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A hotspot of <i>Toxoplasma gondii</i> Africa 1 lineage in Benin: How new genotypes from West Africa contribute to understand the parasite genetic diversity worldwide

PLoS Neglected Tropical Diseases News - 11 February 2021 - 2:00pm

by Azra Hamidović, Jonas Raoul Etougbétché, Arétas Babatounde Nounnagnon Tonouhewa, Lokman Galal, Gauthier Dobigny, Gualbert Houémènou, Honoré Da Zoclanclounon, Richard Amagbégnon, Anatole Laleye, Nadine Fievet, Sylvain Piry, Karine Berthier, Hilda Fátima Jesus Pena, Marie-Laure Dardé, Aurélien Mercier

Through international trades, Europe, Africa and South America share a long history of exchanges, potentially of pathogens. We used the worldwide parasite Toxoplasma gondii to test the hypothesis of a historical influence on pathogen genetic diversity in Benin, a West African country with a longstanding sea trade history. In Africa, T. gondii spatial structure is still non-uniformly studied and very few articles have reported strain genetic diversity in fauna and clinical forms of human toxoplasmosis so far, even in African diaspora. Sera from 758 domestic animals (mainly poultry) in two coastal areas (Cotonou and Ouidah) and two inland areas (Parakou and Natitingou) were tested for T. gondii antibodies using a Modified Agglutination Test (MAT). The hearts and brains of 69 seropositive animals were collected for parasite isolation in a mouse bioassay. Forty-five strains were obtained and 39 genotypes could be described via 15-microsatellite genotyping, with a predominance of the autochthonous African lineage Africa 1 (36/39). The remaining genotypes were Africa 4 variant TUB2 (1/39) and two identical isolates (clone) of Type III (2/39). No difference in terms of genotype distribution between inland and coastal sampling sites was found. In particular, contrarily to what has been described in Senegal, no type II (mostly present in Europe) was isolated in poultry from coastal cities. This result seems to refute a possible role of European maritime trade in Benin despite it was one of the most important hubs during the slave trade period. However, the presence of the Africa 1 genotype in Brazil, predominant in Benin, and genetic analyses suggest that the triangular trade was a route for the intercontinental dissemination of genetic strains from Africa to South America. This supports the possibility of contamination in humans and animals with potentially imported virulent strains.

Progress towards onchocerciasis elimination in Côte d’Ivoire: A geospatial modelling study

PLoS Neglected Tropical Diseases News - 10 February 2021 - 2:00pm

by Obiora A. Eneanya, Benjamin G. Koudou, Meite Aboulaye, Aba Ange Elvis, Yeo Souleymane, Marie-Madeleine Kouakou, Gary J. Weil, Peter U. Fischer

Background

Côte d’Ivoire has had 45 years of intervention for onchocerciasis by vector control (from 1975 to 1991), ivermectin mass drug administration (MDA) (from 1992 to 1994) and community directed treatment with ivermectin (CDTi) from 1995 to the present. We modeled onchocerciasis endemicity during two time periods that correspond to the scale up of vector control and ivermectin distribution, respectively. This analysis illustrates progress towards elimination during these periods, and it has identified potential hotspots areas that are at risk for ongoing transmission.

Methods and findings

The analysis used Ministry of Health skin snip microfilaria (MF) prevalence and intensity data collected between 1975 and 2016. Socio-demographic and environmental factors were incorporated into a predictive, machine learning algorithm to create continuous maps of onchocerciasis endemicity. Overall predicted mean MF prevalence decreased from 51.8% circa 1991 to 3.9% circa 2016. The model predicted infection foci with higher prevalence in the southern region of the country. Predicted mean community MF load (CMFL) decreased from 10.1MF/snip circa 1991 to 0.1MF/snip circa 2016. Again, the model predicts foci with higher Mf densities in the southern region. For assessing model performance, the root mean squared error and R2 values were 1.14 and 0.62 respectively for a model trained with data collected prior to 1991, and 1.28 and 0.57 for the model trained with infection survey data collected later, after the introduction of ivermectin. Finally, our models show that proximity to permanent inland bodies of water and altitude were the most informative variables that correlated with onchocerciasis endemicity.

Conclusion/Significance

This study further documents the significant reduction of onchocerciasis infection following widespread use of ivermectin for onchocerciasis control in Côte d’Ivoire. Maps produced predict areas at risk for ongoing infection and transmission. Onchocerciasis might be eliminated in Côte d’Ivoire in the future with a combination of sustained CDTi with high coverage, active surveillance, and close monitoring for persistent infection in previously hyper-endemic areas.

