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The COVID-19 pandemic should not jeopardize dengue control

PLoS Neglected Tropical Diseases News - 23 September 2020 - 9:00pm

by Marie-Marie Olive, Thierry Baldet, James Devillers, Johanna Fite, Marie-Claire Paty, Christophe Paupy, Philippe Quénel, Elsa Quillery, Jocelyn Raude, Jean-Paul Stahl, Marie Thiann-Bo-Morel, David Roiz

Author summary: The concurrent circulation of dengue and coronavirus disease 2019 (COVID-19) may produce many unfavourable outcomes—such as co-infections; delays in diagnosis, treatment, and mitigation measures; overwhelming of the healthcare system; underreporting of cases; deterioration in surveillance and control interventions; and exacerbation of social inequalities. Indeed, lockdown is greatly compromising the effectiveness of vector control, especially social mobilization campaigns and preventive insecticide spraying in private spaces (indoor and peridomestic spraying). Thus, failure to appropriately implement the full range of vector control interventions can lead to a reduction in their overall effectiveness and an increasing risk of vector-borne diseases circulating. Consequently, the health community and policy makers should develop proactive policies and allocate adequate resources to prevent and manage the resurgence of dengue and other vector-borne diseases in the new era of COVID-19.

Efficacy and safety of praziquantel and dihydroartemisinin piperaquine combination for treatment and control of intestinal schistosomiasis: A randomized, non-inferiority clinical trial

PLoS Neglected Tropical Diseases News - 23 September 2020 - 9:00pm

by Rajabu Hussein Mnkugwe, Omary Minzi, Safari Kinung’hi, Appolinary Kamuhabwa, Eleni Aklillu

Background

Despite the reported success in reducing morbidity, praziquantel alone is insufficient for the control and elimination of schistosomiasis, partly due to its poor efficacy against the juvenile worms. Artemisinin derivatives are effective against juvenile worms but are less effective against adult worms. We compared the safety and efficacy of praziquantel and Dihydroartemisinin-piperaquine combination against the standard praziquantel alone for treatment of intestinal schistosomiasis.

Methods

In this randomized, open-label, non-inferiority trial, 639 Schistosoma mansoni infected children were enrolled and randomized to receive either praziquantel alone or praziquantel plus Dihydroartemisinin-piperaquine combination. Two stool samples were collected on consecutive days at baseline, 3 and 8 weeks post-treatment and analyzed using thick smear Kato Katz method. Efficacy was assessed by cure and egg reduction rates at 3 and 8 weeks post-treatment. Adverse events were assessed within four hours of drugs intake. The primary outcome was cure rates at 8 weeks of post-treatment. Secondary outcomes were egg reduction rates at 8 weeks of post-treatment and treatment-associated adverse events.

Results

At 3 weeks of post-treatment, cure rates were 88.3% (263/298, 95% CI = 84.1%– 91.4%) and 81.2% (277/341, 95% CI = 76.7%– 85.0%) for the combination therapy and praziquantel alone, respectively (p < 0.01, odds ratio (OR) = 1.74, 95% CI of OR = 1.11 to 2.69). At 8 weeks, there was a significant drop in the cure rates in praziquantel alone group to 63.9% (218/341, 95% CI = 58.7%– 68.8%) compared to 81.9% (244/298, 95% CI = 77.1%– 85.8%) in the combination therapy group (p < 0.0001, OR = 2.55, 95%CI of OR = 1.75 to 3.69). Egg reduction rates at 8 weeks post-treatment were significantly higher in the combination therapy group 93.6% (95% CI = 90.8%– 96.4%) compared to 87.9% (95% CI = 84.4%– 91.4%) in the praziquantel only group (p = 0.01). On both Univariate and Multivariate regression analysis, type of treatment received was a significant predictor of cure at week 8 post-treatment. Overall, 30.8% (95% CI = 27.2%– 34.4%) of the study participants experienced mild and transient treatment-associated adverse events, post-treatment abdominal pain (27.1%) being the most common adverse event observed. There was no significant difference in the overall occurrence of adverse events between the two treatment groups.

Conclusion

Praziquantel and Dihydroartemisinin piperaquine combination therapy is safe, and more efficacious compared to praziquantel alone for the treatment of intestinal schistosomiasis. Further studies are needed to explore if the combination therapy can be considered as an option for mass drug administration to control and eventually eliminate schistosomiasis.

