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One-year descriptive analysis of patients treated at an anti-rabies clinic—A retrospective study from Kashmir

PLoS Neglected Tropical Diseases News - 25 August 2020 - 9:00pm

by Khalid Bashir, Inaamul Haq, S. Muhammad Salim Khan, Mariya Amin Qurieshi

Dog bites in humans are a major public health problem in India in general and Kashmir in particular. Canine rabies is almost non-existent in developed countries and exists mainly in the poorer, low socioeconomic strata of society in the developing world. The objective of this study was to determine the characteristics, pattern, and burden of dog bite injuries in the Kashmir valley. Data from Anti-Rabies Clinic of a tertiary care hospital in Srinagar, the summer capital of the state of Jammu & Kashmir, was collated and analyzed. Analysis of records of all the patients who had reported between April 2016 and March 2017 was done. A total of 6172 patients had reported to the Anti-Rabies Clinic for management of animal bites from 1st April 2016 to 31st March 2017. Most of the patients were young males. Almost half (47.7%) of the patients were bitten in the afternoon. Lower limbs were the most common site of bite (71.7%). Most of the bites were of Category III (57.6%) followed by Category II (42.3%); only one case of Category I was recorded. Almost all (98.0%) cases reported being bitten by dogs. Conclusions: Category III dog bites on lower limbs were the most common type of animal bites presenting to the Anti-Rabies Clinic of a tertiary care hospital. Children have more chances of a bite on head and neck region. Serious and workable efforts have to be made to reduce the incidence and consequences of animal bites.

<i>Schistosoma haematobium</i> infection and environmental factors in Southwestern Tanzania: A cross-sectional, population-based study

PLoS Neglected Tropical Diseases News - 24 August 2020 - 9:00pm

by Kirsi M. Manz, Inge Kroidl, Petra Clowes, Martina Gerhardt, Wilbrod Nyembe, Lucas Maganga, Weston Assisya, Nyanda E. Ntinginya, Ursula Berger, Michael Hoelscher, Elmar Saathoff

Schistosomiasis is a leading cause of morbidity in Africa. Understanding the disease ecology and environmental factors that influence its distribution is important to guide control efforts. Geographic information systems have increasingly been used in the field of schistosomiasis environmental epidemiology. This study reports prevalences of Schistosoma haematobium infection and uses remotely sensed and questionnaire data from over 17000 participants to identify environmental and socio-demographic factors that are associated with this parasitic infection. Data regarding socio-demographic status and S. haematobium infection were obtained between May 2006 and May 2007 from 17280 participants (53% females, median age = 17 years) in the Mbeya Region, Tanzania. Combined with remotely sensed environmental data (vegetation cover, altitude, rainfall etc.) this data was analyzed to identify environmental and socio-demographic factors associated with S. haematobium infection, using mixed effects logistic regression and geostatistical modelling. The overall prevalence of S. haematobium infection was 5.3% (95% confidence interval (CI): 5.0–5.6%). Multivariable analysis revealed increased odds of infection for school-aged children (5–15 years, odds ratio (OR) = 7.8, CI: 5.9–10.4) and the age groups 15–25 and 25–35 years (15–25 years: OR = 5.8, CI: 4.3–8.0, 25–35 years: OR = 1.6, CI: 1.1–2.4) compared to persons above 35 years of age, for increasing distance to water courses (OR = 1.4, CI: 1.2–1.6 per km) and for proximity to Lake Nyasa (<1 km, OR = 4.5, CI: 1.8–11.4; 1–2 km, OR = 3.5, CI: 1.7–7.5; 2–4 km; OR = 3.3, CI: 1.7–6.6), when compared to distances >4 km. Odds of infection decreased with higher altitude (OR = 0.7, CI: 0.6–0.8 per 100 m increase) and with increasing enhanced vegetation index EVI (OR = 0.2, CI: 0.1–0.4 per 0.1 units). When additionally adjusting for spatial correlation population density became a significant predictor of schistosomiasis infection (OR = 1.3, CI: 1.1–1.5 per 1000 persons/km2) and altitude turned non-significant. We found highly focal geographical patterns of S. haematobium infection in Mbeya Region in Southwestern Tanzania. Despite low overall prevalence our spatially heterogeneous results show that some of the study sites suffer from a considerable burden of S. haematobium infection, which is related to various socio-demographic and environmental factors. Our results could help to design more effective control strategies in the future, especially targeting school-aged children living in low altitude sites and/or crowded areas as the persons at highest need for preventive chemotherapy.

