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Background: While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012–2013. Methods: The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Findings: Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Conclusions: Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control. [ABSTRACT FROM AUTHOR]

The burden of leptospirosis in humans and animals in Africa is higher than that reported from other parts of the world. However, the disease is not routinely diagnosed in the continent. One of major factors limiting diagnosis is the poor availability of live isolates of locally circulating Leptospira serovars for inclusion in the antigen panel of the gold standard microscopic agglutination test (MAT) for detecting antibodies against leptospirosis. To gain insight in Leptospira serovars and their natural hosts occurring in Tanzania, concomitantly enabling the improvement of the MAT by inclusion of fresh local isolates, a total of 52 Leptospira isolates were obtained from fresh urine and kidney homogenates, collected between 1996 and 2006 from small mammals, cattle and pigs. Isolates were identified by serogrouping, cross agglutination absorption test (CAAT), and molecular typing. Common Leptospira serovars with their respective animal hosts were: Sokoine (cattle and rodents); Kenya (rodents and shrews); Mwogolo (rodents); Lora (rodents); Qunjian (rodent); serogroup Grippotyphosa (cattle); and an unknown serogroup from pigs. Inclusion of local serovars particularly serovar Sokoine in MAT revealed a 10-fold increase in leptospirosis prevalence in Tanzania from 1.9% to 16.9%in rodents and 0.26% to 10.75% in humans. This indicates that local serovars are useful for diagnosis of human and animal leptospirosis in Tanzania and other African countries. [ABSTRACT FROM AUTHOR]

Background: In the Indian subcontinent, Visceral leishmaniasis is endemic in a geographical area coinciding with the Lower Gangetic Plain, at low altitude. VL occurring in residents of hill districts is therefore often considered the result of Leishmania donovani infection during travel. Early 2014 we conducted an outbreak investigation in Okhaldhunga and Bhojpur districts in the Nepal hills where increasing number of VL cases have been reported. Methodology/Principal Findings: A house-to-house survey in six villages documented retrospectively 35 cases of Visceral Leishmaniasis (VL). Anti-Leishmania antibodies were found in 22/23 past-VL cases, in 40/416 (9.6%) persons without VL and in 12/155 (7.7%) domestic animals. An age- and sex- matched case-control study showed that exposure to known VL-endemic regions was no risk factor for VL, but having a VL case in the neighbourhood was. SSU-rDNA PCR for Leishmania sp. was positive in 24 (5%) of the human, in 18 (12%) of the animal samples and in 16 (14%) bloodfed female Phlebotomus argentipes sand flies. L. donovani was confirmed in two asymptomatic individuals and in one sand fly through hsp70-based sequencing. Conclusions/Significance: This is epidemiological and entomological evidence for ongoing local transmission of L. donovani in villages at an altitude above 600 meters in Nepal, in districts considered hitherto non-endemic for VL. The VL Elimination Initiative in Nepal should therefore consider extending its surveillance and control activities in order to assure VL elimination, and the risk map for VL should be redesigned. [ABSTRACT FROM AUTHOR]

Efforts to control the spread of Buruli ulcer – an emerging ulcerative skin infection caused by Mycobacterium ulcerans - have been hampered by our poor understanding of reservoirs and transmission. To help address this issue, we compared whole genomes from 18 clinical M. ulcerans isolates from a 30km2 region within the Asante Akim North District, Ashanti region, Ghana, with 15 other M. ulcerans isolates from elsewhere in Ghana and the surrounding countries of Ivory Coast, Togo, Benin and Nigeria. Contrary to our expectations of finding minor DNA sequence variations among isolates representing a single M. ulcerans circulating genotype, we found instead two distinct genotypes. One genotype was closely related to isolates from neighbouring regions of Amansie West and Densu, consistent with the predicted local endemic clone, but the second genotype (separated by 138 single nucleotide polymorphisms [SNPs] from other Ghanaian strains) most closely matched M. ulcerans from Nigeria, suggesting another introduction of M. ulcerans to Ghana, perhaps from that country. Both the exotic genotype and the local Ghanaian genotype displayed highly restricted intra-strain genetic variation, with less than 50 SNP differences across a 5.2Mbp core genome within each genotype. Interestingly, there was no discernible spatial clustering of genotypes at the local village scale. Interviews revealed no obvious epidemiological links among BU patients who had been infected with identical M. ulcerans genotypes but lived in geographically separate villages. We conclude that M. ulcerans is spread widely across the region, with multiple genotypes present in any one area. These data give us new perspectives on the behaviour of possible reservoirs and subsequent transmission mechanisms of M. ulcerans. These observations also show for the first time that M. ulcerans can be mobilized, introduced to a new area and then spread within a population. Potential reservoirs of M. ulcerans thus might include humans, or perhaps M. ulcerans-infected animals such as livestock that move regularly between countries. Author Summary: In this study we use the power of whole genome sequence comparisons to track the spread of Mycobacterium ulcerans, the causative agent of Buruli ulcer, through several villages in the Ashanti region of Ghana, providing new insights on the behaviour of this enigmatic and emerging pathogen. [ABSTRACT FROM AUTHOR]

