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Bacterial community composition in the salivary glands of triatomines (Hemiptera: Reduviidae)

PLoS Neglected Tropical Diseases News - 13 September 2018 - 9:00pm

by Michele Souza Lima, Marinella Silva Laport, Elias Seixas Lorosa, José Jurberg, Kátia Regina Netto dos Santos, Mário Alberto Cardoso da Silva Neto, Caio Tavora Coelho da Costa Rachid, Georgia Correa Atella

Background

Chagas disease is caused by the parasite Trypanosoma cruzi and is transmitted through triatomines (Hemiptera: Reduviidae). In the last year, many studies of triatomine gut microbiota have outlined its potential role in modulating vector competence. However, little is known about the microbiota present in the salivary glands of triatomines. Bacterial composition of salivary glands in selected triatomine species was investigated, as well as environmental influences on the acquisition of bacterial communities.

Methodology/Principal findings

The diversity of the bacterial communities of 30 pairs of salivary glands of triatomines was studied by sequencing of the V1- V3 variable region of the 16S rRNA using the MiSeq platform (Illumina), and bacteria isolated from skin of three vertebrate hosts were identified based on 16S rRNA gene sequence analysis (targeting the V3–V5 region). In a comparative analysis of microbiota in the salivary glands of triatomine species, operational taxonomic units belonging to Arsenophonous appeared as dominant in Triatoma spp (74% of the total 16S coverage), while these units belonging to unclassified Enterobacteriaceae were dominant in the Rhodnius spp (57% of the total 16S coverage). Some intraspecific changes in the composition of the triatomine microbiota were observed, suggesting that some bacteria may have been acquired from the environment.

Conclusions and significance

Our study revealed the presence of a low-diversity microbiota associated to the salivary glands of the evaluated triatomines. The predominant bacteria genera are associated with triatomine genera and the bacteria can be acquired in the environment in which the insects reside. Further studies are necessary to determine the influence of bacterial communities on vector competence.

Isolation of pathogenic <i>Leptospira</i> strains from naturally infected cattle in Uruguay reveals high serovar diversity, and uncovers a relevant risk for human leptospirosis

PLoS Neglected Tropical Diseases News - 13 September 2018 - 9:00pm

by Leticia Zarantonelli, Alejandra Suanes, Paulina Meny, Florencia Buroni, Cecilia Nieves, Ximena Salaberry, Carolina Briano, Natalia Ashfield, Caroline Da Silva Silveira, Fernando Dutra, Cristina Easton, Martin Fraga, Federico Giannitti, Camila Hamond, Melissa Macías-Rioseco, Clara Menéndez, Alberto Mortola, Mathieu Picardeau, Jair Quintero, Cristina Ríos, Víctor Rodríguez, Agustín Romero, Gustavo Varela, Rodolfo Rivero, Felipe Schelotto, Franklin Riet-Correa, Alejandro Buschiazzo, on behalf of the Grupo de Trabajo Interinstitucional de Leptospirosis Consortium

Leptospirosis is a neglected zoonosis with worldwide distribution. The causative agents are spirochete bacteria of the Leptospira genus, displaying huge diversity of serovars, the identity of which is critical for effective diagnosis and vaccination purposes. Among many other mammalian species, Leptospira infects cattle, eliciting acute signs in calves, and chronic disease in adult animals often leading to abortions. In South America, and including in Uruguay, beef and dairy export are leading sources of national income. Despite the importance of bovine health, food safety, and bovine-related dissemination of leptospirosis to humans, extremely limited information is available as to the identity of Leptospira species and serovars infecting cattle in Uruguay and the South American subcontinent. Here we report a multicentric 3-year study resulting in the isolation and detailed characterization of 40 strains of Leptospira spp. obtained from infected cattle. Combined serologic and molecular typing identified these isolates as L. interrogans serogroup Pomona serovar Kennewicki (20 strains), L. interrogans serogroup Canicola serovar Canicola (1 strain), L. borgpetersenii serogroup Sejroe serovar Hardjo (10 strains) and L. noguchii (9 strains). The latter showed remarkable phenotypic and genetic variability, belonging to 6 distinct serogroups, including 3 that did not react with a large panel of reference serogrouping antisera. Approximately 20% of cattle sampled in the field were found to be shedding pathogenic Leptospira in their urine, uncovering a threat for public health that is being largely neglected. The two L. interrogans serovars that we isolated from cattle displayed identical genetic signatures to those of human isolates that had previously been obtained from leptospirosis patients. This report of local Leptospira strains shall improve diagnostic tools and the understanding of leptospirosis epidemiology in South America. These strains could also be used as new components within bacterin vaccines to protect against the pathogenic Leptospira strains that are actually circulating, a direct measure to reduce the risk of human leptospirosis.

