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Updated evidence of the association between toxocariasis and epilepsy: Systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 20 July 2018 - 9:00pm

by Jaime Luna, Calogero Edoardo Cicero, Guillaume Rateau, Graziella Quattrocchi, Benoit Marin, Elisa Bruno, François Dalmay, Michel Druet-Cabanac, Alessandra Nicoletti, Pierre-Marie Preux

Objective

To gain further insight on the association between human toxocariasis and epilepsy in light of the new evidence in the last years.

Methods

A systematic review was conducted without date and language restriction in the following electronic databases: MEDLINE (PubMed), Ingenta Connect, Science Direct (Elsevier), RefDoc, Scopus, HighWire, Scielo and the database of the Institute of Neuroepidemiology and Tropical Neurology of the Limoges University (IENT). Two investigators independently conducted the search up to November 2017. A pooled odds ratio (OR) was estimated using a random effects model. Meta-regression was conducted to investigate potential sources of heterogeneity.

Results

Database search produced 204 publications. Eleven case-control studies were included that were carried out in 13 countries worldwide. A total number of 4740 subjects were considered (2159 people with epilepsy and 2581 people without epilepsy). The overall pooled OR was 1.69 (95% CI 1.42–2.01) for the association between epilepsy and Toxocara spp. seropositivity. A positive association was constantly reported in the restricted analysis (WB as confirmatory or diagnostic test, younger population, and population–based studies). Meta-regression showed no statistically significant association between covariates and outcome.

Conclusion

The updated meta-analysis provides epidemiological evidence of a positive association between Toxocara seropositivity and epilepsy. New surveys supported the association, mainly population-based studies. On this basis, health strategies to reduce the impact of Toxocara spp are strongly advised. Further research should be performed to understand the physiopathological mechanisms of toxocara-associated epileptogenesis.

Epidemiology and morbidity of hookworm-related cutaneous larva migrans (HrCLM): Results of a cohort study over a period of six months in a resource-poor community in Manaus, Brazil

PLoS Neglected Tropical Diseases News - 19 July 2018 - 9:00pm

by Felix Reichert, Daniel Pilger, Angela Schuster, Hannah Lesshafft, Silas Guedes de Oliveira, Ralf Ignatius, Hermann Feldmeier

Background

Hookworm-related cutaneous larva migrans (HrCLM) is a neglected parasitic skin disease, widespread in resource-poor communities in tropical and subtropical countries. Incidence and risk factors have never been investigated in a cohort study.

Methodology/Principal findings

To understand the seasonal epidemiology of HrCLM, an open cohort of 476 children in a resource-poor community in Manaus, Brazil was examined for HrCLM monthly over a period of 6 months. Monthly prevalence and intensity of infection were correlated with the amount of monthly precipitation. Multivariable Cox regression analysis indicated male sex (hazard ratio [HR] 3.29; 95% confidence interval [CI] 1.95–5.56), walking barefoot on sandy ground (HR 2.30; 95% CI 1.03–5.16), poverty (HR 2.13; 95% CI 1.09–4.17) and age between 10 and 14 years (HR 1.87; 95% CI 1.01–3.46) as predictors of HrCLM. Monthly incidence rates ranged between 0.21 and 1.05 cases per person-year with an overall incidence of 0.52 per person-year.

Conclusions/Significance

HrCLM is a frequent parasitic skin disease in this resource-poor community. Every second child theoretically becomes infected during one year. Boys, 10 to 14 years old, belonging to the poorest households of the community, are the most vulnerable population group. Even in the tropical monsoonal climate of Amazonia there is a considerable seasonal variation with monthly incidence and number of lesions peaking in the rainy season.

Towards a science of global health delivery: A socio-anthropological framework to improve the effectiveness of neglected tropical disease interventions

PLoS Neglected Tropical Diseases News - 19 July 2018 - 9:00pm

by Kevin Louis Bardosh

Background

Over the last decade, implementation research and a science of global health delivery have emerged as important vehicles to improve the effectiveness of interventions. Efforts to control neglected tropical diseases (NTD) operate in challenging circumstances and with marginalized populations, making attention to context-specific details particularly relevant. Socio-anthropological insights have much to offer a science of NTD delivery. In this paper, an accessible and actionable framework for understanding NTD intervention effectiveness, based on socio-anthropological research, is presented and its utility for program planning and monitoring and evaluation is outlined.