Scaling up of insecticide treated nets has contributed to a substantial malaria decline. However, some malaria vectors, and most arbovirus vectors, bite outdoors and in the early evening. Therefore, topically applied insect repellents may provide crucial additional protection against mosquito-borne pathogens. Among topical repellents, DEET is the most commonly used, followed by others such as picaridin. The protective efficacy of two formulated picaridin repellents against mosquito bites, including arbovirus and malaria vectors, was evaluated in a field study in Cambodia. Over a period of two years, human landing collections were performed on repellent treated persons, with rotation to account for the effect of collection place, time and individual collector. Based on a total of 4996 mosquitoes collected on negative control persons, the overall five hour protection rate was 97.4% [95%CI: 97.1–97.8%], not decreasing over time. Picaridin 20% performed equally well as DEET 20% and better than picaridin 10%. Repellents performed better against Mansonia and Culex spp. as compared to aedines and anophelines. A lower performance was observed against Aedes albopictus as compared to Aedes aegypti, and against Anopheles barbirostris as compared to several vector species. Parity rates were higher in vectors collected on repellent treated person as compared to control persons. As such, field evaluation shows that repellents can provide additional personal protection against early and outdoor biting malaria and arbovirus vectors, with excellent protection up to five hours after application. The heterogeneity in repellent sensitivity between mosquito genera and vector species could however impact the efficacy of repellents in public health programs. Considering its excellent performance and potential to protect against early and outdoor biting vectors, as well as its higher acceptability as compared to DEET, picaridin is an appropriate product to evaluate the epidemiological impact of large scale use of topical repellents on arthropod borne diseases. Author Summary: Malaria and arboviruses are transmitted by several mosquitoes. Targeting these mosquitoes instead of the pathogens can contribute to prevention of these diseases. For mosquitoes biting throughout the night, mosquito nets (preferably impregnated with insecticides) are very effective for mosquito control. However, bites of day-, evening- and outdoor-biting mosquitoes have to be prevented in different ways, for example by applying repellents on the skin which contain DEET or other active ingredients such as picaridin. Here we report on the evaluation of the performance of two formulated picaridin repellents (lotion 10% and spray 20%) against mosquito bites, including vectors of arboviruses and malaria in the field in Cambodia. These repellent formulations were compared to a DEET solution (20%). In general, all repellents performed very well, providing more than 97% protection against mosquito bites when used for five consecutive hours. At the highest concentration, the picaridin repellent performed similarly to DEET. However, different mosquito species reacted differently to the repellents. As such, repellents can provide an additional protection against bites of malaria and arbovirus vectors. [ABSTRACT FROM AUTHOR]

Background: The reservoir and mode of transmission of Mycobacterium ulcerans, the causative agent of Buruli ulcer, still remain a mystery. It has been suggested that M. ulcerans persists with difficulty as a free-living organism due to its natural fragility and inability to withstand exposure to direct sunlight, and thus probably persists within a protective host environment. Methodology/Principal Findings: We investigated the role of free-living amoebae as a reservoir of M. ulcerans by screening the bacterium in free-living amoebae (FLA) cultures isolated from environmental specimens using real-time PCR. We also followed the survival of M. ulcerans expressing green fluorescence protein (GFP) in Acanthameoba castellanii by flow cytometry and observed the infected cells using confocal and transmission electron microscopy for four weeks in vitro. IS2404 was detected by quantitative PCR in 4.64% of FLA cultures isolated from water, biofilms, detritus and aerosols. While we could not isolate M. ulcerans, 23 other species of mycobacteria were cultivated from inside FLA and/or other phagocytic microorganisms. Laboratory experiments with GFP-expressing M. ulcerans in A. castellani trophozoites for 28 days indicated the bacteria did not replicate inside amoebae, but they could remain viable at low levels in cysts. Transmission electron microscopy of infected A. castellani confirmed the presence of bacteria within both trophozoite vacuoles and cysts. There was no correlation of BU notification rate with detection of the IS2404 in FLA (r = 0.07, n = 539, p = 0.127). Conclusion/Significance: This study shows that FLA in the environment are positive for the M. ulcerans insertion sequence IS2404. However, the detection frequency and signal strength of IS2404 positive amoabae was low and no link with the occurrence of BU was observed. We conclude that FLA may host M. ulcerans at low levels in the environment without being directly involved in the transmission to humans. Author Summary: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU) is an environmental pathogen known to reside in aquatic habitat. However, the reservoir and modes of transmission to humans still remain unknown. M. ulcerans can probably not live freely due to its natural fragility and inability to withstand exposure to direct sunlight. This study investigated the hypothesis that free-living amoebae (FLA) can serve as a reservoir of M. ulcerans by testing for its presence in amoebae isolated from water bodies in BU endemic and non-endemic communities and whether the pathogen can remain viable when experimentally infected in amoebae in the laboratory. We detected only one (IS2404) of the three (IS2606 and KRB) targets for the presence of M. ulcerans in amoebae cultures and found no correlation between its presence in the environment and BU notification rate. M. ulcerans remained viable at low levels in amoebae for 28 days in vitro. We therefore conclude that FLA may host M. ulcerans at low levels in the environment without being directly involved in the transmission to humans. [ABSTRACT FROM AUTHOR]