Misconceptions and paradoxes in soil-transmitted helminthiases control as a public health problem

PLoS Neglected Tropical Diseases News - 13 September 2018 - 9:00pm

by Alejandro J. Krolewiecki

Soil-transmitted helminthiases (STHs) constitute a public health problem that requires immediate action to resolve the morbidity of those harboring the parasites in their guts, to prevent infection in all those at risk, and to interrupt the vicious circle of poverty and disease in the affected communities, structural poverty being the main determinant of this group of infectious diseases. Since the times of the Rockefeller initiatives over a hundred years ago, the strategy has been viewed as one requiring community-wide efforts rather than pure individual case management. The World Health Organization (WHO) and its regional offices, as the governing institutions endorsed by the countries and their governments, have been the leaders in stating the actual executive measures to reach the goals and endpoints for the management of the problem. With the task of setting a group of activities that could be launched, monitored, and measured, these actions were established with the available resources since this public health problem had to be launched immediately, resources were those available at the moment and not those appearing on a wish list. Considerable progress has been made in the establishment of policies for the achievement of the Millennium Development Goals (MDGs), later followed by the Sustainable Development Goals (SDGs) through WHO-lead actions for the control of neglected tropical diseases (NTDs). With an initial goal of morbidity control, there are already discussions and proposals for elimination of STH if support is sustained and empiric facts confirm data emerging from modeling and small-scale studies. The aim of these comments is to describe and question instances of currently accepted concepts, theories, and practices that conform to the dogmatic status quo that serves as the foundation on top of which the new elimination aspirations are supposed to be built on, which might not be serving the desired purpose if taken unrevised.

Innovative digital technologies for quality assurance of diagnosis of human African trypanosomiasis

PLoS Neglected Tropical Diseases News - 13 September 2018 - 9:00pm

by Epco Hasker, Jean Kwete, Raquel Inocencio da Luz, Alain Mpanya, Nicolas Bebronne, Jacquies Makabuza, Yves Claeys, Jérémie Ilunga, Veerle Lejon, Dieudonné Mumba Ngoyi, Philippe Büscher, Marleen Boelaert, Erick Mwamba Miaka

Isometamidium chloride and homidium chloride fail to cure mice infected with Ethiopian <i>Trypanosoma evansi</i> type A and B

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

by Gebrekrustos Mekonnen, Elmi Fahiye Mohammed, Weldu Kidane, Awol Nesibu, Hagos Yohannes, Nick Van Reet, Philippe Büscher, Hadush Birhanu

Background

Trypanosoma evansi is mechanically transmitted by biting flies and affects camels, equines, and other domestic and wild animals in which it causes a disease called surra. At least two types of Trypanosoma evansi circulate in Ethiopia: type A, which is present in Africa, Latin America and Asia, and type B, which is prevalent in Eastern Africa. Currently, no information is available about the drug sensitivity of any Ethiopian T. evansi type.

Methodology/principal findings

This study was conducted with the objective of determining the in vivo drug sensitivity of two T. evansi type A and two type B stocks that were isolated from camels from the Tigray and Afar regions of Northern Ethiopia. We investigated the efficacy of four trypanocidal drugs to cure T. evansi infected mice: melarsamine hydrochloride (Cymelarsan), diminazene diaceturate (Veriben and Sequzene), isometamidium chloride (Veridium) and homidium chloride (Bovidium). Per experimental group, 6 mice were inoculated intraperitoneally with trypanosomes, treated at first peak parasitemia by daily drug injections for 4 consecutive days and followed-up for 60 days. Cymelarsan at 2 mg/kg and Veriben at 20 mg/kg cured all mice infected with any T. evansi stock, while Sequzene at 20 mg/kg caused relapses in all T. evansi stocks. In contrast, Veridium and Bovidium at 1 mg/kg failed to cure any T. evansi infection in mice.

Conclusions/significance

We conclude that mice infected with Ethiopian T. evansi can be cured with Cymelarsan and Veriben regardless of T. evansi type. In contrast, Veridium and Bovidium are not efficacious to cure any T. evansi type. Although innate resistance to phenanthridines was previously described for T. evansi type A, this report is the first study to show that this phenomenom also occurs in T. evansi type B infections.

