National Institute of Medical Research
National Institute of Medical Research
Turner L.,Copenhagen University |
Lavstsen T.,Copenhagen University |
Berger S.S.,Copenhagen University |
Wang C.W.,Copenhagen University |
And 12 more authors.
Nature | Year: 2013
Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year. Sequestration is mediated by specific interactions between members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins was unknown. Here we identify endothelial protein C receptor (EPCR), which mediates the cytoprotective effects of activated protein C, as the endothelial receptor for DC8 and DC13 PfEMP1. We show that EPCR binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDRα1) of DC8 and group A PfEMP1 subfamilies, and that CIDRα1 interferes with protein C binding to EPCR. This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways, and has implications for understanding malaria pathology and the development of new malaria interventions. © 2013 Macmillan Publishers Limited. All rights reserved.
Ha W.,Peking University |
Salama P.,UNICEF Ethiopia |
Gwavuya S.,UNICEF Zimbabwe |
Kanjala C.,National Institute of Medical Research
Social Science and Medicine | Year: 2014
The Apostolic faith, a rapidly growing and increasingly influential force in Zimbabwe, has received attention in the literature due to its potential role in shaping its followers' attitudes and behaviours towards health. Existing literature, however, has only examined small cross-section samples from a few confined survey sites or has failed to adequately control for the many factors that may mediate the effects of religion. This paper examines the effects of the Apostolic faith on the usage of maternal health and child immunization services in Zimbabwe. It is based on a nationally representative sample from the 2009 Multi-Indicator Monitoring Survey and employs the established Andersen model on access to health services. Well controlled multivariate logit regression models derived from these data show that an affiliation with the Apostolic faith is a substantial and significant risk factor in reducing the utilization of both maternal and child health services. Moreover, even when the services were least costly and readily available and when gaps along other social and economic factors were limited, as in the case of Bacillus Calmette-Guérin vaccination and one visit to antenatal care, women and children from Apostolic faith families still fared significantly worse than others in accessing them. © 2014 Elsevier Ltd.
Theron G.,Lung Infection and Immunity Unit |
Zijenah L.,University of Zimbabwe |
Chanda D.,University of Lusaka |
Clowes P.,National Institute of Medical Research |
And 16 more authors.
The Lancet | Year: 2014
Background: The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa. Methods: In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from five primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials. gov, number NCT01554384. Findings: Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not diff er between groups at 2 months (2 [IQR 0-3] in the smear microscopy group vs 2 [0·25-3] in the MTB/RIF group; p=0·85) or 6 months (1 [0-3] vs 1 [0-3]; p=0·35), nor did median KPS at 2 months (80 [70-90] vs 90 [80-90]; p=0·23) or 6 months (100 [90-100] vs 100 [90-100]; p=0·85). Point-of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0·0001) but similar specificity (517 [95%] 544 vs 540 [96%] of 560; p=0·25), and had similar sensitivity to laboratory-based MTB/RIF (292 [83%] of 351; p=0·99) but higher specificity (952 [92%] of 1037; p=0·0173). 34 (5%) of 744 tests with point-of-care MTB/RIF and 82 (6%) of 1411 with laboratory-based MTB/RIF failed (p=0·22). Compared with the microscopy group, more patients in the MTB/RIF group had a same-day diagnosis (178 [24%] of 744 vs 99 [13%] of 758; p<0·0001) and same-day treatment initiation (168 [23%] of 744 vs 115 [15%] of 758; p=0·0002). Although, by end of the study, more culture-positive patients in the MTB/RIF group were on treatment due to reduced dropout (15 [8%] of 185 in the MTB/RIF group did not receive treatment vs 28 [15%] of 182 in the microscopy group; p=0·0302), the proportions of all patients on treatment in each group by day 56 were similar (320 [43%] of 744 in the MTB/RIF group vs 317 [42%] of 758 in the microscopy group; p=0·6408). Interpretation: Xpert MTB/RIF can be accurately administered by a nurse in primary-care clinics, resulting in more patients starting same-day treatment, more culture-positive patients starting therapy, and a shorter time to treatment. However, the benefits did not translate into lower tuberculosis-related morbidity, partly because of high levels of empirical-evidence-based treatment in smear-negative patients. Funding European and Developing Countries Clinical Trials Partnership, National Research Foundation, and Claude Leon Foundation.