Major antigen and paramyosin proteins as candidate biomarkers for serodiagnosis of canine infection by zoonotic <i>Onchocerca lupi</i>

PLoS Neglected Tropical Diseases News - 10 February 2021 - 2:00pm

by Maria Stefania Latrofa, Giuseppe Palmisano, Giada Annoscia, Ciro Leonardo Pierri, Ramaswamy Chandrashekar, Domenico Otranto

Onchocerca lupi (Spirurida: Onchocercidae) is a filarial worm parasitizing domestic carnivores and humans. Adult nematodes usually localize beneath in the sclera or in the ocular retrobulbar of infected animals, whilst microfilariae are found in the skin. Therefore, diagnosis of O. lupi is achieved by microscopic and/or molecular detection of microfilariae from skin biopsy and/or surgical removal of adults from ocular tissues of infected hosts. An urgent non-invasive diagnostic tool for the diagnosis of O. lupi in dog is mandatory. In this study, an immunoproteomic analyses was performed using a combination of immunoblotting and mass spectrometry techniques. Onchocerca lupi major antigen (Ol-MJA) and paramyosin (Ol-PARA) proteins were identified as potential biomarkers for serodiagnosis. Linear epitopes were herein scanned for both proteins using high-density peptide microarray. Sera collected from dog infected with O. lupi and healthy animal controls led to the identification of 11 immunodominant antigenic peptides (n = 7 for Ol-MJA; n = 4 for Ol-PARA). These peptides were validated using sera of dogs uniquely infected with the most important filarioids infesting dogs either zoonotic (Dirofilaria repens, Dirofilaria immitis) or not (Acanthocheilonema reconditum and Cercopithifilaria bainae). Overall, six antigenic peptides, three for Ol-MJA and for Ol-PARA, respectively, were selected as potential antigens for the serological detection of canine O. lupi infection. The molecular and proteomic dataset herein reported should provide a useful resource for studies on O. lupi toward supporting the development of new interventions (drugs, vaccines and diagnostics) against canine onchocercosis.

Dengue risk assessment using multicriteria decision analysis: A case study of Bhutan

PLoS Neglected Tropical Diseases News - 10 February 2021 - 2:00pm

by Tsheten Tsheten, Archie C. A. Clements, Darren J. Gray, Kinley Wangdi

Background

Dengue is the most rapidly spreading vector-borne disease globally, with a 30-fold increase in global incidence over the last 50 years. In Bhutan, dengue incidence has been on the rise since 2004, with numerous outbreaks reported across the country. The aim of this study was to identify and map areas that are vulnerable to dengue in Bhutan.

Methodology/Principal findings

We conducted a multicriteria decision analysis (MCDA) using a weighted linear combination (WLC) to obtain a vulnerability map of dengue. Risk factors (criteria) were identified and assigned with membership values for vulnerability according to the available literature. Sensitivity analysis and validation of the model was conducted to improve the robustness and predictive ability of the map. Our study revealed marked differences in geographical vulnerability to dengue by location and season. Low-lying areas and those located along the southern border were consistently found to be at higher risk of dengue. The vulnerability extended to higher elevation areas including some areas in the Capital city Thimphu during the summer season. The higher risk was mostly associated with relatively high population density, agricultural and built-up landscapes and relatively good road connectivity.

Conclusions

Using MCDA, our study identified vulnerable areas in Bhutan during specific seasons when and where the transmission of dengue is most likely to occur. This study provides evidence for the National Vector-borne Disease Control programme to optimize the use of limited public health resources for surveillance and vector control, to mitigate the public health threat of dengue.

Diversity, distribution and natural <i>Leishmania</i> infection of sand flies from communities along the Interoceanic Highway in the Southeastern Peruvian Amazon

PLoS Neglected Tropical Diseases News - 10 February 2021 - 2:00pm

by Hugo O. Valdivia, Victor O. Zorrilla, Liz. J. Espada, Jocelyn G. Perez, Hugo R. Razuri, Hubert Vera, Roberto Fernandez, Carlos Tong, Bruno M. Ghersi, Gissella M. Vasquez, Roxanne G. Burrus, Andres G. Lescano, Joel M. Montgomery

