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Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Ryan M. Wallace, Anna Pees, Jesse B. Blanton, Susan M. Moore

Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs’ failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57–1.72, ANOVA p < 0.01). There was no statistical difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12–16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8–30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer.

Correction: Diagnosis of Bacterial Bloodstream Infections: A 16S Metagenomics Approach

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Saskia Decuypere, Conor J. Meehan, Sandra Van Puyvelde, Tessa De Block, Jessica Maltha, Lompo Palpouguini, Marc Tahita, Halidou Tinto, Jan Jacobs, Stijn Deborggraeve

Correction: Use of Oral Cholera Vaccine and Knowledge, Attitudes, and Practices Regarding Safe Water, Sanitation and Hygiene in a Long-Standing Refugee Camp, Thailand, 2012-2014

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Heather M. Scobie, Christina R. Phares, Kathleen A. Wannemuehler, Edith Nyangoma, Eboni M. Taylor, Anna Fulton, Nuttapong Wongjindanon, Naw Rody Aung, Philippe Travers, Kashmira Date

Double impact: natural molluscicide for schistosomiasis vector control also impedes development of <i>Schistosoma mansoni</i> cercariae into adult parasites

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Ronaldo de Carvalho Augusto, Guillaume Tetreau, Philippe Chan, Marie-Laure Walet-Balieu, Clélia Christina Mello-Silva, Claudia Portes Santos, Christoph Grunau

Background

Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite’s biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite’s life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts.

Methodology/Principal findings

We used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics.

Conclusions/Significance

We describe here the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes in the parasite. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without preventing re-infection).

Extensive sonographic ulnar nerve enlargement above the medial epicondyle is a characteristic sign in Hansen’s neuropathy

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Lokesh Bathala, Venkataramana N. Krishnam, Hari Kishan Kumar, Vivekananda Neladimmanahally, Umashankar Nagaraju, Himanshu M. Kumar, Johan A. Telleman, Leo H. Visser

Objective

Earlier studies have shown sonographic enlargement of the ulnar nerve in patients with Hansen’s neuropathy. The present study was performed to determine whether sonography or electrophysiological studies can detect the specific site of ulnar nerve pathology in leprosy.

Methods

Eighteen patients (thirty arms) with Hansen’s disease and an ulnar neuropathy of whom 66% had borderline tuberculoid (BT), 27% lepromatous leprosy (LL) and 7% mid-borderline (BB) leprosy were included in the study. Cross-sectional area (CSA) of ulnar nerve was measured every two centimeters from wrist to medial epicondyle and from there to axilla. All patients underwent standard motor and sensory nerve conduction studies of the ulnar nerve. Thirty age and sex matched controls underwent similar ulnar nerve CSA measurements and conduction studies.

Results

Ulnar nerve was clinically palpable in 19 of the 30 arms of patients. Motor and sensory nerve conduction studies of the ulnar nerve showed a reduced compound motor action potential and sensory nerve action potential amplitude in all patients. Motor Conduction Velocity (MCV) in patients were slower in comparison to controls, especially at the elbow and upper arm, but unable to exactly locate the site of the lesion. In comparison to controls the ulnar nerveCSA was larger in the whole arm in patients and quite specific the maximum enlargement was seen between nulnar sulcus and axilla, peaking at four centimeters above the sulcus.

Conclusions

A unique sonographic pattern of nerve enlargement is noted in patients with ulnar neuropathy due to Hansen’s disease, while this was not the case for the technique used until now, the electrodiagnostic testing. The enlargement starts at ulnar sulcus and is maximum four centimeters above the medial epicondyle and starts reducing further along the tract. This characteristic finding can help especially in diagnosing pure neuritic type of Hansen’s disease, in which skin lesions are absent, and alsoto differentiate leprosy from other neuropathies in which nerve enlargement can occur.