Collocation of avian and mammal antibodies to develop a rapid and sensitive diagnostic tool for Russell's Vipers Snakebite

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

by Jing-Hua Lin, Che-Min Lo, Ssu-Han Chuang, Chao-Hung Chiang, Sheng-Der Wang, Tsung-Yi Lin, Jiunn-Wang Liao, Dong-Zong Hung

Russell’s vipers (RVs) envenoming is an important public health issue in South-East Asia. Disseminated intravascular coagulopathy, systemic bleeding, hemolysis, and acute renal injury are obvious problems that develop in most cases, and neuromuscular junction blocks are an additional problem caused by western RV snakebite. The complex presentations usually are an obstacle to early diagnosis and antivenom administration. Here, we tried to produce highly specific antibodies in goose yolks for use in a paper-based microfluidic diagnostic kit, immunochromatographic test of viper (ICT-Viper), to distinguish RVs from other vipers and even cobra snakebite in Asia. We used indirect ELISA to monitor specific goose IgY production and western blotting to illustrate the interaction of avian or mammal antibody with venom proteins. The ICT-Viper was tested not only in prepared samples but also in stored patient serum to demonstrate its preliminary efficacy. The results revealed that specific anti-Daboia russelii IgY could be raised in goose eggs effectively without inducing adverse effects. When it was collocated with horse anti-Daboia siamensis antibody, which broadly reacted with most of the venom proteins of both types of Russell’s viper, the false cross-reactivity was reduced, and the test showed good performance. The limit of detection was reduced to 10 ng/ml in vitro, and the test showed good detection ability in clinical snake envenoming case samples. The ICT-Viper performed well and could be combined with a cobra venom detection kit (ICT-Cobra) to create a multiple detection strip (ICT-VC), which broadens its applications while maintaining its detection ability for snake envenomation identification. Nonetheless, the use of the ICT-Viper in the South-East Asia region is pending additional laboratory and field investigations and regional collaboration. We believe that the development of this practical diagnostic tool marks the beginning of positive efforts to face the global snakebite issue.

The SARS-CoV-2 crisis and its impact on neglected tropical diseases: Threat or opportunity?

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

by Claire Chaumont, Kimberly Kamara, Elisa Baring, Karen Palacio, Ana Power, Warren Lancaster

Cross-serotypically conserved epitope recommendations for a universal T cell-based dengue vaccine

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

by Syed Faraz Ahmed, Ahmed A. Quadeer, John P. Barton, Matthew R. McKay

Dengue virus (DENV)-associated disease is a growing threat to public health across the globe. Co-circulating as four different serotypes, DENV poses a unique challenge for vaccine design as immunity to one serotype predisposes a person to severe and potentially lethal disease upon infection from other serotypes. Recent experimental studies suggest that an effective vaccine against DENV should elicit a strong T cell response against all serotypes, which could be achieved by directing T cell responses toward cross-serotypically conserved epitopes while avoiding serotype-specific ones. Here, we used experimentally-determined DENV T cell epitopes and patient-derived DENV sequences to assess the cross-serotypic variability of the epitopes. We reveal a distinct near-binary pattern of epitope conservation across serotypes for a large number of DENV epitopes. Based on the conservation profile, we identify a set of 55 epitopes that are highly conserved in at least 3 serotypes. Most of the highly conserved epitopes lie in functionally important regions of DENV non-structural proteins. By considering the global distribution of human leukocyte antigen (HLA) alleles associated with these DENV epitopes, we identify a potentially robust subset of HLA class I and class II restricted epitopes that can serve as targets for a universal T cell-based vaccine against DENV while covering ~99% of the global population.

An in-depth report of quality control on Kato-Katz and data entry in four clinical trials evaluating the efficacy of albendazole against soil-transmitted helminth infections

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

by Johnny Vlaminck, Piet Cools, Marco Albonico, Shaali Ame, Mio Ayana, Daniel Dana, Jennifer Keiser, Leonardo F. Matoso, Antonio Montresor, Zeleke Mekonnen, Rodrigo Corrêa-Oliveira, Simone A. Pinto, Somphou Sayasone, Jozef Vercruysse, Bruno Levecke

Background

Efforts to control soil-transmitted helminth (STH) infections have intensified over the past decade. Field-survey data on STH prevalence, infection intensity and drug efficacy is necessary to guide the implementation of control programs and should be of the best possible quality.

Methodology

During four clinical trials designed to evaluate the efficacy of albendazole against STHs in Brazil, Ethiopia, Lao PDR and Tanzania, quality control (QC) was performed on the duplicate Kato-Katz thick smears and the data entry. We analyzed datasets following QC on both fecal egg counts (FECs) and data entry, and compared the prevalence of any STH infection and moderate-to-heavy intensity (MHI) infections and the drug efficacy against STH infections.

