HIV-exposed uninfected infants show robust memory B cell responses in spite of a delayed accumulation of memory B cells: An observational study in the first two years of life.

Background Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV infected women. Although uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV-exposure predisposing them to increased post-natal infections. Methods We explored the impact of HIV-exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs) and their respective antibody levels in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, B-cell ELISPOT and ELISA, respectively, during the first two years of life. Results For the majority of the B-cell subsets there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and specifically MBCs, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens, or reduce the antigen-specific antibody levels at 18 months of life. Conclusions Although HIV-exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEUs to mount robust MBC and serological responses was unaffected

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 vary markedly by region. We aimed 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, and summarized clinical features and multidrug resistance. RESULTS: Nontyphoidal 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%, respectively. Among 351 NTS isolates serotyped, 160 (45.6%) were Salmonella Enteritidis and 152 (43.3%) were Salmonella Typhimurium. The incidence of NTS in children aged <5 years was 36.6 per 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 human immunodeficiency virus infection, malaria, and malnutrition; the case fatality ratio was 22.1% (71/321) in children aged <5 years and 36.7% (11/30) in adults. Multidrug resistance 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 <5 years of age

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

[PP.01.13] Marked BP distribution shift from casual to ambulatory measurement in Kenya

Objective: Few studies have used ambulatory blood pressure monitoring (ABPM) to describe blood pressure (BP) patterns in sub-Saharan Africa (sSA). We conducted a population-based study in Kilifi, Kenya to determine the usefulness of ABPM in this setting. Methods: Design and method: An age-stratified sample of 1248 individuals were randomly selected from our Demographic Surveillance Area. Of these, 986 underwent casual BP measurement at their homes using an automated Omron™ M10-IT monitor. All individuals with casual BP above 140/90mmHg (mean of 2 out of 3 readings) and a random subset with BP below 140/90mmHg were invited to undergo 24-hour ABPM within one week of screening. ESH defined cutoffs were used to define hypertensive status. Results: Of 415 individuals who underwent both casual and ABPM measurement, 162 (39%) had sustained hypertension, 161 (39%) were normotensive, 58 (14%) had whitecoat hypertension and 34 (8%) had masked hypertension. Population BP was markedly higher when using casual BP compared to ABPM (11mmHg 95% CI [9–13] systolic and 9mmHg [7–11] diastolic). If casual BP measurement only had been used, age standardized population prevalence of hypertension would have been 26.5% (19.3–35.6). ‘True’ prevalence by ABPM was 17.1% (11.0–24.4), masked hypertension 7.6 (2.8–13.7)% and white coat hypertension 3.8% (1.7–6.1) of the population. The sensitivity and specificity of casual BP measurement for ‘diagnosing’ hypertension were 80% (73–86) and 84% (79–88) respectively. The positive and negative predictive values were 80% (74–85) and 84% (79–89). BP indices and validity measures showed strong age related trends; for example sensitivity of casual BP was 9.7% (2.5–24.9) in 30–39 year olds but 91% (83–97) in 60–69 year olds. Non-dipping was present in 9% (3–15) of the population and was strongly associated with masked hypertension (OR 10, [4–27]). Conclusions: Casual BP measurement methods substantially overestimated hypertension prevalence, while failing to identify a significant proportion who were hypertensive on ABPM. Whether ABPM identifies those at risk of future vascular events better than casual methods and is justified on cost effectiveness in sSA are key research questions.</p

Recurrent spontaneous Escherichia coli meningitis in an adult: a case report

Objectives The aim of this study was to characterize an unusual case of spontaneous, community-acquired Escherichia coli meningitis in an adult presenting to a general hospital in Kenya, where initial clinical recovery was followed by reinfection with an MDR, hospital-acquired strain. Patient and methods An adult presented to a hospital in Kenya with meningitis symptoms. E. coli was cultured from CSF. Treatment with ceftriaxone was successful; however, the patient relapsed a few days later. E. coli was cultured from CSF and blood during the reinfection episode, though the patient died during admission. We sequenced the isolates using Illumina MiSeq and performed antimicrobial susceptibility testing, fitness and virulence assays on the bacteria. Results The E. coli isolates from the two episodes were found to be distinct: the initial strain was ST88, serotype O8 H17 while the subsequent episode was caused by an ST167, serotype O101 H5 MDR strain. The ST88 strain was susceptible to all drugs except ampicillin and amoxicillin/clavulanate while the ST167 strain was MDR, including to all β-lactam drugs due to the presence of the carbapenemase gene blaNDM-5. The hospital-acquired ST167 strain was also resistant to newer drugs such as cefiderocol and eravacycline, which are currently not available locally, and had overall lower fitness and virulence in vitro compared with the initial infecting strain. Conclusions Though less fit and virulent in vitro, the MDR strain was fatal, suggesting that host factors, rather than bacterial virulence, may have been of greater importance in this patient’s outcome

