RSS news feeds

A MALDI-TOF MS database with broad genus coverage for species-level identification of <i>Brucella</i>

PLoS Neglected Tropical Diseases News - 18 October 2018 - 9:00pm

by Jennifer Mesureur, Sandrine Arend, Béatrice Cellière, Priscillia Courault, Pierre-Jean Cotte-Pattat, Heather Totty, Parampal Deol, Virginie Mick, Victoria Girard, Joanne Touchberry, Vanessa Burrowes, Jean-Philippe Lavigne, David O’Callaghan, Valérie Monnin, Anne Keriel

Brucella are highly infectious bacterial pathogens responsible for a severely debilitating zoonosis called brucellosis. Half of the human population worldwide is considered to live at risk of exposure, mostly in the poorest rural areas of the world. Prompt diagnosis of brucellosis is essential to prevent complications and to control epidemiology outbreaks, but identification of Brucella isolates may be hampered by the lack of rapid and cost-effective methods. Nowadays, many clinical microbiology laboratories use Matrix-Assisted Laser Desorption Ionization–Time Of Flight mass spectrometry (MALDI-TOF MS) for routine identification. However, lack of reference spectra in the currently commercialized databases does not allow the identification of Brucella isolates. In this work, we constructed a Brucella MALDI-TOF MS reference database using VITEK MS. We generated 590 spectra from 84 different strains (including rare or atypical isolates) to cover this bacterial genus. We then applied a novel biomathematical approach to discriminate different species. This allowed accurate identification of Brucella isolates at the genus level with no misidentifications, in particular as the closely related and less pathogenic Ochrobactrum genus. The main zoonotic species (B. melitensis, B. abortus and B. suis) could also be identified at the species level with an accuracy of 100%, 92.9% and 100%, respectively. This MALDI-TOF reference database will be the first Brucella database validated for diagnostic and accessible to all VITEK MS users in routine. This will improve the diagnosis and control of brucellosis by allowing a rapid identification of these pathogens.

Pakistan: A nation held back by NTDs

PLoS Neglected Tropical Diseases News - 18 October 2018 - 9:00pm

by Alexander J. Blum, M. Farhan Majid, Peter J. Hotez

Uncovering vector, parasite, blood meal and microbiome patterns from mixed-DNA specimens of the Chagas disease vector <i>Triatoma dimidiata</i>

PLoS Neglected Tropical Diseases News - 18 October 2018 - 9:00pm

by Lucia C. Orantes, Carlota Monroy, Patricia L. Dorn, Lori Stevens, Donna M. Rizzo, Leslie Morrissey, John P. Hanley, Antonieta Guadalupe Rodas, Bethany Richards, Kimberly F. Wallin, Sara Helms Cahan

Chagas disease, considered a neglected disease by the World Health Organization, is caused by the protozoan parasite Trypanosoma cruzi, and transmitted by >140 triatomine species across the Americas. In Central America, the main vector is Triatoma dimidiata, an opportunistic blood meal feeder inhabiting both domestic and sylvatic ecotopes. Given the diversity of interacting biological agents involved in the epidemiology of Chagas disease, having simultaneous information on the dynamics of the parasite, vector, the gut microbiome of the vector, and the blood meal source would facilitate identifying key biotic factors associated with the risk of T. cruzi transmission. In this study, we developed a RADseq-based analysis pipeline to study mixed-species DNA extracted from T. dimidiata abdomens. To evaluate the efficacy of the method across spatial scales, we used a nested spatial sampling design that spanned from individual villages within Guatemala to major biogeographic regions of Central America. Information from each biotic source was distinguished with bioinformatics tools and used to evaluate the prevalence of T. cruzi infection and predominant Discrete Typing Units (DTUs) in the region, the population genetic structure of T. dimidiata, gut microbial diversity, and the blood meal history. An average of 3.25 million reads per specimen were obtained, with approximately 1% assigned to the parasite, 20% to the vector, 11% to bacteria, and 4% to putative blood meals. Using a total of 6,405 T. cruzi SNPs, we detected nine infected vectors harboring two distinct DTUs: TcI and a second unidentified strain, possibly TcIV. Vector specimens were sufficiently variable for population genomic analyses, with a total of 25,710 T. dimidiata SNPs across all samples that were sufficient to detect geographic genetic structure at both local and regional scales. We observed a diverse microbiotic community, with significantly higher bacterial species richness in infected T. dimidiata abdomens than those that were not infected. Unifrac analysis suggests a common assemblage of bacteria associated with infection, which co-occurs with the typical gut microbial community derived from the local environment. We identified vertebrate blood meals from five T. dimidiata abdomens, including chicken, dog, duck and human; however, additional detection methods would be necessary to confidently identify blood meal sources from most specimens. Overall, our study shows this method is effective for simultaneously generating genetic data on vectors and their associated parasites, along with ecological information on feeding patterns and microbial interactions that may be followed up with complementary approaches such as PCR-based parasite detection, 18S eukaryotic and 16S bacterial barcoding.