Positive impact of preventative chemotherapy during a national helminth control program: Perception and KAP

PLoS Neglected Tropical Diseases News - 24 August 2020 - 9:00pm

by Francisca Mutapi, Paradzayi Tagwireyi, Rivka Lim, Blessing Mangwanda, Charmaine Fourier, Takafira Mduluza

Helminth control at the national level is currently based on mass drug administration (MDA) programs. Perception of the MDA programs for helminth control by the affected populations influences compliance and future designs of the programs. We determined the perception of Zimbabwe’s National Helminth Control Program (2012–2017) with a specific focus on schistosomiasis in the school children treated with praziquantel, schoolteachers and village health workers (VHW). The study enrolled 409 children from Grades 6 and 7 who had the full benefit of the 6 years of MDA from 2012 to 2017. Thirty-six schoolteachers and 22 VHW serving the schools were also recruited. A structured questionnaire developed in English, translated into the local language Shona, and validated prior to the study was administered to the children and the adults. The questions focused on the perceived impact on health, school attendance and performance and Knowledge Attitudes and Practice (KAP) among the school children. Data were captured electronically on android platforms using the Open Data Kit. Overall, 84% of the children responded that their awareness of schistosomiasis (transmission, disease, treatment and infection avoidance) had improved because of participating in the MDAs. Of the 151 children self-diagnosed with schistosomiasis, 74% reported that their health had improved following treatment with praziquantel. This included resolution of haematuria, painful urination, sore stomach, tiredness and falling asleep during class lessons. The children and teachers reported improvements in both pupil school attendance and performance at school while the VHW and teachers reported an increase in health-seeking behaviour amongst the school children for schistosomiasis treatment in-between MDAs. The majority of VHW (96%) reported improvement in handwashing behaviour, schistosomiasis awareness (96%) and treatment uptake (91%) within the communities where the school children belonged. However, only 59% of the VHW reported improvement in toilet use while only 50% of the VHW reported improvement in clean water use within their communities. This study indicated that the surveyed children perceived the MDA program had improved their health, school attendance, school performance and awareness of schistosomiasis. The VHW also perceived that the MDA program had improved the community KAP.

Correction: Genus-wide <i>Leptospira</i> core genome multilocus sequence typing for strain taxonomy and global surveillance

PLoS Neglected Tropical Diseases News - 21 August 2020 - 9:00pm

by Julien Guglielmini, Pascale Bourhy, Olivier Schiettekatte, Farida Zinini, Sylvain Brisse, Mathieu Picardeau

Chlorination of <i>Schistosoma mansoni</i> cercariae

PLoS Neglected Tropical Diseases News - 21 August 2020 - 9:00pm

by Laura Braun, Yasinta Daniel Sylivester, Meseret Dessalegne Zerefa, Muluwork Maru, Fiona Allan, Feleke Zewge, Aidan M. Emery, Safari Kinung’hi, Michael R. Templeton

Background

Schistosomiasis is a water-based disease acquired through contact with cercaria-infested water. Communities living in endemic regions often rely on parasite-contaminated freshwater bodies for their daily water contact activities, resulting in recurring schistosomiasis infection. In such instances, water treatment can provide safe water on a household or community scale. However, to-date there are no water treatment guidelines that provide information on how to treat water containing schistosome cercariae. Here, we rigorously test the effectiveness of chlorine against Schistosoma mansoni cercariae.

Method

S. mansoni cercariae were chlorinated using sodium hypochlorite under lab and field condition. The water pH was controlled at 6.5, 7.0 or 7.5, the water temperature at 20°C or 27°C, and the chlorine dose at 1, 2 or 3 mg/l. Experiments were conducted up to contact times of 45 minutes. 100 cercariae were used per experiment, thereby achieving up to 2-log10 inactivations of cercariae. Experiments were replicated under field conditions at Lake Victoria, Tanzania.

