PLoS Neglected Tropical Diseases News

Subscribe to PLoS Neglected Tropical Diseases News feed PLoS Neglected Tropical Diseases News
A Peer-Reviewed Open-Access Journal
Updated: 13 hours 26 min ago

The cost of mapping trachoma: Data from the Global Trachoma Mapping Project

18 October 2017 - 9:00pm

by Guillaume Trotignon, Ellen Jones, Thomas Engels, Elena Schmidt, Deborah A. McFarland, Colin K. Macleod, Khaled Amer, Amadou A. Bio, Ana Bakhtiari, Sarah Bovill, Amy H. Doherty, Asad Aslam Khan, Mariamo Mbofana, Siobhain McCullagh, Tom Millar, Consity Mwale, Lisa A. Rotondo, Angela Weaver, Rebecca Willis, Anthony W. Solomon

Background

The Global Trachoma Mapping Project (GTMP) was implemented with the aim of completing the baseline map of trachoma globally. Over 2.6 million people were examined in 1,546 districts across 29 countries between December 2012 and January 2016. The aim of the analysis was to estimate the unit cost and to identify the key cost drivers of trachoma prevalence surveys conducted as part of GTMP.

Methodology and principal findings

In-country and global support costs were obtained using GTMP financial records. In-country expenditure was analysed for 1,164 districts across 17 countries. The mean survey cost was $13,113 per district [median: $11,675; IQR = $8,365-$14,618], $17,566 per evaluation unit [median: $15,839; IQR = $10,773-$19,915], $692 per cluster [median: $625; IQR = $452-$847] and $6.0 per person screened [median: $4.9; IQR = $3.7-$7.9]. Survey unit costs varied substantially across settings, and were driven by parameters such as geographic location, demographic characteristics, seasonal effects, and local operational constraints. Analysis by activities showed that fieldwork constituted the largest share of in-country survey costs (74%), followed by training of survey teams (11%). The main drivers of in-country survey costs were personnel (49%) and transportation (44%). Global support expenditure for all surveyed districts amounted to $5.1m, which included grant management, epidemiological support, and data stewardship.

Conclusion

This study provides the most extensive analysis of the cost of conducting trachoma prevalence surveys to date. The findings can aid planning and budgeting for future trachoma surveys required to measure the impact of trachoma elimination activities. Furthermore, the results of this study can also be used as a cost basis for other disease mapping programmes, where disease or context-specific survey cost data are not available.

Genome-wide SNPs reveal the drivers of gene flow in an urban population of the Asian Tiger Mosquito, <i>Aedes albopictus</i>

18 October 2017 - 9:00pm

by Thomas L. Schmidt, Gordana Rašić, Dongjing Zhang, Xiaoying Zheng, Zhiyong Xi, Ary A. Hoffmann

Aedes albopictus is a highly invasive disease vector with an expanding worldwide distribution. Genetic assays using low to medium resolution markers have found little evidence of spatial genetic structure even at broad geographic scales, suggesting frequent passive movement along human transportation networks. Here we analysed genetic structure of Aedes albopictus collected from 12 sample sites in Guangzhou, China, using thousands of genome-wide single nucleotide polymorphisms (SNPs). We found evidence for passive gene flow, with distance from shipping terminals being the strongest predictor of genetic distance among mosquitoes. As further evidence of passive dispersal, we found multiple pairs of full-siblings distributed between two sample sites 3.7 km apart. After accounting for geographical variability, we also found evidence for isolation by distance, previously undetectable in Ae. albopictus. These findings demonstrate how large SNP datasets and spatially-explicit hypothesis testing can be used to decipher processes at finer geographic scales than formerly possible. Our approach can be used to help predict new invasion pathways of Ae. albopictus and to refine strategies for vector control that involve the transformation or suppression of mosquito populations.

The study of trypanosome species circulating in domestic animals in two human African trypanosomiasis foci of Côte d'Ivoire identifies pigs and cattle as potential reservoirs of <i>Trypanosoma brucei gambiense</i>

18 October 2017 - 9:00pm

by Martial Kassi N’Djetchi, Hamidou Ilboudo, Mathurin Koffi, Jacques Kaboré, Justin Windingoudi Kaboré, Dramane Kaba, Fabrice Courtin, Bamoro Coulibaly, Pierre Fauret, Lingué Kouakou, Sophie Ravel, Stijn Deborggraeve, Philippe Solano, Thierry De Meeûs, Bruno Bucheton, Vincent Jamonneau

Background

Important control efforts have led to a significant reduction of the prevalence of human African trypanosomiasis (HAT) in Côte d’Ivoire, but the disease is still present in several foci. The existence of an animal reservoir of Trypanosoma brucei gambiense may explain disease persistence in these foci where animal breeding is an important source of income but where the prevalence of animal African trypanosomiasis (AAT) is unknown. The aim of this study was to identify the trypanosome species circulating in domestic animals in both Bonon and Sinfra HAT endemic foci.

