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Social determinants, their relationship with leprosy risk and temporal trends in a tri-border region in Latin America

PLoS Neglected Tropical Diseases News - 6 April 2018 - 9:00pm

by Ivaneliza Simionato de Assis, Marcos Augusto Moraes Arcoverde, Antônio Carlos Viera Ramos, Luana Seles Alves, Thais Zamboni Berra, Luiz Henrique Arroyo, Ana Angélica Rêgo de Queiroz, Danielle Talita dos Santos, Aylana de Souza Belchior, Josilene Dália Alves, Flávia Meneguetti Pieri, Reinaldo Antônio Silva-Sobrinho, Ione Carvalho Pinto, Clodis Maria Tavares, Mellina Yamamura, Marco Andrey Cipriani Frade, Pedro Fredemir Palha, Francisco Chiaravalloti-Neto, Ricardo Alexandre Arcêncio

Background

Brazil is the only country in Latin America that has adopted a national health system. This causes differences in access to health among Latin American countries and induces noticeable migration to Brazilian regions to seek healthcare. This phenomenon has led to difficulties in the control and elimination of diseases related to poverty, such as leprosy. The aim of this study was to evaluate social determinants and their relationship with the risk of leprosy, as well as to examine the temporal trend of its occurrence in a Brazilian municipality located on the tri-border area between Brazil, Paraguay and Argentina.

Methods

This ecological study investigated newly-diagnosed cases of leprosy between 2003 and 2015. Exploratory analysis of the data was performed through descriptive statistics. For spatial analysis, geocoding of the data was performed using spatial scan statistic techniques to obtain the Relative Risk (RR) for each census tract, with their respective 95% confidence intervals calculated. The Bivariate Moran I test, Ordinary Least Squares (OLS) and Geographically Weighted Regression (GWR) models were applied to analyze the spatial relationships of social determinants and leprosy risk. The temporal trend of the annual coefficient of new cases was obtained through the Prais-Winsten regression. A standard error of 5% was considered statistically significant (p < 0.05).

Results

Of the 840 new cases identified in the study, there was a predominance of females (n = 427, 50.8%), of white race/color (n = 685, 81.6%), age range 15 to 59 years (n = 624, 74.3%), and incomplete elementary education (n = 504, 60.0%). The results obtained from multivariate analysis revealed that the proportion of households with monthly nominal household income per capita greater than 1 minimum wage (β = 0.025, p = 0.036) and people of brown race (β = -0.101, p = 0.024) were statistically-significantly associated with risk of illness due to leprosy. These results also confirmed that social determinants and risk of leprosy were significantly spatially non-stationary. Regarding the temporal trend, a decrease of 4% (95% CI [-0.053, -0.033], p = 0.000) per year was observed in the rate of detection of new cases of leprosy.

Conclusion

The social determinants income and race/color were associated with the risk of leprosy. The study’s highlighting of these social determinants can contribute to the development of public policies directed toward the elimination of leprosy in the border region.

Efficacy of <i>Aedes aegypti</i> control by indoor Ultra Low Volume (ULV) insecticide spraying in Iquitos, Peru

PLoS Neglected Tropical Diseases News - 6 April 2018 - 9:00pm

by Christian E. Gunning, Kenichi Okamoto, Helvio Astete, Gissella M. Vasquez, Erik Erhardt, Clara Del Aguila, Raul Pinedo, Roldan Cardenas, Carlos Pacheco, Enrique Chalco, Hugo Rodriguez-Ferruci, Thomas W. Scott, Alun L. Lloyd, Fred Gould, Amy C. Morrison

Background

Aedes aegypti is a primary vector of dengue, chikungunya, Zika, and urban yellow fever viruses. Indoor, ultra low volume (ULV) space spraying with pyrethroid insecticides is the main approach used for Ae. aegypti emergency control in many countries. Given the widespread use of this method, the lack of large-scale experiments or detailed evaluations of municipal spray programs is problematic.

Methodology/Principal findings

Two experimental evaluations of non-residual, indoor ULV pyrethroid spraying were conducted in Iquitos, Peru. In each, a central sprayed sector was surrounded by an unsprayed buffer sector. In 2013, spray and buffer sectors included 398 and 765 houses, respectively. Spraying reduced the mean number of adults captured per house by ~83 percent relative to the pre-spray baseline survey. In the 2014 experiment, sprayed and buffer sectors included 1,117 and 1,049 houses, respectively. Here, the sprayed sector’s number of adults per house was reduced ~64 percent relative to baseline. Parity surveys in the sprayed sector during the 2014 spray period indicated an increase in the proportion of very young females. We also evaluated impacts of a 2014 citywide spray program by the local Ministry of Health, which reduced adult populations by ~60 percent. In all cases, adult densities returned to near-baseline levels within one month.

Conclusions/Significance

Our results demonstrate that densities of adult Ae. aegypti can be reduced by experimental and municipal spraying programs. The finding that adult densities return to approximately pre-spray densities in less than a month is similar to results from previous, smaller scale experiments. Our results demonstrate that ULV spraying is best viewed as having a short-term entomological effect. The epidemiological impact of ULV spraying will need evaluation in future trials that measure capacity of insecticide spraying to reduce human infection or disease.

Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers

PLoS Neglected Tropical Diseases News - 6 April 2018 - 9:00pm

by Kamrul Islam, Motaher Hossain, Meagan Kelly, Leslie M. Mayo Smith, Richelle C. Charles, Taufiqur Rahman Bhuiyan, Pavol Kováč, Peng Xu, Regina C. LaRocque, Stephen B. Calderwood, Jakub K. Simon, Wilbur H. Chen, Douglas Haney, Michael Lock, Caroline E. Lyon, Beth D. Kirkpatrick, Mitchell Cohen, Myron M. Levine, Marc Gurwith, Jason B. Harris, Firdausi Qadri, Edward T. Ryan

Background

Cholera is an acute voluminous dehydrating diarrheal disease caused by toxigenic strains of Vibrio cholerae O1 and occasionally O139. A growing body of evidence indicates that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae are involved in mediating protection against cholera. We therefore assessed whether antibody responses against OSP occur after vaccination with live attenuated oral cholera vaccine CVD 103-HgR, and whether such responses correlate with protection against cholera.

Methodology

We assessed adult North American volunteers (n = 46) who were vaccinated with 5 × 108 colony-forming units (CFU) of oral cholera vaccine CVD 103-HgR and then orally challenged with approximately 1 × 105 CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961, either 10 or 90 days post-vaccination.

Principal findings

Vaccination was associated with induction of significant serum IgM and IgA anti-OSP and vibriocidal antibody responses within 10 days of vaccination. There was significant correlation between anti-OSP and vibriocidal antibody responses. IgM and IgA anti-OSP responses on day 10 following vaccination were associated with lower post-challenge stool volume (r = −0.44, P = 0.002; r = −0.36, P = 0.01; respectively), and none of 27 vaccinees who developed a ≥1.5 fold increase in any antibody isotype targeting OSP on day 10 following vaccination compared to baseline developed moderate or severe cholera following experimental challenge, while 5 of 19 who did not develop such anti-OSP responses did (P = 0.01).

Conclusion

Oral vaccination with live attenuated cholera vaccine CVD 103-HgR induces antibodies that target V. cholerae OSP, and these anti-OSP responses correlate with protection against diarrhea following experimental challenge with V. cholerae O1.

Trial registration

ClinicalTrials.gov NCT01895855

Hidden danger: Unexpected scenario in the vector-parasite dynamics of leishmaniases in the Brazil side of triple border (Argentina, Brazil and Paraguay)

PLoS Neglected Tropical Diseases News - 6 April 2018 - 9:00pm

by Vanete Thomaz-Soccol, André Luiz Gonçalves, Claudio Adriano Piechnik, Rafael Antunes Baggio, Walter Antônio Boeger, Themis Leão Buchman, Mario Sergio Michaliszyn, Demilson Rodrigues dos Santos, Adão Celestino, José Aquino Jr, André de Souza Leandro, Otacílio Lopes de Souza da Paz, Marcelo Limont, Alceu Bisetto Jr, Jeffrey Jon Shaw, Zaida Estela Yadon, Oscar Daniel Salomon

Every year about 3 million tourists from around the world visit Brazil, Argentina and Paraguay´s triple border region where the Iguaçu Falls are located. Unfortunately, in recent years an increasing number of autochthonous canine and human visceral leishmaniosis (VL) cases have been reported. The parasite is Leishmania (Leishmania) infantum and it is transmitted by sand flies (Phlebotominae). To assess the risk factors favorable for the establishment and spread of potential vectors the Centers for Disease Control and Prevention light trap (CDC-light trap) collections were made in the Foz do Iguaçu (FI) and Santa Terezinha de Itaipu (STI) townships and along two transects between them. Our study determined the Phlebotominae fauna, the factors that affect the presence and abundance of Lutzomyia longipalpis and Nyssomyia whitmani, the presence of L. (L.) infantum in different sand fly species and which Leishmania species are present in this region. Lutzomyia longipalpis was the prevalent species and its distribution was related to the abundance of dogs. Leishmania (L.) infantum was found in Lu. longipalpis, Ny. whitmani, Ny. neivai and a Lutzomyia sp. All the results are discussed within the Stockholm Paradigm and focus on their importance in the elaboration of public health policies in international border areas. This region has all the properties of stable VL endemic foci that can serve as a source of the disease for neighboring municipalities, states and countries. Most of the urban areas of tropical America are propitious for Lu. longipalpis establishment and have large dog populations. Pan American Health Organization´s initiative in supporting the public health policies in the border areas of this study is crucial and laudable. However, if stakeholders do not act quickly in controlling VL in this region, the scenario will inevitable become worse. Moreover, L. (Viannia) braziliensis found in this study supports the need to develop public health policies to avoid the spread of cutaneous leishmaniasis. The consequences of socioeconomic attributes, boundaries and frontiers on the spread of diseases cannot be neglected. For an efficient control, it is essential that urban planning is articulated with the neighboring cities.

