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Vector competence of <i>Aedes aegypti</i> from Havana, Cuba, for dengue virus type 1, chikungunya, and Zika viruses

PLoS Neglected Tropical Diseases News - 3 December 2020 - 10:00pm

by Gladys Gutiérrez-Bugallo, Antoine Boullis, Yanet Martinez, Lyza Hery, Magdalena Rodríguez, Juan A. Bisset, Anubis Vega-Rúa

Background

Like many countries from the Americas, Cuba is threatened by Aedes aegypti-associated arboviruses such as dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses. Curiously, when CHIKV was actively circulating in the region in 2013–2014, no autochthonous transmission of this virus was detected in Havana, Cuba, despite the importation of chikungunya cases into this city. To investigate if the transmission ability of local mosquito populations could explain this epidemiological scenario, we evaluated for the first time the vector competence of two Ae. aegypti populations (Pasteur and Párraga) collected from Havana for dengue virus type 1 (DENV-1), CHIKV, and ZIKV.

Methodology/Principal findings

Mosquito populations were fed separately using blood containing ZIKV, DENV-1, or CHIKV. Infection, dissemination, and transmission rates, were estimated at 3 (exclusively for CHIKV), 7, and 14 days post exposure (dpe) for each Ae. aegypti population-virus combination. Both mosquito populations were susceptible to DENV-1 and ZIKV, with viral infection and dissemination rates ranging from 24–97% and 6–67% respectively. In addition, CHIKV disseminated in both populations and was subsequently transmitted. Transmission rates were low (<30%) regardless of the mosquito population/virus combination and no ZIKV was detected in saliva of females from the Pasteur population at any dpe.

Conclusions/Significance

Our study demonstrated the ability of Ae. aegypti from Cuba to transmit DENV, ZIKV, and CHIKV. These results, along with the widespread distribution and high abundance of this species in the urban settings throughout the island, highlight the importance of Ae. aegypti control and arbovirus surveillance to prevent future outbreaks.

Adenovirus vectored IFN-α protects mice from lethal challenge of Chikungunya virus infection

PLoS Neglected Tropical Diseases News - 3 December 2020 - 10:00pm

by Huixin Chen, Nyo Min, Luyao Ma, Chee-Keng Mok, Justin Jang Hann Chu

Chikungunya virus (CHIKV) is a mosquito-borne pathogen that is responsible for numerous large and geographical epidemics, causing millions of cases. However, there is no vaccine or therapeutics against CHIKV infection available. Interferon-alpha (IFN-α) has been shown to produce potent antiviral responses during viral infection. Herein we demonstrated the use of an adenovirus-vectored expressed mouse IFN-α (mDEF201) as a prophylactic and therapeutic treatment against CHIKV in vivo. 6-day-old BALB/c mice were pre- or post-treated intranasally with single dose of mDEF201 at 5 x 106 PFU per mouse and challenged with lethal dose of CHIKV. Complete survival protection was observed in mice upon a single dose of mDEF201 administration 1 days prior to virus challenge. Viral load in the serum and multiple organs were significantly reduced upon mDEF201 administration in a dose dependent manner as compare with adenovirus 5 vector placebo set. Histological analysis of the mice tissue revealed that mDEF201 could significantly reduce the tissue morphological abnormities, mainly infiltration of immune cells and muscle fibre necrosis caused by CHIKV infection. In addition, administration of mDEF201 at 6 hours post CHIKV challenge also showed promising inhibitory effect against viral replication and dissemination. In conclusion, single-dose of intranasal administration with mDEF201 as a prophylactic or therapeutic agent within 6 hours post CHIKV infection is highly protective against a lethal challenge of CHIKV in the murine model.

Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice

PLoS Neglected Tropical Diseases News - 3 December 2020 - 10:00pm

by Mariah Hassert, Kyle J. Wolf, Ahmad Rajeh, Courtney Shiebout, Stella G. Hoft, Tae-Hyuk Ahn, Richard J. DiPaolo, James D. Brien, Amelia K. Pinto

