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Identification of antigenic <i>Sarcoptes scabiei</i> proteins for use in a diagnostic test and of non-antigenic proteins that may be immunomodulatory

PLoS Neglected Tropical Diseases News - 12 June 2017 - 9:00pm

by Marjorie S. Morgan, S. Dean Rider Jr., Larry G. Arlian

Background

Scabies, caused by the mite, Sarcoptes scabiei, infects millions of humans, and many wild and domestic mammals. Scabies mites burrow in the lower stratum corneum of the epidermis of the skin and are the source of substances that are antigenic or modulate aspects of the protective response of the host. Ordinary scabies is a difficult disease to diagnose.

Objective

The goal of this project was to identify S. scabiei proteins that may be candidate antigens for use in a diagnostic test or may be used by the mite to modulate the host’s protective response.

Methods

An aqueous extract of S. scabiei was separated by 2-dimensional electrophoresis and proteins were identified by mass spectrometry. A parallel immunoblot was probed with serum from patients with ordinary scabies to identify IgM and/or IgG-binding antigens. The genes coding for 23 selected proteins were cloned into E. coli and the expressed recombinant proteins were screened with serum from patients with confirmed ordinary scabies.

Results

We identified 50 different proteins produced by S. scabiei, 34 of which were not previously identified, and determined that 66% were recognized by patient IgM and/or IgG. Fourteen proteins were screened for use in a diagnostic test but none possessed enough sensitivity and specificity to be useful. Six of the 9 proteins selected for the possibility that they may be immunomodulatory were not recognized by antibodies in patient serum.

Conclusions

Thirty-three proteins that bound IgM and/or IgG from the serum of patients with ordinary scabies were identified. None of the 14 tested were useful for inclusion in a diagnostic test. The identities of 16 proteins that are not recognized as antigens by infected patients were also determined. These could be among the molecules that are responsible for this mite’s ability to modulate its host’s innate and adaptive immune responses.

Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review

PLoS Neglected Tropical Diseases News - 12 June 2017 - 9:00pm

by Giovanni Lo Iacono, Ben Armstrong, Lora E. Fleming, Richard Elson, Sari Kovats, Sotiris Vardoulakis, Gordon L. Nichols

Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE). In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter). Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias, healthcare access) between environmental drivers/exposures and disease detection. Key areas of future research include: disentangling the complex effects of weather/climate on each exposure-health outcome pathway (e.g. person-to-person vs environment-to-person), and linking weather data to individual cases longitudinally.

Deltamethrin resistance in <i>Aedes aegypti</i> results in treatment failure in Merida, Mexico

PLoS Neglected Tropical Diseases News - 12 June 2017 - 9:00pm

by Gonzalo M. Vazquez-Prokopec, Anuar Medina-Barreiro, Azael Che-Mendoza, Felipe Dzul-Manzanilla, Fabian Correa-Morales, Guillermo Guillermo-May, Wilbert Bibiano-Marín, Valentín Uc-Puc, Eduardo Geded-Moreno, José Vadillo-Sánchez, Jorge Palacio-Vargas, Scott A. Ritchie, Audrey Lenhart, Pablo Manrique-Saide

The operational impact of deltamethrin resistance on the efficacy of indoor insecticide applications to control Aedes aegypti was evaluated in Merida, Mexico. A randomized controlled trial quantified the efficacy of indoor residual spraying (IRS) against adult Ae. aegypti in houses treated with either deltamethrin (to which local Ae. aegypti expressed a high degree of resistance) or bendiocarb (to which local Ae. aegypti were fully susceptible) as compared to untreated control houses. All adult Ae. aegypti infestation indices during 3 months post-spraying were significantly lower in houses treated with bendiocarb compared to untreated houses (odds ratio <0.75; incidence rate ratio < 0.65) whereas no statistically significant difference was detected between the untreated and the deltamethrin-treated houses. On average, bendiocarb spraying reduced Ae. aegypti abundance by 60% during a 3-month period. Results demonstrate that vector control efficacy can be significantly compromised when the insecticide resistance status of Ae. aegypti populations is not taken into consideration.

