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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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

PLoS Neglected Tropical Diseases News - 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.

Human macrophages differentiated in the presence of vitamin D<sub>3</sub> restrict dengue virus infection and innate responses by downregulating mannose receptor expression

PLoS Neglected Tropical Diseases News - 11 October 2017 - 9:00pm

by John F. Arboleda Alzate, Izabela A. Rodenhuis-Zybert, Juan C. Hernández, Jolanda M. Smit, Silvio Urcuqui-Inchima

Background

Severe dengue disease is associated with high viral loads and overproduction of pro-inflammatory cytokines, suggesting impairment in the control of dengue virus (DENV) and the mechanisms that regulate cytokine production. Vitamin D3 has been described as an important modulator of immune responses to several pathogens. Interestingly, increasing evidence has associated vitamin D with decreased DENV infection and early disease recovery, yet the molecular mechanisms whereby vitamin D reduces DENV infection are not well understood.

Methods and principal findings

Macrophages represent important cell targets for DENV replication and consequently, they are key drivers of dengue disease. In this study we evaluated the effect of vitamin D3 on the differentiation of monocyte-derived macrophages (MDM) and their susceptibility and cytokine response to DENV. Our data demonstrate that MDM differentiated in the presence of vitamin D3 (D3-MDM) restrict DENV infection and moderate the classical inflammatory cytokine response. Mechanistically, vitamin D3-driven differentiation led to reduced surface expression of C-type lectins including the mannose receptor (MR, CD206) that is known to act as primary receptor for DENV attachment on macrophages and to trigger of immune signaling. Consequently, DENV bound less efficiently to vitamin D3-differentiated macrophages, leading to lower infection. Interestingly, IL-4 enhanced infection was reduced in D3-MDM by restriction of MR expression. Moreover, we detected moderate secretion of TNF-α, IL-1β, and IL-10 in D3-MDM, likely due to less MR engagement during DENV infection.

Conclusions/Significance

Our findings reveal a molecular mechanism by which vitamin D counteracts DENV infection and progression of severe disease, and indicates its potential relevance as a preventive or therapeutic candidate.

Albendazole and ivermectin for the control of soil-transmitted helminths in an area with high prevalence of <i>Strongyloides stercoralis</i> and hookworm in northwestern Argentina: A community-based pragmatic study

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Adriana Echazú, Marisa Juarez, Paola A. Vargas, Silvana P. Cajal, Ruben O. Cimino, Viviana Heredia, Silvia Caropresi, Gladys Paredes, Luis M. Arias, Marcelo Abril, Silvia Gold, Patrick Lammie, Alejandro J. Krolewiecki

Background

Recommendations for soil-transmitted helminth (STH) control give a key role to deworming of school and pre-school age children with albendazole or mebendazole; which might be insufficient to achieve adequate control, particularly against Strongyloides stercoralis. The impact of preventive chemotherapy (PC) against STH morbidity is still incompletely understood. The aim of this study was to assess the effectiveness of a community-based program with albendazole and ivermectin in a high transmission setting for S. stercoralis and hookworm.

Methodology

Community-based pragmatic trial conducted in Tartagal, Argentina; from 2012 to 2015. Six communities (5070 people) were enrolled for community-based PC with albendazole and ivermectin. Two communities (2721 people) were re-treated for second and third rounds. STH prevalence, anemia and malnutrition were explored through consecutive surveys. Anthropometric assessment of children, stool analysis, complete blood count and NIE-ELISA serology for S. stercoralis were performed.

Principal findings

STH infection was associated with anemia and stunting in the baseline survey that included all communities and showed a STH prevalence of 47.6% (almost exclusively hookworm and S. stercoralis). Among communities with multiple interventions, STH prevalence decreased from 62% to 23% (p<0.001) after the first PC; anemia also diminished from 52% to 12% (p<0.001). After two interventions S. stercoralis seroprevalence declined, from 51% to 14% (p<0.001) and stunting prevalence decreased, from 19% to 12% (p = 0.009).

Conclusions

Hookworm’ infections are associated with anemia in the general population and nutritional impairment in children. S. stercoralis is also associated with anemia. Community-based deworming with albendazole and ivermectin is effective for the reduction of STH prevalence and morbidity in communities with high prevalence of hookworm and S. stercoralis.

