The cost of care for children hospitalized with respiratory syncytial virus (RSV) associated lower respiratory infection in Kenya.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the main causes of hospitalization for lower respiratory tract infection in children under five years of age globally. Maternal vaccines and monoclonal antibodies for RSV prevention among infants are approved for use in high income countries. However, data are limited on the economic burden of RSV disease from low- and middle-income countries (LMIC) to inform decision making on prioritization and introduction of such interventions. This study aimed to estimate household and health system costs associated with childhood RSV in Kenya. METHODS: A structured questionnaire was administered to caregivers of children aged < 5 years admitted to referral hospitals in Kilifi (coastal Kenya) and Siaya (western Kenya) with symptoms of acute lower respiratory tract infection (LRTI) during the 2019-2021 RSV seasons. These children had been enrolled in ongoing in-patient surveillance for respiratory viruses. Household expenditures on direct and indirect medical costs were collected 10 days prior to, during, and two weeks post hospitalization. Aggregated health system costs were acquired from the hospital administration and were included to calculate the cost per episode of hospitalized RSV illness. RESULTS: We enrolled a total of 241 and 184 participants from Kilifi and Siaya hospitals, respectively. Out of these, 79 (32.9%) in Kilifi and 21(11.4%) in Siaya, tested positive for RSV infection. The total (health system and household) mean costs per episode of severe RSV illness was USD 329 (95% confidence interval (95% CI): 251-408 ) in Kilifi and USD 527 (95% CI: 405- 649) in Siaya. Household costs were USD 67 (95% CI: 54-80) and USD 172 (95% CI: 131- 214) in Kilifi and Siaya, respectively. Mean direct medical costs to the household during hospitalization were USD 11 (95% CI: 10-12) and USD 67 (95% CI: 51-83) among Kilifi and Siaya participants, respectively. Observed costs were lower in Kilifi due to differences in healthcare administration. CONCLUSIONS: RSV-associated disease among young children leads to a substantial economic burden to both families and the health system in Kenya. This burden may differ between Counties in Kenya and similar multi-site studies are advised to support cost-effectiveness analyses.

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.

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.

Implications of gestational age at antenatal care attendance on the successful implementation of a maternal respiratory syncytial virus (RSV) vaccine program in coastal Kenya.

BACKGROUND: Maternal immunisation to boost respiratory syncytial virus (RSV) specific antibodies in pregnant women is a strategy to enhance infant protection. The timing of maternal vaccination during pregnancy may be critical for its effectiveness. However, Kenya has no documented published data on gestational age distribution of pregnant women attending antenatal care (ANC), or the proportion of women attending ANC during the proposed window period for vaccination, to inform appropriate timing for delivery or estimate potential uptake of this vaccine. METHODS: A cross-sectional survey was conducted within the Kilifi Health and Demographic Surveillance System (KHDSS), coastal Kenya. A simple random sample of 1000 women who had registered pregnant in 2017 to 2018 and with a birth outcome by the time of data collection was taken. The selected women were followed at their homes, and individually written informed consent was obtained. Records of their antenatal attendance during pregnancy were abstracted from their ANC booklet. The proportion of all pregnant women from KHDSS (55%) who attended for one or more ANC in 2018 was used to estimate vaccine coverage. RESULTS: Of the 1000 women selected, 935 were traced with 607/935 (64.9%) available for interview, among whom 470/607 (77.4%) had antenatal care booklets. The median maternal age during pregnancy was 28.6 years. The median (interquartile range) gestational age in weeks at the first to fifth ANC attendance was 26 (21-28), 29 (26-32), 32 (28-34), 34 (32-36) and 36 (34-38), respectively. The proportion of women attending for ANC during a gestational age window for vaccination of 28-32 weeks (recommended), 26-33 weeks and 24-36 weeks was 76.6% (360/470), 84.5% (397/470) and 96.2% (452/470), respectively. Estimated vaccine coverage was 42.1, 46.5 and 52.9% within the narrow, wide and wider gestational age windows, respectively. CONCLUSIONS: In a random sample of pregnant women from Kilifi HDSS, Coastal Kenya with card-confirmed ANC clinic attendance, 76.6% would be reached for maternal RSV vaccination within the gestational age window of 28-32 weeks. Widening the vaccination window (26-33 weeks) or (24-36 weeks) would not dramatically increase vaccine coverage and would require consideration of antibody kinetics data that could affect vaccine efficacy.