Zika virus (ZIKV) is a significant global health threat due to its potential for rapid emergence and association with severe congenital malformations during infection in pregnancy. Despite the urgent need, accurate diagnosis of ZIKV infection is still a major hurdle that must be overcome. Contributing to the inaccuracy of most serologically-based diagnostic assays for ZIKV, is the substantial geographic and antigenic overlap with other flaviviruses, including the four serotypes of dengue virus (DENV). Within this study, we have utilized a novel T cell receptor (TCR) sequencing platform to distinguish between ZIKV and DENV infections. Using high-throughput TCR sequencing of lymphocytes isolated from DENV and ZIKV infected mice, we were able to develop an algorithm which could identify virus-associated TCR sequences uniquely associated with either a prior ZIKV or DENV infection in mice. Using this algorithm, we were then able to separate mice that had been exposed to ZIKV or DENV infection with 97% accuracy. Overall this study serves as a proof-of-principle that T cell receptor sequencing can be used as a diagnostic tool capable of distinguishing between closely related viruses. Our results demonstrate the potential for this innovative platform to be used to accurately diagnose Zika virus infection and potentially the next emerging pathogen(s).

Targeting female flight for genetic control of mosquitoes

PLoS Neglected Tropical Diseases News - 3 December 2020 - 10:00pm

by David Navarro-Payá, Ilona Flis, Michelle A. E. Anderson, Philippa Hawes, Ming Li, Omar S. Akbari, Sanjay Basu, Luke Alphey

Aedes aegypti Act4 is a paralog of the Drosophila melanogaster indirect flight muscle actin gene Act88F. Act88F has been shown to be haploinsufficient for flight in both males and females (amorphic mutants are dominant). Whereas Act88F is expressed in indirect flight muscles of both males and females, expression of Act4 is substantially female-specific. We therefore used CRISPR/Cas9 and homology directed repair to examine the phenotype of Act4 mutants in two Culicine mosquitoes, Aedes aegypti and Culex quinquefasciatus. A screen for dominant female-flightless mutants in Cx. quinquefasciatus identified one such mutant associated with a six base pair deletion in the CxAct4 coding region. A similar screen in Ae. aegypti identified no dominant mutants. Disruption of the AeAct4 gene by homology-dependent insertion of a fluorescent protein marker cassette gave a recessive female-flightless phenotype in Ae. aegypti. Reproducing the six-base deletion from Cx. quinquefasciatus in Ae. aegypti using oligo-directed mutagenesis generated dominant female-flightless mutants and identified additional dominant female-flightless mutants with other in-frame insertions or deletions. Our data indicate that loss of function mutations in the AeAct4 gene are recessive but that short in-frame deletions produce dominant-negative versions of the AeAct4 protein that interfere with flight muscle function. This makes Act4 an interesting candidate for genetic control methods, particularly population-suppression gene drives targeting female viability/fertility.

Actinomycetoma with systemic features: A warning sign for immunosuppression?

PLoS Neglected Tropical Diseases News - 3 December 2020 - 10:00pm

by Rita Fernanda Cortez de Almeida, Roberta Espírito Santo Correia, Andréa Gina Varón, Janice Mery Chicarino de Oliveira Coelho, Ana Paola de Oliveira, Maria Cristina Silva Lourenço, Erica Aparecida dos Santos Ribeiro da Silva, Emilyn Costa Conceição, Cristiane da Cruz Lamas, Dayvison Francis Saraiva Freitas

An unhealing wound and subcutaneous nodules due to <i>Sporothrix globosa</i> after a cat bite

PLoS Neglected Tropical Diseases News - 3 December 2020 - 10:00pm

by Yanbin Liu, Lina Liu, Mei Kang, Zhiyong Zong

A 51-year-old man with 3-month unhealing cat bite wound was diagnosed with sporotrichosis, a subacute-to-chronic infection caused by the worldwide endemic, dimorphic fungus Sporothrix globosa. The case would help clinicians to raise awareness of human sporotrichosis due to cat bites, which remains rare and is likely to be underrecognized and misdiagnosed.

