RSS news feeds

Socioeconomic and environmental determinants of dengue transmission in an urban setting: An ecological study in Nouméa, New Caledonia

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

by Raphaël M. Zellweger, Jorge Cano, Morgan Mangeas, François Taglioni, Alizé Mercier, Marc Despinoy, Christophe E. Menkès, Myrielle Dupont-Rouzeyrol, Birgit Nikolay, Magali Teurlai

Background

Dengue is a mosquito-borne virus that causes extensive morbidity and economic loss in many tropical and subtropical regions of the world. Often present in cities, dengue virus is rapidly spreading due to urbanization, climate change and increased human movements. Dengue cases are often heterogeneously distributed throughout cities, suggesting that small-scale determinants influence dengue urban transmission. A better understanding of these determinants is crucial to efficiently target prevention measures such as vector control and education. The aim of this study was to determine which socioeconomic and environmental determinants were associated with dengue incidence in an urban setting in the Pacific.

Methodology

An ecological study was performed using data summarized by neighborhood (i.e. the neighborhood is the unit of analysis) from the last two dengue epidemics (2008–2009 and 2012–2013) in the city of Nouméa, the capital of New Caledonia. Spatial patterns and hotspots of dengue transmission were assessed using global and local Moran’s I statistics. Multivariable negative binomial regression models were used to investigate the association between dengue incidence and various socioeconomic and environmental factors throughout the city.

Principal findings

The 2008–2009 epidemic was spatially structured, with clusters of high and low incidence neighborhoods. In 2012–2013, dengue incidence rates were more homogeneous throughout the city. In all models tested, higher dengue incidence rates were consistently associated with lower socioeconomic status (higher unemployment, lower revenue or higher percentage of population born in the Pacific, which are interrelated). A higher percentage of apartments was associated with lower dengue incidence rates during both epidemics in all models but one. A link between vegetation coverage and dengue incidence rates was also detected, but the link varied depending on the model used.

Conclusions

This study demonstrates a robust spatial association between dengue incidence rates and socioeconomic status across the different neighborhoods of the city of Nouméa. Our findings provide useful information to guide policy and help target dengue prevention efforts where they are needed most.

An inter- laboratory proficiency testing exercise for rabies diagnosis in Latin America and the Caribbean

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

by Alfonso Clavijo, Mary H. Freire de Carvalho, Lillian A. Orciari, Andres Velasco-Villa, James Ellison, Lauren Greenberg, Pamela A. Yager, Douglas B. Green, Marco A. Vigilato, Ottorino Cosivi, Victor J. Del Rio-Vilas

The direct fluorescent antibody test (DFA), is performed in all rabies reference laboratories across Latin America and the Caribbean (LAC). Despite DFA being a critical capacity in the control of rabies, there is not a standardized protocol in the region. We describe the results of the first inter-laboratory proficiency exercise of national rabies laboratories in LAC countries as part of the regional efforts towards dog-maintained rabies elimination in the American region. Twenty three laboratories affiliated to the Ministries of Health and Ministries of Agriculture participated in this exercise. In addition, the laboratories completed an online questionnaire to assess laboratory practices. Answers to the online questionnaire indicated large variability in the laboratories throughput, equipment used, protocols availability, quality control standards and biosafety requirements. Our results will inform actions to improve and harmonize laboratory rabies capacities across LAC in support for the regional efforts towards elimination of dog-maintained rabies.

Pulmonary shunts in severe hepatosplenic schistosomiasis: Diagnosis by contrast echocardiography and their relationship with abdominal ultrasound findings

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

by Liana Gonçalves-Macedo, Ana Lucia Coutinho Domingues, Edmundo Pessoa Lopes, Carlos Feitosa Luna, Vitor Gomes Mota, Mônica Morais de Chaves Becker, Brivaldo Markman-Filho

Background

Schistosomiasis is endemic to several parts of the world. Among the species that affect humans, Schistosoma mansoni is one of the most common causes of illness. In regions where schistosomiasis mansoni is endemic, reinfection is responsible for the emergence of hepatosplenic schistosomiasis (HSS) with portal hypertension in about 10% of infected individuals. Regardless of its etiology, portal hypertension may bring about the formation of arteriovenous fistulas and pulmonary vascular dilation, thus constituting a pulmonary shunt and its presence has been associated with the occurrence of neurological complications. The objective of this study was to identify pulmonary shunt using TTCE in patients with HSS and esophageal varices, and to compare the abdominal ultrasound and endoscopy findings among patients with and without pulmonary shunt.

