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Prevalence of depression and associated clinical and socio-demographic factors in people living with lymphatic filariasis in Plateau State, Nigeria

PLoS Neglected Tropical Diseases News - 1 June 2017 - 9:00pm

by James Obindo, Jibril Abdulmalik, Emeka Nwefoh, Michael Agbir, Charles Nwoga, Aishatu Armiya’u, Francis Davou, Kurkat Maigida, Emmanuel Otache, Ajuma Ebiloma, Samuel Dakwak, John Umaru, Elisha Samuel, Christopher Ogoshi, Julian Eaton

Background

Lymphatic filariasis is a chronic, disabling and often disfiguring condition that principally impacts the world’s poorest people. In addition to the well-recognised physical disability associated with lymphedema and hydrocele, affected people often experience rejection, stigma and discrimination. The resulting emotional consequences are known to impact on the quality of life and the functioning of the affected individuals. However, the management of this condition has focused on prevention and treatment through mass drug administration, with scant attention paid to the emotional impact of the condition on affected individuals. This study aimed to determine the prevalence and severity of depression among individuals with physical disfigurement from lymphatic filariasis in Plateau State, Nigeria.

Methodology

A cross-sectional 2-stage convenience study was conducted at 5 designated treatment centers across Plateau State, Nigeria. All available and consenting clients with clearly visible physical disfigurement were recruited. A semi-structured socio-demographic questionnaire, Rosenberg Self-esteem and a 9-item Patient Health Questionnaire (PHQ-9) were administered at the first stage. Those who screened positive (with a PHQ-9 score of five and above) were further interviewed using the Depression module of the Composite International Diagnostic Interview (CIDI).

Results

Ninety-eight individuals met the criteria and provided consent. Twenty percent of the respondents met criteria for depression, with the following proportions based on severity: Mild (42.1%), Moderate (31.6%) and Severe (26.3%). History of mental illness (OR 40.83, p = 0.008); Median duration of the illness was 17 years (IQR 7.0–30 years) and being unemployed (OR 12.71, p = 0.003) were predictive of depression. High self-esteem was negatively correlated (OR 0.09, p<0.004).

Conclusion

Prevalence of depression is high among individuals with lymphatic filariasis and depression in sufferers is associated with low self-esteem and low levels of life satisfaction.

qPCR-High resolution melt analysis for drug susceptibility testing of <i>Mycobacterium leprae</i> directly from clinical specimens of leprosy patients

PLoS Neglected Tropical Diseases News - 1 June 2017 - 9:00pm

by Sergio Araujo, Luiz Ricardo Goulart, Richard W. Truman, Isabela Maria B. Goulart, Varalakshmi Vissa, Wei Li, Masanori Matsuoka, Philip Suffys, Amanda B. Fontes, Patricia S. Rosa, David M. Scollard, Diana L. Williams

Background

Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens.

Methodology/Principal findings

The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite’s stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite’s stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to identify mixed infections of susceptible and resistant M. leprae. However, to avoid false positives we recommend that clinical specimens be tested for the presence of the M. leprae using the qPCR-RLEP assay prior to being tested in the qPCR-HRM DST and that all specimens demonstrating drug resistant profiles in this assay be subjected to DNA sequencing.

Conclusion/Significance

Taken together these results further demonstrate the utility of qPCR-HRM DST as an inexpensive screening tool for large-scale drug resistance surveillance in leprosy.

Introducing the TrypanoGEN biobank: A valuable resource for the elimination of human African trypanosomiasis

PLoS Neglected Tropical Diseases News - 1 June 2017 - 9:00pm

by Hamidou Ilboudo, Harry Noyes, Julius Mulindwa, Magambo Phillip Kimuda, Mathurin Koffi, Justin Windingoudi Kaboré, Bernadin Ahouty, Dieudonné Mumba Ngoyi, Olivier Fataki, Gustave Simo, Elvis Ofon, John Enyaru, John Chisi, Kelita Kamoto, Martin Simuunza, Vincent P. Alibu, Veerle Lejon, Vincent Jamonneau, Annette Macleod, Mamadou Camara, Bruno Bucheton, Christiane Hertz-Fowler, Issa Sidibe, Enock Matovu, for the TrypanoGEN Research Group as members of The H3Africa Consortium

Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections

PLoS Neglected Tropical Diseases News - 30 May 2017 - 9:00pm

by Eleonora Cimini, Domenico Viola, Mar Cabeza-Cabrerizo, Antonella Romanelli, Nicola Tumino, Alessandra Sacchi, Veronica Bordoni, Rita Casetti, Federica Turchi, Federico Martini, Joseph A. Bore, Fara Raymond Koundouno, Sophie Duraffour, Janine Michel, Tobias Holm, Elsa Gayle Zekeng, Lauren Cowley, Isabel Garcia Dorival, Juliane Doerrbecker, Nicole Hetzelt, Jonathan H. J. Baum, Jasmine Portmann, Roman Wölfel, Martin Gabriel, Osvaldo Miranda, Graciliano Díaz, José E. Díaz, Yoel A. Fleites, Carlos A. Piñeiro, Carlos M. Castro, Lamine Koivogui, N’Faly Magassouba, Boubacar Diallo, Paula Ruibal, Lisa Oestereich, David M. Wozniak, Anja Lüdtke, Beate Becker-Ziaja, Maria R. Capobianchi, Giuseppe Ippolito, Miles W. Carroll, Stephan Günther, Antonino Di Caro, César Muñoz-Fontela, Chiara Agrati

Background

Human Ebola infection is characterized by a paralysis of the immune system. A signature of αβ T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014–2015 occurred in West Africa, and to assess their association with the clinical outcome.

Methodology/Principal findings

Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector Vδ2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56bright and CD56dim NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56neg NK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome.

Conclusions/Significances

Altogether, the data suggest that both effector Vδ2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of Vδ2 and NK cells.

Vaccination with a <i>Leishmania infantum HSP70-II</i> null mutant confers long-term protective immunity against <i>Leishmania major</i> infection in two mice models

PLoS Neglected Tropical Diseases News - 30 May 2017 - 9:00pm

by José Carlos Solana, Laura Ramírez, Laura Corvo, Camila Indiani de Oliveira, Manoel Barral-Netto, José María Requena, Salvador Iborra, Manuel Soto

Background

The immunization with genetically attenuated Leishmania cell lines has been associated to the induction of memory and effector T cell responses against Leishmania able to control subsequent challenges. A Leishmania infantum null mutant for the HSP70-II genes has been described, possessing a non-virulent phenotype.

Methodology/Principal findings

The L. infantum attenuated parasites (LiΔHSP70-II) were inoculated in BALB/c (intravenously and subcutaneously) and C57BL/6 (subcutaneously) mice. An asymptomatic infection was generated and parasites diminished progressively to become undetectable in most of the analyzed organs. However, inoculation resulted in the long-term induction of parasite specific IFN-γ responses able to control the disease caused by a challenge of L. major infective promastigotes. BALB/c susceptible mice showed very low lesion development and a drastic decrease in parasite burdens in the lymph nodes draining the site of infection and internal organs. C57BL/6 mice did not show clinical manifestation of disease, correlated to the rapid migration of Leishmania specific IFN-γ producing T cells to the site of infection.

Conclusion/Significance

Inoculation of the LiΔHSP70-II attenuated line activates mammalian immune system for inducing moderate pro-inflammatory responses. These responses are able to confer long-term protection in mice against the infection of L. major virulent parasites.

Fine-scale variation in microclimate across an urban landscape shapes variation in mosquito population dynamics and the potential of <i>Aedes albopictus</i> to transmit arboviral disease

PLoS Neglected Tropical Diseases News - 30 May 2017 - 9:00pm

by Courtney C. Murdock, Michelle V. Evans, Taylor D. McClanahan, Kerri L. Miazgowicz, Blanka Tesla