Catalyzing NTD gender and equity research: A call for papers

PLoS Neglected Tropical Diseases News - 18 October 2018 - 9:00pm

by Arianna Rubin Means, Alison Krentel, Sally Theobald, Laura Dean, Pamela Sabina Mbabazi, Thoko Elphick-Pooley, Fiona M. Fleming, Julie Jacobson, Sarah Simpson, Camilla Ducker

What motivates Ebola survivors to donate plasma during an emergency clinical trial? The case of Ebola-Tx in Guinea

PLoS Neglected Tropical Diseases News - 17 October 2018 - 9:00pm

by Maya Ronse, Almudena Marí Sáez, Charlotte Gryseels, Melanie Bannister-Tyrrell, Alexandre Delamou, Alain Guillard, Mustapha Briki, Frédéric Bigey, Nyankoye Haba, Johan van Griensven, Koen Peeters Grietens

Introduction

During the 2014 Ebola Virus Disease (EVD) epidemic, the Ebola-Tx trial evaluated the use of convalescent plasma (CP) in Guinea. The effectiveness of plasmapheresis trials depends on the recruitment of plasma donors. This paper describes what motivated or deterred EVD survivors to donate CP, providing insights for future plasmapheresis trials and epidemic preparedness.

Methods

This qualitative study, part of Ebola-Tx, researched and addressed emergent trial difficulties through interviewing, participant observation and focus group discussions. Sampling was theoretical and retroductive analysis was done in NVivo 10.

Results

Willingness or hesitance to participate in plasma donation depended on factors at the interface of pre-existing social dynamics; the impact of the disease and the consequent emergency response including the trial set-up. For volunteers, motivation to donate was mainly related to the feeling of social responsibility inspired by having survived EVD and to positive perceptions of plasmapheresis technology despite still unknown trial outcomes. Conversely, confidentiality concerns when volunteering due to stigmatization of survivors and perceived decrease in vital strength and in antibodies when donating, leading to fears of loss in protection against EVD, were main deterrents. The dynamic (dis)trust in Ebola Response Actors and in other survivors further determined willingness to participate and lead to the emergence/decline of rumours related to blood stealing and treatment effectiveness. Historic inter-ethnic relations in the health care setting further defined volunteering along socio-economic and ethnic lines. Finally, lack of follow-up and of dedicated care further impacted on motivation to volunteer.

Conclusions

Ebola-Tx was the first trial to solicit and evaluate blood-product donation as an experimental treatment on a large scale in Sub-Saharan Africa. An effective donation system requires directly engaging with emergent social barriers and providing an effective ethical response, including improved and transparent communication, effective follow-up after donation, assuring confidentiality and determining ethical incentives.

Safety, efficacy and acceptability of praziquantel in the treatment of <i>Schistosoma haematobium</i> in pre-school children of Kwale County, Kenya

PLoS Neglected Tropical Diseases News - 17 October 2018 - 9:00pm

by Bridget W. Kimani, Amos K. Mbugua, Jimmy H. Kihara, Murima Ng’ang’a, Doris W. Njomo

Background

The recommended strategy for control of schistosomiasis is preventive chemotherapy with praziquantel (PZQ). Pre-school children (PSC) are excluded from population treatment programs. In high endemic areas, these children are also at risk, and require treatment with PZQ. The Government of Kenya initiated the National School-Based Deworming Programme (NSBDP) where PSC in Early Childhood Development Education (ECDE) Centers are only eligible for treatment with albendazole (ABZ) but not with PZQ.

Methodology/Principal findings

400 PSC were enrolled, from 10 randomly selected ECDE Centers in Kwale County, Kenya where children were treated with crushed PZQ tablets mixed with orange juice, at a single dose of 40 mg/kg. Adverse events were assessed 24 hours post-treatment through questionnaires administered to the parents or guardians. Acceptability was determined by observing if the child spat and/ or vomited all or part of the PZQ dose immediately after treatment. Efficacy was assessed by examining urine samples for Schistosoma haematobium eggs in the 5 weeks post-treatment follow-up. Children testing negative for S. haematobium during the follow-up were considered cured. Egg reduction rate (ERR) was calculated as the decrement in the infection intensity (group’s geometric mean egg counts per 10 ml of urine) following treatment expressed as a proportion of the pre-treatment infection intensity. Before treatment, 80 out of the 400 children enrolled in the study tested positive for S. haematobium (20.0% (95% confidence interval (CI) 16.4–24.2%). Of these, 41 had infections of heavy intensity (51.3%) while the rest (48.7%) were of light intensity. Five weeks post-treatment, 10 children who had heavy intensity infection were diagnosed with S. haematobium (prevalence: 2.5% (95% CI 1.5–4.9%). Infection intensities decreased significantly from 45.9 (95% CI: 31.0–68.0) eggs/ 10 ml urine to1.4 (95% CI: 1.1–1.7) eggs/ 10 ml urine during pre-and post-treatment respectively. The ERR was 96.9%. There were no severe adverse events during follow up 24 hours post treatment. Treatment tolerability among the 400 children was high as none of the children spat and/ or vomited as observed in this study.