Methodology/Principal findings

552 domestic animals (goats, pigs, cattle and sheep) were included. Blood samples were tested for trypanosomes by microscopic observation, species-specific PCR for T. brucei sl, T. congolense, T. vivax and subspecies-specific PCR for T. b. gambiense and T. b. gambiense immune trypanolysis (TL). Infection rates varied significantly between animal species and were by far the highest in pigs (30%). T. brucei s.l was the most prevalent trypanosome species (13.7%) followed by T. congolense. No T. b. gambiense was identified by PCR while high TL positivity rates were observed using T. b. gambiense specific variants (up to 27.6% for pigs in the Bonon focus).

Conclusion

This study shows that domestic animals are highly infected by trypanosomes in the studied foci. This was particularly true for pigs, possibly due to a higher exposure of these animals to tsetse flies. Whereas T. brucei s.l. was the most prevalent species, discordant results were obtained between PCR and TL regarding T. b. gambiense identification. It is therefore crucial to develop better tools to study the epidemiological role of potential animal reservoir for T. b. gambiense. Our study illustrates the importance of “one health” approaches to reach HAT elimination and contribute to AAT control in the studied foci.

Transcriptomic responses of <i>Biomphalaria pfeifferi</i> to <i>Schistosoma mansoni</i>: Investigation of a neglected African snail that supports more <i>S</i>. <i>mansoni</i> transmission than any other snail species

18 October 2017 - 9:00pm

by Sarah K. Buddenborg, Lijing Bu, Si-Ming Zhang, Faye D. Schilkey, Gerald M. Mkoji, Eric S. Loker

Background

Biomphalaria pfeifferi is highly compatible with the widespread human-infecting blood fluke Schistosoma mansoni and transmits more cases of this parasite to people than any other snail species. For these reasons, B. pfeifferi is the world’s most important vector snail for S. mansoni, yet we know relatively little at the molecular level regarding the interactions between B. pfeifferi and S. mansoni from early-stage sporocyst transformation to the development of cercariae.

Methodology/Principal findings

We sought to capture a portrait of the response of B. pfeifferi to S. mansoni as it occurs in nature by undertaking Illumina dual RNA-Seq on uninfected control B. pfeifferi and three intramolluscan developmental stages (1- and 3-days post infection and patent, cercariae-producing infections) using field-derived west Kenyan specimens. A high-quality, well-annotated de novo B. pfeifferi transcriptome was assembled from over a half billion non-S. mansoni paired-end reads. Reads associated with potential symbionts were noted. Some infected snails yielded fewer normalized S. mansoni reads and showed different patterns of transcriptional response than others, an indication that the ability of field-derived snails to support and respond to infection is variable. Alterations in transcripts associated with reproduction were noted, including for the oviposition-related hormone ovipostatin and enzymes involved in metabolism of bioactive amines like dopamine or serotonin. Shedding snails exhibited responses consistent with the need for tissue repair. Both generalized stress and immune factors immune factors (VIgLs, PGRPs, BGBPs, complement C1q-like, chitinases) exhibited complex transcriptional responses in this compatible host-parasite system.

Significance

This study provides for the first time a large sequence data set to help in interpreting the important vector role of the neglected snail B. pfeifferi in transmission of S. mansoni, including with an emphasis on more natural, field-derived specimens. We have identified B. pfeifferi targets particularly responsive during infection that enable further dissection of the functional role of these candidate molecules.

MicroRNA profiling of human primary macrophages exposed to dengue virus identifies miRNA-3614-5p as antiviral and regulator of ADAR1 expression

18 October 2017 - 9:00pm

by Mayra Diosa-Toro, Liliana Echavarría-Consuegra, Jacky Flipse, Geysson Javier Fernández, Joost Kluiver, Anke van den Berg, Silvio Urcuqui-Inchima, Jolanda M. Smit

Background

Due to the high burden of dengue disease worldwide, a better understanding of the interactions between dengue virus (DENV) and its human host cells is of the outmost importance. Although microRNAs modulate the outcome of several viral infections, their contribution to DENV replication is poorly understood.

