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The public health benefit and burden of mass drug administration programs in Vietnamese schoolchildren: Impact of mebendazole

12 November 2018 - 10:00pm

by Sam Debaveye, Claudia Virginia Gonzalez Torres, Delphine De Smedt, Bert Heirman, Shane Kavanagh, Jo Dewulf

Background

Mass anthelmintic drug administration is recommended in developing countries to address infection by soil-transmitted helminthiases (STH). We quantified the public health benefit of treatment with mebendazole in eight million Vietnamese children aged 5–14 years from 2006 to 2011. This was compared to the environmental impact of the pharmaceutical supply chain of mebendazole, as the resource use and emissions associated with pharmaceutical production can be associated with a public health burden, e.g. through emissions of fine particulate matter.

Methodology

Through Markov modelling the disability due to STH was quantified for hookworm, Ascaris lumbricoides and Trichuris trichiura. For each worm type, four levels of intensity of infection were included: none, light, medium and heavy. The treatment effect on patients was quantified in Disability-Adjusted Life Years (DALYs). The public health burden induced by the pharmaceutical supply chain of mebendazole was quantified in DALYs through Life Cycle Assessment.

Principal findings

Compared to ‘no treatment’, the modelled results of five-year treatment averted 116,587 DALYs (68% reduction) for the three worms combined and largely driven by A. lumbricoides. The main change in DALYs occurred in the first year of treatment, after which the results stabilized. The public health burden associated with the pharmaceutical supply chain was 6 DALYs.

Conclusions

The public health benefit of the Mass Drug Administration (MDA) averted substantially more DALYs than those induced by the pharmaceutical supply chain. These results were verified in a sensitivity analysis. The starting prevalence for each worm was the most sensitive model parameter. This methodology is useful for policymakers interested in a holistic approach towards the public health performance of MDA programs, enveloping both the treatment benefit received by the patient and the public health burden associated with the resource consumption and environmental emissions of the pharmaceutical production and supply chain.

Safety of azithromycin in infants under six months of age in Niger: A community randomized trial

12 November 2018 - 10:00pm

by Catherine E. Oldenburg, Ahmed M. Arzika, Ramatou Maliki, Mohamed Salissou Kane, Elodie Lebas, Kathryn J. Ray, Catherine Cook, Sun Y. Cotter, Zhaoxia Zhou, Sheila K. West, Robin Bailey, Travis C. Porco, Jeremy D. Keenan, Thomas M. Lietman

Background

Mass azithromycin distribution reduces under-5 child mortality. Trachoma control programs currently treat infants aged 6 months and older. Here, we report findings from an infant adverse event survey in 1–5 month olds who received azithromycin as part of a large community-randomized trial in Niger.

Methods and principal findings

Active surveillance of infants aged 1–5 months at the time of treatment was conducted in 30 randomly selected communities from within a large cluster randomized trial of biannual mass azithromycin distribution compared to placebo to assess the potential impact on child mortality. We compared the distribution of adverse events reported after treatment among azithromycin-treated versus placebo-treated infants. From January 2015 to February 2018, the caregivers of 1,712 infants were surveyed. Approximately one-third of caregivers reported at least one adverse event (azithromycin: 29.6%, placebo: 34.3%, risk ratio [RR] 0.86, 95% confidence interval [CI] 0.68 to 1.10, P = 0.23). The most commonly reported adverse events included diarrhea (azithromycin: 19.3%, placebo: 28.1%, RR 0.68, 95% CI 0.49 to 0.96, P = 0.03), vomiting (azithromycin: 15.9%, placebo: 21.0%, RR 0.76, 95% CI 0.56 to 1.02, P = 0.07), and skin rash (azithromycin: 12.3%, placebo: 13.6%, RR 0.90, 95% CI 0.59 to 1.37, P = 0.63). No cases of infantile hypertrophic pyloric stenosis were reported.

Conclusions

Azithromycin given to infants aged 1–5 months appeared to be safe. Inclusion of younger infants in larger azithromycin-based child mortality or trachoma control programs could be considered if deemed effective.

Trial registration

ClinicalTrials.gov NCT02048007.

