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

The Malaria-High Blood Pressure Hypothesis.

: 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. : 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. : 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. : 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.<br/

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

Invasive Salmonellosis in Kilifi, Kenya

Background: Invasive salmonelloses are a major cause of morbidity and mortality in Africa but the incidence and case-fatality of each disease varies markedly by region. Objectives: To describe the incidence, clinical characteristics and antimicrobial susceptibility patterns of invasive salmonelloses among children and adults in Kilifi, Kenya Methods: We analyzed integrated clinical and laboratory records for patients presenting to the Kilifi County Hospital between 1998 and 2014. We calculated incidence, summarised clinical features and multidrug resistance (MDR). Results: Non-typhoidal Salmonella (NTS) accounted for 10.8% and 5.8% of bacteremia cases, in children and adults respectively while Salmonella Typhi accounted for 0.5% and 2.1% of bacteremia cases, respectively. Among 351 NTS isolates serotyped, 160 (45.5%) were Salmonella Enteritidis and 152 (43.3%) were Salmonella Typhimurium. The incidence of NTS in children aged <5 years was 36.6/100,000 person-years being highest in infants aged <7 days (174/100,000 person-years). The overall incidence of NTS in children varied markedly by location and declined significantly during the study period; the pattern of dominance of the NTS serotypes also shifted from Salmonella Enteritidis to Salmonella Typhimurium. Risk factors for invasive NTS disease were HIV infection, malaria, and malnutrition; the case fatality ratio was 22.1% (71/321) in children under 5 years and 36.7% (11/30) in adults. MDR was present in 23.9% (84/351) of NTS isolates and 46.2% (12/26) of Salmonella Typhi isolates. Conclusions: In Kilifi, the incidence of invasive NTS was high, especially among newborn infants but typhoid fever was uncommon. NTS remains an important cause of bacteremia in children under 5 years

Effect of previous exposure to malaria on blood pressure in Kilifi, Kenya: A Mendelian randomization study

Background Malaria exposure in childhood may contribute to high blood pressure (BP) in adults. We used sickle cell trait (SCT) and α+thalassemia, genetic variants conferring partial protection against malaria, as tools to test this hypothesis. Methods and Results Study sites were Kilifi, Kenya, which has malaria transmission, and Nairobi, Kenya, and Jackson, Mississippi, where there is no malaria transmission. The primary outcome was 24‐hour systolic BP. Prevalent hypertension, diagnosed using European Society of Hypertension thresholds was a secondary outcome. We performed regression analyses adjusting for age, sex, and estimated glomerular filtration rate. We studied 1127 participants in Kilifi, 516 in Nairobi, and 651 in Jackson. SCT frequency was 21% in Kilifi, 16% in Nairobi, and 9% in Jackson. SCT was associated with −2.4 (95% CI, −4.7 to −0.2) mm Hg lower 24‐hour systolic BP in Kilifi but had no effect in Nairobi/Jackson. The effect of SCT in Kilifi was limited to 30‐ to 59‐year‐old participants, among whom it was associated with −6.1 mm Hg (CI, −10.5 to −1.8) lower 24‐hour systolic BP. In pooled analysis allowing interaction by site, the effect of SCT on 24‐hour systolic BP in Kilifi was −3.5 mm Hg (CI, −6.9 to −0.1), increasing to −5.2 mm Hg (CI, −9.5 to −0.9) when replacing estimated glomerular filtration rate with urine albumin to creatinine ratio as a covariate. In Kilifi, the prevalence ratio for hypertension was 0.86 (CI, 0.76–0.98) for SCT and 0.89 (CI, 0.80–0.99) for α+thalassemia. Conclusions Lifelong malaria protection is associated with lower BP in Kilifi. Confirmation of this finding at other sites and elucidating the mechanisms involved may yield new preventive and therapeutic targets

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

Impact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study

The mortality impact of COVID-19 in Africa remains controversial because most countries lack vital registration. We analysed excess mortality in Kilifi Health and Demographic Surveillance System, Kenya, using 9 years of baseline data. SARS-CoV-2 seroprevalence studies suggest most adults here were infected before May 2022. During 5 waves of COVID-19 (April 2020-May 2022) an overall excess mortality of 4.8% (95% PI 1.2%, 9.4%) concealed a significant excess (11.6%, 95% PI 5.9%, 18.9%) among older adults ( ≥ 65 years) and a deficit among children aged 1–14 years (−7.7%, 95% PI −20.9%, 6.9%). The excess mortality rate for January 2020-December 2021, age-standardised to the Kenyan population, was 27.4/100,000 person-years (95% CI 23.2-31.6). In Coastal Kenya, excess mortality during the pandemic was substantially lower than in most high-income countries but the significant excess mortality in older adults emphasizes the value of achieving high vaccine coverage in this risk group

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%

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