Most statistical and mechanistic models used to predict mosquito borne disease transmission incorporate climate drivers of disease transmission by utilizing environmental data collected at geographic scales that are potentially coarser than what mosquito populations may actually experience. Temperature and relative humidity can vary greatly between indoor and outdoor environments, and can be influenced strongly by variation in landscape features. In the Aedes albopictus system, we conducted a proof-of-concept study in the vicinity of the University of Georgia to explore the effects of fine-scale microclimate variation on mosquito life history and vectorial capacity (VC). We placed Ae. albopictus larvae in artificial pots distributed across three replicate sites within three different land uses–urban, suburban, and rural, which were characterized by high, intermediate, and low proportions of impervious surfaces. Data loggers were placed into each larval environment and in nearby vegetation to record daily variation in water and ambient temperature and relative humidity. The number of adults emerging from each pot and their body size and sex were recorded daily. We found mosquito microclimate to significantly vary across the season as well as with land use. Urban sites were in general warmer and less humid than suburban and rural sites, translating into decreased larval survival, smaller body sizes, and lower per capita growth rates of mosquitoes on urban sites. Dengue transmission potential was predicted to be higher in the summer than the fall. Additionally, the effects of land use on dengue transmission potential varied by season. Warm summers resulted in a higher predicted VC on the cooler, rural sites, while warmer, urban sites had a higher predicted VC during the cooler fall season.

Safety and efficacy of short course combination regimens with AmBisome, miltefosine and paromomycin for the treatment of visceral leishmaniasis (VL) in Bangladesh

PLoS Neglected Tropical Diseases News - 30 May 2017 - 9:00pm

by Ridwanur Rahman, Vishal Goyal, Rashidul Haque, Kazi Jamil, Abul Faiz, Rasheda Samad, Sally Ellis, Manica Balasegaram, Margriet den Boer, Suman Rijal, Nathalie Strub-Wourgaft, Fabiana Alves, Jorge Alvar, Bhawna Sharma

Background

AmBisome therapy for VL has an excellent efficacy and safety profile and has been adopted as a first-line regimen in Bangladesh. Second-line treatment options are limited and should preferably be given in short course combinations in order to prevent the development of resistant strains. Combination regimens including AmBisome, paromomycin and miltefosine have proved to be safe and effective in the treatment of VL in India. In the present study, the safety and efficacy of these same combinations were assessed in field conditions in Bangladesh.

Methods

The safety and efficacy of three combination regimens: a 5 mg/kg single dose of AmBisome + 7 subsequent days of miltefosine (2.5 mg/kg/day), a 5 mg/kg single dose of AmBisome + 10 subsequent days of paromomycin (15 mg/kg/day) and 10 days of paromomycin (15 mg/kg/day) + miltefosine (2.5 mg/kg/day), were compared with a standard regimen of AmBisome 15 mg/kg given in 5 mg/kg doses on days 1, 3 and 5. This was a phase III open label, individually randomized clinical trial. Patients from 5 to 60 years with uncomplicated primary VL were recruited from the Community Based Medical College Bangladesh (CBMC,B) and the Upazila Health Complexes of Trishal, Bhaluka and Fulbaria (all located in Mymensingh district), and randomly assigned to one of the treatments. The objective was to assess safety and definitive cure at 6 months after treatment.

Results

601 patients recruited between July 2010 and September 2013 received either AmBisome monotherapy (n = 158), AmBisome + paromomycin (n = 159), AmBisome + miltefosine (n = 142) or paromomycin + miltefosine (n = 142). At 6 months post- treatment, final cure rates for the intention-to-treat population were 98.1% (95%CI 96.0–100) for AmBisome monotherapy, 99.4% (95%CI 98.2–100) for the AmBisome + paromomycin arm, 94.4% (95%CI 90.6–98.2) for the AmBisome + miltefosine arm, and 97.9% (95%CI 95.5–100) for paromomycin + miltefosine arm. There were 12 serious adverse events in the study in 11 patients that included 3 non-study drug related deaths. There were no relapses or PKDL up to 6 months follow-up. All treatments were well tolerated with no unexpected side effects. Adverse events were most frequent during treatment with miltefosine + paromomycin, three serious adverse events related to the treatment occurred in this arm, all of which resolved.

Conclusion

None of the combinations were inferior to AmBisome in both the intention-to-treat and per-protocol populations. All the combinations demonstrated excellent overall efficacy, were well tolerated and safe, and could be deployed under field conditions in Bangladesh. The trial was conducted by the International Centre for Diarrhoeal Disease Research (ICDDR,B) and the Shaheed Suhrawardy Medical College (ShSMC), Dhaka, in collaboration with the trial sites and sponsored by the Drugs for Neglected Diseases initiative (DNDi).