The impact of passive case detection on the transmission dynamics of gambiense Human African Trypanosomiasis

PLoS Neglected Tropical Diseases News - 6 April 2018 - 9:00pm

by Francesco Checchi, Sebastian Funk, Daniel Chandramohan, François Chappuis, Daniel T. Haydon

Gambiense Human African Trypanosomiasis (HAT), or sleeping sickness, is a vector-borne disease affecting largely rural populations in Western and Central Africa. The main method for detecting and treating cases of gambiense HAT are active screening through mobile teams and passive detection through self-referral of patients to dedicated treatment centres or hospitals. Strategies based on active case finding and treatment have drastically reduced the global incidence of the disease over recent decades. However, little is known about the coverage and transmission impact of passive case detection. We used a mathematical model to analyse data from the period between active screening sessions in hundreds of villages that were monitored as part of three HAT control projects run by Médecins Sans Frontières in Southern Sudan and Uganda in the late 1990s and early 2000s. We found heterogeneity in incidence across villages, with a small minority of villages found to have much higher transmission rates and burdens than the majority. We further found that only a minority of prevalent cases in the first, haemo-lymphatic stage of the disease were detected passively (maximum likelihood estimate <30% in all three settings), whereas around 50% of patients in the second, meningo-encephalitic were detected. We estimated that passive case detection reduced transmission in affected areas by between 30 and 50%, suggesting that there is great potential value in improving rates of passive case detection. As gambiense HAT is driven towards elimination, it will be important to establish good systems of passive screening, and estimates such as the ones here will be of value in assessing the expected impact of moving from a primarily active to a more passive screening regime.

Clinical Cysticercosis epidemiology in Spain based on the hospital discharge database: What's new?

PLoS Neglected Tropical Diseases News - 5 April 2018 - 9:00pm

by Zaida Herrador, Amalia Fernandez-Martinez, Agustín Benito, Rogelio Lopez-Velez

Background

Cysticercosis (CC) is a tissue infection caused by the larval cysts of the pork tapeworm Taenia solium. It is usually acquired by eating contaminated food or drinking water. CC Cysts can develop in the muscles, the eyes, the brain, and/or the spinal cord. T. solium is found worldwide, but its prevalence has decreased in developed countries due to stricter meat inspection and better hygiene and sanitation. Nevertheless, CC is still a leading cause of seizures and epilepsy. In Spain, The disease is not nationally reportable and data on CC infected animals are also missing, despite the European Directive 2003/99/EC.

Methodology/Principal findings

We performed a retrospective descriptive study using the Spanish Hospitalization Minimum Data Set (CMBD). Data with ICD-9 CM cysticercosis code (“123.1”) placed in first or second diagnostic position from 1997 to 2014 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed. A total of 1,912 hospital discharges with clinical cysticercosis were identified. From 1998 to 2008, an increasing trend in the number of CC hospitalizations was observed, decreasing afterwards, in parallel with a decrease in the external migration rate. The Murcia region had the highest median hospitalization rate (13.37 hospitalizations/100,000 population), followed by Navarra and Madrid. The 16–44 age group was the most represented (63.6%). The three most frequent associated diagnoses were epilepsy and convulsions (49.5%), hydrocephalus (11.8%) and encephalitis/myelitis/meningitis (11.6%).

Conclusions/Significance

There is a need for a common strategy on data collection, monitoring and reporting, which would facilitate a more accurate picture on the CC epidemiological scenario. Even if most cases might be imported, improving the human and animal CC surveillance will result useful both in gaining extended disease knowledge and reducing morbidity and related-costs.

A real-time PCR tool for the surveillance of zoonotic <i>Onchocerca lupi</i> in dogs, cats and potential vectors

PLoS Neglected Tropical Diseases News - 4 April 2018 - 9:00pm

by Maria Stefania Latrofa, Giada Annoscia, Vito Colella, Maria Alfonsa Cavalera, Carla Maia, Coralie Martin, Jan Šlapeta, Domenico Otranto

The ocular onchocercosis is caused is by the zoonotic parasite Onchocerca lupi (Spirurida: Onchocercidae). A major hindrance to scientific progress is the absence of a reliable diagnostic test in affected individuals. Microscopic examination of skin snip sediments and the identification of adults embedded in ocular nodules are seldom performed and labour-intensive. A quantitative real-time PCR (qPCR) assay was herein standardized for the detection of O. lupi DNA and the results compared with microscopic examination and conventional PCR (cPCR). The specificity of qPCR and cPCR was assessed by processing the most common filarial nematodes infecting dogs, skin samples from O. lupi infected (n = 35 dogs) or uninfected animals (n = 21 dogs; n = 152 cats) and specimens of potential insect vector (n = 93 blackflies; n = 59 mosquitoes/midges). The analytical sensitivity of both assays was assessed using 10-fold serial dilutions of DNA from adult specimen and from a pool of microfilariae. The qPCR on skin samples revealed an analytical specificity of 100% and a sensitivity up to 8 x 10−1 fg/2μl O. lupi adult-DNA and up to 3.6 x 10−1 pg/2μl of mfs-DNA (corresponding to 1 x 10−2 mfs/2μl). Only 9.5% O. lupi-infected skin samples were positive for cPCR with a sensitivity of 8 x 10−1 pg/2μl of DNA. Out of 152 blackflies and mosquitoes/midges, eight specimens experimentally infected (n = 1 S. erythrocephalum; n = 1 S. ornatum; n = 6 Simulium sp.) were positive by qPCR. The qPCR assay herein standardized represents an important step forward in the diagnosis of zoonotic onchocercosis caused by O. lupi, especially for the detection and quantification of low number of mfs. This assay provides a fundamental contribution for the establishment of surveillance strategies aiming at assessing the presence of O. lupi in carnivores and in insect species acting as potential intermediate hosts. The O. lupi qPCR assay will enable disease progress monitoring as well as the diagnosis of apparently clinical healthy dogs and cats.

