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Crystal Structure of <i>Schistosoma mansoni</i> Adenosine Phosphorylase/5’-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway
by Juliana Roberta Torini, José Brandão-Neto, Ricardo DeMarco, Humberto D'Muniz PereiraSchistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 126.96.36.199) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S. mansoni and could be a promising target for anti-schistosoma therapies. Here, we present 13 SmMTAP structures from the wild type (WT), including three single and one double mutant, and generate a solid structural framework for structure description. These crystal structures of SmMTAP reveal that the active site contains three substitutions within and near the active site when compared to it mammalian counterpart, thus opening up the possibility of developing specific inhibitors to the parasite MTAP. The structural and kinetic data for 5 substrates reveal the structural basis for this interaction, providing substract for inteligent design of new compounds for block this enzyme activity.
Emerging Infectious Disease Implications of Invasive Mammalian Species: The Greater White-Toothed Shrew (<i>Crocidura russula</i>) Is Associated With a Novel Serovar of Pathogenic <i>Leptospira</i> in Ireland
by Jarlath E. Nally, Zbigniew Arent, Darrell O. Bayles, Richard L. Hornsby, Colm Gilmore, Siobhan Regan, Allan D. McDevitt, Jon Yearsley, Séamus Fanning, Barry J. McMahonThe greater white-toothed shrew (Crocidura russula) is an invasive mammalian species that was first recorded in Ireland in 2007. It currently occupies an area of approximately 7,600 km2 on the island. C. russula is normally distributed in Northern Africa and Western Europe, and was previously absent from the British Isles. Whilst invasive species can have dramatic and rapid impacts on faunal and floral communities, they may also be carriers of pathogens facilitating disease transmission in potentially naive populations. Pathogenic leptospires are endemic in Ireland and a significant cause of human and animal disease. From 18 trapped C. russula, 3 isolates of Leptospira were cultured. However, typing of these isolates by standard serological reference methods was negative, and suggested an, as yet, unidentified serovar. Sequence analysis of 16S ribosomal RNA and secY indicated that these novel isolates belong to Leptospira alstonii, a unique pathogenic species of which only 7 isolates have been described to date. Earlier isolations were limited geographically to China, Japan and Malaysia, and this leptospiral species had not previously been cultured from mammals. Restriction enzyme analysis (REA) further confirms the novelty of these strains since no similar patterns were observed with a reference database of leptospires. As with other pathogenic Leptospira species, these isolates contain lipL32 and do not grow in the presence of 8-azagunaine; however no evidence of disease was apparent after experimental infection of hamsters. These isolates are genetically related to L. alstonii but have a novel REA pattern; they represent a new serovar which we designate as serovar Room22. This study demonstrates that invasive mammalian species act as bridge vectors of novel zoonotic pathogens such as Leptospira.
by Julie L. Elser, Laura L. Bigler, Aaron M. Anderson, Joanne L. Maki, Donald H. Lein, Stephanie A. ShwiffRaccoon rabies is endemic in the eastern U.S.; however, an epizootic had not been confirmed on Long Island, New York until 2004. An oral rabies vaccination (ORV) program was initiated soon after the first rabies-positive raccoon was discovered, and continued until raccoon rabies was eliminated from the vaccination zone. The cost-effectiveness and economic impact of this rabies control program were unknown. A public health surveillance data set was evaluated following the ORV program on Long Island, and is used here as a case study in the health economics of rabies prevention and control efforts. A benefit-cost analysis was performed to determine the cost-effectiveness of the program, and a regional economic model was used to estimate the macroeconomic impacts of raccoon rabies elimination to New York State. The cost of the program, approximately $2.6 million, was recovered within eight years by reducing costs associated with post-exposure prophylaxis (PEP) and veterinary diagnostic testing of rabies suspect animals. By 2019, the State of New York is projected to benefit from the ORV program by almost $27 million. The benefit-cost ratio will reach 1.71 in 2019, meaning that for every dollar spent on the program $1.71 will be saved. Regional economic modeling estimated employment growth of over 100 jobs and a Gross Domestic Product (GDP) increase of $9.2 million through 2019. This analysis suggests that baiting to eliminate rabies in a geographically constrained area can provide positive economic returns.
