A study was carried out on 16 cases of leptospirosis with acute renal failure (ARF) detected in adult patients admitted into the Medical and Nephrology wards of the General Hospital, Kuala Lumpur, over a four-year period from 1980 to 1983. Most of the cases were male, Malays and older adults. The predominant infecting serovars were L. celledoni (of the serogroup L. javanica and L. pomona (of the L. pomona serogroup]. All the cases survived, including those who required peritoneal dialysis. The sensitised erythrocyte lysis (SEL) antibody prevalence rate of the chronic renal failure cases (10.4%) was found to be similar to that of the healthy population in West Malaysia (12. 7%), confirming the observation by other workers that leptospirosis is not an important cause of chronic renal failure.
Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira species (Leptospiraceae). LipL32 is an abundant lipoprotein from the outer membrane proteins (OMPs) group, highly conserved among pathogenic and intermediate Leptospira species. Several studies used LipL32 as a specific gene to identify the presence of leptospires. This research was aimed to study the characteristics of LipL32 protein gene code, to fill the knowledge gap concerning the most appropriate gene that can be used as antigen to detect the Leptospira. Here, we investigated the features of LipL32 in fourteen Leptospira pathogenic strains based on comparative analyses of their primary, secondary structures and 3D modeling using a bioinformatics approach. Furthermore, the physicochemical properties of LipL32 in different strains were studied, shedding light on the identity of signal peptides, as well as on the secondary and tertiary structure of the LipL32 protein, supported by 3D modelling assays. The results showed that the LipL32 gene was present in all the fourteen pathogenic Leptospira strains used in this study, with limited diversity in terms of sequence conservation, hydrophobic group, hydrophilic group and number of turns (random coil). Overall, these results add basic knowledge to the characteristics of LipL32 protein, contributing to the identification of potential antigen candidates in future research, in order to ensure prompt and reliable detection of pathogenic Leptospira species.
Pancytopaenia is a rare clinical presentation of severe leptospirosis. We would like to report a case of severe leptospirosis that progressed to pancytopaenia despite initial penicillin therapy. The patient needed a second course of antibiotic with doxycycline to improve his persistent symptoms and cytopaenia. Persistent pancytopaenia in severe leptospirosis and its management were reviewed.
There is a need for identification of new infection markers against common Leptospira isolates in Malaysia. To achieve this goal, seven-day-old cultures of Leptospira interrogans serogroup Icterohemorrhagiae (L44) and Leptospira interrogans serogroup Javanica (L55) were used for antigen preparation by sequential extraction method using 40 mM Tris, 8M Urea and 2M thiourea. Immunoblot analysis of the antigens were performed using serum samples from 46 local patients with confirmed acute leptospirosis, 28 patients with other infections and 14 healthy controls. The patients serum samples used in this study contained heterologous antibody against a number of different leptospira serovars. A strong IgM reactivity to a broad diffuse band of 10-15 kDa was observed. Combining results using L44 and L55 antigens showed sensitivity of 80.4% and specificity of 95.2% for detection of leptospirosis. Proteinase K and periodate treatment indicated that the band is likely to be lipopolysaccharide (LPS) in nature. This study showed that the 10-15 kDa antigen could potentially be useful for serodiagnosis of acute leptospirosis in Malaysia.
This qualitative study aimed to explore the misconceptions, knowledge gaps and constructs of leptospirosis among 72 respondents from rural and urban districts in two states of Malaysia. We conducted focus group discussions and data were examined using thematic analyses. The layman term of 'rat urine disease' contributed the most to the misconceptions regarding leptospirosis. There were gaps in the knowledge among urban and rural respondents in the two states, with the majority of subjects demonstrating a poor understanding of the disease. Construction of knowledge about leptospirosis relied mostly on the information provided by mass and social media; reading materials; word-of-mouth publicity; observations; experiences; and knowledge sharing among families, friends, and communities. The study findings may provide the foundation for the development of educational materials that may reduce the gaps in knowledge, and thereby improve health literacy and enhance preventive health behaviours for avoiding leptospirosis.
This paper reviews the literature on human leptospirosis in Malaysia from its first description in 1925 until the present day. Fletcher diagnosed the first case of human leptospirosis in Malaysia in 1925. Following Fletcher, many investigations on human leptospirosis in Malaysia disclosed a high prevalence of infection. These investigations indicated that the disease was endemic in the country. Examination of 1993 suspected human cases of leptospirosis by Tan indicated 28 % of the cases were positive. In a recent survey, 2190 serum samples from patients with different clinical manifestations in the country disclosed 12.6% were positive for antibodies to leptospires. The risk to leptospiral infection with respect to occupation, location, sex, race and age groups was demonstrated. Both civilians and military personnel were affected. Thirty-seven serovars from thirteen serogroups have been identified in the country. Recent studies on animal leptospirosis showed that the disease was highly endemic in the animal population. It is considered that the majority of leptospirosis cases in humans were due to association of man with animals and disease-infected environment.
