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.

The impact of the COVID-19 pandemic on vaccine coverage in Kilifi, Kenya: A retrospective cohort study.

The COVID-19 pandemic caused unprecedented disruption in health service delivery, globally. This study sought to provide evidence on the impact of the pandemic on vaccine coverage in Kilifi County, Kenya. We conducted a vaccine coverage survey between April and June 2021 within the Kilifi Health and Demographic Surveillance System (KHDSS). Simple random sampling was used to identify 1500 children aged 6 weeks-59 months. Participants were grouped into three retrospective cohorts based on when they became age-eligible for vaccination: before the pandemic, during the first year, or during the second year of the pandemic. Survival analysis with Cox regression was used to evaluate the association between the time-period at which participants became age-eligible for vaccination and the rate of vaccination within a month of age-eligibility for the third dose of pentavalent vaccine (Pentavalent-3) and within three months of age-eligibility for the first dose of Measles vaccine (MCV-1). A total of 1,341 participants were included in the survey. Compared to the pre-COVID-19 baseline period, the rate of vaccination within a month of age-eligibility for Pentavalent-3 was not significantly different in the first year of the pandemic (adjusted hazard ratio [aHR] 1.03, 95 % confidence interval [CI] 0.90-1.18) and was significantly higher during the second year of the pandemic (aHR 1.33, 95 % CI 1.07-1.65). The rate of vaccination with MCV-1 within three months of age-eligibility was not significantly different among those age-eligible for vaccination during the first year of the pandemic (aHR 1.04, 95 % CI 0.88-1.21) and was 35 % higher during the second year of the pandemic (95 % CI 1.11-1.64), compared to those age-eligible pre-COVID-19. After adjusting for known determinants of vaccination, the COVID-19 pandemic did not adversely affect the rate of vaccination within the KHDSS.

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.

Pneumococcal conjugate vaccine dose-ranging studies in humans: A systematic review.

BACKGROUND: Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule are the basis of vaccine-mediated protection. We examined the relationship between the dose of polysaccharide in pneumococcal conjugate vaccines (PCVs) and immunogenicity. METHODS: A systematic search of English publications that evaluated the immunogenicity of varying doses of pneumococcal conjugate vaccines was performed in Medline and Embase (Ovid Sp) databases in August 2019. We included only articles that involved administration of pneumococcal conjugate vaccine in humans and assessed the immunogenicity of more than one serotype-specific saccharide dose. Results were synthesised descriptively due to the heterogeneity of product valency, product content and vaccine schedule. RESULTS: We identified 1691 articles after de-duplication; 9 studies met our inclusion criteria; 2 in adults, 6 in children and 1 in both. Doses of polysaccharide evaluated ranged from 0.44 mcg to 17.6 mcg. In infants, all doses tested elicited IgG geometric mean concentrations (GMCs) above the established correlate of protection (COP; 0.35 mcg/ml). A month after completion of the administered vaccine schedule, 95% confidence intervals of only three out of all the doses evaluated had GMCs that crossed below the COP. In the adult studies, all adults achieved GMCs that would be considered protective in children who have received 3 standard vaccine doses. CONCLUSION: For some products, the mean antibody concentrations induced against some pneumococcal serotypes increased with increasing doses of the polysaccharide conjugate, but for other serotypes, there were no clear dose-response relationships or the dose response curves were negative. Fractional doses of polysaccharide which contain less than is included in currently distributed formulations may be useful in the development of higher valency vaccines, or dose-sparing delivery for paediatric use.

10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.

Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3-45%; P < 0·01), 19F (21-66%; P < 0·01) and 23F (13-36%; P = 0·02), but not serotypes 6B (24-42%; P = 0·24) and 14 (21-40%; P = 0·06). Correlations between antibodies and memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides.

Evaluation of surveillance for surgical site infections in Thika Hospital, Kenya.