The prevalence of lymphatic filariasis infection and disease following six rounds of mass drug administration in Mandalay Region, Myanmar

12 November 2018 - 10:00pm

by Benjamin F. R. Dickson, Patricia M. Graves, Ni Ni Aye, Thet Wai Nwe, Tint Wai, San San Win, Myint Shwe, Janet Douglass, Richard S. Bradbury, William J. McBride

Lymphatic filariasis is widely endemic in Myanmar. Despite the establishment of an elimination program in 2000, knowledge of the remaining burden of disease relies predominantly on programmatic information. To assist the program, we conducted an independent cross-sectional household cluster survey to determine the prevalence of filariasis infection, morbidity and mass-drug administration coverage in four townships of the Mandalay Region: Amarapura, Patheingyi, Tada-U and Wundwin. The survey included 1014 individuals from 430 randomly selected households in 24 villages. Household members one year and older were assessed for antigenaemia using immunochromatographic test cards and if positive, microfilaraemia by night-time thick blood smear. Participants 15 years and older were assessed for filariasis morbidity by ultrasound-assisted clinical examination. The overall prevalence of infection was 2.63% by antigenaemia (95% confidence interval (CI) 1.71–4.04%) and 1.03% by microfilaraemia (95%CI 0.59–1.47%). The prevalence of hydrocoele in adult males was 2.78% (95%CI 1.23–6.15%) and of lymphoedema in both genders was 0% (95%CI 0–0.45%). These results indicate the persistence of filarial infection and transmission despite six rounds of annual mass drug administration and highlight the need for further rounds as well as the implementation of morbidity management programs in the country.

Exploring the parasite load and molecular diversity of <i>Trypanosoma cruzi</i> in patients with chronic Chagas disease from different regions of Brazil

12 November 2018 - 10:00pm

by Ícaro Rodrigues-dos-Santos, Myllena F. Melo, Liane de Castro, Alejandro Marcel Hasslocher-Moreno, Pedro Emmanuel A. A. do Brasil, Andréa Silvestre de Sousa, Constança Britto, Otacilio C. Moreira

Chagas disease is still a major public health issue in many Latin American countries. One of the current major challenges is to find an association between Trypanosoma cruzi discrete typing units (DTUs) and clinical manifestations of the disease. In this study, we used a multilocus conventional PCR and quantitative real time PCR (qPCR) approaches to perform the molecular typing and parasite load quantification directly from blood specimens of 65 chronic Chagas disease patients. All patients were recruited at the same health center, but their place of birth were widely distributed in different geographic regions of Brazil. Of the 65 patients, 35 (53.8%) presented positive amplification by real time qPCR, being 20 (30.7%) with the clinical indeterminate form and 15 (23.1%) with the cardiac form of the disease. The parasite load median for all positive patients was 2.54 [1.43–11.14] parasite equivalents/mL (par. Eq./mL), with the load ranging from 0.12 to 153.66 par. Eq./mL. Noteworthy, the parasite load was significantly higher in patients over 70 years old (median 20.05 [18.29–86.86] par. Eq./mL). Using guanidine-EDTA blood samples spiked with reference T. cruzi strains, belonging to the six DTUs, it was possible to genotype the parasite up to 0.5 par. Eq./mL, with high specificity. Of the patients with positive qPCR, it was possible to identify the T. cruzi DTU in 28 patients (80%). For the remaining patients (20%), at least a partial result was obtained. Analysis of specimens showed prevalences of TcVI, TcII and mixed infection TcVI+TcII equal to 40%, 17.1% and 14.3%, respectively. In addition, two patients were infected by TcV, and one patient was coinfected by TcIII+TcVI, These last three patients were in stage A of chronic chagasic cardiomyopathy (CCC), and they were born at the Bahia State (northeast region of Brazil). When T. cruzi genotypes were compared with the parasite load, more elevated parasite loads were observed in patients infected by TcII in general (parasite load median of 7.56 par. Eq./mL) in comparison to patients infected by TcVI (median of 2.35 par. Eq./mL). However, while the frequency of CCC was 50% in patients infected by TcVI and TcV, only 16.7% of patients infected by TcII evolved to CCC. Taking together, our results contribute to update the epidemiological knowledge of T. cruzi DTUs in Brazil, and highlight the age of patient and infection by TcII as important features that lead to the observation of higher parasitemia levels.

Serological evidence of inter-epizootic/inter-epidemic circulation of Rift Valley fever virus in domestic cattle in Kyela and Morogoro, Tanzania

12 November 2018 - 10:00pm

by Mirende Kichuki Matiko, Linda Peniel Salekwa, Christopher Jacob Kasanga, Sharadhuli Idd Kimera, Magnus Evander, Wambura Philemon Nyangi

Background

Tanzania is among the Rift Valley fever (RVF) epizootic/endemic countries in sub Saharan Africa, where RVF disease outbreaks occur within a range of 3 to 17-year intervals. Detection of Rift Valley fever virus (RVFV) antibodies in animals in regions with no previous history of outbreaks raises the question of whether the disease is overlooked due to lack-of effective surveillance systems, or if there are strains of RVFV with low pathogenicity. Furthermore, which vertebrate hosts are involved in the inter-epidemic and inter-epizootic maintenance of RVFV? In our study region, the Kyela and Morogoro districts in Tanzania, no previous RVF outbreaks have been reported.