Conclusion

A CT (residual chlorine concentration x chlorine contact time) value of 26±4 mg·min/l is required to achieve a 2-log10 inactivation of S. mansoni cercariae under the most conservative condition tested (pH 7.5, 20°C). Field and lab-cultivated cercariae show similar chlorine sensitivities. A CT value of 30 mg·min/l is therefore recommended to disinfect cercaria-infested water, though safety factors may be required, depending on water quality and operating conditions. This CT value can be achieved with a chlorine residual of 1 mg/l after a contact time of 30 minutes, for example. This recommendation can be used to provide safe water for household and recreational water activities in communities that lack safe alternative water sources.

Duplex real-time PCR for sexing <i>Schistosoma japonicum</i> cercariae based on W chromosome-specific genes and its applications

PLoS Neglected Tropical Diseases News - 21 August 2020 - 9:00pm

by Shuai Liu, Xianyu Piao, Nan Hou, Pengfei Cai, Yu Ma, Qijun Chen

As a unique feature among otherwise hermaphroditic trematodes, Schistosoma species are gonochoric parasites whose sex is genetically determined (ZZ for males and ZW for females). However, schistosome larvae are morphologically identical, and sex can only be discriminated by molecular methods. Here, we integrated published Schistosoma. japonicum transcriptome and genome data to identify W chromosome-specific genes as sex biomarkers. Three W chromosome-specific genes of S. japonicum were identified as sex biomarkers from a panel of 12 genes expressed only in females. An efficient duplex real-time PCR (qPCR) method for sexing cercariae was developed which could identify the sex of cercariae within 2 h without DNA extraction. Moreover, this method can be used to identify not only single-sex but also mixed-sex schistosome-infected snails. We observed a nearly equal proportion of single-male, single-female, and mixed-sex schistosome infections in artificially infected snails. Sex-known schistosome-infected snail models can be efficiently constructed with the aid of duplex qPCR. A field study revealed that single-sex schistosome infections were predominant among naturally infected snails. Finally, a schistosomiasis mouse model based on sex-known cercariae infection was shown to be more reliable than a model based on sex-unknown cercariae infection. The developed duplex qPCR method for sexing S. japonicum cercariae can be widely used for schistosomiasis modeling, genetic experiments, and field-based molecular epidemiological studies.

An analysis of preclinical efficacy testing of antivenoms for sub-Saharan Africa: Inadequate independent scrutiny and poor-quality reporting are barriers to improving snakebite treatment and management

PLoS Neglected Tropical Diseases News - 20 August 2020 - 9:00pm

by Stuart Ainsworth, Stefanie K. Menzies, Nicholas R. Casewell, Robert A. Harrison

Background

The World Health Organization’s strategy to halve snakebite mortality and morbidity by 2030 includes an emphasis on a risk-benefit process assessing the preclinical efficacy of antivenoms manufactured for sub-Saharan Africa. To assist this process, we systematically collected, standardised and analysed all publicly available data on the preclinical efficacy of antivenoms designed for sub-Saharan Africa.

Methodology/Principal findings

Using a systematic search of publication databases, we focused on publicly available preclinical reports of the efficacy of 16 antivenom products available in sub Saharan Africa. Publications since 1999 reporting the industry standard intravenous pre-incubation method of murine in vivo neutralisation of venom lethality (median effective dose [ED50]) were included. Eighteen publications met the criteria. To permit comparison of the several different reported ED50 values, it was necessary to standardise these to microlitre of antivenom resulting in 50% survival of mice challenged per milligram of venom (μl/mg). We were unable to identify publicly available preclinical data on four antivenoms, whilst data for six polyspecific antivenoms were restricted to a small number of venoms. Only four antivenoms were tested against a wide range of venoms. Examination of these studies for the reporting of key metrics required for interpreting antivenom ED50s were highly variable, as evidenced by eight different units being used for the described ED50 values.