Background: The reservoir and mode of transmission of Mycobacterium ulcerans, the causative agent of Buruli ulcer, remain unknown. Ecological, genetic and epidemiological information nonetheless suggests that M. ulcerans may reside in aquatic protozoa. Methodology/Principal Findings: We experimentally infected Acanthamoeba polyphaga with M. ulcerans and found that the bacilli were phagocytised, not digested and remained viable for the duration of the experiment. Furthermore, we collected 13 water, 90 biofilm and 45 detritus samples in both Buruli ulcer endemic and non-endemic communities in Ghana, from which we cultivated amoeboid protozoa and mycobacteria. M. ulcerans was not isolated, but other mycobacteria were as frequently isolated from intracellular as from extracellular sources, suggesting that they commonly infect amoebae in nature. We screened the samples as well as the amoeba cultures for the M. ulcerans markers IS2404, IS2606 and KR-B. IS2404 was detected in 2% of the environmental samples and in 4% of the amoeba cultures. The IS2404 positive amoeba cultures included up to 5 different protozoan species, and originated both from Buruli ulcer endemic and non-endemic communities. Conclusions/Significance: This is the first report of experimental infection of amoebae with M. ulcerans and of the detection of the marker IS2404 in amoeba cultures isolated from the environment. We conclude that amoeba are potential natural hosts for M. ulcerans, yet remain sceptical about their implication in the transmission of M. ulcerans to humans and their importance in the epidemiology of Buruli ulcer. Author Summary: Buruli ulcer (BU) is a devastating skin disease caused by Mycobacterium ulcerans, an environmental bacterium that is probably linked to slow-running water. It is unlikely to occur free-living, but even though M. ulcerans DNA has been detected in quite a few different organisms (with most studies focusing on insects), it is still not clear what its real reservoir is. Amoeboid protozoa, inhabitants of biofilms in slow flowing water, are good candidates since all previously tested mycobacteria are resistant to the digestion by these macrophage-like organisms. In this paper we demonstrate that M. ulcerans can indeed infect Acanthamoeba polyphaga in the lab, and remain viable intracellularly. We also collected water, biofilm and detritus samples in BU endemic and non-endemic regions in Ghana. We found that several mycobacteria species commonly occur intracellularly in protozoa in these environments. Amoebae were isolated from almost all samples, and an M. ulcerans marker (IS2404) was detected in 4% of the amoeba cultures. We conclude that amoebae are potential hosts for M. ulcerans. However, because these IS2404 positive amoebae originated from both BU endemic and non-endemic areas, we remain sceptical about their implication in the transmission of M. ulcerans to humans. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article on the distribution of Mycobacterium ulcerans genotypes in a region of Ghana affected by Buruli ulcer. It corrects an error in Table 1 of the article, specifically in the "ENA" column. The corrected table is provided. The document also includes a list of individuals and their corresponding data, collected as part of a study, from various locations in Ghana and Cote d'Ivoire. Additionally, it provides a table of information about different strains of bacteria collected from various locations in Africa, including Nigeria, Democratic Republic of the Congo, and Ghana. This information can be valuable for researchers studying bacterial strains and their geographical distribution in Africa. [Extracted from the article]

Background:Adherence to effective malaria medication is extremely important in the context of Cambodia’s elimination targets and drug resistance containment. Although the public sector health facilities are accessible to the local ethnic minorities of Ratanakiri province (Northeast Cambodia), their illness itineraries often lead them to private pharmacies selling “cocktails” and artemether injections, or to local diviners prescribing animal sacrifices to appease the spirits. Methods:The research design consisted of a mixed methods study, combining qualitative (in-depth interviews and participant observation) and quantitative methods (household and cross-sectional survey). Results:Three broad options for malaria treatment were identified: i) the public sector; ii) the private sector; iii) traditional treatment based on divination and ceremonial sacrifice. Treatment choice was influenced by the availability of treatment and provider, perceived side effects and efficacy of treatments, perceived etiology of symptoms, and patient-health provider encounters. Moreover, treatment paths proved to be highly flexible, changing mostly in relation to the perceived efficacy of a chosen treatment. Conclusions:Despite good availability of anti-malarial treatment in the public health sector, attendance remained low due to both structural and human behavioral factors. The common use and under-dosage of anti-malaria monotherapy in the private sector (single-dose injections, single-day drug cocktails) represents a threat not only for individual case management, but also for the regional plan of drug resistance containment and malaria elimination. [ABSTRACT FROM AUTHOR]