Results

Across the four study sites, a total of 450 out of 4,830 (9.3%) Kato-Katz thick smears were re-examined. Discrepancies in FECs varied from ~3% (hookworms) to ~6.5% (Ascaris lumbricoides and Trichuris trichiura). The difference in STH prevalence and prevalence of MHI infections using the datasets with and without QC of the FECs did not exceed 0.3%, except for hookworm infections in Tanzania, where we noted a 2.2 percentage point increase in MHI infections (pre-QC: 1.6% vs. post-QC: 3.8%). There was a 100% agreement in the classification of drug efficacy of albendazole against STH between the two datasets.In total, 201 of the 28,980 (0.65%) data entries that were made to digitize the FECs were different between both data-entry clerks. Nevertheless, the overall prevalence of STH, the prevalence of MHI infections and the classification of drug efficacy remained largely unaffected.

Conclusion/significance

In these trials, where staff was informed that QC would take place, minimal changes in study outcomes were reported following QC on FECs or data entry. Nevertheless, imposing QC did reduce the number of errors. Therefore, application of QC together with proper training of the personnel and the availability of clear standard operating procedures is expected to support higher data quality.

Land cover affects microclimate and temperature suitability for arbovirus transmission in an urban landscape

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

by Michael C. Wimberly, Justin K. Davis, Michelle V. Evans, Andrea Hess, Philip M. Newberry, Nicole Solano-Asamoah, Courtney C. Murdock

The emergence of mosquito-transmitted viruses poses a global threat to human health. Combining mechanistic epidemiological models based on temperature-trait relationships with climatological data is a powerful technique for environmental risk assessment. However, a limitation of this approach is that the local microclimates experienced by mosquitoes can differ substantially from macroclimate measurements, particularly in heterogeneous urban environments. To address this scaling mismatch, we modeled spatial variation in microclimate temperatures and the thermal potential for dengue transmission by Aedes albopictus across an urban-to-rural gradient in Athens-Clarke County GA. Microclimate data were collected across gradients of tree cover and impervious surface cover. We developed statistical models to predict daily minimum and maximum microclimate temperatures using coarse-resolution gridded macroclimate data (4000 m) and high-resolution land cover data (30 m). The resulting high-resolution microclimate maps were integrated with temperature-dependent mosquito abundance and vectorial capacity models to generate monthly predictions for the summer and early fall of 2018. The highest vectorial capacities were predicted for patches of trees in urban areas with high cover of impervious surfaces. Vectorial capacity was most sensitive to tree cover during the summer and became more sensitive to impervious surfaces in the early fall. Predictions from the same models using temperature data from a local meteorological station consistently over-predicted vectorial capacity compared to the microclimate-based estimates. This work demonstrates that it is feasible to model variation in mosquito microenvironments across an urban-to-rural gradient using satellite Earth observations. Epidemiological models applied to the microclimate maps revealed localized patterns of temperature suitability for disease transmission that would not be detectable using macroclimate data. Incorporating microclimate data into disease transmission models has the potential to yield more spatially precise and ecologically interpretable metrics of mosquito-borne disease transmission risk in urban landscapes.

Evaluation of ocular involvement in patients with Hansen’s disease

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

by Priscila Daiane Pavezzi, Rodrigo Bueno do Prado, Plinio Ângelo Boin Filho, Airton dos Santos Gon, Bruna Tuma, Marco Aurelio Fornazieri, Fabiana de Mari Scalone, Luciana Rigolin Mazoni Alves, Ricardo Hirayama Montero, Antonio Marcelo Barbante Casella

Hansen’s disease (HD) belongs to the group of neglected diseases and can cause physical deformities and disabilities, in addition to leading to social discrimination. Ocular involvement in HD is estimated at 70–75% worldwide. About 10–50% suffer from severe ocular symptoms and loss of vision occurs in approximately 5% of cases. Ocular changes may persist or worsen even after patients are considered cured and it is necessary to better understand these conditions in order to determine the need for additional public policies. The objective of this study was to identify the prevalence of ocular involvement in patients with HD at two specialist referral centers for treatment of the disease. A cross-sectional study was conducted with ophthalmological evaluations of patients with HD from June 2017 to June 2018. Diagnostic ocular findings, corrected visual acuity, and refractive error were described. Findings were correlated with patients’ clinical and epidemiological variables. A total of 86 patients were evaluated, with a mean age of 50.1 years, predominantly males (59.3%), and with multibacillary HD (92%). The prevalence of ophthalmologic changes was 100% and the most common were dysfunction of the Meibomian glands (89.5%) and dry eye syndrome (81.4%). Cataracts were observed in 22 patients (25.6%), but best corrected visual acuity was normal or near normal in 84 patients (97.7%) and there were no cases of bilateral blindness. Patients with some degree of physical disability had more ophthalmological alterations, involving both the ocular adnexa (p = 0.03) and the ocular globe (p = 0.04). Ocular involvement is common in patients with Hansen’s disease, reinforcing the importance of ophthalmologic examination in the evaluation and follow-up of these patients.