Wringe A.,London School of Hygiene and Tropical Medicine |
Floyd S.,London School of Hygiene and Tropical Medicine |
Kazooba P.,Medical Research Council |
Mushati P.,Biomedical Research and Training Institute |
And 6 more authors.
Tropical Medicine and International Health | Year: 2012
Objective To compare socio-demographic patterns in access to antiretroviral therapy (ART) across four community HIV cohort studies in Africa. Methods Data on voluntary counselling and testing and ART use among HIV-infected persons were analysed from Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and Manicaland (Zimbabwe), where free ART provision started between 2004 and 2007. ART coverage was compared across sites by calculating the proportion on ART among those estimated to need treatment, by age, sex and educational attainment. Logistic regression was used to identify socio-demographic characteristics associated with undergoing eligibility screening at an ART clinic within 2years of being diagnosed with HIV, for three sites with information on diagnosis and screening dates. Results Among adults known to be HIV-infected from serological surveys, the proportion who knew their HIV status was 93% in Karonga, 37% in Kisesa, 46% in Masaka and 25% in Manicaland. Estimated ART coverage was highest in Masaka (68%) and lowest in Kisesa (2%). The proportion of HIV-diagnosed persons who were screened for ART eligibility within 2years of diagnosis ranged from 14% in Kisesa to 84% in Masaka, with the probability of screening uptake increasing with age at diagnosis in all sites. Conclusions Higher HIV testing rates among HIV-infected persons in the community do not necessarily correspond with higher uptake of ART, nor more equitable treatment coverage among those in need of treatment. In all sites, young adults tend to be disadvantaged in terms of accessing and initiating ART, even after accounting for their less urgent need. © 2012 Blackwell Publishing Ltd.
News Article | September 7, 2016
“It is amazing, isn't it,” says Paul Nurse, as he stands on a bridge overlooking the grand atrium of the new Francis Crick Institute in London. Light floods in from the building's cathedral-like entrance. “I can't quite believe it's here." Nurse, the institute’s founding director, and his ten lab members are among the first researchers to begin working at the Crick, which opened to the media on 1 September. The UK government and the Crick’s other funders have gambled £700 million (US$927 million) on the institute, in the hope that it will attract some of world’s brightest young biomedical researchers to Britain and catalyse a boom in the UK life-sciences economy. The building will eventually house 1,500 scientists and support staff, making it Europe's largest single-site biomedical institute. They will study a broad portfolio of biomedical research, from immunology to cancer genetics. The 93,000-square-metre glass and steel temple looms over the neighbouring British Library, the largest public structure built in Britain in the twentieth century. But looming over the Crick is the prospect of Brexit. The UK vote on 23 June to leave the European Union poses a range of uncertainties for UK researchers, from access to European funding to the ease of moving between EU countries. “Our vision is to be a major research institute of great significance on the world stage,” says Nurse. “Internationalism is absolutely in our DNA.” The Crick’s first researchers, who began arriving in mid-August, come mostly from two institutes in London: the National Institute of Medical Research, run by the Medical Research Council, and the London Research Institute, run by the charity Cancer Research UK. The ultimate plan is for the Crick to house a growing and ever-changing roster of young group leaders, who will spend up to 12 years there. More than half of the Crick’s current postdocs are from EU countries other than the United Kingdom, Nurse notes, and limits to freedom of movement for EU workers could make it harder to recruit. And if Britain does not secure access to EU research-funding programmes, that could also limit funding for the Crick's scientists. Jernej Ule, a molecular biologist at University College London who will spend three years at the Crick, is emblematic of Nurse’s international vision. Ule is a native of Slovenia and did his PhD and postdoctoral work in the United States. His lab, which studies how changes in gene expression influence motor neuron disease and other neural conditions, includes scientists from Spain, Italy, France, Germany and the United Kingdom. “For me to recruit the best people, I need to have a capacity to throw a net very broadly,” he says. Ule also receives EU funding. After he arrived in the United Kingdom, he won a grant from the European Research Council (ERC) in 2007 to study RNA regulatory networks in neurons, then a nascent area of research. “Having the chance to apply for European funding at this top level is crucial to give us this independence of thinking in very new directions," he says. “Without the ERC I wouldn't be where I am right now.” He and several other scientists who have begun working at the Crick say that the institute’s mission is even more essential in the wake of the Brexit vote. “It’s almost like we have the Crick in spite of Brexit,” says Matthew Swaffer, a postdoc in Nurse’s lab. “I feel like it portrays the exact opposite sentiment that some people feel Brexit represents.” Swaffer's colleague Tiffany Mak, a first-year PhD student, joined the Crick in part because of its allure as a mecca for researchers from a wide variety of disciplines — and that has not diminished. “This project puts so much emphasis on bringing people from all sorts of backgrounds together. Hopefully it will act as a hub and not let politics get in the way of science and collaboration.” The Crick is likely to experience many of the same anxieties over Brexit as other UK research institutions, says Kieron Flanagan, a science-policy researcher at the University of Manchester. But the institute’s high profile — some have described it as “too big to fail” — could even buffer it from some Brexit worries, such as the ability to continue to recruit top scientists from Europe, he says. “They may have fewer problems than the university in the middle of nowhere in attracting people, but there will still be that concern there.”