Methodology

The study was conducted from June 2014 to October 2015 in the Kyela and Morogoro districts, Tanzania. Samples (n = 356) were retrieved from both the local breed of zebu cattle (Bos indicus) and Bos indicus/Bos Taurus cross breed. RVFV antibodies were analyzed by two enzyme-linked immunosorbent assay (ELISA) approaches. Initially, samples were analyzed by a RVFV multi-species competition ELISA (cELISA), which detected both RVFV IgG and IgM antibodies. All serum samples that were positive with the cELISA method were specifically analysed for the presence of RVFV IgM antibodies to trace recent infection. A plaque reduction neutralization assay (PRNT80) was performed to determine presence of RVFV neutralizing antibodies in all cELISA positive samples.

Findings

Overall RVFV seroprevalence rate in cattle by cELISA in both districts was 29.2% (104 of 356) with seroprevalence rates of 33% (47/147) in the Kyela district and 27% (57/209) in the Morogoro district. In total, 8.4% (30/356) of all cattle sampled had RVFV IgM antibodies, indicating current disease transmission. When segregated by districts, the IgM antibody seroprevalence was 2.0% (3/147) and 12.9% (27/209) in Kyela and Morogoro districts respectively. When the 104 cELISA positive samples were analyzed by PRNT80 to confirm that RVFV-specific antibodies were present, the majority (89%, 93/104) had RVFV neutralising antibodies.

Conclusion

The results provided evidence of widespread prevalence of RVFV antibody among cattle during an inter-epizootic/inter-epidemic period in Tanzania in regions with no previous history of outbreaks. There is a need for further investigations of RVFV maintenance and transmission in vertebrates and vectors during the long inter-epizootic/inter-epidemic periods.

Human-pathogenic <i>Anaplasma</i> spp., and <i>Rickettsia</i> spp. in animals in Xi’an, China

12 November 2018 - 10:00pm

by Wen-Ping Guo, Baicheng Huang, Qin Zhao, Gang Xu, Baoyuan Liu, Yi-Han Wang, En-Min Zhou

In China, thirteen species of tick-borne rickettsiales bacteria pathogenic to human have been reported in ticks and host animals, and human patients caused by them also has been identified. However, investigation for rickettsiales bacteria circulating in Xi’an wasn’t performed although diseases resembling human diseases caused by these organisms have been found. In this study, domestic animals and ticks in Xi’an, China, were tested for the presence of rickettsiales bacteria pathogenic to humans. Besides A. ovis, a high prevalence of A. capra was observed suggesting a high public health risk exists. In addition, two novel Anaplasma species closely related to A. phagocytophilum were identified and formed distinct lineages in the phylogenetic trees, with more than 98.3% identities for rrs gene, while divergences up to 20.2% and 37.0% for groEL and gltA genes, respectively. Both of these two novel Anaplasma species were found to circulate in goats and further assessment of their pathogenicity is needed. Ca. R. jingxinensis, with potential pathogenicity, was also detected in H. longicomis ticks with high prevalence. However, other causative agents were not identified although they were distributed in other areas of China.

Molecular analysis of clinical <i>Burkholderia pseudomallei</i> isolates from southwestern coastal region of India, using multi-locus sequence typing

12 November 2018 - 10:00pm

by Aayushi Kamthan, Tushar Shaw, Chiranjay Mukhopadhyay, Subodh Kumar

Background

The Gram-negative soil dwelling bacterium Burkholderia pseudomallei is the etiological agent of melioidosis. The disease is endemic in most parts of Southeast Asia and northern Australia. Over last few years, there has been an increase in number of melioidosis cases from India; however the disease epidemiology is less clearly understood. Multi-locus sequence typing (MLST) is a powerful genotypic method used to characterize the genetic diversity of B. Pseudomallei both within and across the geographic regions.

Methods

In this study, MLST analysis was performed on 64 B. pseudomallei clinical isolates. These isolates were obtained between 2008–2014 from southwestern coastal region of India. Broad population patterns of Indian B. pseudomallei isolates in context with isolates of Southeast Asia or global collection was determined using in silico phylogenetic tools.

Results

A total of 32 Sequence types (STs) were reported among these isolates of which 17 STs (53%) were found to be novel. ST1368 was found as group founder and the most predominant genotype (n = 11, 17%). Most of the B. pseudomallei isolates reported in this study (or other Indian isolates available in MLST database) clustered in one major group suggesting clonality in Indian isolates; however, there were a few outliers. When analyzed by measure of genetic differentiation (FST) and other phylogenetic tools (e.g. PHYLOViZ), Indian STs were found closer to Southeast Asian isolates than Australian isolates. The phylogenetic analysis further revealed that within Asian clade, Indian isolates grouped more closely with isolates from Sri Lanka, Vietnam, Bangladesh and Thailand.