Methodology/Principal findings

The framework was developed inductively by comparatively analyzing three rapid ethnographic studies undertaken in Eastern Africa (2010–2013) on three different large-scale NTD interventions: rabies elimination in Tanzania, sleeping sickness control in Uganda and the prevention of parasitic worms in Zambia. The framework includes five “intervention domains” where the effectiveness of these interventions was negotiated and determined at the local level. This involves: 1) the terrain of intervention (including seasonality and geographical variability); 2) community agency (including local knowledge, risk perceptions, behaviors, leadership and social pressure); 3) the strategies and incentives of field staff (skills, motivations, capabilities and support); 4) the socio-materiality of technology (characteristics of intervention tools and the adoption process itself); and 5) the governance of interventions (policy narratives, available expertise, bureaucracy, politics and the utilization of knowledge). The paper illustrates the importance of each of these domains by drawing on the case study research, presenting lessons learnt and practical recommendations for how such insights could improve intervention delivery.

Conclusions/Significance

To help close the gap between efficacy and effectiveness in NTD programs, it is important that field staff: 1) generate meaningful knowledge about contextual factors; 2) use this knowledge to tailor field strategies; and 3) create routine mechanisms to account for the dynamic process of implementation itself. The framework presented here offers a simple analytical tool to strengthen these knowledge-to-action relationships existing project planning tools, drawing on the insights of socio-anthropology.

High mortality due to snakebites in French Guiana: Time has come to re-evaluate medical management protocols

PLoS Neglected Tropical Diseases News - 19 July 2018 - 9:00pm

by Rémi Mutricy, Xavier Heckmann, Maylis Douine, Christian Marty, Anne Jolivet, Véronique Lambert, Frédérique Perotti, David Boels, Sébastien Larréché, Jean-Philippe Chippaux, Mathieu Nacher, Loïc Epelboin

Determinants for not utilizing trachomatous trichiasis surgery among trachomatous trichiasis patients in Mehalsayint District, North-East Ethiopia

PLoS Neglected Tropical Diseases News - 18 July 2018 - 9:00pm

by Tedla Desta Meshesha, Goitom Halefom Senbete, Getahun Gebre Bogale

Background

Globally, trachoma is the leading cause of infectious blindness. In Ethiopia, the overall Trachomatous Trichiasis (TT) surgical coverage is 41%. Identifying determinants for not utilizing TT surgery among TT patients is important to design and monitor effective intervention programs. Therefore, this study aimed to identify determinants for not utilizing TT surgery among TT patients in Mehalsayint District, North East Ethiopia.

Methodology/Principal findings

A community based unmatched case control study was employed from March 30, 2017 to April 13, 2017. A total of 482 study participants (241 cases and 241 controls) with age of ≥15 years were included in the study. The data was entered with Epi info version 7.2 software and exported to SPSS version 20 for analysis. Bivariate analysis was fitted to screen candidate variables with p<0.2 for the final model. Finally, multivariable logistic regression analysis was employed to identify significant factors (p<0.05) for not utilizing TT surgery. Respondents’ age of 16–30 years (AOR: 10.11; 95% CI: 2.72, 37.59) and widowed respondents (AOR: 0.40; 95% CI: 0.21, 0.77), time to reach the service (AOR: 0.46; 95% CI: 0.24, 0.87), unavailability of TT surgeon (AOR: 5.00; 95% CI: 1.16, 21.38), symptoms of trichiasis (AOR: 7.49; 95% CI: 2.41, 23.26), duration of the problem (AOR: 2.56; 95% CI: 1.44, 4.54), the affected eye (AOR: 2.16; 95% CI: 1.23, 3.80), epilation practice (AOR: 3.22; 95% CI: 1.84, 5.64), and place of TT surgery given (AOR: 4.21; 95% CI: 2.48, 7.14) were significant determinants for not utilizing TT surgical services.

Conclusions/Significance

In this study, TT surgery against trachoma is very low and TT remains public health problem in the district. Being younger age and widowed, time taken to reach the service, absence of TT surgeon, symptoms of trichiasis, duration of problem, the affected eye, epilation practice, and service place were determinants for the inability of TT surgical services. The findings of this study would help in designing effective interventions to reduce trachoma in that district.

Peripheral nerve abnormality in HIV leprosy patients

PLoS Neglected Tropical Diseases News - 18 July 2018 - 9:00pm

by Marilia Brasil Xavier, Mariana Garcia Borges do Nascimento, Keila de Nazare Madureira Batista, Danusa Neves Somensi, Fernando Octavio Machado Juca Neto, Thomaz Xavier Carneiro, Claudia Maria Castro Gomes, Carlos Eduardo Pereira Corbett

Background

The geographical overlap of HIV (human immunodeficiency virus) and leprosy infection has become increasingly frequent and worrying, bringing many clinical issues. Peripheral neuropathy is very frequent in leprosy because of the predilection of its etiologic agent by Schwann cells of the peripheral nervous system, and it also affects individuals with HIV as one of the most common neurological manifestations.

