LEPTOSPIROSISdr. Ardhiyanti PR

BAGIAN BIOKIMIA FAKULTAS KEDOKTERANUNIVERSITAS ISLAM AL AZHAR MATARAM2014

PendahuluanPenyakit yang disebabkan leptospira sp.Termasuk zoonosisMasalah di negara berkembang (tropis & subtropis) ec.curah hujan tinggi dan sanitasi lingkungan buruk.Resiko tinggi pd pekerja tambang, petani, petugas survei hutan, dokter hewan, ptgs Lab & tentara.Resevoir : tikus,babi,sapi,kuda,anjing,kucing, kelelawar,musang,tupai dan landak.*

EpidemiologiSeringkali tidak terdiagnosa & tidak dilaporkan.Insidens di Amerika 0,02-0,04 kasus/ 100.000 penduduk (th 1985-1994).Daerah resiko tinggi : Kep.Caribia, Amerika tengah & Selatan, Asia tenggara & kep. Pasifik.*

Leptospirosis in the worldIncidence of severe cases 300,000-500,000 per year*

Causative Agenthighly motile flexible

helical or coiled

aerobic bacteria

with bent or hooked ends

Yasuda et al. Deoxiribonucleic acid relatedness between seogroups and serovars in the family Leptospiraceae. Int J Sys Bacteriol 1987; 407-415Spirochaeta icterohaemorrhagiae*

killed at 500C in 10 mins or 600C in 10 seconds

susceptible to dessication, hypochlorite disinfectants and pH outside of 6.2 to 8.0

acid urine, non-aerated sewage and polluted water

Sensitivity*

TRANSMISSION CYCLE OF LEPTOSPIROSISINDIRECT CONTACTDIRECT CONTACT contact with moist soil or vegetation contaminated with urine of infected animals swimming or wading in floodwaters accidental immersion occupational abrasion thru tissue or urine of infected animals ingestion of contam food droplet aerosol inhalation*

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PatofisiologiPenularan dari hewan bisa langsung atau melalui air dan tanah yg tercemar urin hewan.Sering terjadi saat banjir,membersihkan selokan atau sungai.Kuman masuk melalui kulit yang tidak intake atau selaput lendir mata,mulut & hidung, masuk dalam darah, proliferasi dan menyebar ke organ2 & jar,tubuh.Pada ginjal,menetap di tubulus, membentuk koloni, masuk dalam urin*

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Gejala klinisGejala amat bervariasi, mulai ringan seperti sakit flu sampai berat & menyebabkan kematian.Masa inkubasi sekitar 2-20 hari, rata-rata 10 hari

Fase gejala leptospiraStadium Pertama (fase leptospiremia) : Demam menggigil Sakit kepala Malaise Muntah Konjungtivitis Rasa nyeri otot betis dan punggung Gejala-gejala diatas akan tampak antara 4-9 hari Gejala yang Kharakteristik : Konjungtivitis tanpa disertai eksudat serous/porulen (kemerahan pada mata) Rasa nyeri pada otot-betis*

Stadium Kedua (fase imun) : Terbentuk antibodi di dalam tubuh penderita Gejala yang timbul lebih bervariasi dibandingkan dengan stadium pertama Apabila demam dengan gejala-gejala lain timbul kemungkinan akan terjadi meningitis. Stadium ini terjadi biasanya antara minggu kedua dan keempat. Stadium ketiga (rekonvalesen) : - terjadi pada minggu ke-2 sampai ke-4 - demam dan nyeri otot berangsur hilang.*

Anicteric leptospirosis First stage 3 -7 days(septicemic) Second stage 0 days - 1 month (immune)Fevermyalgiaheadacheabdominal painvomitingconj. suffusion

meningitisuveitisrashBlood cultureCSF cultureUrine culture:*

Penyakit WeilSatu jenis leptospirosis dengan tampilan klinis berat (10% kasus).Penyebab L.interrogans serovar icterohaemorrhagia.Gejala pd fase I seperti leptospirosis biasa, muncul pd hari ke-3 smp ke-6, penurunan demam kekambuhan beberapa minggu.Hati membesar transaminase, bilirubin,proteinuri meningkat dan azotemia.Dapat terjadi perdarahan epistaksis, hemoptisis, hematemesis-melena,perdarahan adrenal dan pneumonitis hemorargik.Perdarahan otak kematian*