An Intensive, Active Surveillance Reveals Continuous Invasion and High Diversity of Rhinovirus in Households.

We report on infection patterns in 5 households (78 participants) delineating the natural history of human rhinovirus (HRV). Nasopharyngeal collections were obtained every 3-4 days irrespective of symptoms, over a 6-month period, with molecular screening for HRV and typing by sequencing VP4/VP2 junction. Overall, 311/3468 (8.9%) collections were HRV positive: 256 were classified into 3 species: 104 (40.6%) HRV-A; 14 (5.5%) HRV-B, and 138 (53.9%) HRV-C. Twenty-six known HRV types (13 HRV-A, 3 HRV-B, and 10 HRV-C) were identified (A75, C1, and C35 being most frequent). We observed continuous invasion and temporal clustering of HRV types in households (range 5-13 over 6 months). Intrahousehold transmission was independent of clinical status but influenced by age. Most (89.0%) of HRV infection episodes were limited to <14 days. Individual repeat infections were frequent (range 1-7 over 6 months), decreasing with age, and almost invariably heterotypic, indicative of lasting type-specific immunity and low cross-type protection.

Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya.

Background: Human coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime. Methods: Nasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing. Results: HCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching. Conclusions: In this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.

Continuous Invasion by Respiratory Viruses Observed in Rural Households During a Respiratory Syncytial Virus Seasonal Outbreak in Coastal Kenya.

Background: Households are high-intensity close-contact environments favorable for transmission of respiratory viruses, yet little is known for low-income settings. Methods: Active surveillance was completed on 47 households in rural coastal Kenya over 6 months during a respiratory syncytial virus (RSV) season. Nasopharyngeal swabs (NPSs) were taken from 483 household members twice weekly irrespective of symptoms. Using molecular diagnostics, NPSs from 6 households were screened for 15 respiratory viruses and the remainder of households only for the most frequent viruses observed: rhinovirus (RV), human coronavirus (HCoV; comprising strains 229E, OC43, and NL63), adenovirus (AdV), and RSV (A and B). Results: Of 16928 NPSs tested for the common viruses, 4259 (25.2%) were positive for ≥1 target; 596 (13.8%) had coinfections. Detection frequencies were 10.5% RV (1780), 7.5% HCoV (1274), 7.3% AdV (1232), and 3.2% RSV (537). On average, each household and individual had 6 and 3 different viruses detected over the study period, respectively. Rhinovirus and HCoV were detected in all the 47 households while AdV and RSV were detected in 45 (95.7%) and 40 (85.1%) households, respectively. The individual risk of infection over the 6-month period was 93.4%, 80.1%, 71.6%, 61.5%, and 37.1% for any virus, RV, HCoV, AdV, and RSV, respectively. NPSs collected during symptomatic days and from younger age groups had higher prevalence of virus detection relative to respective counterparts. RSV was underrepresented in households relative to hospital admission data. Conclusions: In this household setting, respiratory virus infections and associated illness are ubiquitous. Future studies should address the health and economic implications of these observations.

Local evolutionary patterns of human respiratory syncytial virus derived from whole-genome sequencing.

UNLABELLED: Human respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies. IMPORTANCE: The new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.

Frequent Asymptomatic Respiratory Syncytial Virus Infections During an Epidemic in a Rural Kenyan Household Cohort.

BACKGROUND: The characteristics, determinants, and potential contribution to transmission of asymptomatic cases of respiratory syncytial virus (RSV) infection have not been well described. METHODS: A cohort of 47 households (493 individuals) in coastal Kenya was recruited and followed for a 26-week period spanning a complete RSV season. Nasopharyngeal swab specimens were requested weekly, during the first 4 weeks, and twice weekly thereafter from all household members, regardless of illness status. The samples were screened for a range of respiratory viruses by multiplex real-time polymerase chain reaction. RESULTS: Tests on 16,928 samples yielded 205 RSV infection episodes in 179 individuals (37.1%) from 40 different households. Eighty-six episodes (42.0%) were asymptomatic. Factors independently associated with an increased risk of asymptomatic RSV infection episodes were higher age, shorter duration of infection, bigger household size, lower peak viral load, absence of concurrent RSV infections within the household, infection by RSV group B, and no prior human rhinovirus infections. The propensity of RSV spread in households was dependent on symptom status and amount (duration and load) of virus shed. CONCLUSIONS: While asymptomatic RSV was less likely to spread, the high frequency of symptomless RSV infection episodes highlights a potentially important role of asymptomatic infections in the community transmission of RSV.

