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Different genotypes of <i>Trypanosoma cruzi</i> produce distinctive placental environment genetic response in chronic experimental infection

PLoS Neglected Tropical Diseases News - 8 March 2017 - 10:00pm

by Natalia Anahí Juiz, María Elisa Solana, Gonzalo Raúl Acevedo, Alejandro Francisco Benatar, Juan Carlos Ramirez, Priscilla Almeida da Costa, Andrea Mara Macedo, Silvia Andrea Longhi, Alejandro G. Schijman

Congenital infection of Trypanosoma cruzi allows transmission of this parasite through generations. Despite the problematic that this entails, little is known about the placenta environment genetic response produced against infection. We performed functional genomics by microarray analysis in C57Bl/6J mice comparing placentas from uninfected animals and from animals infected with two different T. cruzi strains: K98, a clone of the non-lethal myotropic CA-I strain (TcI), and VD (TcVI), isolated from a human case of congenital infection. Analysis of networks by GeneMANIA of differentially expressed genes showed that “Secretory Granule” was a pathway down-regulated in both infected groups, whereas “Innate Immune Response” and “Response to Interferon-gamma” were pathways up-regulated in VD infection but not in K98. Applying another approach, the GSEA algorithm that detects small changes in predetermined gene sets, we found that metabolic processes, transcription and macromolecular transport were down-regulated in infected placentas environment and some pathways related to cascade signaling had opposite regulation: over-represented in VD and down-regulated in K98 group. We also have found a stronger tropism to the placental organ by VD strain, by detection of parasite DNA and RNA, suggesting living parasites. Our study is the first one to describe in a murine model the genetic response of placental environment to T. cruzi infection and suggests the development of a strong immune response, parasite genotype-dependent, to the detriment of cellular metabolism, which may contribute to control infection preventing the risk of congenital transmission.

Accuracy of chimeric proteins in the serological diagnosis of chronic chagas disease – a Phase II study

PLoS Neglected Tropical Diseases News - 8 March 2017 - 10:00pm

by Fred Luciano Neves Santos, Paola Alejandra Fiorani Celedon, Nilson Ivo Tonin Zanchin, Wayner Vieira de Souza, Edimilson Domingos da Silva, Leonardo Foti, Marco Aurélio Krieger, Yara de Miranda Gomes

Background

The performance of current serologic tests for diagnosing chronic Chagas disease (CD) is highly variable. The search for new diagnostic markers has been a constant challenge for improving accuracy and reducing the number of inconclusive results.

Methodology/Principal findings

Here, four chimeric proteins (IBMP-8.1 to -8.4) comprising immunodominant regions of different Trypanosoma cruzi antigens were tested by enzyme-linked immunosorbent assay. The proteins were used to detect specific anti-T. cruzi antibodies in the sera of 857 chagasic and 689 non-chagasic individuals to evaluate their accuracy for chronic CD diagnosis. The antigens were recombinantly expressed in Escherichia coli and purified by chromatographic methods. The sensitivity and specificity values ranged from 94.3% to 99.3% and 99.4% to 100%, respectively. The diagnostic odds ratio (DOR) values were 6,462 for IBMP-8.1, 3,807 for IBMP-8.2, 32,095 for IBMP-8.3, and 283,714 for IBMP-8.4. These chimeric antigens presented DORs that were higher than the commercial test Pathozyme Chagas. The antigens IBMP-8.3 and -8.4 also showed DORs higher than the Gold ELISA Chagas test. Mixtures with equimolar concentrations were tested in order to improve the diagnosis accuracy of negative samples with high signal and positive samples with low signal. However, no gain in accuracy was observed relative to the individual antigens. A total of 1,079 additional sera were used to test cross-reactivity to unrelated diseases. The cross-reactivity rates ranged from 0.37% to 0.74% even for Leishmania spp., a pathogen showing relatively high genome sequence identity to T. cruzi. Imprecision analyses showed that IBMP chimeras are very stable and the results are highly reproducible.

Conclusions/Significance

Our findings indicate that the IBMP-8.4 antigen can be safely used in serological tests for T. cruzi screening in blood banks and for chronic CD laboratory diagnosis.

Ethnic groups’ knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya

PLoS Neglected Tropical Diseases News - 8 March 2017 - 10:00pm

by Hippolyte Affognon, Peter Mburu, Osama Ahmed Hassan, Sarah Kingori, Clas Ahlm, Rosemary Sang, Magnus Evander

Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.