Amino acid metabolic signaling influences <i>Aedes aegypti</i> midgut microbiome variability

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Sarah M. Short, Emmanuel F. Mongodin, Hannah J. MacLeod, Octavio A. C. Talyuli, George Dimopoulos

The mosquito midgut microbiota has been shown to influence vector competence for multiple human pathogens. The microbiota is highly variable in the field, and the sources of this variability are not well understood, which limits our ability to understand or predict its effects on pathogen transmission. In this work, we report significant variation in female adult midgut bacterial load between strains of A. aegypti which vary in their susceptibility to dengue virus. Composition of the midgut microbiome was similar overall between the strains, with 81–92% of reads coming from the same five bacterial families, though we did detect differences in the presence of some bacterial families including Flavobacteriaceae and Entobacteriaceae. We conducted transcriptomic analysis on the two mosquito strains that showed the greatest difference in bacterial load, and found that they differ in transcript abundance of many genes implicated in amino acid metabolism, in particular the branched chain amino acid degradation pathway. We then silenced this pathway by targeting multiple genes using RNA interference, which resulted in strain-specific bacterial proliferation, thereby eliminating the difference in midgut bacterial load between the strains. This suggests that the branched chain amino acid (BCAA) degradation pathway controls midgut bacterial load, though the mechanism underlying this remains unclear. Overall, our results indicate that amino acid metabolism can act to influence the midgut microbiota. Moreover, they suggest that genetic or physiological variation in BCAA degradation pathway activity may in part explain midgut microbiota variation in the field.

<i>Leptospira interrogans</i> causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Hiromi Sato, Jenifer Coburn

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection.

Expression of intra- and extracellular granzymes in patients with typhoid fever

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Hanna K. de Jong, Maria Isabel Garcia-Laorden, Arie J. Hoogendijk, Christopher M. Parry, Rapeephan R. Maude, Arjen M. Dondorp, Mohammed Abul Faiz, Tom van der Poll, Willem Joost Wiersinga

Background

Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release.

Methods and principal findings

We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls.

Conclusion

The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.

Adding tsetse control to medical activities contributes to decreasing transmission of sleeping sickness in the Mandoul focus (Chad)

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Mahamat Hissene Mahamat, Mallaye Peka, Jean-Baptiste Rayaisse, Kat S. Rock, Mahamat Abdelrahim Toko, Justin Darnas, Guihini Mollo Brahim, Ali Bachar Alkatib, Wilfrid Yoni, Inaki Tirados, Fabrice Courtin, Samuel P. C. Brand, Cyrus Nersy, Idriss Oumar Alfaroukh, Steve J. Torr, Mike J. Lehane, Philippe Solano

Background

Gambian sleeping sickness or HAT (human African trypanosomiasis) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by riverine species of tsetse. A global programme aims to eliminate the disease as a public health problem by 2020 and stop transmission by 2030. In the South of Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where around 100 HAT cases were still diagnosed and treated annually until 2013. Pre-2014, control of HAT relied solely on case detection and treatment, which lead to a gradual decrease in the number of cases of HAT due to annual screening of the population.

Methods

Because of the persistence of transmission and detection of new cases, we assessed whether the addition of vector control to case detection and treatment could further reduce transmission and consequently, reduce annual incidence of HAT in Mandoul. In particular, we investigated the impact of deploying ‘tiny targets’ which attract and kill tsetse. Before tsetse control commenced, a census of the human population was conducted and their settlements mapped. A pre-intervention survey of tsetse distribution and abundance was implemented in November 2013 and 2600 targets were deployed in the riverine habitats of tsetse in early 2014, 2015 and 2016. Impact on tsetse and on the incidence of sleeping sickness was assessed through nine tsetse monitoring surveys and four medical surveys of the human population in 2014 and 2015. Mathematical modelling was used to assess the relative impact of tsetse control on incidence compared to active and passive screening.

