Determining the causal role of malaria in elevating blood pressure and pulse wave velocity in Kenyan adolescents and adults.
INTRODUCTION: High blood pressure is recognized as a leading risk factor for stroke and death in sub-Saharan Africa (sSA). While many studies have examined the role of established risk factors such as obesity and salt consumption, less is known about other factors, such as infection, that could be of particular importance in sSA. Ambulatory blood pressure measurement has emerged as the optimal method in recent years in Western settings, but there has been limited use to date in sSA. This work presents the results of a study investigating whether malaria, which is widespread in sSA could contribute to the development of high blood pressure using ambulatory measurements. METHODS: Preliminary work involved determining the prevalence of hypertension in Kilifi, Kenya and examining the population-level effects of using ambulatory blood pressure monitoring (ABPM) for diagnosing hypertension. A literature review outlining the basis of the malaria-high blood pressure hypothesis and the Mendelian randomization method for testing the hypothesis was conducted. Sickle cell trait and alpha (+) thalassemia were chosen as instrumental variables to represent malaria exposure because they protect against malaria. Two studies were performed in Nairobi, Kenya among the same cohort to confirm that sickle-cell trait and alpha-thalassemia do not influence blood pressure in the absence of malaria and were therefore valid instrumental variables to test the malaria-high blood pressure hypothesis in Kilifi where there is malaria transmission. A Mendelian randomization study was then conducted in Kilifi, Kenya where 24-hour blood pressure and arterial stiffness indices were compared in individuals with and without sickle cell trait and alpha thalassemia. RESULTS: The prevalence of hypertension in Kilifi, a rural area, was found to be as high as in urban areas of Kenya despite the low frequency of classical risk factors such as obesity and excessive salt consumption. Use of ambulatory blood pressure monitoring for diagnosing hypertension was found to improve the accuracy of detection of high blood pressure. Neither Sickle-cell trait (SCT) nor alpha+ thalassemia influenced blood pressure or arterial stiffness indices among adolescents that had been lifelong residents of Nairobi, where there is no malaria transmission. Among individuals that had been lifelong residents of Kilifi, Kenya where there has been on-going malaria transmission, blood pressure was found to be lower among individuals with SCT, which protects against malaria episodes compared to those without SCT. The difference in BP by SCT status was larger in women than in men. There were no significant differences in arterial stiffness based on SCT status. CONCLUSION: This work suggests that malaria contributes to the burden of hypertension in sSA, and the control of malaria may lead to a reduction in blood pressure in this group. Future work should focus on confirming the findings using alternative study designs such as examining blood pressure in cohorts born before and after complete malaria elimination in parts of the world where this has been achieved. Subsequent work would involve delineating the pathophysiological mechanisms involved in malaria induced BP elevation with a view to generating new drugs to control hypertension.
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Scaling up the primary health integrated care project for chronic conditions in Kenya: study protocol for an implementation research project
INTRODUCTION: Amid the rising number of people with non-communicable diseases (NCDs), Kenya has invested in strengthening primary care and in efforts to expand existing service delivery platforms to integrate NCD care. One such approach is the AMPATH (Academic Model Providing Access to Healthcare) model in western Kenya, which provides the platform for the Primary Health Integrated Care Project for Chronic Conditions (PIC4C), launched in 2018 to further strengthen primary care services for the prevention and control of hypertension, diabetes, breast and cervical cancer. This study seeks to understand how well PIC4C delivers on its intended aims and to inform and support scale up of the PIC4C model for integrated care for people with NCDs in Kenya. METHODS AND ANALYSIS: The study is guided by a conceptual framework on implementing, sustaining and spreading innovation in health service delivery. We use a multimethod design combining qualitative and quantitative approaches, involving: (1) in-depth interviews with health workers and decision-makers to explore experiences of delivering PIC4C; (2) a cross-sectional survey of patients with diabetes or hypertension and in-depth interviews to understand how well PIC4C meets patients' needs; (3) a cohort study with an interrupted time series analysis to evaluate the degree to which PIC4C leads to health benefits such as improved management of hypertension or diabetes; and (4) a cohort study of households to examine the extent to which the national hospital insurance chronic care package provides financial risk protection to people with hypertension or diabetes within PIC4C. ETHICS AND DISSEMINATION: The study has received approvals from Moi University Institutional Research and Ethics Committee (FAN:0003586) and the London School of Hygiene & Tropical Medicine (17940). Workshops with key stakeholders at local, county, national and international levels will ensure early and wide dissemination of our findings to inform scale up of this model of care. We will also publish findings in peer-reviewed journals.
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Emerging Viral Infections, Hypertension, and Cardiovascular Disease in Sub-Saharan Africa: A Narrative Review
BACKGROUND: Sub-Saharan Africa (SSA) has the highest age-adjusted burden of hypertension and cardiovascular disease (CVD). SSA also experiences many viral infections due to unique environmental and societal factors. The purpose of this narrative review is to examine evidence around how hypertension, CVD, and emerging viral infections interact in SSA. METHODS: In September 2021, we conducted a search in MEDLINE, Embase, and Scopus, limited to English language studies published since 1990, and found a total of 1169 articles. Forty-seven original studies were included, with 32 on COVID-19 and 15 on other emerging viruses. RESULTS: Seven articles, including those with the largest sample size and most robust study design, found an association between preexisting hypertension or CVD and COVID-19 severity or death. Ten smaller studies found no association, and 17 did not calculate statistics to compare groups. Two studies assessed the impact of COVID-19 on incident CVD, with one finding an increase in stroke admissions. For other emerging viruses, 3 studies did not find an association between preexisting hypertension or CVD on West Nile and Lassa fever mortality. Twelve studies examined other emerging viral infections and incident CVD, with 4 finding no association and 8 not calculating statistics. CONCLUSIONS: Growing evidence from COVID-19 suggests viruses, hypertension, and CVD interact on multiple levels in SSA, but research gaps remain especially for other emerging viral infections. SSA can and must play a leading role in the study and control of emerging viral infections, with expansion of research and public health infrastructure to address these interactions.