Evaluating vaccination strategies for reducing infant respiratory syncytial virus infection in low-income settings.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and related hospitalization of young children in least developed countries. Individuals are repeatedly infected, but it is the first exposure, often in early infancy, that results in the vast majority of severe RSV disease. Unfortunately, due to immunological immaturity, infants are a problematic RSV vaccine target. Several trials are ongoing to identify a suitable candidate vaccine and target group, but no immunization program is yet in place. METHODS: In this work, an individual-based model that explicitly accounts for the socio-demographic population structure is developed to investigate RSV transmission patterns in a rural setting of Kenya and to evaluate the potential effectiveness of alternative population targets in reducing RSV infant infection. RESULTS: We find that household transmission is responsible for 39% of infant infections and that school-age children are the main source of infection within the household, causing around 55% of cases. Moreover, assuming a vaccine-induced protection equivalent to that of natural infection, our results show that annual vaccination of students is the only alternative strategy to routine immunization of infants able to trigger a relevant and persistent reduction of infant infection (on average, of 35.6% versus 41.5% in 10 years of vaccination). Interestingly, if vaccination of pregnant women boosts maternal antibody protection in infants by an additional 4 months, RSV infant infection will be reduced by 31.5%. CONCLUSIONS: These preliminary evaluations support the efforts to develop vaccines and related strategies that go beyond targeting vaccines to those at highest risk of severe disease.

The source of respiratory syncytial virus infection in infants: a household cohort study in rural Kenya.

BACKGROUND: Respiratory syncytial virus (RSV) vaccine development for direct protection of young infants faces substantial obstacles. Assessing the potential of indirect protection using different strategies, such as targeting older children or mothers, requires knowledge of the source of infection to the infants. METHODS: We undertook a prospective study in rural Kenya. Households with a child born after the preceding RSV epidemic and ≥ 1 elder sibling were recruited. Nasopharyngeal swab samples were collected every 3-4 days irrespective of symptoms from all household members throughout the RSV season of 2009-2010 and tested for RSV using molecular techniques. RESULTS: From 451 participants in 44 households a total of 15 396 nasopharyngeal swab samples were samples were collected, representing 86% of planned sampling. RSV was detected in 37 households (84%) and 173 participants (38%) and 28 study infants (64%). The infants acquired infection from within (15 infants; 54%) or outside (9 infants; 32%) the household; in 4 households the source of infant infection was inconclusive. Older children were index case patients for 11 (73%) of the within-household infant infections, and 10 of these 11 children were attending school. CONCLUSION: We demonstrate that school-going siblings frequently introduce RSV into households, leading to infection in infants.

"When they see us, it's like they have seen the benefits!": experiences of study benefits negotiations in community-based studies on the Kenyan Coast.

BACKGROUND: Benefit sharing in health research has been the focus of international debates for many years, particularly in developing countries. Whilst increasing attention is being given to frameworks that can guide researchers to determine levels of benefits to participants, there is little empirical research from developing countries on the practical application of these frameworks, including in situations of extreme poverty and vulnerability. In addition, the voices of those who often negotiate and face issues related to benefits in practice - frontline researchers and fieldworkers (FWs) - are rarely included in these debates. Against this background, this paper reports on experiences of negotiating research participation and benefits as described by fieldworkers, research participants and researchers in two community based studies. METHODS: The findings reported here are from a broader social science study that explored the nature of interactions between fieldworkers and participants in two community based studies on the Kenyan Coast. Between January and July 2010, data were collected using participant observation, and through group discussions and in-depth interviews with 42 fieldworkers, 4 researchers, and 40 study participants. RESULTS: Participants highly appreciated the benefits provided by studies, particularly health care benefits. Fieldworkers were seen by participants and other community members as the gatekeepers and conduits of benefits, even though those were not their formal roles. Fieldworkers found it challenging to ignore participant and community requests for more benefits, especially in situations of extreme poverty. However, responding to requests by providing different sorts and levels of benefits over time, as inadvertently happened in one study, raised expectations of further benefits and led to continuous negotiations between fieldworkers and participants. CONCLUSIONS: Fieldworkers play an important intermediary role in research; a role imbued with multiple challenges and ethical dilemmas for which they require appropriate support. Further more specific empirical research is needed to inform the development of guidance for researchers on benefit sharing, and on responding to emergency humanitarian needs for this and other similar settings.

