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Snakebite associated thrombotic microangiopathy: a systematic review of clinical features, outcomes, and evidence for interventions including plasmapheresis

PLoS Neglected Tropical Diseases News - 8 December 2020 - 10:00pm

by Tina Noutsos, Bart J. Currie, Rachel A. Lek, Geoffrey K. Isbister

Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication of snakebite associated with acute kidney injury (AKI). Numerous treatments have been attempted based on limited evidence. We conducted a systematic review of TMA following snakebite using a pre-determined case definition of blood film red cell schistocytes or histologically diagnosed TMA. The search strategy included major electronic databases and grey literature. We present a descriptive synthesis for the outcomes of AKI, dialysis free survival (DFS), other end-organ damage, overall survival, and interventions with antivenom and therapeutic plasmapheresis (TPE). This study was prospectively registered with PROSPERO (CRD42019121436). Seventy-two studies reporting 351 cases were included, predominantly small observational studies. Heterogeneity for study selection, design, reporting and outcomes were observed. The commonest envenoming species were hump-nosed vipers (Hypnale spp.), Russell’s viper (Daboia russelii) and Australian brown snakes (Pseudechis spp.). The prevalence of TMA was at least 5.4% in proven and probable Hypnale bites, and 10–15% of Australian elapid envenomings, AKI occurred in 94% (293/312) of TMA cases, excluding case reports. The majority of cases with AKI required dialysis. Included prospective and retrospective cohort studies reporting interventions and renal outcomes showed no evidence for benefit from antivenom or TPE with respect to DFS in dialysis dependant AKI. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment for quality of accumulated evidence for interventions was low. The major complication of TMA following snakebite is AKI. AKI improves in most cases. We found no evidence to support benefit from antivenom in snakebite associated TMA, but antivenom remains the standard of care for snake envenoming. There was no evidence for benefit of TPE in snakebite associated TMA, so TPE cannot be recommended. The quality of accumulated evidence was low, highlighting a need for high quality larger studies.

Sodium-bile acid co-transporter is crucial for survival of a carcinogenic liver fluke <i>Clonorchis sinensis</i> in the bile

PLoS Neglected Tropical Diseases News - 7 December 2020 - 10:00pm

by Fuhong Dai, Won Gi Yoo, Yanyan Lu, Jin-Ho Song, Ji-Yun Lee, Youngro Byun, Jhang Ho Pak, Woon-Mok Sohn, Sung-Jong Hong

The liver fluke Clonorchis sinensis inhabits the bile ducts, where bile concentration disparities across the fluke cell membrane can cause bile intoxication. Sodium-bile acid co-transporter (SBAT) plays a crucial role in bile acid recycling. The process by which SBAT imports bile acids is electrically coupled to sodium ion co-transportation. Here, we report that the SBAT of C. sinensis (CsSBAT) is involved in bile acid transportation. CsSBAT cDNA encoded a putative polypeptide of 546 amino acid residues. Furthermore, CsSBAT consisted of ten putative transmembrane domains, and its 3D structure was predicted to form panel and core domains. The CsSBAT had one bile acid- and three Na+-binding sites, enabling coordination of a symport process. CsSBAT was mainly localized in the mesenchymal tissue throughout the fluke body and sparsely localized in the basement of the tegument, intestinal epithelium, and excretory bladder wall. Bile acid permeated into the adult flukes in a short time and remained at a low concentration level. Bile acid accumulated inside the mesenchymal tissue when CsSBAT was inhibited using polyacrylic acid–tetradeoxycholic acid conjugate. The accumulated bile acid deteriorated the C. sinensis adults leading to death. CsSBAT silencing shortened the lifespan of the fluke when it was placed into bile. Taken together, we propose that CsSBAT transports bile acids in the mesenchymal tissue and coordinate with outward transporters to maintain bile acid homeostasis of C. sinensis adults, contributing to C. sinensis survival in the bile environment.