Distribution of household disinfection kits during the 2014-2015 Ebola virus outbreak in Monrovia, Liberia: The MSF experience

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

by Engy Ali, Guido Benedetti, Rafael Van den Bergh, Anna Halford, Luke Bawo, Moses Massaquoi, Saverio Bellizzi, Peter Maes

During the initial phase of the 2014–2016 Ebola virus disease (EBV) outbreak in Monrovia, Liberia, all hospitals’ isolation capacities were overwhelmed by the sheer caseload. As a stop-gap measure to halt transmission, Medecins sans Frontieres (MSF) distributed household disinfection kits to those who were at high risk of EBV contamination. The kit contained chlorine and personal protective materials to be used for the care of a sick person or the handling of a dead body. This intervention was novel and controversial for MSF. This paper shed the light on this experience of distribution in Monrovia and assess if kits were properly used by recipients. Targeted distribution was conducted to those at high risk of EVD (relatives of confirmed EVD cases) and health staff. Mass distributions were also conducted to households in the most EBV affected urban districts. A health promotion strategy focused on the purpose and use of the kit was integrated into the distribution. Follow-up phone calls to recipients were conducted to enquire about the use of the kit. Overall, 65,609 kits were distributed between September and November 2014. A total of 1,386 recipients were reached by phone. A total of 60 cases of sickness and/or death occurred in households who received a kit. The majority of these (46, 10%) were in households of relatives of confirmed EBV cases. Overall, usage of the kits was documented in 56 out of 60 affected households. Out of the 1322 households that did not experience sickness and/or death after the distribution, 583 (44%) made use of elements of the kit, mainly (94%) chlorine for hand-washing. At the peak of an EBV outbreak, the distribution of household disinfection kits was feasible and kits were appropriately used by the majority of recipients. In similar circumstances in the future, the intervention should be considered.

Epidemiologic and spatiotemporal trends of Zika Virus disease during the 2016 epidemic in Puerto Rico

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

by Tyler M. Sharp, Talia M. Quandelacy, Laura E. Adams, Jomil Torres Aponte, Matthew J. Lozier, Kyle Ryff, Mitchelle Flores, Aidsa Rivera, Gilberto A. Santiago, Jorge L. Muñoz-Jordán, Luisa I. Alvarado, Vanessa Rivera-Amill, Myriam Garcia-Negrón, Stephen H. Waterman, Gabriela Paz-Bailey, Michael A. Johansson, Brenda Rivera-Garcia

Background

After Zika virus (ZIKV) emerged in the Americas, laboratory-based surveillance for arboviral diseases in Puerto Rico was adapted to include ZIKV disease.

Methods and findings

Suspected cases of arboviral disease reported to Puerto Rico Department of Health were tested for evidence of infection with Zika, dengue, and chikungunya viruses by RT-PCR and IgM ELISA. To describe spatiotemporal trends among confirmed ZIKV disease cases, we analyzed the relationship between municipality-level socio-demographic, climatic, and spatial factors, and both time to detection of the first ZIKV disease case and the midpoint of the outbreak. During November 2015–December 2016, a total of 71,618 suspected arboviral disease cases were reported, of which 39,717 (55.5%; 1.1 cases per 100 residents) tested positive for ZIKV infection. The epidemic peaked in August 2016, when 71.5% of arboviral disease cases reported weekly tested positive for ZIKV infection. Incidence of ZIKV disease was highest among 20–29-year-olds (1.6 cases per 100 residents), and most (62.3%) cases were female. The most frequently reported symptoms were rash (83.0%), headache (64.6%), and myalgia (63.3%). Few patients were hospitalized (1.2%), and 13 (<0.1%) died. Early detection of ZIKV disease cases was associated with increased population size (log hazard ratio [HR]: -0.22 [95% confidence interval -0.29, -0.14]), eastern longitude (log HR: -1.04 [-1.17, -0.91]), and proximity to a city (spline estimated degrees of freedom [edf] = 2.0). Earlier midpoints of the outbreak were associated with northern latitude (log HR: -0.30 [-0.32, -0.29]), eastern longitude (spline edf = 6.5), and higher mean monthly temperature (log HR: -0.04 [-0.05, -0.03]). Higher incidence of ZIKV disease was associated with lower mean precipitation, but not socioeconomic factors.

