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

Effect of strikes by health workers on mortality between 2010 and 2016 in Kilifi, Kenya: a population-based cohort analysis

BACKGROUND: Health workers' strikes are a global occurrence. Kenya has had several strikes by health workers in recent years but their effect on mortality is unknown. We assessed the effect on mortality of six strikes by health workers that occurred from 2010 to 2016 in Kilifi, Kenya. METHODS: Using daily mortality data obtained from the Kilifi Health and Demographic Surveillance System, we fitted a negative binomial regression model to estimate the change in mortality during strike periods and in the 2 weeks immediately after strikes. We did subgroup analyses by age, cause of death, and strike week. FINDINGS: Between Jan 1, 2010, and Nov 30, 2016, we recorded 1 829 929 person-years of observation, 6396 deaths, and 128 strike days (median duration of strikes, 18·5 days [range 9-42]). In the primary analysis, no change in all-cause mortality was noted during strike periods (adjusted rate ratio [RR] 0·93, 95% CI 0·81-1·08; p=0·34). Weak evidence was recorded of variation in mortality rates by age group, with an apparent decrease among infants aged 1-11 months (adjusted RR 0·58, 95% CI 0·33-1·03; p=0·064) and an increase among children aged 12-59 months (1·75, 1·11-2·76; p=0·016). No change was noted in mortality rates in post-strike periods and for any category of cause of death. INTERPRETATION: The brief strikes by health workers during the period 2010-16 were not associated with obvious changes in overall mortality in Kilifi. The combined effects of private (and some public) health care during strike periods, a high proportion of out-of-hospital deaths, and a low number of events might have led us to underestimate the effect. FUNDING: Wellcome Trust and MRC Tropical Epidemiology Group

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

Socio-economic factors, gender and smoking as determinants of COPD in a low-income country of sub-Saharan Africa: FRESH AIR Uganda.

In Uganda, biomass smoke seems to be the largest risk factor for the development of COPD, but socio-economic factors and gender may have a role. Therefore, more in-depth research is needed to understand the risk factors. The aim of this study was to investigate the impact of socio-economic factors and gender differences on the COPD prevalence in Uganda. The population comprised 588 randomly selected participants (>30 years) who previously completed the FRESH AIR Uganda study. In this post hoc analysis, the impact of several socio-economic characteristics, gender and smoking on the prevalence of COPD was assessed using a logistic regression model. The main risk factors associated with COPD were non-Bantu ethnicity (odds ratio (OR) 1.73, 95% confidence interval (CI) 1.06-2.82, P=0.030), biomass fuel use for heating (OR 1.76, 95% CI 1.03-3.00, P=0.038), former smoker (OR 1.87, 95% CI 0.97-3.60, P=0.063) and being unmarried (OR 0.087, 95% CI 0.93-2.95, P=0.087). A substantial difference in the prevalence of COPD was seen between the two ethnic groups: non-Bantu 20% and Bantu 12.9%. Additional analysis between these two groups showed significant differences in socio-economic circumstances: non-Bantu people smoked more (57.7% vs 10.7%), lived in tobacco-growing areas (72% vs 14.8%) and were less educated (28.5% vs 12.9% had no education). With regard to gender, men with COPD were unmarried (OR 3.09, 95% CI 1.25-7.61, P=0.015) and used more biomass fuel for heating (OR 2.15, 95% CI 1.02-4.54, P=0.045), and women with COPD were former smokers (OR 3.35, 95% CI 1.22-9.22, P=0.019). Only a few socio-economic factors (i.e., smoking, biomass fuel use for heating, marital status and non-Bantu ethnicity) have been found to be associated with COPD. This applied for gender differences as well (i.e., for men, marital status and biomass fuel for heating, and for women being a former smoker). More research is needed to clarify the complexity of the different risk factors

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 ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334), a genetic variant that confers specific protection against malaria2, 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%

The global impact of non-communicable diseases on macro-economic productivity: a systematic review

© 2015, The Author(s). Non-communicable diseases (NCDs) have large economic impact at multiple levels. To systematically review the literature investigating the economic impact of NCDs [including coronary heart disease (CHD), stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on macro-economic productivity. Systematic search, up to November 6th 2014, of medical databases (Medline, Embase and Google Scholar) without language restrictions. To identify additional publications, we searched the reference lists of retrieved studies and contacted authors in the field. Randomized controlled trials, cohort, case–control, cross-sectional, ecological studies and modelling studies carried out in adults (>18 years old) were included. Two independent reviewers performed all abstract and full text selection. Disagreements were resolved through consensus or consulting a third reviewer. Two independent reviewers extracted data using a predesigned data collection form. Main outcome measure was the impact of the selected NCDs on productivity, measured in DALYs, productivity costs, and labor market participation, including unemployment, return to work and sick leave. From 4542 references, 126 studies met the inclusion criteria, many of which focused on the impact of more than one NCD on productivity. Breast cancer was the most common (n = 45), followed by stroke (n = 31), COPD (n = 24), colon cancer (n = 24), DM (n = 22), lung cancer (n = 16), CVD (n = 15), cervical cancer (n = 7) and CKD (n = 2). Four studies were from the WHO African Region, 52 from the European Region, 53 from the Region of the Americas and 16 from the Western Pacific Region, one from the Eastern Mediterranean Region and none from South East Asia. We found large regional differences in DALYs attributable to NCDs but especially for cervical and lung cancer. Productivity losses in the USA ranged from 88 million US dollars (USD) for COPD to 20.9 billion USD for colon cancer. CHD costs the Australian economy 13.2 billion USD per year. People with DM, COPD and survivors of breast and especially lung cancer are at a higher risk of reduced labor market participation. Overall NCDs generate a large impact on macro-economic productivity in most WHO regions irrespective of continent and income. The absolute global impact in terms of dollars and DALYs remains an elusive challenge due to the wide heterogeneity in the included studies as well as limited information from low- and middle-income countries.WHO; Nestle´ Nutrition (Nestec Ltd.); Metagenics Inc.; and AX