Trial registration

ClinicalTrials.gov NCT01122771

Epitope mapping of recombinant <i>Leishmania donovani</i> virulence factor A2 (rec<i>Ld</i>VFA2) and canine leishmaniasis diagnosis using a derived synthetic bi-epitope

PLoS Neglected Tropical Diseases News - 30 May 2017 - 9:00pm

by Thais Melo Mendes, Eric Henrique Roma, Fernanda Costal-Oliveira, Lucas deCarvalho Dhom-Lemos, Cristina Monerat Toledo-Machado, Oscar Bruna-Romero, DaniellaCastanheiras Bartholomeu, Ricardo Toshio Fujiwara, Carlos Chávez-Olórtegui

Background

Leishmaniasis is one of the most important zoonotic diseases spread in Latin America. Since many species are involved in dog infection with different clinical manifestations, the development of specific diagnostic tests is mandatory for more accurate disease control and vaccine strategies.

Methodology/Principal findings

Seventy-five 15-mer peptides covering the sequence of recombinant Leishmania donovani virulence factor A2 (recLdVFA2) protein were prepared by Spot synthesis. Membrane-bound peptides immunoreactivity with sera from dogs immunized with recLdVFA2 and with a specific anti-recLdVFA2 monoclonal antibody allowed mapping of continuous B-cell epitopes. Five epitopes corresponding to the N-terminal region of recLdVFA2 (MKIRSVRPLVVLLVC, RSVRPLVVLLVCVAA, RPLVVLLVCVAAVLA, VVLLVCVAAVLALSA and LVCVAAVLALSASAE, region 1–28) and one located within the repetitive units (PLSVGPQAVGLSVG, regions 67–81 and 122–135) were identified. A 34-mer recLdVFA2-derived bi-epitope containing the sequence MKIRSVRPLVVLLVC linked to PLSVGPQAVGLSVG by a Gly-Gly spacer was chemically synthesized in its soluble form. The synthetic bi-epitope was used as antigen to coat ELISA plates and assayed with dog sera for in vitro diagnosis of canine visceral leishmaniasis (CVL). The assay proved to be highly sensitive (100%) and specific (100%).

Conclusions/Significance

Our work suggests that synthetic peptide-based ELISA strategy may be useful for the development of a sensitive and highly specific serodiagnosis for CVL or other parasitic diseases.

Optimising cluster survey design for planning schistosomiasis preventive chemotherapy

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

by Sarah C. L. Knowles, Hugh J. W. Sturrock, Hugo Turner, Jane M. Whitton, Charlotte M. Gower, Samuel Jemu, Anna E. Phillips, Aboulaye Meite, Brent Thomas, Karsor Kollie, Catherine Thomas, Maria P. Rebollo, Ben Styles, Michelle Clements, Alan Fenwick, Wendy E. Harrison, Fiona M. Fleming

Background

The cornerstone of current schistosomiasis control programmes is delivery of praziquantel to at-risk populations. Such preventive chemotherapy requires accurate information on the geographic distribution of infection, yet the performance of alternative survey designs for estimating prevalence and converting this into treatment decisions has not been thoroughly evaluated.

Methodology/Principal findings

We used baseline schistosomiasis mapping surveys from three countries (Malawi, Côte d’Ivoire and Liberia) to generate spatially realistic gold standard datasets, against which we tested alternative two-stage cluster survey designs. We assessed how sampling different numbers of schools per district (2–20) and children per school (10–50) influences the accuracy of prevalence estimates and treatment class assignment, and we compared survey cost-efficiency using data from Malawi. Due to the focal nature of schistosomiasis, up to 53% simulated surveys involving 2–5 schools per district failed to detect schistosomiasis in low endemicity areas (1–10% prevalence). Increasing the number of schools surveyed per district improved treatment class assignment far more than increasing the number of children sampled per school. For Malawi, surveys of 15 schools per district and 20–30 children per school reliably detected endemic schistosomiasis and maximised cost-efficiency. In sensitivity analyses where treatment costs and the country considered were varied, optimal survey size was remarkably consistent, with cost-efficiency maximised at 15–20 schools per district.