The microbiome composition of <i>Aedes aegypti</i> is not critical for <i>Wolbachia</i>-mediated inhibition of dengue virus

PLoS Neglected Tropical Diseases News - 7 March 2017 - 10:00pm

by Michelle D. Audsley, Yixin H. Ye, Elizabeth A. McGraw

Background

Dengue virus (DENV) is primarily vectored by the mosquito Aedes aegypti, and is estimated to cause 390 million human infections annually. A novel method for DENV control involves stable transinfection of Ae. aegypti with the common insect endosymbiont Wolbachia, which mediates an antiviral effect. However, the mechanism by which Wolbachia reduces the susceptibility of Ae. aegypti to DENV is not fully understood. In this study we assessed the potential of resident microbiota, which can play important roles in insect physiology and immune responses, to affect Wolbachia-mediated DENV blocking.

Methodology/Findings

The microbiome of Ae. aegypti stably infected with Wolbachia strain wMel was compared to that of Ae. aegypti without Wolbachia, using 16s rDNA profiling. Our results indicate that although Wolbachia affected the relative abundance of several genera, the microbiome of both the Wolbachia-infected and uninfected mosquitoes was dominated by Elizabethkingia and unclassified Enterobacteriaceae. To assess the potential of the resident microbiota to affect the Wolbachia-mediated antiviral effect, we used antibiotic treatment before infection with DENV by blood-meal. In spite of a significant shift in the microbiome composition in response to the antibiotics, we detected no effect of antibiotic treatment on DENV infection rates, or on the DENV load of infected mosquitoes.

Conclusions/Significance

Our findings indicate that stable infection with Wolbachia strain wMel produces few effects on the microbiome of laboratory-reared Ae. aegypti. Moreover, our findings suggest that the microbiome can be significantly altered without affecting the fundamental DENV blocking phenotype in these mosquitoes. Since Ae. aegypti are likely to encounter diverse microbiota in the field, this is a particularly important result in the context of using Wolbachia as a method for DENV control.

Systematic review and meta-analysis estimating association of cysticercosis and neurocysticercosis with epilepsy

PLoS Neglected Tropical Diseases News - 7 March 2017 - 10:00pm

by Gabrielle Debacq, Luz M. Moyano, Héctor H. Garcia, Farid Boumediene, Benoit Marin, Edgard B. Ngoungou, Pierre-Marie Preux

Background

We reviewed studies that analyzed cysticercosis (CC), neurocysticercosis (NCC) and epilepsy across Latin America, Asia and Sub-Saharan Africa, to estimate the odds ratio and etiologic fraction of epilepsy due to CC in tropical regions.

Methodology

We conducted a systematic review of the literature on cysticercosis and epilepsy in the tropics, collecting data from case-control and cross-sectional studies. Exposure criteria for CC included one or more of the following: serum ELISA or EITB positivity, presence of subcutaneous cysts (both not verified and unverified by histology), histology consistent with calcified cysts, and brain CT scan consistent with NCC. A common odds-ratio was then estimated using meta-analysis.

Principal findings

37 studies from 23 countries were included (n = 24,646 subjects, 14,934 with epilepsy and 9,712 without epilepsy). Of these, 29 were case-control (14 matched). The association between CC and epilepsy was significant in 19 scientific articles. Odds ratios ranged from 0.2 to 25.4 (a posteriori power 4.5–100%) and the common odds ratio was 2.7 (95% CI 2.1–3.6, p <0.001). Three subgroup analyses performed gave odds ratios as: 2.2 (EITB-based studies), 3.2 (CT-based studies), 1.9 (neurologist-confirmed epilepsy; door-to-door survey and at least one matched control per case). Etiologic fraction was estimated to be 63% in the exposed group among the population.

Significance

Despite differences in findings, this meta-analysis suggests that cysticercosis is a significant contributor to late-onset epilepsy in tropical regions around the world, and its impact may vary depending on transmission intensity.

Human <i>Treponema pallidum</i> 11q/j isolate belongs to subsp. <i>endemicum</i> but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. <i>pertenue</i> and subsp. <i>pallidum</i>, respectively

PLoS Neglected Tropical Diseases News - 6 March 2017 - 10:00pm

by Lenka Mikalová, Michal Strouhal, Jan Oppelt, Philippe Alain Grange, Michel Janier, Nadjet Benhaddou, Nicolas Dupin, David Šmajs

Background

Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan.

Methodology/Principal findings

The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA) strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE) strains, but not to TEN sequences.

