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Mobile-phone and handheld microscopy for neglected tropical diseases

PLoS Neglected Tropical Diseases News - 6 July 2017 - 9:00pm

by Jason Rajchgot, Jean T. Coulibaly, Jennifer Keiser, Jürg Utzinger, Nathan C. Lo, Michael K. Mondry, Jason R. Andrews, Isaac I. Bogoch

Host-seeking efficiency can explain population dynamics of the tsetse fly <i>Glossina morsitans morsitans</i> in response to host density decline

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Jennifer S. Lord, Zinhle Mthombothi, Vitalis K. Lagat, Fatumah Atuhaire, John W. Hargrove

Females of all blood-feeding arthropod vectors must find and feed on a host in order to produce offspring. For tsetse—vectors of the trypanosomes that cause human and animal African trypanosomiasis—the problem is more extreme, since both sexes feed solely on blood. Host location is thus essential both for survival and reproduction. Host population density should therefore be an important driver of population dynamics for haematophagous insects, and particularly for tsetse, but the role of host density is poorly understood. We investigate the issue using data on changes in numbers of tsetse (Glossina morsitans morsitans Westwood) caught during a host elimination experiment in Zimbabwe in the 1960s. During the experiment, numbers of flies caught declined by 95%. We aimed to assess whether models including starvation-dependent mortality could explain observed changes in tsetse numbers as host density declined. An ordinary differential equation model, including starvation-dependent mortality, captured the initial dynamics of the observed tsetse population. However, whereas small numbers of tsetse were caught throughout the host elimination exercise, the modelled population went extinct. Results of a spatially explicit agent-based model suggest that this discrepancy could be explained by immigration of tsetse into the experimental plot. Variation in host density, as a result of natural and anthropogenic factors, may influence tsetse population dynamics in space and time. This has implications for Trypanosoma brucei rhodesiense transmission. Increased tsetse mortality as a consequence of low host density may decrease trypanosome transmission, but hungrier flies may be more inclined to bite humans, thereby increasing the risk of transmission to humans. Our model provides a way of exploring the role of host density on tsetse population dynamics and could be incorporated into models of trypanosome transmission dynamics to better understand how spatio-temporal variation in host density impacts trypanosome prevalence in mammalian hosts.

Are scabies and impetigo “normalised”? A cross-sectional comparative study of hospitalised children in northern Australia assessing clinical recognition and treatment of skin infections

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Daniel K. Yeoh, Aleisha Anderson, Gavin Cleland, Asha C. Bowen

Background

Complications of scabies and impetigo such as glomerulonephritis and invasive bacterial infection in Australian Aboriginal children remain significant problems and the overall global burden of disease attributable to these skin infections remains high despite the availability of effective treatment. We hypothesised that one factor contributing to this high burden is that skin infection is under-recognised and hence under-treated, in settings where prevalence is high.

Methods

We conducted a prospective, cross-sectional study to assess the burden of scabies, impetigo, tinea and pediculosis in children admitted to two regional Australian hospitals from October 2015 to January 2016. A retrospective chart review of patients admitted in November 2014 (mid-point of the prospective data collection in the preceding year) was performed. Prevalence of documented skin infection was compared in the prospective and retrospective population to assess clinician recognition and treatment of skin infections.

Results

158 patients with median age 3.6 years, 74% Aboriginal, were prospectively recruited. 77 patient records were retrospectively reviewed. Scabies (8.2% vs 0.0%, OR N/A, p = 0.006) and impetigo (49.4% vs 19.5%, OR 4.0 (95% confidence interval [CI 2.1–7.7) were more prevalent in the prospective analysis. Skin examination was only documented in 45.5% of cases in the retrospective review. Patients in the prospective analysis were more likely to be prescribed specific treatment for skin infection compared with those in the retrospective review (31.6% vs 5.2%, OR 8.5 (95% CI 2.9–24.4).

Conclusions

Scabies and impetigo infections are under-recognised and hence under-treated by clinicians. Improving the recognition and treatment of skin infections by clinicians is a priority to reduce the high burden of skin infection and subsequent sequelae in paediatric populations where scabies and impetigo are endemic.

