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- Kengne-Ouafo, Jonas A., et al.
(author)
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The global transcriptome of Plasmodium falciparum midstage gametocytes (stages II–IV) appears largely conserved and gametocyte-specific gene expression patterns vary in clinical isolates
- 2023
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In: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 11:5
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Journal article (peer-reviewed)abstract
- Our overall understanding of the developmental biology of malaria parasites has been greatly enhanced by recent advances in transcriptomic analysis. However, most of these investigations rely on laboratory strains (LS) that were adapted into in vitro culture many years ago, and the transcriptomes of clinical isolates (CI) circulating in human populations have not been assessed. In this study, RNA-seq was used to compare the global transcriptome of mid-stage gametocytes derived from three short-term cultured CI, with gametocytes derived from the NF54 reference laboratory strain. The core transcriptome appeared to be consistent between CI- and LS-derived gametocyte preparations, but some important differences were also observed. A majority of gametocyte-specific genes (43/53) appear to have relatively higher expression in CI-derived gametocytes than in LS-derived gametocytes, but a K-means clustering analysis showed that genes involved in flagellum- and microtubule-based processes (movement/motility) were more abundant in both groups, albeit with some differences between them. In addition, gametocytes from one CI described as CI group II gametocytes (CI:GGII) showed gene expression variation in the form of reduced gametocyte-specific gene expression compared to the other two CI-derived gametocytes (CI gametocyte group I, CI:GGI), although the mixed developmental stages used in our study is a potential confounder, only partially mitigated by the inclusion of multiple replicates for each CI. Overall, our study suggests that there may be subtle differences in the gene expression profiles of mid-stage gametocytes from CI relative to the NF54 reference strain of Plasmodium falciparum. Thus, it is necessary to deploy gametocyte-producing clinical parasite isolates to fully understand the diversity of gene expression strategies that may occur during the sequestered development of parasite sexual stages. IMPORTANCE Maturing gametocytes of Plasmodium falciparum are known to sequester away from peripheral circulation into the bone marrow until they are mature. Blocking gametocyte sequestration can prevent malaria transmission from humans to mosquitoes, but most studies aim to understand gametocyte development utilizing long-term adapted laboratory lines instead of clinical isolates. This is a particular issue for our understanding of the sexual stages, which are known to decrease rapidly during adaptation to long-term culture, meaning that many LS are unable to produce transmissible gametocytes. Using RNA-seq, we investigated the global transcriptome of mid-stage gametocytes derived from three clinical isolates and a reference strain (NF54). This identified important differences in gene expression profiles between immature gametocytes of CI and the NF54 reference strain of P. falciparum, suggesting increased investment in gametocytogenesis in clinical isolates. Our transcriptomic data highlight the use of clinical isolates in studying the morphological, cellular features and molecular biology of gametocytes.
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- Kowal, Paul, et al.
(author)
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Ageing and adult health status in eight lower-income countries : the INDEPTH WHO-SAGE collaboration
- 2010
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In: Global Health Action. - : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 3:Supplement 2, s. 11-22
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Journal article (peer-reviewed)abstract
- Background: Globally, ageing impacts all countries, with a majority of older persons residing in lower- and middle-income countries now and into the future. An understanding of the health and well-being of these ageing populations is important for policy and planning; however, research on ageing and adult health that informs policy predominantly comes from higher-income countries. A collaboration between the WHO Study on global AGEing and adult health (SAGE) and International Network for the Demographic Evaluation of Populations and Their Health in developing countries (INDEPTH), with support from the US National Institute on Aging (NIA) and the Swedish Council for Working Life and Social Research (FAS), has resulted in valuable health, disability and well-being information through a first wave of data collection in 2006-2007 from field sites in South Africa, Tanzania, Kenya, Ghana, Viet Nam, Bangladesh, Indonesia and India.Objective: To provide an overview of the demographic and health characteristics of participating countries, describe the research collaboration and introduce the first dataset and outputs. Methods: Data from two SAGE survey modules implemented in eight Health and Demographic Surveillance Systems (HDSS) were merged with core HDSS data to produce a summary dataset for the site-specific and cross-site analyses described in this supplement. Each participating HDSS site used standardised training materials and survey instruments. Face-to-face interviews were conducted. Ethical clearance was obtained from WHO and the local ethical authority for each participating HDSS site.Results: People aged 50 years and over in the eight participating countries represent over 15% of the current global older population, and is projected to reach 23% by 2030. The Asian HDSS sites have a larger proportion of burden of disease from non-communicable diseases and injuries relative to their African counterparts. A pooled sample of over 46,000 persons aged 50 and over from these eight HDSS sites was produced. The SAGE modules resulted in self-reported health, health status, functioning (from the WHO Disability Assessment Scale (WHODAS-II)) and well-being (from the WHO Quality of Life instrument (WHOQoL) variables). The HDSS databases contributed age, sex, marital status, education, socio-economic status and household size variables.Conclusion: The INDEPTH WHO-SAGE collaboration demonstrates the value and future possibilities for this type of research in informing policy and planning for a number of countries. This INDEPTH WHO- SAGE dataset will be placed in the public domain together with this open-access supplement and will be available through the GHA website (www.globalhealthaction.net) and other repositories. An improved dataset is being developed containing supplementary HDSS variables and vignette-adjusted health variables. This living collaboration is now preparing for a next wave of data collection.