Spatiotemporal analysis of mycolactone distribution <i>in vivo</i> reveals partial diffusion in the central nervous system

PLoS Neglected Tropical Diseases News - 2 December 2020 - 10:00pm

by Emma Colucci-Guyon, Aline Rifflet, Sarah Saint-Auret, Anaëlle da Costa, Laurent Boucontet, Thomas Laval, Christophe Prehaud, Nicolas Blanchard, Jean-Pierre Levraud, Ivo G. Boneca, Caroline Demangel, Laure Guenin-Macé

Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU) disease, is unique amongst human pathogens in its capacity to produce a lipid toxin called mycolactone. While previous studies have demonstrated that bacterially-released mycolactone diffuses beyond infection foci, the spatiotemporal distribution of mycolactone remained largely unknown. Here, we used the zebrafish model to provide the first global kinetic analysis of mycolactone’s diffusion in vivo, and multicellular co-culture systems to address the critical question of the toxin’s access to the brain. Zebrafish larvae were injected with a fluorescent-derivative of mycolactone to visualize the in vivo diffusion of the toxin from the peripheral circulation. A rapid, body-wide distribution of mycolactone was observed, with selective accumulation in tissues near the injection site and brain, together with an important excretion through the gastro-intestinal tract. Our conclusion that mycolactone reached the central nervous system was reinforced by an in cellulo model of human blood brain barrier and a mouse model of M. ulcerans-infection. Here we show that mycolactone has a broad but heterogenous profile of distribution in vivo. Our investigations in vitro and in vivo support the view that a fraction of bacterially-produced mycolactone gains access to the central nervous system. The relative persistence of mycolactone in the bloodstream suggests that assays of circulating mycolactone are relevant for BU disease monitoring and treatment optimization.

Quantitative lipidomic analysis of <i>Ascaris suum</i>

PLoS Neglected Tropical Diseases News - 2 December 2020 - 10:00pm

by Tao Wang, Shuai Nie, Guangxu Ma, Johnny Vlaminck, Peter Geldhof, Nicholas A. Williamson, Gavin E. Reid, Robin B. Gasser

Ascaris is a soil-transmitted nematode that causes ascariasis, a neglected tropical disease affecting predominantly children and adolescents in the tropics and subtropics. Approximately 0.8 billion people are affected worldwide, equating to 0.86 million disability-adjusted life-years (DALYs). Exploring the molecular biology of Ascaris is important to gain a better understanding of the host-parasite interactions and disease processes, and supports the development of novel interventions. Although advances have been made in the genomics, transcriptomics and proteomics of Ascaris, its lipidome has received very limited attention. Lipidomics is an important sub-discipline of systems biology, focused on exploring lipids profiles in tissues and cells, and elucidating their biological and metabolic roles. Here, we characterised the lipidomes of key developmental stages and organ systems of Ascaris of porcine origin via high throughput LC-MS/MS. In total, > 500 lipid species belonging to 18 lipid classes within three lipid categories were identified and quantified–in precise molar amounts in relation to the dry weight of worm material–in different developmental stages/sexes and organ systems. The results showed substantial differences in the composition and abundance of lipids with key roles in cellular processes and functions (e.g. energy storage regulation and membrane structure) among distinct stages and among organ systems, likely reflecting differing demands for lipids, depending on stage of growth and development as well as the need to adapt to constantly changing environments within and outside of the host animal. This work provides the first step toward understanding the biology of lipids in Ascaris, with possibilities to work toward designing new interventions against ascariasis.

Risk mapping of scrub typhus infections in Qingdao city, China

PLoS Neglected Tropical Diseases News - 2 December 2020 - 10:00pm

by Hualei Xin, Peng Fu, Junling Sun, Shengjie Lai, Wenbiao Hu, Archie C. A. Clements, Jianping Sun, Jing Cui, Simon I. Hay, Xiaojing Li, Zhongjie Li

Background

The emergence and re-emergence of scrub typhus has been reported in the past decade in many global regions. In this study, we aim to identify potential scrub typhus infection risk zones with high spatial resolution in Qingdao city, in which scrub typhus is endemic, to guide local prevention and control strategies.

Methodology/Principal findings

Scrub typhus cases in Qingdao city during 2006–2018 were retrieved from the Chinese National Infectious Diseases Reporting System. We divided Qingdao city into 1,101 gridded squares and classified them into two categories: areas with and without recorded scrub typhus cases. A boosted regression tree model was used to explore environmental and socioeconomic covariates associated with scrub typhus occurrence and predict the risk of scrub typhus infection across the whole area of Qingdao city. A total of 989 scrub typhus cases were reported in Qingdao from 2006–2018, with most cases located in rural and suburban areas. The predicted risk map generated by the boosted regression tree models indicated that the highest infection risk areas were mainly concentrated in the mid-east and northeast regions of Qingdao, with gross domestic product (20.9%±1.8% standard error) and annual cumulative precipitation (20.3%±1.1%) contributing the most to the variation in the models. By using a threshold environmental suitability value of 0.26, we identified 757 squares (68.7% of the total) with a favourable environment for scrub typhus infection; 66.2% (501/757) of the squares had not yet recorded cases. It is estimated that 6.32 million people (72.5% of the total population) reside in areas with a high risk of scrub typhus infection.