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Quantifying previous SARS-CoV-2 infection through mixture modelling of antibody levels
As countries decide on vaccination strategies and how to ease movement restrictions, estimating the proportion of the population previously infected with SARS-CoV-2 is important for predicting the future burden of COVID-19. This proportion is usually estimated from serosurvey data in two steps: first the proportion above a threshold antibody level is calculated, then the crude estimate is adjusted using external estimates of sensitivity and specificity. A drawback of this approach is that the PCR-confirmed cases used to estimate the sensitivity of the threshold may not be representative of cases in the wider population-e.g., they may be more recently infected and more severely symptomatic. Mixture modelling offers an alternative approach that does not require external data from PCR-confirmed cases. Here we illustrate the bias in the standard threshold-based approach by comparing both approaches using data from several Kenyan serosurveys. We show that the mixture model analysis produces estimates of previous infection that are often substantially higher than the standard threshold analysis.
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Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immunoglobulin G Antibody Seroprevalence Among Truck Drivers and Assistants in Kenya
In October 2020, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G seroprevalence among truck drivers and their assistants (TDA) in Kenya was 42.3%, higher than among healthcare workers and blood donors. Truck drivers and their assistants transport essential supplies during the coronavirus disease 2019 pandemic, placing them at increased risk of being infected and of transmitting SARS-CoV-2 over a wide geographical area.
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Temporal trends of SARS-CoV-2 seroprevalence during the first wave of the COVID-19 epidemic in Kenya
Observed SARS-CoV-2 infections and deaths are low in tropical Africa raising questions about the extent of transmission. We measured SARS-CoV-2 IgG by ELISA in 9,922 blood donors across Kenya and adjusted for sampling bias and test performance. By 1st September 2020, 577 COVID-19 deaths were observed nationwide and seroprevalence was 9.1% (95%CI 7.6-10.8%). Seroprevalence in Nairobi was 22.7% (18.0-27.7%). Although most people remained susceptible, SARS-CoV-2 had spread widely in Kenya with apparently low associated mortality.
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Nocturnal dipping of heart rate and blood pressure in people with HIV in Tanzania
People with HIV (PWH) have a >2-fold greater risk for development of cardiovascular disease (CVD), which may be associated with abnormalities in 24-h ambulatory blood pressure measurement (ABPM) profile. We conducted a nested case-control study of ABPM in 137 PWH and HIV-uninfected controls with normal and high clinic blood pressure (BP) in Tanzania. Nocturnal non-dipping of heart rate (HR) was significantly more common among PWH than HIV-uninfected controls (p = .01). Nocturnal non-dipping of BP was significantly more common in PWH with normal clinic BP (p = .048). Clinical correlates of nocturnal non-dipping were similar in PWH and HIV-uninfected adults and included higher BMI, higher CD4(+) cell count, and high C-reactive protein for HR and markers of renal disease for BP. In conclusion, nocturnal non-dipping of both BP and HR was more common in PWH but further research is needed to determine causes and consequences of this difference.
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Seroprevalence of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers in Kenya
BACKGROUND: Few studies have assessed the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) in Africa. We report findings from a survey among HCWs in 3 counties in Kenya. METHODS: We recruited 684 HCWs from Kilifi (rural), Busia (rural), and Nairobi (urban) counties. The serosurvey was conducted between 30 July and 4 December 2020. We tested for immunoglobulin G antibodies to SARS-CoV-2 spike protein, using enzyme-linked immunosorbent assay. Assay sensitivity and specificity were 92.7 (95% CI, 87.9-96.1) and 99.0% (95% CI, 98.1-99.5), respectively. We adjusted prevalence estimates, using bayesian modeling to account for assay performance. RESULTS: The crude overall seroprevalence was 19.7% (135 of 684). After adjustment for assay performance, seroprevalence was 20.8% (95% credible interval, 17.5%-24.4%). Seroprevalence varied significantly (P < .001) by site: 43.8% (95% credible interval, 35.8%-52.2%) in Nairobi, 12.6% (8.8%-17.1%) in Busia and 11.5% (7.2%-17.6%) in Kilifi. In a multivariable model controlling for age, sex, and site, professional cadre was not associated with differences in seroprevalence. CONCLUSION: These initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre.
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Malaria is a cause of iron deficiency in African children
Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID(1). To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria(2), as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.
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Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Kenyan blood donors
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Africa is poorly described. The first case of SARS-CoV-2 in Kenya was reported on 12 March 2020, and an overwhelming number of cases and deaths were expected, but by 31 July 2020, there were only 20,636 cases and 341 deaths. However, the extent of SARS-CoV-2 exposure in the community remains unknown. We determined the prevalence of anti-SARS-CoV-2 immunoglobulin G among blood donors in Kenya in April-June 2020. Crude seroprevalence was 5.6% (174 of 3098). Population-weighted, test-performance-adjusted national seroprevalence was 4.3% (95% confidence interval, 2.9 to 5.8%) and was highest in urban counties Mombasa (8.0%), Nairobi (7.3%), and Kisumu (5.5%). SARS-CoV-2 exposure is more extensive than indicated by case-based surveillance, and these results will help guide the pandemic response in Kenya and across Africa.
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