Methods and principal findings

We investigated the microRNA expression profile of primary human macrophages challenged with DENV and deciphered the contribution of microRNAs to infection. To this end, human primary macrophages were challenged with GFP-expressing DENV and sorted to differentiate between truly infected cells (DENV-positive) and DENV-exposed but non-infected cells (DENV-negative cells). The miRNAome was determined by small RNA-Seq analysis and the effect of differentially expressed microRNAs on DENV yield was examined. Five microRNAs were differentially expressed in human macrophages challenged with DENV. Of these, miR-3614-5p was found upregulated in DENV-negative cells and its overexpression reduced DENV infectivity. The cellular targets of miR-3614-5p were identified by liquid chromatography/mass spectrometry and western blot. Adenosine deaminase acting on RNA 1 (ADAR1) was identified as one of the targets of miR-3614-5p and was shown to promote DENV infectivity at early time points post-infection.

Conclusion/Significance

Overall, miRNAs appear to play a limited role in DENV replication in primary human macrophages. The miRNAs that were found upregulated in DENV-infected cells did not control the production of infectious virus particles. On the other hand, miR-3614-5p, which was upregulated in DENV-negative macrophages, reduced DENV infectivity and regulated ADAR1 expression, a protein that facilitates viral replication.

Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa

18 October 2017 - 9:00pm

by Robert A. Harrison, George O. Oluoch, Stuart Ainsworth, Jaffer Alsolaiss, Fiona Bolton, Ana-Silvia Arias, José-María Gutiérrez, Paul Rowley, Stephen Kalya, Hastings Ozwara, Nicholas R. Casewell

Background

Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa.

Methods

We collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a ‘gold standard’ comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom.

Findings

None of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro assays of the abilities of ‘test’ antivenom IgGs to bind venom proteins were not substantially different from that of the ‘gold standard’ antivenoms. The least effective antivenoms had the lowest IgG content/vial.

Conclusions

Manufacture-stated preclinical efficacy statements guide decision making by physicians and antivenom purchasers in sub-Saharan Africa. This is because of the lack of both clinical data on the efficacy of most of the many antivenoms used to treat patients and independent preclinical assessment. Our preclinical efficacy assessment of antivenoms available in Kenya identifies important limitations for two of the most commonly-used antivenoms, and that no antivenom is preclinically effective against all the regionally important snakes. The potential implication to snakebite treatment is of serious concern in Kenya and elsewhere in sub-Saharan Africa, and underscores the dilemma physicians face, the need for clinical data on antivenom efficacy and the medical and societal value of establishing independent preclinical antivenom-efficacy testing facilities throughout the continent.

<i>Schistosoma japonicum</i> transmission risk maps at present and under climate change in mainland China

17 October 2017 - 9:00pm

by Gengping Zhu, Jingyu Fan, A. Townsend Peterson

Background

The South-to-North Water Diversion (SNWD) project is designed to channel fresh water from the Yangtze River north to more industrialized parts of China. An important question is whether future climate change and dispersal via the SNWD may synergistically favor a northward expansion of species involved in hosting and transmitting schistosomiasis in China, specifically the intermediate host, Oncomelania hupensis.

Methodology/ Principal findings

In this study, climate spaces occupied by the four subspecies of O. hupensis (O. h. hupensis, O. h. robertsoni, O. h. guangxiensis and O. h. tangi) were estimated, and niche conservatism tested among each pair of subspecies. Fine-tuned Maxent (fMaxent) and ensemble models were used to anticipate potential distributions of O. hupensis under future climate change scenarios. We were largely unable to reject the null hypothesis that climatic niches are conserved among the four subspecies, so factors other than climate appear to account for the divergence of O. hupensis populations across mainland China. Both model approaches indicated increased suitability and range expansion in O. h. hupensis in the future; an eastward and northward shift in O. h. robertsioni and O. h. guangxiensis, respectively; and relative distributional stability in O. h. gangi.

Conclusions/Significance

The southern parts of the Central Route of SNWD will coincide with suitable areas for O. h. hupensis in 2050–2060; its suitable areas will also expand northward along the southern parts of the Eastern Route by 2080–2090. Our results call for rigorous monitoring and surveillance of schistosomiasis along the southern Central Route and Eastern Route of the SNWD in a future, warmer China.