Nsubuga R.N.,Medical Research Council Uganda Virus Research Institute MRC UVRI |
Maher D.,Medical Research Council Uganda Virus Research Institute MRC UVRI |
Todd J.E.,London School of Hygiene and Tropical Medicine |
Todd J.E.,National Institute of Medical Research
Journal of Acquired Immune Deficiency Syndromes | Year: 2013
Objective: To estimate the contribution to HIV prevalence of lives saved due to the introduction of antiretroviral therapy (ART) in rural Uganda in 2004. Design: Open population-based cohort study. Methods: An open general population cohort with annual demographic and HIV serostatus data is used to estimate annual HIV prevalence, HIV incidence, and mortality from 2000 to 2010. We calculated standardized mortality rates among HIV-positive adults and the expected number of deaths in the cohort if ART had not been available during 2004-2010, based on the average mortality rate in the 4 years (2000-2003) before ART introduction. Results: During 2004-2010, the estimated prevalence increased by 29% from 6.9% to 8.9%. HIV incidence was 5.6 cases per 1000 person-years in 2004, falling to 3.9 cases per 1000 person-years in 2006, and slightly rising to 5.1 in 2010. There was an increase of 182 in the number of HIV-positive participants during that period, cumulatively 228 lives were saved due to ART. Expected lives saved due to ART accounted for an increasing proportion of the estimated HIV prevalence from 4.0% in 2004 to 29.4% in 2010. Conclusions: Expected lives saved due to ART largely accounted for the increased estimated HIV prevalence from 2004 to 2010. Because HIV prevalence survey results are important for planning, programming, and policy, their interpretation requires consideration of the increasing impact of ART in decreasing mortality. Copyright © 2012 by Lippincott Williams & Wilkins.
Poling A.,Western Michigan University |
Weetjens B.J.,Anti Persoonsmijnen Ontmijnende Product Ontwikkeling APOPO |
Cox C.,Anti Persoonsmijnen Ontmijnende Product Ontwikkeling APOPO |
Mgode G.,Anti Persoonsmijnen Ontmijnende Product Ontwikkeling APOPO |
And 4 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2010
In 2009, giant African pouched rats trained to detect tuberculosis (TB) evaluated sputum samples from 10,523 patients whose sputum had previously been evaluated by smear microscopy. Microscopists found 13.3% of the patients to be TB-positive. Simulated second-line screening by the rats revealed 620 new TB-positive patients, increasing the case detection rate by 44%. These data suggest that the rats may be useful for TB detection in developing countries, although further research is needed. Copyright © 2010 by The American Society of Tropical Medicine and Hygiene.
Maestad O.,Chr Michelsen Institute |
Mwisongo A.,National Institute of Medical Research
Health Policy | Year: 2011
Informal payments for health services are common in many transitional and developing countries. The aim of this paper is to investigate the nature of informal payments in the health sector of Tanzania and to identify mechanisms through which informal payments may affect the quality of health care. Our focus is on the effect of informal payments on health worker behaviours, in particular the interpersonal dynamics among health workers at their workplaces. We organised eight focus groups with 58 health workers representing different cadres and levels of care in one rural and one urban district in Tanzania. We found that health workers at all levels receive informal payments in a number of different contexts. Health workers sometimes share the payments received, but only partially, and more rarely within the cadre than across cadres. Our findings indicate that health workers are involved in 'rent-seeking' activities, such as creating artificial shortages and deliberately lowering the quality of service, in order to extract extra payments from patients or to bargain for a higher share of the payments received by their colleagues. The discussions revealed that many health workers think that the distribution of informal payments is grossly unfair. The findings suggest that informal payments can impact negatively on the quality of health care through rent-seeking behaviours and through frustrations created by the unfair allocation of payments. Interestingly, the presence of corruption may also induce non-corrupt workers to reduce the quality of care. Positive impacts can occur because informal payments may induce health workers to increase their efforts, and maybe more so if there is competition among health workers about receiving the payments. Moreover, informal payments add to health workers' incomes and might thus contribute to retention of health workers within the health sector. © 2010 Elsevier Ireland Ltd.