Methodology/Principal findings

The present study compared a cohort of 63 patients diagnosed with leprosy and coinfected with HIV with a cohort of 64 patients with leprosy alone, who were followed at the outpatient clinic of the Nucleus of Tropical Medicine of the Federal University of Pará, Brazil. We observed that HIV-coinfected leprosy patients presented greater odds of overall peripheral nerve damage (nerve function impairment—NFI) than patients with leprosy alone. More sensitive damage was observed, especially in patients coinfected with multibacillary forms. Leprosy patients coinfected with HIV presented higher chances of motor damage with improvement over time using multidrug therapy (MDT) and highly active antiretroviral therapy (HAART), along with a greater extent of damage and occurrence of neuritis. The data suggest that in addition to patients presenting possible damage caused by leprosy, they also had a greater damage gradient attributable to HIV disease, but not related to HAART because most of these patients had been on the treatment for less than a year. Neuritis was treated with prednisone at doses recommended by the WHO, and coinfected patients had the highest rate of clinical improvement in the first 60 days.

Conclusions/Significance

The clinical characteristics of the two diseases should be considered in leprosy patients coinfected with HIV for better diagnosis and treatment of peripheral neuropathy. We suggest that new simplified assessment tools that allow the evaluation of the NFI of these patients be developed for use in the service.

Combining <i>Wolbachia</i>-induced sterility and virus protection to fight <i>Aedes albopictus</i>-borne viruses

PLoS Neglected Tropical Diseases News - 18 July 2018 - 9:00pm

by Riccardo Moretti, Pei-Shi Yen, Vincent Houé, Elena Lampazzi, Angiola Desiderio, Anna-Bella Failloux, Maurizio Calvitti

Among the strategies targeting vector control, the exploitation of the endosymbiont Wolbachia to produce sterile males and/or invasive females with reduced vector competence seems to be promising. A new Aedes albopictus transinfection (ARwP-M) was generated by introducing wMel Wolbachia in the ARwP line which had been established previously by replacing wAlbA and wAlbB Wolbachia with the wPip strain. Various infection and fitness parameters were studied by comparing ARwP-M, ARwP and wild-type (SANG population) Ae. albopictus sharing the same genetic background. Moreover, the vector competence of ARwP-M related to chikungunya, dengue and zika viruses was evaluated in comparison with ARwP. ARwP-M showed a 100% rate of maternal inheritance of wMel and wPip Wolbachia. Survival, female fecundity and egg fertility did not show to differ between the three Ae. albopictus lines. Crosses between ARwP-M males and SANG females were fully unfertile regardless of male age while egg hatch in reverse crosses increased from 0 to about 17% with SANG males aging from 3 to 17 days. When competing with SANG males for SANG females, ARwP-M males induced a level of sterility significantly higher than that expected for an equal mating competitiveness (mean Fried index of 1.71 instead of 1). The overall Wolbachia density in ARwP-M females was about 15 fold higher than in ARwP, mostly due to the wMel infection. This feature corresponded to a strongly reduced vector competence for chikungunya and dengue viruses (in both cases, 5 and 0% rates of transmission at 14 and 21 days post infection) with respect to ARwP females. Results regarding Zika virus did not highlight significant differences between ARwP-M and ARwP. However, none of the tested ARwP-M females was capable at transmitting ZIKV. These findings are expected to promote the exploitation of Wolbachia to suppress the wild-type Ae. albopictus populations.

Zika virus outbreak in the Pacific: Vector competence of regional vectors

PLoS Neglected Tropical Diseases News - 17 July 2018 - 9:00pm

by Elodie Calvez, Laurence Mousson, Marie Vazeille, Olivia O’Connor, Van-Mai Cao-Lormeau, Françoise Mathieu-Daudé, Nicolas Pocquet, Anna-Bella Failloux, Myrielle Dupont-Rouzeyrol

Background

In 2013, Zika virus (ZIKV) emerged in French Polynesia and spread through the Pacific region between 2013 and 2017. Several potential Aedes mosquitoes may have contributed to the ZIKV transmission including Aedes aegypti, the main arbovirus vector in the region, and Aedes polynesiensis, vector of lymphatic filariasis and secondary vector of dengue virus. The aim of this study was to analyze the ability of these two Pacific vectors to transmit ZIKV at a regional scale, through the evaluation and comparison of the vector competence of wild Ae. aegypti and Ae. polynesiensis populations from different Pacific islands for a ZIKV strain which circulated in this region during the 2013–2017 outbreak.