Conclusions

During the ZIKV epidemic in Puerto Rico, 1% of residents were reported to public health authorities and had laboratory evidence of ZIKV disease. Transmission was first detected in urban areas of eastern Puerto Rico, where transmission also peaked earlier. These trends suggest that ZIKV was first introduced to Puerto Rico in the east before disseminating throughout the island.

Strengthening the Bolivian pharmacovigilance system: New surveillance strategies to improve care for Chagas disease and tuberculosis

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

by Nuria Cortes-Serra, Ruth Saravia, Rosse Mary Grágeda, Amílcar Apaza, Jorge Armando González, Brenda Ríos, Joaquim Gascón, Faustino Torrico, María-Jesús Pinazo

Chagas disease (CD) and tuberculosis (TB) are important health problems in Bolivia. Current treatments for both infections require a long period of time, and adverse drug reactions (ADRs) are frequent. This study aims to strengthen the Bolivian pharmacovigilance system, focusing on CD and TB. A situation analysis of pharmacovigilance in the Department of Cochabamba was performed. The use of a new local case report form (CRF) was implemented, together with the CRF established by the Unidad de Medicamentos y Tecnología en Salud (UNIMED), in several healthcare centers. Training and follow-up on drug safety monitoring and ADR reporting was provided to all health professionals involved in CD and TB treatment. A comparative analysis of the reported ADRs using the CRF provided by UNIMED, the new CRF proposal, and medical records, was also performed. Our results showed that out of all patients starting treatment for CD, 37.9% suffered ADRs according to the medical records, and 25.3% of them were classified as moderate/severe (MS). Only 47.4% of MS ADRs were reported to UNIMED. Regarding TB treatment, 9.9% of all patients suffered ADRs, 44% of them were classified as MS, and 75% of MS ADRs were reported to UNIMED. These findings show that the reinforcement of the Bolivian pharmacovigilance system is an ambitious project that should involve a long-term perspective and the engagement of national health workers and other stakeholders at all levels. Continuity and perseverance are essential to achieve a solid ADR reporting system, improving patient safety, drug efficacy and adherence to treatment.

Bayesian estimation of Lassa virus epidemiological parameters: Implications for spillover prevention using wildlife vaccination

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

by Scott L. Nuismer, Christopher H. Remien, Andrew J. Basinski, Tanner Varrelman, Nathan Layman, Kyle Rosenke, Brian Bird, Michael Jarvis, Peter Barry, Patrick W. Hanley, Elisabeth Fichet-Calvet

Lassa virus is a significant burden on human health throughout its endemic region in West Africa, with most human infections the result of spillover from the primary rodent reservoir of the virus, the natal multimammate mouse, M. natalensis. Here we develop a Bayesian methodology for estimating epidemiological parameters of Lassa virus within its rodent reservoir and for generating probabilistic predictions for the efficacy of rodent vaccination programs. Our approach uses Approximate Bayesian Computation (ABC) to integrate mechanistic mathematical models, remotely-sensed precipitation data, and Lassa virus surveillance data from rodent populations. Using simulated data, we show that our method accurately estimates key model parameters, even when surveillance data are available from only a relatively small number of points in space and time. Applying our method to previously published data from two villages in Guinea estimates the time-averaged R0 of Lassa virus to be 1.74 and 1.54 for rodent populations in the villages of Bantou and Tanganya, respectively. Using the posterior distribution for model parameters derived from these Guinean populations, we evaluate the likely efficacy of vaccination programs relying on distribution of vaccine-laced baits. Our results demonstrate that effective and durable reductions in the risk of Lassa virus spillover into the human population will require repeated distribution of large quantities of vaccine.