Methodology/Principal findings

In this case series, a total of 461 patients with schistosomiasis mansoni were prospectively evaluated using abdominal ultrasound and endoscopy and 71 presented with HSS with esophageal varices. Fifty seven patients remained in the final analysis. The mean age of the patients was 55 ± 14 years, and 65% were female. Pulmonary shunts were observed in 19 (33.3%) patients. On comparing the groups with and without pulmonary shunt, no significant differences were observed in relation to the abdominal ultrasound and endoscopic findings. When comparing the two subgroups with pulmonary shunts (grade 1 vs grades 2 and 3), it was observed that the subgroup with shunt grades 2 and 3 presented with a significantly higher frequency of an enlarged splenic vein diameter (>0.9 cm), and an advanced pattern of periportal hepatic fibrosis (P = 0.041 and P = 0.005, respectively). None of the patients with pulmonary shunts had severe neurological complications.

Conclusions/Significance

Our findings suggest that in HSS with esophageal varices the pulmonary shunts may be present in higher grades and that in this condition it was associated with ultrasound findings compatible with advanced HSS.

VivaxGEN: An open access platform for comparative analysis of short tandem repeat genotyping data in <i>Plasmodium vivax</i> Populations

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

by Hidayat Trimarsanto, Ernest D. Benavente, Rintis Noviyanti, Retno Ayu Setya Utami, Leily Trianty, Zuleima Pava, Sisay Getachew, Jung-Yeon Kim, Youn-Kyoung Goo, Sonam Wangchuck, Yaobao Liu, Qi Gao, Simone Dowd, Qin Cheng, Taane G. Clark, Ric N. Price, Sarah Auburn

Background

The control and elimination of Plasmodium vivax will require a better understanding of its transmission dynamics, through the application of genotyping and population genetics analyses. This paper describes VivaxGEN (http://vivaxgen.menzies.edu.au), a web-based platform that has been developed to support P. vivax short tandem repeat data sharing and comparative analyses.

Results

The VivaxGEN platform provides a repository for raw data generated by capillary electrophoresis (FSA files), with fragment analysis and standardized allele calling tools. The query system of the platform enables users to filter, select and differentiate samples and alleles based on their specified criteria. Key population genetic analyses are supported including measures of population differentiation (FST), expected heterozygosity (HE), linkage disequilibrium (IAS), neighbor-joining analysis and Principal Coordinate Analysis. Datasets can also be formatted and exported for application in commonly used population genetic software including GENEPOP, Arlequin and STRUCTURE. To date, data from 10 countries, including 5 publicly available data sets have been shared with VivaxGEN.

Conclusions

VivaxGEN is well placed to facilitate regional overviews of P. vivax transmission dynamics in different endemic settings and capable to be adapted for similar genetic studies of P. falciparum and other organisms.

Knowledge, practices and perceptions of geo-helminthes infection among parents of pre-school age children of Coastal region, Kenya

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

by Janet Masaku, Faith Mwende, Gladys Odhiambo, Rosemary Musuva, Elizabeth Matey, Jimmy H. Kihara, Isaac G. Thuita, Doris Wairimu Njomo

Background

Soil-transmitted helminthes (STHs) are common human parasitic diseases in most of the developing world particularly in Kenya. The ongoing National School-Based Deworming Programme (NSBDP) was launched in 2012 and is currently targeting 28 of the 47 endemic Counties. In an effort to improve treatment intervention strategies among Pre-School Age Children (PSAC) attending Early Childhood Development Centres (ECDC), we sought to assess parents’ knowledge, perceptions and practices on worm infection.

Methodology

We conducted a qualitative cross-sectional study in four endemic sub-counties of two counties of coastal region of Kenya. A total of 20 focus group discussions (FGDs) categorized by gender were conducted among parents of pre-school age children. Participants were purposively selected based on homogenous characteristics with the saturation model determining the number of focus group discussions conducted. The data collected was analyzed manually by study themes.

Findings

The majority of the parents had knowledge on worms and modes of transmission of the parasitic infections among the pre-school children. Also, most of the participants knew the causes of worm infection and the pre- disposing factors mentioned included poor hygiene and sanitation practices. Due to poor knowledge of signs and symptoms, misconceptions about the drugs administered during the NSBDP were common with a large majority of the parents indicating that the drugs were ineffective in worm control. The findings also indicated that most of the participants sought medical care on the onset of the signs and symptoms of worm infestation and preferred services provided at public health facilities as opposed to private health facilities or buying drugs from the local market citing mistrust of such services. Cultural beliefs, high cost of building and availability of vast pieces of land for human waste disposal were factors that contributed to low or lack of latrine ownership and usage by a large majority of the respondents.

Conclusions

Our results show that to a large extent the parents of the pre-school age children have information on worm infections. However, some cultural beliefs and practices on the pathology and mode of transmission mentioned could be a hindrance to prevention and control efforts. There is need to implement health promotion campaigns to strengthen the impact of control strategies and reduce infection.

