Publications by authors named "Shabbar Jaffar"

116 Publications

Integration of non-communicable disease and HIV/AIDS management: a review of healthcare policies and plans in East Africa.

BMJ Glob Health 2021 May;6(5)

Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK

Background: Low-income and middle-income countries are struggling to manage growing numbers of patients with chronic non-communicable diseases (NCDs), while services for patients with HIV infection are well established. There have been calls for integration of HIV and NCD services to increase efficiency and improve coverage of NCD care, although evidence of effectiveness remains unclear. In this review, we assess the extent to which National HIV and NCD policies in East Africa reflect the calls for HIV-NCD service integration.

Methods: Between April 2018 and December 2020, we searched for policies, strategies and guidelines associated with HIV and NCDs programmes in Burundi, Kenya, Rwanda, South Sudan, Tanzania and Uganda. Documents were searched manually for plans for integration of HIV and NCD services. Data were analysed qualitatively using document analysis.

Results: Thirty-one documents were screened, and 13 contained action plans for HIV and NCDs service integration. Integrated delivery of HIV and NCD care is recommended in high level health policies and treatment guidelines in four countries in the East African region; Kenya, Rwanda, Tanzania and Uganda, mostly relating to integrating NCD care into HIV programmes. The increasing burden of NCDs, as well as a move towards person-centred differentiated delivery of services for people living with HIV, is a factor in the recent adoption of integrated HIV and NCD service delivery plans. Both South Sudan and Burundi report a focus on building their healthcare infrastructure and improving coverage and quality of healthcare provision, with no reported plans for HIV and NCD care integration.

Conclusion: Despite the limited evidence of effectiveness, some East African countries have already taken steps towards HIV and NCD service integration. Close monitoring and evaluation of the integrated HIV and NCD programmes is necessary to provide insight into the associated benefits and risks, and to inform future service developments.
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http://dx.doi.org/10.1136/bmjgh-2020-004669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098934PMC
May 2021

Fungal Burden and Raised Intracranial Pressure Are Independently Associated With Visual Loss in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis.

Open Forum Infect Dis 2021 Apr 5;8(4):ofab066. Epub 2021 Feb 5.

Centre for Global Health, Institute of Infection and Immunity, St George's University of London, London, United Kingdom.

Among 472 patients with human immunodeficiency virus-associated cryptococcal meningitis, 16% had severe visual loss at presentation, and 46% of these were 4-week survivors and remained severely impaired. Baseline cerebrospinal fluid opening pressure ≥40 cmHO (adjusted odds ratio [aOR], 2.56; 95% confidence interval [CI], 1.36-4.83; = .02) and fungal burden >6.0 log colonies/mL (aOR, 3.01; 95% CI, 1.58-5.7; = .003) were independently associated with severe visual loss.
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http://dx.doi.org/10.1093/ofid/ofab066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078267PMC
April 2021

Prevalence and Correlates of Cardio-Metabolic Risk Factors Among Regular Street Food Consumers in Dar es Salaam, Tanzania.

Diabetes Metab Syndr Obes 2021 5;14:1011-1024. Epub 2021 Mar 5.

Public Health Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.

Background: Regular street food consumers (RSFCs) in Africa are at an increased risk of unhealthy eating practices, which have been associated with intermediate risk factors of cardio-metabolic diseases. However, knowledge of the magnitude and correlates of these risk factors is limited in Tanzania. This study aimed to fill this gap using data collected from RSFCs in Dar es Salaam, the largest city in Tanzania.

Methodology: A cross-sectional study was carried out among 560 RSFCs in three districts of Dar es Salaam between July and September 2018. Information on socio-economic factors and demographics, behavioral risks, anthropometric and biochemical indicators was collected. Adjusted odds ratios (OR) and prevalence ratio (PR) with corresponding 95% confidence intervals (CI) were estimated using multivariable binary logistic and modified Poisson regression models, respectively.

Results: On average, participants consumed 11 street food meals/week. The prevalence (95% CI) of cardio-metabolic risk factors was 63.9% (60.6-69.9%) for overweight/obesity, 42.5% (38.3-46.9%) for raised blood pressure, 13.5% (10.9-16.8%) for raised triglycerides and 6.6% (4.9-9.3%) for raised glucose levels. The correlates of overweight/obesity were female vs male sex (APR=1.3; 95% CI 1.2-1.5), age of 41-64 vs 25-40 years (APR=1.4; 95% CI 1.2-1.6), high vs low income (APR=1.2; 95% CI 1.04-1.3), being married/cohabiting vs other (APR=1.2; 95% CI 1.01-1.4) and family history of diabetes vs no family history (APR=1.2; 95% CI 1.01-1.3). Age 41-64 vs 25-40 years, was the only significant factor associated with raised blood pressure APR (95% CI) 2.2 (1.7-2.9) and raised glucose AOR (95% CI) 3.9 (1.5-10.5).