Conclusions/Significance

There is a disturbing lack of (i) preclinical efficacy testing of antivenom for sub Saharan Africa, (ii) publicly available reports and (iii) independent scrutiny of this medically important data. Where reports do exist, the methods and metrics used are highly variable. This prevents comprehensive meta-analysis of antivenom preclinical efficacy, and severely reduces the utility of antivenom ED50 results in the decision making of physicians treating patients and of national and international health agencies. Here, we propose the use of a standardised result reporting checklist to resolve this issue. Implementation of these straightforward steps will deliver uniform evaluation of products across laboratories, facilitate meta-analyses, and contribute vital information for designing the clinical trials needed to achieve the WHO target of halving snakebite morbidity and mortality by 2030.

Accuracy of different diagnostic techniques for <i>Schistosoma haematobium</i> to estimate treatment needs in Zimbabwe: Application of a hierarchical Bayesian egg count model

PLoS Neglected Tropical Diseases News - 20 August 2020 - 9:00pm

by Nicholas Midzi, Oliver Bärenbold, Portia Manangazira, Isaac Phiri, Masceline J. Mutsaka-Makuvaza, Gibson Mhlanga, Jürg Utzinger, Penelope Vounatsou

Background

Treatment needs for Schistosoma haematobium are commonly evaluated using urine filtration with detection of parasite eggs under a microscope. A common symptom of S. haematobium is hematuria, the passing of blood in urine. Hence, the use of hematuria-based diagnostic techniques as a proxy for the assessment of treatment needs has been considered. This study evaluates data from a national survey in Zimbabwe, where three hematuria-based diagnostic techniques, that is microhematuria, macrohematuria, and an anamnestic questionnaire pertaining to self-reported blood in urine, have been included in addition to urine filtration in 280 schools across 70 districts.

Methodology

We developed an egg count model, which evaluates the infection intensity-dependent sensitivity and the specificity of each diagnostic technique without relying on a ‘gold’ standard. Subsequently, we determined prevalence thresholds for each diagnostic technique, equivalent to a 10% urine filtration-based prevalence and compared classification of districts according to treatment strategy based on the different diagnostic methods.

Principal findings

A 10% urine filtration prevalence threshold corresponded to a 17.9% and 13.3% prevalence based on questionnaire and microhematuria, respectively. Both the questionnaire and the microhematuria showed a sensitivity and specificity of more than 85% for estimating treatment needs at the above thresholds. For diagnosis at individual level, the questionnaire showed the highest sensitivity at (70.0%) followed by urine filtration (53.8%) and microhematuria (52.2%).

Conclusions/Significance

The high sensitivity and specificity of a simple questionnaire to estimate treatment needs of S. haematobium suggests that it can be used as a rapid, low-cost method to estimate district prevalence. Our modeling approach can be expanded to include setting-dependent specificity of the technique and should be assessed in relation to other diagnostic methods due to potential cross-reaction with other diseases.

Why is noma a neglected-neglected tropical disease?

PLoS Neglected Tropical Diseases News - 20 August 2020 - 9:00pm

by M. Leila Srour, Denise Baratti-Mayer

Noma is an orofacial gangrene affecting primarily children living in extreme poverty in remote parts of subtropical and tropical countries. Mortality and disability are high, and survivors often have physical and functional deformities resulting in stigma and isolation. Many healthcare professionals and primary healthcare workers where noma risk factors exist have no knowledge about noma and its implications. Public health measures to improve nutrition, immunizations, sanitation, and access to healthcare and measures to eliminate extreme poverty can lead to the eradication of noma. Research allocation has been insufficient to study the epidemiology, treatment, and prevention of noma. In a recent editorial by Hotez and colleagues in PLOS Neglected Tropical Diseases (NTDs), “What constitutes an NTD?” Noma is not included. The exclusion of noma from NTDs constitutes this preventable childhood disease as a neglected neglected disease. The purpose of this article is the inclusion of noma with the PLOS NTDs. Increased awareness and attention to noma can lead to the eradication of this disease affecting the world’s most vulnerable.