Conclusion/Significance

The study revealed that crushed PZQ is safe and effective in the treatment of urogenital schistosomiasis in this age group. It is therefore recommended that PZQ should be administered to the PSC in Kwale County.

Effect of schistosomiasis on the outcome of patients infected with HIV-1 starting antiretroviral therapy in rural Tanzania

PLoS Neglected Tropical Diseases News - 17 October 2018 - 9:00pm

by Katarina Stete, Tracy R. Glass, Govert J. van Dam, Alex Ntamatungiro, Emilio Letang, Claudia J. de Dood, Paul L. A. M. Corstjens, Robert Ndege, Herry Mapesi, Winfried V. Kern, Christoph Hatz, Maja Weisser, Jürg Utzinger, Matthias C. Müller

Background

It has been hypothesized that schistosomiasis negatively influences immune reconstitution in people living with HIV starting antiretroviral therapy (ART). In this study, we investigated the effect of schistosomiasis on the course of HIV infection in patients starting ART in a rural part of Tanzania.

Methodology

Retrospective study including patients prospectively enrolled in a HIV cohort in Ifakara, south-central Tanzania between January 1, 2013 and April 1, 2015. Schistosomal circulating anodic antigen (CAA) was assessed in pre-ART cryopreserved plasma. Regression models were utilized to estimate the effect of CAA positivity on virological and immunological failure and a composite outcome of death/loss to follow-up (LFU).

Principal findings

At ART-initiation 19.1% (88/461) of patients were CAA-positive. A tendency of higher CD4 increases was seen in CAA-positive patients (+182 cells/μl, interquartile range (IQR), 87–285 cells/μl) compared to CAA-negative patients (+147 cells/μl, IQR, 55–234 cells/μl, p = 0.09) after 10 months of follow-up. After adjustment for baseline risk factors, CAA-positivity showed no association with virological or immunological failure. In CAA-positive patients, 22.7% (20/88) died or were LFU, compared to 29.5% (110/373) of CAA-negative patients (hazard ratio (HR): 0.76, 95% confidence interval (CI), 0.47–1.22, p = 0.25). After adjustment for age, sex, body mass index, educational attainment, WHO-stage, tuberculosis status, and year of ART initiation, CAA-positivity showed a trend of a decreased hazard of death/LFU (HR: 0.58, 95% CI: 0.32–1.05, p = 0.07), while CD4 count at baseline (HR: 0.86, 95% CI: 0.76–1.00, p = 0.02) and MXD (sum of eosinophils, basophils, and monocytes counts) >1,100 cells/μl (HR: 0.56, 95% CI: 0.34–0.93, p = 0.03) were identified as independently protective factors.

Conclusions/Significance

Schistosomiasis is prevalent in this HIV cohort and may be beneficial for immunological reconstitution, while no effect on virological failure was apparent. A positive effect of schistosomiasis-induced immunomodulation on survival and retention in care needs confirmation in future studies.

Development of an urban molecular xenomonitoring system for lymphatic filariasis in the Recife Metropolitan Region, Brazil

PLoS Neglected Tropical Diseases News - 16 October 2018 - 9:00pm

by Anita Ramesh, Mary Cameron, Kirstin Spence, Remy Hoek Spaans, Maria A. V. Melo-Santos, Marcelo H. S. Paiva, Duschinka R. D. Guedes, Rosangela M. R. Barbosa, Claudia M. F. Oliveira, André Sá, Claire L. Jeffries, Priscila M. S. Castanha, Paula A. S. Oliveira, Thomas Walker, Neal Alexander, Cynthia Braga

Introduction

Molecular xenomonitoring (MX)—pathogen detection in the mosquito rather than human—is a promising tool for lymphatic filariasis (LF) surveillance. In the Recife Metropolitan Region (RMR), the last LF focus in Brazil, Culex quinquefasciatus mosquitoes have been implicated in transmitting Wuchereria bancrofti parasites. This paper presents findings on the ideal mosquito collection method, mosquito dispersion, W. bancrofti infection in mosquitoes and W. bancrofti antigen in humans to aid MX development.

Methods

Experiments occurred within two densely populated urban areas of Olinda, RMR, in July and August 2015. U.S. Centers for Disease Control and Prevention (CDC) light traps were compared to battery-powered aspirators as collection methods, and mosquito dispersion was measured by mosquito mark release recapture (MMRR). Female Cx. quinquefasciatus were tested by PCR for W. bancrofti infection, and study area residents were screened by rapid tests for W. bancrofti antigen.

