The effect of COVID-19 pandemic on healthcare seeking in an urban informal settlement in Nairobi and a rural setting in western Kenya.

The COVID-19 pandemic caused widespread changes and disruptions to healthcare seeking behavior. There are limited studies on the effect of the COVID-19 pandemic on healthcare seeking patterns in low-and middle-income countries (LMICs), especially in settings with inequitable access to healthcare in rural and urban informal settlements. We investigated the effect of the COVID-19 pandemic on reported healthcare seeking at health facilities and chemists using morbidity data from participants in an ongoing population-based infectious disease surveillance platform in Asembo in Siaya County, a rural setting in western Kenya and Kibera, an urban informal settlement in Nairobi County. We described healthcare seeking patterns before (from 1st January 2016 to 12th March 2020) and during the pandemic (from 13th March 2020 to 31st August 2022) by gender and age for any reported illness and select clinical syndromes using frequencies and percentages. We used a generalized estimating equation with an exchangeable correlation structure to assess the effect of the pandemic on healthcare seeking adjusting for gender and age. Overall, there was a 19% (adjusted odds ratio, aOR: 0.81; 95% Confidence Interval, CI: 0.79-0.83) decline in odds of seeking healthcare at health facilities for any illness in Asembo during the pandemic, and a 30% (aOR: 0.70; 95% CI: 0.67-0.73) decline in Kibera. Similarly, there was a decline in seeking healthcare by clinical syndromes, e.g., for ARI, aOR: 0.76; 95% CI:0.73-0.79 in Asembo, and aOR: 0.68; 95% CI:0.64-0.72 in Kibera. The pandemic resulted in increased healthcare seeking at chemists (aOR: 1.23; 95% CI: 1.20-1.27 in Asembo, and aOR: 1.40; 95% CI: 1.35-1.46 in Kibera). This study highlights interruptions to healthcare seeking in resource-limited settings due to the COVID-19 pandemic. The pandemic resulted in a substantial decline in seeking care at health facilities, and an increase of the same at chemists.

Heterogenous transmission and seroprevalence of SARS-CoV-2 in two demographically diverse populations with low vaccination uptake in Kenya, March and June 2021.

Background: SARS-CoV-2 has extensively spread in cities and rural communities, and studies are needed to quantify exposure in the population. We report seroprevalence of SARS-CoV-2 in two well-characterized populations in Kenya at two time points. These data inform the design and delivery of public health mitigation measures. Methods: Leveraging on existing population based infectious disease surveillance (PBIDS) in two demographically diverse settings, a rural site in western Kenya in Asembo, Siaya County, and an urban informal settlement in Kibera, Nairobi County, we set up a longitudinal cohort of randomly selected households with serial sampling of all consenting household members in March and June/July 2021. Both sites included 1,794 and 1,638 participants in the March and June/July 2021, respectively. Individual seroprevalence of SARS-CoV-2 antibodies was expressed as a percentage of the seropositive among the individuals tested, accounting for household clustering and weighted by the PBIDS age and sex distribution. Results: Overall weighted individual seroprevalence increased from 56.2% (95%CI: 52.1, 60.2%) in March 2021 to 63.9% (95%CI: 59.5, 68.0%) in June 2021 in Kibera. For Asembo, the seroprevalence almost doubled from 26.0% (95%CI: 22.4, 30.0%) in March 2021 to 48.7% (95%CI: 44.3, 53.2%) in July 2021. Seroprevalence was highly heterogeneous by age and geography in these populations-higher seroprevalence was observed in the urban informal settlement (compared to the rural setting), and children aged <10 years had the lowest seroprevalence in both sites. Only 1.2% and 1.6% of the study participants reported receipt of at least one dose of the COVID-19 vaccine by the second round of serosurvey-none by the first round. Conclusions: In these two populations, SARS-CoV-2 seroprevalence increased in the first 16 months of the COVID-19 pandemic in Kenya. It is important to prioritize additional mitigation measures, such as vaccine distribution, in crowded and low socioeconomic settings.

SARS-CoV-2 seroprevalence and implications for population immunity: Evidence from two Health and Demographic Surveillance System sites in Kenya, February-December 2022.