Characterization of the Zika virus induced small RNA response in <i>Aedes aegypti</i> cells

17 October 2017 - 9:00pm

by Margus Varjak, Claire L. Donald, Timothy J. Mottram, Vattipally B. Sreenu, Andres Merits, Kevin Maringer, Esther Schnettler, Alain Kohl

RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two different RNAi pathways are involved in antiviral responses: the PIWI-interacting RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are characterized by the production of virus-derived small RNAs of 25–29 and 21 nucleotides, respectively. The exo-siRNA pathway is considered to be the key mosquito antiviral response mechanism. In Aedes aegypti-derived cells, Zika virus (ZIKV)-specific siRNAs were produced and loaded into the exo-siRNA pathway effector protein Argonaute 2 (Ago2); although the knockdown of Ago2 did not enhance virus replication. Enhanced ZIKV replication was observed in a Dcr2-knockout cell line suggesting that the exo-siRNA pathway is implicated in the antiviral response. Although ZIKV-specific piRNA-sized small RNAs were detected, these lacked the characteristic piRNA ping-pong signature motif and were bound to Ago3 but not Piwi5 or Piwi6. Silencing of PIWI proteins indicated that the knockdown of Ago3, Piwi5 or Piwi6 did not enhance ZIKV replication and only Piwi4 displayed antiviral activity. We also report that the expression of ZIKV capsid (C) protein amplified the replication of a reporter alphavirus; although, unlike yellow fever virus C protein, it does not inhibit the exo-siRNA pathway. Our findings elucidate ZIKV-mosquito RNAi interactions that are important for understanding its spread.

Impaired anti-fibrotic effect of bone marrow-derived mesenchymal stem cell in a mouse model of pulmonary paracoccidioidomycosis

17 October 2017 - 9:00pm

by Julián Camilo Arango, Juan David Puerta-Arias, Paula Andrea Pino-Tamayo, Lina María Salazar-Peláez, Mauricio Rojas, Ángel González

Bone marrow-derived mesenchymal stem cells (BMMSCs) have been consider as a promising therapy in fibrotic diseases. Experimental models suggest that BMMSCs may be used as an alternative therapy to treat chemical- or physical-induced pulmonary fibrosis. We investigated the anti-fibrotic potential of BMMSCs in an experimental model of lung fibrosis by infection with Paracoccidioides brasiliensis. BMMSCs were isolated and purified from BALB/c mice using standardized methods. BALB/c male mice were inoculated by intranasal infection of 1.5x106 P. brasiliensis yeasts. Then, 1x106 BMMSCs were administered intra venous at 8th week post-infection (p.i.). An additional group of mice was treated with itraconazole (ITC) two weeks before BMMSCs administration. Animals were sacrificed at 12th week p.i. Histopathological examination, fibrocytes counts, soluble collagen and fibrosis-related genes expression in lungs were evaluated. Additionally, human fibroblasts were treated with homogenized lung supernatants (HLS) to determine induction of collagen expression. Histological analysis showed an increase of granulomatous inflammatory areas in BMMSCs-treated mice. A significant increase of fibrocytes count, soluble collagen and collagen-3α1, TGF-β3, MMP-8 and MMP-15 genes expression were also observed in those mice. Interestingly, when combined therapy BMMSCs/ITC was used there is a decrease of TIMP-1 and MMP-13 gene expression in infected mice. Finally, human fibroblasts stimulated with HLS from infected and BMMSCs-transplanted mice showed a higher expression of collagen I. In conclusion, our findings indicate that late infusion of BMMSCs into mice infected with paracoccidioidomycosis does not have any anti-fibrotic effect; possibly because their interaction with the fungus promotes collagen expression and tissue remodeling.

Serological and spatial analysis of alphavirus and flavivirus prevalence and risk factors in a rural community in western Kenya

17 October 2017 - 9:00pm

by Elysse N. Grossi-Soyster, Elizabeth A. J. Cook, William A. de Glanville, Lian F. Thomas, Amy R. Krystosik, Justin Lee, C. Njeri Wamae, Samuel Kariuki, Eric M. Fèvre, A. Desiree LaBeaud

Alphaviruses, such as chikungunya virus, and flaviviruses, such as dengue virus, are (re)-emerging arboviruses that are endemic in tropical environments. In Africa, arbovirus infections are often undiagnosed and unreported, with febrile illnesses often assumed to be malaria. This cross-sectional study aimed to characterize the seroprevalence of alphaviruses and flaviviruses among children (ages 5–14, n = 250) and adults (ages 15 ≥ 75, n = 250) in western Kenya. Risk factors for seropositivity were explored using Lasso regression. Overall, 67% of participants showed alphavirus seropositivity (CI95 63%–70%), and 1.6% of participants showed flavivirus seropositivity (CI95 0.7%–3%). Children aged 10–14 were more likely to be seropositive to an alphavirus than adults (p < 0.001), suggesting a recent transmission period. Alphavirus and flavivirus seropositivity was detected in the youngest participants (age 5–9), providing evidence of inter-epidemic transmission. Demographic variables that were significantly different amongst those with previous infection versus those without infection included age, education level, and occupation. Behavioral and environmental variables significantly different amongst those in with previous infection to those without infection included taking animals for grazing, fishing, and recent village flooding. Experience of recent fever was also found to be a significant indicator of infection (p = 0.027). These results confirm alphavirus and flavivirus exposure in western Kenya, while illustrating significantly higher alphavirus transmission compared to previous studies.