Results

Aspirators caught 2.6 times more total Cx. quinquefasciatus, including 38 times more blood-fed and 5 times more gravid stages, than CDC light traps. They also collected 123 times more Aedes aegypti. Of the 9,644 marked mosquitoes released, only ten (0.01%) were recaptured, nine of which were < 50m (34.8m median, 85.4m maximum) from the release point. Of 9,169 unmarked mosquitoes captured in the MMR, 38.3% were unfed, 48.8% blood-fed, 5.5% semi-gravid, and 7.3% gravid. PCR on 182 pools (1,556 mosquitoes) found no evidence of W. bancrofti infection in Cx. quinquefasciatus. Rapid tests on 110 of 111 eligible residents were all negative for W. bancrofti antigen.

Conclusions

Aspirators were more effective than CDC light traps at capturing Ae. aegypti and all but unfed stages of Cx. quinquefasciatus. Female Cx. quinquefasciatus traveled short (< 86m) distances in this urban area. Lack of evidence for W. bancrofti infection in mosquitoes and antigen in humans in these fine-scale studies does not indicate that LF transmission has ceased in the RMR. A MX surveillance system should consider vector-specific collection methods, mosquito dispersion, and spatial scale but also local context, environmental factors such as sanitation, and host factors such as infection prevalence and treatment history.

Location, seasonal, and functional characteristics of water holding containers with juvenile and pupal<i>Aedes aegypti</i> in Southern Taiwan: A cross-sectional study using hurdle model analyses

PLoS Neglected Tropical Diseases News - 15 October 2018 - 9:00pm

by Chia-Hsien Lin, Karin Linda Schiøler, Claus Thorn Ekstrøm, Flemming Konradsen

Background

Aedes aegypti carries several viruses of public health importance, including the dengue virus. Dengue is the most rapidly spreading mosquito-borne viral disease in the world. Prevention and control of dengue mainly rely on mosquito control as there is no antiviral treatment or a WHO-approved vaccine. To reduce the Ae. aegypti population, studying the characteristics of their habitats is necessary. Aedes aegypti prefer breeding in artificial water holding containers in peridomestic or domestic settings. Their juveniles (1st - 4th instar larvae and pupae) have a tendency to cluster in certain types of containers. To inform control strategies, it is important to assess whether the pupae subgroup has a distinct distribution by container type as compared to the overall group of juveniles. The objective of this study was to assess for distinct predictors (location, season, and function) of Ae. aegypti juveniles and pupae numbers in water holding containers by applying hurdle model analyses.

Methodology

The field component of this study was carried out from November 2013 to July 2015 in Southern Taiwan where annual autochthonous dengue has been reported for decades. Water holding containers with stagnant water were identified in a predefined urban area in Kaohsiung City (KH) and a rural area in Pingtung County. Given that mosquito survey data often include many containers with zero Ae. aegypti, a negative binomial hurdle model was applied to model the association between location, seasonal and functional characteristics of the water holding containers and the number of Ae. aegypti in each container.

Results

The results showed that Ae. aegypti were almost exclusively present in the urban area. In this area, the negative binomial hurdle model predicted significantly more juveniles as well as pupae Ae. aegypti in water holding containers during the wet season when compared to the dry season. Notably, the model predicted more juveniles in containers located on private property compared to those on government property, irrespective of season. As for pupae, the model predicted higher amounts in indoor containers used for water storage compared to outdoor water storage containers, irrespective of season. However, for the specific category ‘other water receptacle’, higher amounts of pupae were predicted in outdoor compared to indoor in water receptacles, such as flower pot saucers and water catchment buckets.

Conclusions

The difference in predictors for juveniles and the pupae subgroup was identified and it may be of importance to the control strategies of the authorities in KH. At present the authorities focus control activities on all water holding containers found on government property. To improve the ongoing control efforts in KH, the focus of control activities maintained by the KH authorities should be expanded to indoor water storage containers and outdoor water receptacles on both private and government properties to adequately address habitats harboring greater numbers of pupae. In addition, it is proposed to increase community engagement in managing water in all types of water holding containers located on privately owned properties (indoor and outdoor), especially during wet season.

Vector competence of <i>Aedes bromeliae</i> and <i>Aedes vitattus</i> mosquito populations from Kenya for chikungunya virus

PLoS Neglected Tropical Diseases News - 15 October 2018 - 9:00pm

by Francis Mulwa, Joel Lutomiah, Edith Chepkorir, Samwel Okello, Fredrick Eyase, Caroline Tigoi, Michael Kahato, Rosemary Sang

Background

Kenya has experienced outbreaks of chikungunya in the past years with the most recent outbreak occurring in Mandera in the northern region in May 2016 and in Mombasa in the coastal region from November 2017 to February 2018. Despite the outbreaks in Kenya, studies on vector competence have only been conducted on Aedes aegypti. However, the role played by other mosquito species in transmission and maintenance of the virus in endemic areas remains unclear. This study sought to determine the possible role of rural Aedes bromeliae and Aedes vittatus in the transmission of chikungunya virus, focusing on Kilifi and West Pokot regions of Kenya.