The Peruvian-Brazilian border is a highly endemic tegumentary leishmaniasis region in South America. The interoceanic highway is a commercial route that connects Peru and Brazil through Madre de Dios and has raised concerns about its impact on previously undisturbed areas. In order to assess leishmaniasis transmission risk along this highway, we conducted a surveillance study of the sand fly populations in this area. Sand flies were collected between 2009 and 2010 along transects at 200 m, 600 m and 1000 m from six study sites located along the highway (Iberia, La Novia, Alto Libertad, El Carmen, Florida Baja, Mazuko and Mavila) and an undisturbed area (Malinowski). Collected specimens were identified based on morphology and non-engorged females of each species were pooled and screened by kinetoplast PCR to detect natural Leishmania infections. A total of 9,023 specimens were collected belonging to 54 different Lutzomyia species including the first report of Lu. gantieri in Peru. Four species accounted for 50% of all specimens (Lutzomyia carrerai carrerai, Lu. davisi, Lu. shawi and Lu. richardwardi). El Carmen, Alto Libertad, Florida Baja and Malinowski presented higher Shannon diversity indexes (H = 2.36, 2.30, 2.17 and 2.13, respectively) than the most human disturbed sites of Mazuko and La Novia (H = 1.53 and 1.06, respectively). PCR detected 10 positive pools belonging to Lu. carrerai carrerai, Lu. yuilli yuilli, Lu. hirsuta hirsuta, Lu. (Trichophoromyia) spp., and Lu. (Lutzomyia) spp. Positive pools from 1,000 m transects had higher infectivity rates than those from 600 m and 200 m transects (9/169 = 5.3% vs 0/79 = 0% and 1/127 = 0.8%, p = 0.018). El Carmen, accounted for eight out of ten positives whereas one positive was collected in Florida Baja and Mazuko each. Our study has shown differences in sand fly diversity, abundance and species composition across and within sites. Multiple clustered Lutzomyia pools with natural Leishmania infection suggest a complex, diverse and spotty role in leishmaniasis transmission in Madre de Dios, with increased risk farther from the highway.

An epidemiological surveillance of hand foot and mouth disease in paediatric patients and in community: A Singapore retrospective cohort study, 2013–2018

PLoS Neglected Tropical Diseases News - 10 February 2021 - 2:00pm

by Nyo Min, Yasmin Hui Binn Ong, Alvin X. Han, Si Xian Ho, Emmerie Wong Phaik Yen, Kenneth Hon Kim Ban, Sebastian Maurer-Stroh, Chia Yin Chong, Justin Jang Hann Chu

Background

While hand, foot and mouth disease (HFMD) is primarily self-resolving—soaring incidence rate of symptomatic HFMD effectuates economic burden in the Asia-Pacific region. Singapore has seen a conspicuous rise in the number of HFMD cases from 2010s. Here, we aims to identify the serology and genotypes responsible for such outbreaks in hospitals and childcare facilities.

Methods

We studied symptomatic paediatric HFMD cases from 2013 to 2018 in Singapore. Surveillance for subclinical enterovirus infections was also performed in childcares at the same time period.

Results

Genotyping 101 symptomatic HFMD samples revealed CV-A6 as the major etiological agent for recent outbreaks. We detected infections with CV-A6 (41.0%), EV-A71 (7%), CV-A16 (3.0%), coxsackievirus A2, CV-A2 (1.0%) and coxsackievirus A10, CV-A10 (1.0%). Phylogenetic analysis of local CV-A6 strains revealed a high level of heterogeneity compared against others worldwide, dissimilar to other HFMD causative enteroviruses for which the dominant strains and genotypes are highly region specific. We detected sub-clinical enterovirus infections in childcare centres; 17.1% (n = 245) tested positive for enterovirus in saliva, without HFMD indicative symptoms at the point of sample collection.

Conclusions

CV-A6 remained as the dominant HFMD causative strain in Singapore. Silent subclinical enteroviral infections were detected and warrant further investigations.

Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings

PLoS Neglected Tropical Diseases News - 10 February 2021 - 2:00pm

by Jacqueline Kyungah Lim, José Francisco Fernandes, In-Kyu Yoon, Jung-Seok Lee, Regis Obiang Mba, Kang Sung Lee, Suk Namkung, Jae Seung Yang, So Hee Bae, Sl-Ki Lim, Bertrand Lell, Meral Esen, Marguerite Massinga Loembe, Peter G. Kremsner, Neal Alexander, Selidji Todagbe Agnandji

Background

In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon.

Methods

Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR.

Results

Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases.

Conclusion

Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians’ diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection.

Correction: SARS-CoV-2 in the Amazon region: A harbinger of doom for Amerindians

PLoS Neglected Tropical Diseases News - 9 February 2021 - 2:00pm

by Juan David Ramírez, Emilia Mia Sordillo, Eduardo Gotuzzo, Carol Zavaleta, Daniel Caplivski, Juan Carlos Navarro, James Lee Crainey, Sergio Luiz Bessa Luz, Lourdes A. Delgado Noguera, Roxane Schaub, Cyril Rousseau, Giovanny Herrera, Maria A Oliveira-Miranda, Maria Teresa Quispe-Vargas, Peter J. Hotez, Alberto Paniz Mondolfi

The impact of COVID-19 pandemic on AIDS-related mycoses and fungal neglected tropical diseases: Why should we worry?