Methodology/principal findings

Field Ae. aegypti (three populations) and Ae. polynesiensis (two populations) from the Pacific region were collected for this study. Female mosquitoes were orally exposed to ZIKV (107 TCID50/mL) isolated in the region in 2014. At 6, 9, 14 and 21 days post-infection, mosquito bodies (thorax and abdomen), heads and saliva were analyzed to measure infection, dissemination, transmission rates and transmission efficiency, respectively. According to our results, ZIKV infection rates were heterogeneous between the Ae. aegypti populations, but the dissemination rates were moderate and more homogenous between these populations. For Ae. polynesiensis, infection rates were less heterogeneous between the two populations tested. The transmission rate and efficiency results revealed a low vector competence for ZIKV of the different Aedes vector populations under study.

Conclusion/significance

Our results indicated a low ZIKV transmission by Ae. aegypti and Ae. polynesiensis tested from the Pacific region. These results were unexpected and suggest the importance of other factors especially the vector density, the mosquito lifespan or the large immunologically naive fraction of the population that may have contributed to the rapid spread of the ZIKV in the Pacific region during the 2013–2017 outbreak.

Grade 2 disabilities in leprosy patients from Brazil: Need for follow-up after completion of multidrug therapy

PLoS Neglected Tropical Diseases News - 16 July 2018 - 9:00pm

by Marcos Túlio Raposo, Martha Cerqueira Reis, Ana Virgínia de Queiroz Caminha, Jörg Heukelbach, Lucy Anne Parker, Maria Pastor-Valero, Maria Ines Battistella Nemes

Background

Leprosy continues to be a public health problem in many countries. Difficulties faced by health services include late diagnosis, under-reporting of new cases, adequate monitoring of disabilities and treatment. Furthermore, systematic follow-up after completion of treatment is important, when new disabilities may occur, or existing disabilities may get worse. The objective of the present study was to determine the prevalence of leprosy-associated grade 2 disabilities (G2D) after completion of multidrug therapy (MDT) and to identify factors associated with G2D.

Methods

We performed a cross-sectional study of 222 leprosy cases registered in Vitória da Conquista, Bahia state, Brazil from 2001–2014. We performed a clinical examination of the study participants and collected socio-economic and clinical information by interview. We identified factors associated with grade 2 disability (G2D) using logis tic regression.

Results

In total, 38 (17.1%) participants were diagnosed with G2D, and 106 (47.7%) with grade 1 disabilities (G1D). The following independent factors were significantly associated with G2D: occurrence of leprosy reaction (adjusted OR = 2.5; 95%CI = 1.09–5.77), thickening and/or tenderness of one or more nerve trunks (adjusted OR = 3.0; CI = 1.13–8.01) and unemployment (adjusted OR = 7.17; CI = 2.44–21.07).

Conclusions

This study shows that physical disabilities remain after completion of MDT and frequently occur in an endemic area in Brazil. Finding new ways to reduce the burden of disability are urgently needed, and may include systematic follow-up of patients after treatment completion combined with evidence-based preventative measures.

Study on causes of fever in primary healthcare center uncovers pathogens of public health concern in Madagascar

PLoS Neglected Tropical Diseases News - 16 July 2018 - 9:00pm

by Julia Guillebaud, Barivola Bernardson, Tsiry Hasina Randriambolamanantsoa, Laurence Randrianasolo, Jane Léa Randriamampionona, Cesare Augusto Marino, Voahangy Rasolofo, Milijaona Randrianarivelojosia, Ines Vigan-Womas, Voula Stivaktas, Marietjie Venter, Patrice Piola, Jean-Michel Héraud

Background

The increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases.

Methodology

Consenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status.

Principal findings

A total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections.

Conclusions

These results raise questions about etiologies of fever in Malagasy communities. Nevertheless, we noted that viral infections and malaria still represent a significant proportion of causes of febrile illnesses. Interestingly our study allowed the detection of pathogens of public health interest such as Rift Valley Fever Virus but also the first case of laboratory-confirmed leptospirosis infection in Madagascar.