Conclusions

Overall, the results of this study suggest that the Indian B. pseudomallei isolates are closely related with lesser heterogeneity among them and cluster in one major group suggesting clonality of the isolates. However, it appears that there are a few outliers which are distantly related to the majority of Indian STs. Phylogenetic analysis suggest that Indian isolates are closely related to isolates from Southeast Asia, particularly from South Asia.

Estimation of HTLV-1 vertical transmission cases in Brazil per annum

12 November 2018 - 10:00pm

by Carolina Rosadas, Bassit Malik, Graham P. Taylor, Marzia Puccioni-Sohler

Background

Brazil has at least 800,000 HTLV-1 infected individuals. HTLV-1 can be transmitted via sexual intercourse, contact with blood and from mother to child, mainly by breastfeeding. Treatments for the high morbidity/mortality associated diseases (ATL and HAM/TSP) are limited, therefore, infection prevention is of utmost importance. However, antenatal screening is not routinely performed in Brazil. A lack of data regarding the number of individuals infected via breastfeeding impairs the development of government policies. The objective is to estimate the number of HTLV-1 infections occurring annually due to mother to child transmission (MTCT) in Brazil, nationally and regionally.

Methodology

To estimate HTLV-1 MTCT in Brazil the following variables are modelled: number of births, prevalence of HTLV-1 infection in pregnant women, breastfeeding duration rate and transmission risk according to breastfeeding period. The number of cases of HAM/TSP and ATL attributable to MTCT are also estimated.

Principal findings

In 2008, there were 2,934,828 live births in Brazil. HTLV prevalence in pregnant women in Brazil ranges between 0.1–1.05% by region. An estimated 16,548 HTLV-1 infected women are pregnant each year. According to the breastfeeding pattern and HTLV-1 prevalence of each region there are an estimated 3,024 new cases of HTLV-1 infection due to MTCT annually of which 2,610 are preventable through infant feeding advice. These 3,024 transmissions will result in 120–604 cases of ATL and 8–272 of HAM/TSP. North-East region comprises the high number of MTCT cases, followed by South-East.

Conclusions/significance

A high number of new HTLV-1 infections due to MTCT occur every year in Brazil. Antenatal screening and avoiding breastfeeding are essential to prevent subsequent development of HTLV-1-associated diseases.

Use of anthropophilic culicid-based xenosurveillance as a proxy for <i>Plasmodium vivax</i> malaria burden and transmission hotspots identification

12 November 2018 - 10:00pm

by Joabi Nascimento, Vanderson S. Sampaio, Stephan Karl, Andrea Kuehn, Anne Almeida, Sheila Vitor-Silva, Gisely Cardoso de Melo, Djane C. Baia da Silva, Stefanie C. P. Lopes, Nelson F. Fé, José B. Pereira Lima, Maria G. Barbosa Guerra, Paulo F. P. Pimenta, Quique Bassat, Ivo Mueller, Marcus V. G. Lacerda, Wuelton M. Monteiro

Vector-borne diseases account for more than 17% of all infectious diseases, causing more than one million deaths annually. Malaria remains one of the most important public health problems worldwide. These vectors are bloodsucking insects, which can transmit disease-producing microorganisms during a blood meal. The contact of culicids with human populations living in malaria-endemic areas suggests that the identification of Plasmodium genetic material in the blood present in the gut of these mosquitoes may be possible. The process of assessing the blood meal for the presence of pathogens is termed ‘xenosurveillance’. In view of this, the present work investigated the relationship between the frequency with which Plasmodium DNA is found in culicids and the frequency with which individuals are found to be carrying malaria parasites. A cross-sectional study was performed in a peri-urban area of Manaus, in the Western Brazilian Amazon, by simultaneously collecting human blood samples and trapping culicids from households. A total of 875 individuals were included in the study and a total of 13,374mosquito specimens were captured. Malaria prevalence in the study area was 7.7%. The frequency of households with at least one culicid specimen carrying Plasmodium DNA was 6.4%. Plasmodium infection incidence was significantly related to whether any Plasmodium positive blood-fed culicid was found in the same household [IRR 3.49 (CI95% 1.38–8.84); p = 0.008] and for indoor-collected culicids [IRR 4.07 (CI95%1.25–13.24); p = 0.020]. Furthermore, the number of infected people in the house at the time of mosquito collection was related to whether there were any positive blood-fed culicid mosquitoes in that household for collection methods combined [IRR 4.48 (CI95%2.22–9.05); p<0.001] or only for indoor-collected culicids [IRR 4.88 (CI95%2.01–11.82); p<0.001]. Our results suggest that xenosurveillance can be used in endemic tropical regions in order to estimate the malaria burden and identify transmission foci in areas where Plasmodium vivax is predominant.