Methods

Four day old female mosquitoes were orally fed on chikungunya virus-infected blood at a dilution of 1:1 of the viral isolate and blood (106.4 plaque-forming units [PFU]/ml) using artificial membrane feeder (Hemotek system) for 45 minutes. The engorged mosquitoes were picked and incubated at 29–30°C ambient temperature and 70–80% humidity in the insectary. At days 5, 7 and 10 post-infection, the mosquitoes were carefully dissected to separate the legs and wings from the body and their proboscis individually inserted in the capillary tube containing minimum essential media (MEM) to collect salivary expectorate. The resultant homogenates and the salivary expectorates were tested by plaque assay to determine virus infection, dissemination and transmission potential of the mosquitoes.

Results

A total of 515 female mosquitoes (311 Ae. bromeliae and 204 Ae. vittatus) were exposed to the East/Central/South Africa (ECSA) lineage of chikungunya virus. Aedes vittatus showed high susceptibility to the virus ranging between 75–90% and moderate dissemination and transmission rates ranging from 35–50%. Aedes bromeliae had moderate susceptibility ranging between 26–40% with moderate dissemination and transmission rates ranging from 27–55%.

Conclusion

This study demonstrates that both Ae. vittatus and Ae. bromeliae populations from West Pokot and Kilifi counties in Kenya are competent vectors of chikungunya virus. Based on these results, the two areas are at risk of virus transmission in the event of an outbreak. This study underscores the need to institute vector competence studies for populations of potential vector species as a means of evaluating risk of transmission of the emerging and re-emerging arboviruses in diverse regions of Kenya.

Modification and optimization of the FECPAK<sup>G2</sup> protocol for the detection and quantification of soil-transmitted helminth eggs in human stool

PLoS Neglected Tropical Diseases News - 15 October 2018 - 9:00pm

by Mio Ayana, Johnny Vlaminck, Piet Cools, Shaali Ame, Marco Albonico, Daniel Dana, Jennifer Keiser, Helen Manly, Leonardo F. Matoso, Zeleke Mekonnen, Antonio Montresor, Rodrigo Correa-Oliveira, Laura Rinaldi, Somphou Sayasone, Lensa Tesfaye, Jozef Vercruysse, Greg Mirams, Bruno Levecke

Background

Standard diagnosis of human soil-transmitted helminth (STH) infections is based on the microscopic detection of helminth eggs in stool and supports programmatic decision making in control programs. However, the current standard diagnostic techniques still show a number of limitations. Recently, the FECPAKG2 method was developed to detect helminth infections and asses drug efficacy in sheep or cattle. It includes a device that takes digital images of helminth eggs that have been concentrated into one microscopic field of view and stores these images online for future evaluation. The goal of this study was to introduce a standard operating procedure (SOP) for the detection and quantification of human STH eggs using the FECPAKG2 and to optimize 2 crucial steps of the protocol, namely the sedimentation step (aimed at separating sinking eggs from floating debris) and the accumulation step (aimed at concentrating the eggs by flotation).

Methodology/Principal findings

A total of 55 stool samples from naturally infected children were used from 4 different geographical areas (Ethiopia, Laos, Tanzania and Brazil). The results showed that Trichuris eggs generally moved slower than eggs of the other two STH species during both sedimentation in water in the FECPAKG2 sedimenter as during accumulation in flotation solution in the FECPAKG2 cassettes. The highest number of eggs were present in the slurry of the sedimenter after overnight sedimentation (Ascaris: 95.7%, Trichuris: 89.8% and hookworm: 94.2% of the eggs). A minimum of 24 minutes were needed to ensure the accumulation of at least 80% of the eggs from all three STH species in the FECPAKG2 cassette (Ascaris: 96.1%; Trichuris: 88.2% and hookworm: 87.6%).

Conclusions/Significance

This study introduces for the first time a SOP for the FECPAKG2 method. Different aspects of the method for diagnosing human STH infections were optimized. Our study forms the basis for a thorough and objective evaluation of the system as a diagnostic tool that could be implemented in STH control programs.

Risk factors for HTLV-1 infection in Central Africa: A rural population-based survey in Gabon

PLoS Neglected Tropical Diseases News - 12 October 2018 - 9:00pm

by Delia Doreen Djuicy, Augustin Mouinga-Ondémé, Olivier Cassar, Jill-Léa Ramassamy, Antony Idam Mamimandjiami, Rodrigue Bikangui, Arnaud Fontanet, Antoine Gessain

Background

Human T-Lymphotropic Virus type 1 (HTLV-1) is a human oncoretrovirus that infects at least 5 to 10 million people worldwide and is associated with severe diseases. Africa appears as the largest HTLV-1 endemic area. However, the risk factors for the acquisition of HTLV-1 remain poorly understood in Central Africa.

