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.

Leishmaniasis, a neglected tropical disease, is on the decline in South Asia. However, cases of cutaneous leishmaniasis have risen in Sri Lanka since 2001, and the lack of in-depth research on its epidemiologic characteristics hampers control efforts. We analyzed data collected from patients with cutaneous leishmaniasis in Sri Lanka during 2001–2018 to study temporal and geographic trends and identify and monitor disease hotspots. We noted a progression in case rates, including a sharp rise in 2018, showing temporal expansion of disease-prevalent areas and 2 persistent hotspots. The northern hotspot shifted and shrank over time, but the southern hotspot progressively expanded and remained spatially static. In addition, we noted regional incidence differences for age and sex. We provide evidence of temporally progressive and spatially expanding incidence of leishmaniasis in Sri Lanka with distinct geographic patterns and disease hotspots, signaling an urgent need for effective disease control interventions.

BackgroundLeishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis.ResultsClinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group.ConclusionsThe data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5271-z) contains supplementary material, which is available to authorized users.

BackgroundThe use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research.MethodsThis multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important).ResultsOf the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be ‘moderately important’ to ‘very important’ for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively).ConclusionsResearch participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.Electronic supplementary materialThe online version of this article (10.1186/s12910-018-0318-x) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text.

BackgroundThe outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. Leishmaniasis is caused exclusively by L. donovani in Sri Lanka with localized cutaneous leishmaniasis (LCL) being the predominant form. We report here an association study of human leucocyte antigen (HLA) class I and II genes with LCL in Sri Lanka, the first on HLA associations in cutaneous leishmaniasis in a South Asian population.MethodsAn existing DNA repository of 200 each of patients and controls was typed for HLA-DQ by PCR-SSP. Next generation sequencing-based typing for HLA-A, HLA-B and HLA-DRB1 alleles was done in a subset of 280 samples. Association tests were performed on 28,489 genotyped and imputed SNPs spanning a region of 1.4 Mb across the HLA genes. To compare our results with similar studies, we carried out a systematic review to document all HLA associations reported to-date for cutaneous and muco-cutaneous leishmaniasis.ResultsDRB1*04 DQB1*02 (P = 0.03; Pc = 0.09), DRB1*07 DQB1*02 (P = 0.03; Pc = 0.09) haplotypes were absent in patients. B*07 (P = 0.007; Pc = 0.13; OR = 0.36; 95 % CI = 0.17–0.77) allele and DRB1*15 DQB1*06 (P = 0.00; Pc < 0.01; OR = 0.3; 95 % CI = 0.2–.0.6) haplotype were over represented in controls and DRB1*15 (P = 0.002; Pc = 0.01) allele was over represented in patients. Two SNPs (rs281864595/rs1050517) in the antigen recognition region of HLA-B, comprised a haplotype more frequent in controls (P = 0.04). The alleles identified by the systematic review to predispose or to protect from cutaneous/mucocutaneous leishmaniasis remained highly heterogeneous in different populations studied.ConclusionsOur preliminary findings suggest a role for some class I and class II HLA genes in determining predisposition to LCL in this population which should be corroborated with further studies. The systematic review reiterates this need, as the purported susceptibility or protection gained by certain HLA alleles or haplotypes has rarely been independently verified.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1626-8) contains supplementary material, which is available to authorized users.

Background Leishmaniasis is a neglected tropical vector-borne disease, which is on the rise in Sri Lanka. Spatiotemporal and risk factor analyses are useful for understanding transmission dynamics, spatial clustering and predicting future disease distribution and trends to facilitate effective infection control. Methods The nationwide clinically confirmed cutaneous leishmaniasis and climatic data were collected from 2001 to 2019. Hierarchical clustering and spatiotemporal cross-correlation analysis were used to measure the region-wide and local (between neighboring districts) synchrony of transmission. A mixed spatiotemporal regression-autoregression model was built to study the effects of climatic, neighboring-district dispersal, and infection carryover variables on leishmaniasis dynamics and spatial distribution. Same model without climatic variables was used to predict the future distribution and trends of leishmaniasis cases in Sri Lanka. Results A total of 19,361 clinically confirmed leishmaniasis cases have been reported in Sri Lanka from 2001–2019. There were three phases identified: low-transmission phase (2001–2010), parasite population buildup phase (2011–2017), and outbreak phase (2018–2019). Spatially, the districts were divided into three groups based on similarity in temporal dynamics. The global mean correlation among district incidence dynamics was 0.30 (95% CI 0.25–0.35), and the localized mean correlation between neighboring districts was 0.58 (95% CI 0.42–0.73). Risk analysis for the seven districts with the highest incidence rates indicated that precipitation, neighboring-district effect, and infection carryover effect exhibited significant correlation with district-level incidence dynamics. Model-predicted incidence dynamics and case distribution matched well with observed results, except for the outbreak in 2018. The model-predicted 2020 case number is about 5,400 cases, with intensified transmission and expansion of high-transmission area. The predicted case number will be 9115 in 2022 and 19212 in 2025. Conclusions The drastic upsurge in leishmaniasis cases in Sri Lanka in the last few year was unprecedented and it was strongly linked to precipitation, high burden of localized infections and inter-district dispersal. Targeted interventions are urgently needed to arrest an uncontrollable disease spread.

BackgroundWhile a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations. Our objective was to examine the association between common genetic variants in breast cancer related genes and risk of breast cancer in a cohort of Sri Lankan women.MethodsA case-control study of 350 postmenopausal women with breast cancer and 350 healthy postmenopausal women was conducted. Genotyping using the iPLEX GOLD assay was done for 56 haplotype-tagging single nucleotide polymorphisms (SNPs) in 36 breast cancer related genes. Testing for association was done using an additive genetic model. Odds ratios and 95% confidence intervals were calculated using adjusted logistic regression models.ResultsFour SNPs [rs3218550 (XRCC2), rs6917 (PHB), rs1801516 (ATM), and rs13689 (CDH1)] were significantly associated with risk of breast cancer. The rs3218550 T allele and rs6917 A allele increased breast cancer risk by 1.5-fold and 1.4-fold, respectively. The CTC haplotype defined by the SNPs rs3218552|rs3218550|rs3218536 on chromosome 7 (P = 0.0088) and the CA haplotype defined by the SNPs rs1049620|rs6917 on chromosome 17 (P = 0.0067) were significantly associated with increased risk of breast cancer. The rs1801516 A allele and the rs13689 C allele decreased breast cancer risk by 0.6-fold and 0.7-fold, respectively.ConclusionsThese findings suggest that common genetic polymorphisms in the XRCC2, PHB, CDH1 and ATM genes are associated with risk of breast cancer among Sri Lankan postmenopausal women. The exact biological mechanisms of how these variants regulate overall breast cancer risk need further evaluation using functional studies.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4112-4) contains supplementary material, which is available to authorized users.