Population genomic analyses of schistosome parasites highlight critical challenges facing endgame elimination efforts.
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ABSTRACT:
SUBMITTER: Shortt JA
PROVIDER: S-EPMC7994584 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Lymphatic filariasis (LF) is endemic in Ghana, and the country has implemented the GPELF strategy since 2000 with significant progress made in the control of the disease. However, after several years of mass drug administration (MDA) implementation, there is persistent transmission in 17 of the 98 endemic districts in the country. Current approaches to surveillance are clearly unable to target untreated individuals and new strategies are required to address the endgame challenges to enhance LF elimination as a public health problem in endemic countries. Community registers are used during MDAs to enumerate community members, their age, gender, house numbers, and records of their participation in MDAs. These MDA registers represent an untapped opportunity to identify and characterize non-compliance and inform appropriate programmatic actions. In this study, we analyzed the data presented in the registers to assess the coverage and individuals' compliance in MDA. METHODS:The information in the MDA registers were assessed to verify the reported coverages obtained from the district. The community registers were obtained from the district health offices and the data from each individual record was entered into a database. A simple questionnaire was used to cross-check the participation of study participants in the 2017 MDA. The questionnaire solicited data on: participation in the 2017 MDA, reasons for not taking part in the MDA, adverse events experienced, what was done for the adverse events, and willingness to participate in subsequent MDAs. RESULTS:We found that 40.1% of the population in the registers missed at least one MDA in 3 years (2016-2018) and the majority of them were between 10-30 years of age. The results of the questionnaire assessment indicated that 13.8% of the respondents did not receive treatment in 2017 for various reasons, the most prominent among them being "absence/travel" (37.1%). Data in the registers were used to verify the treatment coverage for the years 2017 and 2018, and reviewed against the reported coverage obtained from the district. Significant differences between the reported and verified coverages were only observed in four communities. However, the assessment also revealed that the reported coverage was only accurate in 33.3% of cases. CONCLUSIONS:The MDA registers allow for the identification of eligible individuals who were not reached during any MDA round. Thus, the MDA registers could be utilized at the community and programme levels to identify missing and untreated individuals, appropriately address their non-compliance to MDA, and thereby improve MDA coverage in each implementation unit and monitor the progress towards elimination of LF. The challenges observed through the review of the registers also offer opportunities to improve the training given to the community drug distributors.
| S-EPMC7252669 | biostudies-literature
Project description:BackgroundMalaria causes significant morbidity and mortality each year. In the past few years, the global malaria cases have been declining and many endemic countries are heading towards malaria elimination. Nevertheless, reducing the number of cases seems to be easy than sustained elimination. Therefore to achieve the objective of complete elimination and maintaining the elimination status, it is necessary to assess the gains made during the recent years.Main textWith inclining global support and World Health Organisation (WHO) efforts, the control programmes have been implemented effectively in many endemic countries. Given the aroused interest and investments into malaria elimination programmes at global level, the ambitious goal of elimination appears feasible. Sustainable interventions have played a pivotal role in malaria contraction, however drug and insecticide resistance, social, demographic, cultural and behavioural beliefs and practices, and unreformed health infrastructure could drift back the progress attained so far. Ignoring such impeding factors coupled with certain region specific factors may jeopardise our ability to abide righteous track to achieve global elimination of malaria parasite. Although support beyond the territories is important, but well managed integrated vector management approach at regional and country level using scrupulously selected area specific interventions targeting both vector and parasite along with the community involvement is necessary. A brief incline in malaria during 2016 has raised fresh perturbation on whether elimination could be achieved on time or not.ConclusionsThe intervention tools available currently can most likely reduce transmission but clearing of malaria epicentres from where the disease can flare up any time, is not possible without involving local population. Nevertheless maintaining zero malaria transmission and checks on malaria import in declared malaria free countries, and further speeding up of interventions to stop transmission in elimination countries is most desirable. Strong collaboration backed by adequate political and financial support among the countries with a common objective to eliminate malaria must be on top priority. The present review attempts to assess the progress gained in malaria elimination during the past few years and highlights some issues that could be important in successful malaria elimination.