PLoS Neglected Tropical Diseases News - 9 February 2021 - 2:00pm

by Sanaz Nargesi, Felix Bongomin, Mohammad T. Hedayati

The World Health Organization (WHO) considers mycetoma, chromoblastomycosis, and paracoccidioidomycosis to be fungal neglected tropical diseases (FNTDs). Depending on climatic, cultural, and economic contexts, these diseases have a similar geographical distribution as many other diseases, particularly tuberculosis (TB) and malaria, but are often less targeted by the national and many international healthcare systems. Another subgroup of fungal infections, such as candidiasis, cryptococcosis, pneumocystosis, histoplasmosis, and to a lesser extent, aspergillosis, are known as AIDS-related mycoses. Although antiretroviral therapy (ART) has been able to decrease the mortality rate of these diseases, particularly cryptococcosis, the disproportionately low distribution of funds to their diagnosis and treatment remains an obstacle in saving and improving the lives of patients affected. A new wave of viral diseases dubbed the Coronavirus Disease 2019 (COVID-19) hit the world at the end of 2019. Due to progressive symptoms and high mortality rates of COVID-19 compared to fungal infections, particularly the FNTDs, funding is currently allocated predominantly for diagnostic and therapeutic research on COVID-19. As a result, advances in FNTDs and AIDS-related mycosis care are considerably reduced. This paper explores the association between COVID-19, FNTDs, and AIDS-related mycoses with a predictive perspective.

Paracoccidioimycosis and white individuals: Susceptibility and biogeographic aspects in an important endemic area in Brazil

PLoS Neglected Tropical Diseases News - 9 February 2021 - 2:00pm

by Luciana Bonome Zeminian de Oliveira, Amanda Manoel Della Coletta, Taiane Priscila Gardizani, Ligia Vizeu Barrozo, Hélio Amante Miot, Julio De Faveri, Luciane Alarcão Dias-Melicio

Paracoccidioidomycosis (PCM) is a neglected mycosis most commonly occurring in Latin America. The etiologic agents are thermo dimorphic fungi of the genus Paracoccidioides, and cause an important granulomatous response in affected tissues. The Botucatu Medical School, from São Paulo State University (UNESP), is a PCM study pole, located in São Paulo State Midwest region, which is classified as a hyperendemic area in the Southeast region in Brazil. This study aimed to perform a retrospective epidemiological, geographical, and clinical analysis by the information available in medical records. It was listed as socio-demographic data along with clinical characteristics from patients diagnosed and treated during a 10-year period in Botucatu, totaling 177 patients with Paracoccidioidomycosis confirmed by the histopathological test. It was observed that the main clinical presentation was the chronic type (76,3%), most commonly identified in white male individuals over the age of 29 years old, smokers, males and alcoholics, providing evidences for the first time that white individuals were more affected by the disease, in comparison to non-white individuals that may be more resistant to infection. This data opens new avenues for study within ancestry, resistance and susceptibility in paracoccidioidomycosis.

Establishment of an <i>in vitro</i> culture system to study the developmental biology of <i>Onchocerca volvulus</i> with implications for anti-<i>Onchocerca</i> drug discovery and screening

PLoS Neglected Tropical Diseases News - 9 February 2021 - 2:00pm

by Narcisse V. T. Gandjui, Abdel J. Njouendou, Eric N. Gemeg, Fanny F. Fombad, Manuel Ritter, Chi A. Kien, Valerine C. Chunda, Jerome Fru, Mathias E. Esum, Marc P. Hübner, Peter A. Enyong, Achim Hoerauf, Samuel Wanji

Background

Infections with Onchocerca volvulus nematodes remain a threat in Sub-Saharan Africa after three decades of ivermectin mass drug administration. Despite this effort, there is still an urgent need for understanding the parasite biology especially the mating behaviour and nodule formation as well as the development of more potent drugs that can clear the developmental (L3, L4, L5) and adult stages of the parasite and inhibit parasite reproduction and behaviour.