Safety and Reproducibility of a Clinical Trial System Using Induced Blood Stage <i>Plasmodium vivax</i> Infection and Its Potential as a Model to Evaluate Malaria Transmission
by Paul Griffin, Cielo Pasay, Suzanne Elliott, Silvana Sekuloski, Maggy Sikulu, Leon Hugo, David Khoury, Deborah Cromer, Miles Davenport, Jetsumon Sattabongkot, Karen Ivinson, Christian Ockenhouse, James McCarthyBackground
Interventions to interrupt transmission of malaria from humans to mosquitoes represent an appealing approach to assist malaria elimination. A limitation has been the lack of systems to test the efficacy of such interventions before proceeding to efficacy trials in the field. We have previously demonstrated the feasibility of induced blood stage malaria (IBSM) infection with Plasmodium vivax. In this study, we report further validation of the IBSM model, and its evaluation for assessment of transmission of P. vivax to Anopheles stephensi mosquitoes.Methods
Six healthy subjects (three cohorts, n = 2 per cohort) were infected with P. vivax by inoculation with parasitized erythrocytes. Parasite growth was monitored by quantitative PCR, and gametocytemia by quantitative reverse transcriptase PCR (qRT-PCR) for the mRNA pvs25. Parasite multiplication rate (PMR) and size of inoculum were calculated by linear regression. Mosquito transmission studies were undertaken by direct and membrane feeding assays over 3 days prior to commencement of antimalarial treatment, and midguts of blood fed mosquitoes dissected and checked for presence of oocysts after 7–9 days.Results
The clinical course and parasitemia were consistent across cohorts, with all subjects developing mild to moderate symptoms of malaria. No serious adverse events were reported. Asymptomatic elevated liver function tests were detected in four of six subjects; these resolved without treatment. Direct feeding of mosquitoes was well tolerated. The estimated PMR was 9.9 fold per cycle. Low prevalence of mosquito infection was observed (1.8%; n = 32/1801) from both direct (4.5%; n = 20/411) and membrane (0.9%; n = 12/1360) feeds.Conclusion
The P. vivax IBSM model proved safe and reliable. The clinical course and PMR were reproducible when compared with the previous study using this model. The IBSM model presented in this report shows promise as a system to test transmission-blocking interventions. Further work is required to validate transmission and increase its prevalence.Trial Registration
Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review
by Vittal Mogasale, Enusa Ramani, Hyeseung Wee, Jerome H. KimBackground
Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers.Objectives
To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries.Data sources
Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination.Study eligibility criteria
The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014.Participants
No participants are involved, only costs are collected.Intervention
Oral cholera vaccination and cost estimation.Study appraisal and synthesis method
A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$).Results
Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014).Limitations
The reported cost categories are not standardized at collection point and may lead to misclassification. Costs for some OCV campaigns are not available and analysis does not include direct and indirect costs to vaccine recipients.Conclusions and implications of key findings
Vaccine delivery cost estimation is needed for budgeting and economic analysis of vaccination programs. The cost categorization methodology presented in this study is helpful in collecting OCV delivery costs in a standardized manner, comparing delivery costs, planning vaccination campaigns and informing decision-making.
Isothermal Diagnostic Assays for Monitoring Single Nucleotide Polymorphisms in <i>Necator americanus</i> Associated with Benzimidazole Drug Resistance
by Nour Rashwan, Catherine Bourguinat, Kathy Keller, Nipul Kithsiri Gunawardena, Nilanthi de Silva, Roger PrichardBackground
Soil-transmitted helminths (STHs) are the most prevalent intestinal helminths of humans, and a major cause of morbidity in tropical and subtropical countries. The benzimidazole (BZ) drugs albendazole (ABZ) and mebendazole (MBZ) are used for treatment of human STH infections and this use is increasing dramatically with massive drug donations. Frequent and prolonged use of these drugs could lead to the emergence of anthelmintic resistance as has occurred in nematodes of livestock. Previous molecular assays for putative resistance mutations have been based mainly on PCR amplification and sequencing. However, these techniques are complicated and time consuming and not suitable for resource-constrained situations. A simple, rapid and sensitive genotyping method is required to monitor for possible developing resistance to BZ drugs.Methods
To address this problem, single nucleotide polymorphism (SNP) detection assays were developed based on the Smart amplification method (SmartAmp2) to target codons 167, 198, and 200 in the β-tubulin isotype 1 gene for the hookworm Necator americanus.Findings
Diagnostic assays were developed and applied to analyze hookworm samples by both SmartAmp2 and conventional sequencing methods and the results showed high concordance. Additionally, fecal samples spiked with N. americanus larvae were assessed and the results showed that the Aac polymerase used has high tolerance to inhibitors in fecal samples.Conclusion
The N. americanus SmartAmp2 SNP detection assay is a new genotyping tool that is rapid, sensitive, highly specific and efficient with the potential to be used as a field tool for monitoring SNPs associated with BZ resistance. However, further validation on large numbers of field samples is required.