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

Implementation strategies to improve outcomes in patients with established cardiovascular disease in sub-Saharan Africa: A systematic review

Sub-Saharan Africa (SSA) is experiencing an epidemic of cardiovascular disease (CVD). Despite numerous evidence-based therapies and management guidelines for patients with acute or established CVD, significant gaps persist in their implementation in SSA. This systematic review aims to describe, synthesise and identify key gaps in the implementation strategies of evidence-based approaches that can improve clinical outcomes for patients with acute or established CVD in SSA. We searched four databases for studies that examined the implementation strategies of evidence-based interventions for patients with acute or established CVD in SSA. Studies that did not focus on interventions were excluded. The primary outcome was major adverse cardiovascular events including myocardial infarction, stroke, cardiovascular death or hospitalisation. Secondary outcomes included adherence to treatment, improvement in modifiable risk factors, symptom measures, treatment complications, and psychosocial metrics, particularly those related to quality of life. Nineteen studies met the inclusion criteria (nine evaluated patients with heart failure, three evaluated heart failure or ischaemic heart disease, three evaluated ischaemic heart disease, and four evaluated stroke). Of the 19 studies, 14 were targeted at healthcare recipients, two at healthcare workers and three at the healthcare organisation. The most common interventions evaluated were in the field of cardiac rehabilitation. Only three studies (two evaluating stroke and one heart failure) implemented an intervention in the acute setting with the rest evaluating strategies at discharge or in the ambulatory population. No studies evaluated implementation strategies in hospitalised patients with ischaemic heart disease. This study highlights significant gaps in the implementation of interventions in patients with established cardiovascular disease. Gaps were highlighted in the acute care setting, specifically related to cardiac pathologies and implementation strategies targeting pharmacotherapeutic optimisations. We also highlight a notable lack of studies focusing on effective implementation strategies in primary care facilities and lower-level hospital settings. SYSTEMATIC REVIEW REGISTRATION The protocol was registered in PROSPERO prior to the study implementation (ID: CRD42023465781). The protocol can be accessed at crd.york.ac.uk/PROSPERO/display_record.php?RecordID=46578

Where do those data go? Reuse of screening results from clinical trials to estimate population prevalence of HBV infection in adults in Kilifi, Kenya

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the WHO African Region (AFRO). This means the full extent of HBV infection is not well described, leading to a lack of investment in diagnostics, treatment and disease prevention. Clinical trials in the WHO AFRO region have been increasing over time and many test for infectious diseases including hepatitis B virus (HBV) to determine baseline eligibility for participants, however these screening data are not reported. Here we review data from six clinical trials completed at the KEMRI-Wellcome Trust Research Programme between 2016 and 2023 that screened for HBV using hepatitis B surface antigen (HBsAg) as part of the trial exclusion criteria. 1727 people had HBsAg results available, of which 60 tested positive. We generated a crude period HBV prevalence estimate of 3.5% (95% CI 2.6–4.5%), and after standardisation for sex and age to account for the population structure of the Kilifi Health Demographics Surveillance System (KHDSS), the prevalence estimate increased to 5.0% (95% CI 3.4–6.6%). The underrepresentation of women in these trials was striking with 1263/1641 (77%) of participants being male. Alanine aminotransferase (ALT) was significantly higher in the HBsAg positive group but was not outside the normal range. We argue that routine collation and publishing of data from clinical trials could increase precision and geographical representation of global HBV prevalence estimates, enabling evidence-based provision of clinical care pathways and public health interventions to support progress towards global elimination targets. We do acknowledge when using clinical trials data for seroprevalence estimates, that local population structure data is necessary to allow standardisation of results, and the point of care tests used here are limited in sensitivity and specificity