Methodology/Principal findings

Prior to culture, freshly harvested O. volvulus L3 larvae from dissected Simulium damnosum flies were purified by centrifugation using a 30% Percoll solution to eliminate fly tissue debris and contaminants. Parasites were cultured in both cell-free and cell-based co-culture systems and monitored daily by microscopic visual inspection. Exhausted culture medium was replenished every 2–3 days. The cell-free culture system (DMEM supplemented with 10% NCS) supported the viability and motility of O. volvulus larvae for up to 84 days, while the co-culture system (DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells) extended worm survival for up to 315 days. Co-culture systems alone promoted two consecutive parasite moults (L3 to L4 and L4 to L5) with highest moulting rates (69.2±30%) observed in DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells, while no moult was observed in DMEM supplemented with 10% NCS and seeded on LEC feeder cells. In DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells, O. volvulus adult male worms attached to the vulva region of adult female worms and may have mated in vitro. Apparent early initiation of nodulogenesis was observed in both DMEM supplemented with 10% FBS and seeded on LLC-MK2 and DMEM supplemented with 10% NCS and seeded on LLC-MK2 systems.

Conclusions/Significance

The present study describes an in vitro system in which O. volvulus L3 larvae can be maintained in culture leading to the development of adult stages. Thus, this in vitro system may provide a platform to investigate mating behaviour and early stage of nodulogenesis of O. volvulus adult worms that can be used as additional targets for macrofilaricidal drug screening.

Afrotropical sand fly-host plant relationships in a leishmaniasis endemic area, Kenya

PLoS Neglected Tropical Diseases News - 8 February 2021 - 2:00pm

by Iman B. Hassaballa, Catherine L. Sole, Xavier Cheseto, Baldwyn Torto, David P. Tchouassi

The bioecology of phlebotomine sand flies is intimately linked to the utilization of environmental resources including plant feeding. However, plant feeding behavior of sand flies remains largely understudied for Afrotropical species. Here, using a combination of biochemical, molecular, and chemical approaches, we decipher specific plant-feeding associations in field-collected sand flies from a dry ecology endemic for leishmaniasis in Kenya. Cold-anthrone test indicative of recent plant feeding showed that fructose positivity rates were similar in both sand fly sexes and between those sampled indoors and outdoors. Analysis of derived sequences of the ribulose bisphosphate carboxylase gene large subunit (rbcL) from fructose-positive specimens implicated mainly Acacia plants in the family Fabaceae (73%) as those readily foraged on by both sexes of Phlebotomus and Sergentomyia. Chemical analysis by high performance liquid chromatography detected fructose as the most common sugar in sand flies and leaves of selected plant species in the Fabaceae family. Analysis of similarities (ANOSIM) of the headspace volatile profiles of selected Fabaceae plants identified benzyl alcohol, (Z)-linalool oxide, (E)-β-ocimene, p-cymene, p-cresol, and m-cresol, as discriminating compounds between the plant volatiles. These results indicate selective sand fly plant feeding and suggest that the discriminating volatile organic compounds could be exploited in attractive toxic sugar- and odor- bait technologies control strategies.

Antineoplastic kinase inhibitors: A new class of potent anti-amoebic compounds

PLoS Neglected Tropical Diseases News - 8 February 2021 - 2:00pm

by Conall Sauvey, Gretchen Ehrenkaufer, Da Shi, Anjan Debnath, Ruben Abagyan

Entamoeba histolytica is a protozoan parasite which infects approximately 50 million people worldwide, resulting in an estimated 70,000 deaths every year. Since the 1960s E. histolytica infection has been successfully treated with metronidazole. However, drawbacks to metronidazole therapy exist, including adverse effects, a long treatment course, and the need for an additional drug to prevent cyst-mediated transmission. E. histolytica possesses a kinome with approximately 300–400 members, some of which have been previously studied as potential targets for the development of amoebicidal drug candidates. However, while these efforts have uncovered novel potent inhibitors of E. histolytica kinases, none have resulted in approved drugs. In this study we took the alternative approach of testing a set of twelve previously FDA-approved antineoplastic kinase inhibitors against E. histolytica trophozoites in vitro. This resulted in the identification of dasatinib, bosutinib, and ibrutinib as amoebicidal agents at low-micromolar concentrations. Next, we utilized a recently developed computational tool to identify twelve additional drugs with human protein target profiles similar to the three initial hits. Testing of these additional twelve drugs led to the identification of ponatinib, neratinib, and olmutinib were identified as highly potent, with EC50 values in the sub-micromolar range. All of these six drugs were found to kill E. histolytica trophozoites as rapidly as metronidazole. Furthermore, ibrutinib was found to kill the transmissible cyst stage of the model organism E. invadens. Ibrutinib thus possesses both amoebicidal and cysticidal properties, in contrast to all drugs used in the current therapeutic strategy. These findings together reveal antineoplastic kinase inhibitors as a highly promising class of potent drugs against this widespread and devastating disease.

