Dataset Information

Molecular characterisation and disease severity of leptospirosis in Sri Lanka.

ABSTRACT: Leptospirosis is a re-emerging zoonotic disease all over the world, important in tropical and subtropical areas. A majority of leptospirosis infected patients present as subclinical or mild disease while 5-10% may develop severe infection requiring hospitalisation and critical care. It is possible that several factors, such as the infecting serovar, level of leptospiraemia, host genetic factors and host immune response, may be important in predisposition towards severe disease. Different Leptospira strains circulate in different geographical regions contributing to variable disease severity. Therefore, it is important to investigate the circulating strains at geographical locations during each outbreak for epidemiological studies and to support the clinical management of the patients. In this study immunochromatography, microscopic agglutination test and polymerase chain reaction were used to diagnose leptospirosis. Further restriction fragment length polymorphism and DNA sequencing methods were used to identify the circulating strains in two selected geographical regions of Sri Lanka. Leptospira interrogans, Leptospira borgpetersenii and Leptospira kirschneri strains were identified to be circulating in western and southern provinces. L. interrogans was the predominant species circulating in western and southern provinces in 2013 and its presence was mainly associated with renal failure.

SUBMITTER: Bandara KK

PROVIDER: S-EPMC4501411 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Molecular characterisation and disease severity of leptospirosis in Sri Lanka.

Bandara Kanchana Kumari KK Weerasekera Manjula M Gunasekara Chinthika P CP Ranasinghe Nilantha N Marasinghe Chamil C Fernando Neluka N

Memorias do Instituto Oswaldo Cruz 20150609 4

Leptospirosis is a re-emerging zoonotic disease all over the world, important in tropical and subtropical areas. A majority of leptospirosis infected patients present as subclinical or mild disease while 5-10% may develop severe infection requiring hospitalisation and critical care. It is possible that several factors, such as the infecting serovar, level of leptospiraemia, host genetic factors and host immune response, may be important in predisposition towards severe disease. Different Leptosp ...[more]

PMID: 26061234

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Project description:Leptospirosis is considered a neglected tropical disease despite its considerable mortality and morbidity. Lack of prediction remains a major reason for underestimating the disease. Although many models have been developed, most of them focused on the districts situated in the wet zone due to higher case numbers in that region. However, leptospirosis remains a major disease even in the dry zone of Sri Lanka. The objective of this study is to develop a time series model to predict leptospirosis in the Anuradhapura district situated in the dry zone of Sri Lanka. Time series data on monthly leptospirosis incidences from January 2008 to December 2018 and monthly rainfall, rainy days, temperature, and relative humidity were considered in model fitting. The first 72 months (55%) were used to fit the model, and the subsequent 60 months(45%) were used to validate the model. The log-transformed dependent variable was employed for fitting the Univariate seasonal ARIMA model. Based on the stationarity of the mean of the five variables, the ARDL model was selected as the multivariate time series technique. Residuals analysis was performed on normality, heteroskedasticity, and serial correlation to validate the model. The lowest AIC and MAPE were used to select the best model. Univariate models could not be fitted without adjusting the outliers. Adjusting seasonal outliers yielded better results than the models without adjustments. Best fitted Univariate model was ARIMA(1,0,0)(0,1,1)12,(AIC-1.08, MAPE-19.8). Best fitted ARDL model was ARDL(1, 3, 2, 1, 0),(AIC-2.04,MAPE-30.4). The number of patients reported in the previous month, rainfall, rainy days, and temperature showed a positive association, while relative humidity was negatively associated with leptospirosis. Multivariate models fitted better than univariate models for the original data. Best-fitted models indicate the necessity of including other explanatory variables such as patient, host, and epidemiological factors to yield better results.

Project description:BackgroundLeptospirosis is a bacterial zoonosis. Leptospirosis incidence (LI) in Sri Lanka is high. Infected animals excrete leptospires into the environment via their urine. Survival of leptospires in the environment until they enter into a person and several other factors that influence leptospirosis transmission are dependent upon local weather. Past studies show that rainfall and other weather parameters are correlated with the LI in the Kandy district, Sri Lanka. El Niño Southern Oscillation (ENSO), ENSO Modoki, and the Indian Ocean Dipole (IOD) are teleconnections known to be modulating rainfall in Sri Lanka. There is a severe dearth of published studies on the correlations between indices of these teleconnections and LI.MethodsWe acquired the counts of leptospirosis cases notified and midyear estimated population data of the Kandy district from 2004 to 2019, respectively, from weekly epidemiology reports of the Ministry of Health and Department of Census and Statistics of Sri Lanka. We estimated weekly and monthly LI of Kandy. We obtained weekly and monthly teleconnection indices data for the same period from the National Oceanic and Atmospheric Administration (NOAA) of the USA and Japan Agency for Marine-Earth Science and Technology (JAMSTEC). We performed wavelet time series analysis to determine correlations with lag periods between teleconnection indices and LI time series. Then, we did time-lagged detrended cross-correlation analysis (DCCA) to verify wavelet analysis results and to find the magnitudes of the correlations detected.ResultsWavelet analysis displayed indices of ENSO, IOD, and ENSO Modoki were correlated with the LI of Kandy with 1.9-11.5-month lags. Indices of ENSO showed two correlation patterns with Kandy LI. Time-lagged DCCA results show all indices of the three teleconnections studied were significantly correlated with the LI of Kandy with 2-5-month lag periods.ConclusionsResults of the two analysis methods generally agree indicating that ENSO and IOD modulate LI in Kandy by modulating local rainfall and probably other weather parameters. We recommend further studies about the ENSO Modoki and LI correlation in Sri Lanka. Monitoring for extreme teleconnection events and enhancing preventive measures during lag periods can blunt LI peaks that may follow.