A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus

PLoS Neglected Tropical Diseases News - 12 June 2017 - 9:00pm

by Diogo M. Magnani, Cassia G. T. Silveira, Brandon C. Rosen, Michael J. Ricciardi, Núria Pedreño-Lopez, Martin J. Gutman, Varian K. Bailey, Helen S. Maxwell, Aline Domingues, Lucas Gonzalez-Nieto, Vivian I. Avelino-Silva, Mateus Trindade, Juliana Nogueira, Consuelo S. Oliveira, Alvino Maestri, Alvina Clara Felix, José Eduardo Levi, Mauricio L. Nogueira, Mauricio A. Martins, José M. Martinez-Navio, Sebastian P. Fuchs, Stephen S. Whitehead, Dennis R. Burton, Ronald C. Desrosiers, Esper G. Kallas, David I. Watkins

The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut50 ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.

Burden and impact of <i>Plasmodium vivax</i> in pregnancy: A multi-centre prospective observational study

PLoS Neglected Tropical Diseases News - 12 June 2017 - 9:00pm

by Azucena Bardají, Flor Ernestina Martínez-Espinosa, Myriam Arévalo-Herrera, Norma Padilla, Swati Kochar, Maria Ome-Kaius, Camila Bôtto-Menezes, María Eugenia Castellanos, Dhanpat Kumar Kochar, Sanjay Kumar Kochar, Inoni Betuela, Ivo Mueller, Stephen Rogerson, Chetan Chitnis, Dhiraj Hans, Michela Menegon, Carlo Severini, Hernando del Portillo, Carlota Dobaño, Alfredo Mayor, Jaume Ordi, Mireia Piqueras, Sergi Sanz, Mats Wahlgren, Laurence Slutsker, Meghna Desai, Clara Menéndez, on behalf of the PregVax Study Group

Background

Despite that over 90 million pregnancies are at risk of Plasmodium vivax infection annually, little is known about the epidemiology and impact of the infection in pregnancy.

Methodology and principal findings

We undertook a health facility-based prospective observational study in pregnant women from Guatemala (GT), Colombia (CO), Brazil (BR), India (IN) and Papua New Guinea PNG). Malaria and anemia were determined during pregnancy and fetal outcomes assessed at delivery. A total of 9388 women were enrolled at antennal care (ANC), of whom 53% (4957) were followed until delivery. Prevalence of P. vivax monoinfection in maternal blood at delivery was 0.4% (20/4461) by microscopy [GT 0.1%, CO 0.5%, BR 0.1%, IN 0.2%, PNG 1.2%] and 7% (104/1488) by PCR. P. falciparum monoinfection was found in 0.5% (22/4463) of women by microscopy [GT 0%, CO 0.5%, BR 0%, IN 0%, PNG 2%]. P. vivax infection was observed in 0.4% (14/3725) of placentas examined by microscopy and in 3.7% (19/508) by PCR. P. vivax in newborn blood was detected in 0.02% (1/4302) of samples examined by microscopy [in cord blood; 0.05% (2/4040) by microscopy, and 2.6% (13/497) by PCR]. Clinical P. vivax infection was associated with increased risk of maternal anemia (Odds Ratio-OR, 5.48, [95% CI 1.83–16.41]; p = 0.009), while submicroscopic vivax infection was not associated with increased risk of moderate-severe anemia (Hb<8g/dL) (OR, 1.16, [95% CI 0.52–2.59]; p = 0.717), or low birth weight (<2500g) (OR, 0.52, [95% CI, 0.23–1.16]; p = 0.110).

Conclusions

In this multicenter study, the prevalence of P. vivax infection in pregnancy by microscopy was overall low across all endemic study sites; however, molecular methods revealed a significant number of submicroscopic infections. Clinical vivax infection in pregnancy was associated with maternal anemia, which may be deleterious for infant’s health. These results may help to guide maternal health programs in settings where vivax malaria is endemic; they also highlight the need of addressing a vulnerable population such as pregnant women while embracing malaria elimination in endemic countries.