Developmental outcomes in children exposed to Zika virus in utero from a Brazilian urban slum cohort study

PLoS Neglected Tropical Diseases News - 5 February 2021 - 2:00pm

by Juan P. Aguilar Ticona, Nivison Nery Jr., Joseph B. Ladines-Lim, Claudia Gambrah, Gielson Sacramento, Bruno de Paula Freitas, Joseane Bouzon, Jamary Oliveira-Filho, Ana Borja, Haritha Adhikarla, Magelda Montoya, Athena Chin, Elsio A. Wunder Jr., Verena Ballalai, Carina Vieira, Rubens Belfort, Antonio R. P. Almeida, Mitermayer G. Reis, Eva Harris, Albert I. Ko, Federico Costa

Background

The prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure.

Methodology/Principal findings

We performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1–24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3–26.9), with a PAF of 59.5%.

Conclusions

A significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure.

The presence of knockdown resistance mutations reduces male mating competitiveness in the major arbovirus vector, <i>Aedes aegypti</i>

PLoS Neglected Tropical Diseases News - 5 February 2021 - 2:00pm

by Lisa M. Rigby, Brian J. Johnson, Gordana Rašić, Christopher L. Peatey, Leon E. Hugo, Nigel W. Beebe, Gunter F. Hartel, Gregor J. Devine

Background

The development of insecticide resistance in mosquitoes can have pleiotropic effects on key behaviours such as mating competition and host-location. Documenting these effects is crucial for understanding the dynamics and costs of insecticide resistance and may give researchers an evidence base for promoting vector control programs that aim to restore or conserve insecticide susceptibility.

Methods and findings

We evaluated changes in behaviour in a backcrossed strain of Aedes aegypti, homozygous for two knockdown resistance (kdr) mutations (V1016G and S989P) isolated in an otherwise fully susceptible genetic background. We compared biting activity, host location behaviours, wing beat frequency (WBF) and mating competition between the backcrossed strain, and the fully susceptible and resistant parental strains from which it was derived. The presence of the homozygous kdr mutations did not have significant effects on blood avidity, the time to locate a host, or WBF in females. There was, however, a significant reduction in mean WBF in males and a significant reduction in estimated male mating success (17.3%), associated with the isolated kdr genotype.

Conclusions

Our results demonstrate a cost of insecticide resistance associated with an isolated kdr genotype and manifest as a reduction in male mating success. While there was no recorded difference in WBF between the females of our strains, the significant reduction in male WBF recorded in our backcrossed strain might contribute to mate-recognition and mating disruption. These consequences of resistance evolution, especially when combined with other pleiotropic fitness costs that have been previously described, may encourage reversion to susceptibility in the absence of insecticide selection pressures. This offers justification for the implementation of insecticide resistance management strategies based on the rotation or alternation of different insecticide classes in space and time.

Endemicity of <i>Paragonimus</i> and paragonimiasis in Sub-Saharan Africa: A systematic review and mapping reveals stability of transmission in endemic foci for a multi-host parasite system

PLoS Neglected Tropical Diseases News - 5 February 2021 - 2:00pm

by Muriel Rabone, Joris Wiethase, Paul F. Clark, David Rollinson, Neil Cumberlidge, Aidan M. Emery

Paragonimiasis is caused by zoonotic trematodes of Paragonimus spp., found in Asia, the Americas and Africa, particularly in tropical regions. These parasites have a complex, multi-host life cycle, with mammalian definitive hosts and larval stages cycling through two intermediate hosts (snails and freshwater crabs). In Africa, paragonimiasis is particularly neglected, and remains the only human parasitic disease without a fully characterised life cycle. However paragonimiasis has potentially significant impacts on public health in Africa, and prevalence has likely been underestimated through under-reporting and misdiagnosis as tuberculosis due to a similar clinical presentation. We identified the need to synthesise current knowledge and map endemic foci for African Paragonimus spp. together with Poikilorchis congolensis, a rare, taxonomically distant trematode with a similar distribution and morphology. We present the first systematic review of the literature relating to African paragonimiasis, combined with mapping of all reported occurrences of Paragonimus spp. throughout Africa, from the 1910s to the present. In human surveys, numerous reports of significant recent transmission in Southeast Nigeria were uncovered, with high prevalence and intensity of infection. Overall prevalence was significantly higher for P. uterobilateralis compared to P. africanus across studies. The potential endemicity of P. africanus in Cote d’Ivoire is also reported. In freshwater crab intermediate hosts, differences in prevalence and intensity of either P. uterobilateralis or P. africanus were evident across genus and species, suggesting differences in susceptibility. Mapping showed temporal stability of endemic foci, with the majority of known occurrences of Paragonimus found in the rainforest zone of West and Central Africa, but with several outliers elsewhere on the continent. This suggests substantial under sampling and localised infection where potential host distributions overlap. Our review highlights the urgent need for increased sampling in active disease foci in Africa, particularly using molecular analysis to fully characterise Paragonimus species and their hosts.