Conclusion: Our study revealed that RSFCs are at risk of cardio-metabolic health problems, especially women, middle-aged people and those with higher incomes. Transdisciplinary studies to understand the drivers of street food consumption are needed in order to inform interventions to mitigate the risk of developing cardio-metabolic diseases. These interventions should target both street food vendors and their consumers.
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http://dx.doi.org/10.2147/DMSO.S287999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943326PMC
March 2021

Strengthening integration of chronic care in Africa: protocol for the qualitative process evaluation of integrated HIV, diabetes and hypertension care in a cluster randomised controlled trial in Tanzania and Uganda.

BMJ Open 2020 10 7;10(10):e039237. Epub 2020 Oct 7.

Department of International Public Health, Liverpool School of Tropical Medicine, Liverpool, Liverpool, UK.

Introduction: In sub-Saharan Africa, the burden of non-communicable diseases (NCDs), particularly diabetes mellitus (DM) and hypertension, has increased rapidly in recent years, although HIV infection remains a leading cause of death among young-middle-aged adults. Health service coverage for NCDs remains very low in contrast to HIV, despite the increasing prevalence of comorbidity of NCDs with HIV. There is an urgent need to expand healthcare capacity to provide integrated services to address these chronic conditions.

Methods And Analysis: This protocol describes procedures for a qualitative process evaluation of INTE-AFRICA, a cluster randomised trial comparing integrated health service provision for HIV infection, DM and hypertension, to the current stand-alone vertical care. Interviews, focus group discussions and observations of consultations and other care processes in two clinics (in Tanzania, Uganda) will be used to explore the experiences of stakeholders. These stakeholders will include health service users, policy-makers, healthcare providers, community leaders and members, researchers, non-governmental and international organisations. The exploration will be carried out during the implementation of the project, alongside an understanding of the impact of broader structural and contextual factors.

Ethics And Dissemination: Ethical approval was granted by the Liverpool School of Tropical Medicine (UK), the National Institute of Medical Research (Tanzania) and TASO Research Ethics Committee (Uganda) in 2020. The evaluation will provide the opportunity to document the implementation of integration over several timepoints (6, 12 and 18 months) and refine integrated service provision prior to scale up. This synergistic approach to evaluate, understand and respond will support service integration and inform monitoring, policy and practice development efforts to involve and educate communities in Tanzania and Uganda. It will create a model of care and a platform of good practices and lessons learnt for other countries implementing integrated and decentralised community health services.

Trial Registration Number: ISRCTN43896688; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-039237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542920PMC
October 2020

A comparison of the associations between adiposity and lipids in Malawi and the United Kingdom.

BMC Med 2020 07 16;18(1):181. Epub 2020 Jul 16.

MRC Integrated Epidemiology Unit, University of Bristol, Bristol, UK.

Background: The prevalence of excess adiposity, as measured by elevated body mass index (BMI) and waist-hip ratio (WHR), is increasing in sub-Saharan African (SSA) populations. This could add a considerable burden of cardiovascular and metabolic diseases for which these populations are currently ill-prepared. Evidence from white, European origin populations shows that higher adiposity leads to an adverse lipid profile; whether these associations are similar in all SSA populations requires further exploration. This study compared the association of BMI and WHR with lipid profile in urban Malawi with a contemporary cohort with contrasting socioeconomic, demographic, and ethnic characteristics in the United Kingdom (UK).

Methods: We used data from 1248 adolescents (mean 18.7 years) and 2277 Malawian adults (mean 49.8 years), all urban-dwelling, and from 3201 adolescents (mean 17.8 years) and 6323 adults (mean 49.7 years) resident in the UK. Adiposity measures and fasting lipids were assessed in both settings, and the associations of BMI and WHR with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed by sex and age groups in both studies.

Results: Malawian female adults were more adipose and had more adverse lipid profiles than their UK counterparts. In contrast, Malawian adolescent and adult males were leaner and had more favourable lipid profiles than in the UK. Higher BMI and WHR were associated with increased TC, LDL-C and TG and reduced HDL-C in both settings. The magnitude of the associations of BMI and WHR with lipids was mostly similar or slightly weaker in the Malawian compared with the UK cohort in both adolescents and adults. One exception was the stronger association between increasing adiposity and elevated TC and LDL-C in Malawian compared to UK men.

Conclusions: Malawian adult women have greater adiposity and more adverse lipid profiles compared with their UK counterparts. Similar associations of adiposity with adverse lipid profiles were observed for Malawian and UK adults in most age and sex groups studied. Sustained efforts are urgently needed to address the excess adiposity and adverse lipid profiles in Malawi to mitigate a future epidemic of cardio-metabolic disease among the poorest populations.
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http://dx.doi.org/10.1186/s12916-020-01648-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364601PMC
July 2020

Sex and area differences in the association between adiposity and lipid profile in Malawi.

BMJ Glob Health 2019 11;4(5):e001542. Epub 2019 Sep 11.

Malawi Epidemiology and Intervention Research Unit (MEIRU), Lilongwe and Karonga, Malawi.