Challenges and prospects of snake antivenom supply in sub-Saharan Africa

PLoS Neglected Tropical Diseases News - 20 August 2020 - 9:00pm

by Abdulrazaq G. Habib, Baba M. Musa, Garba Iliyasu, Muhammad Hamza, Andreas Kuznik, Jean-Philippe Chippaux

Dengue in a crowded megacity: Lessons learnt from 2019 outbreak in Dhaka, Bangladesh

PLoS Neglected Tropical Diseases News - 20 August 2020 - 9:00pm

by Mohammad Sorowar Hossain, Mahbubul H. Siddiqee, Umme Ruman Siddiqi, Enayetur Raheem, Rokeya Akter, Wenbiao Hu

Differentiation-dependent susceptibility of human muscle cells to Zika virus infection

PLoS Neglected Tropical Diseases News - 20 August 2020 - 9:00pm

by Vincent Legros, Patricia Jeannin, Julien Burlaud-Gaillard, Thibault Chaze, Quentin Giai Gianetto, Gillian Butler-Browne, Vincent Mouly, Jim Zoladek, Philippe V. Afonso, Mariela-Natacha Gonzàlez, Mariette Matondo, Ingo Riederer, Philippe Roingeard, Antoine Gessain, Valérie Choumet, Pierre-Emmanuel Ceccaldi

Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, that may be involved in the physiopathological course of the infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human primary myoblasts that can be differentiated into myotubes, we found that myoblasts can be productively infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection, suggesting a differentiation-dependent susceptibility. Infection was accompanied by a caspase-independent cytopathic effect, associated with paraptosis-like cytoplasmic vacuolization. Proteomic profiling was performed 24h and 48h post-infection in cells infected with two different isolates. Proteome changes indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, and differentiation-dependent restriction of infection from myoblasts to myotubes. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences in ZIKV infection pathogenesis.

Genetic diversity and evolution of Hantaan virus in China and its neighbors

PLoS Neglected Tropical Diseases News - 20 August 2020 - 9:00pm

by Naizhe Li, Aqian Li, Yang Liu, Wei Wu, Chuan Li, Dongyang Yu, Yu Zhu, Jiandong Li, Dexin Li, Shiwen Wang, Mifang Liang

Background

Hantaan virus (HTNV; family Hantaviridae, order Bunyavirales) causes hemorrhagic fever with renal syndrome (HFRS), which has raised serious concerns in Eurasia, especially in China, Russia, and South Korea. Previous studies reported genetic diversity and phylogenetic features of HTNV in different parts of China, but the analyses from the holistic perspective are rare.

Methodology and principal findings

To better understand HTNV genetic diversity and gene evolution, we analyzed all available complete sequences derived from the small (S) and medium (M) segments with bioinformatic tools. Eleven phylogenetic groups were defined and showed geographic clustering; 42 significant amino acid variant sites were found, and 19 of them were located in immune epitopes; nine recombinant events and eight reassortments with highly divergent sequences were found and analyzed. We found that sequences from Guizhou showed high genetic divergence, contributing to multiple lineages of the phylogenetic tree and also to the recombination and reassortment events. Bayesian stochastic search variable selection analysis revealed that Heilongjiang, Shaanxi, and Guizhou played important roles in HTNV evolution and migration; the virus may originate from Zhejiang Province in the eastern part of China; and the virus population size expanded from the 1980s to 1990s.

Conclusions/significance

These findings revealed the original and evolutionary features of HTNV, which will help to illustrate hantavirus epidemic trends, thus aiding in disease control and prevention.

The <i>Aedes albopictus</i> (Diptera: Culicidae) microbiome varies spatially and with Ascogregarine infection