Implementing active community-based surveillance-response system for Buruli ulcer early case detection and management in Ghana

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

by Collins S. K. Ahorlu, Daniel Okyere, Edwin Ampadu

Background

Buruli Ulcer (BU) is one of the most neglected debilitating tropical diseases caused by Mycobacterium ulcerans, which causes considerable morbidity and disability. Building on earlier findings that community-based interventions could enhance case detection and reduce treatment dropout and defaulter rates, we established an active surveillance-response system in an endemic sub-district in the Ga West municipality of Ghana to enhance early case detection, diagnosis and treatment to reduce or eliminate severe ulcers and its related disabilities.

Methods

We established surveillance response system, implemented in collaboration with the sub-district disease control officers, selected clinical staff and trained community-based volunteers. The active community-based surveillance- response system was implemented for 12 months. Also, pre and post intervention surveys were conducted to document any change in perceptions on BU in the study population over the period. The baseline and endline surveys were conducted in August 2016 and August 2017 respectively.

Results

On average, each person was seen 11 times in 12 months. In all 75 skin lesions were detected during surveillance rounds, out of which 17 were suspected to be BU and 12 out of the 17 were confirmed as BU using Polymerase chain reaction (PCR). Out of the 12, five, three and four were categories I, II and III lesions respectively. Physical examination was done on 94% of the people seen during the surveillance rounds. Knowledge on BU has also increased in the communities at the end of the study.

Conclusion

The findings from this study have demonstrated that it is possible to establish surveillance-response system for BU and by extension, other neglected tropical diseases to enhance control and elimination efforts through the use of community-based volunteers.

Contact tracing performance during the Ebola epidemic in Liberia, 2014-2015

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

by Krista C. Swanson, Chiara Altare, Chea Sanford Wesseh, Tolbert Nyenswah, Tashrik Ahmed, Nir Eyal, Esther L. Hamblion, Justin Lessler, David H. Peters, Mathias Altmann

Background

During the Ebola virus disease (EVD) epidemic in Liberia, contact tracing was implemented to rapidly detect new cases and prevent further transmission. We describe the scope and characteristics of contact tracing in Liberia and assess its performance during the 2014–2015 EVD epidemic.

Methodology/Principal findings

We performed a retrospective descriptive analysis of data collection forms for contact tracing conducted in six counties during June 2014–July 2015. EVD case counts from situation reports in the same counties were used to assess contact tracing coverage and sensitivity. Contacts who presented with symptoms and/or died, and monitoring was stopped, were classified as “potential cases”. Positive predictive value (PPV) was defined as the proportion of traced contacts who were identified as potential cases. Bivariate and multivariate logistic regression models were used to identify characteristics among potential cases.We analyzed 25,830 contact tracing records for contacts who had monitoring initiated or were last exposed between June 4, 2014 and July 13, 2015. Contact tracing was initiated for 26.7% of total EVD cases and detected 3.6% of all new cases during this period. Eighty-eight percent of contacts completed monitoring, and 334 contacts were identified as potential cases (PPV = 1.4%). Potential cases were more likely to be detected early in the outbreak; hail from rural areas; report multiple exposures and symptoms; have household contact or direct bodily or fluid contact; and report nausea, fever, or weakness compared to contacts who completed monitoring.

Conclusions/Significance

Contact tracing was a critical intervention in Liberia and represented one of the largest contact tracing efforts during an epidemic in history. While there were notable improvements in implementation over time, these data suggest there were limitations to its performance—particularly in urban districts and during peak transmission. Recommendations for improving performance include integrated surveillance, decentralized management of multidisciplinary teams, comprehensive protocols, and community-led strategies.

Distribution and breeding sites of <i>Aedes aegypti</i> and <i>Aedes albopictus</i> in 32 urban/peri-urban districts of Mozambique: implication for assessing the risk of arbovirus outbreaks

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

by Ana Paula Abílio, Gastão Abudasse, Ayubo Kampango, Baltazar Candrinho, Salomão Sitoi, Jacinta Luciano, Dário Tembisse, Samira Sibindy, António Paulo Gouveia de Almeida, Gabriela Azambuja Garcia, Mariana Rocha David, Rafael Maciel-de-Freitas, Eduardo Samo Gudo

Background

Aedes-borne arboviruses have emerged as an important public health problem worldwide and, in Mozambique, the number of cases and its geographical spread have been growing. However, information on the occurrence, distribution and ecology of Aedes aegypti and Ae. albopictus mosquitoes remain poorly known in the country.

Methods

Between March and April 2016, a cross-sectional study was conducted in 32 districts in Mozambique to determine the distribution and breeding sites of Ae. aegypti and Ae. albopictus. Larvae and pupae were collected from a total of 2,807 water-holding containers using pipette, dipper, funnel and sweeping procedures, depending on the container type and location. Both outdoor and indoor water-holding containers were inspected. The immature forms were reared to adults and the identifications of the mosquito species was carried out with a stereomicroscope using a taxonomic key.

