Sumadhya Deepika Fernando

Drug treatment of scrub typhus

Scrub typhus is a vector-borne disease caused by the pathogen Orientia tsutsugamushi. We review the published literature for evidence on drug treatment in scrub typhus. Doxycycline has a proven efficacy in several trials and a meta-analysis, although resistance has been documented in parts of northern Thailand. Macrolides are equally efficacious and have less adverse effects, but they are expensive. Azithromycin is the recommended drug in pregnancy and for children. Rifampicin is effective in areas where doxycycline resistance is present. Quinolones have shown some degree of efficacy but the evidence is scant. Most clinical evidence on drug treatment is from cases of mild-to-moderate scrub typhus. Further study is needed on the efficacy of different antibiotics in the treatment of severe, life-threatening scrub typhus.

Antibiotics for human toxoplasmosis: a systematic review of randomized trials

Abstract The efficacy of different treatment regimens in clinical syndromes of toxoplasmosis were assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE, EMBASE, and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on the clinical entity of toxoplasmosis. Risk of bias was evaluated and quality of evidence was graded. Fourteen randomized trials were included of which one was a non-comparative study. One well-designed trial showed that trimethoprim-sulphamethoxazole was more effective than placebo for clinical recovery of toxoplasmic lymphadenopathy in immunocompetent hosts. For toxoplasmic encephalopathy, efficacy of pyrimethamine+sulphadiazine and trimethoprim+sulphamethoxazole were similar, whereas pyrimethamine+sulphadiazine versus pyrimathamine+clindamycin showed no difference, irrespective of the outcome. Intravitreal clindamycin+dexamethasone and conventional treatment with oral pyrimethamine+sulphadiazine had similar efficacy with regard to all outcome measures in ocular toxoplasmosis, and intravitreal therapy was found to be safe. Adverse effects seemed more common with pyrimethamine+sulphadiazine. Most trials for encephalitis and ocular manifestations had a high risk of bias and were of poor methodological quality. There were no trials evaluating drugs for toxoplasmosis in pregnancy, or for congenital toxoplasmosis. Pyrimethamine+sulphadiazine is an effective therapy for treatment of toxoplasmic encephalitis; trimethoprim+sulphamethoxazole and pyrimethamine+clindamycin are possible alternatives. Treatment with either oral or intravitreal antibiotics seems reasonable for ocular toxoplasmosis. Overall, trial evidence for the efficacy of these drugs for toxoplasmosis is poor, and further well-designed trials are needed.

Community factors affecting long-lasting impregnated mosquito net use for malaria control in Sri Lanka

The Anti Malaria Campaign distributed approximately 300,000 long-lasting impregnated nets (LLINs) to malaria-endemic areas in Sri Lanka during the years 2005 to 2007. We conducted a community-based cross-sectional survey among 2467 households distributed among the three major ethnic groups of Sri Lanka to study the perceptions and practices with regard to the use of LLINs in order to improve their use. In a majority of households the number of LLINs available was not sufficient for the number of people, although there was a small percentage of households that had excess nets. The information and advice given at the time of distribution regarding use of the nets differed amongst the three groups and was not consistent. Dissemination of this knowledge within the family was not observed. A relationship between knowledge regarding LLINs and reported practices on washing and drying of LLINs was found. It was noted that net shape may influence net use, with cone shaped nets being more popular. Efforts to increase knowledge on LLINs using behaviour change communication techniques would have more effectively contributed to achieve planned outcomes. Proper use of LLINs will undoubtedly contribute to further reduction of malaria in Sri Lanka.

A meta-analysis of magnesium for tetanus.

Uncontrolled studies suggest that magnesium sulphate controls spasms in patients with established tetanus. We performed a meta‐analysis of controlled trials that compared magnesium sulphate with placebo or diazepam for the treatment of patients with tetanus. We searched PubMed, Scopus, Embase and the Cochrane clinical trials registry. Three studies met the inclusion criteria, containing 275 participants (199 male patients, 72.4%). Magnesium sulphate did not reduce mortality, relative risk (95% CI): vs placebo, 0.80 (0.41–1.58); vs diazepam, 1.11 (0.70–1.75). The data on duration of total intensive care unit stay, total hospital stay and the need for ventilatory support were conflicting and pooling of results could not be done due to methodological differences of individual trials. More controlled trials are needed to assess the effect of magnesium sulphate on reducing autonomic instability, spasms, duration of intensive care and hospital stays and the need for mechanical ventilation.

Imported malaria: a possible threat to the elimination of malaria from Sri Lanka?

To discuss epidemiological aspects of imported malaria and the potential impact of imported malaria cases reported in Sri Lanka 2008–2011 in terms of a possible resurgence of the disease.

Current Evidence on the Use of Antifilarial Agents in the Management of Bancroftian Filariasis

Many trials have explored the efficacy of individual drugs and drug combinations to treat bancroftian filariasis. This narrative review summarizes the current evidence for drug management of bancroftian filariasis. Diethylcarbamazine (DEC) remains the prime antifilarial agent with a well-established microfilaricidal and some macrofilaricidal effects. Ivermectin (IVM) is highly microfilaricidal but minimally macrofilaricidal. The role of albendazole (ALB) in treatment regimens is not well established though the drug has a microfilaricidal effect. The combination of DEC+ALB has a better long-term impact than IVM+ALB. Recent trials have shown that doxycycline therapy against Wolbachia, an endosymbiotic bacterium of the parasite, is capable of reducing microfilaria rates and adult worm activity. Followup studies on mass drug administration (MDA) are yet to show a complete interruption of transmission, though the infection rates are reduced to a very low level.