Background: Evidence from high-income countries shows that higher adiposity results in an adverse lipid profile, but it is unclear whether this association is similar in Sub-Saharan African (SSA) populations. This study aimed to assess the association between total and central adiposity measures and lipid profile in Malawi, exploring differences by sex and area of residence (rural/urban).

Methods: In this cross-sectional study, data from 12 096 rural and 12 847 urban Malawian residents were used. The associations of body mass index (BMI) and waist to hip ratio (WHR) with fasting lipids (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)) were assessed by area and sex.

Results: After adjusting for potential confounders, higher BMI and WHR were linearly associated with increased TC, LDL-C and TG and reduced HDL-C. BMI was more strongly related to fasting lipids than was WHR. The associations of adiposity with adverse lipid profile were stronger in rural compared with urban residents. For instance, one SD increase in BMI was associated with 0.23 mmol/L (95% CI 0.19 to 0.26) increase in TC in rural women and 0.13 mmol/L (95% CI 0.11 to 0.15) in urban women. Sex differences in the associations between adiposity and lipids were less evident.

Conclusions: The consistent associations observed of higher adiposity with adverse lipid profiles in men and women living in rural and urban areas of Malawi highlight the emerging adverse cardio-metabolic epidemic in this poor population. Our findings underline the potential utility of BMI in estimating cardiovascular risk and highlight the need for greater investment to understand the long-term health outcomes of obesity and adverse lipid profiles and the extent to which lifestyle changes and treatments effectively prevent and modify adverse cardio-metabolic outcomes.
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http://dx.doi.org/10.1136/bmjgh-2019-001542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747887PMC
September 2019

One-year Mortality Outcomes From the Advancing Cryptococcal Meningitis Treatment for Africa Trial of Cryptococcal Meningitis Treatment in Malawi.

Clin Infect Dis 2020 01;70(3):521-524

Centre for Global Health, Institute for Infection and Immunity, St George's University of London, United Kingdom.

In Malawi, 236 participants from the Advancing Cryptococcal Meningitis Treatment for Africa trial were followed for 12 months. The trial outcomes reported at 10 weeks were sustained to 1 year. One-week amphotericin B plus flucytosine was associated with the lowest 1 year mortality (27.5% [95% confidence interval, 16.3 to 44.1]).
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http://dx.doi.org/10.1093/cid/ciz454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105249PMC
January 2020

Cryptococcal Meningitis Screening and Community-based Early Adherence Support in People With Advanced Human Immunodeficiency Virus Infection Starting Antiretroviral Therapy in Tanzania and Zambia: A Cost-effectiveness Analysis.

Clin Infect Dis 2020 04;70(8):1652-1657

Department of International Public Health, Liverpool School of Tropical Medicine, United Kingdom.

Background: A randomized trial demonstrated that among people living with late-stage human immunodeficiency virus (HIV) infection initiating antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness.

Methods: HIV-infected adults with CD4 count <200 cells/μL were randomized to either CrAg screening plus 4 weekly home visits to provide adherence support or to standard clinic-based care in Dar es Salaam and Lusaka. The primary economic outcome was health service care cost per life-year saved as the incremental cost-effectiveness ratio (ICER), based on 2017 US dollars. We used nonparametric bootstrapping to assess uncertainties and univariate deterministic sensitivity analysis to examine the impact of individual parameters on the ICER.

Results: Among the intervention and standard arms, 1001 and 998 participants, respectively, were enrolled. The annual mean cost per participant in the intervention arm was US$339 (95% confidence interval [CI], $331-$347), resulting in an incremental cost of the intervention of US$77 (95% CI, $66-$88). The incremental cost was similar when analysis was restricted to persons with CD4 count <100 cells/μL. The ICER for the intervention vs standard care, per life-year saved, was US$70 (95% CI, $43-$211) for all participants with CD4 count up to 200 cells/μL and US$91 (95% CI, $49-$443) among those with CD4 counts <100 cells /μL. Cost-effectveness was most sensitive to mortality estimates.

Conclusions: Screening for cryptococcal antigen combined with a short period of adherence support, is cost-effective in resource-limited settings.
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http://dx.doi.org/10.1093/cid/ciz453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146002PMC
April 2020

AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study.

BMJ Open 2019 04 1;9(4):e026288. Epub 2019 Apr 1.

Department of Clinical Sciences and International Public Health, Liverpool School of Tropical Medicine, Liverpool, UK.

Introduction: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation.

Methods And Analysis: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial.

Ethics And Dissemination: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings.

Trial Registration: ISRCTN 7250 9687; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-026288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500286PMC
April 2019

Healthcare Costs and Life-years Gained From Treatments Within the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) Trial on Cryptococcal Meningitis: A Comparison of Antifungal Induction Strategies in Sub-Saharan Africa.

Clin Infect Dis 2019 08;69(4):588-595

Liverpool School of Tropical Medicine, United Kingdom.

Background: Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses.

Methods: Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done.

Results: Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91-1210) per life-year saved.

Clinical Trials Registration: ISRCTN45035509.