Conclusions/Significance

A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.

Selective inhibition of RNA polymerase I transcription as a potential approach to treat African trypanosomiasis

PLoS Neglected Tropical Diseases News - 6 March 2017 - 10:00pm

by Louise E. Kerry, Elaine E. Pegg, Donald P. Cameron, James Budzak, Gretchen Poortinga, Kate Hannan, Ross D. Hannan, Gloria Rudenko

Trypanosoma brucei relies on an essential Variant Surface Glycoprotein (VSG) coat for survival in the mammalian bloodstream. High VSG expression within an expression site body (ESB) is mediated by RNA polymerase I (Pol I), which in other eukaryotes exclusively transcribes ribosomal RNA genes (rDNA). As T. brucei is reliant on Pol I for VSG transcription, we investigated Pol I transcription inhibitors for selective anti-trypanosomal activity. The Pol I inhibitors quarfloxin (CX-3543), CX-5461, and BMH-21 are currently under investigation for treating cancer, as rapidly dividing cancer cells are particularly dependent on high levels of Pol I transcription compared with nontransformed cells. In T. brucei all three Pol I inhibitors have IC50 concentrations for cell proliferation in the nanomolar range: quarfloxin (155 nM), CX-5461 (279 nM) or BMH-21 (134 nM) compared with IC50 concentrations in the MCF10A human breast epithelial cell line (4.44 μM, 6.89 μM or 460 nM, respectively). T. brucei was therefore 29-fold more sensitive to quarfloxin, 25-fold more sensitive to CX-5461 and 3.4-fold more sensitive to BMH-21. Cell death in T. brucei was due to rapid inhibition of Pol I transcription, as within 15 minutes treatment with the inhibitors rRNA precursor transcript was reduced 97-98% and VSG precursor transcript 91-94%. Incubation with Pol I transcription inhibitors also resulted in disintegration of the ESB as well as the nucleolus subnuclear structures, within one hour. Rapid ESB loss following the block in Pol I transcription argues that the ESB is a Pol I transcription nucleated structure, similar to the nucleolus. In addition to providing insight into Pol I transcription and ES control, Pol I transcription inhibitors potentially also provide new approaches to treat trypanosomiasis.

Significance of major international seaports in the distribution of murine typhus in Taiwan

PLoS Neglected Tropical Diseases News - 6 March 2017 - 10:00pm

by Chi-Chien Kuo, Nicola Wardrop, Chung-Te Chang, Hsi-Chieh Wang, Peter M. Atkinson

Background

International seaports are hotspots for disease invasion and pathogens can persist in seaports even after ports are abandoned. Transmitted by fleas infected by Rickettsia typhi, murine typhus, a largely neglected and easily misdiagnosed disease, is known to occur primarily in large seaports. However, the significance of seaports in the occurrence of murine typhus has never been validated quantitatively.

Methodology/Principal findings

We studied the spatial distribution of murine typhus, a notifiable disease, in Taiwan. We investigated whether risk of infection was correlated with distance to international seaports and a collection of environmental and socioeconomic factors, using a Bayesian negative binomial conditionally autoregressive model, followed with geographically weighted regression. Seaports that are currently in use and those that operated in the 19th century for trade with China, but were later abandoned due to siltation were analyzed. A total of 476 human cases of murine typhus were reported during 2000–2014 in the main island of Taiwan, with spatial clustering in districts in southwest and central-west Taiwan. A higher incidence rate (case/population) was associated with a smaller distance to currently in-use international seaports and lower rainfall and temperature, but was uncorrelated with distance to abandoned ports. Geographically weighted regression revealed a geographic heterogeneity in the importance of distance to in-use seaports near the four international seaports of Taiwan.

Conclusions/Significance

Our study suggests that murine typhus is associated with international seaports, especially for those with large trading volume. Thus, one of the costs of global trade in Taiwan might be elevated risks of murine typhus. Globalization has accelerated the spread of infectious diseases, but the burden of disease varies geographically, with regions surrounding major international seaports warranting particular surveillance.

The epidemiology and clinical features of melioidosis in Far North Queensland: Implications for patient management

PLoS Neglected Tropical Diseases News - 6 March 2017 - 10:00pm

by James D. Stewart, Simon Smith, Enzo Binotto, William J. McBride, Bart J. Currie, Josh Hanson

Background

The epidemiology, clinical presentation and management of melioidosis vary around the world. It is essential to define the disease’s local features to optimise its management.