The clinical burden of human cystic echinococcosis in Palestine, 2010-2015

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Amer Al-Jawabreh, Suheir Ereqat, Kamal Dumaidi, Abdelmajeed Nasereddin, Hanan Al-Jawabreh, Kifaya Azmi, Nahed Al-Laham, Moath Nairat, Adriano Casulli, Husni Maqboul, Ziad Abdeen

Background

Cystic echinococcosis (CE) is classified by the WHO as a neglected disease inflicting economic losses on the health systems of many countries worldwide. The aim of this case-series study was to investigate the burden of human CE in Palestine during the period between 2010 and 2015.

Methodology/Principal findings

Records of surgically confirmed CE patients from 13 public and private hospitals in the West Bank and Gaza Strip were reviewed. Patients’ cysts were collected from surgical wards and formalin-fixed paraffin-embedded (FFPE) blocks were collected from histopathology departments. Molecular identification of CE species /genotypes was conducted by targeting a repeat DNA sequence (EgG1 Hae III) within Echinococcus nuclear genome and a fragment within the mitochondrial cytochrome c oxidase subunit 1, (CO1). Confirmation of CE species/genotypes was carried out using sequencing followed by BLAST analysis and the construction of maximum likelihood consensus dendrogram. CE cases were map-spotted and statistically significant foci identified by spatial analysis. A total of 353 CE patients were identified in 108 localities from the West Bank and Gaza Strip. The average surgical incidence in the West Bank was 2.1 per 100,000. Spot-mapping and purely spatial analysis showed 13 out of 16 Palestinian districts had cases of CE, of which 9 were in the West Bank and 4 in Gaza Strip. Al-Khalil and Bethlehem were statistically significant foci of CE in Palestine with a six-year average incidence of 4.2 and 3.7 per 100,000, respectively.

Conclusions/Significance

To the best of our knowledge, this is the first confirmation of human CE causative agent in Palestine. This study revealed that E. granulosus sensu stricto (s.s.) was the predominating species responsible for CE in humans with 11 samples identified as G1 genotype and 2 as G3 genotype. This study emphasizes the need for a stringent surveillance system and risk assessment studies in the rural areas of high incidence as a prerequisite for control measures.

A leprosy clinical severity scale for erythema nodosum leprosum: An international, multicentre validation study of the ENLIST ENL Severity Scale

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Stephen L. Walker, Anna M. Sales, C. Ruth Butlin, Mahesh Shah, Armi Maghanoy, Saba M. Lambert, Joydeepa Darlong, Benjamin Jewel Rozario, Vivek V. Pai, Marivic Balagon, Shimelis N. Doni, Deanna A. Hagge, José A. C. Nery, Kapil D. Neupane, Suwash Baral, Biliom A. Sangma, Digafe T. Alembo, Abeba M. Yetaye, Belaynesh A. Hassan, Mohammed B. Shelemo, Peter G. Nicholls, Diana N. J. Lockwood, on behalf of the Erythema Nodosum Leprosum International STudy Group

Objectives

We wished to validate our recently devised 16-item ENLIST ENL Severity Scale, a clinical tool for measuring the severity of the serious leprosy associated complication of erythema nodosum leprosum (ENL). We also wished to assess the responsiveness of the ENLIST ENL Severity Scale in detecting clinical change in patients with ENL.

Methods

Participants, recruited from seven centres in six leprosy endemic countries, were assessed using the ENLIST ENL Severity Scale by two researchers, one of whom categorised the severity of ENL. At a subsequent visit a further assessment using the scale was made and both participant and physician rated the change in ENL using the subjective categories of “Much better”, “somewhat better”, “somewhat worse” and “much worse” compared with “No change” or “about the same”.

Results

447 participants were assessed with the ENLIST ENL Severity Scale. The Cronbach alpha of the scale and each item was calculated to determine the internal consistency of the scale. The ENLIST ENL Severity Scale had good internal consistency and this improved following removal of six items to give a Cronbach’s alpha of 0.77. The cut off between mild ENL and more severe disease was 9 determined using ROC curves. The minimal important difference of the scale was determined to be 5 using both participant and physician ratings of change.

Conclusions

The 10-item ENLIST ENL Severity Scale is the first valid, reliable and responsive measure of ENL severity and improves our ability to assess and compare patients and their treatments in this severe and difficult to manage complication of leprosy.The ENLIST ENL Severity Scale will assist physicians in the monitoring and treatment of patients with ENL. The ENLIST ENL Severity Scale is easy to apply and will be useful as an outcome measure in treatment studies and enable the standardisation of other clinical and laboratory ENL research.