Epidemic risk of arboviral diseases: Determining the habitats, spatial-temporal distribution, and abundance of immature <i>Aedes aegypti</i> in the Urban and Rural areas of Zanzibar, Tanzania

PLoS Neglected Tropical Diseases News - 7 December 2020 - 10:00pm

by Fatma Saleh, Jovin Kitau, Flemming Konradsen, Ayubo Kampango, Rahibu Abassi, Karin Linda Schiøler


In Zanzibar, little is known about the arboviral disease vector Aedes aegypti in terms of abundance, spatio-temporal distribution of its larval habitats or factors associated with its proliferation. Effective control of the vector requires knowledge on ecology and habitat characteristics and is currently the only available option for reducing the risk of arboviral epidemics in the island nation of Zanzibar.


We conducted entomological surveys in households and surrounding compounds from February to May 2018 in the urban (Mwembemakumbi and Chumbuni) and rural (Chuini and Kama) Shehias (lowest government administrative unit) situated in the Urban-West region of Unguja island, Zanzibar. Larvae and pupae were collected, transported to the insectary, reared to adult, and identified to species level. Characteristics and types of water containers were also recorded on site. Generalized linear mixed models with binomial and negative binomial distributions were applied to determine factors associated with presence of Ae. aegypti immatures (i.e. both larvae and pupae) or pupae, alone and significant predictors of the abundance of immature Ae. aegypti or pupae, respectively.


The survey provided evidence of widespread presence and abundance of Ae. aegypti mosquitoes in both urban and rural settings of Unguja Island. Interestingly, rural setting had higher numbers of infested containers, all immatures, and pupae than urban setting. Likewise, higher House and Breteau indices were recorded in rural compared to the urban setting. There was no statistically significant difference in Stegomyia indices between seasons across settings. Plastics, metal containers and car tires were identified as the most productive habitats which collectively produced over 90% of all Ae. aegypti pupae. Water storage, sun exposure, vegetation, and organic matter were significant predictors of the abundance of immature Ae. aegypti.


Widespread presence and abundance of Ae. aegypti were found in rural and urban areas of Unguja, the main island of Zanzibar. Information on productive habitats and predictors of colonization of water containers are important for the development of a routine Aedes surveillance system and targeted control interventions in Zanzibar and similar settings.

The prevalence of scabies in Monrovia, Liberia: A population-based survey

PLoS Neglected Tropical Diseases News - 7 December 2020 - 10:00pm

by Shelui Collinson, Joseph Timothy, Samuel K. Zayzay, Karsor K. Kollie, Eglantine Lebas, Neima Candy, Katherine E. Halliday, Rachel Pullan, Mosoka Fallah, Stephen L. Walker, Michael Marks

Scabies is known to be a public health problem in many settings but the majority of recent data is from rural settings in the Pacific. There is a need for high quality data from sub-Saharan Africa and peri-Urban settings to inform scale up of scabies control efforts. There have been anecdotal reports of scabies being a public health problem in Liberia but robust data are lacking. We conducted a cross-sectional cluster-randomised prevalence survey for scabies in a peri-urban community in Monrovia, Liberia in February-March 2020. Participants underwent a standardised examination conducted by trained local health care workers. Health related quality of life (HRQoL) was assessed using age-appropriate versions of the dermatology life quality index (DLQI). Prevalence estimates were calculated accounting for clustering at community and household levels and associations with key demographic variables assessed through multivariable random-effects logistic regression. 1,318 participants from 477 households were surveyed. The prevalence of scabies was 9.3% (95% CI: 6.5–13.2%), across 75 (19.7%) households; impetigo or infected scabies prevalence was 0.8% (95% CI: 0.4–1.9%). The majority (52%) of scabies cases were classified as severe. Scabies prevalence was lower in females and higher in the youngest age group; no associations were found with other collected demographic or socio-economic variables. DLQI scores indicated a very or extremely large effect on HRQoL in 29% of adults and 18% of children diagnosed with scabies. Our study indicates a substantial burden of scabies in this peri-Urban population in Liberia. This was associated with significant impact on quality of life, highlighting the need for action to control scabies in this population. Further work is needed to assess the impact of interventions in this context on both the prevalence of scabies and quality of life.

Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections

PLoS Neglected Tropical Diseases News - 7 December 2020 - 10:00pm

by Andrea Schiefer, Marc P. Hübner, Anna Krome, Christine Lämmer, Alexandra Ehrens, Tilman Aden, Marianne Koschel, Helene Neufeld, Lillibeth Chaverra-Muñoz, Rolf Jansen, Stefan Kehraus, Gabriele M. König, Domen Pogorevc, Rolf Müller, Marc Stadler, Stephan Hüttel, Thomas Hesterkamp, Karl Wagner, Kenneth Pfarr, Achim Hoerauf

Current efforts to eliminate the neglected tropical diseases onchocerciasis and lymphatic filariasis, caused by the filarial nematodes Onchocerca volvulus and Wuchereria bancrofti or Brugia spp., respectively, are hampered by lack of a short-course macrofilaricidal–adult-worm killing–treatment. Anti-wolbachial antibiotics, e.g. doxycycline, target the essential Wolbachia endosymbionts of filariae and are a safe prototype adult-worm-sterilizing and macrofilaricidal regimen, in contrast to standard treatments with ivermectin or diethylcarbamazine, which mainly target the microfilariae. However, treatment regimens of 4–5 weeks necessary for doxycycline and contraindications limit its use. Therefore, we tested the preclinical anti-Wolbachia drug candidate Corallopyronin A (CorA) for in vivo efficacy during initial and chronic filarial infections in the Litomosoides sigmodontis rodent model. CorA treatment for 14 days beginning immediately after infection cleared >90% of Wolbachia endosymbionts from filariae and prevented development into adult worms. CorA treatment of patently infected microfilaremic gerbils for 14 days with 30 mg/kg twice a day (BID) achieved a sustained reduction of >99% of Wolbachia endosymbionts from adult filariae and microfilariae, followed by complete inhibition of filarial embryogenesis resulting in clearance of microfilariae. Combined treatment of CorA and albendazole, a drug currently co-administered during mass drug administrations and previously shown to enhance efficacy of anti-Wolbachia drugs, achieved microfilarial clearance after 7 days of treatment at a lower BID dose of 10 mg/kg CorA, a Human Equivalent Dose of 1.4 mg/kg. Importantly, this combination led to a significant reduction in the adult worm burden, which has not yet been published with other anti-Wolbachia candidates tested in this model. In summary, CorA is a preclinical candidate for filariasis, which significantly reduces treatment times required to achieve sustained Wolbachia depletion, clearance of microfilariae, and inhibition of embryogenesis. In combination with albendazole, CorA is robustly macrofilaricidal after 7 days of treatment and fulfills the Target Product Profile for a macrofilaricidal drug.

Risk assessment and evaluation of China’s policy to prevent COVID-19 cases imported by plane

PLoS Neglected Tropical Diseases News - 7 December 2020 - 10:00pm

by Jinhua Pan, Jie Tian, Haiyan Xiong, Zhixi Liu, Ye Yao, Yesheng Wang, Wenlong Zhu, Yue Wang, Weibing Wang

