3. Factors Responsible For The Emergence Of Leptospirosis
4. Modes of Transmission
5. High Risk Groups
6. Clinical Manifestations
7. Case Classifications
7.1 Suspected case
7.2 Probable case
7.3 Confirmed case
11.1 Hospital Based Surveillance
11.2 Serosurveillance (Laboratory Based Surveillance)
11.3 Active Surveillance
12. Outbreak Response
13. Prevention and Control
vi..List Of Annex
Annex 1 Collection and Transportation of Sample (Clinical & Environmental) and
Criteria for Water Sampling
1a - Laboratory Request Form from IMR
1b - Laboratory Request Form from MKAK (MKAK-BPUI-U01)
1c - Laboratory Request Form from MKAK (MKAK-PER-104B-02/1)
Annex 2a Rev/2010 Form (Notification Form) in National Language
Annex 2b Rev/2010 Form (Notification Form) in English
Annex 3 Leptospirosis Case Investigation Form
Annex 4 Example of Leptospirosis database format
Annex 5 Outbreaks Preliminary Report BKP/WABAK/01/2005
Annex 6 Flow Chart of Notification of cases/outbreak
Annex 7a Example of Risk Assessment Form (Man made Recreational Park)
Annex 7b Example of Risk Assessment Form (Natural Recreational Park)
Annex 8a Example of Health Hazard Signage In National Language
Annex 8b Example of Health Hazard Signage In English
Leptospirosis is a common public health problem worldwide with an estimated anuual incidence ranging from 0.1 to 1 per 100 000 per year in temperate climates to 10 or more per 100 000 per year in the humid tropics (1). The estimated case-fatality rates in different parts of the world have been reported to range from <5% to 30% (1). These figures however are probably grossly underestimated because in many countries especially those where the disease is highly endemic, diagnostic capabilities are not readily available resulting in significantly poor surveillance and reporting of leptospirosis (2). Leptospirosis is an infectious disease with broad range of clinical manifestations, ranging from mild flu-like illness to very severe disease with haemorrhagic manifestations and multiorgan failures. Severe leptospirosis commonly resulted in case fatalities if aggressive managements are not instituted at an early stage (1). In Malaysia, an increasing number of reported cases and outbreaks which had resulted in significant number of deaths have been observed over the past decade. There is a great need for improvement is case surveillance, in order to define strategies in control and prevention of case morbidity and mortality related to this disease. Thus, under the Prevention and Control of Infectious Diseases Act 1988 leptospirosis has been gazetted as a notifiable disease on 9 December 2010. This guideline is drawn up through joint efforts of various Ministry of Health experts to Provide information on the disease and guides on diagnostic criteria, management of diagnostic samples and notification procedures.
The aims of this guideline include:
• To increase awareness among the healthcare personnel on the importance of leptospirosis.
• To guide in diagnostic procedures in order to obtain early diagnosis so that prompt and appropriate management can be instituted and prevention and control measures can be carried out at the earliest possible stage to reduce morbidity and mortality.
• To quantify and monitor leptospirosis disease burden and its distribution throughout the country.
• To obtain good epidemiological and clinical data on leptospirosis which is important for improving strategies in prevention and control of the disease.
Leptospirosis is an infectious disease caused by pathogenic spirochete bacteria of the genus leptospira that are transmitted directly or indirectly from animals to human (i.e., azoonotic disease). Pathogenic leptospires belong to the species Leptospira interrogans, which is subdivided into more than 200 serovars with 25 serogroups (3). The leptospiral serovars are naturally carried in the renal tubules of rodents, wild and
Leptospirosis is usually a seasonal disease that starts at the onset of the rainy season and declines as the rainfall recedes. Sporadic cases may occur throughout the year with outbreaks associated with extreme changing weather events such as heavy rainfall and flooding (2).
The incidence of Leptospirosis was not well documented in Malaysia due to it not being a notifiable disease, previously. Currently available leptospirosis country data for Malaysia is based on the Report of Morbidity and Mortality for Ministry of Health Hospitals. Since these cases were from hospital records, it is not known whether they were sporadic cases or related to clusters (epidemiological link).
3. FACTORS RESPONSIBLE FOR THE EMERGENCE OF LEPTOSPIROSIS
The conditions that are favourable for maintenance and transmission of Leptospirosis are:
a) Reservoir and carrier hosts
Leptospirosis has a very wide range of natural rodent, and non-rodent reservoir hosts especially rats, cattle, dogs, foxes, rabbits, etc. The animals act as carriers of the leptospires and excrete large number of Leptospires in their urine, thus responsible for the contamination of large and small water bodies as well as soil.
b) Flooding, drainage congestion
Flooding and drainage congestion may be risk factors for contamination of water bodies with infected animal urine. Water logged areas may force rodent population to abandon their burrows and contaminate the stagnant water by their urine.
c) Animal-Human Interface
The potential for infection increases through exposure from occupational or recreational activities without proper protection. Poor cleanliness/sanitation in recreational areas may attract animal host such as rodent thus increases the risk of contamination. These may be due to poor maintenance of facilities, improper disposal of waste and public attitude/ apathy.
d) Human host risk factors
Several sections of the population are more susceptible to infection such as those not previously exposed to the bacteria in their environment (naïve immunities), and those with chronic disease and open skin wounds.