Prevalence of Lassa Virus Disease (LVD) in Nigerian children with fever or fever and convulsions in an endemic area

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Odigie C. Akhuemokhan, Rosemary O. Ewah-Odiase, Nosa Akpede, Jacqueline Ehimuan, Donatus I. Adomeh, Ikpomwonsa Odia, Sylvia C. Olomu, Meike Pahlmann, Beate Becker-Ziaja, Christian T. Happi, Danny A. Asogun, Sylvanus A. Okogbenin, Peter O. Okokhere, Osagie S. Dawodu, Irekpono U. Omoike, Pardis C. Sabeti, Stephan Günther, George O. Akpede

Background

Convulsions with fever in children is a common neurologic emergency in the tropics, and determining the contribution of endemic viral infections can be challenging. In particular, there is a dearth of data on the prevalence and clinical differentiation of Lassa virus disease (LVD) in febrile children in endemic areas of Nigeria, which has multiple lineages of the virus. The aim of this study was to determine the prevalence and presentation of LVD in febrile children with and without convulsions.

Methodology/Principal findings

This was a prospective study of consecutive febrile children aged ≥1 month– 15 years admitted to the Children’s Emergency Room of Irrua Specialist Teaching Hospital over a period of 1 year. Febrile children with convulsions (Cases) were compared with those without convulsions (Controls). LVD was defined by the presence of a positive Lassa virus RT-PCR test. Rates were compared between groups using χ2 or Fisher’s exact tests and p <0.05 taken as significant. 373 (40.9%) of 913 admissions had fever. Of these, 108/373 (29%) presented with convulsions. The overall prevalence of LVD was 13/373 (3.5%; 95% CI = 1.9%, 5.7%) in febrile admissions, 3/108 (2.8%) in Cases and 10/265 (3.8%) in Controls [(Odds Ratio (95% Confidence Interval) (OR (95% CI)) of LVD in Cases versus Controls = 0.73 (0.2, 2.7)]. Only vomiting (OR (95% CI) = 0.09 (0.01, 0.70)) and bleeding (OR (95% CI) = 39.56 (8.52, 183.7)) were significantly associated with an increased prevalence of LVD.

Conclusions/Significance

LVD is an important cause of fever, including undifferentiated fever in children in endemic areas, but it is not significantly associated with convulsions associated with fever. Its prevalence, and lack of clinical differentiation on presentation, underscores the importance of a high index of suspicion in diagnosis. Screening of febrile children with undifferentiated fever in endemic areas for LVD could be an important medical and public health control measure.

Lineage-dependent differences in the disease progression of Zika virus infection in type-I interferon receptor knockout (A129) mice

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Stuart D. Dowall, Victoria A. Graham, Emma Rayner, Laura Hunter, Barry Atkinson, Geoff Pearson, Mike Dennis, Roger Hewson

Zika virus (ZIKV) falls into two lineages: African (ZIKVAF) and Asian (ZIKVAS). These lineages have not been tested comprehensively in parallel for disease progression using an animal model system. Here, using the established type-I interferon receptor knockout (A129) mouse model, it is first demonstrated that ZIKVAF causes lethal infection, with different kinetics of disease manifestations according to the challenge dose. Animals challenged with a low dose of 10 plaque-forming units (pfu) developed more neurological symptoms than those challenged with 5-log higher doses. By contrast, animals challenged with ZIKVAS displayed no clinical signs or mortality, even at doses of 106 pfu. However, viral RNA was detected in the tissues of animals infected with ZIKV strains from both lineages and similar histological changes were observed. The present study highlights strain specific virulence differences between the African and Asian lineages in a ZIKV mouse model.

Bayesian dynamic modeling of time series of dengue disease case counts

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Daniel Adyro Martínez-Bello, Antonio López-Quílez, Alexander Torres-Prieto