Refractoriness of <i>Sergentomyia schwetzi</i> to <i>Leishmania</i> spp is mediated by the peritrophic matrix

PLoS Neglected Tropical Diseases News - 4 April 2018 - 9:00pm

by Jovana Sadlova, Miroslav Homola, Jitka Myskova, Magda Jancarova, Petr Volf

Background

The peritrophic matrix (PM) is an acellular chitin-containing envelope which in most blood sucking insects encloses the ingested blood meal and protects the midgut epithelium. Type I PM present in sand flies and other blood sucking batch feeders is secreted around the meal by the entire midgut in response to feeding. Here we tested the hypothesis that in Sergentomyia schwetzi the PM creates a physical barrier that prevents escape of Leishmania parasites from the endoperitrophic space.

Methodology/Principal findings

Morphology and ultrastructure of the PM as well the production of endogenous chitinase in S. schwetzi were compared with three sand fly species, which are natural vectors of Leishmania. Long persistence of the PM in S. schwetzi was not accompanied by different morphology or decreased production of chitinase. To confirm the role of the PM in refractoriness of S. schwetzi to Leishmania parasites, culture supernatant from the fungus Beauveria bassiana containing chitinase was added to the infective blood meal to disintegrate the PM artificially. In females treated with Beauveria bassiana culture supernatants the PM was weakened and permeable, lacking multilayered inner structure; Leishmania colonized the midgut and the stomodeal valve and produced metacyclic forms. In control females Leishmania infections were lost during defecation.

Conclusions/Significance

Persistence of the PM till defecation of the bloodmeal represents an important factor responsible for refractoriness of S. schwetzi to Leishmania development. Leishmania major as well as L. donovani promastigotes survived defecation and developed late-stage infections only in females with PM disintegrated artificially by B. bassiana culture supernatants containing exogenous chitinase.

Expanding the toolbox for <i>Trypanosoma cruzi</i>: A parasite line incorporating a bioluminescence-fluorescence dual reporter and streamlined CRISPR/Cas9 functionality for rapid <i>in vivo</i> localisation and phenotyping

PLoS Neglected Tropical Diseases News - 2 April 2018 - 9:00pm

by Fernanda Cristina Costa, Amanda Fortes Francisco, Shiromani Jayawardhana, Simone Guedes Calderano, Michael D. Lewis, Francisco Olmo, Tom Beneke, Eva Gluenz, Jack Sunter, Samuel Dean, John Morrison Kelly, Martin Craig Taylor

Background

Infection with Trypanosoma cruzi causes Chagas disease, a major public health problem throughout Latin America. There is no vaccine and the only drugs have severe side effects. Efforts to generate new therapies are hampered by limitations in our understanding of parasite biology and disease pathogenesis. Studies are compromised by the complexity of the disease, the long-term nature of the infection, and the fact that parasites are barely detectable during the chronic stage. In addition, functional dissection of T. cruzi biology has been restricted by the limited flexibility of the genetic manipulation technology applicable to this parasite.

Methodology/Principal findings

Here, we describe two technical innovations, which will allow the role of the parasite in disease progression to be better assessed. First, we generated a T. cruzi reporter strain that expresses a fusion protein comprising red-shifted luciferase and green fluorescent protein domains. Bioluminescence allows the kinetics of infection to be followed within a single animal, and specific foci of infection to be pinpointed in excised tissues. Fluorescence can then be used to visualise individual parasites in tissue sections to study host-parasite interactions at a cellular level. Using this strategy, we have been routinely able to find individual parasites within chronically infected murine tissues for the first time. The second advance is the incorporation of a streamlined CRISPR/Cas9 functionality into this reporter strain that can facilitate genome editing using a PCR-based approach that does not require DNA cloning. This system allows the rapid generation of null mutants and fluorescently tagged parasites in a background where the in vivo phenotype can be rapidly assessed.

Conclusions/Significance

The techniques described here will have multiple applications for studying aspects of T. cruzi biology and Chagas disease pathogenesis previously inaccessible to conventional approaches. The reagents and cell lines have been generated as a community resource and are freely available on request.

The effectiveness of water treatment processes against schistosome cercariae: A systematic review

PLoS Neglected Tropical Diseases News - 2 April 2018 - 9:00pm

by Laura Braun, Jack E. T. Grimes, Michael R. Templeton

Background

Schistosomiasis is one of the most disabling neglected tropical diseases, ranking second in terms of years lived with disability. While treatment with the drug praziquantel can have immediate beneficial effects, reinfection can occur rapidly if people are in contact with cercaria-infested water. Water treatment for schistosomiasis control seeks to eliminate viable cercariae from water, thereby providing safe alternative water supplies for recreational and domestic activities including laundry and bathing. This provision may reduce contact with infested water, which is crucial for reducing reinfection following chemotherapy and cutting schistosome transmission.