Principal findings

Between 1998 and 2016 there were 197 cases of culture confirmed melioidosis in Far North Queensland; 154 (78%) presented in the December-April wet season. 145 (74%) patients were bacteraemic, 58 (29%) were admitted to the Intensive Care Unit and 27 (14%) died; nine (33%) of these deaths occurred within 48 hours of presentation. Pneumonia was the most frequent clinical finding, present in 101 (61%) of the 166 with available imaging. A recognised risk factor for melioidosis (diabetes, hazardous alcohol use, chronic renal disease, chronic lung disease, immunosuppression or malignancy) was present in 148 (91%) of 162 patients with complete comorbidity data. Despite representing only 9% of the region’s population, Aboriginal and Torres Strait Island (ATSI) people comprised 59% of the cases. ATSI patients were younger than non-ATSI patients (median (interquartile range): 46 (38–56) years versus 59 (43–69) years (p<0.001) and had a higher case-fatality rate (22/117 (19%) versus 5/80 (6.3%) (p = 0.01)). In the 155 patients surviving the initial intensive intravenous phase of treatment, eleven (7.1%) had disease recurrence, despite the fact that nine (82%) of these patients had received prolonged intravenous therapy. Recurrence was usually due to inadequate source control or poor adherence to oral eradication therapy. The case fatality rate declined from 12/44 (27%) in the first five years of the study to 7/76 (9%) in the last five (p = 0.009), reflecting national improvements in sepsis management.

Conclusions

Melioidosis in Far North Queensland is a seasonal, opportunistic infection of patients with specific comorbidities. The ATSI population bear the greatest burden of disease. Although the case-fatality rate is declining, deaths frequently occur early after hospitalisation, reinforcing the importance of prompt, targeted therapy in high-risk patients.

Dengue Baidu Search Index data can improve the prediction of local dengue epidemic: A case study in Guangzhou, China

PLoS Neglected Tropical Diseases News - 6 March 2017 - 10:00pm

by Zhihao Li, Tao Liu, Guanghu Zhu, Hualiang Lin, Yonghui Zhang, Jianfeng He, Aiping Deng, Zhiqiang Peng, Jianpeng Xiao, Shannon Rutherford, Runsheng Xie, Weilin Zeng, Xing Li, Wenjun Ma

Background

Dengue fever (DF) in Guangzhou, Guangdong province in China is an important public health issue. The problem was highlighted in 2014 by a large, unprecedented outbreak. In order to respond in a more timely manner and hence better control such potential outbreaks in the future, this study develops an early warning model that integrates internet-based query data into traditional surveillance data.

Methodology and principal findings

A Dengue Baidu Search Index (DBSI) was collected from the Baidu website for developing a predictive model of dengue fever in combination with meteorological and demographic factors. Generalized additive models (GAM) with or without DBSI were established. The generalized cross validation (GCV) score and deviance explained indexes, intraclass correlation coefficient (ICC) and root mean squared error (RMSE), were respectively applied to measure the fitness and the prediction capability of the models. Our results show that the DBSI with one-week lag has a positive linear relationship with the local DF occurrence, and the model with DBSI (ICC:0.94 and RMSE:59.86) has a better prediction capability than the model without DBSI (ICC:0.72 and RMSE:203.29).

Conclusions

Our study suggests that a DSBI combined with traditional disease surveillance and meteorological data can improve the dengue early warning system in Guangzhou.

Mechanism study on a plague outbreak driven by the construction of a large reservoir in southwest china (surveillance from 2000-2015)

PLoS Neglected Tropical Diseases News - 3 March 2017 - 10:00pm

by Xin Wang, Xiaoyu Wei, Zhizhong Song, Mingliu Wang, Jinxiao Xi, Junrong Liang, Yun Liang, Ran Duan, Kecheng Tian, Yong Zhao, Guangpeng Tang, Lv You, Guirong Yang, Xuebin Liu, Yuhuang Chen, Jun Zeng, Shengrong Wu, Shoujun Luo, Gang Qin, Huijing Hao, Huaiqi Jing

Background

Plague, a Yersinia pestis infection, is a fatal disease with tremendous transmission capacity. However, the mechanism of how the pathogen stays in a reservoir, circulates and then re-emerges is an enigma.

Methodology/Principal findings

We studied a plague outbreak caused by the construction of a large reservoir in southwest China followed 16-years’ surveillance.