BACKGROUND: We sought to estimate SARS-CoV-2 antibody seroprevalence within representative samples of the Kenyan population during the third year of the COVID-19 pandemic and the second year of COVID-19 vaccine use. METHODS: We conducted cross-sectional serosurveys among randomly selected, age-stratified samples of Health and Demographic Surveillance System (HDSS) residents in Kilifi and Nairobi. Anti-spike (anti-S) immunoglobulin G (IgG) serostatus was measured using a validated in-house ELISA and antibody concentrations estimated with reference to the WHO International Standard for anti-SARS-CoV-2 immunoglobulin. RESULTS: HDSS residents were sampled in February-June 2022 (Kilifi HDSS N = 852; Nairobi Urban HDSS N = 851) and in August-December 2022 (N = 850 for both sites). Population-weighted coverage for ≥1 doses of COVID-19 vaccine were 11.1% (9.1-13.2%) among Kilifi HDSS residents by November 2022 and 34.2% (30.7-37.6%) among Nairobi Urban HDSS residents by December 2022. Population-weighted anti-S IgG seroprevalence among Kilifi HDSS residents increased from 69.1% (65.8-72.3%) by May 2022 to 77.4% (74.4-80.2%) by November 2022. Within the Nairobi Urban HDSS, seroprevalence by June 2022 was 88.5% (86.1-90.6%), comparable with seroprevalence by December 2022 (92.2%; 90.2-93.9%). For both surveys, seroprevalence was significantly lower among Kilifi HDSS residents than among Nairobi Urban HDSS residents, as were antibody concentrations (p < 0.001). CONCLUSION: More than 70% of Kilifi residents and 90% of Nairobi residents were seropositive for anti-S IgG by the end of 2022. There is a potential immunity gap in rural Kenya; implementation of interventions to improve COVID-19 vaccine uptake among sub-groups at increased risk of severe COVID-19 in rural settings is recommended.

Assessment of gestational age at antenatal care visits among Kenyan women to inform delivery of a maternal respiratory syncytial virus (RSV) vaccine in low- and middle-income countries.

Background: Maternal respiratory syncytial virus (RSV) vaccines that are likely to be implementable in low- and middle-income countries (LMICs) are in final stages of clinical trials. Data on the number of women presenting for antenatal care (ANC) per day and proportion attending within the proposed gestational window for vaccine delivery, is a prerequisite to guide development of vaccine vial size and inform vaccine uptake in this setting. Methods: We undertook administrative review and abstraction of ANC attendance records from 2019 registers of 24 selected health facilities, stratified by the level of care, from Kilifi, Siaya and Nairobi counties in Kenya. Additional data were obtained from Mother and Child Health (MCH) booklets of women in each of the Health and Demographic Surveillance System (HDSS) areas of Kilifi, Nairobi and Siaya. Data analysis involved descriptive summaries of the number (mean, median) and proportion of women attending ANC within the gestational window period of 28-32 weeks and 24-36 weeks. Results: A total of 62,153 ANC records were abstracted, 33,872 from Kilifi, 19,438 from Siaya and 8,943 from Nairobi Counties. The median (Interquartile range, IQR) number of women attending ANC per day at a gestational age window of 28-32 and 24-36 weeks, respectively, were: 4 (2-6) and 7 (4-12) in dispensaries, 5 (2-9) and 10 (4-19) in health centres and 6 (4-11) and 16 (10-26) in county referral hospitals. In the HDSS areas of Kilifi, Siaya and Nairobi, pregnant women attending at least one ANC visit, within a window of 28-32 weeks, were: 77% (360/470), 75% (590/791) and 67% (547/821), respectively. Conclusions: About 70% of pregnant women across three distinct geographical regions in Kenya, attend ANC within 28-32 weeks of gestation. A multidose vial size with about five doses per vial, approximates daily ANC attendance and would not incur possible wastage in similar settings.

Value profile for respiratory syncytial virus vaccines and monoclonal antibodies.

Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Respiratory Syncytial Virus (RSV) Disease and Prevention Products: Knowledge, Attitudes, and Preferences of Kenyan Healthcare Workers in Two Counties in 2021.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) among infants under 6 months of age. Yet, in Kenya, little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions around RSV disease and the prevention products under development. Between September and October 2021, we conducted a mixed methods cross-sectional survey to assess HCWs' knowledge, attitudes, and perceptions of RSV disease and RSV vaccinations in two counties. We enrolled HCWs delivering services directly at maternal and child health (MCH) departments in selected health facilities (frontline HCWs) and health management officers (HMOs). Of the 106 respondents, 94 (88.7%) were frontline HCWs, while 12 were HMOs. Two of the HMOs were members of the Kenya National Immunization Technical Advisory Group (KENITAG). Of the 104 non-KENITAG HCWs, only 41 (39.4%) had heard about RSV disease, and 38/41 (92.7%) felt that pregnant women should be vaccinated against RSV. Most participants would recommend a single-dose vaccine schedule (n = 62, 58.5%) for maximal adherence and compliance (n = 38/62, 61.3%), single dose/device vaccines (n = 50/86, 58.1%) to prevent wastage and contamination, and maternal vaccination through antenatal care clinics (n = 53, 50%). We found the need for increased knowledge about RSV disease and prevention among Kenyan HCWs.