Conclusions/Significance

Many locations in Qingdao city with no recorded scrub typhus cases were identified as being at risk for scrub typhus occurrence. In these at-risk areas, awareness and capacity for case diagnosis and treatment should be enhanced in the local medical service institutes.

Transmission competence of a new mesonivirus, Yichang virus, in mosquitoes and its interference with representative flaviviruses

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Guoguo Ye, Yujuan Wang, Xiaoyun Liu, Qiannan Dong, Quanxing Cai, Zhiming Yuan, Han Xia

Advances in technology have greatly stimulated the understanding of insect-specific viruses (ISVs). Unfortunately, most of these findings are based on sequencing technology, and laboratory data are scarce on the transmission dynamics of ISVs in nature and the potential effects of these viruses on arboviruses. Mesonivirus is a class of ISVs with a wide geographical distribution. Recently, our laboratory reported the isolation of a novel strain of mesonivirus, Yichang virus (YCV), from Culex mosquitoes, China. In this study, the experimental infection of YCV by the oral route for adult and larvae mosquitoes, and the vertical transmission has been conducted, which suggests that YCV could adopt a mixed-mode transmission. Controlled experiments showed that the infectivity of YCV depends on the mosquito species, virus dose, and infection route. The proliferation curve and tissue distribution of YCV in Cx. quinquefasciatus and Ae. albopictus showed that YCV is more susceptible to Ae. albopictus and is located in the midgut. Furthermore, we also assessed the interference of YCV with flaviviruses both in vitro and in vivo. YCV significantly inhibited the proliferation of DENV-2 and ZIKV, in cell culture, and reduced transmission rate of DENV-2 in Ae. albopictus. Our work provides insights into the transmission of ISVs in different mosquito species during ontogeny and their potential ability to interact with mosquito-borne viruses.

Time delays in treatment of snakebite patients in rural Sri Lanka and the need for rapid diagnostic tests

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Anjana Silva, Jiri Hlusicka, Nipuna Siribaddana, Subodha Waiddyanatha, Senaka Pilapitiya, Prasanna Weerawansa, Niroshan Lokunarangoda, Sujeewa Thalgaspitiya, Sisira Siribaddana, Geoffrey K. Isbister

Delays in treatment seeking and antivenom administration remain problematic for snake envenoming. We aimed to describe the treatment seeking pattern and delays in admission to hospital and administration of antivenom in a cohort of authenticated snakebite patients. Adults (> 16 years), who presented with a confirmed snakebite from August 2013 to October 2014 were recruited from Anuradhapura Hospital. Demographic data, information on the circumstances of the bite, first aid, health-seeking behaviour, hospital admission, clinical features, outcomes and antivenom treatment were documented prospectively. There were 742 snakebite patients [median age: 40 years (IQR:27–51; males: 476 (64%)]. One hundred and five (14%) patients intentionally delayed treatment by a median of 45min (IQR:20-120min). Antivenom was administered a median of 230min (IQR:180–360min) post-bite, which didn’t differ between directly admitted and transferred patients; 21 (8%) receiving antivenom within 2h and 141 (55%) within 4h of the bite. However, transferred patients received antivenom sooner after admission to Anuradhapura hospital than those directly admitted (60min [IQR:30-120min] versus 120min [IQR:52-265min; p<0.0001]). A significantly greater proportion of transferred patients had features of systemic envenoming on admission compared to those directly admitted (166/212 [78%] versus 5/43 [12%]; p<0.0001), and had positive clotting tests on admission (123/212 [58%] versus 10/43 [23%]; p<0.0001). Sri Lankan snakebite patients present early to hospital, but there remains a delay until antivenom administration. This delay reflects a delay in the appearance of observable or measurable features of envenoming and a lack of reliable early diagnostic tests. Improved early antivenom treatment will require reliable, rapid diagnostics for systemic envenoming.