Pediatric melioidosis in Sarawak, Malaysia: Epidemiological, clinical and microbiological characteristics

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

by Anand Mohan, Yuwana Podin, Nickson Tai, Chae-Hee Chieng, Vanessa Rigas, Barbara Machunter, Mark Mayo, Desiree Wong, Su-Lin Chien, Lee-See Tan, Charles Goh, Reginal Bantin, Alexander Mijen, Wen-Yi Chua, King-Ching Hii, See-Chang Wong, Hie-Ung Ngian, Jin-Shyan Wong, Jamilah Hashim, Bart J. Currie, Mong-How Ooi

Background

Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak.

Methods

A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics.

Findings

Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster.

Conclusions

Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor.

Extraparenchymal neurocysticercosis: Demographic, clinicoradiological, and inflammatory features

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

by Mariana Marcin Sierra, Mariana Arroyo, May Cadena Torres, Nancy Ramírez Cruz, Fernando García Hernández, Diana Taboada, Ángeles Galicia Martínez, Tzipe Govezensky, Edda Sciutto, Andrea Toledo, Agnès Fleury

Background

Extraparenchymal neurocysticercosis (ExPNCC), an infection caused by Taenia solium cysticerci that mainly occurs in the ventricular compartment (Ve) or the basal subarachnoid space (SAb), is more severe but less frequent and much less studied than parenchymal neurocysticercosis (ParNCC). Demographic, clinical, radiological, and lumbar cerebrospinal fluid features of patients affected by ExPNCC are herein described and compared with those of ParNCC patients.

Methodology and principal findings

429 patients with a confirmed diagnosis of neurocysticercosis, attending the Instituto Nacional de Neurología y Neurocirugía, a tertiary reference center in Mexico City, from 2000 through 2014, were included. Demographic information, signs and symptoms, radiological patterns, and lumbar cerebrospinal fluid (CSF) laboratory values were retrieved from medical records for all patients. Data were statistically analyzed to assess potential differences depending on cyst location and to determine the effects of age and sex on the disease presentation. In total, 238 ExPNCC and 191 ParNCC patients were included. With respect to parenchymal cysts, extraparenchymal parasites were diagnosed at an older age (P = 0.002), chiefly caused intracranial hypertension (P < 0.0001), were more frequently multiple and vesicular (P < 0.0001), and CSF from these patients showed higher protein concentration and cell count (P < 0.0001). SAb patients were diagnosed at an older age than Ve patients, and showed more frequently seizures, vesicular cysticerci, and higher CSF cellularity. Gender and age modulated some traits of the disease.

Conclusions

This study evidenced clear clinical, radiological, and inflammatory differences between ExPNCC and ParNCC, and between SAb and Ve patients, and demonstrated that parasite location determines different pathological entities.

Expression of inhibitory receptors and polyfunctional responses of T cells are linked to the risk of congenital transmission of <i>T</i>. <i>cruzi</i>

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

by Adriana Egui, Paola Lasso, María Carmen Thomas, Bartolomé Carrilero, John Mario González, Adriana Cuéllar, Manuel Segovia, Concepción Judith Puerta, Manuel Carlos López