| S-EPMC6375178 | biostudies-literature
Project description:BackgroundTremendous progress has been made in the last ten years in reducing morbidity and mortality caused by malaria, in part because of increases in global funding for malaria control and elimination. Today, many countries are striving for malaria elimination. However, a major challenge is the neglect of cross-border and regional initiatives in malaria control and elimination. This paper seeks to better understand Global Fund support for multi-country initiatives.MethodsDocuments and proposals were extracted and reviewed from two main sources, the Global Fund website and Aidspan.org. Documents and reports from the Global Fund Technical Review Panel, Board, and Secretariat documents such as guidelines and proposal templates were reviewed to establish the type of policies enacted and guidance provided from the Global Fund on multi-country initiatives and applications. From reviewing this information, the researchers created 29 variables according to eight dimensions to use in a review of Round 10 applications. All Round 10 multi-country applications (for HIV, malaria and tuberculosis) and all malaria multi-country applications (6) from Rounds 1 - 10 were extracted from the Global Fund website. A blind review was conducted of Round 10 applications using the 29 variables as a framework, followed by a review of four of the six successful malaria multi-country grant applications from Rounds 1 - 10.FindingsDuring Rounds 3 - 10 of the Global Fund, only 5.8% of grants submitted were for multi-country initiatives. Out of 83 multi-country proposals submitted, 25.3% were approved by the Technical Review Panel (TRP) for funding, compared to 44.9% of single-country applications. The majority of approved multi-country applications were for HIV (76.2%), followed by malaria (19.0%), then tuberculosis (4.8%). TRP recommendations resulted in improvements to application forms, although guidance was generally vague. The in-depth review of Round 10 multi-country proposals showed that applicants described their projects in one of two ways: a regional 'network approach' by which benefits are derived from economies of scale or from enhanced opportunities for mutual support and learning or the development of common policies and approaches; or a 'cross-border' approach for enabling activities to be more effectively delivered towards border-crossing populations or vectors. In Round 10, only those with a 'network approach' were recommended for funding. The Global Fund has only ever approved six malaria multi-country applications. Four approved applications stated strong arguments for a multi-country initiative, combining both 'cross-border' and 'network' approaches.ConclusionWith the cancellation of Round 11 and the proposal that the Global Fund adopt a more targeted and strategic approach to funding, the time is opportune for the Global Fund to develop a clear consensus about the key factors and criteria for funding malaria specific multi-country initiatives. This study found that currently there was a lack of guidance on the key features that a successful multi-country proposal needs to be approved and that applications directed towards the 'network' approach were most successful in Round 10. This type of multi-country proposal may favour other diseases such as HIV, whereas the need for malaria control and elimination is different, focusing on cross-border coordination and delivery of interventions to specific groups. The Global Fund should seek to address these issues and give better guidance to countries and regions and investigate disease-specific calls for multi-country and regional applications.
| S-EPMC3506506 | biostudies-literature
Project description:Malaria remains one of the leading health problems of the developing world, and Uganda bears a particularly large burden from the disease. Our understanding is limited by a lack of reliable data, but it is clear that the prevalence of malaria infection, incidence of disease, and mortality from severe malaria all remain very high. Uganda has made progress in implementing key malaria control measures, in particular distribution of insecticide-impregnated bednets, indoor residual spraying of insecticides, utilization of artemisinin-based combination therapy to treat uncomplicated malaria, and provision of intermittent preventive therapy for pregnant women. However, despite enthusiasm regarding the potential for the elimination of malaria in other areas, there is no convincing evidence that the burden of malaria has decreased in Uganda in recent years. Major challenges to malaria control in Uganda include very high malaria transmission intensity, inadequate health care resources, a weak health system, inadequate understanding of malaria epidemiology and the impact of control interventions, increasing resistance of parasites to drugs and of mosquitoes to insecticides, inappropriate case management, inadequate utilization of drugs to prevent malaria, and inadequate epidemic preparedness and response. Despite these challenges, prospects for the control of malaria have improved, and with attention to underlying challenges, progress toward the control of malaria in Uganda can be expected.
| S-EPMC3156969 | biostudies-literature
Project description:Although few measles cases were reported in France during 2006 and 2007, suggesting the country might have been close to eliminating the disease, a dramatic outbreak of >20,000 cases occurred during 2008-2011. Adolescents and young adults accounted for more than half of cases; median patient age increased from 12 to 16 years during the outbreak. The highest incidence rate was observed in children <1 year of age, reaching 135 cases/100,000 infants during the last epidemic wave. Almost 5,000 patients were hospitalized, including 1,023 for severe pneumonia and 27 for encephalitis/myelitis; 10 patients died. More than 80% of the cases during this period occurred in unvaccinated persons, reflecting heterogeneous vaccination coverage, where pockets of susceptible persons still remain. Although vaccine coverage among children improved, convincing susceptible young adults to get vaccinated remains a critical issue if the target to eliminate the disease by 2015 is to be met.