Transcriptomic profiling of the digestive tract of the rat flea, <i>Xenopsylla cheopis</i>, following blood feeding and infection with <i>Yersinia pestis</i>

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

by David M. Bland, Craig A. Martens, Kimmo Virtaneva, Kishore Kanakabandi, Dan Long, Rebecca Rosenke, Greg A. Saturday, Forrest H. Hoyt, Daniel P. Bruno, José M. Ribeiro, B. Joseph Hinnebusch

Yersinia pestis, the causative agent of plague, is a highly lethal pathogen transmitted by the bite of infected fleas. Once ingested by a flea, Y. pestis establish a replicative niche in the gut and produce a biofilm that promotes foregut colonization and transmission. The rat flea Xenopsylla cheopis is an important vector to several zoonotic bacterial pathogens including Y. pestis. Some fleas naturally clear themselves of infection; however, the physiological and immunological mechanisms by which this occurs are largely uncharacterized. To address this, RNA was extracted, sequenced, and distinct transcript profiles were assembled de novo from X. cheopis digestive tracts isolated from fleas that were either: 1) not fed for 5 days; 2) fed sterile blood; or 3) fed blood containing ~5x108 CFU/ml Y. pestis KIM6+. Analysis and comparison of the transcript profiles resulted in identification of 23 annotated (and 11 unknown or uncharacterized) digestive tract transcripts that comprise the early transcriptional response of the rat flea gut to infection with Y. pestis. The data indicate that production of antimicrobial peptides regulated by the immune-deficiency pathway (IMD) is the primary flea immune response to infection with Y. pestis. The remaining infection-responsive transcripts, not obviously associated with the immune response, were involved in at least one of 3 physiological themes: 1) alterations to chemosensation and gut peristalsis; 2) modification of digestion and metabolism; and 3) production of chitin-binding proteins (peritrophins). Despite producing several peritrophin transcripts shortly after feeding, including a subset that were infection-responsive, no thick peritrophic membrane was detectable by histochemistry or electron microscopy of rat flea guts for the first 24 hours following blood-feeding. Here we discuss the physiological implications of rat flea infection-responsive transcripts, the function of X. cheopis peritrophins, and the mechanisms by which Y. pestis may be cleared from the flea gut.

Expanded genome-wide comparisons give novel insights into population structure and genetic heterogeneity of <i>Leishmania tropica</i> complex

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

by Tamara Salloum, Rim Moussa, Ryan Rahy, Jospin Al Deek, Ibrahim Khalifeh, Rana El Hajj, Neil Hall, Robert P. Hirt, Sima Tokajian

Leishmania tropica is one of the main causative agents of cutaneous leishmaniasis (CL). Population structures of L. tropica appear to be genetically highly diverse. However, the relationship between L. tropica strains genomic diversity, protein coding gene evolution and biogeography are still poorly understood. In this study, we sequenced the genomes of three new clinical L. tropica isolates, two derived from a recent outbreak of CL in camps hosting Syrian refugees in Lebanon and one historical isolate from Azerbaijan to further refine comparative genome analyses. In silico multilocus microsatellite typing (MLMT) was performed to integrate the current diversity of genome sequence data in the wider available MLMT genetic population framework. Single nucleotide polymorphism (SNPs), gene copy number variations (CNVs) and chromosome ploidy were investigated across the available 18 L. tropica genomes with a main focus on protein coding genes. MLMT divided the strains in three populations that broadly correlated with their geographical distribution but not populations defined by SNPs. Unique SNPs profiles divided the 18 strains into five populations based on principal component analysis. Gene ontology enrichment analysis of the protein coding genes with population specific SNPs profiles revealed various biological processes, including iron acquisition, sterols synthesis and drug resistance. This study further highlights the complex links between L. tropica important genomic heterogeneity and the parasite broad geographic distribution. Unique sequence features in protein coding genes identified in distinct populations reveal potential novel markers that could be exploited for the development of more accurate typing schemes to further improve our knowledge of the evolution and epidemiology of the parasite as well as highlighting protein variants of potential functional importance underlying L. tropica specific biology.

Impact of a 3-year mass drug administration pilot project for taeniasis control in Madagascar

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

by Noromanana Sylvia Ramiandrasoa, Pascaline Ravoniarimbinina, Armand Rafalimanantsoa Solofoniaina, Iharilanto Patricia Andrianjafy Rakotomanga, Samuel Hermas Andrianarisoa, Sophie Molia, Anne-Marie Labouche, Anna Sophie Fahrion, Meritxell Donadeu, Bernadette Abela-Ridder, Davidra Rajaonatahina