The aim of this study is to model the association between weekly time series of dengue case counts and meteorological variables, in a high-incidence city of Colombia, applying Bayesian hierarchical dynamic generalized linear models over the period January 2008 to August 2015. Additionally, we evaluate the model’s short-term performance for predicting dengue cases. The methodology shows dynamic Poisson log link models including constant or time-varying coefficients for the meteorological variables. Calendar effects were modeled using constant or first- or second-order random walk time-varying coefficients. The meteorological variables were modeled using constant coefficients and first-order random walk time-varying coefficients. We applied Markov Chain Monte Carlo simulations for parameter estimation, and deviance information criterion statistic (DIC) for model selection. We assessed the short-term predictive performance of the selected final model, at several time points within the study period using the mean absolute percentage error. The results showed the best model including first-order random walk time-varying coefficients for calendar trend and first-order random walk time-varying coefficients for the meteorological variables. Besides the computational challenges, interpreting the results implies a complete analysis of the time series of dengue with respect to the parameter estimates of the meteorological effects. We found small values of the mean absolute percentage errors at one or two weeks out-of-sample predictions for most prediction points, associated with low volatility periods in the dengue counts. We discuss the advantages and limitations of the dynamic Poisson models for studying the association between time series of dengue disease and meteorological variables. The key conclusion of the study is that dynamic Poisson models account for the dynamic nature of the variables involved in the modeling of time series of dengue disease, producing useful models for decision-making in public health.

Clearance of viable <i>Mycobacterium ulcerans</i> from Buruli ulcer lesions during antibiotic treatment as determined by combined 16S rRNA reverse transcriptase /IS 2404 qPCR assay

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Mabel Sarpong-Duah, Michael Frimpong, Marcus Beissner, Malkin Saar, Ken Laing, Francisca Sarpong, Aloysius Dzigbordi Loglo, Kabiru Mohammed Abass, Margaret Frempong, Fred Stephen Sarfo, Gisela Bretzel, Mark Wansbrough-Jones, Richard Odame Phillips

Introduction

Buruli ulcer (BU) caused by Mycobacterium ulcerans is effectively treated with rifampicin and streptomycin for 8 weeks but some lesions take several months to heal. We have shown previously that some slowly healing lesions contain mycolactone suggesting continuing infection after antibiotic therapy. Now we have determined how rapidly combined M. ulcerans 16S rRNA reverse transcriptase / IS2404 qPCR assay (16S rRNA) became negative during antibiotic treatment and investigated its influence on healing.

Methods

Fine needle aspirates and swab samples were obtained for culture, acid fast bacilli (AFB) and detection of M. ulcerans 16S rRNA and IS2404 by qPCR (16S rRNA) from patients with IS2404 PCR confirmed BU at baseline, during antibiotic and after treatment. Patients were followed up at 2 weekly intervals to determine the rate of healing. The Kaplan-Meier survival analysis was used to analyse the time to clearance of M. ulcerans 16S rRNA and the influence of persistent M ulcerans 16S rRNA on time to healing. The Mann Whitney test was used to compare the bacillary load at baseline in patients with or without viable organisms at week 4, and to analyse rate of healing at week 4 in relation to detection of viable organisms.

Results

Out of 129 patients, 16S rRNA was detected in 65% of lesions at baseline. The M. ulcerans 16S rRNA remained positive in 78% of patients with unhealed lesions at 4 weeks, 52% at 8 weeks, 23% at 12 weeks and 10% at week 16. The median time to clearance of M. ulcerans 16S rRNA was 12 weeks. BU lesions with positive 16S rRNA after antibiotic treatment had significantly higher bacterial load at baseline, longer healing time and lower healing rate at week 4 compared with those in which 16S rRNA was not detected at baseline or had become undetectable by week 4.

Conclusions

Current antibiotic therapy for BU is highly successful in most patients but it may be possible to abbreviate treatment to 4 weeks in patients with a low initial bacterial load. On the other hand persistent infection contributes to slow healing in patients with a high bacterial load at baseline, some of whom may need antibiotic treatment extended beyond 8 weeks. Bacterial load was estimated from a single sample taken at baseline. A better estimate could be made by taking multiple samples or biopsies but this was not ethically acceptable.

Mosquitoes on a plane: Disinsection will not stop the spread of vector-borne pathogens, a simulation study

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Luis Mier-y-Teran-Romero, Andrew J. Tatem, Michael A. Johansson