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- Ng, Nawi, et al.
(author)
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Health inequalities among older men and women in Africa and Asia : evidence from eight Health and Demographic Surveillance System sites in the INDEPTH WHO-SAGE Study
- 2010
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In: Global Health Action. - : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 3:Supplement 2, s. 96-107
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Journal article (peer-reviewed)abstract
- Background: Declining rates of fertility and mortality are driving demographic transition in all regions of the world, leading to global population ageing and consequently changing patterns of global morbidity and mortality. Understanding sex-related health differences, recognising groups at risk of poor health and identifying determinants of poor health are therefore very important for both improving health trajectories and planning for the health needs of ageing populations.Objectives: To determine the extent to which demographic and socio-economic factors impact upon measures of health in older populations in Africa and Asia; to examine sex differences in health and further explain how these differences can be attributed to demographic and socio-economic determinants.Methods: A total of 46,269 individuals aged 50 years and over in eight Health and Demographic Surveillance System (HDSS) sites within the INDEPTH Network were studied during 2006-2007 using an abbreviated version of the WHO Study on global AGEing and adult health (SAGE) Wave I instrument The survey data were then linked to longitudinal HDSS background information. A health score was calculated based on self-reported health derived from eight health domains. Multivariable regression and post-regression decomposition provide ways of measuring and explaining the health score gap between men and women.Results: Older men have better self-reported health than older women. Differences in household socioeconomic levels, age, education levels, marital status and living arrangements explained from about 82% and 71% of the gaps in health score observed between men and women in South Africa and Kenya, respectively, to almost nothing in Bangladesh. Different health domains contributed differently to the overall health scores for men and women in each country.Conclusion: This study confirmed the existence of sex differences in self-reported health in low- and middleincome countries even after adjustments for differences in demographic and socio-economic factors. A decomposition analysis suggested that sex differences in health differed across the HDSS sites, with the greatest level of inequality found in Bangladesh. The analysis showed considerable variation in how differences in socio-demographic and economic characteristics explained the gaps in self-reported health observed between older men and women in African and Asian settings. The overall health score was a robust indicator of health, with two domains, pain and sleep/energy, contributing consistently across the HDSS sites. Further studies are warranted to understand other significant individual and contextual determinants to which these sex differences in health can be attributed. This will lay a foundation for a more evidence-based approach to resource allocation, and to developing health promotion programmes for older men and women in these settings.
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- Streatfield, P. Kim, et al.
(author)
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Malaria mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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In: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7, s. 25369-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies.OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions.DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality.RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level.CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.
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- Warsame, Marian, et al.
(author)
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Pre-referral Rectal Artesunate Treatment by Community-Based Treatment Providers in Ghana, Guinea-Bissau, Tanzania, and Uganda (Study 18): A Cluster-Randomized Trial.
- 2016
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In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 63:suppl 5
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Journal article (peer-reviewed)abstract
- If malaria patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate prior to hospital referral can prevent death and disability. The goal is to reduce death from malaria by having rectal artesunate treatment available and used. How best to do this remains unknown.Villages remote from a health facility were randomized to different community-based treatment providers trained to provide rectal artesunate in Ghana, Guinea-Bissau, Tanzania, and Uganda. Prereferral rectal artesunate treatment was provided in 272 villages: 109 through community-based health workers (CHWs), 112 via trained mothers (MUMs), 25 via trained traditional healers (THs), and 26 through trained community-chosen personnel (COMs); episodes eligible for rectal artesunate were established through regular household surveys of febrile illnesses recording symptoms eligible for prereferral treatment. Differences in treatment coverage with rectal artesunate in children aged <5 years in MUM vs CHW (standard-of-care) villages were assessed using the odds ratio (OR); the predictive probability of treatment was derived from a logistic regression analysis, adjusting for heterogeneity between clusters (villages) using random effects.Over 19 months, 54 013 children had 102 504 febrile episodes, of which 32% (31 817 episodes) had symptoms eligible for prereferral therapy; 14% (4460) children received treatment. Episodes with altered consciousness, coma, or convulsions constituted 36.6% of all episodes in treated children. The overall OR of treatment between MUM vs CHW villages, adjusting for country, was 1.84 (95% confidence interval [CI], 1.20-2.83; P = .005). Adjusting for heterogeneity, this translated into a 1.67 higher average probability of a child being treated in MUM vs CHW villages. Referral compliance was 81% and significantly higher with CHWs vs MUMs: 87% vs 82% (risk ratio [RR], 1.1 [95% CI, 1.0-1.1]; P < .0001). There were more deaths in the TH cluster than elsewhere (RR, 2.7 [95% CI, 1.4-5.6]; P = .0040).Prereferral episodes were almost one-third of all febrile episodes. More than one-third of patients treated had convulsions, altered consciousness, or coma. Mothers were effective in treating patients, and achieved higher coverage than other providers. Treatment access was low.ISRCTN58046240.
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