Findings

The census indicated that a population of 38674 inhabitants lived in the vicinity of the Mandoul focus. Within this focus in November 2013, the vector is Glossina fuscipes fuscipes and the mean catch of tsetse from traps was 0.7 flies/trap/day (range, 0–26). The catch of tsetse from 44 sentinel biconical traps declined after target deployment with only five tsetse being caught in nine surveys giving a mean catch of 0.005 tsetse/trap/day. Modelling indicates that 70.4% (95% CI: 51–95%) of the reduction in reported cases between 2013 and 2015 can be attributed to vector control with the rest due to medical intervention. Similarly tiny targets are estimated to have reduced new infections dramatically with 62.8% (95% CI: 59–66%) of the reduction due to tsetse control, and 8.5% (95% 8–9%) to enhanced passive detection. Model predictions anticipate that elimination as a public health problem could be achieved by 2018 in this focus if vector control and screening continue at the present level and, furthermore, there may have been virtually no transmission since 2015.

Conclusion

This work shows that tiny targets reduced the numbers of tsetse in this focus in Chad, which may have interrupted transmission and the combination of tsetse control to medical detection and treatment has played a major role in reducing in HAT incidence in 2014 and 2015.

Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Seung-Ji Kang, Hye-Mi Jin, Young-Nan Cho, Seong Eun Kim, Uh Jin Kim, Kyung-Hwa Park, Hee-Chang Jang, Sook-In Jung, Seung-Jung Kee, Yong-Wook Park

Background

Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus.

Methodology/Principal findings

This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase.

Conclusions

This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients.

A novel rapid test for detecting antibody responses to <i>Loa loa</i> infections

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Bijan Pedram, Valérie Pasquetto, Papa M. Drame, Yongchang Ji, Maria J. Gonzalez-Moa, Richard K. Baldwin, Thomas B. Nutman, Marco A. Biamonte

Ivermectin-based mass drug administration (MDA) programs have achieved remarkable success towards the elimination of onchocerciasis and lymphatic filariasis. However, their full implementation has been hindered in Central Africa by the occurrence of ivermectin-related severe adverse events (SAEs) in a subset of individuals with high circulating levels of Loa loa microfilariae. Extending MDA to areas with coincident L. loa infection is problematic, and inexpensive point-of-care tests for L. loa are acutely needed. Herein, we present a lateral flow assay (LFA) to identify subjects with a serological response to Ll-SXP-1, a specific and validated marker of L. loa. The test was evaluated on serum samples from patients infected with L. loa (n = 109) and other helminths (n = 204), as well as on uninfected controls (n = 77). When read with the naked eye, the test was 94% sensitive for L. loa infection and was 100% specific when sera from healthy endemic and non-endemic controls or from those with S. stercoralis infections were used as the comparators. When sera of patients with O. volvulus, W. bancrofti, or M. perstans were used as the comparators, the specificity of the LFA was 82%, 87%, and 88%, respectively. A companion smartphone reader allowed measurement of the test line intensities and establishment of cutoff values. With a cutoff of 600 Units, the assay sensitivity decreased to 71%, but the specificity increased to 96% for O. volvulus, 100% for W. bancrofti, and 100% for M. perstans-infected individuals. The LFA may find applications in refining the current maps of L. loa prevalence, which are needed to eliminate onchocerciasis and lymphatic filariasis from the African continent.

Transmission risk of two chikungunya lineages by invasive mosquito vectors from Florida and the Dominican Republic

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Barry W. Alto, Keenan Wiggins, Bradley Eastmond, Daniel Velez, L. Philip Lounibos, Cynthia C. Lord