Mosquito-borne diseases are increasingly being recognized as global threats, with increased air travel accelerating their occurrence in travelers and their spread to new locations. Since the early days of aviation, concern over the possible transportation of infected mosquitoes has led to recommendations to disinsect aircraft. Despite rare reports of mosquitoes, most likely transported on aircraft, infecting people far from endemics areas, it is unclear how important the role of incidentally transported mosquitoes is compared to the role of traveling humans. We used data for Plasmodium falciparum and dengue viruses to estimate the probability of introduction of these pathogens by mosquitoes and by humans via aircraft under ideal conditions. The probability of introduction of either pathogen by mosquitoes is low due to few mosquitoes being found on aircraft, low infection prevalence among mosquitoes, and high mortality. Even without disinsection, introduction via infected human travelers was far more likely than introduction by infected mosquitoes; more than 1000 times more likely for P. falciparum and more than 200 times more likely for dengue viruses. Even in the absence of disinsection and under the most favorable conditions, introduction of mosquito-borne pathogens via air travel is far more likely to occur as a result of an infected human travelling rather than the incidental transportation of infected mosquitoes. Thus, while disinsection may serve a role in preventing the spread of vector species and other invasive insects, it is unlikely to impact the spread of mosquito-borne pathogens.

Predominance of asymptomatic and sub-microscopic infections characterizes the <i>Plasmodium</i> gametocyte reservoir in the Peruvian Amazon

PLoS Neglected Tropical Diseases News - 3 July 2017 - 9:00pm

by Eduard Rovira-Vallbona, Juan José Contreras-Mancilla, Roberson Ramirez, Mitchel Guzmán-Guzmán, Gabriel Carrasco-Escobar, Alejandro Llanos-Cuentas, Joseph M. Vinetz, Dionicia Gamboa, Anna Rosanas-Urgell

Malaria transmission requires that Anopheles mosquitoes ingest Plasmodium gametocyte stages circulating in the human bloodstream. In the context of malaria elimination, understanding the epidemiology of gametocytes relative to all Plasmodium infections and the contribution of asymptomatic and sub-microscopic parasite carriers to the gametocyte reservoir is necessary, especially in low endemic settings with predominance of P.vivax. A 13-month longitudinal study was conducted in two communities (n = 1935 individuals) of Loreto Department, Peru, with five active screenings for Plasmodium infections and gametocyte stages by quantitative real-time PCR (qPCR) and reverse transcription (RT)-qPCR, respectively. Parasite prevalence by qPCR was 7.2% for P.vivax (n = 520/7235; range by survey 6.0%-8.1%) and 3.2% for P.falciparum (n = 235/7235; range by survey 0.4%-7.7%). Sub-microscopic infections accounted for 73.5% of P.vivax (range by survey 60%-89%) and almost the totality of P.falciparum cases. Gametocytes were found in 28.4% P.vivax infections (range by survey 18.7%-34.1%), with a peak of 61.5% in one community at the start of the transmission season. About 59.8% of all P.vivax gametocyte carriers were asymptomatic and 31.9% were sub-microscopic. Age patterns for gametocyte prevalence paralleled asexual stage infections and peaked among 15–25 year old individuals. Asexual parasite density was found to be the strongest predictor for P.vivax gametocyte presence in longitudinal multivariate analysis (odds ratio 2.33 [95% confidence interval 1.96, 2.78]; P<0.001). Despite significant differences in seasonality patterns and P.vivax prevalence found at the local scale, sub-microscopic and asymptomatic infections predominate and contribute significantly to the gametocyte reservoir in different communities of the Peruvian Amazon. Control and elimination campaigns need sensitive tools to detect all infections that escape routine malaria surveillance, which may contribute to maintain transmission in the region.

Intrinsic and extrinsic factors related to pathogen infection in wild small mammals in intensive milk cattle and swine production systems

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

by Rosario Lovera, María Soledad Fernández, Jens Jacob, Nidia Lucero, Gabriel Morici, Bibiana Brihuega, María Isabel Farace, Jorge Caracostantogolo, Regino Cavia

Background

Understanding the ecological processes that are involved in the transmission of zoonotic pathogens by small mammals may aid adequate and effective management measures. Few attempts have been made to analyze the ecological aspects that influence pathogen infection in small mammals in livestock production systems. We describe the infection of small mammals with Leptospira spp., Brucella spp., Trichinella spp. and Cysticercus fasciolaris and assess the related intrinsic and extrinsic factors in livestock production systems in central Argentina at the small mammal community, population and individual levels.