by Eduardo Samo Gudo, Kerstin I. Falk, Sadia Ali, Argentina Felisbela Muianga, Vanessa Monteiro, Julie Cliff
<i>Plasmodium vivax</i> but Not <i>Plasmodium falciparum</i> Blood-Stage Infection in Humans Is Associated with the Expansion of a CD8<sup>+</sup> T Cell Population with Cytotoxic Potential
by Julie G. Burel, Simon H. Apte, James S. McCarthy, Denise L. DoolanTrial Registration
anzctr.org.au ACTRN12612000814875; anzctr.org.au ACTRN12613000565741; anzctr.org.au ACTRN12613001040752; ClinicalTrials.gov NCT02281344; anzctr.org.au ACTRN12612001096842; anzctr.org.au ACTRN12613001008718
by Cédric Abat, Philippe Colson, Hervé Chaudet, Jean-Marc Rolain, Hubert Bassene, Aldiouma Diallo, Oleg Mediannikov, Florence Fenollar, Didier Raoult, Cheikh SokhnaInfectious diseases still represent a major challenge for humanity. In this context, their surveillance is critical. From 2010 to 2016, two Point-Of-Care (POC) laboratories have been successfully implemented in the rural Saloum region of Senegal. In parallel, a homemade syndromic surveillance system called EPIMIC was implemented to monitor infectious diseases using data produced by the POC laboratory of the Timone hospital in Marseille, France. The aim of this study is to describe the steps necessary for implementing EPIMIC using data routinely produced by two POC laboratories (POC-L) established in rural Senegal villages. After improving EPIMIC, we started to monitor the 15 pathogens routinely diagnosed in the two POC-L using the same methodology we used in France. In 5 years, 2,577 deduplicated patients-samples couples from 775 different patients have been tested in the Dielmo and Ndiop POC-L. 739 deduplicated patients-samples couples were found to be positive to at least one of the tested pathogens. The retrospective analysis of the Dielmo and Ndiop POC data with EPIMIC allowed to generate 443 alarms. Since January 2016, 316 deduplicated patients-samples couples collected from 298 different patients were processed in the Niakhar POC laboratory. 56 deduplicated patients-samples couples were found to be positive to at least one of the tested pathogens. The retrospective analysis of the data of the Niakhar POC laboratory with EPIMIC allowed to generate 14 alarms. Although some improvements are still needed, EPIMIC has been successfully spread using data routinely produced by two rural POC-L in Senegal, West Africa.