PLoS Neglected Tropical Diseases News - 19 August 2020 - 9:00pm

by Priscilla Seabourn, Helen Spafford, Nicole Yoneishi, Matthew Medeiros

The mosquito microbiome alters the physiological traits of medically important mosquitoes, which can scale to impact how mosquito populations sustain disease transmission. The mosquito microbiome varies significantly within individual mosquitoes and among populations, however the ecological and environmental factors that contribute to this variation are poorly understood. To further understand the factors that influence variation and diversity of the mosquito microbiome, we conducted a survey of the bacterial microbiome in the medically important mosquito, Aedes albopictus, on the high Pacific island of Maui, Hawai‘i. We detected three bacterial Phyla and twelve bacterial families: Proteobacteria, Acitinobacteria, and Firmicutes; and Anaplasmataceae, Acetobacteraceae, Enterobacteriaceae, Burkholderiaceae, Xanthobacteraceae, Pseudomonadaceae, Streptomycetaceae, Staphylococcaceae, Xanthomonadaceae, Beijerinckiaceae, Rhizobiaceae, and Sphingomonadaceae. The Ae. albopictus bacterial microbiota varied among geographic locations, but temperature and rainfall were uncorrelated with this spatial variation. Infection status with an ampicomplexan pathosymbiont Ascogregarina taiwanensis was significantly associated with the composition of the Ae. albopictus bacteriome. The bacteriomes of mosquitoes with an A. taiwanensis infection were more likely to include several bacterial symbionts, including the most abundant lineage of Wolbachia sp. Other symbionts like Asaia sp. and several Enterobacteriaceae lineages were less prevalent in A. taiwanensis-infected mosquitoes. This highlights the possibility that inter- and intra-domain interactions may structure the Ae. albopictus microbiome.

Epidemiology of dengue fever in Guatemala

PLoS Neglected Tropical Diseases News - 19 August 2020 - 9:00pm

by Leticia del Carmen Castillo Signor, Thomas Edwards, Luis E. Escobar, Yolanda Mencos, Agnes Matope, Mariana Castaneda-Guzman, Emily R. Adams, Luis E. Cuevas

Dengue fever occurs worldwide and about 1% of cases progress to severe haemorrhage and shock. Dengue is endemic in Guatemala and its surveillance system could document long term trends. We analysed 17 years of country-wide dengue surveillance data in Guatemala to describe epidemiological trends from 2000 to 2016.Data from the national dengue surveillance database were analysed to describe dengue serotype frequency, seasonality, and outbreaks. We used Poisson regression models to compare the number of cases each year with subsequent years and to estimate incidence ratios within serotype adjusted by age and gender. 91,554 samples were tested. Dengue was confirmed by RT-qPCR, culture or NS1-ELISA in 7097 (7.8%) cases and was IgM ELISA-positive in 19,290 (21.1%) cases. DENV1, DENV2, DENV3, and DENV4 were detected in 2218 (39.5%), 2580 (45.9%), 591 (10.5%), and 230 (4.1%) cases. DENV1 and DENV2 were the predominant serotypes, but all serotypes caused epidemics. The largest outbreak occurred in 2010 with 1080 DENV2 cases reported. The incidence was higher among adults during epidemic years, with significant increases in 2005, 2007, and 2013 DENV1 outbreaks, the 2010 DENV2 and 2003 DENV3 outbreaks. Adults had a lower incidence immediately after epidemics, which is likely linked to increased immunity.

Marked mitochondrial genetic variation in individuals and populations of the carcinogenic liver fluke <i>Clonorchis sinensis</i>

PLoS Neglected Tropical Diseases News - 19 August 2020 - 9:00pm

by Liina Kinkar, Pasi K. Korhonen, Daxi Wang, Xing-Quan Zhu, Galina N. Chelomina, Tao Wang, Ross S. Hall, Anson V. Koehler, Ivon Harliwong, Bicheng Yang, J. Lynn Fink, Neil D. Young, Robin B. Gasser

Clonorchiasis is a neglected tropical disease caused by the Chinese liver fluke, Clonorchis sinensis, and is often associated with a malignant form of bile duct cancer (cholangiocarcinoma). Although some aspects of the epidemiology of clonorchiasis are understood, little is known about the genetics of C. sinensis populations. Here, we conducted a comprehensive genetic exploration of C. sinensis from endemic geographic regions using complete mitochondrial protein gene sets. Genomic DNA samples from C. sinensis individuals (n = 183) collected from cats and dogs in China (provinces of Guangdong, Guangxi, Hunan, Heilongjiang and Jilin) as well as from rats infected with metacercariae from cyprinid fish from the Russian Far East (Primorsky Krai region) were deep sequenced using the BGISEQ-500 platform. Informatic analyses of mitochondrial protein gene data sets revealed marked genetic variation within C. sinensis; significant variation was identified within and among individual worms from distinct geographical locations. No clear affiliation with a particular location or host species was evident, suggesting a high rate of dispersal of the parasite across endemic regions. The present work provides a foundation for future biological, epidemiological and ecological studies using mitochondrial protein gene data sets, which could aid in elucidating associations between particular C. sinensis genotypes/haplotypes and the pathogenesis or severity of clonorchiasis and its complications (including cholangiocarcinoma) in humans.