BACKGROUND: In low-income countries, surgical site infections (SSIs) are a very frequent form of hospital-acquired infection. Surveillance is an important method for controlling SSI but it is unclear how this can best be performed in low-income settings. AIM: To examine the epidemiological characteristics of various components of an SSI surveillance programme in a single Kenyan hospital. METHODS: The study assessed the inter-observer consistency of the surgical wound class (SWC) and American Society of Anesthesiologists (ASA) scores using the kappa statistic. Post-discharge telephone calls were evaluated against an outpatient clinician review 'gold standard'. The predictive value of components of the Centers for Disease Control and Prevention - National Healthcare Safety Network (CDC-NHNS) risk index was examined in patients having major obstetric or gynaecological surgery (O&G) between August 2010 and February 2011. FINDINGS: After appropriate training, surgeons and anaesthetists were found to be consistent in their use of the SWC and ASA scores respectively. Telephone calls were found to have a sensitivity of 70% [95% confidence interval (CI): 47-87] and a specificity of 100% (95% CI: 95-100) for detection of post-discharge SSI in this setting. In 954 patients undergoing major O&G operations, the SWC score was the only parameter in the CDC-NHNS risk index model associated with the risk of SSI (odds ratio: 4.00; 95% CI: 1.21-13.2; P = 0.02). CONCLUSIONS: Surveillance for SSI can be conducted in a low-income hospital setting, although dedicated staff, intensive training and local modifications to surveillance methods are necessary. Surveillance for post-discharge SSI using telephone calls is imperfect but provides a practical alternative to clinic-based diagnosis. The SWC score was the only predictor of SSI risk in O&G surgery in this context.

The preventable burden of pneumococcal disease in the developing world.

The efficacy of pneumococcal conjugate vaccines (PCV) and their remarkable success in operational use in North America challenge us to define the burden of pneumococcal disease and the likely benefits of PCV use in developing countries. Community-based incidence studies of invasive pneumococcal disease (IPD) and vaccine probe analyses of efficacy trials suggest there are approximately 814,000 pneumococcal deaths in children aged <5 years in developing countries each year and 1-4 million episodes of pneumococcal pneumonia in Africa alone. PCV will be effective where there is a demonstrable burden of IPD attributable to vaccine serotypes but herd protection and serotype replacement effects are unpredictable given existing knowledge of pneumococcal epidemiology in developing countries. Operational use of PCV in well-monitored settings is required to estimate these effects.

Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study.

BACKGROUND: Estimates of the burden of invasive bacterial disease in sub-Saharan Africa have previously relied on selected groups of patients, such as inpatients; they are, therefore, probably underestimated, potentially hampering vaccine implementation. Our aim was to assess the incidence of bacteraemia in all children presenting to a hospital in Kenya, irrespective of clinical presentation or decision to admit. METHODS: We did a community-based observational study for which we cultured blood from 1093 children who visited a Kenyan hospital outpatient department. We estimated bacteraemia incidence with a Demographic Surveillance System, and investigated the clinical significance of bacteraemia and the capacity of clinical signs to identify cases. RESULTS: The yearly incidence of bacteraemia per 100,000 children aged younger than 2 years and younger than 5 years was 2440 (95% CI 1307-3573) and 1192 (692-1693), respectively. Incidence of pneumococcal bacteraemia was 597 (416-778) per 100,000 person-years of observation in children younger than age 5 years. Three-quarters of episodes had a clinical focus or required admission, or both; one in six was fatal. After exclusion of children with occult bacteraemia, the incidence of clinically significant bacteraemia per 100,000 children younger than age 2 years or 5 years fell to 1741 (790-2692) and 909 (475-1343), respectively, and the yearly incidence of clinically significant pneumococcal bacteraemia was 436 (132-739) per 100,000 children younger than 5 years old. Clinical signs identified bacteraemia poorly. INTERPRETATION: Clinically significant bacteraemia in children in Kilifi is twice as common, and pneumococcal bacteraemia four times as common, as previously estimated. Our data support the introduction of pneumococcal vaccine in sub-Saharan Africa.

Effects of sample collection and storage methods on antipneumococcal immunoglobulin A in saliva.

Saliva contains components of both the mucosal and systemic immune systems. Variable flow rates, immunoglobulin proteases, and variation in collection and storage methods all introduce differences in the estimated concentrations of antibodies. We evaluated the effect of four collection methods and three storage protocols on the concentrations of immunoglobulin A (IgA) antibodies to pneumococcal capsular antigens 1, 5, 6B, and 14 and to pneumococcal surface adhesin A (PsaA) in saliva. Specimens were collected from 30 healthy Kenyan adults by collecting drool, by pipette suction, and with two commercial kits, OraSure and Oracol. Aliquots from each specimen were snap-frozen with glycerol in liquid nitrogen or stored for 4 to 8 h at +4 degrees C either with or without the addition of protease enzyme inhibitors prior to storage at -70 degrees C. Anticapsular IgA concentrations were not significantly different with different collection methods, but snap-freezing the specimens in liquid nitrogen led to concentrations 41 to 47% higher than those of specimens stored by the other methods (P < 0.0005).