4. MODES OF TRANSMISSION
Infection is acquired from contact through skin, mucosa/ conjunctiva with water or soil contaminated with the urine of rodents, carrier or diseased animals in the environment. Ingestion of contaminated water may also cause infection. There is no documentation of human to human transmission.
5. HIGH RISK GROUPS
Exposure depends on chance contacts between human and infected animals or a contaminated environment through occupational and/or recreational activities. Some groups are at higher risk to contract the disease such as:
• Workers in the agricultural sectors
• Sewerage workers
• Livestock handlers
• Pet shops workers
• Military personnel
• Search and rescue workers in high risk environment
• Disaster relief workers (e.g. during floods)
• People involved with outdoor/recreational activities such as water recreational activities, jungle trekking, etc.
• Travelers who are not previously exposed to the bacteria in their environment especially those travelers and/or participants in jungle adventure trips or outdoor sport activities
• People with chronic disease and open skin wounds.
6. CLINICAL MANIFESTATIONS
The incubation period is usually 10 days, with a range of 2 to 30 days (3). The clinical manifestations are highly variable. Typically, the disease presents in four broad clinical categories (1):
(i) a mild, influenza-like illness (ILI);
(ii) Weil's syndrome characterized by jaundice, renal failure, haemorrhage and myocarditis with arrhythmias;
(iii) meningitis / meningoencephalitis;
(iv) pulmonary haemorrhage with respiratory failure.
Clinical diagnosis is difficult because of the varied and non-specific presentation. Confusion with other diseases, e.g. dengue and other haemorrhagic fevers, malaria, typhoid, melioidosis, influenza, etc. is particularly common in the tropics. Presentations may also overlap as the infection progresses.
7. CASE CLASSIFICATION
Leptospirosis is difficult to distinguish from a number of other diseases on clinical
grounds alone. History of possible exposure is paramount to aid clinical diagnosis.
7.1 Clinical case
A case that is compatible with the following clinical description: Acute febrile illness with history of exposure to water and/or environment possibly contaminated with infected animal urine with ANY of the following
• Myalgia particularly associated with the calf muscles and lumbar region
• Conjunctival suffusion
• Meningeal irritation
• Anuria or oliguria and/or proteinuria
• Hemorrhages (from the intestines and lungs)
• Cardiac arrhythmia or failure
• Skin rash
• Gastrointestinal symptoms such as nausea, vomiting, abdominal pain, diarrhea
7.2 Probable Case
- A clinical case AND positive ELISA/other Rapid tests.
7.3 Confirmed case:
- A confirmed case of leptospirosis is a suspected OR probable case with any one 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 (samples should be taken within 10 days of disease onset)
• Positive culture for pathogenic leptospires (blood samples should be taken within 7 days of onset and urine sample after the 10th day)
• Demonstration of leptospires in tissues using immunohistochemical staining (e.g. in post mortem cases)
• In places where the laboratory capacity is not well established, a case can be considered as confirmed if the result is positive by two (2) different rapid diagnostic tests.
Cases that require confirmation are:-
• Hospitalized cases
• All suspected leptospirosis death cases
Notes on Laboratory Diagnosis
• In cases which needed to be confirmed (hospitalized and suspected death cases), serum samples should be sent for confirmation by MAT. The MAT is considered the "gold standard" or cornerstone of serodiagnosis because of its unsurpassed diagnostic (serovar/serogroup) specificity in comparison with other currently available tests. Second serum samples must be taken to detect fourfold or greater rise in titre.
• Simple serological screening method can be done using the rapid test kit for Leptospira. Reminder: any leptospirosis rapid test kit to be used must be validated/approved by IMR.
• The ELISA/other rapid tests detect IgM antibodies. The presence of IgM antibodies may indicate current or recent leptospirosis. A patient’s serum may be positive 5 to 10 days after onset of symptoms but not usually before this. Reminder: IgM-class antibodies may remain detectable for several years.
• If the initial sample was taken at an early stage in the infection, the ELISA test may be positive but MAT negative. Therefore a follow-up sample is required. Test may be negative if the serogroup of the infecting strain does not react with the Patoc 1 serovar strain used as the antigen. If antibiotics are given from the beginning of the illness, the immune and antibody response may be delayed.