National reporting of deaths after enhanced Ebola surveillance in Sierra Leone

PLoS Neglected Tropical Diseases News - 18 August 2020 - 9:00pm

by Mohamed F. Jalloh, Reinhard Kaiser, Mariam Diop, Amara Jambai, John T. Redd, Rebecca E. Bunnell, Evelyn Castle, Charles Alpren, Sara Hersey, Anna Mia Ekström, Helena Nordenstedt

Background

Sierra Leone experienced the largest documented epidemic of Ebola Virus Disease in 2014–2015. The government implemented a national tollfree telephone line (1-1-7) for public reporting of illness and deaths to improve the detection of Ebola cases. Reporting of deaths declined substantially after the epidemic ended. To inform routine mortality surveillance, we aimed to describe the trends in deaths reported to the 1-1-7 system and to quantify people’s motivations to continue reporting deaths after the epidemic.

Methods

First, we described the monthly trends in the number of deaths reported to the 1-1-7 system between September 2014 and September 2019. Second, we conducted a telephone survey in April 2017 with a national sample of individuals who reported a death to the 1-1-7 system between December 2016 and April 2017. We described the reported deaths and used ordered logistic regression modeling to examine the potential drivers of reporting motivations.

Findings

Analysis of the number of deaths reported to the 1-1-7 system showed that 12% of the expected deaths were captured in 2017 compared to approximately 34% in 2016 and over 100% in 2015. We interviewed 1,291 death reporters in the survey. Family members reported 56% of the deaths. Nearly every respondent (94%) expressed that they wanted the 1-1-7 system to continue. The most common motivation to report was to obey the government’s mandate (82%). Respondents felt more motivated to report if the decedent exhibited Ebola-like symptoms (adjusted odds ratio 2.3; 95% confidence interval 1.8–2.9).

Conclusions

Motivation to report deaths that resembled Ebola in the post-outbreak setting may have been influenced by knowledge and experiences from the prolonged epidemic. Transitioning the system to a routine mortality surveillance tool may require a robust social mobilization component to match the high reporting levels during the epidemic, which exceeded more than 100% of expected deaths in 2015.

Prevalence of scabies in long-term care hospitals in South Korea

PLoS Neglected Tropical Diseases News - 18 August 2020 - 9:00pm

by Dong-Hee Kim, Sook Young Yun, Young Choon Park, Shin Ae Kang, Hak Sun Yu

Background

Scabies is a common contagious skin disease. With the economic growth in South Korea, the incidence of scabies has decreased. However, with the recent advancements in medical facilities, mainly the establishment of long-term care hospitals (LTCHs), scabies is now considered an emerging public health problem.

Methodology/Principal findings

To examine the prevalence and management of scabies in LTCHs in South Korea, we contacted all 1,336 LTCHs registered at the Health Insurance Review and Assessment Service in South Korea in 2018. A total of 110 LTCHs completed a questionnaire, and we analyzed their responses. In the last 5 years, 71.8% (79/110) of LTCHs had a high incidence of scabies (suspected/confirmed cases). Usually, patients aged older than 80 years (45.5%) were diagnosed with the disease, with more women being affected than men. Only 30.0% of the patients were transferred to scabies-restricted rooms, and very few LTCHs (7.0%) had special departments for scabies. Fifty-five (61.1%) of 90 LTCHs reported contact between scabies patients and nurses, nurse aides, caregivers, and other employees (hereinafter, referred to as primary exposure), with 29 (32.2%) LTCHs reporting infections due to primary exposure. The most common challenges in managing scabies were patient isolation (47.8%), diagnosis (31.1%), management of individuals exposed to an individual with scabies (17.8%), lack of staff for managing the patients (16.7%), and treatment (11.1%).

Conclusions

The incidence rate of scabies in LTCHs in South Korea has increased. Regular and enhanced staff training is needed, considering that most hospitals rarely focused on the handling of equipment and furniture used by scabies patients and on educating their healthcare staff. These findings can be used to develop various strategies to reduce the prevalence of scabies.