Protecting cows in small holder farms in East Africa from tsetse flies by mimicking the odor profile of a non-host bovid

17 October 2017 - 9:00pm

by Rajinder K. Saini, Benedict O. Orindi, Norber Mbahin, John A. Andoke, Peter N. Muasa, David M. Mbuvi, Caroline M. Muya, John A. Pickett, Christian W. Borgemeister

Background

For the first time, differential attraction of pathogen vectors to vertebrate animals is investigated for novel repellents which when applied to preferred host animals turn them into non-hosts thereby providing a new paradigm for innovative vector control. For effectively controlling tsetse flies (Glossina spp.), vectors of African trypanosomosis, causing nagana, repellents more powerful than plant derived, from a non-host animal the waterbuck, Kobus ellipsiprymnus defassa, have recently been identified. Here we investigate these repellents in the field to protect cattle from nagana by making cattle as unattractive as the buck.

Methodology/Principal findings

To dispense the waterbuck repellents comprising guaiacol, geranylacetone, pentanoic acid and δ-octalactone, (patent application) we developed an innovative collar-mounted release system for individual cattle. We tested protecting cattle, under natural tsetse challenge, from tsetse transmitted nagana in a large field trial comprising 1,100 cattle with repellent collars in Kenya for 24 months. The collars provided substantial protection to livestock from trypanosome infection by reducing disease levels >80%. Protected cattle were healthier, showed significantly reduced disease levels, higher packed cell volume and significantly increased weight. Collars >60% reduced trypanocide use, 72.7% increase in ownership of oxen per household and enhanced traction power (protected animals ploughed 66% more land than unprotected). Land under cultivation increased by 73.4%. Increase in traction power of protected animals reduced by 69.1% acres tilled by hand per household per ploughing season. Improved food security and household income from very high acceptance of collars (99%) motivated the farmers to form a registered community based organization promoting collars for integrated tsetse control and their commercialization.

Conclusion/Significance

Clear demonstration that repellents from un-preferred hosts prevent contact between host and vector, thereby preventing disease transmission: a new paradigm for vector control. Evidence that deploying water buck repellents converts cattle into non-hosts for tsetse flies—‘cows in waterbuck clothing’.

Developing a dengue forecast model using machine learning: A case study in China

16 October 2017 - 9:00pm

by Pi Guo, Tao Liu, Qin Zhang, Li Wang, Jianpeng Xiao, Qingying Zhang, Ganfeng Luo, Zhihao Li, Jianfeng He, Yonghui Zhang, Wenjun Ma

Background

In China, dengue remains an important public health issue with expanded areas and increased incidence recently. Accurate and timely forecasts of dengue incidence in China are still lacking. We aimed to use the state-of-the-art machine learning algorithms to develop an accurate predictive model of dengue.

Methodology/Principal findings

Weekly dengue cases, Baidu search queries and climate factors (mean temperature, relative humidity and rainfall) during 2011–2014 in Guangdong were gathered. A dengue search index was constructed for developing the predictive models in combination with climate factors. The observed year and week were also included in the models to control for the long-term trend and seasonality. Several machine learning algorithms, including the support vector regression (SVR) algorithm, step-down linear regression model, gradient boosted regression tree algorithm (GBM), negative binomial regression model (NBM), least absolute shrinkage and selection operator (LASSO) linear regression model and generalized additive model (GAM), were used as candidate models to predict dengue incidence. Performance and goodness of fit of the models were assessed using the root-mean-square error (RMSE) and R-squared measures. The residuals of the models were examined using the autocorrelation and partial autocorrelation function analyses to check the validity of the models. The models were further validated using dengue surveillance data from five other provinces. The epidemics during the last 12 weeks and the peak of the 2014 large outbreak were accurately forecasted by the SVR model selected by a cross-validation technique. Moreover, the SVR model had the consistently smallest prediction error rates for tracking the dynamics of dengue and forecasting the outbreaks in other areas in China.

Conclusion and significance

The proposed SVR model achieved a superior performance in comparison with other forecasting techniques assessed in this study. The findings can help the government and community respond early to dengue epidemics.