Broad diversity of <i>Mycobacterium tuberculosis</i> complex strains isolated from humans and cattle in Northern Algeria suggests a zoonotic transmission cycle

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Hanane Damene, Djamel Tahir, Maren Diels, Ali Berber, Naima Sahraoui, Leen Rigouts

Mycobacterium tuberculosis complex (MTBC) comprises closely related species responsible for human and animal tuberculosis (TB). Efficient species determination is useful for epidemiological purposes, especially for the elucidation of the zoonotic contribution. In Algeria, data on MTBC genotypes are largely unknown. In this study, we aimed to investigate the occurrence and diversity of MTBC genotypes causing human and bovine TB in Northern Algeria. During a two-year sampling period (2017–2019) in two regions of Northern Algeria, we observed an overall prevalence of 6.5% of tuberculosis (TB) among slaughtered cattle, which is higher than previous Algerian data yet comparable to neighboring countries. A total of 296 Mycobacterium tuberculosis complex (MTBC) isolates were genotyped by spoligotyping: 181 from tissues with TB-like lesions collected from 181 cattle carcasses and 115 from TB patients. In human isolates, we identified 107 M. tuberculosis, seven M. bovis and one “M. pinnipedii-like”, while for bovine samples, 174 isolates were identified as M. bovis, three as M. caprae, three as “M. pinnipedii-like” and one as “M. microti-like”. The majority of isolates (89.2%) belonged to 72 different known Shared International Types (SIT) or M. bovis spoligotypes (SB), while we also identified seven new SB profiles (SB2695 to SB2701). Twenty-eight of the SB profiles were new to Algeria. Our data suggest zoonotic transmission in Sétif, where significantly more TB was observed among cattle (20%) compared to the slaughterhouses from the three other regions (5.4%–7.3%) (p < 0.0001), with the isolation of the same M. bovis genotypes from TB patients. The present study showed a high genetic diversity of MTBC isolated from human and cattle in Northern Algeria. Even though relatively small in terms of numbers, our data suggest the zoonotic transmission of TB from cattle to humans, suggesting the need for stronger eradication strategies for bovine TB.

Evaluation of the sensitivity and specificity of GST-tagged recombinant antigens 2B2t, Ag5t and DIPOL in ELISA for the diagnosis and follow up of patients with cystic echinococcosis

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Carlos Sánchez-Ovejero, Eylem Akdur, Raúl Manzano-Román, Ana Hernández-González, María González-Sánchez, David Becerro-Recio, Javier González-Miguel, 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 a neglected zoonotic disease caused by Echinococcus granulosus sensu lato. Diagnosis and monitoring of CE rely primarily on imaging while serology is used as a confirmatory test. However, imaging is not always conclusive and currently available serological assays have suboptimal sensitivity and specificity, lack standardization, and are not useful for patients´ follow-up. Seroassays for CE are usually based on hydatid fluid (HF), a complex, variable antigenic mixture, and cross-reactivity exists especially with alveolar echinococcosis. Recombinant proteins based on immunogenic antigens most abundant in HF, such as AgB1, AgB2 and Ag5, have been used to overcome these limitations. None of them so far showed potential to replace HF; however, their performance have been largely tested on a limited number of samples, and comparison of different antigens using the same cohort has been rarely performed. The combination of several immunogenic epitopes in a single recombinant protein could enhance test sensitivity. For the diagnosis and follow-up of patients with CE, we compared the performance of the crude HF, previously described recombinant 2B2t antigen, and GST-tagged version of 2B2t, and novel designed recombinants (GST-Ag5t and the GST-DIPOL chimera containing AgB1, AgBB2 and Ag5 epitopes) by IgG-ELISA format. Samples belong to a retrospective cohort of 253 well-characterized patients with CE, previously described for the evaluation of the 2B2t antigen, 92 patients with alveolar echinococcosis, and 82 healthy donors. The reference standard for CE diagnosis was the presence of a CE lesion as diagnosed by ultrasonography. The highest sensitivity was obtained with HF [86.7%, 95% confidence interval (CI): 81.2–91.0], followed by GST-2B2t (70.0%, 95% CI: 63.1–76.2), 2B2t (65.5%, 95% CI: 58.5–72.0), GST-Ag5t (64.5%, 95% CI: 57.5–71.1) and GST-DIPOL (63.1%, 95% CI: 56.0–69.7). The GST-2B2t had the best specificity (95.8%, 95% CI: 88.3–99.1) and the lowest cross-reactivity (38.7%, 95% CI: 27.6–50.6). Good response to treatment also correlated to negative test results in the GST-2B2t ELISA. While none of the tested recombinant antigen appears suitable to replace HF for the diagnosis of CE, GST-2B2t should be further explored as a confirmation test, based on its high specificity and low cross-reactivity, and for the follow-up after treatment in those patients with positive serology for this antigen.