Congenital T. cruzi infections involve multiple factors in which complex interactions between the parasite and the immune system of pregnant women play important roles. In this study, we used an experimental murine model of chronic infection with T. cruzi to evaluate the changes in the expression of inhibitory receptors and the polyfunctionality of T cells during gestation and their association with congenital transmission rate of T. cruzi infection. The results showed that pregnant naïve mice had a higher percentage of CD4+ and CD8+ T cells that expressed inhibitory receptors than cells from non-pregnant naïve mice. However, in mice chronically infected with T. cruzi, gestation induced a significant decrease in the frequency of T cells that expressed or co-expressed inhibitory receptors, as well as an increase in the frequency of polyfunctional CD4+ and CD8+ T cells. This different behavior may be due to the breakdown in the infected mice of the gestation-induced immune homeostasis, probably to control the parasite load. Remarkably, it was observed that the mothers that transmitted the parasite had a higher frequency of T cells that expressed and co-expressed inhibitory receptors as well as a lower frequency of polyfunctional parasite-specific T cells than those that did not transmit it, even though the parasitemia load was similar in both groups. All together these data suggest that the maternal immune profile of the CD4+ and CD8+ T cells could be a determining factor in the congenital transmission of T. cruzi.

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage

PLoS Neglected Tropical Diseases News - 8 June 2017 - 9:00pm

by Lucy A. Parker, John Rumunu, Christine Jamet, Yona Kenyi, Richard Laku Lino, Joseph F. Wamala, Allan M. Mpairwe, Vincent Muller, Augusto E. Llosa, Florent Uzzeni, Francisco J. Luquero, Iza Ciglenecki, Andrew S. Azman

Introduction

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area.

Methodology/Principal findings

Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign (‘case-triggered’ interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0–73.7) and was highest among children ages 5–14 years (90.0%, 95% CI 85.7–94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68–0.96). In the case-triggered interventions, each lasting 1–2 days, coverage varied (range: 30–87%) with an average of 51.0% (95% CI 41.7–60.3).

Conclusions/Significance

Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

An individual-level meta-analysis assessing the impact of community-level sanitation access on child stunting, anemia, and diarrhea: Evidence from DHS and MICS surveys

PLoS Neglected Tropical Diseases News - 8 June 2017 - 9:00pm

by David A. Larsen, Thomas Grisham, Erik Slawsky, Lutchmie Narine

Background

A lack of access to sanitation is an important risk factor child health, facilitating fecal-oral transmission of pathogens including soil-transmitted helminthes and various causes of diarrheal disease. We conducted a meta-analysis of cross-sectional surveys to determine the impact that community-level sanitation access has on child health for children with and without household sanitation access.

Methodology/Principal findings

Using 301 two-stage demographic health surveys and multiple indicator cluster surveys conducted between 1990 and 2015 we calculated the sanitation access in the community as the proportion of households in the sampled cluster that had household access to any type of sanitation facility. We then conducted exact matching of children based on various predictors of living in a community with high access to sanitation. Using logistic regression with the matched group as a random intercept we examined the association between the child health outcomes of stunted growth, any anemia, moderate or severe anemia, and diarrhea in the previous two weeks and the exposure of living in a community with varying degrees of community-level sanitation access. For children with household-level sanitation access, living in a community with 100% sanitation access was associated with lowered odds of stunting (adjusted odds ratio [AOR] = 0.97, 95%; confidence interval (CI) = 0.94–1.00; n = 14,153 matched groups, 1,175,167 children), any anemia (AOR = 0.73; 95% CI = 0.67–0.78; n = 5,319 matched groups, 299,033 children), moderate or severe anemia (AOR = 0.72, 95% CI = 0.68–0.77; n = 5,319 matched groups, 299,033 children) and diarrhea (AOR = 0.94; 95% CI = 0.91–0.97); n = 16,379 matched groups, 1,603,731 children) compared to living in a community with < 30% sanitation access. For children without household-level sanitation access, living in communities with 0% sanitation access was associated with higher odds of stunting (AOR = 1.04, 95% CI = 1.02–1.06; n = 14,153 matched groups, 1,175,167 children), any anemia (AOR = 1.05, 95% CI = 1.00–1.09; n = 5,319 matched groups, 299,033 children), moderate or severe anemia (AOR = 1.04, 95% CI = 1.00–1.09; n = 5,319 matched groups, 299,033 children) but not diarrhea (AOR = 1.00, 95% CI = 0.98–1.02; n = 16,379 matched groups, 1,603,731 children) compared to children without household-level sanitation access living in communities with 1–30% sanitation access.