Comparison of O-polysaccharide and hemolysin co-regulated protein as target antigens for serodiagnosis of melioidosis

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

by Apinya Pumpuang, Susanna J. Dunachie, Phornpun Phokrai, Kemajittra Jenjaroen, Kitisak Sintiprungrat, Siriphan Boonsilp, Paul J. Brett, Mary N. Burtnick, Narisara Chantratita

Background

Melioidosis is a severe disease caused by Burkholderia pseudomallei. Clinical manifestations are diverse and acute infections require immediate treatment with effective antibiotics. While culture is the current diagnostic standard, it is time-consuming and has low sensitivity. In endemic areas, inaccessibility to biosafety level 3 facilities and a lack of good serodiagnostic tools can impede diagnosis and disease surveillance. Recent studies have suggested that O-polysaccharide (OPS) and hemolysin co-regulated protein 1 (Hcp1) are promising target antigens for serodiagnosis of melioidosis.

Methodology/Principle findings

We evaluated rapid ELISAs using crude antigens, purified OPS and Hcp1 to measure antibody levels in three sets of sera: (i) 419 serum samples from melioidosis patients, Thai and U.S. healthy donors, (ii) 120 serum samples from patients with other bacterial infections, and (iii) 423 serum samples from 200 melioidosis patients obtained upon admission and at 12 and 52 weeks post-recovery. We observed significantly higher antibody levels using the crude antigen prepared from wild type B. pseudomallei K96243 compared to that of an OPS-mutant. The areas under receiver operator characteristics (AUROCCs) for diagnosis were compared for individual Hcp1-ELISA or OPS-ELISA or combined Hcp1/OPS-ELISA. For Thai donors, AUROCCs were highest and comparable between the Hcp1-ELISA and the combined Hcp1/OPS-ELISA (0.95 versus 0.94). For U.S. donors, the AUROCC was highest for the combined Hcp1/OPS-ELISA (0.96). Significantly higher seropositivity was observed in diabetic patients compared to those without diabetes for both the Hcp1-ELISA (87.3% versus 69.7%) and OPS-ELISA (88.1% versus 60.6%). Although antibody levels for Hcp1 were highest upon admission, the titers declined by week 52 post-recovery.

Conclusions/Significance

Hcp1 and OPS are promising candidates for serodiagnosis of melioidosis in different groups of patients. The Hcp1-ELISA performed better than the OPS-ELISA in endemic areas, thus, Hcp1 represents a promising target antigen for the development of POC tests for acute melioidosis.

Defining <i>Brugia malayi</i> and <i>Wolbachia</i> symbiosis by stage-specific dual RNA-seq

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

by Alexandra Grote, Denis Voronin, Tao Ding, Alan Twaddle, Thomas R. Unnasch, Sara Lustigman, Elodie Ghedin

Background

Filarial nematodes currently infect up to 54 million people worldwide, with millions more at risk for infection, representing the leading cause of disability in the developing world. Brugia malayi is one of the causative agents of lymphatic filariasis and remains the only human filarial parasite that can be maintained in small laboratory animals. Many filarial nematode species, including B. malayi, carry an obligate endosymbiont, the alpha-proteobacteria Wolbachia, which can be eliminated through antibiotic treatment. Elimination of the endosymbiont interferes with development, reproduction, and survival of the worms within the mamalian host, a clear indicator that the Wolbachia are crucial for survival of the parasite. Little is understood about the mechanism underlying this symbiosis.

Methodology/ Principle findings

To better understand the molecular interplay between these two organisms we profiled the transcriptomes of B. malayi and Wolbachia by dual RNA-seq across the life cycle of the parasite. This helped identify functional pathways involved in this essential symbiotic relationship provided by the co-expression of nematode and bacterial genes. We have identified significant stage-specific and gender-specific differential expression in Wolbachia during the nematode’s development. For example, during female worm development we find that Wolbachia upregulate genes involved in ATP production and purine biosynthesis, as well as genes involved in the oxidative stress response.

Conclusions/ Significance

This global transcriptional analysis has highlighted specific pathways to which both Wolbachia and B. malayi contribute concurrently over the life cycle of the parasite, paving the way for the development of novel intervention strategies.

AZALEP a randomized controlled trial of azathioprine to treat leprosy nerve damage and Type 1 reactions in India: Main findings

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

by Diana N. J. Lockwood, Joydeepa Darlong, Pitchaimani Govindharaj, Royce Kurian, Pamidipani Sundarrao, Annamma S. John

Background

Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R.

Methodology

Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome.

Principal findings

345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia.

Conclusions

Azathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve damage do not improve. Future studies should test giving azathioprine in the treatment of nerve damage and giving a higher dose for 48 weeks to patients. These findings highlight the difficulty in switching off leprosy inflammation and the need for better treatments for reactions and nerve damage. There is also a research need to identify patients who have recurrences and optimize treatments for them. Patients with recurrences may benefit from combined treatment with steroids and azathioprine. We have also shown that significant numbers of patients treated with steroids develop adverse effects and this needs to be highlighted in leprosy programmes. Research is needed to identify patients who do not respond to steroid treatment and develop alternative treatments for them.