Conclusions: Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments.
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http://dx.doi.org/10.1093/cid/ciy971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669289PMC
August 2019

Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis.

Clin Infect Dis 2020 01;70(1):26-29

Centre for Global Health, Institute for Infection and Immunity, St George's University of London, United Kingdom.

Background: Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain.

Methods: The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER.

Results: The mean costs per patient were US $847 (95% confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95% CI $557-709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9-41.7%) with FLU+5FC and 53.8% (95% CI 43.1-64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved.

Conclusions: The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.
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http://dx.doi.org/10.1093/cid/ciz163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912152PMC
January 2020

Growth in early life and physical and intellectual development at school age: a cohort study.

Br J Nutr 2019 04 11;121(8):866-876. Epub 2019 Feb 11.

1Department of Epidemiology and Biostatistics,School of Public Health,Xi'an Jiaotong University Health Science Center,Xi'an,710061,People's Republic of China.

The associations between growth during early life and subsequent cognitive development and physical outcomes are not widely known in low-resource settings. We examined postnatal weight and height gain through early life and related these measurements to the nutritional status and intellectual development of the same children when they were between 7 and 9 years old. Mothers had enrolled in an randomised controlled trial to evaluate the effect of prenatal micronutrient supplementation on birth weight. Their children were born in 2004, their height and weight were measured at 6, 12, 18 and 24 months of age and were followed up between October 2012 and September 2013 (at ages 7-9 years, n 650). Height-for-age, weight-for-age and BMI-for-age were used to describe the nutritional status, and the Wechsler Intelligence Scale for Children fourth edition was used to measure the intellectual function. Multilevel linear and logistic modelling was used to estimate the association between early growth and subsequent growth and intellectual function. After adjustment, weight gain from 6 to 12 months of age was associated with Full-scale Intelligence Quotient, Verbal Comprehension Index, Working Memory Index and Perceptual Reasoning Index. Weight gain during early life was associated with subsequent nutritional status. For every 1 kg increase in weight during the 0- to 6-month period, the OR for underweight, thinness and stunting at 7-9 years of age were 0·19 (95 % CI 0·09, 0·37), 0·34 (95 % CI 0·19, 0·59) and 0·40 (95 % CI 0·19, 0·83), respectively. Weight gain during the periods of 6-12 months of age and 18-24 months of age was also associated with a lower risk of being underweight. Weight gain during early life was associated with better growth outcomes and improved intellectual development in young school-aged children.
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http://dx.doi.org/10.1017/S0007114519000060DOI Listing
April 2019

AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial.

Trials 2018 Nov 23;19(1):649. Epub 2018 Nov 23.

Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Background: Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretroviral therapy (ART). Mortality is driven in part by limited availability of amphotericin-based treatment, drug-induced toxicities of amphotericin B deoxycholate and prolonged hospital admissions. A single, high-dose of liposomal amphotericin (L-AmB, Ambisome) on a fluconazole backbone has been reported as non-inferior to 14 days of standard dose L-AmB in reducing fungal burden. This trial examines whether single, high-dose L-AmB given with high-dose fluconazole and flucytosine is non-inferior to a seven-day course of amphotericin B deoxycholate plus flucytosine (the current World Health Organization [WHO] recommended treatment regimen).

Methods: An open-label phase III randomised controlled non-inferiority trial conducted in five countries in sub-Saharan Africa: Botswana, Malawi, South Africa, Uganda and Zimbabwe. The trial will compare CM induction therapy with (1) a single dose (10 mg/kg) of L-AmB given with 14 days of fluconazole (1200 mg/day) and flucytosine (100 mg/kg/day) to (2) seven days amphotericin B deoxycholate (1 mg/kg/day) given alongside seven days of flucytosine (100 mg/kg/day) followed by seven days of fluconazole (1200 mg/day). The primary endpoint is all-cause mortality at ten weeks with a non-inferiority margin of 10% and 90% power. Secondary endpoints are early fungicidal activity, proportion of grade III/IV adverse events, pharmacokinetic parameters and pharmacokinetic/pharmacodynamic associations, health service costs, all-cause mortality within the first two and four weeks, all-cause mortality within the first ten weeks (superiority analysis) and rates of CM relapse, immune reconstitution inflammatory syndrome and disability at ten weeks. A total of 850 patients aged ≥ 18 years with a first episode of HIV-associated CM will be enrolled (425 randomised to each arm). All patients will be followed for 16 weeks. All patients will receive consolidation therapy with fluconazole 800 mg/day to complete ten weeks of treatment, followed by fluconazole maintenance and ART as per local guidance.

Discussion: A safe, sustainable and easy to administer regimen of L-AmB that is non-inferior to seven days of daily amphotericin B deoxycholate therapy may reduce the number of adverse events seen in patients treated with amphotericin B deoxycholate and shorten hospital admissions, providing a highly favourable and implementable alternative to the current WHO recommended first-line treatment.