Evaluation of Lymphatic Filariasis and Onchocerciasis in Three Senegalese Districts Treated for Onchocerciasis with Ivermectin
by Nana O. Wilson, Alioune Badara Ly, Vitaliano A. Cama, Paul T. Cantey, Daniel Cohn, Lamine Diawara, Abdel Direny, Mawo Fall, Karla R. Feeser, LeAnne M. Fox, Achille Kabore, Amadou F. Seck, Ngayo Sy, Daouda Ndiaye, Christine DubrayIn Africa, onchocerciasis and lymphatic filariasis (LF) are co-endemic in many areas. Current efforts to eliminate both diseases are through ivermectin-based mass drug administration (MDA). Years of ivermectin distribution for onchocerciasis may have interrupted LF transmission in certain areas. The Kédougou region, Senegal, is co-endemic for LF and onchocerciasis. Though MDA for onchocerciasis started in 1988, in 2014 albendazole had not yet been added for LF. The objective of this study was to assess in an integrated manner the LF and onchocerciasis status in the three districts of the Kédougou region after ≥10 years of ivermectin-based MDA. The study employed an African Programme for Onchocerciasis Control (APOC) onchocerciasis-related methodology. In the three districts, 14 villages close to three rivers that have Simulium damnosum breeding sites were surveyed. Convenience sampling of residents ≥5 years old was performed. Assessment for LF antigenemia by immunochromatographic testing (ICT) was added to skin snip microscopy for onchocerciasis. Participants were also tested for antibodies against Wb123 (LF) and Ov16 (onchocerciasis) antigens. In two districts, no participants were ICT or skin snip positive. In the third district, 3.5% were ICT positive and 0.7% were skin snip positive. In all the three districts, Wb123 prevalence was 0.6%. Overall, Ov16 prevalence was 6.9%. Ov16 prevalence among children 5–9 years old in the study was 2.5%. LF antigenemia prevalence was still above treatment threshold in one district despite ≥10 years of ivermectin-based MDA. The presence of Ov16 positive children suggested recent transmission of Onchocerca volvulus. This study showed the feasibility of integrated evaluation of onchocerciasis and LF but development of integrated robust methods for assessing transmission of both LF and onchocerciasis are needed to determine where MDA can be stopped safely in co-endemic areas.
by John M. Humphrey, Natalie B. Cleton, Chantal B. E. M. Reusken, Marshall J. Glesby, Marion P. G. Koopmans, Laith J. Abu-RaddadBackground
Dengue virus (DENV) infection is widespread and its disease burden has increased in past decades. However, little is known about the epidemiology of dengue in the Middle East and North Africa (MENA).Methodology / Principal Findings
Following Cochrane Collaboration guidelines and reporting our findings following PRISMA guidelines, we systematically reviewed available records across MENA describing dengue occurrence in humans (prevalence studies, incidence studies, and outbreak reports), occurrence of suitable vectors (Aedes aegypti and Aedes albopictus), and DENV vector infection rates. We identified 105 human prevalence measures in 13 of 24 MENA countries; 81 outbreaks reported from 9 countries from 1941–2015; and reports of Ae. aegypti and/or Ae. albopictus occurrence in 15 countries. The majority of seroprevalence studies were reported from the Red Sea region and Pakistan, with multiple studies indicating >20% DENV seroprevalence in general populations (median 25%, range 0–62%) in these subregions. Fifty percent of these studies were conducted prior to 1990. Multiple studies utilized assays susceptible to serologic cross-reactions and 5% of seroprevalence studies utilized viral neutralization testing. There was considerable heterogeneity in study design and outbreak reporting, as well as variability in subregional study coverage, study populations, and laboratory methods used for diagnosis.Conclusions / Significance
DENV seroprevalence in the MENA is high among some populations in the Red Sea region and Pakistan, while recent outbreaks in these subregions suggest increasing incidence of DENV which may be driven by a variety of ecologic and social factors. However, there is insufficient study coverage to draw conclusions about Aedes or DENV presence in multiple MENA countries. These findings illustrate the epidemiology of DENV in the MENA while revealing priorities for DENV surveillance and Aedes control.