Between 2014 and 2016 more than 3,800 imported human cases of chikungunya fever in Florida highlight the high risk for local transmission. To examine the potential for sustained local transmission of chikungunya virus (CHIKV) in Florida we tested whether local populations of Aedes aegypti and Aedes albopictus show differences in susceptibility to infection and transmission to two emergent lineages of CHIKV, Indian Ocean (IOC) and Asian genotypes (AC) in laboratory experiments. All examined populations of Ae. aegypti and Ae. albopictus mosquitoes displayed susceptibility to infection, rapid viral dissemination into the hemocoel, and transmission for both emergent lineages of CHIKV. Aedes albopictus had higher disseminated infection and transmission of IOC sooner after ingesting CHIKV infected blood than Ae. aegypti. Aedes aegypti had higher disseminated infection and transmission later during infection with AC than Ae. albopictus. Viral dissemination and transmission of AC declined during the extrinsic incubation period, suggesting that transmission risk declines with length of infection. Interestingly, the reduction in transmission of AC was less in Ae. aegypti than Ae. albopictus, suggesting that older Ae. aegypti females are relatively more competent vectors than similar aged Ae. albopictus females. Aedes aegypti originating from the Dominican Republic had viral dissemination and transmission rates for IOC and AC strains that were lower than for Florida vectors. We identified small-scale geographic variation in vector competence among Ae. aegypti and Ae. albopictus that may contribute to regional differences in risk of CHIKV transmission in Florida.

Participation of women and children in hunting activities in Sierra Leone and implications for control of zoonotic infections

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Jesse Bonwitt, Martin Kandeh, Michael Dawson, Rashid Ansumana, Foday Sahr, Ann H. Kelly, Hannah Brown

The emergence of infectious diseases of zoonotic origin highlights the need to understand social practices at the animal-human interface. This study provides a qualitative account of interactions between humans and wild animals in predominantly Mende villages of southern Sierra Leone. We conducted fieldwork over 4 months including participant and direct observations, semi-structured interviews (n = 47), spontaneously occurring focus group discussions (n = 12), school essays and informal interviews to describe behaviours that may serve as pathways for zoonotic infection. In this region, hunting is the primary form of contact with wild animals. We describe how these interactions are shaped by socio-cultural contexts, including opportunities to access economic resources and by social obligations and constraints. Our research suggests that the potential for exposure to zoonotic pathogens is more widely distributed across different age, gender and social groups than previously appreciated. We highlight the role of children in hunting, an age group that has previously not been discussed in the context of hunting. The breadth of the "at risk" population forces reconsideration of how we conceptualize, trace and monitor pathogen exposure.

<i>Aedes ægypti</i> control in urban areas: A systemic approach to a complex dynamic

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Marilia Sá Carvalho, Nildimar Alves Honorio, Leandro Martin Totaro Garcia, Luiz Carlos de Sá Carvalho

Author summary: The available strategy for controlling the diseases transmitted by Aedes ægypti (dengue fever, Zika, and chikungunya) relies on continued community participation. Despite slogans emphasizing how easy it should be, no country has achieved it since the seventies. To better investigate potentially sustainable interventions, we developed a systemic model based on a multidisciplinary approach, integrating as deeply as possible specialized knowledge and field experience. The resulting model is composed of 4 external and 8 internal subsystems and 31 relationships, consistent with the literature and checked over multiple iterations with specialists of the many areas. We analyzed the model and the main feedback loops responsible for the system’s stability, searching for possible interventions that could shift the existing balance. We suggest the introduction of 1 more player, the local primary health care structure, with the potential to change the undesired equilibrium. The health agents in the areas are the first to detect disease cases, and they could stimulate individuals to inform about potential mosquitoes’ breeding sites and bring timely information to the vector-control program. Triggering such an action could introduce changes in people's attitude through a positive feedback loop in the desired direction.

Genome-wide analysis of ivermectin response by <i>Onchocerca volvulus</i> reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

PLoS Neglected Tropical Diseases News - 26 July 2017 - 9:00pm

by Stephen R. Doyle, Catherine Bourguinat, Hugues C. Nana-Djeunga, Jonas A. Kengne-Ouafo, Sébastien D. S. Pion, Jean Bopda, Joseph Kamgno, Samuel Wanji, Hua Che, Annette C. Kuesel, Martin Walker, Maria-Gloria Basáñez, Daniel A. Boakye, Mike Y. Osei-Atweneboana, Michel Boussinesq, Roger K. Prichard, Warwick N. Grant

Background

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana—exposed to more than a decade of regular ivermectin treatment—have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.