Heterogeneity of <i>Orientia tsutsugamushi</i> genotypes in field-collected trombiculid mites from wild-caught small mammals in Thailand

PLoS Neglected Tropical Diseases News - 16 July 2018 - 9:00pm

by Ratree Takhampunya, Achareeya Korkusol, Sommai Promsthaporn, Bousaraporn Tippayachai, Surachai Leepitakrat, Allen L. Richards, Silas A. Davidson

Trombiculid mites are the vectors of scrub typhus, with infected larval mites (chiggers) transmitting the causative agent, Orientia tsutsugamushi, during feeding. Co-existence of multiple O. tsutsugamushi strains within infected mites has previously been reported in naturally infected, laboratory-reared mite lines using molecular methods to characterize the 56-kDa type-specific antigen (TSA) gene. In the current study, more advanced next-generation sequencing technology was used to reveal the heterogeneity of O. tsutsugamushi genotypes in field-collected trombiculid mites from rodents and small mammals in scrub typhus-endemic areas of Thailand. Twenty-eight trombiculid mites collected from 10 small mammals were positive for O. tsutsugamushi, corresponding to a prevalence rate of 0.7% within the mite population. Twenty-four of the infected mites were Leptotrombidium spp., indicating that this genus is the main vector for O. tsutsugamushi transmission in Thailand. In addition, O. tsutsugamushi was detected in the mite genera Ascoschoengastia, Blankaartia, Gahrliepia, and Lorillatum. Of the 10 infested small animal hosts, six had 2–10 infected mites feeding at the time of collection. Deep sequencing was used to characterize mixed infections (two to three O. tsutsugamushi genotypes within an individual mite), and 5 of the 28 infected mites (17.9%) contained mixed infections. Additionally, 56-kDa TSA gene sequence analysis revealed identical bacterial genotypes among co-feeding mites with single or mixed infections. These results suggest that co-feeding transmission may occur during the feeding process, and could explain the occurrence of mixed infections in individual mites, as well as the recovery of multiple infected mites from the same host. This study also revealed highly diverse within-host O. tsutsugamushi genotypes. The occurrence of multiple O. tsutsugamushi genotypes within individual mites has important implications, and could provide a mechanism for pathogen evolution/diversification in the mite vector.

Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge

PLoS Neglected Tropical Diseases News - 16 July 2018 - 9:00pm

by Marko Zivcec, David Safronetz, Dana P. Scott, Shelly Robertson, Heinz Feldmann

Crimean-Congo hemorrhagic fever (CCHF) is an acute, often fatal viral disease characterized by rapid onset of febrile symptoms followed by hemorrhagic manifestations. The etiologic agent, CCHF orthonairovirus (CCHFV), can infect several mammals in nature but only seems to cause clinical disease in humans. Over the past two decades there has been an increase in total number of CCHF case reports, including imported CCHF patients, and an expansion of CCHF endemic areas. Despite its increased public health burden there are currently no licensed vaccines or treatments to prevent CCHF. We here report the development and assessment of the protective efficacy of an adenovirus (Ad)-based vaccine expressing the nucleocapsid protein (N) of CCHFV (Ad-N) in a lethal immunocompromised mouse model of CCHF. The results show that Ad-N can protect mice from CCHF mortality and that this platform should be considered for future CCHFV vaccine strategies. Article summary line: We have developed and evaluated the protective efficacy of an adenovirus based vaccine using a lethal mouse model of Crimean-Congo hemorrhagic fever.

Dengue infection in India: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 16 July 2018 - 9:00pm

by Parasuraman Ganeshkumar, Manoj V. Murhekar, Veeraraghavadoss Poornima, Velusamy Saravanakumar, Krishnendu Sukumaran, Anandan Anandaselvasankar, Denny John, Sanjay M. Mehendale

Introduction

Dengue is the most extensively spread mosquito-borne disease; endemic in more than 100 countries. Information about dengue disease burden, its prevalence, incidence and geographic distribution is critical in planning appropriate control measures against dengue fever. We conducted a systematic review and meta-analysis of dengue fever in India

Methods

We searched for studies published until 2017 reporting the incidence, the prevalence or case fatality of dengue in India. Our primary outcomes were (a) prevalence of laboratory confirmed dengue infection among clinically suspected patients, (b) seroprevalence in the general population and (c) case fatality ratio among laboratory confirmed dengue patients. We used binomial–normal mixed effects regression model to estimate the pooled proportion of dengue infections. Forest plots were used to display pooled estimates. The metafor package of R software was used to conduct meta-analysis.

Results

Of the 2285 identified articles on dengue, we included 233 in the analysis wherein 180 reported prevalence of laboratory confirmed dengue infection, seven reported seroprevalence as evidenced by IgG or neutralizing antibodies against dengue and 77 reported case fatality. The overall estimate of the prevalence of laboratory confirmed dengue infection among clinically suspected patients was 38.3% (95% CI: 34.8%–41.8%). The pooled estimate of dengue seroprevalence in the general population and CFR among laboratory confirmed patients was 56.9% (95% CI: 37.5–74.4) and 2.6% (95% CI: 2–3.4) respectively. There was significant heterogeneity in reported outcomes (p-values<0.001).

Conclusions

Identified gaps in the understanding of dengue epidemiology in India emphasize the need to initiate community-based cohort studies representing different geographic regions to generate reliable estimates of age-specific incidence of dengue and studies to generate dengue seroprevalence data in the country.