• The diagnosis is also confirmed by isolation of Leptospires from blood (first 7 days) or CSF (days 4-10) during the acute illness, from urine (days 7) and from tissue samples, by using special media. Inoculation of young guinea pigs hamsters or gerbils can also be carried out for isolation of leptospires.Leptospires die quickly in urine. Clean urine sample should be inoculated into appropriate culture medium not more than 2 hours after voiding. Survival in acid urine may be increased by making it neutral.
For postmortem diagnosis, in addition to serology and culture, leptospires can bedemonstrated in tissues using PCR or immunohistochemical staining, notably by direct immunofluorescence.
Note: Biphasic nature of leptospirosis and relevant investigations at different stages of disease. Specimens 1 and 2 for serology are acute convalescent-phase sample which may facilitate detection of a delayed immune response, and 4 and 5 are follow information, such as the presumptive infecting serogroup Refer to Annex 1 for collection and transportation of clinical and environmental samples for leptospirosis and criteria for water sampling. Acute-phase specimens, 3 is a ponse, follow-up samples which can provide epidemiological
For the purpose of 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 (Annex 2).
• All notified cases must be investigated using the Investigation Form (Annex 3).
• Early treatment with antibiotics is essential.
• Severe cases are usually treated with high doses of IV C-penicillin (2 M units 6 hourly for 5-7 days). Less severe cases treated orally with antibiotics such as doxycycline (2 mg/kg up to 100 mg 12-hourly for 5-7 days), tetracycline, ampicillin or amoxicillin.
• Third generation cephalosporins, such as ceftriaxone and cefotaxime, and quinolone antibiotics may also be effective. Jarisch-Herxheimer reactions may occur after the start of antimicrobial therapy.
• Monitoring and supportive care as appropriate, e.g. dialysis, mechanical ventilation.
Penicillin G 100000U/kg/dose IV 6hourly x7days
Alternative ...8yrs: Doxycycline 4mg/kg/dose oral 12hourly x 7days <8yrs:
Ampicillin 75-100mg/kg/dose oral 6hourly x 7days or Amoxicillin 50mg/kg/dose oral 6-8hourly x 7days
Penicillin: use in moderate to severe disease caution in impaired renal function Jarisch-Herxheimer reaction has been described in patients with leptospirosis
Doxycycline: used for only mild disease can cause permanent discoloration of teeth
Ampicillin/Amoxycillin: 2nd line agent or for pts < 8yrs.
The cost effectiveness and risk versus benefits of antibiotic prophylaxis for leptospirosis remains unclear. If prophylaxis is considered, the possible options include:
• May be considered for people at high risk of exposure to potentially contaminated sources e.g. soldiers going into jungles, rescue team, persons involved in activities in possible high risk areas e.g. adventurous sports.
Doxycycline 200mg stat dose then weekly throughout the stay OR Azithromycin 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.)
Empirical treatment for Post-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.
• Azithromycin 1gm on Day-1, followed by Azithromycin 500mg daily for 2 days (For pregnant women and those who are allergic to Doxycycline)
The role of prophylaxis in children has not been adequately studied.
Reliable data on the incidence and prevalence of leptospirosis in many parts of the world are scarce and most probably overlooked and underreported (1). Studies may be performed on selected groups (rice farmers, meat workers, etc.) in a population that is likely to be exposed to leptospires. While the incidence rate for the whole of the population in an area may be low, it may be very high in a selected risk group.
Preventive methods may be focused on selected risk groups. In order to obtain the actual disease burden leptospirosis is made a notifiable disease in Malaysia under the Prevention and Control of Communicable Diseases Act 1988 since 2010. For the purpose of surveillance, the State Health Departments must compile a database for Leptospirosis. This database must have information on possible source of infection (Annex 4).
11.1 Hospital-based surveillance The diagnosis should be confirmed by laboratory tests as the clinical manifestations of leptospirosis are often atypical. Leptospirosis should be suspected in patients presenting with symptoms such as fever, severe headache, prostration, aching muscles or conjunctival suffusion, or patients presenting with signs of aseptic meningitis, adult respiratory distress syndrome with pulmonary haemorrhage, kidney failure or jaundice.
Data should be collected on the age, sex, occupation and exposure history (place, date, conditions of animal contact or contact with contaminated environment) of the patient. Laboratory methods are required to confirm the diagnosis. Isolation followed by typing is essential for surveillance as it provides information about the leptospires circulating in a certain area. In addition, typing data can be compared with the clinical manifestations of the disease in the area concerned. Serology is also important but, because of cross reactions, the information obtained is of limited value in terms of causative serovars.
Mild cases may not be admitted to hospital, so hospital-based surveillance may result in a bias towards severity in assessing the public health importance of leptospirosis. Very severe cases may also be missed as patients may die at an early stage of the disease before the diagnosis can be established. Especially in these cases, culture,
PCR and immunohistochemistry may be useful methods of demonstrating the leptospiral aetiology in post-mortem samples.