This paper reviews the literature on leptospirosis in Malaysia from its first description in 1928 until the present day. Most of the early reports were on investigations of leptospirosis in wildlife and man and up-to-date, thirty-seven leptospiral serovars from thirteen serogroups have been bacteriologically identified. The thirteen serogroups are: Australis, Autumnalis Bataviae, Canicola, Celledoni, Grippotyphosa, Hebdomadis, Icterohaemorrhagiae, Javanica, Pomona, Pyrogenes, Sejroe and Tarassovi. Rats have been ascribed as the principal maintenance host of leptospires in Malaysia. However, serovars from the Pomona, Pyrogenes and Sejroe serogroups have yet to be isolated from rats. It is considered that the majority of leptospirosis cases in man were due to association of man with an environment where rats were plentiful. Recent investigations on domestic animals disclosed a high prevalence of infection in cattle and pigs and they were suspected as being the maintenance host for serovar hardjo and pomona respectively. There is ample scope for research in leptospirosis, particularly in the epidemiology and control of the disease in domestic animals. The strategy to control the infection in domestic animals and man in Malaysia is bound to be different from that of the temperate countries, basically due to the presence of a large number of leptospiral serovars in wildlife, further confounded by geographical and financial constraints.
A 20-year-old, previously healthy woman, presented with high fever, headache and myalgia 3 days after her return from a holiday in Southeast Asia. Laboratory data on admission demonstrated a pronounced increase in plasma creatinine, marked thrombocytopenia and moderately elevated liver aminotransferases. After having ruled out malaria, dengue fever was primarily suspected and supportive intravenous fluid therapy was initiated. Still, 1 day after admission, platelet counts dropped even further and she became anuric although she did not appear hypovolemic. On day 2 after admission, urine production commenced spontaneously and the patient slowly recovered. All laboratory test results had returned to normal approximately 2 months later. Serological analysis for dengue fever was negative. It turned out that the patient had been trekking in the jungle while in Thailand and we, therefore, analyzed serology for Leptospira spirochetes which was clearly positive. The patient was diagnosed with leptospirosis which is a serious condition associated with a high mortality when complicated by acute renal failure. Differential diagnoses in patients with acute renal failure and tropical infections are reviewed. The importance of early recognition of leptospirosis, and prompt treatment with antibiotics in suspected cases, is emphasized.
Considerable progress has been made in the field of leptospiral vaccines development since its first use as a killed vaccine in guinea pigs. Despite the fact that the immunity conferred is restricted to serovars with closely related lipopolysaccharide antigen, certain vaccines have remained useful, especially in endemic regions, for the protection of high-risk individuals. Other conventional vaccines such as the live-attenuated vaccine and lipopolysaccharide (LPS) vaccine have not gained popularity due to the reactive response that follows their administration and the lack of understanding of the pathogenesis of leptospirosis. With the recent breakthrough and availability of complete genome sequences of Leptospira, development of novel vaccine including recombinant protein vaccine using reverse vaccinology approaches has yielded encouraging results. However, factors hindering the development of effective leptospiral vaccines include variation in serovar distribution from region to region, establishment of renal carrier status following vaccination and determination of the dose and endpoint titres acceptable as definitive indicators of protective immunity. In this review, advancements and progress made in LPS-based vaccines, killed- and live-attenuated vaccines, recombinant peptide vaccines and DNA vaccines against leptospirosis are highlighted.
Icteric patients with clinical and biochemical evidence of liver disease, admitted into various hospitals in Malaysia, were investigated to determine the cause of their infection. Of these patients, 11.0% (16/145) were found positive for IgM anti-HAV (EIA), 4.1% (6/145) for IgM anti-HBc (EIA), 1.0% (1/102) for IgM anti-CMV (ELISA), 17.2% (16/64) for rising titres of leptospiral agglutinin, and none for heterophile antibody of EBV. Hepatitis NANB accounted for 67.9% of cases. The mean serum transaminases (ALT and AST) values in patients with hepatitis A and B were higher (more than 500IU) than in patients with leptospirosis or non-A, non-B hepatitis, whereas serum bilirubin levels were higher in patients with hepatitis A and leptospirosis than in patients with hepatitis B.