<i>Plasmodium falciparum</i> Infection Status among Children with <i>Schistosoma</i> in Sub-Saharan Africa: A Systematic Review and Meta-analysis
by Abraham Degarege, Dawit Degarege, Emir Veledar, Berhanu Erko, Mathieu Nacher, Consuelo M. Beck-Sague, Purnima MadhivananBackground
It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level, but the nature of this interaction remains unclear. This systematic review synthesized evidence on the relationship of S. haematobium or S. mansoni infection with the occurrence of P. falciparum malaria, Plasmodium density and related reduction in haemoglobin level among children in sub-Saharan Africa (SSA).Methodology/Principal findings
A systematic review in according with PRISMA guidelines was conducted. All published articles available in PubMed, Embase, Cochrane library and CINAHL databases before May 20, 2015 were searched without any limits. Two reviewers independently screened, reviewed and assessed all the studies. Cochrane Q and Moran’s I2 were used to assess heterogeneity and the Egger test was used to examine publication bias. The summary odds ratio (OR), summary regression co-efficient (β) and 95% confidence intervals (CI) were estimated using a random-effects model. Out of 2,920 citations screened, 12 articles (five cross-sectional, seven prospective cohort) were eligible to be included in the systematic review and 11 in the meta-analysis. The 12 studies involved 9,337 children in eight SSA countries. Eight studies compared the odds of asymptomatic/uncomplicated P. falciparum infection, two studies compared the incidence of uncomplicated P. falciparum infection, six studies compared P. falciparum density and four studies compared mean haemoglobin level between children infected and uninfected with S. haematobium or S. mansoni. Summary estimates of the eight studies based on 6,018 children showed a higher odds of asymptomatic/uncomplicated P. falciparum infection in children infected with S. mansoni or S. haematobium compared to those uninfected with Schistosoma (summary OR: 1.82; 95%CI: 1.41, 2.35; I2: 52.3%). The increase in odds of asymptomatic/uncomplicated P. falciparum infection among children infected with Schistosoma remained significant when subgroup analysis was conducted for S. haematobium (summary OR: 1.68; 95%CI: 1.18, 2.41; I2: 53.2%) and S. mansoni (summary OR: 2.15; 95%CI: 1.89, 2.46: I2: 0.0%) infection. However, the density of P. falciparum infection was lower in children co-infected with S. haematobium compared to those uninfected with Schistosoma (summary-β: -0.14; 95% CI: -0.24, -0.01; I2: 39.7%). The mean haemoglobin level was higher among children co-infected with S. haematobium and P. falciparum than those infected with only P. falciparum (summary-mean haemoglobin difference: 0.49; 95% CI: 0.04, 0.95; I2: 66.4%)Conclusions/Significance
The current review suggests S. mansoni or S. haematobium co-infection may be associated with increased prevalence of asymptomatic/uncomplicated P. falciparum infection in children, but may protect against high density P. falciparum infection and related reduction in haemoglobin level.
<i>Schistosoma mansoni</i> Infection Can Jeopardize the Duration of Protective Levels of Antibody Responses to Immunizations against Hepatitis B and Tetanus Toxoid
by Diana K. Riner, Eric M. Ndombi, Jennifer M. Carter, Amos Omondi, Nupur Kittur, Emmy Kavere, Harrison K. Korir, Briana Flaherty, Diana Karanja, Daniel G. ColleyBackground
Schistosomiasis is a disease of major public health importance in sub-Saharan Africa. Immunoregulation begins early in schistosome infection and is characterized by hyporesponsiveness to parasite and bystander antigens, suggesting that a schistosome infection at the time of immunization could negatively impact the induction of protective vaccine responses. This study examined whether having a Schistosoma mansoni infection at the time of immunization with hepatitis B and tetanus toxoid (TT) vaccines impacts an individual’s ability to achieve and maintain protective antibody levels against hepatitis B surface antigen or TT.Methods
Adults were recruited from Kisumu Polytechnic College in Western Kenya. At enrollment, participants were screened for schistosomiasis and soil transmitted helminths (STHs) and assigned to groups based on helminth status. The vaccines were then administered and helminth infections treated a week after the first hepatitis B boost. Over an 8 month period, 3 blood specimens were obtained for the evaluation of humoral and cytokine responses to the vaccine antigens and for immunophenotyping.Results
146 individuals were available for final analysis and 26% were S. mansoni positive (Sm+). Schistosomiasis did not impede the generation of initial minimum protective antibody levels to either hepatitis B or TT vaccines. However, median hepatitis B surface antibody levels were significantly lower in the Sm+ group after the first boost and remained lower, but not significantly lower, following praziquantel (PZQ) treatment and final boost. In addition, 8 months following TT boost and 7 months following PZQ treatment, Sm+ individuals were more likely to have anti-TT antibody levels fall below levels considered optimal for long term protection. IL-5 levels in response to in vitro TT stimulation of whole blood were significantly higher in the Sm+ group at the 8 month time period as well.Conclusions
Individuals with schistosomiasis at the start the immunizations were capable of responding appropriately to the vaccines as measured by antibody responses. However, they may be at risk of a more rapid decline in antibody levels over time, suggesting that treating schistosome infections with praziquantel before immunizations could be beneficial. The timing of the treatment as well as its full impact on the maintenance of antibodies against vaccine antigens remains to be elucidated.