Trial Registration: ISRCTN, ISRCTN72509687 . Registered on 13 July 2017.
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http://dx.doi.org/10.1186/s13063-018-3026-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251219PMC
November 2018

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries.

Lancet Infect Dis 2019 04 18;19(4):e143-e147. Epub 2018 Oct 18.

Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.
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http://dx.doi.org/10.1016/S1473-3099(18)30493-6DOI Listing
April 2019

Integrated care for human immunodeficiency virus, diabetes and hypertension in Africa.

Trans R Soc Trop Med Hyg 2019 12;113(12):809-812

Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.

The rising burden from non-communicable diseases (NCDs) poses a huge challenge for health care delivery in Africa, where health systems are already struggling with the long-term care requirements for the millions of people now on antiretroviral therapy requiring regular visits to health facilities for monitoring, adherence support and drugs. The HIV chronic disease management programme is comparatively well-funded, well-organised and well-informed and offers many insights and opportunities for the expansion of NCD prevention and treatment services. Some degree of human immunodeficiency virus (HIV) and NCD service integration is essential, but how to do this without risking the HIV treatment gains is unclear. Both HIV and NCD services must expand within a resource-constrained environment and policymakers are in urgent need of evidence to guide cost-effective and acceptable changes in these health services.
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http://dx.doi.org/10.1093/trstmh/try098DOI Listing
December 2019

Association of Antenatal Micronutrient Supplementation With Adolescent Intellectual Development in Rural Western China: 14-Year Follow-up From a Randomized Clinical Trial.

JAMA Pediatr 2018 09;172(9):832-841

The Sydney School of Public Health, Faculty of Medicine, The University of Sydney, New South Wales, Australia.

Importance: The association of micronutrient supplementation during pregnancy with the intellectual development of adolescent offspring is unknown.

Objective: To assess the long-term association of antenatal micronutrient supplementation with adolescent intellectual development.

Design, Setting, And Participants: This 14-year follow-up study of a randomized clinical trial of micronutrient supplementation in pregnancy was conducted in 2 counties in rural western China in 2118 adolescent offspring (aged 10 to 14 years) of mothers who were randomized to take a daily capsule of either folic acid, folic acid plus iron, or multiple micronutrients from August 1, 2002, through February 28, 2006. Follow-up was conducted from June 1, 2016, through December 31, 2016. Data analyses took place from April 1, 2017, to June 20, 2017.

Main Outcomes And Measures: Adolescent full-scale intelligence quotient and aspects of verbal comprehension, working memory, perceptual reasoning, and processing speed indexes were assessed by the Wechsler Intelligence Scale for Children.

Results: Of 2118 adolescent offspring, 1252 (59.1%) were boys and 866 (40.9%) were girls, with a mean (SD) age of 11.7 (0.87) years, representing 47.2% of the 4488 single live births that were eligible to participate. Compared with folic acid supplementation, multiple micronutrient supplementation was associated with a 1.13-point higher full-scale intelligence quotient (95% CI, 0.15-2.10) and a 2.03-point higher verbal comprehension index (95% CI, 0.61-3.45); similar results were found in comparison with folic acid plus iron. When mothers initiated supplementation early (<12 weeks of gestation) and had an adequate dose (≥180 capsules), multiple micronutrient capsules were associated with a 2.16-point higher full-scale intelligence quotient (95% CI, 0.41-3.90) and 4.29-point higher verbal comprehension index (95% CI, 1.33-7.24) compared with folic acid capsules. The mean test scores were lower in the substratum of supplementation initiated late (≥12 weeks of gestation) and with an inadequate dose (<180 capsules). The multiple micronutrient group had higher scores than the other 2 treatment groups, and significant differences were observed for full-scale intelligence quotient (adjusted mean difference, 2.46; 95% CI, 0.98-3.94) when compared with the folic acid plus iron group.

Conclusions And Relevance: Compared with folic acid plus iron or folic acid capsules supplementation, antenatal multiple micronutrient supplementation appeared to be associated with increased adolescent intellectual development; initiating supplementation in the first trimester and then continuing for at least 180 days were associated with the greatest rewards.

Trial Registration: isrctn.org Identifier: ISRCTN08850194.
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http://dx.doi.org/10.1001/jamapediatrics.2018.1401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143069PMC
September 2018

Dietary sodium intake in urban and rural Malawi, and directions for future interventions.

Am J Clin Nutr 2018 09;108(3):587-593

Departments of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: High dietary sodium intake is a major risk factor for hypertension. Data on population sodium intake are scanty in sub-Saharan Africa, despite a high hypertension prevalence in most countries.

Objective: We aimed to determine daily sodium intake in urban and rural communities in Malawi.

Design: In an observational cross-sectional survey, data were collected on estimated household-level per capita sodium intake, based on how long participants reported that a defined quantity of plain salt lasts in a household. In a subset of 2078 participants, 24-h urinary sodium was estimated from a morning spot urine sample.