Results

Aedes aegypti was found in every district sampled, while Ae. albopictus was only found in Moatize district, situated in Tete Province in the central part of the country. Six hundred and twenty-eight of 2,807 (22.4%) containers were positive for Ae. aegypti but only one (0.03%) was positive for Ae. albopictus. The Container Index (CI) of Aedes was highest in densely populated suburban areas of the central region (260/604; 43.0%), followed by suburban areas in northern areas (228/617; 36.9%) whilst the lowest proportion was found in urbanized southern areas (140/1586; 8.8%). The highest CI of Aedes was found in used tires (448/1268; 35.3%), cement tanks (20/62; 32.3%) and drums (21/95; 22.1%).

Conclusion

Data from our study showed that Ae. aegypti is present nation-wide, since it occurred in every sampled district, whilst Ae. albopictus had a limited distribution. Therefore, the risk of transmission of dengue and chikungunya is likely to have been underestimated in Mozambique. This study highlights the need for the establishment of a national entomological surveillance program for Aedes spp. in Mozambique in order to gain a better understanding about vector bionomics and to support the development of informed effective vector control strategies.

Tick-borne zoonoses in the Order Rickettsiales and Legionellales in Iran: A systematic review

PLoS Neglected Tropical Diseases News - 11 September 2018 - 9:00pm

by Faham Khamesipour, Gabriel O. Dida, Douglas N. Anyona, Mostafa Razavi, Ehsan Rakhshandehroo

Background

Tick-borne zoonoses in the Order Rickettsiales and Legionellales cause infections that often manifest as undifferentiated fevers that are not easy to distinguish from other causes of acute febrile illnesses clinically. This is partly attributed to difficulty in laboratory confirmation since convalescent sera, specific diagnostic reagents, and the required expertise may not be readily available. As a result, a number of tick-borne zoonoses are underappreciated resulting in unnecessary morbidity, mortality and huge economic loses. In Iran, a significant proportion of human infectious diseases are tick-borne, with anecdotal evidence suggesting that tick-borne zoonoses are widespread but underreported in the country. Epidemiological review is therefore necessary to aid in the effective control and prevention of tick-borne zonooses in Iran. The aim of this review is to provide an in-depth and comprehensive overview of anaplasmosis, ehrlichiosis, spotted fever group rickettsioses and coxiellosis in Iran.

Methods

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, all relevant publications on tick-borne zoonoses in the Order Rickettsiales and Legionellales in Iran were searched using a number of search terms. The search was confined to authentic resources from repositories of popular data bases among them PubMed, Web of Science, Google Scholar, Science Direct, SpringerLink and SCOPUS. The search items included peer reviewed journals, books and book chapters published between 1996 and 2017.

Results

A total of 1 205 scientific publications and reports were sourced, of which 63 met the search criteria and were reviewed. Of the 63 articles reviewed, 36 (57.1%) reported on coxiellosis, 15 (23.8%) on anaplasmosis, 11 (17.5%) on ehrlichiosis and 1(1.6%) on spotted fever group rickettsiae in a large scale study involving four countries, among them Iran. The existence of tick-borne pathogens in the Order Rickettsiales and Legionellales was confirmed by molecular, serological and microscopic techniques conducted on samples obtained from sheep, cattle, goats, camels, poultry, animal products (milk and eggs), dogs, ticks and even human subjects in different parts of the country; pointing to a countrywide distribution.

Discussion

Based on the review, coxiellosis, anaplasmosis, ehrlichiosis, and SFG rickettsiae can be categorized as emerging tick-borne zoonotic diseases in Iran given the presence of their causiative agents (C. burnetii, A. phagocytophilum, A. marginale, A. bovis, A. ovis, A. central, E. canis, E. ewingii, E. chaffeensis and R. conorii) collectively reported in a variety of domestic animals, animal products, arthropods and human beings drawn from 22 provinces in Iran.

Conclusion

Given the asymptomatic nature of some of these zoonoses, there is a high likelihood of silent transmission to humans in many parts of the country, which should be considered a public health concern. Presently, information on the transmission intensity of tick-borne zoonoses caused by pathogens in the Order Rickettsiales and Legionellales to humans and its public health impact in Iran is scanty.