Conclusions/Significance

Community-level sanitation access is associated with improved child health outcomes independent of household-level sanitation access. The proportion of children living in communities with 100% sanitation access throughout the world is appallingly low. Ensuring sanitation access to all by 2030 will greatly improve child health.

Should the WHO withdraw support for mass deworming?

PLoS Neglected Tropical Diseases News - 8 June 2017 - 9:00pm

by Kevin Croke, Joan Hamory Hicks, Eric Hsu, Michael Kremer, Edward Miguel

The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery

PLoS Neglected Tropical Diseases News - 8 June 2017 - 9:00pm

by Suzanne Lamotte, Gerald F. Späth, Najma Rachidi, Eric Prina

The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.

LAMP-2 absence interfere with plasma membrane repair and decreases <i>T</i>. <i>cruzi</i> host cell invasion

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

by Natália Fernando Couto, Dina Pedersane, Luisa Rezende, Patrícia P. Dias, Tayanne L. Corbani, Lívia C. Bentini, Anny C. S. Oliveira, Ludmila F. Kelles, Thiago Castro-Gomes, Luciana O. Andrade

Trypanosoma cruzi enters host cells by subverting the mechanism of cell membrane repair. In this process, the parasite induces small injuries in the host cell membrane leading to calcium entry and lysosomal exocytosis, which are followed by compensatory endocytosis events that drive parasites into host cells. We have previously shown that absence of both LAMP-1 and 2, major components of lysosomal membranes, decreases invasion of T. cruzi into host cells, but the mechanism by which they interfere with parasite invasion has not been described. Here we investigated the role of these proteins in parasitophorous vacuole morphology, host cell lysosomal exocytosis, and membrane repair ability. First, we showed that cells lacking only LAMP-2 present the same invasion phenotype as LAMP1/2-/- cells, indicating that LAMP-2 is an important player during T. cruzi invasion process. Second, neither vacuole morphology nor lysosomal exocytosis was altered in LAMP-2 lacking cells (LAMP2-/- and LAMP1/2-/- cells). We then investigated the ability of LAMP-2 deficient cells to perform compensatory endocytosis upon lysosomal secretion, the mechanism by which cells repair their membrane and T. cruzi ultimately enters cells. We observed that these cells perform less endocytosis upon injury when compared to WT cells. This was a consequence of impaired cholesterol traffic in cells lacking LAMP-2 and its influence in the distribution of caveolin-1 at the cell plasma membrane, which is crucial for plasma membrane repair. The results presented here show the major role of LAMP-2 in caveolin traffic and membrane repair and consequently in T. cruzi invasion.

Transmission dynamics and control of <i>Rickettsia rickettsii</i> in populations of <i>Hydrochoerus hydrochaeris</i> and <i>Amblyomma sculptum</i>

PLoS Neglected Tropical Diseases News - 5 June 2017 - 9:00pm

by Gina Polo, Carlos Mera Acosta, Marcelo B. Labruna, Fernando Ferreira

Background

Brazilian Spotted Fever (BSF), caused by the bacterium Rickettsia rickettsii, is the tick-borne disease that generates the largest number of human deaths in the world. In Brazil, the current increase of BSF human cases has been associated with the presence and expansion of capybaras Hydrochoerus hydrochaeris, which act as primary hosts for the tick Amblyomma sculptum, vector of the R. rickettsii in this area.

Methods

We proposed a semi-discrete-time stochastic model to evaluate the role of capybaras in the transmission dynamics of R. rickettsii. Through a sensitivity analysis, we identified the parameters with significant influence on the R. rickettsii establishment. Afterward, we implemented the Gillespie’s algorithm to simulate the impact of potential public health interventions to prevent BSF human cases.