Substantial population structure of <i>Plasmodium vivax</i> in Thailand facilitates identification of the sources of residual transmission

16 October 2017 - 9:00pm

by Veerayuth Kittichai, Cristian Koepfli, Wang Nguitragool, Jetsumon Sattabongkot, Liwang Cui

Background

Plasmodium vivax transmission in Thailand has been substantially reduced over the past 10 years, yet it remains highly endemic along international borders. Understanding the genetic relationship of residual parasite populations can help track the origins of the parasites that are reintroduced into malaria-free regions within the country.

Methodology/Results

A total of 127 P. vivax isolates were genotyped from two western provinces (Tak and Kanchanaburi) and one eastern province (Ubon Ratchathani) of Thailand using 10 microsatellite markers. Genetic diversity was high, but recent clonal expansion was detected in all three provinces. Substantial population structure and genetic differentiation of parasites among provinces suggest limited gene flow among these sites. There was no haplotype sharing among the three sites, and a reduced panel of four microsatellite markers was sufficient to assign the parasites to their provincial origins.

Conclusion/Significance

Significant parasite genetic differentiation between provinces shows successful interruption of parasite spread within Thailand, but high diversity along international borders implies a substantial parasite population size in these regions. The provincial origin of P. vivax cases can be reliably determined by genotyping four microsatellite markers, which should be useful for monitoring parasite reintroduction after malaria elimination.

A recombinase polymerase amplification assay for rapid detection of Crimean-Congo Haemorrhagic fever Virus infection

13 October 2017 - 9:00pm

by Laura C. Bonney, Robert J. Watson, Babak Afrough, Manija Mullojonova, Viktoriya Dzhuraeva, Farida Tishkova, Roger Hewson

Background

Crimean-Congo Haemorrhagic fever Virus (CCHFV) is a rapidly emerging vector-borne pathogen and the cause of a virulent haemorrhagic fever affecting large parts of Europe, Africa, the Middle East and Asia.

Methodology/principle findings

An isothermal recombinase polymerase amplification (RPA) assay was successfully developed for molecular detection of CCHFV. The assay showed rapid (under 10 minutes) detection of viral extracts/synthetic virus RNA of all 7 S-segment clades of CCHFV, with high target specificity. The assay was shown to tolerate the presence of inhibitors in crude preparations of mock field samples, indicating that this assay may be suitable for use in the field with minimal sample preparation. The CCHFV RPA was successfully used to screen and detect CCHFV positives from a panel of clinical samples from Tajikistan.

Conclusions/significance

The assay is a rapid, isothermal, simple-to-perform molecular diagnostic, which can be performed on a light, portable real-time detection device. It is ideally placed therefore for use as a field-diagnostic or in-low resource laboratories, for monitoring of CCHF outbreaks at the point-of-need, such as in remote rural regions in affected countries.

Clinico-pathological features of erythema nodosum leprosum: A case-control study at ALERT hospital, Ethiopia

13 October 2017 - 9:00pm

by Edessa Negera, Stephen L. Walker, Selfu Girma, Shimelis N. Doni, Degafe Tsegaye, Saba M. Lambert, Munir H. Idriss, Yohanis Tsegay, Hazel M. Dockrell, Abraham Aseffa, Diana N. Lockwood

Background

Leprosy reactions are a significant cause of morbidity in leprosy population. Erythema nodosum leprosum (ENL) is an immunological complication affecting approximately 50% of patients with lepromatous leprosy (LL) and 10% of borderline lepromatous (BL) leprosy. ENL is associated with clinical features such as skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. ENL is treated mainly with corticosteroids and corticosteroids are often required for extended periods of time which may lead to serious adverse effects. High mortality rate and increased morbidity associated with corticosteroid treatment of ENL has been reported. For improved and evidence-based treatment of ENL, documenting the systems affected by ENL is important. We report here the clinical features of ENL in a cohort of patients with acute ENL who were recruited for a clinico-pathological study before and after prednisolone treatment.

Materials and methods

A case–control study was performed at ALERT hospital, Ethiopia. Forty-six LL patients with ENL and 31 non-reactional LL matched controls were enrolled to the study and followed for 28 weeks. Clinical features were systematically documented at three visits (before, during and after predinsolone treatment of ENL cases) using a specifically designed form. Skin biopsy samples were obtained from each patient before and after treatment and used for histopathological investigations to supplement the clinical data.

Results

Pain was the most common symptom reported (98%) by patients with ENL. Eighty percent of them had reported skin pain and more than 70% had nerve and joint pain at enrolment. About 40% of the patients developed chronic ENL. Most individuals 95.7% had nodular skin lesions. Over half of patients with ENL had old nerve function impairment (NFI) while 13% had new NFI at enrolment. Facial and limb oedema were present in 60% patients. Regarding pathological findings before treatment, dermal neutrophilic infiltration was noted in 58.8% of patients with ENL compared to 14.3% in LL controls. Only 14.7% patients with ENL had evidence of vasculitis at enrolment.