From October 13 to October 21, 1999, a total of 46 males, aged 8 to 19 years, were admitted to Beaufort Hospital after swimming in the creek near an oil palm plantation in Kampung (Kg) Kebatu, Beaufort. Thirty (30) presented with symptoms including fever, vomiting, bodyache, giddiness, headache, chest pain and cough, while 16 others, were asymptomatic. One, a 15 year old boy, died from haemorrhagic shock secondary to pulmonary haemorrhage. The onset of the illness was from 11 October to 19 October 1999. A case-control study found that the outbreak was associated with swimming in the creek (p<0.0001). A total of 44 paired sera samples were sent for microscopic agglutination test (MAT), 5 pairs showed sero-conversion, 3 pairs had 4 fold rise in titre and 18 pairs were positive at >320. The findings indicated that Leptospirosis was the cause of the outbreak of this illness and the contaminated creek water was the source of the infection. The occurrence of flooding and stagnation in the creek following the heavy rainfall during the first week of October 1999 could have contributed to the timing of the outbreak.
Here, we investigated an outbreak of leptospirosis among reserve military recruits that occurred following a survival exercise in the Hulu Perdik forest within the Hulu Langat district, Kuala Lumpur, Malaysia. Blood samples from the 12 patients that presented symptoms for febrile illness on clinical examination were subjected to laboratory investigation, comprising Lepto IgM rapid test, IgM ELISA, and microscopic agglutination test (MAT). All these patients were interviewed for possible risk factors for leptospirosis. Rodent trapping and environmental sampling for possible isolation of leptospires in the outbreak site was performed. The isolated leptospires were genetically characterized and investigated for the potential epidemiological link with human leptospirosis. Among the 12 patients, two (2/12; 16.6%) were confirmed positive for leptospirosis by microscopic agglutination test (MAT with titers 400-800; serovar autumnalis and hardjobovis). Two Leptospira species from rodents (L. interrogans and L. borgpetersenii) and two from the environment (L. kmetyi and L. wolffii) were identified. The possible epidemiological link between human serovars and animal Leptospira species indicates rodents as the potential reservoir while the environment (soil and water) serves as a transmission route. This investigation highlights the robust presence of pathogenic leptospires on Malaysian environment and rodents which may present the risk of infection, especially among high-risk individuals. Hence, occupational risk individuals are cautioned to observe appropriate preventive measures including prophylaxis and seek immediate medical attention for any illness following similar activities.
In recent years leptospirosis has been shown to be an important cause of human febrile illness in Malaya. Studies were therefore undertaken to determine its animal reservoirs and the factors influencing spread of infection from them to man and domestic animals. This paper presents the board picture obtained. A wide range of animal species were trapped in forest localities, ricefield areas, areas of scrub and cultivation and in several towns and villages. The maintenance hosts of leptospirosis in Malaya appear to be mainly or entirely rats, although evidence of infection has been found throughout the animal kingdom. Some rat species have characteristics which suggest that they are better maintenance hosts than others. Evidence was found of practically every serogroup of leptospires infecting animals in Malaya. Altogether 104 strains were isolated and identified, and 155 animals were found to have serological evidence of infection. Of 1763 rodents examined, 194 had evidence of infection, and 41 of 1083 other animals. A serum survey of domestic animals showed the highest incidence of antibodies to be in goats and the lowest in oxen.
In a previous paper the authors reported on the methods and zoogeographical background of a survey of animal leptospirosis in Malaya, giving a broad analysis of results. In the present paper the localities studied in towns and villages, in ricefields, in secondary forest and scrub and in primary forest are compared in detail. In towns and villages infection rates in rats were low, except in a seaport town where the invading R. norvegicus was heavily infected. In ricefields infection is maintained in R. argentiventer, alone or in association with R. exulans. In secondary forest and scrub there is overlap with forest species and the main hosts of leptospires appear to be R. exulans and R. jalorensis. In primary forest giant rats and, to a lesser degree, spiny rats are the main hosts.Ground-living rats appear to be better maintenance hosts than those scrambling on vegetation or arboreal rats. With some exceptions the incidence of infection of a rat species in an area was found to be in direct relation to the proportion that species formed of the total rat population. The critical number of rats for maintenance of leptospirosis in an area is estimated to be about two rats of the maintenance species per hectare.
In previous papers it has been demonstrated that ground-dwelling rats are the principal reservoir of leptospirosis in Malaya. The present paper considers the distribution of infection by sex and weight in the ten principal rat species. There appears to be a general tendency for females to be infected more frequently than males, but significant differences were demonstrated only in R. sabanus (more than three times as many females as males infected) and R. whiteheadi. In Malaya, where seasonal changes are minimal, weights can be used as a good index of age in rats. In rat species with a low incidence of infection the incidence appeared to rise steadily with age. In species with a medium incidence the infection rate rose at first with age, fell in the 6-8-month age-group, and then rose again. In high-incidence species the rate rose rapidly from the second month.There appear to be three types of enzootic infection; (1) intensive transmission of a single serogroup in a crowded population of rats of a single species (transmission probably being through urinary contamination of damp soil); (2) low-intensity transmission of several serogroups among ground-rats frequenting wet places (probably with urinary transmission); and (3) low-intensity transmission of several serogroups among ground-rats in dry places (the transmission may be venereal).