Evidence of vertical transmission of Zika virus in field-collected eggs of <i>Aedes aegypti</i> in the Brazilian Amazon

PLoS Neglected Tropical Diseases News - 16 July 2018 - 9:00pm

by Cristiano Fernandes da Costa, Arlesson Viana da Silva, Valdinete Alves do Nascimento, Victor Costa de Souza, Dana Cristina da Silva Monteiro, Wagner Cosme Morhy Terrazas, Ricardo Augusto dos Passos, Suzete Nascimento, José Bento Pereira Lima, Felipe Gomes Naveca

Background

Arboviruses are viruses transmitted to humans and other animals by the bite of hematophagous arthropods. Infections caused by chikungunya virus (CHIKV), dengue virus (DENV), Zika virus (ZIKV), and the deadlier yellow fever virus (YFV) are current public health problems in several countries, mainly those located in tropical and subtropical regions. One of the main prevention strategies continues to be vector control, with the elimination of breeding sites and surveillance of infested areas. The use of ovitraps for Aedes mosquitos monitoring has already demonstrated promising results, and maybe be also useful for arboviral surveillance.

Methods

This work aimed to detect natural vertical transmission of arboviruses in Aedes aegypti and Aedes albopictus. Mosquito egg collection was carried out using ovitraps in Itacoatiara, a mid-size city in Amazonas state, Brazil. Collected eggs were allowed to hatch and larvae were tested for CHIKV, DENV, and ZIKV RNA by RT-qPCR.

Results

A total of 2,057 specimens (1,793 Ae. aegypti and 264 Ae. albopictus), in 154 larvae pools were processed. Results showed one positive pool for CHIKV and one positive pool for ZIKV. The active ZIKV infection was further confirmed by the detection of the negative-strand viral RNA and nucleotide sequencing which confirmed the Asian genotype. The Infection Rate per 1,000 mosquitoes tested was assessed by Maximum Likelihood Estimation (MLE) with 0.45 and 0.44 for CHIKV and ZIKV, respectively, and by Minimum Infection Rate (MIR) with 0.45 for both viruses.

Conclusion

To our knowledge, this is the first detection of ZIKV in natural vertical transmission in the Ae. aegypti, a fact that may contribute to ZIKV maintenance in nature during epidemics periods. Furthermore, our results highlight that the use of ovitraps and the molecular detection of arbovirus may contribute to health surveillance, directing the efforts to more efficient transmission blockade.

Identifying residual transmission of lymphatic filariasis after mass drug administration: Comparing school-based versus community-based surveillance - American Samoa, 2016

PLoS Neglected Tropical Diseases News - 16 July 2018 - 9:00pm

by Meru Sheel, Sarah Sheridan, Katherine Gass, Kimberly Won, Saipale Fuimaono, Martyn Kirk, Amor Gonzales, Shannon M. Hedtke, Patricia M. Graves, Colleen L. Lau

Introduction

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration (MDA) from 2000–2006. The World Health Organization recommends systematic post-MDA surveillance using Transmission Assessment Surveys (TAS) for epidemiological assessment of recent LF transmission. We compared the effectiveness of two survey designs for post-MDA surveillance: a school-based survey of children aged 6–7 years, and a community-based survey targeting people aged ≥8 years.

Methods

In 2016, we conducted a systematic school-based TAS in all elementary schools (N = 29) and a cluster survey in 28 villages on the two main islands of American Samoa. We collected information on demographics and risk factors for infection using electronic questionnaires, and recorded geo-locations of schools and households. Blood samples were collected to test for circulating filarial antigen (CFA) using the Alere Filariasis Test Strip. For those who tested positive, we prepared slides for microscopic examination of microfilaria and provided treatment. Descriptive statistics were performed for questionnaire variables. Data were weighted and adjusted to account for sampling design and sex for both surveys, and for age in the community survey.

Results

The school-based TAS (n = 1143) identified nine antigen-positive children and found an overall adjusted CFA prevalence of 0.7% (95% CI: 0.3–1.8). Of the nine positive children, we identified one microfilariaemic 7-year-old child. The community-based survey (n = 2507, 711 households) identified 102 antigen-positive people, and estimated an overall adjusted CFA prevalence of 6.2% (95% CI: 4.5–8.6). Adjusted village-level prevalence ranged from 0–47.1%. CFA prevalence increased with age and was higher in males. Of 86 antigen-positive community members from whom slides were prepared, 22 (25.6%) were microfilaraemic. School-based TAS had limited sensitivity (range 0–23.8%) and negative predictive value (range 25–83.3%) but had high specificity (range 83.3–100%) and positive predictive value (range 0–100%) for identifying villages with ongoing transmission.