Icteric leptospirosis (Weils disease) First stage 3 -7 days(septicemic)Second stage 10 - 30 days (immune)Feverjaundicehemorrhagerenal failuremyocarditisBlood cultureCSF cultureUrine culture*

feverImportantClinical findingsLeptopresent*

Anicteric LeptospirosisIcteric Leptospirosis Weil's SyndromeFirst stage 3-7 days SepticemicSecond stage 0-1 month ImmuneFirst stage 3-7 days SepticemicSecond stage 10-30 days Immune

Myalgia/MyositisAbdominal painConjunctival suffusionMeningitisUveitisRashFeverJaundice Hemorrhage Renal failure MyocarditisMeningitis Pulmonary hemorrhage Respiratory failure Blood CSF

urine Blood CSF

urine

DIFFERENT STAGES OF LEPTOSPIROSIS*

LEVEL AND DURATION OF IgM ANTIBODIES AT DIFFERENT TIME INTERVALS*

Komplikasi leptospirosis

Pada hati : kekuningan yang terjadi pada hari ke 4 dan ke 6 Pada ginjal : gagal ginjal yang dapat menyebabkan kematian. Pada jantung : berdebar tidak teratur, jantung membengkak dan gagal jantung yang dapat mengikabatkan kematian mendadak. Pada paru-paru : batuk darah, nyeri dada, sesak nafas. Perdarahan karena adanya kerusakan pembuluh darah dari saluran pernafasan, saluran pencernaan, ginjal, saluran genitalia, dan mata (konjungtiva). Pada kehamilan : keguguran, prematur, bayi lahir cacat dan lahir mati. *

Pemeriksaan laboratoriumDarah rutin mungkin ditemukan lekositosis, peningkatan LED,ureum kreatinin, transaminase, bilirubin serta anemia.Mikroskop lapangan gelap atau imunofluoresen dapat menemukan leptospira.Kultur darah atau cairan spinal dapat positif pd 7-10 hari pertama, selanjutnya leptospira dapat ditemukan dalam urin.Serologi dengan MAT Pemeriksaan lain : ELISA,PCR,Dipstik*

Mikroskop lapangan gelapMikroskop imunofluoresen

TerapiObat : - Penisilin G 1,5 jt U/6 jam selama 7 hari - Doxysiklin 2x100 mg selama 7 hari - Ampisilin 750 mg/6 jam selama 7 hari - Amoksilin 4x500 mg/hari selama 7 hari

Dialisis atau ventilator jika diperlukan.

Pencegahan pada yg beresiko tinggi seperti pekerja tambang atau tentara yang bertugas didaerah endemis dengan doxysiklin 200 mg sekali seminggu*

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Leptospirosis*

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*Leptospirosis actually occurs worldwide. It has a wide geographic distribution and occurs in tropical, subtropical and temperate climatic zones. Most South and Southeast Asian countries are endemic to leptospirosis. It is considered as the most widespread zoonosis.The disease is considered to be occupationallyrelated where yearly incidence and outbreaks attributed to farmers in rice producing regions have been reported. Abattoir workers, sewer workers and miners have also been implicated. In developed countries, cases have been recorded in relation to recreational activities. But frequent outbreaks occur following natural calamities like typhoon especially in developing countries like the Philippines.

*The discoverers named the organism Spirochaeta icterohaemorrhagiae and described them as highly motile, flexible, helical aerobic bacteria with one or both ends of the organism bent or hooked.

*Leptospires are grown at 28C to 30C with pH in the range of 7-8. At 30C the generation time varies between 7-12 h and yields of 100 to 200 million cells per ml can be obtained in 7-10 days. The pathogenic leptospires can survive for many days or even months in wet soil and fresh water with neutral or slightly alkaline pH. It has also been shown to survive in animal tissue kept at low temperature. In salt water the survival time is only few hours. The following conditions listed in this slide will inactivate the leptospires.