Methodology/Principal findings

Ten pig farms and eight dairy farms were studied by removal trapping of small mammals from 2008 to 2011. Each farm was sampled seasonally over the course of one year with cage and Sherman live traps. The 505 small mammals captured (14,359 trap-nights) included three introduced murine rodents, four native rodents and two opossums. Leptospira spp., anti-Brucella spp. antibodies and Trichinella spp. were found in the three murine rodents and both opossums. Rattus norvegicus was also infected with C. fasciolaris; Akodon azarae and Oligoryzomys flavescens with Leptospira spp.; anti-Brucella spp. antibodies were found in A. azarae. Two or more pathogens occurred simultaneously on 89% of the farms, and each pathogen was found on at least 50% of the farms. Pathogen infections increased with host abundance. Infection by Leptospira spp. also increased with precipitation and during warm seasons. The occurrence of anti-Brucella spp. antibodies was higher on dairy farms and during the winter and summer. The host abundances limit values, from which farms are expected to be free of the studied pathogens, are reported.

Conclusions/Significance

Murine rodents maintain pathogens within farms, whereas other native species are likely dispersing pathogens among farms. Hence, we recommend preventing and controlling murines in farm dwellings and isolating farms from their surroundings to avoid contact with other wild mammals.

Post-dengue acute disseminated encephalomyelitis: A case report and meta-analysis

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

by Mohamed Gomaa Kamel, Nguyen Tran Nam, Nguyen Huu Bao Han, Abd-Elaziz El-Shabouny, Abd-ElRahman Mohamed Makram, Fatma Abd-Elshahed Abd-Elhay, Tran Ngoc Dang, Nguyen Le Trung Hieu, Vu Thi Que Huong, Trinh Huu Tung, Kenji Hirayama, Nguyen Tien Huy

Background

Dengue is one of the most common infectious diseases. The aim of this study was to systematically review acute disseminated encephalomyelitis (ADEM) and to represent a new case.

Methodology/Principal findings

We searched for articles in nine databases for case reports, series or previous reviews reporting ADEM cases in human. We used Fisher’s exact and Mann-Whitney U tests. Classification trees were used to find the predictors of the disease outcomes. We combined findings using fixed- and random-effects models. A 13-year-old girl was admitted to the hospital due to fever. She has a urinary retention. The neurological examinations revealed that she became lethargic and quadriplegic. She had upper limbs weakness and lower limbs complete paraplegia. Her status gradually improved after the treatment. She was nearly intact with the proximal part of her legs had a mild weakness in discharge. The prevalence of ADEM among dengue patients was 0.4% [95% confidence intervals (95% CI) 0.1–2.5%], all neurological disorders among dengue was 2.6% [95% CI 1.8–3.8%], and ADEM among neurological disorders was 6.8% [95% CI 3.4–13%]. The most frequent manifestation of ADEM was altered sensorium/consciousness (58%), seizures and urination problems (35%), vision problems (31%), slurred speech (23%), walk problems (15%) then ataxia (12%). There was a significant difference between cases having complete recovery or bad outcomes in the onset day of neurological manifestations being earlier and in temperature being higher in cases having bad outcomes (p-value < 0.05). This was confirmed by classification trees which included these two variables.

Conclusions/Significance

The prevalence of ADEM among dengue and other dengue-related neurological disorders is not too rare. The high fever of ADEM cases at admission and earlier onset day of neurological manifestations are associated with the bad outcomes.

Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions

PLoS Neglected Tropical Diseases News - 29 June 2017 - 9:00pm

by Leah M. Wachsmuth, Meredith G. Johnson, Jason Gavenonis

Parasitic diseases caused by kinetoplastid parasites of the genera Trypanosoma and Leishmania are an urgent public health crisis in the developing world. These closely related species possess a number of multimeric enzymes in highly conserved pathways involved in vital functions, such as redox homeostasis and nucleotide synthesis. Computational alanine scanning of these protein-protein interfaces has revealed a host of potentially ligandable sites on several established and emerging anti-parasitic drug targets. Analysis of interfaces with multiple clustered hotspots has suggested several potentially inhibitable protein-protein interactions that may have been overlooked by previous large-scale analyses focusing solely on secondary structure. These protein-protein interactions provide a promising lead for the development of new peptide and macrocycle inhibitors of these enzymes.

Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

PLoS Neglected Tropical Diseases News - 29 June 2017 - 9:00pm

by Gustavo Adolfo Sierra Romero, Dorcas Lamounier Costa, Carlos Henrique Nery Costa, Roque Pacheco de Almeida, Enaldo Viera de Melo, Sílvio Fernando Guimarães de Carvalho, Ana Rabello, Andréa Lucchesi de Carvalho, Anastácio de Queiroz Sousa, Robério Dias Leite, Simone Soares Lima, Thais Alves Amaral, Fabiana Piovesan Alves, Joelle Rode, the Collaborative LVBrasil Group

Background

There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option.