Multi-annual performance evaluation of laboratories in post-mortem diagnosis of animal rabies: Which techniques lead to the most reliable results in practice?

PLoS Neglected Tropical Diseases News - 5 February 2021 - 2:00pm

by Emmanuelle Robardet, Alexandre Servat, Jonathan Rieder, Evelyne Picard-Meyer, Florence Cliquet

Rabies diagnosis proficiency tests on animal specimens using four techniques (FAT, RTCIT, conventional RT-PCR and real-time RT-PCR) were organised over 10 years (2009–2019). Seventy-three laboratories, of which 59% were from Europe, took part. As the panels were prepared with experimentally-infected samples, the error rate of laboratories on positive and negative samples was accurately estimated. Based on fitted values produced by mixed modelling including the variable “laboratory” as a random variable to take into account the longitudinal design of our dataset, the technique that provided the most concordant results was conventional RT-PCR (99.3%; 95% CI 99.0–99.6), closely followed by FAT (99.1%; 95% CI 98.7–99.4), real-time RT-PCR (98.7%; 95% CI 98.1–99.3) and then RTCIT (96.8%; 95% CI 95.8–97.7). We also found that conventional RT-PCR provided a better diagnostic sensitivity level (99.3% ±4.4%) than FAT (98.7% ±1.6%), real-time RT-PCR (97.9% ±0.8%) and RTCIT (95.3% ±5.1%). Regarding diagnostic specificity, RTCIT was the most specific technique (96.4% ±3.9%) followed closely by FAT (95.6% ±3.8%), real-time RT-PCR (95.0% ±1.8%) and conventional RT-PCR (92.9% ±0.5%). Due to multiple testing of the samples with different techniques, the overall diagnostic conclusion was also evaluated, and found to reach an inter-laboratory concordance level of 99.3%. The concordance for diagnostic sensitivity was 99.6% ±2.0% and for diagnostic specificity, 98.0% ±8.5%. Molecular biology techniques were, however, found to be less specific than expected. The potential reasons for such findings are discussed herein. The regular organisation of performance tests has contributed to an increase in the performance of participating laboratories over time, demonstrating the benefits of such testing. Maintaining a high-quality rabies diagnosis capability on a global scale is key to achieving the goal of eliminating dog-mediated human rabies deaths. The regular organisation of exercises on each continent using selected local strains to be tested according to the local epidemiological situation is one factor that could help increase reliable diagnosis worldwide. Rabies diagnosis capabilities could indeed be enhanced by providing adequate and sustainable proficiency testing on a large scale and in the long term

Sialotranscriptomics of the argasid tick <i>Ornithodoros moubata</i> along the trophogonic cycle

PLoS Neglected Tropical Diseases News - 5 February 2021 - 2:00pm

by Ana Oleaga, Beatriz Soriano, Carlos Llorens, Ricardo Pérez-Sánchez

The argasid tick Ornithodoros moubata is the main vector of human relapsing fever (HRF) and African swine fever (ASF) in Africa. Salivary proteins are part of the host-tick interface and play vital roles in the tick feeding process and the host infection by tick-borne pathogens; they represent interesting targets for immune interventions aimed at tick control. The present work describes the transcriptome profile of salivary glands of O. moubata and assesses the gene expression dynamics along the trophogonic cycle using Illumina sequencing. De novo transcriptome assembling resulted in 71,194 transcript clusters and 41,011 annotated transcripts, which represent 57.6% of the annotation success. Most salivary gene expression takes place during the first 7 days after feeding (6,287 upregulated transcripts), while a minority of genes (203 upregulated transcripts) are differentially expressed between 7 and 14 days after feeding. The functional protein groups more abundantly overrepresented after blood feeding were lipocalins, proteases (especially metalloproteases), protease inhibitors including the Kunitz/BPTI-family, proteins with phospholipase A2 activity, acid tail proteins, basic tail proteins, vitellogenins, the 7DB family and proteins involved in tick immunity and defence. The complexity and functional redundancy observed in the sialotranscriptome of O. moubata are comparable to those of the sialomes of other argasid and ixodid ticks. This transcriptome provides a valuable reference database for ongoing proteomics studies of the salivary glands and saliva of O. moubata aimed at confirming and expanding previous data on the O. moubata sialoproteome.

