg relatif neutrofilia (>80%), limfopenia 3. trombosit < 100.000 sel/mm 4. bilirubin > 2mg%; peningkatan ringan SGPT/SGOT peningkatan amilase atau CPK *) Jika ada akses rujukan ke Lab referensi Leptospirosis  Leptospirosis 3. Confirmed case (diagnosis pasti) Kasus Suspect case or Probable case with at lease one of:  Leptospira isolation from clinical sample ( blood,urine)  PCR positive  Serokonversion MAT from negativepositif or increasing 4x  Titer MAT ≥ 320 (400) on the single sample Management of Leptospirosis (1) Kasus SUSPECT dapat ditangani di Unit Pelayanan Dasar (Puskesmas/Puskesmas Pembantu) atau rawat jalan. Antibiotik untuk kasus SUSPECT: - Pilihan utama: Doksisiklin 2 x 100mg (7 hari) kecuali anak, ibu hamil, atau bila ada kontraindikasi. - Alternatif (bila tidak dapat diberikan doksisiklin): Amoksisilin 3 x 500mg/hari pada dewasa atau 10-20mg/kgBB per 8 jam pada anak (7 hari) - Bila alergi amoksisilin: diberikan makrolid Doksisiklin: aman, efek samping amat jarang (esofagitis, kulit kemerahan dll) Untuk hindari esofagitis: telan obat sesudah makan dengan air minum yg banyak jangan berbaring setelah minum obat  Management of Leptospirosis (2) PROBABLE case (yang dirawat / klinis berat) - Ceftriaxon 1-2 gram iv per hari (7 hari) - Penisilin Prokain 1.5 juta unit im per 6 jam (7hari) - Ampisilin 4 x 1 gram iv per hari (7 hari) Terapi suportif untuk: gagal ginjal, perdarahan organ (paru, saluran cerna, saluran kemih, serebral dll), gangguan neurologi, syok (kardiogenik, hipovolemik, septik)  Management of Leptospirosis (3) Supportive therapy  Keseimbangan cairan dan elektrolit  Diuretika pada keadaan oliguri  Transfusi darah (trombosit atau PRC)  Ventilator untuk pasien dg gagal nafas / ARDS  Dialisis (hemodialisis atau peritoneal dialisis) NB: Pasien sebaiknya dirawat di HND/ICU  Management of Leptospirosis (4) Semua kasus probable dengan manifestasi klinis yang mengarah ke “Leptospirosis berat” :  gagal ginjal (oliguria, anuria)  ikterus  sepsis, gagal multi-organ  perdarahan organ (paru, gastrointestinal, serebral dsb)  syok (hipovolemik dan atau septik dan/atau kardiak)  gangguan kesadaran (asidosis metabolik, meningitis aseptik dll)  harus dirujuk / dirawat di RSUD atau RS Provinsi atau RS lain dengan fasilitas yang memadai Catatan: Kasus probable yg “ringan” misal dg nyeri betis, bisa rawat jalan atau dirawat di Puskesmas Immunity There are two types of immunity:  - Active immunity results when exposure to an agent triggers the immune system to produce antibodies to that disease .- Passive immunity is provided when a person is given antibodies to a disease rather than producing them through his or her own immune system 48 Routine prevention activities  Promote public awareness of possible transmission risk when undertaking recreational water-based activities including wading, swimming and white water rafting.  Provide staff working in hazardous occupations with appropriate protective equipment to prevent contamination, including when working with potentially infected animals, their tissues or secretions.  Ensure cuts and skin abrasions are covered by watertight dressings and encourage frequent hand washing during exposure to high risk settings or environments.  Implement rodent control measures around homes, outbuildings and other areas attracting rodents, e.g. grain or animal feed stores and refuse disposal areas.  Animal owners should seek veterinary advice about preventing leptospirosis in companion animals or livestock. Vaccination aims to reduce the burden of disease in animals but can also reduce the potential for human exposure. 49 Prognostic factors for death in leptospirosis  Mortality increase in age and Weil’s disease  Icteric patients mortality 5% among patients age group