Conclusions/Significance

The results show the prevalence of plague within the natural plague focus is closely related to the stability of local ecology. Before and during the decade of construction the reservoir on the Nanpan River, no confirmed plague has ever emerged. With the impoundment of reservoir and destruction of drowned farmland and vegetation, the infected rodent population previously dispersed was concentrated together in a flood-free area and turned a rest focus alive. Human plague broke out after the enzootic plague via the flea bite. With the construction completed and ecology gradually of human residential environment, animal population and type of vegetation settling down to a new balance, the natural plague foci returned to a rest period. With the rodent density decreased as some of them died, the flea density increased as the rodents lived near or in local farm houses where had more domestic animals, and human has a more concentrated population. In contrast, in the Himalayan marmot foci of the Qinghai-Tibet Plateau in the Qilian Mountains. There are few human inhabitants and the local ecology is relatively stable; plague is prevalence, showing no rest period. Thus the plague can be significantly affected by ecological shifts.

A multistrain approach to studying the mechanisms underlying compatibility in the interaction between <i>Biomphalaria glabrata</i> and <i>Schistosoma mansoni</i>

PLoS Neglected Tropical Diseases News - 2 March 2017 - 10:00pm

by Richard Galinier, Emmanuel Roger, Yves Moné, David Duval, Anaïs Portet, Silvain Pinaud, Cristian Chaparro, Christoph Grunau, Clémence Genthon, Emeric Dubois, Anne Rognon, Nathalie Arancibia, Bernard Dejean, André Théron, Benjamin Gourbal, Guillaume Mitta

In recent decades, numerous studies have sought to better understand the mechanisms underlying the compatibility between Biomphalaria glabrata and Schistosoma mansoni. The developments of comparative transcriptomics, comparative genomics, interactomics and more targeted approaches have enabled researchers to identify a series of candidate genes. However, no molecular comparative work has yet been performed on multiple populations displaying different levels of compatibility. Here, we seek to fill this gap in the literature. We focused on B. glabrata FREPs and S. mansoni SmPoMucs, which were previously demonstrated to be involved in snail/schistosome compatibility. We studied the expression and polymorphisms of these factors in combinations of snail and schistosome isolates that display different levels of compatibility. We found that the polymorphism and expression levels of FREPs and SmPoMucs could be linked to the compatibility level of S. mansoni. These data and our complementary results obtained by RNA-seq of samples from various snail strains indicate that the mechanism of compatibility is much more complex than previously thought, and that it is likely to be highly variable within and between populations. This complexity must be taken into account if we hope to identify the molecular pathways that are most likely to be good targets for strategies aimed at blocking transmission of the parasite through the snail intermediate host.

Risk mapping of clonorchiasis in the People’s Republic of China: A systematic review and Bayesian geostatistical analysis

PLoS Neglected Tropical Diseases News - 2 March 2017 - 10:00pm

by Ying-Si Lai, Xiao-Nong Zhou, Zhi-Heng Pan, Jürg Utzinger, Penelope Vounatsou

Background

Clonorchiasis, one of the most important food-borne trematodiases, affects more than 12 million people in the People’s Republic of China (P.R. China). Spatially explicit risk estimates of Clonorchis sinensis infection are needed in order to target control interventions.

Methodology

Georeferenced survey data pertaining to infection prevalence of C. sinensis in P.R. China from 2000 onwards were obtained via a systematic review in PubMed, ISI Web of Science, Chinese National Knowledge Internet, and Wanfang Data from January 1, 2000 until January 10, 2016, with no restriction of language or study design. Additional disease data were provided by the National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention in Shanghai. Environmental and socioeconomic proxies were extracted from remote-sensing and other data sources. Bayesian variable selection was carried out to identify the most important predictors of C. sinensis risk. Geostatistical models were applied to quantify the association between infection risk and the predictors of the disease, and to predict the risk of infection across P.R. China at high spatial resolution (over a grid with grid cell size of 5×5 km).

Principal findings

We obtained clonorchiasis survey data at 633 unique locations in P.R. China. We observed that the risk of C. sinensis infection increased over time, particularly from 2005 onwards. We estimate that around 14.8 million (95% Bayesian credible interval 13.8–15.8 million) people in P.R. China were infected with C. sinensis in 2010. Highly endemic areas (≥ 20%) were concentrated in southern and northeastern parts of the country. The provinces with the highest risk of infection and the largest number of infected people were Guangdong, Guangxi, and Heilongjiang.