Public Health Interventions for <i>Aedes</i> Control in the Time of Zikavirus– A Meta-Review on Effectiveness of Vector Control Strategies
by Maha Bouzid, Julii Brainard, Lee Hooper, Paul R. HunterBackground
There is renewed interest in effective measures to control Zika and dengue vectors. A synthesis of published literature with a focus on the quality of evidence is warranted to determine the effectiveness of vector control strategies.Methodology
We conducted a meta-review assessing the effectiveness of any Aedes control measure. We searched Scopus and Medline for relevant reviews through to May 2016. Titles, abstracts and full texts were assessed independently for inclusion by two authors. Data extraction was performed in duplicate and validity of the evidence was assessed using GRADE criteria.Findings
13 systematic reviews that investigated the effect of control measures on entomological parameters or disease incidence were included. Biological controls seem to achieve better reduction of entomological indices than chemical controls, while educational campaigns can reduce breeding habitats. Integrated vector control strategies may not always increase effectiveness. The efficacy of any control programme is dependent on local settings, intervention type, resources and study duration, which may partly explain the varying degree of success between studies. Nevertheless, the quality of evidence was mostly low to very low due to poor reporting of study design, observational methodologies, heterogeneity, and indirect outcomes, thus hindering an evidence-based recommendation.Conclusions
The evidence for the effectiveness of Aedes control measures is mixed. Chemical control, which is commonly used, does not appear to be associated with sustainable reductions of mosquito populations over time. Indeed, by contributing to a false sense of security, chemical control may reduce the effectiveness of educational interventions aimed at encouraging local people to remove mosquito breeding sites. Better quality studies of the impact of vector control interventions on the incidence of human infections with Dengue or Zika are still needed.
Uncovering the Pathogenic Landscape of Helminth (<i>Opisthorchis viverrini</i>) Infections: A Cross-Sectional Study on Contributions of Physical and Social Environment and Healthcare Interventions
by Xueyuan Ong, Yi-Chen Wang, Paiboon Sithithaworn, Jutamas Namsanor, David Taylor, Luxana LaithavewatBackground
Helminth infections have proven recalcitrant to control by chemotherapy in many parts of Southeast Asia and indeed farther afield. This study isolates and examines the influence of different aspects of the physical and social environment, and uneven intervention effort contributing to the pathogenic landscape of human Opisthorchis viverrini infections.Methodology
A cross-sectional survey, involving 632 participants, was conducted in four villages in northeast Thailand to examine the impact on prevalence and parasite burden of the reservoir dam environment, socio-economic, demographic, and behavioral factors, and health center intervention efforts. Formalin-ether concentration technique was used for diagnoses, and multivariate models were used for analyses.Principal Findings
The importance attributed to O. viverrini infections varied among health centers in the four study villages. Villages where O. viverrini infections were not prioritized by the health centers as the healthcare focus were at a higher risk of infection (prevalence) with odds ratio (risk factor) of 5.73 (3.32–10.27) and p-value < 0.01. Priority of healthcare focus, however, did not appear to influence behavior, as the consumption of raw fish, the main source of O. viverrini infections in the study area, was 11.4% higher in villages that prioritized O. viverrini infections than those that did not (p-value = 0.01). Landscape variation, notably proximity to reservoir, affects vulnerability of local population to infection. Infection intensity was higher in population located closer to the reservoir with risk ratio of 2.09 (1.12–4.02) and p-value < 0.01. Patterns of infection intensities among humans were found to match fish infection intensity, where higher infection intensities were associated with fish obtained from the reservoir waterbody type (p-value = 0.023).Conclusions/Significance
This study demonstrated the importance of environmental influence and healthcare focus as risk factors of infections in addition to the socio-economic, demographic, and behavioral factors commonly explored in existing studies. The reservoir was identified as a crucial source to target for opisthorchiasis intervention efforts and the need to consider infection intensity in disease control efforts was highlighted. The holistic approach in this study, which underscores the close relationship between the environment, animals, and humans in development of human infections or diseases, is an important contribution to the framework of One Health approach, where consideration of helminth diseases has largely been overlooked.