Extracellular non-coding RNA signatures of the metacestode stage of <i>Echinococcus multilocularis</i>

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by María Eugenia Ancarola, Gabriel Lichtenstein, Johannes Herbig, Nancy Holroyd, Mara Mariconti, Enrico Brunetti, Matthew Berriman, Krystyna Albrecht, Antonio Marcilla, Mara Cecilia Rosenzvit, Laura Kamenetzky, Klaus Brehm, Marcela Cucher

Extracellular RNAs (ex-RNAs) are secreted by cells through different means that may involve association with proteins, lipoproteins or extracellular vesicles (EV). In the context of parasitism, ex-RNAs represent new and exciting communication intermediaries with promising potential as novel biomarkers. In the last years, it was shown that helminth parasites secrete ex-RNAs, however, most work mainly focused on RNA secretion mediated by EV. Ex-RNA study is of special interest in those helminth infections that still lack biomarkers for early and/or follow-up diagnosis, such as echinococcosis, a neglected zoonotic disease caused by cestodes of the genus Echinococcus. In this work, we have characterised the ex-RNA profile secreted by in vitro grown metacestodes of Echinococcus multilocularis, the casuative agent of alveolar echinococcosis. We have used high throughput RNA-sequencing together with RT-qPCR to characterise the ex-RNA profile secreted towards the extra- and intra-parasite milieus in EV-enriched and EV-depleted fractions. We show that a polarized secretion of small RNAs takes place, with microRNAs mainly secreted to the extra-parasite milieu and rRNA- and tRNA-derived sequences mostly secreted to the intra-parasite milieu. In addition, we show by nanoparticle tracking analyses that viable metacestodes secrete EV mainly into the metacestode inner vesicular fluid (MVF); however, the number of nanoparticles in culture medium and MVF increases > 10-fold when metacestodes show signs of tegument impairment. Interestingly, we confirm the presence of host miRNAs in the intra-parasite milieu, implying their internalization and transport through the tegument towards the MVF. Finally, our assessment of the detection of Echinococcus miRNAs in patient samples by RT-qPCR yielded negative results suggesting the tested miRNAs may not be good biomarkers for this disease. A comprehensive study of the secretion mechanisms throughout the life cycle of these parasites will help to understand parasite interaction with the host and also, improve current diagnostic tools.

Epilepsy surveillance in normocephalic children with and without prenatal Zika virus exposure

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Karen Blackmon, Randall Waechter, Barbara Landon, Trevor Noël, Calum Macpherson, Tyhiesia Donald, Nikita Cudjoe, Roberta Evans, Kemi S. Burgen, Piumi Jayatilake, Vivian Oyegunle, Otto Pedraza, Samah Abdel Baki, Thomas Thesen, Dennis Dlugos, Geetha Chari, Archana A. Patel, Elysse N. Grossi-Soyster, Amy R. Krystosik, A. Desiree LaBeaud

Children with Congenital Zika Syndrome and microcephaly are at high risk for epilepsy; however, the risk is unclear in normocephalic children with prenatal Zika virus (ZIKV) exposure [Exposed Children (EC)]. In this prospective cohort study, we performed epilepsy screening in normocephalic EC alongside a parallel group of normocephalic unexposed children [Unexposed Children (UC)]. We compared the incidence rate of epilepsy among EC and UC at one year of life to global incidence rates. Pregnant women were recruited from public health centers during the ZIKV outbreak in Grenada, West Indies and assessed for prior ZIKV infection using a plasmonic-gold platform that measures IgG antibodies in serum. Normocephalic children born to mothers with positive ZIKV results during pregnancy were classified as EC and those born to mothers with negative ZIKV results during and after pregnancy were classified as UC. Epilepsy screening procedures included a pediatric epilepsy screening questionnaire and video electroencephalography (vEEG). vEEG was collected using a multi-channel microEEG® system for a minimum of 20 minutes along with video recording of participant behavior time-locked to the EEG. vEEGs were interpreted independently by two pediatric epileptologists, who were blinded to ZIKV status, via telemedicine platform. Positive screening cases were referred to a local pediatrician for an epilepsy diagnostic evaluation. Epilepsy screens were positive in 2/71 EC (IR: 0.028; 95% CI: 0.003–0.098) and 0/71 UC. In both epilepsy-positive cases, questionnaire responses and interictal vEEGs were consistent with focal, rather than generalized, seizures. Both children met criteria for a clinical diagnosis of epilepsy and good seizure control was achieved with carbamazepine. Our results indicate that epilepsy rates are modestly elevated in EC. Given our small sample size, results should be considered preliminary. They support the use of epilepsy screening procedures in larger epidemiological studies of children with congenital ZIKV exposure, even in the absence of microcephaly, and provide guidance for conducting epilepsy surveillance in resource limited settings.