Results: Of 29,074 participants, 52.8% of rural and 50.1% of urban individuals lived in households with an estimated per capita plain salt consumption >5 g/d. Of participants with urinary sodium data, 90.8% of rural and 95.9% of urban participants had estimated 24-h urinary sodium >2 g/d; there was no correlation between household per capita salt intake and estimated 24-h urinary sodium excretion. Younger adults were more likely to have high urinary sodium and to eat food prepared outside the home than were those over the age of 60 y. Households with a member with previously diagnosed hypertension had reduced odds (OR: 0.59; 95% CI: 0.51, 0.68) of per capita household plain salt intake >5 g/d, compared with those where hypertension was undiagnosed.

Conclusions: Sodium consumption exceeds the recommended amounts for most of the population in rural and urban Malawi. Population-level interventions for sodium intake reduction with a wide focus are needed, targeting both sources outside the home as well as home cooking. This trial was registered at clinicaltrials.gov as NCT03422185.
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http://dx.doi.org/10.1093/ajcn/nqy125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134286PMC
September 2018

Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial.

Clin Infect Dis 2019 01;68(3):393-401

Centre for Global Health, Institute for Infection and Immunity, St George's University of London, United Kingdom.

Background: We performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana.

Methods: Human immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day.

Results: Eighty participants were enrolled. EFA for daily L-AmB was -0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was -0.11 (95% CI, -.29 to .07) log10 CFU/mL/day faster with single dose (n = 16); -0.05 (95% CI, -.20 to .10) log10 CFU/mL/day faster with 2 doses (n = 18); and -0.13 (95% CI, -.35 to .09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated.

Conclusions: Single-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial.

Clinical Trials Registration: ISRCTN 10248064.
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http://dx.doi.org/10.1093/cid/ciy515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336908PMC
January 2019

Statin use and all-cause mortality in people living with HIV: a systematic review and meta-analysis.

BMC Infect Dis 2018 06 5;18(1):258. Epub 2018 Jun 5.

Warwick-Centre for Applied Health Research and Delivery (WCAHRD), Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.

Background: It is unknown whether statin use among people living with HIV results in a reduction in all-cause mortality. We aimed to evaluate the effect of statin use on all-cause mortality among people living with HIV.

Methods: We conducted comprehensive literature searches of Medline, Embase, CINAHL, the Cochrane Library, and cross-references up to April 2018. We included randomised, quasi-randomised trials and prospective cohort studies that examined the association between statin use and cardio-protective and mortality outcomes among people living with HIV. Two reviewers independently abstracted the data. Hazard ratios (HRs) were pooled using empirical Bayesian random-effect meta-analysis. A number of sensitivity analyses were conducted.

Results: We included seven studies with a total of 35,708 participants. The percentage of participants on statins across the studies ranged from 8 to 35%. Where reported, the percentage of participants with hypertension ranged from 14 to 35% and 7 to 10% had been diagnosed with diabetes mellitus. Statin use was associated with a 33% reduction in all-cause mortality (pooled HR = 0.67, 95% Credible Interval 0.39 to 0.96). The probability that statin use conferred a moderate mortality benefit (i.e. decreased risk of mortality of at least 25%, HR ≤ 0.75) was 71.5%. Down-weighting and excluding the lower quality studies resulted in a more conservative estimate of the pooled HR.

Conclusion: Statin use appears to confer moderate mortality benefits in people living with HIV.
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http://dx.doi.org/10.1186/s12879-018-3162-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987595PMC
June 2018

Glycated haemoglobin A (HbA) for detection of diabetes mellitus and impaired fasting glucose in Malawi: a diagnostic accuracy study.

BMJ Open 2018 05 5;8(5):e020972. Epub 2018 May 5.

Department of Infectious Disease Epidemiology at London School of Hygiene and Tropical Medicine, London School of Hygiene and Tropical Medicine, London, UK.

Objectives: To examine the accuracy of glycated haemoglobin A (HbA) in detecting type 2 diabetes and impaired fasting glucose among adults living in Malawi.

Design: A diagnostic validation study of HbA. Fasting plasma glucose (FPG) ≥7.0 mmol/L was the reference standard for type 2 diabetes, and FPG between 6.1 and 6.9 mmol/L as impaired fasting glucose.

Participants: 3645 adults (of whom 63% were women) recruited from two demographic surveillance study sites in urban and rural Malawi. This analysis excluded those who had a previous diagnosis of diabetes or had history of taking diabetes medication.

Results: HbA demonstrated excellent validity to detect FPG-defined diabetes, with an area under the receiver operating characteristic (AUROC) curve of 0.92 (95% CI 0.90 to 0.94). At HbA ≥6.5% (140 mg/dL), sensitivity was 78.7% and specificity was 94.0%. Subgroup AUROCs ranged from 0.86 for participants with anaemia to 0.94 for participants in urban Malawi. There were clinical and metabolic differences between participants with true diabetes versus false positives when HbA was ≥6.5% (140 mg/dL).