T-cell regulation in Erythema Nodosum Leprosum

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Edessa Negera, Steven L. Walker, Kidist Bobosha, Rawleigh Howe, Abraham Aseffa, Hazel M. Dokrell, Diana N. Lockwood

Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is an immune-mediated inflammatory complication, which causes significant morbidity in affected leprosy patients. The underlying cause of ENL is not conclusively known. However, immune-complexes and cell-mediated immunity have been suggested in the pathogenesis of ENL. The aim of this study was to investigate the regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT Hospital, Ethiopia were enrolled to the study. Blood samples were obtained before, during and after prednisolone treatment of ENL cases. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27 and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and histopathological data were obtained as supplementary information. All patients had been followed for 28 weeks. Patients with ENL reactions had a lower percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at diagnosis of ENL before treatment. After treatment, the percentage of CD4+regulatory T-cells was not significantly different between the two groups. The percentage of CD8+ regulatory T-cells was not significantly different in ENL and LL controls before and after treatment. Furthermore, patients with ENL had higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was not significantly different in ENL and LL controls suggesting that CD25 expression is not associated with ENL reactions while FoxP3 expression on CD4+ T-cells was significantly lower in patients with ENL than in LL controls. We also found that prednisolone treatment of patients with ENL reactions suppresses CD4+ T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that this loss of regulation is one of the causes of ENL.

Characterization of the catalytic center of the Ebola virus L polymerase

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Marie Luisa Schmidt, Thomas Hoenen

Background

Ebola virus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates. While no licensed therapeutics are available, recently there has been tremendous progress in developing antivirals. Targeting the ribonucleoprotein complex (RNP) proteins, which facilitate genome replication and transcription, and particularly the polymerase L, is a promising antiviral approach since these processes are essential for the virus life cycle. However, until now little is known about L in terms of its structure and function, and in particular the catalytic center of the RNA-dependent RNA polymerase (RdRp) of L, which is one of the most promising molecular targets, has never been experimentally characterized.

Methodology/Principal findings

Using multiple sequence alignments with other negative sense single-stranded RNA viruses we identified the putative catalytic center of the EBOV RdRp. An L protein with mutations in this center was then generated and characterized using various life cycle modelling systems. These systems are based on minigenomes, i.e. miniature versions of the viral genome, in which the viral genes are exchanged against a reporter gene. When such minigenomes are coexpressed with RNP proteins in mammalian cells, the RNP proteins recognize them as authentic templates for replication and transcription, resulting in reporter activity reflecting these processes. Replication-competent minigenome systems indicated that our L catalytic domain mutant was impaired in genome replication and/or transcription, and by using replication-deficient minigenome systems, as well as a novel RT-qPCR-based genome replication assay, we showed that it indeed no longer supported either of these processes. However, it still showed similar expression to wild-type L, and retained its ability to be incorporated into inclusion bodies, which are the sites of EBOV genome replication.

Conclusions/Significance

We have experimentally defined the catalytic center of the EBOV RdRp, and thus a promising antiviral target regulating an essential aspect of the EBOV life cycle.

Application of a loop-mediated isothermal amplification (LAMP) assay targeting <i>cox1</i> gene for the detection of <i>Clonorchis sinensis</i> in human fecal samples

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by S. M. Mazidur Rahman, Hyun Beom Song, Yan Jin, Jin-Kyoung Oh, Min Kyung Lim, Sung-Tae Hong, Min-Ho Choi

Background

Clonorchiasis is prevalent in the Far East, and a major health problem in endemic areas. Infected persons may experience, if not treated, serious complications such as bile stone formation, pyogenic cholangitis, and even cholangiocarcinoma. Early diagnosis and treatment are important to prevent serious complications and, therefore, the simple and reliable diagnostic method is necessary to control clonorchiasis in endemic areas, where resources for the diagnosis are limited.