Conclusions/Significance

Among two-stage cluster surveys for schistosomiasis, our simulations indicated that surveying 15–20 schools per district and 20–30 children per school optimised cost-efficiency and minimised the risk of under-treatment, with surveys involving more schools of greater cost-efficiency as treatment costs rose.

Albendazole increases the inflammatory response and the amount of Em2-positive small particles of <i>Echinococcus multilocularis</i> (spems) in human hepatic alveolar echinococcosis lesions

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

by Franz J. Ricken, Juliane Nell, Beate Grüner, Julian Schmidberger, Tanja Kaltenbach, Wolfgang Kratzer, Andreas Hillenbrand, Doris Henne-Bruns, Peter Deplazes, Peter Möller, Peter Kern, Thomas F. E. Barth

Background

Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. The inflammatory response to this infection is influenced by the interaction of the parasite with the host. We aimed to analyze human liver lesions infected with Echinococcus multilocularis and the changes of the cellular infiltrates during albendazole (ABZ) treatment.

Methodology/Principal findings

We analyzed liver tissue samples from 8 untreated patients, 5 patients treated with two daily doses of 400 mg ABZ for up to two months and 7 patients treated for more than two months with the same ABZ therapy. A broad panel of monoclonal antibodies was used to characterize the lesion by immunohistochemistry. A change in the cellular infiltrate was observed between the different chemotherapy times. During the initial phases of treatment an increase in CD15+ granulocytes and CD68+ histocytes as well as in small particles of Echinococcus multilocularis (spems) was observed in the tissue surrounding the metacestode. Furthermore, we observed an increase in CD4+ T cells, CD20+ B cells and CD38+ plasma cells during a longer duration of treatment.

Conclusions/Significance

ABZ treatment of AE leads to morphological changes characterized by an initial, predominantly acute, inflammatory response which is gradually replaced by a response of the adaptive immune system.

Hookworm infection is associated with decreased CD4<sup>+</sup> T cell counts in HIV-infected adult Ugandans

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

by Bozena M. Morawski, Miya Yunus, Emmanuel Kerukadho, Grace Turyasingura, Logose Barbra, Andrew Mijumbi Ojok, Andrew DiNardo, Stefanie Sowinski, David R. Boulware, Rojelio Mejia

Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes. Contrasting with previous studies, we measured parasitic infection with a quantitative, highly sensitive and specific polymerase chain reaction (PCR) method. This cohort study enrolled HIV-infected Ugandans from August-September 2013 in Mbale, Uganda and collected stool and blood samples at enrollment. Real-time PCR quantified stool: Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica, and Giardia intestinalis infection. Generalized linear models assessed relationships between parasitic infection and clinical or demographic data. 35% of participants (71/202) tested positive for ≥1 helminth, mainly N. americanus (55/199, 28%), and 4.5% (9/202) were infected with ≥2 stool parasites. Participants with hookworm infection had lower average CD4+ cell counts (-94 cells/mcL, 95%CI: -141, -48 cells/mcL; p<0.001) after adjustment for sex, CD4+ nadir at clinic entry, and time on ART. The high prevalence of parasitic infection and correlation with decreased CD4+ concentrations highlight the need to re-examine the effects of invasive helminth co-infection in rural, HIV-infected populations in the era of widely available ART. Elucidating the relationship between hookworm infection and immune recovery could provide opportunities for health optimization, e.g. integrated deworming, in these vulnerable populations.

Unravelling the rate of action of hits in the <i>Leishmania donovani</i> box using standard drugs amphotericin B and miltefosine