Methodology/Principal findings

Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.

Conclusions/Significance

This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations.

Transmission dynamics of co-endemic <i>Plasmodium vivax</i> and <i>P</i>. <i>falciparum</i> in Ethiopia and prevalence of antimalarial resistant genotypes

PLoS Neglected Tropical Diseases News - 26 July 2017 - 9:00pm

by Eugenia Lo, Elizabeth Hemming-Schroeder, Delenasaw Yewhalaw, Jennifer Nguyen, Estifanos Kebede, Endalew Zemene, Sisay Getachew, Kora Tushune, Daibin Zhong, Guofa Zhou, Beyene Petros, Guiyun Yan

Ethiopia is one of the few African countries where Plasmodium vivax is co-endemic with P. falciparum. Malaria transmission is seasonal and transmission intensity varies mainly by landscape and climate. Although the recent emergence of drug resistant parasites presents a major issue to malaria control in Ethiopia, little is known about the transmission pathways of parasite species and prevalence of resistant markers. This study used microsatellites to determine population diversity and gene flow patterns of P. falciparum (N = 226) and P. vivax (N = 205), as well as prevalence of drug resistant markers to infer the impact of gene flow and existing malaria treatment regimes. Plasmodium falciparum indicated a higher rate of polyclonal infections than P. vivax. Both species revealed moderate genetic diversity and similar population structure. Populations in the northern highlands were closely related to the eastern Rift Valley, but slightly distinct from the southern basin area. Gene flow via human migrations between the northern and eastern populations were frequent and mostly bidirectional. Landscape genetic analyses indicated that environmental heterogeneity and geographical distance did not constrain parasite gene flow. This may partly explain similar patterns of resistant marker prevalence. In P. falciparum, a high prevalence of mutant alleles was detected in codons related to chloroquine (pfcrt and pfmdr1) and sulfadoxine-pyrimethamine (pfdhps and pfdhfr) resistance. Over 60% of the samples showed pfmdr1 duplications. Nevertheless, no mutation was detected in pfK13 that relates to artemisinin resistance. In P. vivax, while sequences of pvcrt-o were highly conserved and less than 5% of the samples showed pvmdr duplications, over 50% of the samples had pvmdr1 976F mutation. It remains to be tested if this mutation relates to chloroquine resistance. Monitoring the extent of malaria spread and markers of drug resistance is imperative to inform policy for evidence-based antimalarial choice and interventions. To effectively reduce malaria burden in Ethiopia, control efforts should focus on seasonal migrant populations.

The disease burden of human cystic echinococcosis based on HDRs from 2001 to 2014 in Italy

PLoS Neglected Tropical Diseases News - 26 July 2017 - 9:00pm

by Toni Piseddu, Diego Brundu, Giovanni Stegel, Federica Loi, Sandro Rolesu, Gabriella Masu, Salvatore Ledda, Giovanna Masala

Background

Cystic echinococcosis (CE) is an important neglected zoonotic parasitic infection belonging to the subgroup of seven Neglected Zoonotic Disease (NZDs) included in the World Health Organization’s official list of 18 Neglected Tropical Diseases (NTDs). CE causes serious global human health concerns and leads to significant economic losses arising from the costs of medical treatment, morbidity, life impairments and fatality rates in human cases. Moreover, CE is endemic in several Italian Regions. The aim of this study is to perform a detailed analysis of the economic burden of hospitalization and treatment costs and to estimate the Disability Adjusted Life Years (DALYs) of CE in Italy.

Methods and findings

In the period from 2001 to 2014, the direct costs of 21,050 Hospital Discharge Records (HDRs) belonging to 12,619 patients with at least one CE-related diagnosis codes were analyzed in order to quantify the economic burden of CE. CE cases average per annum are 901 (min—max = 480–1,583). Direct costs include expenses for hospitalizations, medical and surgical treatment incurred by public and private hospitals and were computed on an individual basis according to Italian Health Ministry legislation. Moreover, we estimated the DALYs for each patient. The Italian financial burden of CE is around € 53 million; the national average economic burden per annum is around € 4 million; the DALYs of the population from 2001 to 2014 are 223.35 annually and 5.26 DALYs per 105 inhabitants.