The malaria-high blood pressure hypothesis

Rationale Several studies have demonstrated links between infectious diseases and cardiovascular conditions. Malaria and hypertension are widespread in many low- and middle-income countries, but the possible link between them has not been considered. Objective In this article, we outline the basis for a possible link between malaria and hypertension and discuss how the hypothesis could be confirmed or refuted. Methods and Results We reviewed published literature on factors associated with hypertension and checked whether any of these were also associated with malaria. We then considered various study designs that could be used to test the hypothesis. Malaria causes low birth weight, malnutrition, and inflammation, all of which are associated with hypertension in high-income countries. The hypothetical link between malaria and hypertension can be tested through the use of ecological, cohort, or Mendelian randomization studies, each of which poses specific challenges. Conclusions Confirmation of the existence of a causative link with malaria would be a paradigm shift in efforts to prevent and control hypertension and would stimulate wider research on the links between infectious and noncommunicable disease.</p

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

Pharmacotherapy for hypertension in Sub-Saharan Africa: a systematic review and network meta-analysis

Background The highest burden of hypertension is found in Sub-Saharan Africa (SSA) with a threefold greater mortality from stroke and other associated diseases. Ethnicity is known to influence the response to antihypertensives, especially in black populations living in North America and Europe. We sought to outline the impact of all commonly used pharmacological agents on both blood pressure reduction and cardiovascular morbidity and mortality in SSA. Methods We used similar criteria to previous large meta-analyses of blood pressure agents but restricted results to populations in SSA. Quality of evidence was assessed using a risk of bias tool. Network meta-analysis with random effects was used to compare the effects across interventions and meta-regression to explore participant heterogeneity. Results Thirty-two studies of 2860 participants were identified. Most were small studies from single, urban centres. Compared with placebo, any pharmacotherapy lowered SBP/DBP by 8.51/8.04 mmHg, and calcium channel blockers (CCBs) were the most efficacious first-line agent with 18.46/11.6 mmHg reduction. Fewer studies assessing combination therapy were available, but there was a trend towards superiority for CCBs plus ACE inhibitors or diuretics compared to other combinations. No studies examined the effect of antihypertensive therapy on morbidity or mortality outcomes. Conclusion Evidence broadly supports current guidelines and provides a clear rationale for promoting CCBs as first-line agents and early initiation of combination therapy. However, there is a clear requirement for more evidence to provide a nuanced understanding of stroke and other cardiovascular disease prevention amongst diverse populations on the continent. Trial registration PROSPERO, CRD42019122490. This review was registered in January 2019

Clinical and epidemiological implications of 24-Hour ambulatory blood pressure monitoring for the diagnosis of hypertension in Kenyan adults: A population-based study

Background The clinical and epidemiological implications of using ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension have not been studied at a population level in sub‐Saharan Africa. We examined the impact of ABPM use among Kenyan adults. Methods and Results We performed a nested case–control study of diagnostic accuracy. We selected an age‐stratified random sample of 1248 adults from the list of residents of the Kilifi Health and Demographic Surveillance System in Kenya. All participants underwent a screening blood pressure (BP) measurement. All those with screening BP ≥140/90 mm Hg and a random subset of those with screening BP &lt;140/90 mm Hg were invited to undergo ABPM. Based on the 2 tests, participants were categorized as sustained hypertensive, masked hypertensive, “white coat” hypertensive, or normotensive. Analyses were weighted by the probability of undergoing ABPM. Screening BP ≥140/90 mm Hg was present in 359 of 986 participants, translating to a crude population prevalence of 23.1% (95% CI 16.5–31.5%). Age standardized prevalence of screening BP ≥140/90 mm Hg was 26.5% (95% CI 19.3–35.6%). On ABPM, 186 of 415 participants were confirmed to be hypertensive, with crude prevalence of 15.6% (95% CI 9.4–23.1%) and age‐standardized prevalence of 17.1% (95% CI 11.0–24.4%). Age‐standardized prevalence of masked and white coat hypertension were 7.6% (95% CI 2.8–13.7%) and 3.8% (95% CI 1.7–6.1%), respectively. The sensitivity and specificity of screening BP measurements were 80% (95% CI 73–86%) and 84% (95% CI 79–88%), respectively. BP indices and validity measures showed strong age‐related trends. Conclusions Screening BP measurement significantly overestimated hypertension prevalence while failing to identify ≈50% of true hypertension diagnosed by ABPM. Our findings suggest significant clinical and epidemiological benefits of ABPM use for diagnosing hypertension in Kenyan adults