Dynamic Incidence of Typhoid Fever over a 10-Year Period (2010-2019) in Kibera, an Urban Informal Settlement in Nairobi, Kenya.

Typhoid fever burden can vary over time. Long-term data can inform prevention strategies; however, such data are lacking in many African settings. We reexamined typhoid fever incidence and antimicrobial resistance (AMR) over a 10-year period in Kibera, a densely populated urban informal settlement where a high burden has been previously described. We used data from the Population Based Infectious Diseases Surveillance platform to estimate crude and adjusted incidence rates and prevalence of AMR in nearly 26,000 individuals of all ages. Demographic and healthcare-seeking information was collected through household visits. Blood cultures were processed for patients with acute fever or lower respiratory infection. Between 2010 and 2019, 16,437 participants were eligible for blood culture and 11,848 (72.1%) had a culture performed. Among 11,417 noncontaminated cultures (96.4%), 237 grew Salmonella enterica serovar Typhi (2.1%). Overall crude and adjusted incidences were 95 and 188 cases per 100,000 person-years of observation (pyo), respectively. Annual crude incidence varied from 144 to 233 between 2010 and 2012 and from 9 to 55 between 2013 and 2018 and reached 130 per 100,000 pyo in 2019. Children 5-9 years old had the highest overall incidence (crude, 208; adjusted, 359 per 100,000 pyo). Among isolates tested, 156 of 217 were multidrug resistant (resistant to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole [71.9%]) and 6 of 223 were resistant to ciprofloxacin (2.7%). Typhoid fever incidence resurged in 2019 after a prolonged period of low rates, with the highest incidence among children. Typhoid fever control measures, including vaccines, could reduce morbidity in this setting.

Estimates of the national burden of respiratory syncytial virus in Kenyan children aged under 5 years, 2010-2018.

BACKGROUND: Respiratory syncytial virus (RSV) is among the leading childhood causes of viral pneumonia worldwide. Establishing RSV-associated morbidity and mortality is important in informing the development, delivery strategies, and evaluation of interventions. METHODS: Using data collected during 2010-2018 from base regions (population-based surveillance studies in western Kenya and the Kilifi Health and Demographic Surveillance Study), we estimated age-specific rates of acute respiratory illness (ARI), severe acute respiratory illness (SARI-defined as hospitalization with cough or difficulty breathing with onset within the past 10 days), and SARI-associated deaths. We extrapolated the rates from the base regions to other regions of Kenya, while adjusting for risk factors of ARI and healthcare seeking behavior, and finally applied the proportions of RSV-positive cases identified from various sentinel and study facilities to the rates to obtain regional age-specific rates of RSV-associated outpatient and non-medically attended ARI and hospitalized SARI and severe ARI that was not hospitalized (non-hospitalized SARI). We applied age-specific RSV case fatality ratios to SARI to obtain estimates of RSV-associated in- and out-of-hospital deaths. RESULTS: Among Kenyan children aged < 5 years, the estimated annual incidence of outpatient and non-medically attended RSV-associated ARI was 206 (95% credible interval, CI; 186-229) and 226 (95% CI; 204-252) per 1000 children, respectively. The estimated annual rates of hospitalized and non-hospitalized RSV-associated SARI were 349 (95% CI; 303-404) and 1077 (95% CI; 934-1247) per 100,000 children respectively. The estimated annual number of in- and out-of-hospital deaths associated with RSV infection in Kenya were 539 (95% CI; 420-779) and 1921 (95% CI; 1495-2774), respectively. Children aged < 6 months had the highest burden of RSV-associated severe disease: 2075 (95% CI; 1818-2394) and 44 (95% CI 25-71) cases per 100,000 children for hospitalized SARI and in-hospital deaths, respectively. CONCLUSIONS: Our findings suggest a substantial disease burden due to RSV infection, particularly among younger children. Prioritizing development and use of maternal vaccines and affordable long-lasting monoclonal antibodies could help reduce this burden.