Conclusions

American Samoa failed the school-based TAS in 2016, and the community-based survey identified higher than expected numbers of antigen-positive people. School-based TAS was logistically simpler and enabled sampling of a larger proportion of the target population, but the results did not provide a good indication of the overall CFA prevalence in older age groups and was not sensitive at identifying foci of ongoing transmission. The community-based survey, although operationally more challenging, identified antigen-positive individuals of all ages, and foci of high antigen prevalence. Both surveys confirmed recrudescence of LF transmission.

Current challenges and implications for dengue, chikungunya and Zika seroprevalence studies worldwide: A scoping review

PLoS Neglected Tropical Diseases News - 16 July 2018 - 9:00pm

by Camille Fritzell, Dominique Rousset, Antoine Adde, Mirdad Kazanji, Maria D. Van Kerkhove, Claude Flamand

Background

Arboviral infections are a public health concern and an escalating problem worldwide. Estimating the burden of these diseases represents a major challenge that is complicated by the large number of unapparent infections, especially those of dengue fever. Serological surveys are thus required to identify the distribution of these diseases and measure their impact. Therefore, we undertook a scoping review of the literature to describe and summarize epidemiological practices, findings and insights related to seroprevalence studies of dengue, chikungunya and Zika virus, which have rapidly expanded across the globe in recent years.

Methodology/Principal findings

Relevant studies were retrieved through a literature search of MEDLINE, WHOLIS, Lilacs, SciELO and Scopus (2000 to 2018). In total, 1389 publications were identified. Studies addressing the seroprevalence of dengue, chikungunya and/or Zika written in English or French and meeting the inclusion and exclusion criteria were included. In total, 147 studies were included, from which 185 data points were retrieved, as some studies used several different samples. Most of the studies were exclusively conducted on dengue (66.5%), but 16% were exclusively conducted on chikungunya, and 7 were exclusively conducted on Zika; the remainder were conducted on multiple arboviruses. A wide range of designs were applied, but most studies were conducted in the general population (39%) and in households (41%). Although several assays were used, enzyme-linked immunosorbent assays (ELISAs) were the predominant test used (77%). The temporal distribution of chikungunya studies followed the virus during its rapid expansion since 2004. The results revealed heterogeneity of arboviruses seroprevalence between continents and within a given country for dengue, chikungunya and Zika viruses, ranging from 0 to 100%, 76% and 73% respectively.

Conclusions/Significance

Serological surveys provide the most direct measurement for defining the immunity landscape for infectious diseases, but the methodology remains difficult to implement. Overall, dengue, chikungunya and Zika serosurveys followed the expansion of these arboviruses, but there remain gaps in their geographic distribution. This review addresses the challenges for researchers regarding study design biases. Moreover, the development of reliable, rapid and affordable diagnosis tools represents a significant issue concerning the ability of seroprevalence surveys to differentiate infections when multiple viruses co-circulate.

Nitrosporeusine analogue ameliorates Chandipura virus induced inflammatory response in CNS via NFκb inactivation in microglia

PLoS Neglected Tropical Diseases News - 12 July 2018 - 9:00pm

by Abhishek Kumar Verma, Trushnal S. Waghmare, Gorakhnath R. Jachak, Satish Chandra Philkhana, D. Srinivas Reddy, Anirban Basu

Chandipura Virus (CHPV), a negative-stranded RNA virus belonging to the Rhabdoviridae family, has been previously reported to bring neuronal apoptosis by activating several factors leading to neurodegeneration. Following virus infection of the central nervous system, microglia, the ontogenetic and functional equivalents of macrophages in somatic tissues gets activated and starts secreting chemokines, thereby recruiting peripheral leukocytes into the brain parenchyma. In the present study, we have systemically examined the effect of CHPV on microglia and the activation of cellular signalling pathways leading to chemokine expression upon CHPV infection. Protein and mRNA expression profiles of chemokine genes revealed that CHPV infection strongly induces the expression of CXC chemokine ligand 10 (CXCL10) and CC chemokine ligand 5 (CCL5) in microglia. CHPV infection triggered the activation of signalling pathways mediated by mitogen-activated protein kinases, including p38, JNK 1 and 2, and nuclear factor κB (NF-kappaB). CHPV-induced expression of CXCL10 and CCL5 was achieved by the activation of p38 and NF-kappaB pathways. Considering the important role of inflammation in neurodegeneration, we have targeted NF-kappaB using a newly synthesised natural product nitrosporeusine analogue and showed incapability of microglial supernatant of inducing apoptosis in neurons after treatment.