Trial Registration

ClinicalTrials.gov This trial was registered with the Indian Council of Medical research clinical Trial register as a clinical trial Number—REFCTRI/2016/12/007558

Human African Trypanosomiasis in a Spanish traveler returning from Tanzania

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

by Joan Gómez-Junyent, María Jesús Pinazo, Pedro Castro, Sara Fernández, Jordi Mas, Cristian Chaguaceda, Martina Pellicé, Joaquim Gascón, José Muñoz

Acute juvenile Paracoccidioidomycosis: A 9-year cohort study in the endemic area of Rio de Janeiro, Brazil

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

by Priscila Marques de Macedo, Rodrigo Almeida-Paes, Dayvison Francis Saraiva Freitas, Andréa Gina Varon, Ariane Gomes Paixão, Anselmo Rocha Romão, Ziadir Francisco Coutinho, Claudia Vera Pizzini, Rosely Maria Zancopé-Oliveira, Antonio Carlos Francesconi do Valle

Background

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by pathogenic dimorphic fungi of the genus Paracoccidioides. It is the most important systemic mycosis in Latin America and the leading cause of hospitalizations and death among them in Brazil. Acute PCM is less frequent but relevant because vulnerable young patients are affected and the severity is usually higher than that of the chronic type.

Methods

The authors performed a retrospective cohort study from 2001 to 2009 including acute juvenile PCM patients from a reference center in Rio de Janeiro, Brazil. Clinical, epidemiological, diagnostic, therapeutic, and prognostic data were reported.

Results

Twenty-nine patients were included. The average age was 23 years old and the male to female ratio was 1:1.07. All cases were referred from 3 of 9 existing health areas in the state of Rio de Janeiro, predominantly from urban areas (96.5%). Lymph nodes were the most affected organs (100%), followed by the skin and the spleen (31% each). Twenty-eight patients completed treatment (median 25 months) and progressed to clinical and serological cure; 1 death occurred. Twenty-four patients completed 48-month median follow-up. Four patients abandoned follow-up after the end of treatment. The most frequent sequela was low adrenal reserve. Paracoccidioides brasiliensis S1 was identified by partial sequencing of the arf and gp43 genes from 4 patients who presented a viable fungal culture.

Conclusion

Acute juvenile PCM is a severe disease with a high rate of complications. There are few cohort clinical studies of acute PCM in the literature. More studies should be developed to promote improvement in patients’ healthcare.

Pre-control relationship of onchocercal skin disease with onchocercal infection in Guinea Savanna, Northern Nigeria

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

by Michele E. Murdoch, Ian E. Murdoch, Jennifer Evans, Haliru Yahaya, Ngozi Njepuome, Simon Cousens, Barrie R. Jones, Adenike Abiose

Background

Onchocerca volvulus infection can result in blindness, itching and skin lesions. Previous research concentrated on blindness.

Methods

A clinical classification system of the cutaneous changes in onchocerciasis was used for the first time in this study within the context of an early ivermectin drug trial in the savanna region of Kaduna State, northern Nigeria. Skin examinations were performed in 6,790 individuals aged 5+ years in endemic communities and 1,343 individuals in nonendemic communities.

Results / Discussion

There was increased risk for all forms of onchocercal skin disease in endemic communities with the most common finding being the presence of nodules (1,438 individuals, 21.2%), followed by atrophy (367, 6.1% of those < 50 years), acute papular onchodermatitis, APOD (233, 3.4%), depigmentation (216, 3.2%) and chronic papular onchodermatitis, CPOD (155, 2.3%). A further 645 individuals (9.5%) complained of pruritus but had completely normal skin. APOD was more common in males whereas atrophy, hanging groin and nodules were more common in females. After controlling for age and sex, microfilarial positivity was a risk factor for CPOD, depigmentation, hanging groin and nodules (OR 1.54, p = 0.046; OR 2.29, p = 0.002; OR 2.18, p = 0.002 and OR 3.80, p <0.01 respectively). Comparable results were found using presence of nodules as the marker for infection. Microfilarial load showed similar, though weaker, results. A total of 2621(38.6%) endemic residents had itching with normal skin, or had one or more types of onchocercal skin disease including nodules, which may be considered as a composite index of the overall prevalence of onchocercal skin disease.

Conclusion

Significant levels of onchocercal skin disease were documented in this savanna area, which subsequently resulted in a reassessment of the true burden of skin disease in onchocerciasis. This paper represents the first detailed report of the association of onchocercal skin disease with markers for onchocercal infection.

sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis

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

by Ricardo Luís Louzada Silva, Marcio B. Santos, Priscila L. S. Almeida, Thayse S. Barros, Lucas Magalhães, Rodrigo A. Cazzaniga, Patrícia R. M. Souza, Nívea F. Luz, Jaqueline França-Costa, Valeria M. Borges, Djalma S. Lima-Junior, Michael W. Lipscomb, Malcolm S. Duthie, Steven G. Reed, Roque Pacheco Almeida, Amélia Ribeiro Jesus

Background

CD163, receptor for the haptoglobin–hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163) has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.e. lepromatous leprosy (LL)), as well as tuberculosis. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens.