Comparison of individual and pooled diagnostic examination strategies during the national mapping of soil-transmitted helminths and <i>Schistosoma mansoni</i> in Ethiopia

PLoS Neglected Tropical Diseases News - 10 September 2018 - 9:00pm

by Gemechu Tadesse Leta, Mike French, Pierre Dorny, Jozef Vercruysse, Bruno Levecke

Background

Laboratory-based studies have highlighted that pooling stool and urine samples can reduce costs and diagnostic burden without a negative impact on the ability to estimate the intensity of soil-transmitted helminth (STH, Ascaris lumbricoides, Trichuris trichiura and hookworms) and schistosome infections (Schistosoma mansoni and S. haematobium). In this study, we compare individual and pooled stool examination strategies in a programmatic setting.

Methods

Stool samples were collected from 2,650 children in 53 primary schools in Amhara Regional State, Ethiopia, during the national mapping of STHs and schistosome infections. Eggs of STHs and S. mansoni were quantified in both individual and pooled samples (pools were made from 10 individual samples) using a single Kato-Katz smear.

Principal findings

A pooled diagnostic examination strategy provided comparable estimates of infection intensity with higher fecal egg count (expressed in eggs per gram of stool (EPG)) than those based on individual strategy (Ascaris: 45.1 EPG vs. 93.9, p = 0.03; Trichuris: 1.8 EPG vs. 2.1 EPG, p = 0.95; hookworms: 17.5 EPG vs. 28.5 EPG, p = 0.18; S. mansoni: 1.6 EPG vs. 3.4 EPG, p = 0.02), but had lower sensitivity (Ascaris: 90.0% vs. 55.0%; Trichuris: 91.7% vs. 16.7%; hookworms: 92.6% vs. 61.8%; S. mansoni: 100% vs. 51.7%, p < 0.001). A pooled approach resulted in a ~70% reduction in time required for sample testing, but reduced total operational costs by only ~11%.

Conclusions/Significance

A pooled approach holds promise for the rapid assessment of intensity of helminth infections in a programmatic setting, but it is not major cost-saving strategy. Further investigation is required to determine when and how pooling can be utilized. Such work should also include validation of statistical methods to estimate prevalence based on pooling samples. Finally, the comparison of operational costs across different scenarios of national program management will help determine whether pooling is indeed worthwhile considering.

Feasibility and initial outcomes of a multifaceted prevention programme of melioidosis in diabetic patients in Ubon Ratchathani, northeast Thailand

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

by Pornpan Suntornsut, Wipada Chaowagul, Wilasinee Thongklang, Thidarat Phosri, Nicholas P. J. Day, Susan Michie, Direk Limmathurotsakul

Background

Melioidosis is an infection caused by Burkholderia pseudomallei, a Gram-negative bacillus found in soil and water. Diabetes mellitus is the most important risk factor for melioidosis. The recommendations for disease prevention include avoiding direct contact with soil and water, and drinking only boiled or bottled water.

Methods

A prospective intervention study was conducted to evaluate the feasibility and behavioural outcomes of a multifaceted prevention programme for melioidosis. Participants were diabetic adults in Ubon Ratchathani, northeast Thailand. Ten behavioural support groups consisting of 6 to 10 participants per group were conducted. Twelve behaviour change techniques were used: information about health consequences, credible source, adding objects to the environment, reconstructing the physical environment, instruction on how to perform a behaviour, demonstration of the behaviour, commitment, prompts/cues, self-monitoring of behaviour, goal setting, feedback on behaviour, and social support, and their feasibilities evaluated.

Results

There were 70 participants, of median age 59 years and 52 (74%) were female. Participants found the intervention beneficial, interesting and engaging. Participants indicated that they liked to watch videos with information about melioidosis delivered by local doctors and patients who survived melioidosis, and videos showing use of over-the-knee boots by local farmers. Participants felt engaged in the sessions that trialed protective gear and that made calendars with individual photographs and self-pledges as a reminder tool. The proportions of participants reporting that they always wore boots while working in rice fields increased from 30% (10/33) to 77% (28/37, p = 0.04), and that they drank only boiled or bottle water increased from 43% (30/70) to 86% (59/69, p<0.001) at 6 months post intervention.

Conclusion

The programme is highly acceptable to participants, and can support behaviour change. Policy makers should consider implementing the programme in areas where melioidosis is endemic. Making calendars with individual photographs and self-pledges as a reminder tool could be powerful in behaviour change interventions, and further research on this component is needed.