Conclusions: The findings from this study provide justification to use HbA to detect type 2 diabetes. As HbA testing is substantially less burdensome to patients than either FPG testing or oral glucose tolerance testing, it represents a useful option for expanding access to diabetes care in sub-Saharan Africa.
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http://dx.doi.org/10.1136/bmjopen-2017-020972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942411PMC
May 2018

Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa.

N Engl J Med 2018 03;378(11):1004-1017

From the Centre for Global Health, Institute for Infection and Immunity, St. George's University of London (S.F.M., A.L., N.S., N. Karunaharan, J.A., T.B., T.S.H.), University College London (R.S.H.), and the MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine (J.B.), London, and Liverpool School of Tropical Medicine, Liverpool (T.C., D.G.L., D.W., S.J.) - all in the United Kingdom; the University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe (C. Kanyama, C.C., C.H., M.C.H.), Malawi-Liverpool-Wellcome Trust Clinical Research Programme (R.S.H., N. Kalata, K.G., M.P., J.E.) and the College of Medicine, University of Malawi (R.S.H., N. Kalata, K.G., M.P., J.E., J.J.O.), Blantyre, and Dignitas International, Zomba Central Hospital, Zomba (A.K.C., P.B., D.L., J.J.O.) - all in Malawi; University of Dschang, Dschang (C. Kouanfack), Hôpital Central Yaoundé/Site Agence Nationale de Recherche sur le Sida (ANRS) Cameroun, Yaoundé (C. Kouanfack, S. Lontsi, J.-G.N., V.S.), and Douala General Hospital (E.T., Y.N.M.) and University of Douala (Y.N.M.), Douala - all in Cameroon; the Institute for Medical Research and Training (D.C., N.S., N. Karunaharan, P.B.), University Teaching Hospital (D.C., S. Lakhi, N.S., N. Karunaharan, P.B.), and the Department of Internal Medicine and Directorate of Research and Postgraduate Studies, Lusaka Apex Medical University (P.M.), Lusaka, Zambia; the National Institute for Medical Research, Muhimbili Medical Research Centre, Dar Es Salaam, Tanzania (S.M., S. Lesikari); Institut Pasteur, Molecular Mycology Unit (E.T., O.L.), and Paris Descartes University, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, IHU Imagine, Assistance Publique-Hôpitaux de Paris (O.L.), Paris; the Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto (A.K.C.); and the University of North Carolina, Chapel Hill (C.H., M.C.H.).

Background: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy.

Methods: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks.

Results: A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen.

Conclusions: One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509 .).
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http://dx.doi.org/10.1056/NEJMoa1710922DOI Listing
March 2018

Prevalence of obesity, hypertension, and diabetes, and cascade of care in sub-Saharan Africa: a cross-sectional, population-based study in rural and urban Malawi.

Lancet Diabetes Endocrinol 2018 03 19;6(3):208-222. Epub 2018 Jan 19.

Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; Malawi Epidemiology and Intervention Research Unit, Lilongwe and Karonga, Malawi.

Background: Sub-Saharan Africa is in rapid demographic transition, and non-communicable diseases are increasingly important causes of morbidity and mortality. We investigated the burden of diabetes, overweight and obesity, hypertension, and multimorbidity, their treatment, and their associations with lifestyle and other factors in Malawi, a very poor country with a predominantly rural-but rapidly growing urban-population, to identify high-risk populations and inform appropriate interventions.

Methods: In this cross-sectional, population-based study, we enrolled all adults (≥18 years) residing in two defined geographical areas within Karonga District and Lilongwe city. All adults self-defining as usually resident in the study areas were eligible, and recruited at household level. Participants were interviewed, had anthropometry and blood pressure measured, and had fasting blood samples collected. The study outcomes were prevalence estimates and risk ratios for diabetes (defined as fasting blood glucose of at least 7·0 mmol/L or self-report of a previous diagnosis of diabetes), hypertension (systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or self-report of current antihypertensive medication), overweight (BMI of 25·0-29·9 kg/m) and obesity (BMI of 30·0 kg/m or more), and multimorbidity (two or more of the above conditions) by location-specific (urban vs rural), age-specific, and sex-specific groups, calculated using negative binomial regression. We used χ likelihood ratio tests to assess heterogeneity by age, location, and sex.

Findings: Between May 16, 2013, and Feb 8, 2016, we enrolled 15 013 (62%) of 24 367 eligible urban adults in Lilongwe and 13 878 (88%) of 15 806 eligible rural adults in Karonga District. Overweight and obesity, hypertension, and diabetes were highly prevalent, more so in urban residents, the less poor, and better educated than in rural, the poorest, and least educated participants. 18% of urban men (961 of 5211 participants) and 44% (4115 of 9282) of urban women, and 9% (521 of 5834) of rural men and 27% (2038 of 7497) of rural women were overweight or obese; 16% (859 of 5212), 14% (1349 of 9793), 13% (787 of 5847), and 14% (1101 of 8025) had hypertension; and 3% (133 of 3928), 3% (225 of 7867), 2% (84 of 5004), and 2% (124 of 7116) had diabetes, respectively. Of 566 participants with diabetes, 233 (41%) were undiagnosed, and of 4096 participants with hypertension, 2388 (58%) were undiagnosed. Fewer than half the participants on medication for diabetes or hypertension had well controlled diabetes (84 [41%] of 207 participants) or blood pressure (440 [37%] of 1183 participants). Multimorbidity was highest in urban women (n=519, 7%).