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

by Diana Tegazzini, Juan Cantizani, Imanol Peña, Julio Martín, Jose M. Coterón

In recent years, the neglected diseases drug discovery community has elected phenotypic screening as the key approach for the identification of novel hit compounds. However, when this approach is applied, important questions related to the mode of action for these compounds remain unanswered. One of such questions is related to the rate of action, a useful piece of information when facing the challenge of prioritising the most promising hit compounds. In the present work, compounds of the “Leishmania donovani box” were evaluated using a rate of action assay adapted from a replicative intracellular high content assay recently developed. The potency of each compound was determined every 24 hours up to 96 hours, and standard drugs amphotericin B and miltefosine were used as references to group these compounds according to their rate of action. Independently of this biological assessment, compounds were also clustered according to their minimal chemical scaffold. Comparison of the results showed a complete correlation between the chemical scaffold and the biological group for the vast majority of compounds, demonstrating how the assay was able to bring information on the rate of action for each chemical series, a property directly linked to the mode of action. Overall, the assay here described permitted us to evaluate the rate of action of the “Leishmania donovani box” using two of the currently available drugs as references and, also, to propose a number of fast-acting chemical scaffolds present in the box as starting points for future drug discovery projects to the wider scientific community. The results here presented validate the use of this assay for the determination of the rate of action early in the discovery process, to assist in the prioritisation of hit compounds.

Health beliefs of school-age rural children in podoconiosis-affected families: A qualitative study in Southern Ethiopia

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

by Abebayehu Tora, Getnet Tadele, Abraham Aseffa, Colleen M. McBride, Gail Davey

Background

Several studies have suggested investigation of health beliefs in children to be an important pre-condition for primary prevention of disease. However, little effort has been made to understand these in the context of podoconiosis. This study therefore aimed to explore the health beliefs of school-age rural children in podoconiosis-affected families.

Methodology/Principal findings

A cross sectional qualitative study was conducted in March 2016 in Wolaita Zone, Southern Ethiopia. Data were collected through in-depth individual interviews (IDIs) and focus group discussions (FGDs), with a total of one hundred seventeen 9 to15-year-old children recruited from podoconiosis affected families. The study revealed various misconceptions regarding risk factors for podoconiosis. Most children believed barefoot exposure to dew, worms, snake bite, frog urine, other forms of poison, and contact with affected people to be major causes of the disease. Their knowledge about the role of heredity and that of long term barefoot exposure to irritant mineral particles was also weak. Though most participants correctly appraised their susceptibility to podoconiosis in relation to regular use of footwear and foot hygiene, others based their risk perceptions on factors they think beyond their control. They described several barriers to preventive behaviour, including uncomfortable footwear, shortage and poor adaptability of footwear for farm activities and sports, and shortage of soap for washing. Children also perceived low self-efficacy to practice preventive behaviour in spite of the barriers.

Conclusion/Significance

Health education interventions may enhance school-age children’s health literacy and be translated to preventive action. Overcoming practical challenges such as shortage of footwear and other hygiene facilities requires other forms of interventions such as livelihood strengthening activities. Linking podoconiosis-affected families with local governmental or non-governmental organizations providing socio-economic support for households may assist school-age children in those families to sustainably engage in preventive behaviours.

<i>Clonorchis sinensis</i> antigens alter hepatic macrophage polarization <i>in vitro</i> and <i>in vivo</i>

PLoS Neglected Tropical Diseases News - 24 May 2017 - 9:00pm

by Eun-Min Kim, You Shine Kwak, Myung-Hee YI, Ju Yeong Kim, Woon-Mok Sohn, Tai-Soon Yong

Clonorchis sinensis infection elicits hepatic inflammation, which can lead to cholangitis, periductal hepatic fibrosis, liver cirrhosis, and even cholangiocarcinoma. Hepatic macrophages are an intrinsic element of both innate and acquired immunity. This study was conducted to demonstrate the dynamics of hepatic macrophage polarization during C. sinensis infection in mice and to identify factors regulating this polarization. Treatment of hepatic macrophages isolated from normal mice with C. sinensis excretory/secretory products (ESPs) resulted in the preferential generation of classically activated hepatic macrophages (M1 macrophages) and the production of pro-inflammatory cytokines. Additionally, cells stimulated with C. sinensis ESPs exhibited changes in cellular morphology. During the early stages of C. sinensis infection, hepatic macrophages preferentially differentiated into M1 macrophages; however, during the C. sinensis mature worm stage, when eggs are released, there were significant increases in the abundance of both M1 macrophages and alternatively activated hepatic macrophages (M2 macrophages). Moreover, there was a further increase in the M2 macrophage count during the fibrotic and cirrhotic stage of infection. Notably, this fibrotic and cirrhotic stage promoted a strong increase in the proportion of Arg-1-producing macrophages (M2 phenotype), which were associated with fibrosis and tissue repair in the liver. Our results suggest that the dynamic polarization of hepatic macrophages as C. sinensis infection progresses is related to the histological lesions present in liver tissue. Hepatic macrophages thus play an important role in local immunity during C. sinensis infection.