Methods

We conducted an epidemiological survey between 2013 and 2017, in rural areas of 6 provinces of Gabon, in a rainforest environment. Epidemiological data were obtained and blood samples were collected after informed consent. Plasma were screened for HTLV-1 antibodies by ELISA and the positive samples were then tested by Western blot (WB). Genomic DNA derived from buffy-coat was subjected to two semi-nested PCRs amplifying either HTLV-1 env gene or LTR region fragments.

Results

We recruited 2,060 individuals over 15 years old, including 1,205 men and 855 women (mean age: 49 years). Of these, 299 were found to be ELISA HTLV-1/2 seropositive. According to WB criteria, 136 were HTLV-1 (6.6%), 25 HTLV-1/2 (1.2%) and 9 HTLV seroreactive (0.4%). PCR results showed that 146 individuals were positive for at least one PCR: 104 for the env gene and 131 for the LTR region. Based on both serological and molecular results, 179 individuals were considered infected with HTLV-1, leading to an overall prevalence of 8.7%. The distribution of HTLV-1 infection was heterogeneous across the country. Based on multivariable analyses, female gender, increasing age, ethnicity (Pygmy) and multiple hospitalizations (more than 5 times) were found to be independent risk factors for HTLV-1 infection. Furthermore, a non-human primate bite appeared to be marginally associated with a higher risk of HTLV-1 infection.

Conclusion

Based on state-of-the-art serological and molecular methods, we have demonstrated that rural adult populations in Gabon are highly endemic for HTLV-1. Our results regarding risk factors should lead to public health actions aiming to reduce HTLV-1 transmission.

Estimating the economic impact of canine rabies to Viet Nam 2005–2014

PLoS Neglected Tropical Diseases News - 11 October 2018 - 9:00pm

by Stephanie A. Shwiff, Vienna R. Brown, Thu Trang Dao, Julie Elser, Hoang Xuan Trung, Nguyen Ngoc Tien, Nguyen Thi Huong, Nguyen Thi Thanh Huong, Arthorn Riewpaiboon, Karina Ernst, Steven Shwiff, David Payne

The global economic impact of canine rabies has been estimated by several studies. Asia bears a disproportionate burden of this zoonosis due to high levels of human deaths and rates of post-exposure prophylaxis (PEP), but low investment in preventative dog vaccination. The same factors that cause rabies to burden much of Asia are also present in Viet Nam. This study estimated the economic burden of canine rabies in a societal perspective including direct and indirect cost of rabies in dogs, livestock, and humans. Using data collected from personal interviews, published literature, published and supplementary reports, and primary data collection, we estimated the economic impact of canine rabies in Viet Nam over a ten year period (2005–2014). We incorporated the direct and indirect costs for PEP, dog vaccination efforts, livestock losses, and disability adjusted life years (DALYs) into the analysis. General findings from this analysis indicated that over the 10 year study period, the total economic impact of canine rabies was over $719 million USD. The largest portion of impacts (92%) were made up of PEP-related costs. Canine rabies created between 36,560 and 45,700 DALYs, measured in years of life lost (YLL). A total of 914 human deaths were reported over the study period. Deaths/100,000 people were 0.11, which is lower than the reported level for Asian countries. The cost per dog vaccinated was $1.75 USD. Our results indicate that canine rabies impacts in Viet Nam are consistent with the burden elsewhere reported in Asia, with large expenditures on PEP and very small investments in dog vaccination.

A gene expression comparison of <i>Trypanosoma brucei</i> and <i>Trypanosoma congolense</i> in the bloodstream of the mammalian host reveals species-specific adaptations to density-dependent development

PLoS Neglected Tropical Diseases News - 11 October 2018 - 9:00pm

by Eleanor Silvester, Alasdair Ivens, Keith R. Matthews

In the bloodstream of mammalian hosts Trypanosoma brucei undergoes well-characterised density-dependent growth control and developmental adaptation for transmission. This involves the differentiation from proliferative, morphologically ‘slender’ forms to quiescent ‘stumpy’ forms that preferentially infect the tsetse fly vector. Another important livestock trypanosome, Trypanosoma congolense, also undergoes density-dependent cell-cycle arrest although this is not linked to obvious morphological transformation. Here we have compared the gene expression profile of T. brucei and T. congolense during the ascending phase of the parasitaemia and at peak parasitaemia in mice, analysing species and developmental differences between proliferating and cell-cycle arrested forms. Despite underlying conservation of their quorum sensing signalling pathway, each species exhibits distinct profiles of gene regulation when analysed by orthogroup and cell surface phylome profiling. This analysis of peak parasitaemia T. congolense provides the first molecular signatures of potential developmental competence, assisting life cycle developmental studies in these important livestock parasites. Furthermore, comparison with T. brucei identifies candidate molecules from each species that may be important for their survival in the mammalian host, transmission or distinct tropism in the tsetse vector.