Typhoid fever in Santiago, Chile: Insights from a mathematical model utilizing venerable archived data from a successful disease control program

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

by Jillian S. Gauld, Hao Hu, Daniel Klein, Myron M. Levine

Typhoid fever is endemic in many developing countries. In the early 20th century, newly industrializing countries including the United States successfully controlled typhoid as water treatment (chlorination/sand filtration) and improved sanitation became widespread. Enigmatically, typhoid remained endemic through the 1980s in Santiago, Chile, despite potable municipal water and widespread household sanitation. Data were collected across multiple stages of endemicity and control in Santiago, offering a unique resource for gaining insight into drivers of transmission in modern settings. We developed an individual-based mathematical model of typhoid transmission, with model components including distinctions between long-cycle and short-cycle transmission routes. Data used to fit the model included the prevalence of chronic carriers, seasonality, longitudinal incidence, and age-specific distributions of typhoid infection and disease. Our model captured the dynamics seen in Santiago across endemicity, vaccination, and environmental control. Both vaccination and diminished exposure to seasonal amplified long-cycle transmission contributed to the observed declines in typhoid incidence, with the vaccine estimated to elicit herd effects. Vaccines are important tools for controlling endemic typhoid, with even limited coverage eliciting herd effects in this setting. Removing the vehicles responsible for amplified long-cycle transmission and assessing the role of chronic carriers in endemic settings are additional key elements in designing programs to achieve accelerated control of endemic typhoid.

Evaluation of the recombinant antigens B2t and 2B2t, compared with hydatid fluid, in IgG-ELISA and immunostrips for the diagnosis and follow up of CE patients

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

by Ana Hernández-González, Carlos Sánchez-Ovejero, Raúl Manzano-Román, María González Sánchez, José Manuel Delgado, Teresa Pardo-García, Francisco Soriano-Gálvez, Okan Akhan, Carmen M. Cretu, Kamenna Vutova, Francesca Tamarozzi, Mara Mariconti, Enrico Brunetti, Ambra Vola, Massimo Fabiani, Adriano Casulli, Mar Siles-Lucas

Cystic echinococcosis (CE) is one of the most widespread helminthic zoonoses and is caused by the tapeworm Echinococcus granulosus complex. CE diagnosis and monitoring primarily rely on imaging techniques, complemented by serology. This is usually approached by the detection of IgG antibodies against hydatid fluid (HF), but the use of this heterogeneous antigenic mixture results in a variable percentage of false positive and negative results, and has shown to be useless for follow-up due to the long persistence of anti-HF antibodies in cured patients. To improve test performances and standardization, a number of recombinant antigens mainly derived from HF have been described, among them the B2t and 2B2t antigens. The performance of these antigens in the diagnosis and follow up of patients with CE has been so far evaluated on a limited number of samples. Here, we evaluated the performances of tests based on B2t and 2B2t recombinant antigens compared to HF in IgG-ELISA and immunochromatography (IC) for the diagnosis and follow-up of patients with CE in a retrospective cohort study. A total of 721 serum samples were collected: 587 from 253 patients with CE diagnosed by ultrasonography (US), 42 from patients with alveolar echinococcosis and 92 from healthy donors from Salamanca (Spain). The highest overall sensitivity was obtained with HF in ELISA (85.5%), followed by IC containing HF and 2B2t-HF (83.0% and 78.2%, respectively). The lowest sensitivity was obtained with B2t and 2B2t in ELISA (51.8%). The highest specificity was obtained with IC containing 2B2t-HF (100%), and the lowest with HF-ELISA (78.0%). The lowest cross-reactivity with sera from patients with alveolar echinococcosis was detected with the recombinant antigens in ELISA (9.5% - 16.7%) and the highest with the HF-IC (64.3%). The results of B2t and 2B2t-ELISA were influenced by cyst stage, as classified by US according to the WHO-Informal Working Group on Echinococcosis (WHO-IWGE), with low sensitivity for inactive (CE4 and CE5) cysts, and by the drug treatment, with higher sensitivity in patients after drug treatment compared with patients not subjected to drug treatment. The two recombinant antigens in ELISA provided promising results for monitoring patients in follow-up, although their use is limited to patients with positive serology against them at the beginning of the follow-up. Potential biological reasons behind the low sensitivity of the recombinant antigens and possible strategies to enhance the performance of CE serology are discussed.