Methodology/Principal findings

To assess this hypothesis, sCD163 levels were measured in the serum of leprosy and visceral leishmaniasis (VL) patients stratified by severity of the clinical presentation. sCD163 levels were significantly higher in patients with these diseases than those observed in healthy control individuals. Further analyses on infection and disease status of leprosy and VL patients revealed a clear association of sCD163 levels with clinical parameters of disease severity. In vitro culture assays revealed that Leishmania infection induced CD163 expression on the surface of both monocyte/macrophages and neutrophils, suggesting these cells as possible sources of sCD163. FACS analyses shows that the cells expressing CD163 produces both TNF-α and IL-4.

Conclusions/Significance

Taken together, our results reveal sCD163 as a potential biomarker of severity of diseases caused by intracellular pathogens M. leprae and Leishmania spp. and have a modulatory role, with a mix of an inflammatory property induced by TNF-α release, but that potentially induces an anti-inflammatory T cell response, related to IL-4 release.

An integrated overview of the midgut bacterial flora composition of <i>Phlebotomus perniciosus</i>, a vector of zoonotic visceral leishmaniasis in the Western Mediterranean Basin

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

by Wael Fraihi, Wasfi Fares, Pascale Perrin, Franck Dorkeld, Denis Sereno, Walid Barhoumi, Imed Sbissi, Saifedine Cherni, Ifhem Chelbi, Ravi Durvasula, Marcelo Ramalho-Ortigao, Maher Gtari, Elyes Zhioua

Background

The Leishmania developmental life cycle within its sand fly vector occurs exclusively in the lumen of the insect’s digestive tract in the presence of symbiotic bacteria. The composition of the gut microbiota and the factors that influence its composition are currently poorly understood. A set of factors, including the host and its environment, may influence this composition. It has been demonstrated that the insect gut microbiota influences the development of several human pathogens, such as Plasmodium falciparum. For sand flies and Leishmania, understanding the interactions between the parasite and the microbial environment of the vector midgut can provide new tools to control Leishmania transmission.

Methodology/Principal findings

The midguts of female Phlebotomus perniciosus from laboratory colonies or from the field were collected during the months of July, September and October 2011 and dissected. The midguts were analyzed by culture-dependent and culture-independent methods. A total of 441 and 115 cultivable isolates were assigned to 30 and 11 phylotypes from field-collected and colonized P. perniciosus, respectively. Analysis of monthly variations in microbiota composition shows a species diversity decline in October, which is to the end of the Leishmania infantum transmission period. In parallel, a compilation and a meta-analysis of all available data concerning the microbiota of two Psychodidae genera, namely Phlebotomus and Lutzomyia, was performed and compared to P. perniciosus, data obtained herein. This integrated analysis did not reveal any substantial divergences between Old and New world sand flies with regards to the midgut bacterial phyla and genera diversity. But clearly, most bacterial species (>76%) are sparsely distributed between Phlebotominae species.

Conclusion/Significance

Our results pinpoint the need for a more exhaustive understanding of the bacterial richness and abundance at the species level in Phlebotominae sand flies in order to capture the role of midgut bacteria during Leishmania development and transmission. The occurrence of Bacillus subtilis in P. perniciosus and at least two other sand fly species studied so far suggests that this bacterial species is a potential candidate for paratransgenic or biolological approaches for the control of sand fly populations in order to prevent Leishmania transmission.

Modulation of the immune response by <i>Fonsecaea pedrosoi</i> morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity

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

by Isaque Medeiros Siqueira, Raffael Júnio Araújo de Castro, Luiza Chaves de Miranda Leonhardt, Márcio Sousa Jerônimo, Aluízio Carlos Soares, Tainá Raiol, Christiane Nishibe, Nalvo Almeida, Aldo Henrique Tavares, Christian Hoffmann, Anamelia Lorenzetti Bocca

A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM), a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this study we show that hyphae and muriform cells are able to establish a murine CBM with skin lesions and histopathological aspects similar to that found in humans, with muriform cells being the most persistent fungal form, whereas mice infected with conidia do not reach the chronic phase of the disease. Moreover, in injured tissue the presence of hyphae and especially muriform cells, but not conidia, is correlated with intense production of pro-inflammatory cytokines in vivo. High-throughput RNA sequencing analysis (RNA-Seq) performed at early time points showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to muriform cells, but not conidia. We also demonstrate that only muriform cells required FcγR and Dectin-1 recognition to be internalized in vitro, and this is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Furthermore, our findings reveal two different fungal-host interaction strategies according to fungal morphotype, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections.