Using G6PD tests to enable the safe treatment of <i>Plasmodium vivax</i> infections with primaquine on the Thailand-Myanmar border: A cost-effectiveness analysis

PLoS Neglected Tropical Diseases News - 24 May 2017 - 9:00pm

by Angela Devine, Minnie Parmiter, Cindy S. Chu, Germana Bancone, François Nosten, Ric N. Price, Yoel Lubell, Shunmay Yeung

Background

Primaquine is the only licensed antimalarial for the radical cure of Plasmodium vivax infections. Many countries, however, do not administer primaquine due to fear of hemolysis in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In other settings, primaquine is given without G6PD testing, putting patients at risk of hemolysis. New rapid diagnostic tests (RDTs) offer the opportunity to screen for G6PD deficiency prior to treatment with primaquine. Here we assessed the cost-effectiveness of using G6PD RDTs on the Thailand-Myanmar border and provide the model as an online tool for use in other settings.

Methods/Principal findings

Decision tree models for the management of P. vivax malaria evaluated the costs and disability-adjusted life-years (DALYs) associated with recurrences and primaquine-induced hemolysis from a health care provider perspective. Screening with G6PD RDTs before primaquine use was compared to (1) giving chloroquine alone and (2) giving primaquine without screening. Data were taken from a recent study on the impact of primaquine on P. vivax recurrences and a literature review. Compared to the use of chloroquine alone, the screening strategy had similar costs while averting 0.026 and 0.024 DALYs per primary infection in males and females respectively. Compared to primaquine administered without screening, the screening strategy provided modest cost savings while averting 0.011 and 0.004 DALYs in males and females respectively. The probabilistic sensitivity analyses resulted in a greater than 75% certainty that the screening strategy was cost-effective at a willingness to pay threshold of US$500, which is well below the common benchmark of per capita gross domestic product for Myanmar.

Conclusions/Significance

In this setting G6PD RDTs could avert DALYs by reducing recurrences and reducing hemolytic risk in G6PD deficient patients at low costs or cost savings. The model results are limited by the paucity of data available in the literature for some parameter values, including the mortality rates for both primaquine-induced hemolysis and P. vivax. The online model provides an opportunity to use different parameter estimates to examine the validity of these findings in other settings.

“We do not bury dead livestock like human beings”: Community behaviors and risk of Rift Valley Fever virus infection in Baringo County, Kenya

PLoS Neglected Tropical Diseases News - 24 May 2017 - 9:00pm

by Edna N. Mutua, Salome A. Bukachi, Bernard K. Bett, Benson A. Estambale, Isaac K. Nyamongo

Background

Rift Valley Fever (RVF), is a viral zoonotic disease transmitted by Aedes and Culex mosquitoes. In Kenya, its occurrence is associated with increased rains. In Baringo County, RVF was first reported in 2006 resulting in 85 human cases and 5 human deaths, besides livestock losses and livelihood disruptions. This study sought to investigate the county’s current RVF risk status.

Methodology and principal findings

A cross-sectional study on the knowledge, attitudes and practices of RVF was conducted through a mixed methods approach utilizing a questionnaire survey (n = 560) and 26 focus group discussions (n = 231). Results indicate that study participants had little knowledge of RVF causes, its signs and symptoms and transmission mechanisms to humans and livestock. However, most of them indicated that a person could be infected with zoonotic diseases through consumption of meat (79.2%) and milk (73.7%) or contact with blood (40%) from sick animals. There was a statistically significant relationship between being male and milking sick animals, consumption of milk from sick animals, consuming raw or cooked blood, slaughtering sick livestock or dead animals for consumption (all at p≤0.001), and handling sick livestock with bare hands (p = 0.025) with more men than women engaging in the risky practices. Only a few respondents relied on trained personnel or local experts to inspect meat for safety of consumption every time they slaughtered an animal at home. Sick livestock were treated using conventional and herbal medicines often without consulting veterinary officers.