Methodology

A qualitative systematic review was carried out to summarize the existing knowledge on the effectiveness of water treatment in removing or inactivating human schistosome cercariae. Four online databases were searched. Studies were screened and categorized into five water treatment processes: storage, heating, chlorination, filtration, and ultraviolet (UV) disinfection.

Conclusions

All five water treatment methods can remove or inactivate cercariae in water, and hence produce cercaria-free water. However, reliable design guidelines for treating water do not exist as there are insufficient data. Overall, the review found that cercariae are inactivated when storing water for 10–72 hours (depending on temperature), or with chlorination values of 3–30 mg-min/l. UV fluences between 3–60 mJ/cm2 may significantly damage or kill cercariae, and sand filters with 0.18–0.35 mm grain size have been shown to remove cercariae. This systematic review identified 67 studies about water treatment and schistosomiasis published in the past 106 years. It highlights the many factors that influence the results of water treatment experiments, which include different water quality conditions and methods for measuring key parameters. Variation in these factors limit comparability, and therefore currently available information is insufficient for providing complete water treatment design recommendations.

Development of a <i>Trypanosoma cruzi</i> strain typing assay using MS2 peptide spectral libraries (Tc-STAMS2)

PLoS Neglected Tropical Diseases News - 2 April 2018 - 9:00pm

by Gilberto Santos de Oliveira, Rebeca Kawahara, Livia Rosa-Fernandes, Simon Ngao Mule, Carla Cristi Avila, Marta M. G. Teixeira, Martin R. Larsen, Giuseppe Palmisano

Background

Chagas disease also known as American trypanosomiasis is caused by the protozoan Trypanosoma cruzi. Over the last 30 years, Chagas disease has expanded from a neglected parasitic infection of the rural population to an urbanized chronic disease, becoming a potentially emergent global health problem. T. cruzi strains were assigned to seven genetic groups (TcI-TcVI and TcBat), named discrete typing units (DTUs), which represent a set of isolates that differ in virulence, pathogenicity and immunological features. Indeed, diverse clinical manifestations (from asymptomatic to highly severe disease) have been attempted to be related to T.cruzi genetic variability. Due to that, several DTU typing methods have been introduced. Each method has its own advantages and drawbacks such as high complexity and analysis time and all of them are based on genetic signatures. Recently, a novel method discriminated bacterial strains using a peptide identification-free, genome sequence-independent shotgun proteomics workflow. Here, we aimed to develop a Trypanosoma cruzi Strain Typing Assay using MS/MS peptide spectral libraries, named Tc-STAMS2.

Methods/Principal findings

The Tc-STAMS2 method uses shotgun proteomics combined with spectral library search to assign and discriminate T. cruzi strains independently on the genome knowledge. The method is based on the construction of a library of MS/MS peptide spectra built using genotyped T. cruzi reference strains. For identification, the MS/MS peptide spectra of unknown T. cruzi cells are identified using the spectral matching algorithm SpectraST. The Tc-STAMS2 method allowed correct identification of all DTUs with high confidence. The method was robust towards different sample preparations, length of chromatographic gradients and fragmentation techniques. Moreover, a pilot inter-laboratory study showed the applicability to different MS platforms.

Conclusions and significance

This is the first study that develops a MS-based platform for T. cruzi strain typing. Indeed, the Tc-STAMS2 method allows T. cruzi strain typing using MS/MS spectra as discriminatory features and allows the differentiation of TcI-TcVI DTUs. Similar to genomic-based strategies, the Tc-STAMS2 method allows identification of strains within DTUs. Its robustness towards different experimental and biological variables makes it a valuable complementary strategy to the current T. cruzi genotyping assays. Moreover, this method can be used to identify DTU-specific features correlated with the strain phenotype.

A field study of the survival and dispersal pattern of <i>Lutzomyia longipalpis</i> in an endemic area of visceral leishmaniasis in Brazil

PLoS Neglected Tropical Diseases News - 2 April 2018 - 9:00pm

by Fredy Galvis-Ovallos, Claudio Casanova, Denise Pimentel Bergamaschi, Eunice Aparecida Bianchi Galati

Zoonotic Visceral leishmaniasis (ZVL) is a neglected tropical disease that in the Americas is caused by the infection of Leishmania infantum and the domestic dog (Canis familiaris) is the main parasite reservoir in urban areas. The parasite is mainly transmitted by populations of the sibling species Lutzomyia longipalpis that has been spreading in countries including Brazil, Argentina, Paraguay and more recently Uruguay. Although bionomic parameters such as population survival and the duration of the gonotrophic cycle are critical in evaluating vector capacity, field studies have rarely been applied to sand fly populations. The present study sought to evaluate basic bionomic parameters related to the vectorial capacity of the (S)-9-methylgermacrene-B population of the Lu. longipalpis complex in a visceral leishmaniasis area of Sao Paulo state. The daily survival rate, the duration of the gonotrophic cycle and the dispersal pattern were evaluated through the mark- release-recapture method. A total of 1,547 males and 401 females were marked and released in five experiments carried out between February 2013 and February 2014. The higher recapture rates occurred within 100 meters of the release point and the estimated daily survival rates varied between 0.69 and 0.89 for females and between 0.69 and 0.79 for males. The minimum duration of the gonotrophic cycle observed was five days. The absolute population size, calculated ranged from 900 to 4,857 females and from 2,882 to 9,543 males. Our results demonstrate a high survival rate of this vector population and low dispersal that could be associated with the presence of all necessary conditions for its establishment and maintenance in the peridomiciles of this area. Our findings contribute to the basic data necessary for the understanding of ZVL dynamics and the evaluation of the implementation of prevention and control measures.