Protective immune responses against <i>Schistosoma mansoni</i> infection by immunization with functionally active gut-derived cysteine peptidases alone and in combination with glyceraldehyde 3-phosphate dehydrogenase

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

by Hatem Tallima, Jan Dvořák, Sahira Kareem, Marwa Abou El Dahab, Nada Abdel Aziz, John Pius Dalton, Rashika El Ridi

Background

Schistosomiasis, a severe disease caused by parasites of the genus Schistosoma, is prevalent in 74 countries, affecting more than 250 million people, particularly children. We have previously shown that the Schistosoma mansoni gut-derived cysteine peptidase, cathepsin B1 (SmCB1), administered without adjuvant, elicits protection (>60%) against challenge infection of S. mansoni or S. haematobium in outbred, CD-1 mice. Here we compare the immunogenicity and protective potential of another gut-derived cysteine peptidase, S. mansoni cathepsin L3 (SmCL3), alone, and in combination with SmCB1. We also examined whether protective responses could be boosted by including a third non-peptidase schistosome secreted molecule, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH), with the two peptidases.

Methodology/Principal findings

While adjuvant-free SmCB1 and SmCL3 induced type 2 polarized responses in CD-1 outbred mice those elicited by SmCL3 were far weaker than those induced by SmCB1. Nevertheless, both cysteine peptidases evoked highly significant (P < 0.005) reduction in challenge worm burden (54–65%) as well as worm egg counts and viability. A combination of SmCL3 and SmCB1 did not induce significantly stronger immune responses or higher protection than that achieved using each peptidase alone. However, when the two peptidases were combined with SG3PDH the levels of protection against challenge S. mansoni infection reached 70–76% and were accompanied by highly significant (P < 0.005) decreases in worm egg counts and viability. Similarly, high levels of protection were achieved in hamsters immunized with the cysteine peptidase/SG3PDH-based vaccine.

Conclusions/Significance

Gut-derived cysteine peptidases are highly protective against schistosome challenge infection when administered subcutaneously without adjuvant to outbred CD-1 mice and hamsters, and can also act to enhance the efficacy of other schistosome antigens, such as SG3PDH. This cysteine peptidase-based vaccine should now be advanced to experiments in non-human primates and, if shown promise, progressed to Phase 1 safety trials in humans.

Water, Sanitation and Hygiene (WASH) and environmental risk factors for soil-transmitted helminth intensity of infection in Timor-Leste, using real time PCR

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

by Suzy J. Campbell, Susana V. Nery, Rebecca Wardell, Catherine A. D’Este, Darren J. Gray, James S. McCarthy, Rebecca J. Traub, Ross M. Andrews, Stacey Llewellyn, Andrew J. Vallely, Gail M. Williams, Archie C. A. Clements

Background

No investigations have been undertaken of risk factors for intensity of soil-transmitted helminth (STH) infection in Timor-Leste. This study provides the first analysis of risk factors for intensity of STH infection, as determined by quantitative PCR (qPCR), examining a broad range of water, sanitation and hygiene (WASH) and environmental factors, among communities in Manufahi District, Timor-Leste.

Methods

A baseline cross-sectional survey of 18 communities was undertaken as part of a cluster randomised controlled trial, with additional identically-collected data from six other communities. qPCR was used to assess STH infection from stool samples, and questionnaires administered to collect WASH, demographic, and socioeconomic data. Environmental information was obtained from open-access sources and linked to infection outcomes. Mixed-effects multinomial logistic regression was undertaken to assess risk factors for intensity of Necator americanus and Ascaris infection.

Results

2152 participants provided stool and questionnaire information for this analysis. In adjusted models incorporating WASH, demographic and environmental variables, environmental variables were generally associated with infection intensity for both N. americanus and Ascaris spp. Precipitation (in centimetres) was associated with increased risk of moderate-intensity (adjusted relative risk [ARR] 6.1; 95% confidence interval [CI] 1.9–19.3) and heavy-intensity (ARR 6.6; 95% CI 3.1–14.1) N. americanus infection, as was sandy-loam soil around households (moderate-intensity ARR 2.1; 95% CI 1.0–4.3; heavy-intensity ARR 2.7; 95% CI 1.6–4.5; compared to no infection). For Ascaris, alkaline soil around the household was associated with reduced risk of moderate-intensity infection (ARR 0.21; 95% CI 0.09–0.51), and heavy-intensity infection (ARR 0.04; 95% CI 0.01–0.25). Few WASH risk factors were significant.

Conclusion

In this high-prevalence setting, strong risk associations with environmental factors indicate that anthelmintic treatment alone will be insufficient to interrupt STH transmission, as conditions are favourable for ongoing environmental transmission. Integrated STH control strategies should be explored as a priority.