Conclusion

In our study, painful nodular skin lesions were present in all ENL patients. Only 58% patients had dermal polymorphonuclear cell infiltration showing that not all clinically confirmed ENL cases have neutrophilic infiltration in lesions. Very few patients had histological evidence of vasculitis. Many patients developed chronic ENL and these patients require inpatient corticosteroid treatment for extended periods which challenges the health service facility in resource poor settings, as well as the patient’s quality of life.

Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control

13 October 2017 - 9:00pm

by Ian T. Kracalik, Ernest Kenu, Evans Nsoh Ayamdooh, Emmanuel Allegye-Cudjoe, Paul Nokuma Polkuu, Joseph Asamoah Frimpong, Kofi Mensah Nyarko, William A. Bower, Rita Traxler, Jason K. Blackburn

Anthrax is hyper-endemic in West Africa. Despite the effectiveness of livestock vaccines in controlling anthrax, underreporting, logistics, and limited resources makes implementing vaccination campaigns difficult. To better understand the geographic limits of anthrax, elucidate environmental factors related to its occurrence, and identify human and livestock populations at risk, we developed predictive models of the environmental suitability of anthrax in Ghana. We obtained data on the location and date of livestock anthrax from veterinary and outbreak response records in Ghana during 2005–2016, as well as livestock vaccination registers and population estimates of characteristically high-risk groups. To predict the environmental suitability of anthrax, we used an ensemble of random forest (RF) models built using a combination of climatic and environmental factors. From 2005 through the first six months of 2016, there were 67 anthrax outbreaks (851 cases) in livestock; outbreaks showed a seasonal peak during February through April and primarily involved cattle. There was a median of 19,709 vaccine doses [range: 0–175 thousand] administered annually. Results from the RF model suggest a marked ecological divide separating the broad areas of environmental suitability in northern Ghana from the southern part of the country. Increasing alkaline soil pH was associated with a higher probability of anthrax occurrence. We estimated 2.2 (95% CI: 2.0, 2.5) million livestock and 805 (95% CI: 519, 890) thousand low income rural livestock keepers were located in anthrax risk areas. Based on our estimates, the current anthrax vaccination efforts in Ghana cover a fraction of the livestock potentially at risk, thus control efforts should be focused on improving vaccine coverage among high risk groups.

Human cellular and humoral immune responses to <i>Phlebotomus papatasi</i> salivary gland antigens in endemic areas differing in prevalence of <i>Leishmania major</i> infection

12 October 2017 - 9:00pm

by Wafa Kammoun-Rebai, Narges Bahi-Jaber, Ikbel Naouar, Amine Toumi, Afif Ben Salah, Hechmi Louzir, Amel Meddeb-Garnaoui

Background

Sand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome. Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding their effect on parasite transmission and establishment in humans.

Methodology/Principal findings

We explored the cellular and humoral immune responses to Phlebotomus (P.) papatasi salivary gland extracts (SGE) in individuals living in cutaneous leishmaniasis (CL) old or emerging foci (OF, EF). OF was characterized by a higher infection prevalence as assessed by higher proportions of leishmanin skin test (LST) positive individuals compared to EF. Subjects were further subdivided into healed, asymptomatic or naïve groups. We showed anti-SGE proliferation in less than 30% of the individuals, regardless of the immune status, in both foci. IFN-γ production was higher in OF and only observed in immune individuals from OF and naïve subjects from EF. Although IL-10 was not detected, addition of anti-human IL-10 antibodies revealed an increase in proliferation and IFN-γ production only in individuals from OF. The percentage of seropositive individuals was similar in immune and naïves groups but was significantly higher in OF. No correlation was observed between anti-saliva immune responses and LST response. High anti-SGE-IgG responses were associated with an increased risk of developing ZCL. No differences were observed for anti-SGE humoral or cellular responses among naïve individuals who converted or not their LST response or developed or not ZCL after the transmission season.

Conclusions/Significance

These data suggest that individuals living in an old focus characterized by a frequent exposure to sand fly bites and a high prevalence of infection, develop higher anti-saliva IgG responses and IFN-γ levels and a skew towards a Th2-type cellular response, probably in favor of parasite establishment, compared to those living in an emerging focus.