Genetic characteristics of <i>Bacillus anthracis</i> isolated from northwestern China from 1990 to 2016

12 November 2018 - 10:00pm

by Huijuan Zhang, Enmin Zhang, Jinrong He, Wei Li, Jianchun Wei

Anthrax is a global re-emerging zoonotic disease and is an endemic disease in China, especially in rural regions. In this study, the general characteristics of human anthrax outbreaks that occurred in areas of northwestern China over the past decade have been described. Meanwhile, the genetic characteristics of Bacillus anthracis isolated from these areas from 1990 to 2016 were analyzed by means of canonical single-nucleotide polymorphism (canSNP) analysis and multilocus variable-number tandem repeat analysis (MLVA) with 15 markers. Five sublineages/subgroups, namely, A.Br.001/002, A.Br.Vollum, A.Br.Aust94, A.Br.Ames and A.Br.008/009, were detected by using 13 canSNP sites. All of the sublineages were found in Xinjiang province, while one sublineage was found in Shaanxi, two in Gansu, three in Qinghai and four in Inner Mongolia. However, the geographical distribution of the B. anthracis populations exhibited different canSNP characteristics from those of the strains isolated before 1990 in China. In contrast to previous data, the A.Br.Ames subgroup was also observed to be scattered from Inner Mongolia to other provinces. All 106 strains were assigned to 36 MLVA15 genotypes, and 21 of these types were first observed in this study. The strains collected from anthrax outbreaks in recent decade were classified as subgroups A.Br.001/002 and A.Br.Ames and identified as genotypes MLVA15-28, MLVA15-30, MLVA15-31, MLVA15-38, MLVA15-CHN3, and MLVA15-CHN18. By canSNP analysis and MLVA, we found that the diversification of MLVA genotypes and the geographical distribution of B. anthracis populations is gradually becoming balanced across northwestern China. This study also provides preliminary survey results regarding the population diversity of B. anthracis in China, which will help promote the prevention and control of this important disease.

Growth and adaptation of Zika virus in mammalian and mosquito cells

12 November 2018 - 10:00pm

by Lindsey A. Moser, Brendan T. Boylan, Fernando R. Moreira, Laurel J. Myers, Emma L. Svenson, Nadia B. Fedorova, Brett E. Pickett, Kristen A. Bernard

The recent emergence of Zika virus (ZIKV) in the Americas coincident with increased caseloads of microcephalic infants and Guillain-Barre syndrome has prompted a flurry of research on ZIKV. Much of the research is difficult to compare or repeat because individual laboratories use different virus isolates, growth conditions, and quantitative assays. Here we obtained three readily available contemporary ZIKV isolates and the prototype Ugandan isolate. We generated stocks of each on Vero mammalian cells (ZIKVmam) and C6/36 mosquito cells (ZIKVmos), determined titers by different assays side-by-side, compared growth characteristics using one-step and multi-step growth curves on Vero and C6/36 cells, and examined plaque phenotype. ZIKV titers consistently peaked earlier on Vero cells than on C6/36 cells. Contemporary ZIKV isolates reached peak titer most quickly in a multi-step growth curve when the amplifying cell line was the same as the titering cell line (e.g., ZIKVmam titered on Vero cells). Growth of ZIKVmam on mosquito cells was particularly delayed. These data suggest that the ability to infect and/or replicate in insect cells is limited after growth in mammalian cells. In addition, ZIKVmos typically had smaller, more homogenous plaques than ZIKVmam in a standard plaque assay. We hypothesized that the plaque size difference represented early adaptation to growth in mammalian cells. We plaque purified representative-sized plaques from ZIKVmos and ZIKVmam. ZIKVmos isolates maintained the initial phenotype while plaques from ZIKVmam isolates became larger with passaging. Our results underscore the importance of the cells used to produce viral stocks and the potential for adaptation with minimal cell passages. In addition, these studies provide a foundation to compare current and emerging ZIKV isolates in vitro and in vivo.