| S-EPMC3647670 | biostudies-literature
Project description:Background & aimsCoronavirus disease 2019 (COVID-19) has placed a significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in HCV liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination programs.MethodsPreviously developed models were adapted for 110 countries to include a status quo or 'no delay' scenario and a '1-year delay' scenario assuming significant disruption in interventions (screening, diagnosis, and treatment) in the year 2020. Annual country-level model outcomes were extracted, and weighted averages were used to calculate regional (WHO and World Bank Income Group) and global estimates from 2020 to 2030. The incremental annual change in outcomes was calculated by subtracting the 'no-delay' estimates from the '1-year delay' estimates.ResultsThe '1-year delay' scenario resulted in 44,800 (95% uncertainty interval [UI]: 43,800-49,300) excess hepatocellular carcinoma cases and 72,300 (95% UI: 70,600-79,400) excess liver-related deaths, relative to the 'no-delay' scenario globally, from 2020 to 2030. Most missed treatments would be in lower-middle income countries, whereas most excess hepatocellular carcinoma and liver-related deaths would be among high-income countries.ConclusionsThe impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. To mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so.Lay summaryCOVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. A 1-year delay in hepatitis diagnosis and treatment could result in an additional 44,800 liver cancers and 72,300 deaths from HCV globally by 2030. Countries have committed to hepatitis elimination by 2030, so attention should shift back to hepatitis programming as soon as it becomes appropriate to do so.
| S-EPMC7411379 | biostudies-literature
Project description:Myocyte enhancer factor 2 protein (Mef2) is an evolutionarily conserved activator of transcription that is critical to induce and control complex processes in myogenesis and neurogenesis in vertebrates and insects, and osteogenesis in vertebrates. In Drosophila, Mef2 null mutants are unable to produce differentiated muscle cells, and in vertebrates, Mef2 mutants are embryonic lethal. Schistosome worms are responsible for over 200 million cases of schistosomiasis globally, but little is known about early development of schistosome parasites after infecting a vertebrate host. Understanding basic schistosome development could be crucial to delineating potential drug targets. Here, we identify and characterize Mef2 from the schistosome worm Schistosoma mansoni (SmMef2). We initially identified SmMef2 as a homolog to the yeast Mef2 homolog, Resistance to Lethality of MKK1P386 overexpression (Rlm1), and we show that SmMef2 is homologous to conserved Mef2 family proteins. Using a genetics approach, we demonstrate that SmMef2 is a transactivator that can induce transcription of four separate heterologous reporter genes by yeast one-hybrid analysis. We also show that Mef2 is expressed during several stages of schistosome development by quantitative PCR and that it can bind to conserved Mef2 DNA consensus binding sequences.
| S-EPMC3250504 | biostudies-literature
Project description:XY systems usually show chromosome-wide compensation of X-linked genes, while in many ZW systems, compensation is restricted to a minority of dosage-sensitive genes. Why such differences arose is still unclear. Here, we combine comparative genomics, transcriptomics and proteomics to obtain a complete overview of the evolution of gene dosage on the Z-chromosome of Schistosoma parasites. We compare the Z-chromosome gene content of African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes and describe lineage-specific evolutionary strata. We use these to assess gene expression evolution following sex-linkage. The resulting patterns suggest a reduction in expression of Z-linked genes in females, combined with upregulation of the Z in both sexes, in line with the first step of Ohno's classic model of dosage compensation evolution. Quantitative proteomics suggest that post-transcriptional mechanisms do not play a major role in balancing the expression of Z-linked genes.
| S-EPMC6089595 | biostudies-literature
Project description:Both theory and experimental data from pathogens suggest that the production of transmission stages should be strongly associated with virulence, but the genetic bases of parasite transmission/virulence traits are poorly understood. The blood fluke Schistosoma mansoni shows extensive variation in numbers of cercariae larvae shed and in their virulence to infected snail hosts, consistent with expected trade-offs between parasite transmission and virulence. We crossed schistosomes from two populations that differ 8-fold in cercarial shedding and in their virulence to Biomphalaria glabrata snail hosts, and determined four-week cercarial shedding profiles in F0 parents, F1 parents and 376 F2 progeny from two independent crosses in inbred snails. Sequencing and linkage analysis revealed that cercarial production is polygenic and controlled by five QTLs (i.e. Quantitative Trait Loci). These QTLs act additively, explaining 28.56% of the phenotypic variation. These results demonstrate that the genetic architecture of key traits relevant to schistosome ecology can be dissected using classical linkage mapping approaches.
| S-EPMC8237990 | biostudies-literature
Project description:Increasingly sophisticated experiments, coupled with large-scale computational models, have the potential to systematically test biological hypotheses to drive our understanding of multicellular systems. In this short review, we explore key challenges that must be overcome to achieve robust, repeatable data-driven multicellular systems biology. If these challenges can be solved, we can grow beyond the current state of isolated tools and datasets to a community-driven ecosystem of interoperable data, software utilities, and computational modeling platforms. Progress is within our grasp, but it will take community (and financial) commitment.
| S-EPMC6812467 | biostudies-literature