Rapid Surveillance for Vector Presence (RSVP): Development of a novel system for detecting <i>Aedes aegypti</i> and <i>Aedes albopictus</i>

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

by Brian L. Montgomery, Martin A. Shivas, Sonja Hall-Mendelin, Jim Edwards, Nicholas A. Hamilton, Cassie C. Jansen, Jamie L. McMahon, David Warrilow, Andrew F. van den Hurk

Background

The globally important Zika, dengue and chikungunya viruses are primarily transmitted by the invasive mosquitoes, Aedes aegypti and Aedes albopictus. In Australia, there is an increasing risk that these species may invade highly urbanized regions and trigger outbreaks. We describe the development of a Rapid Surveillance for Vector Presence (RSVP) system to expedite presence- absence surveys for both species.

Methodology/Principal findings

We developed a methodology that uses molecular assays to efficiently screen pooled ovitrap (egg trap) samples for traces of target species ribosomal RNA. Firstly, specific real-time reverse transcription-polymerase chain reaction (RT-PCR) assays were developed which detect a single Ae. aegypti or Ae. albopictus first instar larva in samples containing 4,999 and 999 non-target mosquitoes, respectively. ImageJ software was evaluated as an automated egg counting tool using ovitrap collections obtained from Brisbane, Australia. Qualitative assessment of ovistrips was required prior to automation because ImageJ did not differentiate between Aedes eggs and other objects or contaminants on 44.5% of ovistrips assessed, thus compromising the accuracy of egg counts. As a proof of concept, the RSVP was evaluated in Brisbane, Rockhampton and Goomeri, locations where Ae. aegypti is considered absent, present, and at the margin of its range, respectively. In Brisbane, Ae. aegypti was not detected in 25 pools formed from 477 ovitraps, comprising ≈ 54,300 eggs. In Rockhampton, Ae. aegypti was detected in 4/6 pools derived from 45 ovitraps, comprising ≈ 1,700 eggs. In Goomeri, Ae. aegypti was detected in 5/8 pools derived from 62 ovitraps, comprising ≈ 4,200 eggs.

Conclusions/Significance

RSVP can rapidly detect nucleic acids from low numbers of target species within large samples of endemic species aggregated from multiple ovitraps. This screening capability facilitates deployment of ovitrap configurations of varying spatial scales, from a single residential block to entire suburbs or towns. RSVP is a powerful tool for surveillance of invasive Aedes spp., validation of species eradication and quality assurance for vector control operations implemented during disease outbreaks.

Vector status of <i>Aedes</i> species determines geographical risk of autochthonous Zika virus establishment

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

by Lauren Gardner, Nan Chen, Sahotra Sarkar

Background

The 2015-16 Zika virus pandemic originating in Latin America led to predictions of a catastrophic global spread of the disease. Since the current outbreak began in Brazil in May 2015 local transmission of Zika has been reported in over 60 countries and territories, with over 750 thousand confirmed and suspected cases. As a result of its range expansion attention has focused on possible modes of transmission, of which the arthropod vector-based disease spread cycle involving Aedes species is believed to be the most important. Additional causes of concern are the emerging new links between Zika disease and Guillain-Barre Syndrome (GBS), and a once rare congenital disease, microcephaly.

Methodology/principal findings

Like dengue and chikungunya, the geographic establishment of Zika is thought to be limited by the occurrence of its principal vector mosquito species, Ae. aegypti and, possibly, Ae. albopictus. While Ae. albopictus populations are more widely established than those of Ae. aegypti, the relative competence of these species as a Zika vector is unknown. The analysis reported here presents a global risk model that considers the role of each vector species independently, and quantifies the potential spreading risk of Zika into new regions. Six scenarios are evaluated which vary in the weight assigned to Ae. albopictus as a possible spreading vector. The scenarios are bounded by the extreme assumptions that spread is driven by air travel and Ae. aegypti presence alone and spread driven equally by both species. For each scenario destination cities at highest risk of Zika outbreaks are prioritized, as are source cities in affected regions. Finally, intercontinental air travel routes that pose the highest risk for Zika spread are also ranked. The results are compared between scenarios.

Conclusions/significance

Results from the analysis reveal that if Ae. aegypti is the only competent Zika vector, then risk is geographically limited; in North America mainly to Florida and Texas. However, if Ae. albopictus proves to be a competent vector of Zika, which does not yet appear to be the case, then there is risk of local establishment in all American regions including Canada and Chile, much of Western Europe, Australia, New Zealand, as well as South and East Asia, with a substantial increase in risk to Asia due to the more recent local establishment of Zika in Singapore.

Dengue seroprevalence, seroconversion and risk factors in Dhaka, Bangladesh

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

by Parnali Dhar-Chowdhury, Kishor Kumar Paul, C. Emdad Haque, Shakhawat Hossain, L. Robbin Lindsay, Antonia Dibernardo, W. Abdullah Brooks, Michael A. Drebot

Background

Dengue virus (DENV) activity has been reported in Dhaka, Bangladesh since the early 1960s with the greatest burden of dengue fever and dengue hemorrhagic fever cases observed in 2000. Since this time, the intensity of dengue activity has varied from year to year, and its determining factors remained relatively unknown. In light of such gaps in knowledge, the main objectives of this study were to determine the magnitude of seroprevalence and seroconversion among the surveyed population, and establish the individual/household level risk factors for the presence of DENV antibodies among all age groups of target populations in the city of Dhaka.