As of October 5, 2020, China has reported 2,921 cases imported from overseas. Assessing the effectiveness of China's current policies on imported cases abroad is very important for China and other countries that are facing or will face overseas imported cases. In April, we used a susceptible-exposed-infectious-recovered metapopulation model to simulate the epidemic in seven foreign countries, China and the three Chinese key cities. Based on the model outside China, we estimated the proportion of people in incubation period and calculated the risk indexes for Chinese cities through analyzing aviation traffic data from these countries. Based on the model in China and the three key cities, we collected information on control measures and quantified the effectiveness of implementing the current policies at different times and intensities. Our model results showed that Shanghai, Beijing, Qingdao, Guangzhou, and Tianjin have the top five risk indexes. As of April 20, 2020, under current measures, the number of confirmed cases could be reduced by 99% compared with no air traffic restrictions and isolation measures; the reduction could be 93% with isolation of passengers only from key countries. If the current policy were postponed for 7, 10, or 20 days, the increase in the number of confirmed cases would be 1,329, 5,524, and 779,245 respectively, which is 2.1, 5.7, and 662.9 times the number of confirmed cases under current measures. Our research indicates that the importation control measures currently taken by China were implemented at an appropriate time to prevent the epidemic spreading and have achieved relatively good control results. However, it is necessary to remain vigilant; otherwise, another outbreak peak could occur.

Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children

PLoS Neglected Tropical Diseases News - 7 December 2020 - 10:00pm

by Amanda Gwee, Stephen Duffull, Xiao Zhu, Steven Y. C. Tong, Noel Cranswick, Brett McWhinney, Jacobus Ungerer, Joshua Francis, Andrew C. Steer

Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulnerable to scabies and its secondary complications. Therefore, this study aimed to determine an appropriate ivermectin dose for children aged 2 to 4 years and weighing ≤15 kg. We conducted a prospective, pharmacokinetic study of ivermectin in Indigenous Australian children aged between 5 and 15 years and weighing >15 kg. Doses of 200 μg/kg rounded to the nearest whole or half 3 mg tablet were given to children with scabies and ivermectin concentrations determined at two time points after dosing. A population pharmacokinetic model was developed using non-linear mixed effects modelling. A separate covariate database of children aged 2 to 4 years and weighing <15 kg was used to generate 1000 virtual patients and simulate the dose required to achieve equivalent drug exposure in young children as those aged ≥5 years. Overall, 26 children who had 48 ivermectin concentrations determined were included, 11 (42%) were male, the median age was 10.9 years and median body weight 37.6 kg. The final model was a two-compartment model with first-order absorption and linear elimination. For simulated children aged 2 to 4 years, a dose of 3 mg in children weighing 10–15 kg produced similar drug exposures to those >5 years. The median simulated area under the concentration-time curve was 976 μg∙h/L. Using modelling, we have identified a dosing strategy for ivermectin in children aged 2 to 4 years and weighing less than 15 kg that can be prospectively evaluated for safety and efficacy.

Diagnostic accuracy of an in-house Scrub Typhus Enzyme linked immunoassay for the detection of IgM and IgG antibodies in Laos

PLoS Neglected Tropical Diseases News - 7 December 2020 - 10:00pm

by Philip N. D. Elders, Sandhya Dhawan, Ampai Tanganuchitcharnchai, Koukeo Phommasone, Vilada Chansamouth, Nicholas P. J. Day, Jose A. Garcia-Rivera, Jeffrey C. Hertz, Mayfong Mayxay, Manivanh Vongsouvath, Audrey Dubot-Pérès, Matthew T. Robinson, Paul N. Newton, Stuart D. Blacksell