Conclusions

Communities in Baringo County engage in behaviour that may increase their risk to RVF infections during an outbreak. The authors recommend community education to improve their response during outbreaks.

The impact of health promotion on trachoma knowledge, attitudes and practice (KAP) of staff in three work settings in remote Indigenous communities in the Northern Territory

PLoS Neglected Tropical Diseases News - 24 May 2017 - 9:00pm

by Fiona D. Lange, Kelly Jones, Rebecca Ritte, Haley E. Brown, Hugh R. Taylor

Background

Globally, trachoma is the leading cause of infectious blindness and Australia is the only developed country with endemic trachoma. It is found in remote Indigenous communities burdened with poverty, overcrowding and poor hygiene. Lack of culturally appropriate health promotion, a small trachoma workforce and lack of awareness and support for trachoma elimination in general, were early barriers.

Methods

A cross-sectional pre-post study using a convenience sample, was conducted in clinics, schools and community work-settings from 63 of the 82 remote Aboriginal communities identified as being at risk of trachoma in the Northern Territory (NT). The study assessed the effect of a multi-component health promotion strategy aimed at increasing knowledge, attitude and practice amongst health, education and community support settings staff. Data were collected between 2010 and 2012. The health promotion initiatives were introduced in communities in staggered delivery over a one-year period; 272 participants were surveyed at baseline and 261 at follow-up.

Results

Trachoma related knowledge, attitudes and practice increased across all settings and for all primary outcome measures. Across all settings, there was a significant increase in the proportion of participants reporting the most important thing to do if a child has a ‘dirty’ face is to ‘wash it every time its dirty’ (61.6% cf 69.7%; X2p = 0.047), a significant reduction in the proportion of respondents answering ‘no’ to the question “Is it normal for kids to have dirty faces in your community’ (40.5% cf 29.6%; X2p = 0.009) and a significant increase in reported capacity to teach others about trachoma prevention (70.8% cf 83.3%; X2p <0.001).

Conclusion

Health promotion was associated with increased trachoma knowledge, attitude and practice amongst health, education and community support staff working with children and in remote NT communities. In the early stages of the trachoma health promotion program, this increased trachoma awareness and improved local workforce capacity and support for trachoma elimination in three health promotion settings in remote communities in the NT.

MiR-277/4989 regulate transcriptional landscape during juvenile to adult transition in the parasitic helminth <i>Schistosoma mansoni</i>

PLoS Neglected Tropical Diseases News - 23 May 2017 - 9:00pm

by Anna V. Protasio, Stijn van Dongen, Julie Collins, Leonor Quintais, Diogo M. Ribeiro, Florian Sessler, Martin Hunt, Gabriel Rinaldi, James J. Collins, Anton J. Enright, Matthew Berriman

Schistosomes are parasitic helminths that cause schistosomiasis, a disease affecting circa 200 million people, primarily in underprivileged regions of the world. Schistosoma mansoni is the most experimentally tractable schistosome species due to its ease of propagation in the laboratory and the high quality of its genome assembly and annotation. Although there is growing interest in microRNAs (miRNAs) in trematodes, little is known about the role these molecules play in the context of developmental processes. We use the completely unaware “miRNA-blind” bioinformatics tool Sylamer to analyse the 3’-UTRs of transcripts differentially expressed between the juvenile and adult stages. We show that the miR-277/4989 family target sequence is the only one significantly enriched in the transition from juvenile to adult worms. Further, we describe a novel miRNA, sma-miR-4989 showing that its proximal genomic location to sma-miR-277 suggests that they form a miRNA cluster, and we propose hairpin folds for both miRNAs compatible with the miRNA pathway. In addition, we found that expression of sma-miR-277/4989 miRNAs are up-regulated in adults while their predicted targets are characterised by significant down-regulation in paired adult worms but remain largely undisturbed in immature “virgin” females. Finally, we show that sma-miR-4989 is expressed in tegumental cells located proximal to the oesophagus gland and also distributed throughout the male worms’ body. Our results indicate that sma-miR-277/4989 might play a dominant role in post-transcriptional regulation during development of juvenile worms and suggest an important role in the sexual development of female schistosomes.

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