Results

The introduction of a single infected capybara with at least one infected attached tick is enough to trigger the disease in a non-endemic area. We found that to avoid the formation of new BSF-endemic areas, it is crucial to impede the emigration of capybaras from endemic areas by reducing their birth rate by more than 58%. Model results were corroborated by ex-situ data generated from field studies, and this supports our proposal to prevent BSF human cases by implementing control strategies focused on capybaras.

Conclusion

The proposed stochastic model illustrates how strategies for the control and prevention of vector-borne infectious diseases can be focused on amplifier hosts management practices. This work provides a basis for future prevention strategies for other neglected vector-borne diseases.

Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis

PLoS Neglected Tropical Diseases News - 5 June 2017 - 9:00pm

by Anna Beltrame, Massimo Guerriero, Andrea Angheben, Federico Gobbi, Ana Requena-Mendez, Lorenzo Zammarchi, Fabio Formenti, Francesca Perandin, Dora Buonfrate, Zeno Bisoffi

Background

Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting.

Methodology/Principal findings

A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone.

Conclusions

The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants.

Increased miltefosine tolerance in clinical isolates of <i>Leishmania donovani</i> is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress

PLoS Neglected Tropical Diseases News - 2 June 2017 - 9:00pm

by Deepak Kumar Deep, Ruchi Singh, Vasundhra Bhandari, Aditya Verma, Vanila Sharma, Saima Wajid, Shyam Sundar, V. Ramesh, Jean Claude Dujardin, Poonam Salotra

Background

Miltefosine (MIL) is an oral antileishmanial drug used for treatment of visceral leishmaniasis (VL) in the Indian subcontinent. Recent reports indicate a significant decline in its efficacy with a high rate of relapse in VL as well as post kala-azar dermal leishmaniasis (PKDL). We investigated the parasitic factors apparently involved in miltefosine unresponsiveness in clinical isolates of Leishmania donovani.

Methodology

L. donovani isolated from patients of VL and PKDL at pretreatment stage (LdPreTx, n = 9), patients that relapsed after MIL treatment (LdRelapse, n = 7) and parasites made experimentally resistant to MIL (LdM30) were included in this study. MIL uptake was estimated using liquid chromatography coupled mass spectrometry. Reactive oxygen species and intracellular thiol content were measured fluorometrically. Q-PCR was used to assess the differential expression of genes associated with MIL resistance.

Results

LdRelapse parasites exhibited higher IC50 both at promastigote level (7.92 ± 1.30 μM) and at intracellular amastigote level (11.35 ± 6.48 μM) when compared with LdPreTx parasites (3.27 ± 1.52 μM) and (3.85 ± 3.11 μM), respectively. The percent infectivity (72 hrs post infection) of LdRelapse parasites was significantly higher (80.71 ± 5.67%, P<0.001) in comparison to LdPreTx (60.44 ± 2.80%). MIL accumulation was significantly lower in LdRelapse parasites (1.7 fold, P<0.001) and in LdM30 parasites (2.4 fold, P<0.001) when compared with LdPreTx parasites. MIL induced ROS levels were significantly lower (p<0.05) in macrophages infected with LdRelapse while intracellular thiol content were significantly higher in LdRelapse compared to LdPreTx, indicating a better tolerance for oxidative stress in LdRelapse isolates. Genes associated with oxidative stress, metabolic processes and transporters showed modulated expression in LdRelapse and LdM30 parasites in comparison with LdPreTx parasites.

Conclusion

The present study highlights the parasitic factors and pathways responsible for miltefosine unresponsiveness in VL and PKDL.

Radiological evolution of porcine neurocysticercosis after combined antiparasitic treatment with praziquantel and albendazole

PLoS Neglected Tropical Diseases News - 2 June 2017 - 9:00pm

by Carla Cangalaya, Javier A. Bustos, Juan Calcina, Ana Vargas-Calla, Javier Mamani, Diego Suarez, Gianfranco Arroyo, Armando E. Gonzalez, Juan Chacaltana, Cristina Guerra-Giraldez, Siddhartha Mahanty, Theodore E. Nash, Héctor H. García, for the Cysticercosis Working Group in Peru

Background

The onset of anthelmintic treatment of neurocysticercosis (NCC) provokes an acute immune response of the host, which in human cases is associated with exacerbation of neurological symptoms. This inflammation can occur at the first days of therapy. So, changes in the brain cysts appearance may be detected by medical imaging. We evaluated radiological changes in the appearance of brain cysts (enhancement and size) on days two and five after the onset of antiparasitic treatment using naturally infected pigs as a model for human NCC.