Comparative transcriptome analysis and RNA interference reveal <i>CYP6A8</i> and SNPs related to pyrethroid resistance in <i>Aedes albopictus</i>

12 November 2018 - 10:00pm

by Jiabao Xu, Xinghua Su, Mariangela Bonizzoni, Daibin Zhong, Yiji Li, Guofa Zhou, Hoan Nguyen, Sarah Tong, Guiyun Yan, Xiao-Guang Chen

Wide and improper application of pyrethroid insecticides for mosquito control has resulted in widespread resistance in Aedes albopictus mosquitoes, an important dengue vector. Therefore, understanding the molecular regulation of insecticide resistance is urgently needed to provide a basis for developing novel resistance diagnostic methods and vector control approaches. We investigated the transcriptional profiles of deltamethrin-resistant and -susceptible Ae. albopictus by performing paired-end sequencing for RNA expression analysis. The analysis used 24 independent libraries constructed from 12 wild-caught resistant and 12 susceptible Ae. albopictus female adults. A total of 674,503,592 and 612,512,034 reads were obtained, mapped to the Ae. albopictus genome and assembled into 20,091 Ae. albopictus transcripts. A total of 1,130 significantly differentially expressed genes included 874 up-regulated genes and 256 down-regulated genes in the deltamethrin-resistant individuals. These differentially expressed genes code for cytochrome P450s, cuticle proteins, glutathione S-transferase, serine proteases, heat shock proteins, esterase, and others. We selected three highly differentially expressed candidate genes, CYP6A8 and two genes of unknown function (CCG013931 and CCG000656), to test the association between these 3 genes and deltamethrin resistance using RNAi through microinjection in adult mosquitoes and oral feeding in larval mosquitoes. We found that expression knockdown of these three genes caused significant changes in resistance. Further, we detected 1,162 single nucleotide polymorphisms (SNPs) with a frequency difference of more than 50%. Among them, 5 SNPs in 4 cytochrome P450 gene families were found to be significantly associated with resistance in a genotype-phenotype association study using independent field-collected mosquitoes of known resistance phenotypes. Altogether, a combination of novel individually based transcriptome profiling, RNAi, and genetic association study identified both differentially expressed genes and SNPs associated with pyrethroid resistance in Ae. albopictus mosquitoes, and laid a useful foundation for further studies on insecticide resistance mechanisms.

Estimating the elimination feasibility in the 'end game' of control efforts for parasites subjected to regular mass drug administration: Methods and their application to schistosomiasis

12 November 2018 - 10:00pm

by Arathi Arakala, Christopher M. Hoover, John M. Marshall, Susanne H. Sokolow, Giulio A. De Leo, Jason R. Rohr, Justin V. Remais, Manoj Gambhir

Progress towards controlling and eliminating parasitic worms, including schistosomiasis, onchocerciasis, and lymphatic filariasis, is advancing rapidly as national governments, multinational NGOs, and pharmaceutical companies launch collaborative chemotherapeutic control campaigns. Critical questions remain regarding the potential for achieving elimination of these infections, and analytical methods can help to quickly estimate progress towards—and the probability of achieving—elimination over specific timeframes. Here, we propose the effective reproduction number, Reff, as a proxy of elimination potential for sexually reproducing worms that are subject to poor mating success at very low abundance (positive density dependence, or Allee effects). Reff is the number of parasites produced by a single reproductive parasite at a given stage in the transmission cycle, over the parasite’s lifetime—it is the generalized form of the more familiar basic reproduction number, R0, which only applies at the beginning of an epidemic—and it can be estimated in a ‘model-free’ manner by an estimator (‘ε’). We introduce ε, demonstrate its estimation using simulated data, and discuss how it may be used in planning and evaluation of ongoing elimination efforts for a range of parasitic diseases.

Conserved motifs in the hypervariable domain of chikungunya virus nsP3 required for transmission by <i>Aedes aegypti</i> mosquitoes

9 November 2018 - 10:00pm

by Giel P. Göertz, Marit Lingemann, Corinne Geertsema, Marleen H. C. Abma-Henkens, Chantal B. F. Vogels, Constantianus J. M. Koenraadt, Monique M. van Oers, Gorben P. Pijlman

Background

Chikungunya virus (CHIKV) is a re-emerging arthropod-borne (arbo)virus that causes chikungunya fever in humans and is predominantly transmitted by Aedes aegypti mosquitoes. The CHIKV replication machinery consists of four non-structural proteins (nsP1-4) that additionally require the presence of a number of host proteins for replication of the viral RNA. NsP3 is essential for CHIKV replication and has a conserved macro, central and C-terminal hypervariable domain (HVD). The HVD is intrinsically disordered and interacts with various host proteins via conserved short peptide motifs: A proline-rich (P-rich) motif that has affinity for SH3-domain containing proteins and duplicate FGDF motifs with affinity for G3BP and its mosquito homologue Rasputin. The importance of these motifs for infection of mammalian cells has previously been implicated. However, their role during CHIKV infection of mosquito cells and transmission by mosquitoes remains unclear.