Project description:BackgroundLeptospirosis is a tropical disease associated with life threatening complications. Identifying clinical and investigation-based parameters that predict mortality and morbidity is vital to provide optimal supportive care.MethodsWe conducted an observational study in an endemic setting, in the southern Sri Lanka. Consecutive patients having complicated leptospirosis were recruited over 18 months. Clinical, investigational and treatment data were collected and the predictors of mortality were analysed.ResultsOut of 88 patients having complicated leptospirosis, 89% were male. Mean age was 47yrs (±16.0). Among the total major complications 94.3% had acute kidney injury, 38.6% pulmonary haemorrhages, 12.5% fulminant hepatic failure, 60.2% hemodynamic instability and 33% myocarditis. An acute significant reduction of haemoglobin (Hb) was observed in 79.4% of patients with pulmonary haemorrhage. The mean of the highest haemoglobin reduction in patients with pulmonary haemorrhage was 3.1g/dL. The presence of pulmonary haemorrhage (PH) and hemodynamic instability within first 48 hours of admission significantly predicted mortality (p<0.05) in severe leptospirosis. Additionally, within first 48 hours of admission, elevated SGOT (AST), presence of atrial fibrillation, presence of significant haemoglobin reduction, higher number of inotropes used, prolonged shock, invasive ventilation and admission to ICU significantly predicted mortality. Out of major complications during the first week after admission, pulmonary haemorrhage and fulminant hepatic failure (FHF) combination had significant adjusted odds of mortality (OR = 6.5 and 4.8, p<0.05). Six patients with severe respiratory failure due to PH underwent ECMO and four survived. The overall mortality in complicated leptospirosis was 17%. In PH and FHF, the mortality rate was higher reaching 35.4% and 54.5%, respectively.ConclusionsWithin first 48 hours of admission, major complications such as pulmonary haemorrhage and haemodynamic instability and other parameters such as atrial fibrillation, acute haemoglobin reduction, elevated SGOT level could be used as early parameters predictive of mortality in severe leptospirosis. PH and FHF during the first week of admission in leptospirosis are associated with high morbidity and mortality requiring prolonged ICU care and hospitalisation. Above parameters could be used as parameters indicating severity for triaging and intensifying treatment. Using ECMO is a plausible treatment option in patients with severe pulmonary haemorrhage.

Project description:Background:Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of the phagocytic cells, which results in absent or diminished levels of microbicidal reactive oxygen species. The disease occurs due to germline mutations in the genes encoding the five subunits of NADPH oxidase complex. The present study is a pilot study to understand the clinical and genetic aspects of CGD in Sri Lanka. Methods:Clinical records of thirteen CGD patients were analysed and compared with similar studies performed in different countries and regions to identify patterns in demographics, clinical manifestations and infectious agents. Genomic DNA and cDNA were analysed in eight patients to identify mutations in CYBB and NCF1 genes, thereby to ascertain the potential X-linked and autosomal recessive (AR) CGD patients. Results:The onset of symptoms in the patient cohort was very early (mean 4.6 months) compared to 20 months in India and 23.9 months in Latin America. Similarly, the age at diagnosis was lower (mean 1.6 years after birth) compared to other studies; 4.5 years in India and 6.1 years in Europe. Pulmonary manifestations were the most common (85%), followed by skin/subcutaneous infections (77%) and lymphadenopathy (62%). The death rate of local patients (38%) was higher than other countries (India 35%, Europe 20%). Majority (77%) were treated for tuberculosis at some point in life. Genetic analysis confirmed six out of eight patients as X-linked CGD cases with mutations in CYBB gene. A novel splice site mutation was identified in P-07 at position c.141+6 which resulted in the deletion of entire exon 2. Two siblings (P-05 and P-06) from consanguineous parents, were identified with AR-CGD based on the homozygous GT deletion mutation in NCF1 gene. Conclusions:The clinical presentation, manifestations and genetic subtypes in the local cohort, appear to be comparable with global trends. Mycobacterial infections should be investigated and treated with more prominence. Effective treatment options are required to control the high mortality rate.

Dataset Information

Molecular characterisation and disease severity of leptospirosis in Sri Lanka.

Publications

Molecular characterisation and disease severity of leptospirosis in Sri Lanka.

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