Methods and results

Contrast T1-weighted magnetic resonance imaging with gadolinium was performed before and after antiparasitic treatment. Eight NCC-infected pigs were treated with praziquantel plus albendazole and euthanized two (n = 4) and five (n = 4) days after treatment; another group of four infected pigs served as untreated controls. For each lesion, gadolinium enhancement intensity (GEI) and cyst volume were measured at baseline and after antiparasitic treatment. Volume and GEI quantification ratios (post/pre-treatment measures) were used to appraise the effect of treatment. Cysts from untreated pigs showed little variations between their basal and post treatment measures. At days 2 and 5 there were significant increases in GEI ratio compared with the untreated group (1.32 and 1.47 vs 1.01, p = 0.021 and p = 0.021). Cyst volume ratios were significantly lower at days 2 and 5 compared with the untreated group (0.60 and 0.22 vs 0.95, p = 0.04 and p = 0.02). Cysts with lower cyst volume ratios showed more marked post-treatment inflammation, loss of vesicular fluid and cyst wall wrinkling.

Conclusion/Significance

A significant and drastic reduction of cyst size and increased pericystic enhancement occur in the initial days after antiparasitic treatment as an effect of acute perilesional immune response. These significant changes showed that early anthelmintic efficacy (day two) can be detected using magnetic resonance imaging.

Ebola virus disease contact tracing activities, lessons learned and best practices during the Duport Road outbreak in Monrovia, Liberia, November 2015

PLoS Neglected Tropical Diseases News - 2 June 2017 - 9:00pm

by Caitlin M. Wolfe, Esther L. Hamblion, Jacqueline Schulte, Parker Williams, Augustine Koryon, Jonathan Enders, Varlee Sanor, Yatta Wapoe, Dash Kwayon, David Blackey, Anthony S. Laney, Emily J. Weston, Emily K. Dokubo, Gloria Davies-Wayne, Annika Wendland, Valerie T. S. Daw, Mehboob Badini, Peter Clement, Nuha Mahmoud, Desmond Williams, Alex Gasasira, Tolbert G. Nyenswah, Mosoka Fallah

Background

Contact tracing is one of the key response activities necessary for halting Ebola Virus Disease (EVD) transmission. Key elements of contact tracing include identification of persons who have been in contact with confirmed EVD cases and careful monitoring for EVD symptoms, but the details of implementation likely influence their effectiveness. In November 2015, several months after a major Ebola outbreak was controlled in Liberia, three members of a family were confirmed positive for EVD in the Duport Road area of Monrovia. The cluster provided an opportunity to implement and evaluate modified approaches to contact tracing.

Methods

The approaches employed for improved contact tracing included classification and risk-based management of identified contacts (including facility based isolation of some high risk contacts, provision of support to persons being monitored, and school-based surveillance for some persons with potential exposure but not listed as contacts), use of phone records to help locate missing contacts, and modifications to data management tools. We recorded details about the implementation of these approaches, report the overall outcomes of the contact tracing efforts and the challenges encountered, and provide recommendations for management of future outbreaks.

Results

165 contacts were identified (with over 150 identified within 48 hours of confirmation of the EVD cases) and all initially missing contacts were located. Contacts were closely monitored and promptly tested if symptomatic; no contacts developed disease. Encountered challenges related to knowledge gaps among contact tracing staff, data management, and coordination of contact tracing activities with efforts to offer Ebola vaccine.