Methods

A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption.

Results

378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003).

Conclusions

Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738.

Trial registration

ClinicalTrials.gov NCT01310738

High risk for chikungunya virus to initiate an enzootic sylvatic cycle in the tropical Americas

PLoS Neglected Tropical Diseases News - 29 June 2017 - 9:00pm

by Ricardo Lourenço-de-Oliveira, Anna-Bella Failloux

Background

Chikungunya virus (CHIKV) has dispersed in the Americas since 2013, and its range of distribution has overlapped large forested areas. Herein, we assess vector competence of two sylvatic Neotropical mosquito species, Haemagogus leucocelaenus and Aedes terrens, to evaluate the risk of CHIKV to initiate a sylvatic cycle in the continent.

Methodology/Principal findings

Haemagogus leucocelaenus and Ae. terrens from the state of Rio de Janeiro, Brazil were orally challenged with the two CHIKV lineages circulating in the Americas. Fully engorged females were kept in incubators at 28±1°C and 70±10% humidity and examined at 3 and 7 days after virus exposure. Body (thorax plus abdomen), head and saliva samples were analyzed for respectively determining infection, dissemination and transmission. Both Hg. leucocelaenus and Ae. terrens exhibited high infection and dissemination rates with both CHIKV isolates at 7 dpi, demonstrating that they are susceptible to CHIKV, regardless of the lineage. Remarkably, Hg. leucocelaenus expectorated infectious viral particles as rapidly as 3 days after the infectious blood meal, displaying higher values of transmission rate and efficiency than Ae. terrens. Nevertheless, both species were competent to experimentally transmit both CHIKV genotypes, exhibiting vector competence similar to several American Aedes aegypti.

Conclusions/Significance

These results point out the high risk for CHIKV to establish a sylvatic transmission cycle in the Americas, which could be a serious health issue as CHIKV would become another zoonotic infection difficult to control in the continent.

First evidence of lymphatic filariasis transmission interruption in Cameroon: Progress towards elimination

PLoS Neglected Tropical Diseases News - 29 June 2017 - 9:00pm

by Hugues C. Nana-Djeunga, Magellan Tchouakui, Guy R. Njitchouang, Jules B. Tchatchueng-Mbougua, Philippe Nwane, André Domche, Jean Bopda, Stève Mbickmen-Tchana, Julie Akame, Ann Tarini, Emilienne Epée, Benjamin D. Biholong, Yaobi Zhang, Jean J. Tougoue, Achille Kabore, Flobert Njiokou, Joseph Kamgno

Background

Lymphatic filariasis (LF) is among the 10 neglected tropical diseases targeted for control or elimination by 2020. For LF elimination, the World Health Organization (WHO) has proposed a comprehensive strategy including (i) interruption of LF transmission through large-scale annual treatment (or mass drug administration (MDA)) of all eligible individuals in endemic areas, and (ii) alleviation of LF-associated suffering through morbidity management and disability prevention. In Cameroon, once-yearly mass administration of ivermectin and albendazole has been implemented since 2008. The aim of this study was to assess progress towards the elimination goal, looking specifically at the impact of six rounds of MDA on LF transmission in northern Cameroon.

Methodology

The study was conducted in the North and Far North Regions of Cameroon. Five health districts that successfully completed six rounds of MDA (defined as achieving a treatment coverage ≥ 65% each year) and reported no positive results for Wuchereria bancrofti microfilariaemia during routine surveys following the fifth MDA were grouped into three evaluation units (EU) according to WHO criteria. LF transmission was assessed through a community-based transmission assessment survey (TAS) using an immunochromatographic test (ICT) for the detection of circulating filarial antigen (CFA) in children aged 5–8 years old.

Principal findings

A total of 5292 children (male/female ratio 1.04) aged 5–8 years old were examined in 97 communities. Positive CFA results were observed in 2, 8 and 11 cases, with a CFA prevalence of 0.13% (95% CI: 0.04–0.46) in EU#1, 0.57% (95% CI: 0.32–1.02) in EU#2, and 0.45% (95% CI: 0.23–0.89) in EU#3.

Conclusion/Significance

The positive CFA cases were below WHO defined critical cut-off thresholds for stopping treatment and suggest that transmission can no longer be sustained. Post-MDA surveillance activities should be organized to evaluate whether recrudescence can occur.

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