Scrub typhus is a major cause of morbidity and mortality in Southeast Asia. Diagnosis of scrub typhus is difficult due to a lack of accessible validated diagnostic tools. Despite its objectivity, the diagnostic accuracy of ELISA tests is influenced by methodological and patient factors. This study aims to evaluate the performance of a novel in-house ELISA developed in the Mahidol Oxford Tropical Medicine Research Unit (MORU) for anti-scrub typhus group IgM and IgG compared to the “gold standard” reference IFA and PCR, and to determine whether the in-house ELISA can be used as a seroepidemiological screening tool and/or stand-alone test for scrub typhus. A total of 1,976 admission and 1,438 participant follow-up sera collected in the Lao PDR (Laos) were tested with ELISA for IgM and IgG. Samples with an ELISA OD≥0.50 were tested with IFA for IgM and/or IgG. A strong positive relationship was present between ELISA ODs and IFA titers for admission IgM (r2: 0.70, p <0.005) and IgG (r2: 0.76, p<0.005), and for follow-up IgM and IgG (both r2: 0.76, p<0.005) samples. The best compromise between sensitivity and specificity for the ELISA OD cut-off is likely to be between 0.8–1.0 for IgM antibodies and 1.2–1.8 for IgG antibodies. These results demonstrate that the diagnostic accuracy of the MORU in-house scrub typhus group ELISA is comparable to that of IFA, with similar results as reported for the commonly used InBios Scrub Typhus Detect ELISA, validating the use of the in-house ELISA. The optimal ELISA cut-off would depend on the use of the test, and the desired sensitivity and specificity. Further studies are required to authenticate the use of these cut-offs in other endemic regions. This in-house ELISA has the potential to replace the imperfect IFA, which could ultimately reduce the burden of scrub typhus by improving the rate of scrub typhus diagnoses in endemic low-resource areas.

Post-intervention epidemiology of STH in Bangladesh: Data to sustain the gains

PLoS Neglected Tropical Diseases News - 7 December 2020 - 10:00pm

by Sanjaya Dhakal, Mohammad Jahirul Karim, Abdullah Al Kawsar, Jasmine Irish, Mujibur Rahman, Cara Tupps, Ashraful Kabir, Rubina Imtiaz

In 2008, Bangladesh initiated Preventive Chemotherapy (PCT) for school-age children (SAC) through bi-annual school-based mass drug administration (MDA) to control Soil-Transmitted Helminth (STH) infections. In 2016, the Ministry of Health and Family Welfare’s Program on Lymphatic Filariasis Elimination and STH (ELFSTH) initiated district-level community impact assessments with Children Without Worms (CWW) using standardized, population-based sampling to measure the post-intervention STH burden across all ages (≥ 1 yr) for the three STH species. The Integrated Community-based Survey for Program Monitoring (ICSPM) was developed by CWW and was used to survey 12 districts in Bangladesh from 2017–2020. We excluded the first two district data as piloting caused some sampling errors and combined the individual demographic and parasite-specific characteristics from the subsequent 10 districts, linking them with the laboratory data for collective analysis. Our analysis identified district-specific epidemiologic findings, important for program decisions. Of the 17,874 enrolled individuals, our results are based on 10,824 (61.0%) stool samples. Overall, the prevalence of any STH species was substantially reduced to 14% from 79.8% in 2005. The impact was similar across all ages. STH prevalence was 14% in 10 districts collectively, but remained high in four districts, despite their high reported PCT coverage in previous years. Among all, Bhola district was unique because it was the only district with high T.trichuris prevalence. Bangladesh successfully lowered STH prevalence across all ages despite targeting SAC only. Data from the survey indicate a significant number of adults and pre-school age children (PSAC) were self-deworming with purchased pills. This may account for the flat impact curve across all ages. Overall prevalence varied across surveyed districts, with persistent high transmission in the northeastern districts and a district in the central flood zone, indicating possible service and ecological factors. Discrepancies in the impact between districts highlight the need for district-level data to evaluate program implementation after consistent high PCT coverage.

Recombinant Rift Valley fever viruses encoding bluetongue virus (BTV) antigens: Immunity and efficacy studies upon a BTV-4 challenge

PLoS Neglected Tropical Diseases News - 4 December 2020 - 10:00pm

by Sandra Moreno, Eva Calvo-Pinilla, Stephanie Devignot, Friedemann Weber, Javier Ortego, Alejandro Brun


Many ruminant diseases of viral aetiology can be effectively prevented using appropriate vaccination measures. For diseases such as Rift Valley fever (RVF) the long inter-epizootic periods make routine vaccination programs unfeasible. Coupling RVF prophylaxis with seasonal vaccination programmes by means of multivalent vaccine platforms would help to reduce the risk of new RVF outbreaks.