Conclusions/Significance

Our results provide spatially relevant information for guiding clonorchiasis control interventions in P.R. China. The trend toward higher risk of C. sinensis infection in the recent past urges the Chinese government to pay more attention to the public health importance of clonorchiasis and to target interventions to high-risk areas.

Single locus genotyping to track <i>Leishmania donovani</i> in the Indian subcontinent: Application in Nepal

PLoS Neglected Tropical Diseases News - 1 March 2017 - 10:00pm

by Keshav Rai, Narayan Raj Bhattarai, Manu Vanaerschot, Hideo Imamura, Gebreyohans Gebru, Basudha Khanal, Suman Rijal, Marleen Boelaert, Chiranjib Pal, Prahlad Karki, Jean-Claude Dujardin, Gert Van der Auwera

Background

We designed a straightforward method for discriminating circulating Leishmania populations in the Indian subcontinent (ISC). Research on transmission dynamics of visceral leishmaniasis (VL, or Kala-azar) was recently identified as one of the key research priorities for elimination of the disease in the ISC. VL in Bangladesh, India, and Nepal is caused by genetically homogeneous populations of Leishmania donovani parasites, transmitted by female sandflies. Classical methods to study diversity of these protozoa in other regions of the world, such as microsatellite typing, have proven of little use in the area, as they are not able to discriminate most genotypes. Recently, whole genome sequencing (WGS) so far identified 10 different populations termed ISC001-ISC010.

Methodology / Principle findings

As an alternative to WGS for epidemiological or clinical studies, we designed assays based on PCR amplification followed by dideoxynucleotide sequencing for identification of the non-recombinant genotypes ISC001 up to ISC007. These assays were applied on 106 parasite isolates collected in Nepal between 2011 and 2014. Combined with data from WGS on strains collected in the period 2002–2011, we provide a proof-of-principle for the application of genotyping to study treatment outcome, and differential geographic distribution.

Conclusions / Significance

Our method can aid in epidemiological follow-up of visceral leishmaniasis in the Indian subcontinent, a necessity in the frame of the Kala-azar elimination initiative in the region.

First identification of <i>Rickettsia helvetica</i> in questing ticks from a French Northern Brittany Forest

PLoS Neglected Tropical Diseases News - 1 March 2017 - 10:00pm

by Sarah I. Bonnet, Richard E. L. Paul, Emmanuel Bischoff, Martine Cote, Evelyne Le Naour

Tick-borne rickettsiae are considered to be emerging, but data about their presence in western Europe are scarce. Ixodes ricinus ticks, the most abundant and widespread tick species in western Europe, were collected and tested for the presence of several tick-borne pathogens in western France, a region never previously explored in this context. There was a high tick abundance with a mean of 4 females, 4.5 males, and 23.3 nymphs collected per hour per collector. Out of 622 tested ticks, specific PCR amplification showed the presence of tick symbionts as well as low prevalence of Borrelia burgdorferi (0.8%), Bartonella spp. (0.17%), and Anaplasma phagocytophilum (0.09%). The most prevalent pathogen was Rickettsia helvetica (4.17%). This is the first time that this bacteria has been detected in ticks in this region, and this result raises the possibility that bacteria other than those classically implicated may be involved in rickettsial diseases in western France.

Chikungunya virus disease outbreak in Yap State, Federated States of Micronesia

PLoS Neglected Tropical Diseases News - 1 March 2017 - 10:00pm

by Daniel M. Pastula, W. Thane Hancock, Martin Bel, Holly Biggs, Maria Marfel, Robert Lanciotti, Janeen Laven, Tai-Ho Chen, J. Erin Staples, Marc Fischer, Susan L. Hills

Background

Chikungunya virus is a mosquito-borne alphavirus which causes an acute febrile illness associated with polyarthralgia. Beginning in August 2013, clinicians from the Yap State Department of Health in the Federated States of Micronesia (FSM) identified an unusual cluster of illness which was subsequently confirmed to be chikungunya virus disease. Chikungunya virus disease previously had not been recognized in FSM.

Methodology/Principal findings

Information from patients presenting to healthcare facilities was collected and analyzed. During August 11, 2013, to August 10, 2014, a total of 1,761 clinical cases were reported for an attack rate of 155 clinical cases per 1,000 population. Among residents of Yap Main Island, 3% were hospitalized. There were no deaths. The outbreak began on Yap Main Island and rapidly spread throughout Yap Main Island and to three neighboring islands.