Kampala manifesto: Building community-based One Health approaches to disease surveillance and response—The Ebola Legacy—Lessons from a peer-led capacity-building initiative

PLoS Neglected Tropical Diseases News - 2 April 2018 - 9:00pm

by Petra Dickmann, Andrew Kitua, Franklin Apfel, Nigel Lightfoot

Overview

International activities to respond to the Ebola crisis in West Africa were mainly developed and focussed around the biomedical paradigm of Western health systems. This approach was often insensitive to societal perception, attitude, and behavioural determinants and clashed with community-based health traditions, narratives, and roles, e.g., of community health workers. In this peer-led capacity-building initiative, these deficiencies were identified and analysed. Innovative, more locally focussed, community-based solutions were articulated. The new approaches described put local people at the centre of all preparedness, response, and recovery strategies. This paradigm shift reframed the role of communities from victims to active managers of their response and reacknowledged the strength of community-based One Health. We conclude that strategies should aim at empowering, not just engaging, communities. Communities can improve short-term crisis management and build longer-term resilience and capacities that are much needed in the current global health climate.

Background

The Ebola outbreak in West Africa, 2014–2016, was unprecedented in scale, extent, and duration. The international community was slow to step up its assistance in this global public health emergency and then faltered when its infection control management approaches clashed with West African realities [1]. Outbreak response evaluations have identified the need to better integrate social science intelligence [2], better collaborate with communities [3,4], more effectively draw on the strength of community health workers [5], and critically question the paradigm of Western health systems, which focus on imposing ‘evidence-based’ solutions that lack external validity in affected communities; i.e., they too often recommend actions that are inconsistent with, ignore, or violate traditional behaviours [6].While there appears to be a consensus now on what needs to be done, how to achieve these goals remains a challenge.

Pyrethroid resistance persists after ten years without usage against <i>Aedes aegypti</i> in governmental campaigns: Lessons from São Paulo State, Brazil

PLoS Neglected Tropical Diseases News - 30 March 2018 - 9:00pm

by Maria de Lourdes Macoris, Ademir Jesus Martins, Maria Teresa Macoris Andrighetti, José Bento Pereira Lima, Denise Valle

Background

Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is found at high densities in tropical urban areas. The dissemination of this vector is partially the consequence of failures in current vector control methods, still mainly relying upon insecticides. In the State of São Paulo (SP), Brazil, public health managers employed pyrethroids against Ae. aegypti adults from 1989 to 2000, when a robust insecticide resistance monitoring system detected resistance to pyrethroids in several Ae. aegypti populations. However, pyrethroids are also the preferred compounds engaged in household applications due to their rapid knockdown effect, lower toxicity to mammals and less irritating smell.

Methodology/Principal findings

We evaluated pyrethroid resistance in Ae. aegypti populations over the course of a decade, from 2004 to 2015, after interruption of pyrethroid public applications in SP. Qualitative bioassays with papers impregnated with a deltamethrin diagnostic dose (DD) performed with insects from seven SP municipalities and evaluated yearly from 2006 to 2014, detected resistance in most of the cases. Quantitative bioassays were also carried out with four populations in 2011, suggesting a positive correlation between resistance level and survivorship in the DD bioassays. Biochemical tests conducted with seven insect populations in 2006 and 2015, detected increasing metabolic alterations of all major classes of detoxifying enzymes, mostly of mixed function oxidases. Genotyping of the voltage-gated sodium channel (AaNaV, the pyrethroid target-site) with a TaqMan real time PCR based technique was performed from 2004 to 2014 in all seven localities. The two kdr mutations, Val1016Ile and Phe1534Cys, known to be spread throughout Brazil, were always present with a severe decrease of the susceptible allele over time.

Conclusions/Significance

These results are discussed in the context of public and domestic insecticide use, the necessity of implementation of a strong integrated vector control strategy and the conceptual misunderstanding between 'vector control' and 'chemical control of vectors'.

<i>Trypanosoma cruzi</i> 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine

PLoS Neglected Tropical Diseases News - 30 March 2018 - 9:00pm

by Augusto E. Bivona, Andrés Sánchez Alberti, Marina N. Matos, Natacha Cerny, Alejandro C. Cardoso, Celina Morales, Germán González, Silvia I. Cazorla, Emilio L. Malchiodi

Background

Chagas disease, also known as American Trypanosomiasis, is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection. Despite of being endemic on 21 Latin-American countries, Chagas disease has become a global concern due to migratory movements. Unfortunately, available drugs for the treatment have several limitations and they are generally administered during the chronic phase of the infection, when its efficacy is considered controversial. Thus, prophylactic and/or therapeutic vaccines are emerging as interesting control alternatives. In this work, we proposed Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a new antigen for vaccine development against Chagas disease.