Methodology/Principal findings

In this work we generated recombinant attenuated Rift Valley fever viruses (RVFVs) encoding in place of the virulence factor NSs either the VP2 capsid protein or a truncated form of the non-structural NS1 protein of bluetongue virus serotype 4 (BTV-4). The recombinant viruses were able to carry and express the heterologous BTV genes upon consecutive passages in cell cultures. In murine models, a single immunization was sufficient to protect mice upon RVFV challenge and to elicit a specific immune response against BTV-4 antigens that was fully protective after a BTV-4 boost. In sheep, a natural host for RVFV and BTV, both vaccines proved immunogenic although conferred only partial protection after a virulent BTV-4 reassortant Morocco strain challenge.


Though additional optimization will be needed to improve the efficacy data against BTV in sheep, our findings warrant further developments of attenuated RVFV as a dual vaccine platform carrying heterologous immune relevant antigens for ruminant diseases in RVF risk areas.

Halogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form <i>Trypanosoma brucei</i>

PLoS Neglected Tropical Diseases News - 4 December 2020 - 10:00pm

by Peter E. Cockram, Emily A. Dickie, Michael P. Barrett, Terry K. Smith

Amino acid metabolism within Trypanosoma brucei, the causative agent of human African trypanosomiasis, is critical for parasite survival and virulence. Of these metabolic processes, the transamination of aromatic amino acids is one of the most important. In this study, a series of halogenated tryptophan analogues were investigated for their anti-parasitic potency. Several of these analogues showed significant trypanocidal activity. Metabolomics analysis of compound-treated parasites revealed key differences occurring within aromatic amino acid metabolism, particularly within the widely reported and essential transamination processes of this parasite.

Community perspectives on scabies, impetigo and mass drug administration in Fiji: A qualitative study

PLoS Neglected Tropical Diseases News - 4 December 2020 - 10:00pm

by Elke Mitchell, Stephen Bell, Li Jun Thean, Aalisha Sahukhan, Mike Kama, Aminiasi Koroivueti, John Kaldor, Andrew Steer, Lucia Romani

Scabies is endemic in Fiji and is a significant cause of morbidity. Little is known about the sociocultural beliefs and practices that affect the occurrence of scabies and impetigo, or community attitudes towards the strategy of mass drug administration that is emerging as a public health option for scabies and impetigo control in Fiji and other countries. Data were collected during semi-structured interviews with 33 community members in four locations in Fiji’s Northern Division. Thematic analysis examined participants’ lived experiences of scabies and impetigo; community knowledge and perceptions about scabies and impetigo aetiology and transmission; community-based treatment and prevention measures; and attitudes towards mass drug administration. Many indigenous Fijian (iTaukei) participants noted extensive and ongoing experience of scabies and impetigo among children in their families and communities, but only one participant of Indian descent (Indo-Fijian) identified personal childhood experience of scabies. Scabies and impetigo were perceived as diseases affecting children, impacting on school attendance and families’ quality of sleep. Awareness of scabies and impetigo was considerable, but there were major misconceptions around disease causation and transmission. Traditional remedies were preferred for scabies treatment, followed by biomedicines provided by local health centres and hospitals. Treatment of close household contacts was not prioritised. Attitudes towards mass drug administration to control scabies were mostly positive, although some concerns were noted about adverse effects and hesitation to participate in the planned scabies elimination programme. Findings from this first study to document perspectives and experiences related to scabies and impetigo and their management in the Asia Pacific region illustrate that a community-centred approach to scabies and impetigo is needed for the success of control efforts in Fiji, and most likely in other affected countries. This includes community-based health promotion messaging on the social dynamics of scabies transmission, and a campaign of education and community engagement prior to mass drug administration.

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


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.


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.