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.

Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) meeting, virtual gathering, 26 February-1 March 2024.

The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.

Spatio-temporal distribution of rhinovirus types in Kenya: a retrospective analysis, 2014.

The epidemiology and circulation patterns of various rhinovirus types within populations remains under-explored. We generated 803 VP4/VP2 gene sequences from rhinovirus-positive samples collected from acute respiratory illness (ARI) patients, including both in-patient and outpatient cases, between 1st January and 31st December 2014 from eleven surveillance sites across Kenya and used phylogenetics to characterise virus introductions and spread. RVs were detected throughout the year, with the highest detection rates observed from January to March and June to July. We detected a total of 114 of the 169 currently classified types. Our analysis revealed numerous virus introductions into Kenya characterized by local expansion and extinction, and extensive spatial mixing of types within the country due to the widespread transmission of the virus after an introduction. This work demonstrates that in a single year, the circulation of rhinovirus in Kenya was characterized by substantial genetic diversity, multiple introductions, and extensive geographical spread.

Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) ad hoc meeting, 28 June - 1 July 2024.

The World Health Organization's Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) serves to independently review and evaluate vaccine-related research to maximize the potential impact of vaccination programs. From 28 June - 1 July 2024, IVIR-AC was convened for an ad hoc meeting to discuss new evidence on criteria for rubella vaccine introduction and the risk of congenital rubella syndrome. This report summarizes background information on rubella virus transmission and the burden of congenital rubella syndrome, meeting structure and presentations, proceedings, and recommendations.

Long-term impact of 10-valent pneumococcal conjugate vaccine in Kenya: Nasopharyngeal carriage among children in a rural and an urban site six years after introduction.

BACKGROUND: Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya. METHODS: We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November-December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1-4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung. RESULTS: We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes. CONCLUSION: Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch.

The respiratory syncytial virus vaccine and monoclonal antibody landscape: the road to global access.

Respiratory syncytial virus (RSV) is the second most common pathogen causing infant mortality. Additionally, RSV is a major cause of morbidity and mortality in older adults (age ≥60 years) similar to influenza. A protein-based maternal vaccine and monoclonal antibody (mAb) are now market-approved to protect infants, while an mRNA and two protein-based vaccines are approved for older adults. First-year experience protecting infants with nirsevimab in high-income countries shows a major public health benefit. It is expected that the RSV vaccine landscape will continue to develop in the coming years to protect all people globally. The vaccine and mAb landscape remain active with 30 candidates in clinical development using four approaches: protein-based, live-attenuated and chimeric vector, mRNA, and mAbs. Candidates in late-phase trials aim to protect young infants using mAbs, older infants and toddlers with live-attenuated vaccines, and children and adults using protein-based and mRNA vaccines. This Review provides an overview of RSV vaccines highlighting different target populations, antigens, and trial results. As RSV vaccines have not yet reached low-income and middle-income countries, we outline urgent next steps to minimise the vaccine delay.

Severe lower respiratory tract infection in early infancy and pneumonia hospitalizations among children, Kenya.

Severe lower respiratory tract infection (LRTI) in infants caused by respiratory syncytial virus (RSV) has been associated with later pneumonia hospitalization among children. To determine risk for pneumonia after RSV hospitalization in infancy, we conducted a retrospective cohort analysis of 2,813 infants admitted to a hospital in Kenya and identified readmissions for pneumonia among this group during early childhood (<60 months of age). Incidence of readmission for pneumonia was higher for children whose first admission as infants was for LRTI and who were <3 months of age than for children who were first admitted as infants for non-LRTI, irrespective of RSV status. Incidence of readmission for pneumonia with wheeze was higher for children whose first admission involved RSV compared with those who had non-RSV LRTI. Excess pneumonia risk persisted for 2 years after the initial hospitalization. Close postdischarge follow-up of infants with LRTI, with or without RSV, could help prevent severe pneumonia later in childhood.