Conclusions/Significance

Chikungunya virus can cause explosive outbreaks with substantial morbidity. Given the increasing globalization of chikungunya virus, strong surveillance systems and access to laboratory testing are essential to detect outbreaks.

Diversification of <i>Orientia tsutsugamushi</i> genotypes by intragenic recombination and their potential expansion in endemic areas

PLoS Neglected Tropical Diseases News - 1 March 2017 - 10:00pm

by Gwanghun Kim, Na-Young Ha, Chan-Ki Min, Hong-Il Kim, Nguyen Thi Hai Yen, Keun-Hwa Lee, Inbo Oh, Jae-Seung Kang, Myung-Sik Choi, Ik-Sang Kim, Nam-Hyuk Cho

Background

Scrub typhus is a mite-borne febrile disease caused by O. tsutsugamushi infection. Recently, emergence of scrub typhus has attracted considerable attention in several endemic countries in Asia and the western Pacific. In addition, the antigenic diversity of the intracellular pathogen has been a serious obstacle for developing effective diagnostics and vaccine.

Methodology/Principal findings

To understand the evolutionary pathway of genotypic diversification of O. tsutsugamushi and the environmental factors associated with the epidemiological features of scrub typhus, we analyzed sequence data, including spatiotemporal information, of the tsa56 gene encoding a major outer membrane protein responsible for antigenic variation. A total of 324 tsa56 sequences covering more than 85% of its open reading frame were analyzed and classified into 17 genotypes based on phylogenetic relationship. Extensive sequence analysis of tsa56 genes using diverse informatics tools revealed multiple intragenic recombination events, as well as a substantially higher mutation rate than other house-keeping genes. This suggests that genetic diversification occurred via frequent point mutations and subsequent genetic recombination. Interestingly, more diverse bacterial genotypes and dominant vector species prevail in Taiwan compared to other endemic regions. Furthermore, the co-presence of identical and sub-identical clones of tsa56 gene in geographically distant areas implies potential spread of O. tsutsugamushi genotypes.

Conclusions/Significance

Fluctuation and diversification of vector species harboring O. tsutsugamushi in local endemic areas may facilitate genetic recombination among diverse genotypes. Therefore, careful monitoring of dominant vector species, as well as the prevalence of O. tsutsugamushi genotypes may be advisable to enable proper anticipation of epidemiological changes of scrub typhus.

Human cystic echinococcosis in Morocco: Ultrasound screening in the Mid Atlas through an Italian-Moroccan partnership

PLoS Neglected Tropical Diseases News - 1 March 2017 - 10:00pm

by Houda Chebli, Abderrhamane Laamrani El Idrissi, Mustapha Benazzouz, Badre Eddine Lmimouni, Haddou Nhammi, Mourad Elabandouni, Mohammed Youbi, Rajaa Afifi, Sara Tahiri, Abdellah Essayd El Feydi, Adbellatif Settaf, Carmine Tinelli, Annalisa De Silvestri, Souad Bouhout, Bernadette Abela-Ridder, Simone Magnino, Enrico Brunetti, Carlo Filice, Francesca Tamarozzi

Background

Cystic echinococcosis (CE) is a neglected parasitic zoonosis with considerable socioeconomic impact on affected pastoral communities. CE is endemic throughout the Mediterranean, including Morocco, where the Mid Atlas is the most prevalent area for both human and animal infection. The highest hospital annual incidence of human CE is recorded in the provinces of Ifrane and El Hajeb. However, hospital-based statistics likely underestimate the real prevalence of infection, as a proportion of cases never reach medical attention or official records.

Methodology/Principal findings

In 2012, a project on clinical management of CE in Morocco was launched with the aims of estimating the prevalence of human abdominal CE in selected rural communes of the above mentioned provinces using ultrasound (US) screening and training local physicians to implement US-based focused assessment and rational clinical management of CE according to the WHO-IWGE Expert Consensus. A total of 5367 people received abdominal US during four campaigns in April-May 2014. During the campaigns, 24 local general practitioners received >24 hours of hands-on training and 143 health education sessions were organized for local communities. We found an overall CE prevalence of 1.9%, with significantly higher values in the rural communes of Ifrane than El Hajeb (2.6% vs 1.3%; p<0.001). CE cysts were predominantly in inactive stage, especially in older age groups. However, active cysts were present also in adults, indicating acquisition of infection at all ages. Province of residence was the only risk factor consistently associated with CE infection.