The health and nutritional status of school children in two rural communities in Sri Lanka.

SummaryThere is growing evidence of considerable burden of morbidity and mortality due to infectious diseases and undernutrition in school children. This study describes the nutritional status and parasitic infections of school children in two areas of rural Sri Lanka. All children in four primary schools in the Moneragala district of Sri Lanka were included in the study. The height and weight of children were measured and anthropometric indices calculated. Stool and blood samples were examined for evidence of intestinal helminthiasis, malaria and anaemia. A greater proportion of boys than girls were underweight, wasted and stunted. Over 80% of the children were anaemic but did not apparently have iron deficiency anaemia according to their blood picture. The prevalence of parasitic infections such as hookworm and Plasmodium spp that may contribute to anaemia was low.

Clinical manifestations of cutaneous leishmaniasis in Sri Lanka - possible evidence for genetic susceptibility among the Sinhalese.

Abstract Human cutaneous leishmaniasis (CL) caused by Leishmania donovani, a pathogen more usually associated with visceral leishmaniasis, is now endemic in Sri Lanka. This report details the characteristics of 200 patients with locally acquired CL, who were recruited prospectively for an ongoing study into the genetic susceptibility to CL in Sri Lanka. In each case, the CL was confirmed by the demonstration of amastigotes in a direct smear and/or promastigotes in a culture. Although only 82% of the Sri Lankan population is Sinhalese, all 200 patients belonged to this ethnic group. The patients had a median age of 32 years (range=4–80 years). Most of them each had a single, non-tender, non-itching and dry lesion which had started as a papule and then gradually enlarged and ulcerated, with changes in the surrounding skin. None of the patients had any signs of systemic disease. Eleven (5.5%) each had at least one other affected family member. Patients with multiple lesions were most likely to be found in families with more than one affected member (P=0.002) but multiple lesions were not associated with diabetes mellitus (P>0.05). Although the results of passive detection under-estimate the true occurrence of a disease, the present data point towards enhanced susceptibility to CL among the Sinhalese and/or certain individuals, possibly determined by genetic factors.

Genetic polymorphisms associated with anti-malarial antibody levels in a low and unstable malaria transmission area in southern Sri Lanka

BackgroundThe incidence of malaria in Sri Lanka has significantly declined in recent years. Similar trends were seen in Kataragama, a known malaria endemic location within the southern province of the country, over the past five years. This is a descriptive study of anti-malarial antibody levels and selected host genetic mutations in residents of Kataragama, under low malaria transmission conditions.MethodsSera were collected from 1,011 individuals residing in Kataragama and anti-malarial antibodies and total IgE levels were measured by a standardized ELISA technique. Host DNA was extracted and used for genotyping of selected SNPs in known genes associated with malaria. The antibody levels were analysed in relation to the past history of malaria (during past 10 years), age, sex, the location of residence within Kataragama and selected host genetic markers.ResultsA significant increase in antibodies against Plasmodium falciparum antigens AMA1, MSP2, NANP and Plasmodium vivax antigen MSP1 in individuals with past history of malaria were observed when compared to those who did not. A marked increase of anti-MSP1(Pf) and anti-AMA1(Pv) was also evident in individuals between 45–59 years (when compared to other age groups). Allele frequencies for two SNPs in genes that code for IL-13 and TRIM-5 were found to be significantly different between those who have experienced one or more malaria attacks within past 10 years and those who did not. When antibody levels were classified into a low-high binary trait, significant associations were found with four SNPs for anti-AMA1(Pf); two SNPs for anti-MSP1(Pf); eight SNPs for anti-NANP(Pf); three SNPs for anti-AMA1(Pv); seven SNPs for anti-MSP1(Pv); and nine SNPs for total IgE. Eleven of these SNPs with significant associations with anti-malarial antibody levels were found to be non–synonymous.ConclusionsEvidence is suggestive of an age–acquired immunity in this study population in spite of low malaria transmission levels. Several SNPs were in linkage disequilibrium and had a significant association with elevated antibody levels, suggesting that these host genetic mutations might have an individual or collective effect on inducing or/and maintaining high anti–malarial antibody levels.

Current immunological and molecular tools for leptospirosis: diagnostics, vaccine design, and biomarkers for predicting severity

Leptospirosis is a zoonotic spirochaetal illness that is endemic in many tropical countries. The research base on leptospirosis is not as strong as other tropical infections such as malaria. However, it is a lethal infection that can attack many vital organs in its severe form, leading to multi-organ dysfunction syndrome and death. There are many gaps in knowledge regarding the pathophysiology of leptospirosis and the role of host immunity in causing symptoms. This hinders essential steps in combating disease, such as developing a potential vaccine. Another major problem with leptospirosis is the lack of an easy to perform, accurate diagnostic tests. Many clinicians in resource limited settings resort to clinical judgment in diagnosing leptospirosis. This is unfortunate, as many other diseases such as dengue, hanta virus, rickettsial infections, and even severe bacterial sepsis, can mimic leptospirosis. Another interesting problem is the prediction of disease severity at the onset of the illness. The majority of patients recover from leptospirosis with only a mild febrile illness, while a few others have severe illness with multi-organ failure. Clinical features are poor predictors of potential severity of infection, and therefore the search is on for potential biomarkers that can serve as early warnings for severe disease. This review concentrates on these three important aspects of this neglected tropical disease: diagnostics, developing a vaccine, and potential biomarkers to predict disease severity.