Immunoreactivity and neutralization study of Chinese <i>Bungarus multicinctus</i> antivenin and lab-prepared anti-bungarotoxin antisera towards purified bungarotoxins and snake venoms

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Bo Lin, Jia-Rui Zhang, Hui-Juan Lu, Lin Zhao, Jing Chen, Hong-Fei Zhang, Xue-Song Wei, Liang-Yu Zhang, Xiao-Bing Wu, Wen-Hui Lee

Bungarus multicinctus is the most venomous snake distributed in China and neighboring countries of Myanmar, Laos, north Vietnam and Thailand. The high mortality rate of B. multicinctus envenomation is attributed to the lethal components of α-, β-, γ- and κ- bungarotoxins contained in the venom. Although anti-B. multicinctus sera were produced in Shanghai, Taiwan and Vietnam, the most widely clinic used product was term as B. multicinctus antivenin and manufactured by Shanghai Serum Bio-technology Co. Ltd. In the present investigation, high purity α-, β- and γ-bungarotoxins were separately isolated from B. multicinctus crude venom. Rabbit anti- α-, β- and γ-bungarotoxin antisera were prepared by common methods, respectively. LD50 values of α-, β- and γ-bungarotoxins were systematically determined via three administration pathways (intraperitoneal, intramuscular and intravenous injections) in Kunming mice. LD50 values of β-bungarotoxin were closely related with injection routines but those of both α- and γ-bungarotoxins were not dependent on the injection routines. Commercial B. multicinctus antivenin showed strong immunoreaction with high molecular weight fractions of the B. multicinctus but weakly recognized low molecular weight fractions like α- and γ-bungarotoxins. Although B. multicinctus antivenin showed immunoreaction with high molecular weight fractions of Bungarus fasciatus, Naja atra, Ophiophagus hannah venoms but the antivenin only demonstrated animal protection efficacy against O. hannah venom. These results indicated that the high molecular weight fractions of the O. hannah played an important role in venom lethality but those of B. fasciatus and N. atra did not have such a role.

Analyses of the performance of the Ebola virus disease alert management system in South Sudan: August 2018 to November 2019

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Olushayo Oluseun Olu, Richard Lako, Sudhir Bunga, Kibebu Berta, Matthew Kol, Patrick Otim Ramadan, Caroline Ryan, Ifeanyi Udenweze, Argata Guracha Guyo, Ishata Conteh, Qudsia Huda, Malick Gai, Dina Saulo, Heather Papowitz, Henry John Gray, Alex Chimbaru, Kencho Wangdi, Steven M. Grube, Beth Tippett Barr, Joseph Francis Wamala

South Sudan implemented Ebola virus disease preparedness interventions aiming at preventing and rapidly containing any importation of the virus from the Democratic Republic of Congo starting from August 2018. One of these interventions was a surveillance system which included an Ebola alert management system. This study analyzed the performance of this system. A descriptive cross-sectional study of the Ebola virus disease alerts which were reported in South Sudan from August 2018 to November 2019 was conducted using both quantitative and qualitative methods. As of 30 November 2019, a total of 107 alerts had been detected in the country out of which 51 (47.7%) met the case definition and were investigated with blood samples collected for laboratory confirmation. Most (81%) of the investigated alerts were South Sudanese nationals. The alerts were identified by health workers (53.1%) at health facilities, at the community (20.4%) and by screeners at the points of entry (12.2%). Most of the investigated alerts were detected from the high-risk states of Gbudwe (46.9%), Jubek (16.3%) and Torit (10.2%). The investigated alerts commonly presented with fever, bleeding, headache and vomiting. The median timeliness for deployment of Rapid Response Team was less than one day and significantly different between the 6-month time periods (K-W = 7.7567; df = 2; p = 0.0024) from 2018 to 2019. Strengths of the alert management system included existence of a dedicated national alert hotline, case definition for alerts and rapid response teams while the weaknesses were occasional inability to access the alert toll-free hotline and lack of transport for deployment of the rapid response teams which often constrain quick response. This study demonstrates that the Ebola virus disease alert management system in South Sudan was fully functional despite the associated challenges and provides evidence to further improve Ebola preparedness in the country.