Interpretation: Overweight and obesity, hypertension, and diabetes are highly prevalent in urban and rural Malawi, yet many patients are undiagnosed and management is limited. Local-evidence-informed multisectoral, innovative, and targeted interventions are needed urgently to manage the already high burden.

Funding: Wellcome Trust.
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http://dx.doi.org/10.1016/S2213-8587(17)30432-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835666PMC
March 2018

The crisis of diabetes in sub-Saharan Africa.

Lancet Diabetes Endocrinol 2017 08 5;5(8):574-575. Epub 2017 Jul 5.

Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.

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http://dx.doi.org/10.1016/S2213-8587(17)30219-XDOI Listing
August 2017

The costs of providing antiretroviral therapy services to HIV-infected individuals presenting with advanced HIV disease at public health centres in Dar es Salaam, Tanzania: Findings from a randomised trial evaluating different health care strategies.

PLoS One 2017 24;12(2):e0171917. Epub 2017 Feb 24.

Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Understanding the costs associated with health care delivery strategies is essential for planning. There are few data on health service resources used by patients and their associated costs within antiretroviral (ART) programmes in Africa.

Material And Methods: The study was nested within a large trial, which evaluated screening for cryptococcal meningitis and tuberculosis and a short initial period of home-based adherence support for patients initiating ART with advanced HIV disease in Tanzania and Zambia. The economic evaluation was done in Tanzania alone. We estimated costs of providing routine ART services from the health service provider's perspective using a micro-costing approach. Incremental costs for the different novel components of service delivery were also estimated. All costs were converted into US dollars (US$) and based on 2012 prices.

Results: Of 870 individuals enrolled in Tanzania, 434 were enrolled in the intervention arm and 436 in the standard care/control arm. Overall, the median (IQR) age and CD4 cell count at enrolment were 38 [31, 44] years and 52 [20, 89] cells/mm3, respectively. The mean per patient costs over the first three months and over a one year period of follow up following ART initiation in the standard care arm were US$ 107 (95%CI 101-112) and US$ 265 (95%CI 254-275) respectively. ART drugs, clinic visits and hospital admission constituted 50%, 19%, and 19% of the total cost per patient year, while diagnostic tests and non-ART drugs (co-trimoxazole) accounted for 10% and 2% of total per patient year costs. The incremental costs of the intervention to the health service over the first three months was US$ 59 (p<0.001; 95%CI 52-67) and over a one year period was US$ 67(p<0.001; 95%CI 50-83). This is equivalent to an increase of 55% (95%CI 51%-59%) in the mean cost of care over the first three months, and 25% (95%CI 20%-30%) increase over one year of follow up.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171917PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325220PMC
August 2017

Effectiveness of Membrane Filtration to Improve Drinking Water: A Quasi-Experimental Study from Rural Southern India.

Am J Trop Med Hyg 2016 Nov 6;95(5):1192-1200. Epub 2016 Sep 6.

Society for Applied Studies, Vellore, India.

Since point-of-use methods of water filtration have shown limited acceptance in Vellore, southern India, this study evaluated the effectiveness of decentralized membrane filtration 1) with safe storage, 2) without safe storage, versus 3) no intervention, consisting of central chlorination as per government guidelines, in improving the microbiological quality of drinking water and preventing childhood diarrhea. Periodic testing of water sources, pre-/postfiltration samples, and household water, and a biweekly follow up of children less than 2 years of age was done for 1 year. The membrane filters achieved a log reduction of 0.86 (0.69-1.06), 1.14 (0.99-1.30), and 0.79 (0.67-0.94) for total coliforms, fecal coliforms, and Escherichia coli, respectively, in field conditions. A 24% (incidence rate ratio, IRR [95% confidence interval, CI] = 0.76 [0.51-1.13]; P = 0.178) reduction in diarrheal incidence in the intervention village with safe storage and a 14% (IRR [95% CI] = 1.14 [0.75-1.77]; P = 0.530) increase in incidence for the intervention village without safe storage versus no intervention village was observed, although not statistically significant. Microbiologically, the membrane filters decreased fecal contamination; however, provision of decentralized membrane-filtered water with or without safe storage was not protective against childhood diarrhea.
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http://dx.doi.org/10.4269/ajtmh.15-0675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094238PMC
November 2016

Diabetes and other non-communicable diseases in Africa: a potential disaster in the waiting.

Authors:
Shabbar Jaffar

Lancet Diabetes Endocrinol 2016 11 7;4(11):875-877. Epub 2016 Oct 7.

Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. Electronic address:

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http://dx.doi.org/10.1016/S2213-8587(16)30216-9DOI Listing
November 2016