Conclusion

In Italy, human CE is responsible for significant economic losses in the public health sector. In humans, costs associated with CE have been shown to have a great impact on affected individuals, their families and the community as a whole. This study could be used as a tool to prioritize and make decisions with regard to a surveillance system for this largely preventable yet neglected disease. It demonstrates the need of implementing a CE control program aimed at preventing the considerable economic and social losses it causes in high incidence areas.

Risk of exposure to potential vector mosquitoes for rural workers in Northern Lao PDR

PLoS Neglected Tropical Diseases News - 25 July 2017 - 9:00pm

by Julie-Anne A. Tangena, Phoutmany Thammavong, Steve W. Lindsay, Paul T. Brey

Background

One major consequence of economic development in South-East Asia has been a rapid expansion of rubber plantations, in which outbreaks of dengue and malaria have occurred. Here we explored the difference in risk of exposure to potential dengue, Japanese encephalitis (JE), and malaria vectors between rubber workers and those engaged in traditional forest activities in northern Laos PDR.

Methodology/Principal findings

Adult mosquitoes were collected for nine months in secondary forests, mature and immature rubber plantations, and villages. Human behavior data were collected using rapid participatory rural appraisals and surveys. Exposure risk was assessed by combining vector and human behavior and calculating the basic reproduction number (R0) in different typologies. Compared to those that stayed in the village, the risk of dengue vector exposure was higher for those that visited the secondary forests during the day (odds ratio (OR) 36.0), for those living and working in rubber plantations (OR 16.2) and for those that tapped rubber (OR 3.2). Exposure to JE vectors was also higher in the forest (OR 1.4) and, similar when working (OR 1.0) and living in the plantations (OR 0.8). Exposure to malaria vectors was greater in the forest (OR 1.3), similar when working in the plantations (OR 0.9) and lower when living in the plantations (OR 0.6). R0 for dengue was >2.8 for all habitats surveyed, except villages where R0≤0.06. The main malaria vector in all habitats was Anopheles maculatus s.l. in the rainy season and An. minimus s.l. in the dry season.

Conclusions/Significance

The highest risk of exposure to vector mosquitoes occurred when people visit natural forests. However, since rubber workers spend long periods in the rubber plantations, their risk of exposure is increased greatly compared to those who temporarily enter natural forests or remain in the village. This study highlights the necessity of broadening mosquito control to include rubber plantations.

Wetlands, wild Bovidae species richness and sheep density delineate risk of Rift Valley fever outbreaks in the African continent and Arabian Peninsula

PLoS Neglected Tropical Diseases News - 25 July 2017 - 9:00pm

by Michael G. Walsh, Allard Willem de Smalen, Siobhan M. Mor

Rift Valley fever (RVF) is an emerging, vector-borne viral zoonosis that has significantly impacted public health, livestock health and production, and food security over the last three decades across large regions of the African continent and the Arabian Peninsula. The potential for expansion of RVF outbreaks within and beyond the range of previous occurrence is unknown. Despite many large national and international epidemics, the landscape epidemiology of RVF remains obscure, particularly with respect to the ecological roles of wildlife reservoirs and surface water features. The current investigation modeled RVF risk throughout Africa and the Arabian Peninsula as a function of a suite of biotic and abiotic landscape features using machine learning methods. Intermittent wetland, wild Bovidae species richness and sheep density were associated with increased landscape suitability to RVF outbreaks. These results suggest the role of wildlife hosts and distinct hydrogeographic landscapes in RVF virus circulation and subsequent outbreaks may be underestimated. These results await validation by studies employing a deeper, field-based interrogation of potential wildlife hosts within high risk taxa.

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