Taenia solium is endemic in Madagascar and presents a significant burden on the population and the health system. The parasite cycles through humans who host the adult tapeworm, and pigs that host the larval stages. Accidental infection of humans may occur with the larval stages which encyst in the nervous central system causing neurocysticercosis, a major cause of seizure disorders and a public health problem. One of the interventions to facilitate the control of the disease is mass drug administration (MDA) of the human population with taeniacide. Here we describe a pilot project conducted in Antanifotsy district of Madagascar from 2015 to 2017 where three annual rounds of MDA (praziquantel, 10mg/Kg) were undertaken in 52 villages. Changes in the prevalence of taeniasis were assessed before, during and after the treatments. A total of 221,308 treatments were given to all eligible people above 5 years of age representing a 95% coverage of the targeted population. No major adverse effects were notified related to the implementation of the MDA. The prevalence of taeniasis was measured using Kato-Katz and copro-antigen techniques. Analyses undertaken combining the results of the Kato-Katz with copro-antigen, or using the Kato-Katz results alone, showed that there was a significant reduction in taeniasis 4 months after the last MDA, but 12 months later (16 months after the last MDA) the taeniasis prevalence had returned to its original levels. Results of the pilot project emphasize the need of a multi-sectorial One-Health approach for the sustained control of T. solium.

Long-Term Mosquito culture with SkitoSnack, an artificial blood meal replacement

PLoS Neglected Tropical Diseases News - 17 September 2020 - 9:00pm

by Yashoda Kandel, Soumi Mitra, Xavier Jimenez, Stacy D. Rodriguez, Alvaro Romero, Brittny N. Blakely, Sang Yeon Cho, Charles Pelzman, Immo A. Hansen

The reliance on blood is a limiting factor for mass rearing of mosquitoes for Sterile-Insect-Technique (SIT) and other mosquito-based control strategies. To solve this problem, we have developed SkitoSnack, a formulated diet for Aedes aegypti (L) mosquitoes, as an alternative for vertebrate blood. Here we addressed the question if long-term yellow fever mosquito culture with SkitoSnack resulted in changed life history traits and fitness of the offspring compared to blood-raised mosquitoes. We also explored if SkitoSnack is suitable to raise Asian tiger mosquitos, Aedes albopictus (L.), and the human bed bug, Cimex lectularius (L). We measured life history traits for 30th generation SkitoSnack-raised Ae. aegypti and 11th generation SkitoSnack-raised Ae. albopictus, and compared them with control mosquitoes raised on blood only. We compared meal preference, flight performance, and reproductive fitness in Ae. aegypti raised on SkitoSnack or blood. We also offered SkitoSnack to bed bug nymphs. We found that long-term culture with SkitoSnack resulted in mosquitoes with similar life history traits compared to bovine blood-raised mosquitoes in both species we studied. Also, Ae. aegypti mosquitoes raised on SkitoSnack had similar flight performance compared to blood raised mosquitoes, were still strongly attracted by human smell and had equal mating success. Minimal feeding occurred in bed bugs. Our results suggest that long-term culture with the blood-meal replacement SkitoSnack results in healthy, fit mosquitoes. Therefore, artificial diets like SkitoSnack can be considered as a viable alternative for vertebrate blood in laboratory mosquito culture as well as for mosquito mass production for Sterile-Insect-Technique mosquito control interventions. SkitoSnack was not suitable to induce engorgement of bed bugs.

Knowledge, attitudes, and practices related to Coronavirus disease 2019 during the outbreak among workers in China: A large cross-sectional study

PLoS Neglected Tropical Diseases News - 17 September 2020 - 9:00pm

by Zhi-Hao Li, Xi-Ru Zhang, Wen-Fang Zhong, Wei-Qi Song, Zheng-He Wang, Qing Chen, Dan Liu, Qing-Mei Huang, Dong Shen, Pei-Liang Chen, Ang Mao, Duo Zhang, Xingfen Yang, Xian-Bo Wu, Chen Mao

Coronavirus disease 2019 (COVID-19) has recently emerged as a global threat. Understanding workers’ knowledge, attitudes, and practices (KAP) regarding this new infectious disease is crucial to preventing and controlling it. This study aimed to assess KAP regarding COVID-19 during the outbreak among workers in China. The present study was part of a cross-sectional online survey study conducted based on a large labor-intensive factory, which has 180,000 workers from various Chinese provinces, from 2 February 2020 to 7 February 2020. KAP related to COVID-19 were measured by 32 items, each item was measured with an agree/disagree/unclear format, and only correct responses were given 1 point. KAP regarding COVID-19 were measured with 20 items, 6 items and 6 items, respectively. A total of 123,768 valid responses (68.8%) were included in the analysis. Generally, the levels of knowledge (mean: 16.3 out of 20 points), attitudes (mean: 4.5 out of 6 points), and practices (mean: 5.8 out of 6 points) related to COVID-19 were high. Only 36,373 respondents (29.4%) disagreed that gargling with salt water is effective in protecting against COVID-19. Moreover, older respondents had decreased levels of knowledge and practices related to COVID-19 (both P values for the trend <0.001), while better-educated respondents had increased levels of knowledge and practices related to COVID-19 (both P values for the trend <0.001). These results suggest that Chinese workers are highly aware of COVID-19, but health authorities still need to provide correct information on COVID-19 prevention and strengthen health interventions, particularly for older and less-educated workers.