Methodology/Principal findings

In a murine model, we analyzed the immune response triggered by different immunization protocols based on Tc80 and evaluated their ability to confer protection against a challenge with the parasite. Immunized mice developed Tc80-specific antibodies which were able to carry out different functions such as: enzymatic inhibition, neutralization of parasite infection and complement-mediated lysis of trypomastigotes. Furthermore, vaccinated mice elicited strong cell-mediated immunity. Spleen cells from immunized mice proliferated and secreted Th1 cytokines (IL-2, IFN-γ and TNF-α) upon re-stimulation with rTc80. Moreover, we found Tc80-specific polyfunctional CD4 T cells, and cytotoxic T lymphocyte activity against one Tc80 MHC-I peptide.Immunization protocols conferred protection against a T. cruzi lethal challenge. Immunized groups showed a decreased parasitemia and higher survival rate compared with non-immunized control mice. Moreover, during the chronic phase of the infection, immunized mice presented: lower levels of myopathy-linked enzymes, parasite burden, electrocardiographic disorders and inflammatory cells.

Conclusions/Significance

Considering that an early control of parasite burden and tissue damage might contribute to avoid the progression towards symptomatic forms of chronic Chagas disease, the efficacy of Tc80-based vaccines make this molecule a promising immunogen for a mono or multicomponent vaccine against T. cruzi infection.

Discovery of genomic intervals that underlie nematode responses to benzimidazoles

PLoS Neglected Tropical Diseases News - 30 March 2018 - 9:00pm

by Mostafa Zamanian, Daniel E. Cook, Stefan Zdraljevic, Shannon C. Brady, Daehan Lee, Junho Lee, Erik C. Andersen

Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to these critical drugs remains largely unexplored. Here, we exploit natural variation in the model nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely used in human and animal medicine. High-throughput phenotyping of albendazole, fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant lines led to the discovery of over 15 QTL in C. elegans and four QTL in C. briggsae associated with divergent responses to these anthelmintics. Many of these QTL are conserved across benzimidazole derivatives, but others show drug and dose specificity. We used near-isogenic lines to recapitulate and narrow the C. elegans albendazole QTL of largest effect and identified candidate variants correlated with the resistance phenotype. These QTL do not overlap with known benzimidazole target resistance genes from parasitic nematodes and present specific new leads for the discovery of novel mechanisms of nematode benzimidazole resistance. Analyses of orthologous genes reveal conservation of candidate benzimidazole resistance genes in medically important parasitic nematodes. These data provide a basis for extending these approaches to other anthelmintic drug classes and a pathway towards validating new markers for anthelmintic resistance that can be deployed to improve parasite disease control.

Ten years of surveillance of the Yulong plague focus in China and the molecular typing and source tracing of the isolates

PLoS Neglected Tropical Diseases News - 30 March 2018 - 9:00pm

by Peng Wang, Liyuan Shi, Fuxin Zhang, Ying Guo, Zhikai Zhang, Hongli Tan, Zhigang Cui, Yibo Ding, Ying Liang, Yun Liang, Dongzheng Yu, Jianguo Xu, Wei Li, Zhizhong Song

Plague, caused by Yersinia pestis, was classified as a reemerging infectious disease by the World Health Organization. The five human pneumonic plague cases in Yulong County in 2005 gave rise to the discovery of a Yulong plague focus in Yunnan province, China. Thereafter, continuous wild rodent plague (sylvatic plague) was identified as the main plague reservoir of this focus. In this study, the epizootics in Yulong focus were described, and three molecular typing methods, including the different region (DFR) analysis, clustered regularly interspaced short palindromic repeats (CRISPRs), and the multiple-locus variable number of tandem repeats (VNTR) analysis (MLVA) (14+12), were used for the molecular typing and source tracing of Y. pestis isolates in the Yulong plague focus. Simultaneously, several isolates from the vicinity of Yunnan were used as controls. The results showed that during the 10-year period from 2006 to 2016, an animal plague epidemic occurred in 6 of those years, and 5 villages underwent an animal plague epidemic within a 30-km2 area of the Yulong plague focus. Searching for dead mice was the most effective monitoring method in this plague focus. No positive sample has been found in 6937 captured live rodents thus far, suggesting that the virulence of strains in the Yulong plague focus is stronger and the survival time of mice is shorter after infection. Strains from Lijiang, Sichuan and Tibet were of the same complex based on a typing analysis of DFR and CRISPR. The genetic relationship of Y. pestis illustrated by MLVA “14+12” demonstrates that Tibet and Sichuan strains evolved from the strains 1.IN2 (Qinghai, 1970 and Tibet, 1976), and Lijiang strains are closer to Batang strains (Batang County in Sichuan province, 2011, Himalaya marmot plague foci) in terms of genetic or phylogenic relationships. In conclusion, we have a deeper understanding of this new plague focus throughout this study, which provides a basis for effective prevention and control.