11.2 Serosurveillance (Laboratory based surveillance) The detection of persisting antibodies by the microscopic agglutination test (MAT) may give an indication of the prevalence of leptospirosis in an area. It is best to carry out the MAT using a panel of antigens that is representative of the locally circulating leptospires. If the local strains are not fully known, a broad panel with representative strains of all currently known serogroups should be used. Persisting antibodies from a past infection are usually serogroup-specific. Titres to serovars used as antigens and 12 their frequency of distribution may give information on the prevalence of these serovars or on antigenically similar serovars belonging to the same serogroup.
ELISA tests provide information only on recent or current cases and no information on the circulating serovars because they use a broadly reactive so-called genus-specific antigen to check for IgM antibodies.
11.3 Active Surveillance In certain circumstances, active surveillance can be carried out and helpful in determining the incidence of leptospirosis in a community. Such active surveillance may provide valuable information on the "normal" incidence of leptospirosis in a community and may identify serovars present in the area. Arrangement with public health laboratories may enable samples to be analysed.
12. OUTBREAK RESPONSE
An outbreak is defined as more than one probable or confirmed cases of leptospirosis with an epidemiological link within one incubation period. • All cases must be investigated and control measures taken wherever possible. During an outbreak, the District Health Office should also investigate the clinical cases. All symptomatic cases in an outbreak should be admitted to hospital for laboratory confirmation and treatment.
• All outbreaks must be notified to National Crisis Preparedness and Response Centre (CPRC) KKM by phone or text/sms to on-call surveillance at 013-6699700 or email to email@example.com
• Send all outbreak preliminary reports to the CPRC, Disease Control Division by e-mail, text/sms, and fax using the BKP/WABAK/01/2005 Form (Annex 5) within 24 hours.
• A final report must be produced after 1 month the outbreak ends and sent to CPRC, Disease Control Division.
Refer Annex 6 for Flow Chart of Notification of cases/outbreak. 13
13. PREVENTION & CONTROL
Because of the large number of serovars, variety of infection sources and the wide differences in transmission conditions, the prevention and control of leptospirosis is complex. Effective prevention and control can be achieved by controlling the reservoir or reducing infection in animal reservoir populations such as dogs or livestock via treatment or vaccination of the animals. Control of wild animals may be difficult. Preventive measures must be based on knowledge of the groups at particular risk of infection and the local epidemiological factors.
Prevention and control should be targeted at:
(a) The infection source;
(b) The route of transmission between the infection source and the human host;
(c) Prompt and proper treatment of infection.
13.1 Preventive and Control Measures
• Health Education: Health education activities are to be carried out to create awareness among the public about the disease and motivate them to take
preventive actions. This needs to be done through multiple strategies in order to reach the specific target groups. This could be done by using the electronic, printed and interpersonal means. It is important to ensure that messages delivered are relevant, timely and culturally acceptable to the target groups. A proper needs assessment has to done to ascertain the target groups’ needs in order to alleviate their fear and concerns.
• Risk assessment of possible contaminated water sources/bodies. Examples of risk assessment forms used by Perak State Health Department are attached in Annex 7a & 7b.
Reminder: The formats are flexible and changes can be made according to the situation in respective states.
• Alert public or users regarding the hazards of possible contaminated areas. Health hazard warning signage (examples as in Annex 8a & 8b) should be posted in areas found to be contaminated through environment risk assessment (co-operation with local authorities).
• Persons with occupational or recreational exposure to potentially contaminated water or soil should:-
o Wear waterproof protective clothing such as rubber boots and gloves.
o Cover skin lesions with waterproof dressings.
o Wash with clean water immediately after exposure.14
o Seek immediate medical treatment if develop symptoms within the incubation period.
• Advise public to keep their homes and premises free from rodents.
• Advise people to vaccinate their pets against leptospirosis.
• Promote cleanliness at the recreational areas, food premises as well as housing area.
• Promote interagency collaboration such as with local authorities, Wildlife
Department (PERHILITAN), Department of Veterinary Services (JPV), National Training Service Department (JLKN), etc. to maintain cleanliness in the respective environmental settings, especially rodent control. 15
1. World Health Organization. Human leptospirosis: guidance for diagnosis, surveillance and control; 2003.
2. World Health Organization. Report of the First Meeting of the Leptospirosis Burden Epidemiology Reference Group. Geneva; 2010
3. Heymann DL, editor. Control of Communicable Diseases Manual. 18th ed. Washington, DC: American Public Health Association; 2004.
4. Levett PN. Leptospirosis. Clinical Microbiology Reviews. 2001;14(2):296-326.