A case for adoption of continuous albendazole treatment regimen for human echinococcal infections

PLoS Neglected Tropical Diseases News - 17 September 2020 - 9:00pm

by Francesca Tamarozzi, John Horton, Marin Muhtarov, Michael Ramharter, Mar Siles-Lucas, Beate Gruener, Dominique A. Vuitton, Solange Bresson-Hadni, Tommaso Manciulli, Enrico Brunetti

Cystic (CE) and alveolar (AE) echinococcosis are chronic, neglected parasitic diseases burdened by high morbidity and, for AE, by high mortality, if left untreated. CE and AE have a widespread distribution, including Europe. Albendazole (ABZ), a broad-spectrum benzimidazole drug widely used to treat parasitic infections, is the drug of choice for the management of CE and AE, and is parasitostatic on echinococcal metacestodes. In Europe, ABZ is licensed for interrupted “cyclic” treatment, for a maximum of 3 cycles. However, better efficacy with no increased side effects has been shown when the drug is administered continuously and for longer periods. Current international recommendations, on the basis of clinical, pharmacological, and biological studies, recommend continuous administration of ABZ for months to years for the treatment of CE and AE, and this schedule has been widely in use for the past 20 years. However, in Europe this internationally recommended schedule, with the exception of France, is technically “off-label”, and, as such, requires an informed consent by the patient and, in some countries, even precludes the reimbursement of the drug cost. Adding to the very high cost of the drug, frequent “out-of-stock” situation, and packaging format impractical for long therapies, these conditions put patients with CE and AE regularly at risk of treatment discontinuation and disease progression. European regulations envisage variations to marketing authorization, but postauthorization studies should be carried out by the holder of the license of the drug, in the form of randomized controlled trials. While such studies do not seem feasible and would probably not be ethically justified for CE and AE, European regulations envisage other possibilities in particular situations, which apply to CE and AE, but there is limited interest to invest in this perspective. We urge a coordination between stakeholders to find effective and feasible ways to take action to revise the benzimidazole dosage regimens for CE and AE and to ensure a fair, regular, and easy access to the appropriate treatment to those suffering from these serious diseases.

Autochthonous leprosy in Spain: Has the transmission of <i>Mycobacterium leprae</i> stopped?

PLoS Neglected Tropical Diseases News - 16 September 2020 - 9:00pm

by Inés Suárez-García, Diana Gómez-Barroso, Paul E. M. Fine

Background

The aim of this study is to explore whether transmission of M. leprae has ceased in Spain, based upon the patterns and trends of notified cases.

Methodology

Data on new cases reported to the National Leprosy Registry between the years 2003–2018 were extracted. In absence of detailed travel history, cases were considered “autochthonous” or “imported” based on whether they were born within or outside of Spain. These data were analyzed by age, sex, clinical type, country of origin, and location of residence at time of notification.

Principal findings

Data were available on 61 autochthonous and 199 imported cases since 2003. There were clear declines in incidence in both groups, and more imported than autochthonous cases every year since 2006. Autochthonous cases were more frequently multibacillary and had older age at diagnosis compared to imported cases. All the autochthonous cases had been born before 1985 and were more than 25 years old at diagnosis. Male-to-female ratio increased with time for autochthonous cases (except for the last time period). The imported cases originated from 25 countries, half of them from Brasil and Paraguay. Autochthonous cases were mainly distributed in the traditionally endemic regions, especially Andalucía and the eastern Mediterranean coast.

Conclusions

Autochthonous and imported cases have different epidemiologic patterns in Spain. There was a clear decline in incidence rates of autochthonous disease, and patterns consistent with those reported from other regions where transmission has ceased. Autochthonous transmission of M. leprae is likely to have now effectively stopped in Spain.

Post-exposure prophylaxis (PEP) efficacy of rifampin, rifapentine, moxifloxacin, minocycline, and clarithromycin in a susceptible-subclinical model of leprosy

PLoS Neglected Tropical Diseases News - 16 September 2020 - 9:00pm

by Shannon M. Lenz, Jaymes H. Collins, Nashone A. Ray, Deanna A. Hagge, Ramanuj Lahiri, Linda B. Adams

Background

Subclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials.

Methodology/Principal findings

Athymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation.

Conclusions/Significance

The delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3–4 months) and late (8–9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission.

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