Methodology / Principal findings

Here, we show that in-frame deletion of the P-rich motif is lethal for CHIKV replication in both mosquito and mammalian cells. However, while mutagenesis of the P-rich motif negatively affects replication both in mammalian and mosquito cells, it did not compromise the infection and transmission of CHIKV by Ae. aegypti mosquitoes. Mutagenesis of both FGDF motifs together completely inactivated CHIKV replication in both mammalian and mosquito cells. Importantly, mutation of a single FGDF motif attenuated CHIKV replication in mammalian cells, while replication in mosquito cells was similar to wild type. Surprisingly, CHIKV mutants containing only a single FGDF motif were efficiently transmitted by Ae. aegypti.

Conclusions / Significance

The P-rich motif in CHIKV nsP3 is dispensable for transmission by mosquitoes. A single FGDF motif is sufficient for infection and dissemination in mosquitoes, but duplicate FGDF motifs are required for the efficient infection from the mosquito saliva to a vertebrate host. These results contribute to understanding the dynamics of the alphavirus transmission cycle and may help the development of arboviral intervention strategies.

Seasonal and interannual risks of dengue introduction from South-East Asia into China, 2005-2015

9 November 2018 - 10:00pm

by Shengjie Lai, Michael A. Johansson, Wenwu Yin, Nicola A. Wardrop, Willem G. van Panhuis, Amy Wesolowski, Moritz U. G. Kraemer, Isaac I. Bogoch, Dylain Kain, Aidan Findlater, Marc Choisy, Zhuojie Huang, Di Mu, Yu Li, Yangni He, Qiulan Chen, Juan Yang, Kamran Khan, Andrew J. Tatem, Hongjie Yu

Due to worldwide increased human mobility, air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens. However, the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and validated. We constructed a modelling framework, integrating air travel, epidemiological, demographical, entomological and meteorological data, to measure the seasonal probability of dengue introduction from endemic countries. This framework has been applied retrospectively to elucidate spatiotemporal patterns and increasing seasonal risk of dengue importation from South-East Asia into China via air travel in multiple populations, Chinese travelers and local residents, over a decade of 2005–15. We found that the volume of airline travelers from South-East Asia into China has quadrupled from 2005 to 2015 with Chinese travelers increased rapidly. Following the growth of air traffic, the probability of dengue importation from South-East Asia into China has increased dramatically from 2005 to 2015. This study also revealed seasonal asymmetries of transmission routes: Sri Lanka and Maldives have emerged as origins; neglected cities at central and coastal China have been increasingly vulnerable to dengue importation and onward transmission. Compared to the monthly occurrence of dengue reported in China, our model performed robustly for importation and onward transmission risk estimates. The approach and evidence could facilitate to understand and mitigate the changing seasonal threat of arbovirus from endemic regions.

Exploring the effect of human and animal population growth on vector-borne disease transmission with an agent-based model of Rhodesian human African trypanosomiasis in eastern province, Zambia

8 November 2018 - 10:00pm

by Simon Alderton, Ewan T. Macleod, Neil E. Anderson, Noreen Machila, Martin Simuunza, Susan C. Welburn, Peter M. Atkinson

This paper presents the development of an agent-based model (ABM) to investigate Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) disease transmission. The ABM model, fitted at a fine spatial scale, was used to explore the impact of a growing host population on the spread of disease along a 75 km transect in the Luangwa Valley, Zambia. The model was used to gain a greater understanding of how increases in human and domestic animal population could impact the contact network between vector and host, the subsequent transmission patterns, and disease incidence outcomes in the region. Modelled incidence rates showed increases in rHAT transmission in both humans and cattle. The primary demographic attribution of infection switched dramatically from young children of both sexes attending school, to adult women performing activities with shorter but more frequent trips, such as water and firewood collection, with men more protected due to the presence of cattle in their routines. The interpretation of model output provides a plausible insight into both population development and disease transmission in the near future in the region and such techniques could aid well-targeted mitigation strategies in the future.

Barriers to access to visceral leishmaniasis diagnosis and care among seasonal mobile workers in Western Tigray, Northern Ethiopia: A qualitative study

8 November 2018 - 10:00pm

by Rebecca Marie Coulborn, Tesfay Gebregzabher Gebrehiwot, Martin Schneider, Sibylle Gerstl, Cherinet Adera, Mercè Herrero, Klaudia Porten, Margriet den Boer, Koert Ritmeijer, Jorge Alvar, Abrahim Hassen, Afework Mulugeta

Background

Ethiopia bears a high burden of visceral leishmaniasis (VL). Early access to VL diagnosis and care improves clinical prognosis and reduces transmission from infected humans; however, significant obstacles exist. The approximate 250,000 seasonal mobile workers (MW) employed annually in northwestern Ethiopia may be particularly disadvantaged and at risk of VL acquisition and death. Our study aimed to assess barriers, and recommend interventions to increase access, to VL diagnosis and care among MWs.