Methodology/Principal findings

Considering the lack of fine scale investigations on the factors driving dengue activity in Bangladesh, a prospective cohort study involving serological surveys was undertaken with participant interviews and blood donation across the city of Dhaka in 2012. Study participants were recruited from 12 of 90 wards and blood samples were collected during both the pre-monsoon (n = 1125) and post-monsoon (n = 600) seasons of 2012. The findings revealed that the seroprevalence in all pre-monsoon samples was 80.0% (900/1125) while the seropositivity in the pre-monsoon samples that had paired post-monsoon samples was 83.3% (503/600). Of the 97 paired samples that were negative at the pre-monsoon time point, 56 were positive at the post-monsoon time point. This resulted in a seroprevalence of 93.2% (559/600) among individuals tested during the post-monsoon period. Seroprevalence trended higher with age with children exhibiting a lower seropositivity as compared to adults. Results from this study also indicated that DENV strains were the only flaviviruses circulating in Dhaka in 2012. A multivariate analysis revealed that age, possession of indoor potted plants, and types of mosquito control measures were significant factors associated with dengue seroprevalence; while attendance in public/mass gatherings, and use of mosquito control measures were significantly associated with DENV seroconversion after adjusting for all other variables.

Conclusions/Significance

Our study suggests that there is a high level of endemic dengue virus circulation in the city of Dhaka which has resulted in significant DENV seroprevalence among its residents. Seropositivity increased with age, however, a substantial proportion of children are at risk for DENV infections. Our serological analysis also documents considerable DENV seroconversions among study participants which indicates that a large proportion of the population in the city of Dhaka were newly exposed to DENV during the study period (pre-and post-monsoon 2012). High levels of seroconversion suggest that there was an intense circulation of DENV in 2012 and this may have resulted in a significant risk for viral associated illness. Findings of our study further indicated that home-based interventions, such as removing indoor potted plants and increased bed net use, in addition to vector control measures in public parks, would reduce exposure to DENV and further decrease risk of viral associated disease.

Interdisciplinary approach at the primary healthcare level for Bolivian immigrants with Chagas disease in the city of São Paulo

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

by Maria Aparecida Shikanai Yasuda, Camila Gonçalves Sátolo, Noemia Barbosa Carvalho, Magda Maya Atala, Rosario Quiroga Ferrufino, Ruth Moreira Leite, Célia Regina Furucho, Expedito Luna, Rubens Antonio Silva, Marcia Hage, Caroline Medeji Ramos de Oliveira, Felipe Delatorre Busser, Vera Lucia Teixeira de Freitas, Dalva Marli Valerio Wanderley, Luzia Martinelli, Sonia Regina Almeida, Pedro Albajar Viñas, Nivaldo Carneiro Jr.

Background/Methods

In a pioneering cross-sectional study among Bolivian immigrants in the city of São Paulo, Brazil, the epidemiological profile, clinical manifestations and morbidity of Chagas disease were described. The feasibility of the management of Chagas disease at primary healthcare clinics using a biomedical and psychosocial interdisciplinary approach was also tested. Previously, a Trypanosoma cruzi (T. cruzi) infection rate of 4.4% among 633 immigrants was reported. The samples were screened using two commercial enzyme-linked immunoassay (ELISA) tests generated with epimastigote antigens, and those with discrepant or seropositive results were analyzed by confirmatory tests: indirect immunofluorescence (IFI), TESA-blot and a commercial recombinant ELISA. PCR and blood cultures were performed in seropositive patients.

Results

The majority of the 28 seropositive patients were women, of whom 88.89% were of child-bearing age. The predominant clinical forms of Chagas disease were the indeterminate and atypical cardiac forms. Less than 50% received the recommended antiparasitic treatment of benznidazole. An interdisciplinary team was centered on primary healthcare physicians who applied guidelines for the management of patients. Infectologists, cardiologists, pediatricians and other specialists acted as reference professionals. Confirmatory serology and molecular biology tests, as well as echocardiography, Holter and other tests, were performed for the assessment of affected organs in secondary healthcare centers. The published high performance of two commercial ELISA tests was not confirmed.

Conclusion

An interdisciplinary approach including antiparasitic treatment is feasible at the primary healthcare level for the management of Chagas disease in Bolivian immigrants. The itinerant feature of immigration was associated with a lack of adherence to antiparasitic treatment and was considered a main challenge for the clinical management of this population. This approach is recommended for management of the infected population in endemic and nonendemic areas, although different strategies are needed depending on the severity of the disease and the structure of the healthcare system.

Pages