Predictive risk mapping of an environmentally-driven infectious disease using spatial Bayesian networks: A case study of leptospirosis in Fiji

PLoS Neglected Tropical Diseases News - 11 October 2018 - 9:00pm

by Helen J. Mayfield, Carl S. Smith, John H. Lowry, Conall H. Watson, Michael G. Baker, Mike Kama, Eric J. Nilles, Colleen L. Lau

Introduction

Leptospirosis is a zoonotic disease responsible for over 1 million severe cases and 60,000 deaths annually. The wide range of animal hosts and complex environmental drivers of transmission make targeted interventions challenging, particularly when restricted to regression-based analyses which have limited ability to deal with complexity. In Fiji, important environmental and socio-demographic factors include living in rural areas, poverty, and livestock exposure. This study aims to examine drivers of transmission under different scenarios of environmental and livestock exposures.

Methods

Spatial Bayesian networks (SBN) were used to analyse the influence of livestock and poverty on the risk of leptospirosis infection in urban compared to rural areas. The SBN models used a combination of spatially-explicit field data from previous work and publically available census information. Predictive risk maps were produced for overall risk, and for scenarios related to poverty, livestock, and urban/rural setting.

Results

While high, rather than low, commercial dairy farm density similarly increased the risk of infection in both urban (12% to 18%) and rural areas (70% to 79%), the presence of pigs in a village had different impact in rural (43% to 84%) compared with urban areas (4% to 24%). Areas with high poverty rates were predicted to have 26.6% and 18.0% higher probability of above average seroprevalence in rural and urban areas, respectively. In urban areas, this represents >300% difference between areas of low and high poverty, compared to 43% difference in rural areas.

Conclusions

Our study demonstrates the use of SBN to provide valuable insights into the drivers of leptospirosis transmission under complex scenarios. By estimating the risk of leptospirosis infection under different scenarios, such as urban versus rural areas, these subgroups or areas can be targeted with more precise interventions that focus on the most relevant key drivers of infection.

A systematic review of antimicrobial resistance in <i>Salmonella enterica</i> serovar Typhi, the etiological agent of typhoid

PLoS Neglected Tropical Diseases News - 11 October 2018 - 9:00pm

by Carl D. Britto, Vanessa K. Wong, Gordan Dougan, Andrew J. Pollard

Background

The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well as planning sustainable prevention strategies.

Methodology and findings

To identify the phenotypic trends in AMR, 13,833 individual S. Typhi isolates, reported from 1973 to 2018 in 62 publications, were analysed to determine the AMR preponderance over time. Separate analyses of molecular resistance determinants present in over 4,000 isolates reported in 61 publications were also conducted. Multi-drug resistant (MDR) typhoid is in decline in Asia in a setting of high fluoroquinolone resistance while it is on the increase in Africa. Mutations in QRDRs in gyrA (S83F, D87N) and parC (S80I) are the most common mechanisms responsible for fluoroquinolone resistance. Cephalosporin resistant S. Typhi, dubbed extensively drug-resistant (XDR) is a real threat and underscores the urgency in deploying the Vi-conjugate vaccines.

Conclusion

From these observations, it appears that AMR in S. Typhi will continue to emerge leading to treatment failure, changes in antimicrobial policy and further resistance developing in S. Typhi isolates and other Gram-negative bacteria in endemic regions. The deployment of typhoid conjugate vaccines to control the disease in endemic regions may be the best defence.

Rutin (quercetin-3-rutinoside) modulates the hemostatic disturbances and redox imbalance induced by <i>Bothrops jararaca</i> snake venom in mice