by Sebastian Funk, Adam J. Kucharski, Anton Camacho, Rosalind M. Eggo, Laith Yakob, Lawrence M. Murray, W. John EdmundsThe pacific islands of Micronesia have experienced several outbreaks of mosquito-borne diseases over the past decade. In outbreaks on small islands, the susceptible population is usually well defined, and there is no co-circulation of pathogens. Because of this, analysing such outbreaks can be useful for understanding the transmission dynamics of the pathogens involved, and particularly so for yet understudied pathogens such as Zika virus. Here, we compared three outbreaks of dengue and Zika virus in two different island settings in Micronesia, the Yap Main Islands and Fais, using a mathematical model of transmission dynamics and making full use of commonalities in disease and setting between the outbreaks. We found that the estimated reproduction numbers for Zika and dengue were similar when considered in the same setting, but that, conversely, reproduction number for the same disease can vary considerably by setting. On the Yap Main Islands, we estimated a reproduction number of 8.0–16 (95% Credible Interval (CI)) for the dengue outbreak and 4.8–14 (95% CI) for the Zika outbreak, whereas for the dengue outbreak on Fais our estimate was 28–102 (95% CI). We further found that the proportion of cases of Zika reported was smaller (95% CI 1.4%–1.9%) than that of dengue (95% CI: 47%–61%). We confirmed these results in extensive sensitivity analysis. They suggest that models for dengue transmission can be useful for estimating the predicted dynamics of Zika transmission, but care must be taken when extrapolating findings from one setting to another.
Intensive Circulation of Japanese Encephalitis Virus in Peri-urban Sentinel Pigs near Phnom Penh, Cambodia
by Julien Cappelle, Veasna Duong, Long Pring, Lida Kong, Maud Yakovleff, Didot Budi Prasetyo, Borin Peng, Rithy Choeung, Raphaël Duboz, Sivuth Ong, San Sorn, Philippe Dussart, Arnaud Tarantola, Philippe Buchy, Véronique ChevalierDespite the increased use of vaccination in several Asian countries, Japanese Encephalitis (JE) remains the most important cause of viral encephalitis in Asia in humans with an estimated 68,000 cases annually. Considered a rural disease occurring mainly in paddy-field dominated landscapes where pigs are amplifying hosts, JE may nevertheless circulate in a wider range of environment given the diversity of its potential hosts and vectors. The main objective of this study was to assess the intensity of JE transmission to pigs in a peri-urban environment in the outskirt of Phnom Penh, Cambodia. We estimated the force of JE infection in two cohorts of 15 sentinel pigs by fitting a generalised linear model on seroprevalence monitoring data observed during two four-month periods in 2014. Our results provide evidence for intensive circulation of JE virus in a periurban area near Phnom Penh, the capital and most populated city of Cambodia. Understanding JE virus transmission in different environments is important for planning JE virus control in the long term and is also an interesting model to study the complexity of vector-borne diseases. Collecting quantitative data such as the force of infection will help calibrate epidemiological model that can be used to better understand complex vector-borne disease epidemiological cycles.
Serological and Virological Evidence of Crimean-Congo Haemorrhagic Fever Virus Circulation in the Human Population of Borno State, Northeastern Nigeria
by David N. Bukbuk, Stuart D. Dowall, Kuiama Lewandowski, Andrew Bosworth, Saka S. Baba, Anitha Varghese, Robert J. Watson, Andrew Bell, Barry Atkinson, Roger HewsonBackground
Despite several studies on the seroprevalence of antibodies against Crimean-Congo Haemorrhagic Fever virus (CCHFV) from humans and cattle in Nigeria, detailed investigation looking at IgG and IgM have not been reported. Additionally, there have been no confirmed cases of human CCHFV infection reported from Nigeria.Principal Findings
Samples from sera (n = 1189) collected from four Local Government Areas in Borno State (Askira/Uba, Damboa, Jere and Maiduguri) were assessed for the presence of IgG and IgM antibodies. The positivity rates for IgG and IgM were 10.6% and 3.5%, respectively. Additionally, sera from undiagnosed febrile patients (n = 380) were assessed by RT-PCR assay for the presence of CCHFV RNA. One positive sample was characterised by further by next generation sequencing (NGS) resulting in complete S, M and L segment sequences.Conclusions
This article provides evidence for the continued exposure of the human population of Nigeria to CCHFV. The genomic analysis provides the first published evidence of a human case of CCHFV in Nigeria and its phylogenetic context.