Towards elimination of visceral leishmaniasis in the Indian subcontinent—Translating research to practice to public health

12 October 2017 - 9:00pm

by Siddhivinayak Hirve, Axel Kroeger, Greg Matlashewski, Dinesh Mondal, Megha Raj Banjara, Pradeep Das, Ahmed Be-Nazir, Byron Arana, Piero Olliaro

Background

The decade following the Regional Strategic Framework for Visceral Leishmaniasis (VL) elimination in 2005 has shown compelling progress in the reduction of VL burden in the Indian subcontinent. The Special Programme for Research and Training in Tropical Diseases (TDR), hosted by the World Health Organization (WHO) and other stakeholders, has coordinated and financed research for the development of new innovative tools and strategies to support the regional VL elimination initiative. This paper describes the process of the TDR’s engagement and contribution to this initiative.

Methodology/principal findings

Multiple databases were searched to identify 152 scientific papers and reports with WHO funding or authorship affiliation around the following 3 framework strategies: detection of new cases, morbidity reduction, and prevention of infection. TDR has played a critical role in the evaluation and subsequent use of the 39-aminoacid–recombinant kinesin antigen (rK39) rapid diagnostic test (RDT) as a confirmatory test for VL in the national program. TDR has supported the clinical research and development of miltefosine and single-dose liposomal amphotericin B as a first-line treatment against VL. TDR has engaged with in-country researchers, national programme managers, and partners to generate evidence-based interventions for early detection and treatment of VL patients. TDR evaluated the quality, community acceptance, and cost effectiveness of indoor residual spraying, insecticide-treated bed nets, insecticide-impregnated durable wall linings, insecticidal paint, and environmental management as tools for integrated vector management in reducing sandfly density.

Conclusions/significance

TDR’s engagement with country policy makers, scientists, and clinicians in the development of effective diagnosis, treatment, case detection, and vector control represents an important example of TDR’s stewardship toward the elimination of VL in the Indian subcontinent.

Is mass drug administration against lymphatic filariasis required in urban settings? The experience in Kano, Nigeria

11 October 2017 - 9:00pm

by Dung D. Pam, Dziedzom K. de Souza, Susan Walker, Millicent Opoku, Safiya Sanda, Ibrahim Nazaradeen, Ifeoma N. Anagbogu, Chukwu Okoronkwo, Emmanuel Davies, Elisabeth Elhassan, David Molyneux, Moses J. Bockarie, Benjamin G. Koudou

Background

The Global Programme to Eliminate Lymphatic Filariasis (GPELF), launched in 2000, has the target of eliminating the disease as a public health problem by the year 2020. The strategy adopted is mass drug administration (MDA) to all eligible individuals in endemic communities and the implementation of measures to reduce the morbidity of those suffering from chronic disease. Success has been recorded in many rural endemic communities in which elimination efforts have centered. However, implementation has been challenging in several urban African cities. The large cities of West Africa, exemplified in Nigeria in Kano are challenging for LF elimination program because reaching 65% therapeutic coverage during MDA is difficult. There is therefore a need to define a strategy which could complement MDA. Thus, in Kano State, Nigeria, while LF MDA had reached 33 of the 44 Local Government Areas (LGAs) there remained eleven ‘urban’ LGAs which had not been covered by MDA. Given the challenges of achieving at least 65% coverage during MDA implementation over several years in order to achieve elimination, it may be challenging to eliminate LF in such settings. In order to plan the LF control activities, this study was undertaken to confirm the LF infection prevalence in the human and mosquito populations in three urban LGAs.

Methods

The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in 981 people in three urban LGAs of Kano state, Nigeria. Mosquitoes were collected over a period of 4 months from May to August 2015 using exit traps, gravid traps and pyrethrum knock-down spray sheet collections (PSC) in different households. A proportion of mosquitoes were analyzed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR).

Results

The results showed that none of the 981 subjects (constituted of <21% of children 5–10 years old) tested had detectable levels of CFA in their blood. Entomological results showed that An. gambiae s.l. had W. bancrofti DNA detectable in pools in Kano; W. bancrofti DNA was detected in between 0.96% and 6.78% and to a lesser extent in Culex mosquitoes where DNA was detected at rates of between 0.19% and 0.64%. DNA analysis showed that An. coluzzii constituted 9.9% of the collected mosquitoes and the remaining 90.1% of the mosquitoes were Culex mosquitoes.

Conclusion

Despite detection of W. bancrofti DNA within mosquito specimens collected in three Kano urban LGAs, we were not able to find a subject with detectable level of CFA. Together with other evidence suggesting that LF transmission in urban areas in West Africa may not be of significant importance, the Federal Ministry of Health advised that two rounds of MDA be undertaken in the urban areas of Kano. It is recommended that the prevalence of W. bancrofti infection in the human and mosquito populations be re-assessed after a couple of years.

Pages