Phylogenomic analysis unravels evolution of yellow fever virus within hosts

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

by Chen Chen, Dong Jiang, Ming Ni, Jing Li, Zhihai Chen, Jingyuan Liu, Hanhui Ye, Gary Wong, Wei Li, Yuanyuan Zhang, Beibei Wang, Yuhai Bi, Danying Chen, Ping Zhang, Xuesen Zhao, Yaxian Kong, Weifeng Shi, Pengcheng Du, Gengfu Xiao, Juncai Ma, George F. Gao, Jie Cui, Fujie Zhang, Wenjun Liu, Xiaochen Bo, Ang Li, Hui Zeng, Di Liu

The yellow fever virus (YFV) recently reemerged in the large outbreaks in Africa and Brazil, and the first imported patients into Asia have recalled the concerns of YFV evolution. Here we show phylogenomics of YFV with serial clinical samples of the 2016 YFV infections. Phylogenetics exhibited that the 2016 strains were close to Angola 1971 strains and only three amino acid changes presented new to other lineages. Deep sequencing of viral genomes discovered 101 intrahost single nucleotide variations (iSNVs) and 234 single nucleotide polymorphisms (SNPs). Analysis of iSNV distribution and mutated allele frequency revealed that the coding regions were under purifying selection. Comparison of the evolutionary rates estimated by iSNV and SNP showed that the intrahost rate was ~2.25 times higher than the epidemic rate, and both rates were higher than the long-term YFV substitution rate, as expected. In addition, the result also hinted that short viremia duration of YFV might further hinder the evolution of YFV.

Burden of leishmaniasis in Brazil and federated units, 1990-2016: Findings from Global Burden of Disease Study 2016

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

by Juliana Maria Trindade Bezerra, Valdelaine Etelvina Miranda de Araújo, David Soeiro Barbosa, Francisco Rogerlândio Martins-Melo, Guilherme Loureiro Werneck, Mariângela Carneiro

Background

The study presents estimates for the burden of visceral leishmaniasis (VL) and cutaneous and mucocutaneous leishmaniasis (CML) in Brazil and its 27 federated units using data from the Global Burden of Disease Study (GBD) 2016.

Methodology

We report the incidence, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY) for leishmaniasis in Brazil from 1990 to 2016. The metrics are presented as age-standardized rates per 100,000 inhabitants with their respective uncertainty intervals (95%UI) and relative percentages of change.

Principal findings

The age-standardized incidence rate of leishmaniasis decreased 48.5% from 1990 (71.0, 95%UI 24.3–150.7) to 2016 (36.5, 95%UI 24.7–50.9), whereas the age-standardized DALY increased 83.6% over the studied period from 12.2 (95%UI 7.9–18.8) to 22.4 (95%UI 13.3–36.2). The age-standardized incidence rate and YLL for VL increased by 52.9% and 108% from 1990 to 2016, respectively. Considering CML, the age-standardized incidence rate and YLD decreased by 51% and 31.8% respectively for the same period. For VL, similar profiles for male and female were observed, with YLL and DALY increasing over time; with males presenting slightly higher values. The highest YLL rates were among "under 1-year old" children, which increased 131.2% from 1990 to 2016. Regarding CML, the highest values of YLD and DALY were verified among males, and YLD values showed a similar profile, with rates increasing with age. The VL burden increased in some states in the Northeast and Southeast regions and decreased for CML in some Northern states.

Conclusion

The increase of VL burden over the study period might be associated with the difficulties in controlling the disease spread. Information regarding the weight of VL and CML, including the death and disability tolls that they cause, highlights the impact of these neglected diseases on public health and the importance of effective prevention and treatment.

Human rabies in Côte d'Ivoire 2014-2016: Results following reinforcements to rabies surveillance

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

by Issaka Tiembré, Anaïs Broban, Joseph Bénié, Mathilde Tetchi, Sophie Druelles, Maïna L’Azou

In Côte d’Ivoire, rabies is endemic and remains largely uncontrolled. The numbers of human exposures and rabies cases are unknown and are probably much higher than reported. Data on human rabies cases are collected by the National Institute of Public Health (NIPH) Anti-rabies Center in Abidjan through a network of 28 NIPH local units, which cover the population of the entire country. During 2014, the NIPH initiated a program to reinforce the human rabies surveillance system in those 28 NIPH local units, with specific goals of improving the infrastructure, training, communication, and government involvement. Here, we report the progress and findings during 2014–2016. The reinforced system recorded 50 cases of human rabies (15–18 cases/year; annual incidence = 0.06−0.08 per 100,000) and more than 30,000 animal exposures (annual incidence = 41.8−48.0 per 100,000). Almost one-half of the human rabies cases were in children ≤15 years old. All were fatal and dog bites were the most common route by which rabies virus was transmitted. In the 32 cases where samples of sufficient quality for analysis were available, rabies was confirmed by reverse transcription-polymerase chain reaction RT-PCR. Post-exposure prophylaxis with rabies vaccine was administered to all animal exposure victims presenting at the NIPH local units, although only about 57% completed the full immunization schedule. All available reports were provided by the NIPH local units, indicating effective communication between them and the NIPH Anti-rabies Center. These findings indicate that the reinforcements resulted in highly specific detection of human rabies, provided detailed epidemiological data about these cases, and improved estimates of animal exposure numbers. These represent substantial advances, but further improvements to the surveillance system are needed to increase disease awareness and capture cases that are currently missed by the system. In the future, better communication between local health centers and the NIPH units, surveillance at the local health center level, and increased veterinarian engagement will help provide a more complete picture of the rabies burden in Côte d’Ivoire.