Self-limiting paratransgenesis

PLoS Neglected Tropical Diseases News - 18 August 2020 - 9:00pm

by Wei Huang, Sibao Wang, Marcelo Jacobs-Lorena

Presently, the principal tools to combat malaria are restricted to killing the parasite in infected people and killing the mosquito vector to thwart transmission. While successful, these approaches are losing effectiveness in view of parasite resistance to drugs and mosquito resistance to insecticides. Clearly, new approaches to fight this deadly disease need to be developed. Recently, one such approach–engineering mosquito resident bacteria to secrete anti-parasite compounds–has proven in the laboratory to be highly effective. However, implementation of this strategy requires approval from regulators as it involves introduction of recombinant bacteria into the field. A frequent argument by regulators is that if something unexpectedly goes wrong after release, there must be a recall mechanism. This report addresses this concern. Previously we have shown that a Serratia bacterium isolated from a mosquito ovary is able to spread through mosquito populations and is amenable to be engineered to secrete anti-plasmodial compounds. We have introduced a plasmid into this bacterium that carries a fluorescent protein gene and show that when cultured in the laboratory, the plasmid is completely lost in about 130 bacterial generations. Importantly, when these bacteria were introduced into mosquitoes, the bacteria were transmitted from one generation to the next, but the plasmid was lost after three mosquito generations, rendering the bacteria non-recombinant (wild type). Furthermore, no evidence was obtained for horizontal transfer of the plasmid to other bacteria either in culture or in the mosquito. Prior to release, it is imperative to demonstrate that the genes that thwart parasite development in the mosquito are safe to the environment. This report describes a methodology to safely achieve this goal, utilizing transient expression from a plasmid that is gradually lost, returning the bacterium to wild type status.

An iterative process produces oxamniquine derivatives that kill the major species of schistosomes infecting humans

PLoS Neglected Tropical Diseases News - 18 August 2020 - 9:00pm

by Meghan A. Guzman, Anastasia R. Rugel, Reid S. Tarpley, Sevan N. Alwan, Frédéric D. Chevalier, Dmytro P. Kovalskyy, Xiaohang Cao, Stephen P. Holloway, Timothy J. C. Anderson, Alexander B. Taylor, Stanton F. McHardy, Philip T. LoVerde

Currently there is only one method of treatment for human schistosomiasis, the drug praziquantel. Strong selective pressure has caused a serious concern for a rise in resistance to praziquantel leading to the necessity for additional pharmaceuticals, with a distinctly different mechanism of action, to be used in combination therapy with praziquantel. Previous treatment of Schistosoma mansoni included the use of oxamniquine (OXA), a prodrug that is enzymatically activated in S. mansoni but is ineffective against S. haematobium and S. japonicum. The oxamniquine activating enzyme was identified as a S. mansoni sulfotransferase (SmSULT-OR). Structural data have allowed for directed drug development in reengineering oxamniquine to be effective against S. haematobium and S. japonicum. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust SAR program that tested over 300 derivatives and identified several new lead compounds with effective worm killing in vitro. Previous studies resulted in the discovery of compound CIDD-0066790, which demonstrated broad-species activity in killing of schistosome species. As these compounds are racemic mixtures, we tested and demonstrate that the R enantiomer CIDD-007229 kills S. mansoni, S. haematobium and S. japonicum better than the parent drug (CIDD-0066790). The search for derivatives that kill better than CIDD-0066790 has resulted in a derivative (CIDD- 149830) that kills 100% of S. mansoni, S. haematobium and S. japonicum adult worms within 7 days. We hypothesize that the difference in activation and thus killing by the derivatives is due to the ability of the derivative to fit in the binding pocket of each sulfotransferase (SmSULT-OR, ShSULT-OR, SjSULT-OR) and to be efficiently sulfated. The purpose of this research is to develop a second drug to be used in conjunction with praziquantel to treat the major human species of Schistosoma. Collectively, our findings show that CIDD-00149830 and CIDD-0072229 are promising novel drugs for the treatment of human schistosomiasis and strongly support further development and in vivo testing.

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