Methodology/Principle findings

The loop-mediated isothermal amplification (LAMP) assay has been applied for the detection of Clonorchis sinensis DNA. Six primers targeting eight locations on the cytochrome c oxidase subunit 1 gene of C. sinensis were designed for species-specific amplification using the LAMP assay. The LAMP assay was sensitive enough to detect as little as 100 fg of C. sinensis genomic DNA and the detection limit in 100 mg of stool was as low as one egg. The assay was highly specific because no cross-reactivity was observed with the DNA of other helminths, protozoa or Escherichia coli. Then, LAMP assay was applied to human fecal samples collected from an endemic area of clonorchiasis in Korea. Using samples showing consistent results by both Kato-Katz method and real-time PCR as reference standards, the LAMP assay showed 97.1% (95% CI, 90.1–99.2) of sensitivity and 100% (95% CI, 92.9–100) of specificity. In stool samples with more than 100 eggs per gram of feces, the sensitivity achieved 100%.

Conclusions

To detect C. sinensis in human fecal samples, the LAMP assay was applied and achieved high sensitivity and specificity. The LAMP assay can be utilized in field laboratories as a powerful tool for diagnosis and epidemiological survey of clonorchiasis.

Mitochondrial dual-coding genes in <i>Trypanosome brucei</i>

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Laura E. Kirby, Donna Koslowsky

Trypanosoma brucei is transmitted between mammalian hosts by the tsetse fly. In the mammal, they are exclusively extracellular, continuously replicating within the bloodstream. During this stage, the mitochondrion lacks a functional electron transport chain (ETC). Successful transition to the fly, requires activation of the ETC and ATP synthesis via oxidative phosphorylation. This life cycle leads to a major problem: in the bloodstream, the mitochondrial genes are not under selection and are subject to genetic drift that endangers their integrity. Exacerbating this, T. brucei undergoes repeated population bottlenecks as they evade the host immune system that would create additional forces of genetic drift. These parasites possess several unique genetic features, including RNA editing of mitochondrial transcripts. RNA editing creates open reading frames by the guided insertion and deletion of U-residues within the mRNA. A major question in the field has been why this metabolically expensive system of RNA editing would evolve and persist. Here, we show that many of the edited mRNAs can alter the choice of start codon and the open reading frame by alternative editing of the 5’ end. Analyses of mutational bias indicate that six of the mitochondrial genes may be dual-coding and that RNA editing allows access to both reading frames. We hypothesize that dual-coding genes can protect genetic information by essentially hiding a non-selected gene within one that remains under selection. Thus, the complex RNA editing system found in the mitochondria of trypanosomes provides a unique molecular strategy to combat genetic drift in non-selective conditions.

Health-related impact on quality of life and coping strategies for chikungunya: A qualitative study in Curaçao

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Jelte Elsinga, Martin P. Grobusch, Adriana Tami, Izzy Gerstenbluth, Ajay Bailey

Introduction

Chikungunya is an emerging public health problem in tropical and subtropical regions, due to ongoing transmission and its incapacitating acute disease phase, and chronic sequelae. The disease is responsible for a major impact on Health Related Quality of Life (HRQoL), which may last several years. To our knowledge, this study is the first qualitative examination of HRQoL and coping strategies of chikungunya-infected individuals.

Methods

Qualitative research methods consisted of 20 in-depth interviews and seven Focus Group Discussions (FGDs), n = 50. Analysis was based on the principles of the grounded theory.

Results

Different impacts on HRQoL were reported. The physical and emotional domains of the HRQoL were mainly affected by chikungunya, while social and individual financial consequences were limited. Individual financial impact was limited through the universal health care program of Curaçao. Long-term lingering musculoskeletal and other manifestations caused significant pain and limited mobility. Hence, participants experienced dependency, impairment of normal daily life activities, moodiness, hopelessness, a change of identity, and insecurity about their future. The unpredictable nature and consequences of chikungunya gave rise to various coping strategies. Problem-focused coping styles led to higher uptake of medical care and were linked to more negative impact of HRQoL, whereas emotional coping strategies focusing on acceptance of the situation were linked to less uptake of medical care and more positive impact on HRQoL.

Conclusions

This study provides an in-depth understanding of acute and long-term HRQoL impact of chikungunya. The results can better inform health promotion policies and interventions. Messages to the public should focus on promoting healthy and efficient coping strategies, in order to prevent additional stress in affected individuals.

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