Improving systematic rabies surveillance in Cameroon: A pilot initiative and results for 2014-2016

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

by Casimir Ledoux Sofeu, Anaïs Broban, Amadou Njifou Njimah, Jean Blaise Momo, Serge Alain Sadeuh-Mba, Sophie Druelles, Maïna L’Azou, Mathurin Cyrille Tejiokem

Canine rabies is endemic in Cameroon, but human rabies exposures and cases are likely underreported because of inadequate surveillance. In 2014, the surveillance network in the West region of Cameroon was reinforced by introducing a new anti-rabies center, a framework for data collection and evaluation, provisions for sample collecting and laboratory confirmation, and training for health professionals. The objective of this observational cohort study was to describe the incidence and characteristics of reported exposures and human and animal rabies cases following this reinforcement of the existing rabies surveillance system. The surveillance network consisted of local, regional, and national health and veterinary authorities in 11 of the 20 West region districts, and was completely integrated within the existing national rabies surveillance network. Animal exposures and suspected rabies exposures, the suspected rabid animals involved, and laboratory confirmation of human and animal rabies cases were recorded in a centralized information database. Between January 2014 and June 2016, the network recorded 1340 animal exposure cases for an overall incidence rate of 38.2 animal exposures per 100,000 people, four confirmed rabies-positive animals, and one confirmed human rabies case out of four clinically suspected cases. In contrast, 62 animal exposures and an overall incidence rate of 6.1 exposures per 100,000 people were reported for the West region districts not participating in the reinforced surveillance. Of the 925 animal exposure victims for whom a detailed case report form was completed, 703 were considered to be at risk of rabies and only 428 (61%) of these received any post-exposure prophylaxis in the form of rabies vaccine. Obstacles encountered within the network included low rates of animal sample submission and animal follow-up by veterinarians. Reinforced rabies surveillance in the West region of Cameroon has provided the most accurate estimate of the region’s disease and exposure burdens to date, and indicates that animal exposures are substantially underreported. The reinforced network also signaled that greater access to post-exposure prophylaxis is needed. Integration of regions not covered by the surveillance network and efforts to improve engagement of veterinary services will be needed to reveal the true burden of rabies in Cameroon.

Bolstering human rabies surveillance in Africa is crucial to eliminating canine-mediated rabies

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

by Anaïs Broban, Mathurin C. Tejiokem, Issaka Tiembré, Sophie Druelles, Maïna L’Azou

Optimization of sand fly embryo microinjection for gene editing by CRISPR/Cas9

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

by Ines Martin-Martin, Azadeh Aryan, Claudio Meneses, Zach N. Adelman, Eric Calvo

Background

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology has rapidly emerged as a very effective tool for gene editing. Although great advances on gene editing in the medical entomology field have arisen, no attempts of gene editing have been reported in sand flies, the vectors of Leishmaniasis.

Methodology/Principal findings

Here, we described a detailed protocol for sand fly embryo microinjection taking into consideration the sand fly life cycle, and manipulation and oviposition requirements of this non-model organism. Following our microinjection protocol, a hatching rate of injected embryos of 11.90%-14.22% was achieved, a rate consistent with other non-model organism dipterans such as mosquitoes. Essential factors for the adaptation of CRISPR/Cas9 technology to the sand fly field were addressed including the selection of a target gene and the design and production of sgRNA. An in vitro cleavage assay was optimized to test the activity of each sgRNA and a protocol for Streptococcus pyogenes Cas9 (spCas9) protein expression and purification was described. Relevant considerations for a successful gene editing in the sand fly such as specifics of embryology and double-stranded break DNA repair mechanisms were discussed.

Conclusion and significance

The step-by-step methodology reported in this article will be of significant use for setting up a sand fly embryo microinjection station for the incorporation of CRISPR/Cas9 technology in the sand fly field. Gene editing strategies used in mosquitoes and other model insects have been adapted to work with sand flies, providing the tools and relevant information for adapting gene editing techniques to the vectors of Leishmaniasis. Gene editing in sand flies will provide essential information on the biology of these vectors of medical and veterinary relevance and will rise a better understanding of vector-parasite-host interactions.

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