Methodology/Principal findings

In 2017, 50 interviews and 11 focus group discussions were conducted with MWs, mobile residents, VL patients and caretakers, community leaders and healthcare workers in Kafta Humera District, Tigray. Participants reported high vulnerability to VL among MWs and residents engaged in transitory work. Multiple visits to health facilities were consistently needed to access VL diagnosis. Inadequate healthcare worker training, diagnostic test kit unavailability at the primary healthcare level, lack of VL awareness, insufficient finances for care-seeking and prioritization of income-generating activities were significant barriers to diagnosis and care. Social (decision-making and financial) support strongly and positively influenced care-seeking; workers unable to receive salary advances, compensation for partial work, or peer assistance for contract completion were particularly disadvantaged. Participants recommended the government/stakeholders intervene to ensure: MWs access to bed-nets, food, shelter, water, and healthcare at farms or sick leave; decentralization of diagnostic tests to primary healthcare facilities; surplus medications/staff during the peak season; improved referral/feedback/reporting/training within the health system; free comprehensive healthcare for all VL-related services; and community health education.

Conclusions/Significance

Contrary to what health policy for VL dictates in this endemic setting, study participants reported very poor access to diagnosis and, consequently, significantly delayed access to treatment. Interventions tailored to the socio-economic and health needs of MWs (and other persons suffering from VL) are urgently needed to reduce health disparities and the VL burden.

<i>Anopheles</i> mosquitoes may drive invasion and transmission of Mayaro virus across geographically diverse regions

7 November 2018 - 10:00pm

by Marco Brustolin, Sujit Pujhari, Cory A. Henderson, Jason L. Rasgon

The Togavirus (Alphavirus) Mayaro virus (MAYV) was initially described in 1954 from Mayaro County (Trinidad) and has been responsible for outbreaks in South America and the Caribbean. Imported MAYV cases are on the rise, leading to invasion concerns similar to Chikungunya and Zika viruses. Little is known about the range of mosquito species that are competent MAYV vectors. We tested vector competence of 2 MAYV genotypes in laboratory strains of six mosquito species (Aedes aegypti, Anopheles freeborni, An. gambiae, An. quadrimaculatus, An. stephensi, Culex quinquefasciatus). Ae. aegypti and Cx. quinquefasciatus were poor MAYV vectors, and had either poor or null infection and transmission rates at the tested viral challenge titers. In contrast, all Anopheles species were able to transmit MAYV, and 3 of the 4 species transmitted both genotypes. The Anopheles species tested are divergent and native to widely separated geographic regions (Africa, Asia, North America), suggesting that Anopheles may be important in the invasion and spread of MAYV across diverse regions of the world.

A decade of vector control activities: Progress and limitations of Chagas disease prevention in a region of Guatemala with persistent <i>Triatoma dimidiata</i> infestation

6 November 2018 - 10:00pm

by Jose G. Juarez, Pamela M. Pennington, Joe P. Bryan, Robert E. Klein, Charles B. Beard, Elsa Berganza, Nidia Rizzo, Celia Cordon-Rosales

Introduction

Chagas disease, a neglected tropical disease that affects millions of Latin Americans, has been effectively controlled in Guatemala after multiple rounds of indoor residual insecticide spraying (IRS). However, a few foci remain with persistent Triatoma dimidiata infestation. One such area is the municipality of Comapa, Department of Jutiapa, in the southeastern region of Guatemala, where control interventions appear less effective. We carried out three cross sectional entomological and serological surveys in Comapa to evaluate a decade of vector control activities. Baseline serological (1999) and entomological (2001–2) surveys were followed by three rounds of insecticide applications (2003–2005) and intermittent focal spraying of infested houses, until approximately 2012. Household inspections to determine entomological indices and construction materials were conducted in 2001, 2007 and 2011. Seroprevalence surveys were conducted in school-age children in 1999, 2007 and 2015, and in women of child bearing age (15–44 years) only in 2015. After multiple rounds of indoor residual sprayings (IRS), the infestation index decreased significantly from 39% (2001–2) to 27% (2011). Household construction materials alone predicted <10% of infested houses. Chagas seroprevalence in Comapa declined in school-aged children by 10–fold, from 10% (1999) to 1% (2015). However, seroprevalence in women of child bearing age remains >10%.

Conclusion

After a decade of vector control activities in Comapa, there is evidence of significantly reduced transmission. However, the continued risk for vector-borne and congenital transmission pose a threat to the 2022 Chagas disease elimination goal. Systematic integrated vector control and improved Chagas disease screening and treatment programs for congenital and vector-borne disease are needed to reach the elimination goal in regions with persistent vector infestation.

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