Prevalence of intestinal parasite among patients attending two hospitals in French Guiana: A 6-year retrospective study

PLoS Neglected Tropical Diseases News - 5 February 2021 - 2:00pm

by Alolia Aboikoni, Manon Allaire, Dominique Louvel, Denis Blanchet, Thong Dao, Jean-François Carod, Magalie Demar

Introduction

Intestinal parasitic diseases are a global health problem. Due to its equatorial climate, vast territory with isolated areas and the precariousness of its population, intestinal parasitosis is considered to be a major issue in French Guiana but only few data are available and these mainly focus on specific population. We aimed at determining the parasitic index and at describing the characteristics of these infections in order to develop preventive strategies.

Material and methods

We retrospectively analysed all the parasitological samples recorded in the register of the two main laboratories of French Guiana between 2011 and 2016. The parasitic index was the percentage of parasitised patients in comparison with the total number of subjects studied. A patient who underwent several positive parasitological examinations was considered only once in the analysis at the time of the first sampling.

Results

A total of 15,220 parasitological samples of 9,555 patients were analysed and 2,916 were positive in 1,521 patients. The average infestation rate and parasitic index were 19.2% and 16.0%, respectively. The parasitic index remained stable between 2011 (18.2%) and 2016 (18.3%). The patients were mainly men (66.4%), with a median age of 33.0 years (26.3% of patients were under 18 years of age) and lived mainly in the Central Agglomeration (48.2%) and in West Guiana (37.4%). Hookworms were the most common parasite (25.2%) followed by Entamoeba coli (13.3%), Strongyloides stercoralis (10.9%) and Giardia intestinalis (10.8%). Among the infected patients, 31.0% presented mixed infections and 67.5% of them had at least one pathogenic parasite. The patients aged from 0 to 18 years presented significantly more polyparasitism (30.9%) than monoparasitism (24.3%, p<0.001). Ancylostoma sp and Strongyloides stercoralis were mainly diagnosed during the rainy season (59.5% and 64.7% respectively), in men (78.6% and 81.1% respectively) and in patients aged from 18 to 65 years (86.6% and 76.6% respectively) whereas, Giardia intestinalis infected mostly children under 5 years (59.5%) of age.

Conclusion

Although it may not be representative of the entire Guyanese population, the parasitic index remained high and stable from 2011 and 2016 and it justifies the need for an active prevention program as it was already done in the other French overseas departments such as Martinique and Guadeloupe.

Weaknesses in primary health care favor the growth of acquired syphilis

PLoS Neglected Tropical Diseases News - 5 February 2021 - 2:00pm

by Marquiony Marques dos Santos, Tatyana Maria Silva de Souza Rosendo, Ana Karla Bezerra Lopes, Angelo Giuseppe Roncalli, Kenio Costa de Lima

Acquired syphilis is a sexually transmitted infection that affects the general population and has been growing in recent years in many countries. A study was developed aiming to analyze the trends of acquired syphilis associated with sociodemographic aspects and primary health care in Brazil, in the period from 2011 to 2019. This study used secondary data from the national notification systems of the 5570 Brazilian cities and a database of 37,350 primary health care teams, as well as socioeconomic and municipal demographic indicators. The trends of acquired syphilis at the municipal level were calculated from the log-linear regression, crossing them with variables of primary health care and sociodemographic indicators. Finally, a multiple model was built from logistic regression. 724,310 cases of acquired syphilis have been reported. In primary care units, 47.8% had partial coverage and 74.1% had health teams with poor or regular scores. 52.6% had rapid test for syphilis partially available. Male and female condoms are available in 85.9% and 62.9% respectively and 54.4% had penicillin available in the health facility. The increase in trends of acquired syphilis was associated with better availability of the rapid test; lower availability of male condoms; lower availability of female condoms; lower availability of benzathine penicillin; partial coverage of the teams in primary health care; limited application of penicillin in primary health care; higher proportion of teams classified as Poor/Regular in primary health care; higher proportion of women aged 10 to 17 years who had children; higher HDI; higher proportion of people aged 15 to 24 years who do not study, do not work and are vulnerable; and population size with more than 100,000 inhabitants. The following variables remained in the multiple model: not all primary health care teams apply penicillin; higher proportion of primary health care teams with poor/regular scores; population size >100000 inhabitants; partially available female condom. Thus, the weakness of primary health care linked to population size may have favored the growth of the acquired syphilis epidemic in Brazilian cities.

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