Clinical, environmental, and behavioral characteristics associated with <i>Cryptosporidium</i> infection among children with moderate-to-severe diarrhea in rural western Kenya, 2008–2012: The Global Enteric Multicenter Study (GEMS)

PLoS Neglected Tropical Diseases News - 12 July 2018 - 9:00pm

by Miranda J. Delahoy, Richard Omore, Tracy L. Ayers, Katharine A. Schilling, Anna J. Blackstock, J. Benjamin Ochieng, Feny Moke, Peter Jaron, Alex Awuor, Caleb Okonji, Jane Juma, Tamer H. Farag, Dilruba Nasrin, Sandra Panchalingam, James P. Nataro, Karen L. Kotloff, Myron M. Levine, Joseph Oundo, Dawn M. Roellig, Lihua Xiao, Michele B. Parsons, Kayla Laserson, Eric D. Mintz, Robert F. Breiman, Ciara E. O'Reilly

Background

Cryptosporidium is a leading cause of moderate-to-severe diarrhea (MSD) in young children in Africa. We examined factors associated with Cryptosporidium infection in MSD cases enrolled at the rural western Kenya Global Enteric Multicenter Study (GEMS) site from 2008-2012.

Methodology/Principal findings

At health facility enrollment, stool samples were tested for enteric pathogens and data on clinical, environmental, and behavioral characteristics collected. Each child’s health status was recorded at 60-day follow-up. Data were analyzed using logistic regression. Of the 1,778 children with MSD enrolled as cases in the GEMS-Kenya case-control study, 11% had Cryptosporidium detected in stool by enzyme immunoassay; in a genotyped subset, 81% were C. hominis. Among MSD cases, being an infant, having mucus in stool, and having prolonged/persistent duration diarrhea were associated with being Cryptosporidium-positive. Both boiling drinking water and using rainwater as the main drinking water source were protective factors for being Cryptosporidium-positive. At follow-up, Cryptosporidium-positive cases had increased odds of being stunted (adjusted odds ratio [aOR] = 1.65, 95% CI: 1.06–2.57), underweight (aOR = 2.08, 95% CI: 1.34–3.22), or wasted (aOR = 2.04, 95% CI: 1.21–3.43), and had significantly larger negative changes in height- and weight-for-age z-scores from enrollment.

Conclusions/Significance

Cryptosporidium contributes significantly to diarrheal illness in young children in western Kenya. Advances in point of care detection, prevention/control approaches, effective water treatment technologies, and clinical management options for children with cryptosporidiosis are needed.

Development of NanoLuc-PEST expressing <i>Leishmania mexicana</i> as a new drug discovery tool for axenic- and intramacrophage-based assays

PLoS Neglected Tropical Diseases News - 12 July 2018 - 9:00pm

by Sarah L. Berry, Hamza Hameed, Anna Thomason, Marissa L. Maciej-Hulme, Somaia Saif Abou-Akkada, Paul Horrocks, Helen P. Price

The protozoan parasite Leishmania causes leishmaniasis; a spectrum of diseases of which there are an estimated 1 million new cases each year. Current treatments are toxic, expensive, difficult to administer, and resistance to them is emerging. New therapeutics are urgently needed, however, screening the infective amastigote form of the parasite is challenging. Only certain species can be differentiated into axenic amastigotes, and compound activity against these does not always correlate with efficacy against the parasite in its intracellular niche. Methods used to assess compound efficacy on intracellular amastigotes often rely on microscopy-based assays. These are laborious, require specialist equipment and can only determine parasite burden, not parasite viability. We have addressed this clear need in the anti-leishmanial drug discovery process by producing a transgenic L. mexicana cell line that expresses the luciferase NanoLuc-PEST. We tested the sensitivity and versatility of this transgenic strain, in comparison with strains expressing NanoLuc and the red-shifted firefly luciferase. We then compared the NanoLuc-PEST luciferase to the current methods in both axenic and intramacrophage amastigotes following treatment with a supralethal dose of Amphotericin B. NanoLuc-PEST was a more dynamic indicator of cell viability due to its high turnover rate and high signal:background ratio. This, coupled with its sensitivity in the intramacrophage assay, led us to validate the NanoLuc-PEST expressing cell line using the MMV Pathogen Box in a two-step process: i) identify hits against axenic amastigotes, ii) screen these hits using our bioluminescence-based intramacrophage assay. The data obtained from this highlights the potential of compounds active against M. tuberculosis to be re-purposed for use against Leishmania. Our transgenic L. mexicana cell line is therefore a highly sensitive and dynamic system suitable for Leishmania drug discovery in axenic and intramacrophage amastigote models.

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