The natural habitat of leptospires is the renal tubules of carrier animals. The animal hosts of leptospires are broadly categorized as carrier hosts, in whom the carrier state is temporary ranging from a few months to years, and reservoir hosts in whom the carrier state is life long. The reservoir hosts are the primary source of leptospires. They infect both animals and human beings. The carrier hosts who get infection either from reservoir hosts or from other carrier hosts can also act as the source of infection to human beings. Man to man transmission is very rare and leptospiral infection in human beings is a dead end of transmission chain. Therefore, the source of infection both in animals and humans is the carrier animal, though infection may actually occur through various environmental vehicles.There are two modes of transmission of the organism: the direct and indirect means.Direct transmission occurs when leptospires from tissues, body fl uids or urine of acutely infected or asymptomatic carrier animals enter the body of the new host and initiate infection. Infection may occur from direct contact with the tissues or urine of infected animals and occasionally through ingesting food contaminated with urine of infected animals or from droplet aerosol inhalation of contaminated fluids.Indirect transmission occurs when an animal or human being acquires leptospirosis from environmental leptospires, originating in the urine of excretor animals.Infection in humans may also occur indirectly when the bacteria come into contact with the skin (especially if damaged) or the mucous membranes. It can also result from contact with moist soil or vegetation that is contaminated with the urine of infected animals, or with contaminated water as a result of swimming or wading in floodwaters, accidental immersion or occupational abrasion. This is the most common way of infection with the leptospires.

*The environment plays a very important role in the transmission of the organism. In the tropical region where there is plenty of rainfall, it is often difficult to avoid exposure of the people to animals or contaminated environment especially since the bacteria is well adapted to the environment. Although leptospires are susceptible to various environmental factors, particularly drying, acidic pH, salinity and presence of detergents and other bactericidal agents, they can survive for long periods in water and wet soil under favourable conditions.

****Leptospirosis can present with a wide spectrum of clinical manifestations, ranging from asymptomatic to fatal. The incubation period is usually 7-14 days but may range from 2-21 days. Sub clinical and mild infections are quite common. Only a small proportion of cases develop severe leptospirosis or what is known as Weils disease.Other complications include acute respiratory failure, severe pulmonary haemorrhage, myocarditis,meningitis and renal failure. Uveitis has recently been recognized as a late complication of leptospirosis. Pulmonary haemorrhage is perhaps the most fatal complication in leptospirosis. The other most common fatal complication is renal failure.

As mentioned earlier, leptospirosis may follow a biphasic course: septicemic and immune phase

During the fi rst 10 days, there isa phase of leptospiraemia when the leptospiresmultiply in blood and spread to different organs.The chances of recovery of leptospires fromblood or other tissues or body fl uids is usuallyhigh during this stage.

This phase is followedby immune phase or leptospirurea phase whenthe organisms are excreted in the urine. Inthis phase, chances of recovery of organismsfrom the blood is low. The ideal specimen forisolation or demonstration of leptosires duringimmune phase is urine.*Immunity to leptospires is mostly humoral in nature.The antibodies usually develop within 2-12 daysafter the onset of illness. IgM antibody startsappearing early in the course of the diseaseand reaches detectable levels within one weekor as early as on third or fourth day of illness.They reach peak levels during third or fourthweek and then decline slowly over months andbecome undetectable within six months. RarelyIgM may persist at low level for several years. The antibodies usually develop within 2-12 daysafter the onset of illness. IgM antibody startsappearing early in the course of the diseaseand reaches detectable levels within one weekor as early as on third or fourth day of illness.They reach peak levels during third or fourthweek and then decline slowly over months andbecome undetectable within six months. RarelyIgM may persist at low level for several years.

In a small proportion of patients (about 10%)IgM antibodies may not develop at detectablelevel and the fi rst appearing antibody may be IgG.

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