Conclusions/Significance

Our results show a high prevalence and on-going, likely environmental transmission of CE in the investigated provinces of Morocco, supporting the implementation of control activities in the area by national health authorities and encouraging the acceptance and divulgation of diagnosis and treatment algorithms based on imaging for CE at both national and local level.

Comparative analysis of gut microbiota of mosquito communities in central Illinois

PLoS Neglected Tropical Diseases News - 28 February 2017 - 10:00pm

by Ephantus J. Muturi, Jose L. Ramirez, Alejandro P. Rooney, Chang-Hyun Kim

Background

The composition and structure of microbial communities that inhabit the mosquito midguts are poorly understood despite their well-documented potential to impede pathogen transmission.

Methodology/Principal findings

We used MiSeq sequencing of the 16S rRNA gene to characterize the bacterial communities of field-collected populations of 12 mosquito species. After quality filtering and rarefaction, the remaining sequences were assigned to 181 operational taxonomic units (OTUs). Approximately 58% of these OTUs occurred in at least two mosquito species but only three OTUs: Gluconobacter (OTU 1), Propionibacterium (OTU 9), and Staphylococcus (OTU 31) occurred in all 12 mosquito species. Individuals of different mosquito species shared similar gut microbiota and it was common for individuals of the same species from the same study site and collection date to harbor different gut microbiota. On average, the microbiota of Aedes albopictus was the least diverse and significantly less even compared to Anopheles crucians, An. quadrimaculatus, Ae. triseriatus, Ae. vexans, Ae. japonicus, Culex restuans, and Culiseta inornata. The microbial community of Cx. pipiens and Ae. albopictus differed significantly from all other mosquitoes species and was primarily driven by the dominance of Wolbachia.

Conclusion and significance

These findings expand the range of mosquito species whose gut microbiota has been characterized and sets the foundation for further studies to determine the influence of these microbiota on vector susceptibility to pathogens.

Assessing and managing wounds of Buruli ulcer patients at the primary and secondary health care levels in Ghana

PLoS Neglected Tropical Diseases News - 28 February 2017 - 10:00pm

by Naa Okaikor Addison, Stefanie Pfau, Eric Koka, Samuel Yaw Aboagye, Grace Kpeli, Gerd Pluschke, Dorothy Yeboah-Manu, Thomas Junghanss

Background

Beyond Mycobacterium ulcerans—specific therapy, sound general wound management is required for successful management of Buruli ulcer (BU) patients which places them among the large and diverse group of patients in poor countries with a broken skin barrier.

Methods

Clinically BU suspicious patients were enrolled between October 2013 and August 2015 at a primary health care (PHC) center and a municipal hospital, secondary health care (SHC) center in Ghana. All patients were IS2404 PCR tested and divided into IS2404 PCR positive and negative groups. The course of wound healing was prospectively investigated including predictors of wound closure and assessment of infrastructure, supply and health staff performance.

Results

53 IS2404 PCR positive patients—31 at the PHC center and 22 at the SHC center were enrolled—and additionally, 80 clinically BU suspicious, IS2404 PCR negative patients at the PHC center. The majority of the skin ulcers at the PHC center closed, without the need for surgical intervention (86.7%) compared to 40% at the SHC center, where the majority required split-skin grafting (75%) or excision (12.5%). Only 9% of wounds at the PHC center, but 50% at the SHC center were complicated by bacterial infection. The majority of patients, 54.8% at the PHC center and 68.4% at the SHC center, experienced wound pain, mostly severe and associated with wound dressing. Failure of ulcers to heal was reliably predicted by wound area reduction between week 2 and 4 after initiation of treatment in 75% at the PHC center, and 90% at the SHC center. Obvious reasons for arrested wound healing or deterioration of wound were missed additional severe pathology; at the PHC center (chronic osteomyelitis, chronic lymphedema, squamous cell carcinoma) and at the SHC center (malignant ulceration, chronic lymphedema) in addition to hygiene and wound care deficiencies.When clinically suspicious, but IS2404 PCR negative patients were recaptured in the community, 76/77 (98.7%) of analyzed wounds were either completely closed (85.7%) or almost closed (13%). Five percent were found to have important missed severe pathology (chronic osteomyelitis, ossified fibroma and suspected malignancy).

Conclusion

The wounds of most BU patients attending the primary health care level can be adequately managed. Additionally, the patients are closer to their families and means of livelihood. Non-healing wounds can be predicted by wound area reduction between 2 to 4 weeks after initiation of treatment. Patients with clinically BU suspicious, but PCR negative ulcers need to be followed up to capture missed diagnoses.

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