Conclusions

The Duport Road EVD cluster was promptly controlled. Missing contacts were effectively identified, and identified contacts were effectively monitored and rapidly tested. There is a persistent risk of EVD reemergence in Liberia; the experience controlling each cluster can help inform future Ebola control efforts in Liberia and elsewhere.

Mosquito co-infection with Zika and chikungunya virus allows simultaneous transmission without affecting vector competence of <i>Aedes aegypti</i>

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

by Giel P. Göertz, Chantal B. F. Vogels, Corinne Geertsema, Constantianus J. M. Koenraadt, Gorben P. Pijlman

Background

Zika virus (ZIKV) and chikungunya virus (CHIKV) are highly pathogenic arthropod-borne viruses that are currently a serious health burden in the Americas, and elsewhere in the world. ZIKV and CHIKV co-circulate in the same geographical regions and are mainly transmitted by Aedes aegypti mosquitoes. There is a growing number of case reports of ZIKV and CHIKV co-infections in humans, but it is uncertain whether co-infection occurs via single or multiple mosquito bites. Here we investigate the potential of Ae. aegypti mosquitoes to transmit both ZIKV and CHIKV in one bite, and we assess the consequences of co-infection on vector competence.

Methodology/Principal findings

First, growth curves indicated that co-infection with CHIKV negatively affects ZIKV production in mammalian, but not in mosquito cells. Next, Ae. aegypti mosquitoes were infected with ZIKV, CHIKV, or co-infected via an infectious blood meal or intrathoracic injections. Infection and transmission rates, as well as viral titers of positive mosquitoes, were determined at 14 days after blood meal or 7 days after injection. Saliva and bodies of (co-)infected mosquitoes were scored concurrently for the presence of ZIKV and/or CHIKV using a dual-colour immunofluorescence assay. The results show that orally exposed Ae. aegypti mosquitoes are highly competent, with transmission rates of up to 73% for ZIKV, 21% for CHIKV, and 12% of mosquitoes transmitting both viruses in one bite. However, simultaneous oral exposure to both viruses did not change infection and transmission rates compared to exposure to a single virus. Intrathoracic injections indicate that the selected strain of Ae. aegypti has a strong salivary gland barrier for CHIKV, but a less profound barrier for ZIKV.

Conclusions/Significance

This study shows that Ae. aegypti can transmit both ZIKV and CHIKV via a single bite. Furthermore, co-infection of ZIKV and CHIKV does not influence the vector competence of Ae. aegypti.

Rabies surveillance in dogs in Lao PDR from 2010-2016

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

by Bounlom Douangngeun, Watthana Theppangna, Phouvong Phommachanh, Keo Chomdara, Sithong Phiphakhavong, Syseng Khounsy, Mavuto Mukaka, David A. B. Dance, Stuart D. Blacksell

Background

Rabies is a fatal viral disease that continues to threaten both human and animal health in endemic countries. The Lao People’s Democratic Republic (Lao PDR) is a rabies-endemic country in which dogs are the main reservoir and continue to present health risks for both human and animals throughout the country.

Methods

Passive, laboratory–based rabies surveillance was performed for suspected cases of dog rabies in Vientiane Capital during 2010–2016 and eight additional provinces between 2015–2016 using the Direct Fluorescent Antibody Test (DFAT).

Results

There were 284 rabies positive cases from 415 dog samples submitted for diagnosis. 257 cases were from Vientiane Capital (2010–2016) and the remaining 27 cases were submitted during 2015–2016 from Champassak (16 cases), Vientiane Province (4 cases) Xieng Kuang (3 cases) Luang Prabang (2 cases), Saravan (1 case), Saisomboun (1 case) and Bokeo (1 case). There was a significant increase in rabies cases during the dry season (p = 0.004) (November to April; i.e., <100mm of rainfall per month). No significant differences were noted between age, sex, locality of rabies cases.

Conclusion

The use of laboratory-based rabies surveillance is a useful method of monitoring rabies in Lao PDR and should be expanded to other provincial centers, particularly where there are active rabies control programs.

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