Nalwoga A.,Medical Research Council Uganda Virus Research Institute MRC UVRI |
Maher D.,Medical Research Council Uganda Virus Research Institute MRC UVRI |
Todd J.,National Institute of Medical Research |
Karabarinde A.,Medical Research Council Uganda Virus Research Institute MRC UVRI |
And 2 more authors.
Tropical Medicine and International Health | Year: 2010
Objectives: To assess the nutritional status of children in a rural community with high HIV prevalence in rural Uganda and to examine the impact of HIV infection at the individual and population level. Methods: Cross-sectional population-based survey of children aged 0-12 in a cohort comprising the residents of 25 neighbouring villages in rural southwest Uganda. Anthropometric indicators of nutritional status (height for age, weight for age and weight for height) were assessed in relation to children's HIV serostatus, maternal HIV serostatus and maternal vital status. Children with a Z score of <-2 were defined as undernourished, with a Z score <-2 for weight for age defining underweight, for height for age defining stunting and for weight for height defining wasting. Results: Of 5951 children surveyed, 91% underwent anthropometric measurement: 30% were underweight, 42% stunted and 10% wasted. HIV seroprevalence among children aged 2-12 was 0.7%. The prevalence of underweight was significantly higher in HIV-positive than in HIV-negative children (52% vs. 30%), as was the prevalence of stunting (68% vs. 42%), but there was no significant difference in the prevalence of wasting (4% vs. 9%). There were no significant differences in the prevalences of indicators of undernutrition in children classified by maternal HIV and vital status. Conclusions: Chronic childhood undernutrition is common in this rural community. HIV infection had a direct effect in worsening children's nutritional status, but no indirect effect in terms of maternal HIV infection or maternal death. The population-level impact of childhood HIV infection on nutritional status is limited on account of the low HIV prevalence in children. The response to undernutrition in children in Africa requires action on many fronts: not only delivering community-wide HIV and nutritional interventions but also addressing the many interacting factors that contributed to childhood undernutrition before the HIV era and still do so now. © 2010 Blackwell Publishing Ltd.
Kabali C.,Boston University |
Kabali C.,National Institute of Medical Research |
Cheng D.M.,Boston University |
Brooks D.R.,Boston University |
And 3 more authors.
AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV | Year: 2011
The association between smoking and HIV disease progression has been examined in several studies; however, findings have been inconsistent. We examined the effect of recent cigarette smoking on CD4+ T cell count/l (CD4 count) and HIV RNA concentration (HIV viral load (VL)) among two HIV-infected cohorts with alcohol problems in Massachusetts in the periods 1997-2001 and 2001-2006 using a prospective cohort design and linear mixed models. Smoking groups were defined as: minimal or non-smokers, light smokers, moderate smokers, and heavy smokers. Age, alcohol use, injection drug use, depressive symptoms, gender, annual income, and antiretroviral therapy adherence were considered as potential confounders. Among 462 subjects, no significant differences in CD4 count or VL were found between smoking groups. Using minimal or non-smokers as the reference group, the adjusted mean differences in CD4 count were: 8.2 (95% confidence interval (CI): -17.4, 33.8) for heavy smokers; -0.1 (95% CI: -25.4, 5.1) for moderate smokers; and -2.6 (95% CI: -28.3, 3.0) for light smokers. For log10 VL, the adjusted differences were: 0.03 (95% CI: -0.12, 0.17) for heavy smokers; -0.06 (95% CI: -0.20, 0.08) for moderate smokers; and 0.14 (95% CI -0.01, 0.28) for light smokers. This study did not find an association between smoking cigarettes and HIV disease progression as measured by CD4 cell count and VL. © 2011 Taylor & Francis.