<i>Brugia malayi</i> infection in ferrets – A small mammal model of lymphatic filariasis

PLoS Neglected Tropical Diseases News - 30 March 2018 - 9:00pm

by Belinda M. Jackson-Thompson, So Young Kim, Shalini Jaiswal, Jessica R. Scott, Scott R. Jones, C. Paul Morris, J. Judd Fite, Karen Laurie, Andrew R. Hoy, Bernard J. Dardzinski, Edward Mitre

Background

The lack of effective short-course therapies for treatment of the adult stage of filarial worms is a major limitation in the global effort to eliminate lymphatic filariasis. Studies using current small mammal models of lymphatic filariasis are limited by difficulties in quantifying adult worm numbers and in assessing lymphatic anatomy and function.

Methodology/Principal findings

Here, we re-established Brugia malayi infection of ferrets as a model for lymphatic filariasis and demonstrated parasitological, immunological, and histological parallels with human infection. Subcutaneous injection of L3 larvae into a hind-footpad resulted in a mean of 18 adult worms recovered 16 weeks post-infection, primarily from the draining inguinal and femoral lymphatics of the injected limb. Infected ferrets developed microfilaremia, with patency lasting from 12–26 weeks post-infection. Quantitative PCR assessing cytokine transcription by antigen-stimulated lymph node cells demonstrated a mixed Th1/Th2 response occurring during early infection. Immunoregulation with production of down-regulatory cytokine IL-10 occurred just prior to peak microfilaremia. Histological analysis revealed progressive inflammation of the lymphatic vessel walls, with intimal thickening and disorganization of collagen fibers. Inflammation was observed as early as 8 weeks post-infection and extended into the perivascular and subcutaneous tissues by 16 weeks post-infection. Finally, we developed a novel ferret PET/CT lymphoscintigraphy method demonstrating substantial changes in lymphatic anatomy and function as early as 3 weeks post-infection, with progression over the course of infection.

Conclusions/Significance

B. malayi infection of ferrets is a robust model of human lymphatic filariasis that can be utilized to study efficacy of novel antifilarial agents against adult worms residing within lymphatic vessels. In conjunction with PET/CT lymphoscintigraphy, this model can also be used to investigate pathogenesis of lymphatic dysfunction in lymphatic filariasis and efficacy of medications aimed at reversing lymphatic dysfunction after clearance of adult worms.

Development and evaluation of antibody-capture immunoassays for detection of Lassa virus nucleoprotein-specific immunoglobulin M and G

PLoS Neglected Tropical Diseases News - 29 March 2018 - 9:00pm

by Martin Gabriel, Donatus I. Adomeh, Jacqueline Ehimuan, Jennifer Oyakhilome, Emmanuel O. Omomoh, Yemisi Ighodalo, Thomas Olokor, Kofi Bonney, Meike Pahlmann, Petra Emmerich, Michaela Lelke, Linda Brunotte, Stephan Ölschläger, Corinna Thomé-Bolduan, Beate Becker-Ziaja, Carola Busch, Ikponmwonsa Odia, Ephraim Ogbaini-Emovon, Peter O. Okokhere, Sylvanus A. Okogbenin, George O. Akpede, Herbert Schmitz, Danny A. Asogun, Stephan Günther

Background

The classical method for detection of Lassa virus-specific antibodies is the immunofluorescence assay (IFA) using virus-infected cells as antigen. However, IFA requires laboratories of biosafety level 4 for assay production and an experienced investigator to interpret the fluorescence signals. Therefore, we aimed to establish and evaluate enzyme-linked immunosorbent assays (ELISA) using recombinant Lassa virus nucleoprotein (NP) as antigen.

Methodology/Principal findings

The IgM ELISA is based on capturing IgM antibodies using anti-IgM, and the IgG ELISA is based on capturing IgG antibody–antigen complexes using rheumatoid factor or Fc gamma receptor CD32a. Analytical and clinical evaluation was performed with 880 sera from Lassa fever endemic (Nigeria) and non-endemic (Ghana and Germany) areas. Using the IFA as reference method, we observed 91.5–94.3% analytical accuracy of the ELISAs in detecting Lassa virus-specific antibodies. Evaluation of the ELISAs for diagnosis of Lassa fever on admission to hospital in an endemic area revealed a clinical sensitivity for the stand-alone IgM ELISA of 31% (95% CI 25–37) and for combined IgM/IgG detection of 26% (95% CI 21–32) compared to RT-PCR. The specificity of IgM and IgG ELISA was estimated at 96% (95% CI 93–98) and 100% (95% CI 99–100), respectively, in non-Lassa fever patients from non-endemic areas. In patients who seroconverted during follow-up, Lassa virus-specific IgM and IgG developed simultaneously rather than sequentially. Consistent with this finding, isolated IgM reactivity, i.e. IgM in the absence of IgG, had no diagnostic value.

Conclusions/Significance

The ELISAs are not equivalent to RT-PCR for early diagnosis of Lassa fever; however, they are of value in diagnosing patients at later stage. The IgG ELISA may be useful for epidemiological studies and clinical trials due its high specificity, and the higher throughput rate and easier operation compared to IFA.

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