A community survey of coverage and adverse events following country-wide triple-drug mass drug administration for lymphatic filariasis elimination, Samoa 2018

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Gabriela A. Willis, Helen Mayfield, Therese Kearns, Take Naseri, Robert Thomsen, Katherine Gass, Sarah Sheridan, Patricia M. Graves, Colleen L. Lau

The Global Programme to Eliminate Lymphatic Filariasis has made considerable progress but is experiencing challenges in meeting targets in some countries. Recent World Health Organization guidelines have recommended two rounds of triple-drug therapy with ivermectin, diethylcarbamazine (DEC), and albendazole (IDA), in areas where mass drug administration (MDA) results with two drugs (DEC and albendazole) have been suboptimal, as is the case in Samoa. In August 2018, Samoa was the first country in the world to implement countrywide triple-drug MDA. This paper aims to describe Samoa’s experience with program coverage and adverse events (AEs) in the first round of triple-drug MDA. We conducted a large cross-sectional community survey to assess MDA awareness, reach, compliance, coverage and AEs in September/October 2018, 7–11 weeks after the first round of triple-drug MDA. In our sample of 4420 people aged ≥2 years (2.2% of the population), age-adjusted estimates indicated that 89.0% of the eligible population were offered MDA, 83.9% of the eligible population took MDA (program coverage), and 80.2% of the total population took MDA (epidemiological coverage). Overall, 83.8% (2986/3563) reported that they did not feel unwell at all after taking MDA. Mild AEs (feeling unwell but able to do normal everyday things) were reported by 13.3% (476/3563) and moderate or severe AEs (feeling unwell and being unable to do normal everyday activities such as going to work or school) by 2.9% (103/3563) of participants. This study following the 2018 triple-drug MDA in Samoa demonstrated a high reported program awareness and reach of 90.8% and 89.0%, respectively. Age-adjusted program coverage of 83.9% of the total population showed that MDA was well accepted and well tolerated by the community.

The economic burden of dengue fever in the Kingdom of Saudi Arabia

PLoS Neglected Tropical Diseases News - 30 November 2020 - 10:00pm

by Naeema A. Akbar, Abdullah M. Assiri, Omima I. Shabouni, Osama M. Alwafi, Rajaa Al-Raddadi, Mohamad H. Alzahrani, Esam I. Azhar, Ashraf Amir, Abdullah M. Aljiffri, Abdulhakeem O. Althaqafi

Rapid urbanization, global trade, and the exceptionally great numbers of worldwide visitors during Hajj and Umrah have all placed the Kingdom of Saudi Arabia at a significant risk of introducing several vector-borne tropical diseases, such as dengue fever virus (DENV) infection. In this study we estimated DENV infection cost of illness (COI) in Saudi Arabia in the period 2013–2017, by processing national data including all declared cases recorded in referral centers in the western region, being the endemic region of the country. Using a statistically validated predictive model that was built on a representative sample of 717 laboratory-confirmed cases of DENV infection, direct costs, due to care-related expenditures, were estimated by applying the predictive equation to national data. However, indirect costs, which are due to productivity loss, were estimated using the human capital model based on gross domestic product adjusted for invalidity duration. Further, under-reporting was adjusted by using an expansion factor EF = 3. We observed highest estimated costs in 2016 with over US$168.5 Million total costs, including direct (US$29.0 Million) and indirect (US$139.5 Million) costs, for a total 4415 confirmed cases. The total DENV COI for the five years was estimated as US$551.0 Million for a total 15,369 patients (59.7%) out of 25,745 declared cases, resulting in an average cost of US$11 947.6 by patient. Depending on the year, productivity years loss costs accounted for 63.3% to 83.8% of the estimated total costs. Dengue has a substantial local economic burden that costs US$110.2 Million per year, stressing the urgent need for an effective national prevention strategy to perform considerable cost-savings besides reducing morbidity.

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