Estimating the cost-effectiveness of maternal vaccination and monoclonal antibodies for respiratory syncytial virus in Kenya and South Africa.

BACKGROUND: Respiratory syncytial virus (RSV) causes a substantial burden of acute lower respiratory infection in children under 5 years, particularly in low- and middle-income countries (LMICs). Maternal vaccine (MV) and next-generation monoclonal antibody (mAb) candidates have been shown to reduce RSV disease in infants in phase 3 clinical trials. The cost-effectiveness of these biologics has been estimated using disease burden data from global meta-analyses, but these are sensitive to the detailed age breakdown of paediatric RSV disease, for which there have previously been limited data. METHODS: We use original hospital-based incidence data from South Africa (ZAF) and Kenya (KEN) collected between 2010 and 2018 of RSV-associated acute respiratory infection (ARI), influenza-like illness (ILI), and severe acute respiratory infection (SARI) as well as deaths with monthly age-stratification, supplemented with data on healthcare-seeking behaviour and costs to the healthcare system and households. We estimated the incremental cost per DALY averted (incremental cost-effectiveness ratio or ICER) of public health interventions by MV or mAb for a plausible range of prices (5-50 USD for MV, 10-125 USD for mAb), using an adjusted version of a previously published health economic model of RSV immunisation. RESULTS: Our data show higher disease incidence for infants younger than 6 months of age in the case of Kenya and South Africa than suggested by earlier projections from community incidence-based meta-analyses of LMIC data. Since MV and mAb provide protection for these youngest age groups, this leads to a substantially larger reduction of disease burden and, therefore, more favourable cost-effectiveness of both interventions in both countries. Using the latest efficacy data and inferred coverage levels based on antenatal care (ANC-3) coverage (KEN: 61.7%, ZAF: 75.2%), our median estimate of the reduction in RSV-associated deaths in children under 5 years in Kenya is 10.5% (95% CI: 7.9, 13.3) for MV and 13.5% (10.7, 16.4) for mAb, while in South Africa, it is 27.4% (21.6, 32.3) and 37.9% (32.3, 43.0), respectively. Starting from a dose price of 5 USD, in Kenya, net cost (for the healthcare system) per (undiscounted) DALY averted for MV is 179 (126, 267) USD, rising to 1512 (1166, 2070) USD at 30 USD per dose; for mAb, it is 684 (543, 895) USD at 20 USD per dose and 1496 (1203, 1934) USD at 40 USD per dose. In South Africa, a MV at 5 USD per dose would be net cost-saving for the healthcare system and net cost per DALY averted is still below the ZAF's GDP per capita at 40 USD dose price (median: 2350, 95% CI: 1720, 3346). For mAb in ZAF, net cost per DALY averted is 247 (46, 510) USD at 20 USD per dose, rising to 2028 (1565, 2638) USD at 50 USD per dose and to 6481 (5364, 7959) USD at 125 USD per dose. CONCLUSIONS: Incorporation of new data indicating the disease burden is highly concentrated in the first 6 months of life in two African settings suggests that interventions against RSV disease may be more cost-effective than previously estimated.

Diagnostic accuracy of the Panbio COVID-19 antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation.

BACKGROUND: Accurate and timely diagnosis is essential in limiting the spread of SARS-CoV-2 infection. The reference standard, rRT-PCR, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen RDTs provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%. METHODS: This evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention's (CDC) rRT-PCR test. RESULTS: We evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms <5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those with onset of symptoms >7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30. CONCLUSION: The overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool only for symptomatic patients in high-risk settings with limited access to rRT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.

Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape.

Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralising antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. An extended half-life monoclonal antibody for all infants is likely to be within 1 year of regulatory approval (from August, 2022) for high-income countries. Live-attenuated vaccines are in development for older infants (aged >6 months). Subunit vaccines are in late-stage trials for pregnant women to protect infants, whereas vector, subunit, and nucleic acid approaches are being developed for older adults. Urgent next steps include ensuring access and affordability of a respiratory syncytial virus vaccine globally. This review gives an overview of respiratory syncytial virus vaccines and monoclonal antibodies in clinical development highlighting different target populations, antigens, and trial results.

Rhinovirus dynamics across different social structures.