PLoS Neglected Tropical Diseases News - 11 October 2018 - 9:00pm

by Ana Teresa Azevedo Sachetto, Jaqueline Gomes Rosa, Marcelo Larami Santoro

Snakebites are a major Collective Health problem worldwide. In Brazil, Bothrops jararaca snake venom (BjV) evokes hemostatic disturbances, bleeding manifestations, and redox status imbalance. Specific antivenom therapy, although efficacious to revert most snakebite-induced manifestations, is incapable of treating secondary manifestations, such as oxidative/nitrosative stress. Searching for new complementary therapies that could attenuate physiological derangements triggered by envenomation, we elected to test quercetin-3-rutinoside (rutin) by its potential as both a potent antioxidant and a hemostasis modulatory compound. The activity of rutin was evaluated both on the biological activities of crude BjV in vitro, and in vivo by the ability of rutin (14.4 mg/kg b.w.) to modulate hematological, hemostatic and redox status markers altered by BjV injection (1.6 mg/kg b.w., s.c.) in mice. In vitro, rutin failed to inhibit BjV-induced platelet aggregation and biological activities of major BjV enzymes (metalloproteinases, phospholipases A2, serine proteases, and L-amino acid oxidases). On the other hand, rutin attenuated local hemorrhage, and the increase in reactive species, prevented the fall in RBC counts and fibrinogen levels, diminished tail bleeding and shortened prothrombin time (PT) evoked by envenomation. Furthermore, rutin reduced tissue factor (TF) activity and altered the protein expression of TF in liver, lungs, heart and skin. In conclusion, the disturbances in redox status and hemostatic system induced by B. jararaca envenomation were modulated by rutin, suggesting it has a great potential to be used as an ancillary therapeutic agent for snakebites.

Optimising sampling regimes and data collection to inform surveillance for trachoma control

PLoS Neglected Tropical Diseases News - 11 October 2018 - 9:00pm

by Amy Pinsent, T. Dèirdre Hollingsworth

It is estimated that 190 million individuals are at risk of blindness from trachoma, and that control by mass drug administration (MDA) is reducing this risk in many populations. Programs are monitored using prevalence of follicular trachoma disease (TF) in children. However, as programs progress to low prevalence there are challenges interpreting this indirect measure of infection. PCR and sero-surveillance are being considered as complementary tools to monitor low-level transmission, but there are questions on how they can be most effectively used. We use a previously-published, mathematical model to explore the dynamic relationship between TF and PCR throughout a control program and a sero-catalytic model to evaluate the utility of two cross-sectional sero-surveys for estimating sero-conversion rates. The simulations show that whilst PCR is more sensitive than TF at detecting infection, the probability of detecting at least one positive individual declines during an MDA program more quickly for PCR than for TF (for the same sample size). Towards the end of a program there is a moderate chance of a random sample showing both low PCR prevalence and higher TF prevalence, which may contribute to the lack of correlation observed in epidemiological studies. We also show that conducting two cross-sectional sero-surveys 10 years apart can provide more precise and accurate estimation of epidemiological parameters than a single survey, supporting previous findings that whilst serology holds great promise, multiple cross-sections from the same community are needed to generate the most valuable information about transmission. These results highlight that the quantitative dynamics of infection and disease should be included alongside the many logistical and practical factors to be considered in designing a monitoring and evaluation strategy at the operational research level, in order to help subsequently inform data collection for individual country programs. Whilst our simulations provide some insight, they also highlight that some level of longitudinal, individual-level data on reinfection and disease may be needed to monitor elimination progress.

Complete genome sequences of two strains of <i>Treponema pallidum</i> subsp. <i>pertenue</i> from Indonesia: Modular structure of several treponemal genes

PLoS Neglected Tropical Diseases News - 10 October 2018 - 9:00pm

by Michal Strouhal, Lenka Mikalová, Jan Haviernik, Sascha Knauf, Sylvia Bruisten, Gerda T. Noordhoek, Jan Oppelt, Darina Čejková, David Šmajs

Background

Treponema pallidum subsp. pertenue (TPE) is the causative agent of yaws, a multistage disease endemic in tropical regions in Africa, Asia, Oceania, and South America. To date, seven TPE strains have been completely sequenced and analyzed including five TPE strains of human origin (CDC-2, CDC 2575, Gauthier, Ghana-051, and Samoa D) and two TPE strains isolated from the baboons (Fribourg-Blanc and LMNP-1). This study revealed the complete genome sequences of two TPE strains, Kampung Dalan K363 and Sei Geringging K403, isolated in 1990 from villages in the Pariaman region of Sumatra, Indonesia and compared these genome sequences with other known TPE genomes.

Methodology/principal findings

The genomes were determined using the pooled segment genome sequencing method combined with the Illumina sequencing platform resulting in an average coverage depth of 1,021x and 644x for the TPE Kampung Dalan K363 and TPE Sei Geringging K403 genomes, respectively. Both Indonesian TPE strains were genetically related to each other and were more distantly related to other, previously characterized TPE strains. The modular character of several genes, including TP0136 and TP0858 gene orthologs, was identified by analysis of the corresponding sequences. To systematically detect genes potentially having a modular genetic structure, we performed a whole genome analysis-of-occurrence of direct or inverted repeats of 17 or more nucleotides in length. Besides in tpr genes, a frequent presence of repeats was found in the genetic regions spanning TP0126–TP0136, TP0856–TP0858, and TP0896 genes.

Conclusions/significance

Comparisons of genome sequences of TPE Kampung Dalan K363 and Sei Geringging K403 with other TPE strains revealed a modular structure of several genomic loci including the TP0136, TP0856, and TP0858 genes. Diversification of TPE genomes appears to be facilitated by intra-strain genome recombination events.

Pages