Rhinoviruses (RV), common human respiratory viruses, exhibit significant antigenic diversity, yet their dynamics across distinct social structures remain poorly understood. Our study delves into RV dynamics within Kenya by analysing VP4/2 sequences across four different social structures: households, a public primary school, outpatient clinics in the Kilifi Health and Demographics Surveillance System (HDSS), and countrywide hospital admissions and outpatients. The study revealed the greatest diversity of RV infections at the countrywide level (114 types), followed by the Kilifi HDSS (78 types), the school (47 types), and households (40 types), cumulatively representing >90% of all known RV types. Notably, RV diversity correlated directly with the size of the population under observation, and several RV type variants occasionally fuelled RV infection waves. Our findings highlight the critical role of social structures in shaping RV dynamics, information that can be leveraged to enhance public health strategies. Future research should incorporate whole-genome analysis to understand fine-scale evolution across various social structures.

Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020-2021.

Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020-October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Drivers of respiratory syncytial virus seasonal epidemics in children under 5 years in Kilifi, coastal Kenya.

Respiratory syncytial virus (RSV) causes significant childhood morbidity and mortality in the developing world. The determinants of RSV seasonality are of importance in designing interventions. They are poorly understood in tropical and sub-tropical regions in low- and middle-income countries. Our study utilized long-term surveillance data on cases of RSV associated with severe or very severe pneumonia in children aged 1 day to 59 months admitted to the Kilifi County Hospital. A generalized additive model was used to investigate the association between RSV admissions and meteorological variables (maximum temperature, rainfall, absolute humidity); weekly number of births within the catchment population; and school term dates. Furthermore, a time-series-susceptible-infected-recovered (TSIR) model was used to reconstruct an empirical transmission rate which was used as a dependent variable in linear regression and generalized additive models with meteorological variables and school term dates. Maximum temperature, absolute humidity, and weekly number of births were significantly associated with RSV activity in the generalized additive model. Results from the TSIR model indicated that maximum temperature and absolute humidity were significant factors. Rainfall and school term did not yield significant relationships. Our study indicates that meteorological parameters and weekly number of births potentially play a role in the RSV seasonality in this region. More research is required to explore the underlying mechanisms underpinning the observed relationships.

Molecular characterization of circulating Salmonella Typhi strains in an urban informal settlement in Kenya.

A high burden of Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) bacteremia has been reported from urban informal settlements in sub-Saharan Africa, yet little is known about the introduction of these strains to the region. Understanding regional differences in the predominant strains of S. Typhi can provide insight into the genomic epidemiology. We genetically characterized 310 S. Typhi isolates from typhoid fever surveillance conducted over a 12-year period (2007-2019) in Kibera, an urban informal settlement in Nairobi, Kenya, to assess the circulating strains, their antimicrobial resistance attributes, and how they relate to global S. Typhi isolates. Whole genome multi-locus sequence typing (wgMLST) identified 4 clades, with up to 303 pairwise allelic differences. The identified genotypes correlated with wgMLST clades. The predominant clade contained 290 (93.5%) isolates with a median of 14 allele differences (range 0-52) and consisted entirely of genotypes 4.3.1.1 and 4.3.1.2. Resistance determinants were identified exclusively in the predominant clade. Determinants associated with resistance to aminoglycosides were observed in 245 isolates (79.0%), sulphonamide in 243 isolates (78.4%), trimethoprim in 247 isolates (79.7%), tetracycline in 224 isolates (72.3%), chloramphenicol in 247 isolates (79.6%), ß-lactams in 239 isolates (77.1%) and quinolones in 62 isolates (20.0%). Multidrug resistance (MDR) determinants (defined as determinants conferring resistance to ampicillin, chloramphenicol and cotrimoxazole) were found in 235 (75.8%) isolates. The prevalence of MDR associated genes was similar throughout the study period (2007-2012: 203, 76.3% vs 2013-2019: 32, 72.7%; Fisher's Exact Test: P = 0.5478, while the proportion of isolates harboring quinolone resistance determinants increased (2007-2012: 42, 15.8% and 2013-2019: 20, 45.5%; Fisher's Exact Test: P<0.0001) following a decline in S. Typhi in Kibera. Some isolates (49, 15.8%) harbored both MDR and quinolone resistance determinants. There were no determinants associated with resistance to cephalosporins or azithromycin detected among the isolates sequenced in this study. Plasmid markers were only identified in the main clade including IncHI1A and IncHI1B(R27) in 226 (72.9%) isolates, and IncQ1 in 238 (76.8%) isolates. Molecular clock analysis of global typhoid isolates and isolates from Kibera suggests that genotype 4.3.1 has been introduced multiple times in Kibera. Several genomes from Kibera formed a clade with genomes from Kenya, Malawi, South Africa, and Tanzania. The most recent common ancestor (MRCA) for these isolates was from around 1997. Another isolate from Kibera grouped with several isolates from Uganda, sharing a common ancestor from around 2009. In summary, S. Typhi in Kibera belong to four wgMLST clades one of which is frequently associated with MDR genes and this poses a challenge in treatment and control.

Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya.

Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal transfer ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06-0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07-0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting.

Identification of missed viruses by metagenomic sequencing of clinical respiratory samples from Kenya.

Pneumonia remains a major cause of mortality and morbidity. Most molecular diagnoses of viruses rely on polymerase chain reaction (PCR) assays that however can fail due to primer mismatch. We investigated the performance of routine virus diagnostics in Kilifi, Kenya, using random-primed viral next generation sequencing (viral NGS) on respiratory samples which tested negative for the common viral respiratory pathogens by a local standard diagnostic panel. Among 95 hospitalised pneumonia patients and 95 household-cohort individuals, analysis of viral NGS identified at least one respiratory-associated virus in 35 (37%) and 23 (24%) samples, respectively. The majority (66%; 42/64) belonged to the Picornaviridae family. The NGS data analysis identified a number of viruses that were missed by the diagnostic panel (rhinovirus, human metapneumovirus, respiratory syncytial virus and parainfluenza virus), and these failures could be attributed to PCR primer/probe binding site mismatches. Unexpected viruses identified included parvovirus B19, enterovirus D68, coxsackievirus A16 and A24 and rubella virus. The regular application of such viral NGS could help evaluate assay performance, identify molecular causes of missed diagnoses and reveal gaps in the respiratory virus set used for local screening assays. The results can provide actionable information to improve the local pneumonia diagnostics and reveal locally important viral pathogens.

Infection patterns of endemic human coronaviruses in rural households in coastal Kenya.

Background: The natural history and transmission patterns of endemic human coronaviruses are of increased interest following the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods: In rural Kenya 483 individuals from 47 households were followed for six months (2009-10) with nasopharyngeal swabs collected twice weekly regardless of symptoms. A total of 16,918 swabs were tested for human coronavirus (hCoV) OC43, NL63 and 229E and other respiratory viruses using polymerase chain reaction. Results: From 346 (71.6%) household members, 629 hCoV infection episodes were defined, with 36.3% being symptomatic: varying by hCoV type and decreasing with age. Symptomatic episodes (aHR=0.6 (95% CI:0.5-0.8) or those with elevated peak viral load (medium aHR=0.4 (0.3-0.6); high aHR=0.31 (0.2-0.4)) had longer viral shedding compared to their respective counterparts. Homologous reinfections were observed in 99 (19.9%) of 497 first infections. School-age children (55%) were the most common index cases with those having medium (aOR=5.3 (2.3 - 12.0)) or high (8.1 (2.9 - 22.5)) peak viral load most often generating secondary cases. Conclusion: Household coronavirus infection was common, frequently asymptomatic and mostly introduced by school-age children. Secondary transmission was influenced by viral load of index cases. Homologous-type reinfection was common. These data may be insightful for SARS-CoV-2.

High seroprevalence of SARS-CoV-2 but low infection fatality ratio eight months after introduction in Nairobi, Kenya.

BACKGROUND: The lower than expected COVID-19 morbidity and mortality in Africa has been attributed to multiple factors, including weak surveillance. This study estimated the burden of SARS-CoV-2 infections eight months into the epidemic in Nairobi, Kenya. METHODS: A population-based, cross-sectional survey was conducted using multi-stage random sampling to select households within Nairobi in November 2020. Sera from consenting household members were tested for antibodies to SARS-CoV-2. Seroprevalence was estimated after adjusting for population structure and test performance. Infection fatality ratios (IFRs) were calculated by comparing study estimates with reported cases and deaths. RESULTS: Among 1,164 individuals, the adjusted seroprevalence was 34.7% (95% CI 31.8-37.6). Half of the enrolled households had at least one positive participant. Seropositivity increased in more densely populated areas (spearman's r=0.63; p=0.009). Individuals aged 20-59 years had at least two-fold higher seropositivity than those aged 0-9 years. The IFR was 40 per 100,000 infections, with individuals ≥60 years old having higher IFRs. CONCLUSION: Over one-third of Nairobi residents had been exposed to SARS-CoV-2 by November 2020, indicating extensive transmission. However, the IFR was >10-fold lower than that reported in Europe and the USA, supporting the perceived lower morbidity and mortality in sub-Saharan Africa.