Rabies vaccine and immunoglobulin supply and logistics: Challenges and opportunities for rabies elimination in Kenya

Prompt provision of post-exposure-prophylaxis (PEP) including vaccines and rabies immunoglobulin (RIG) to persons bitten by suspect rabid dogs is a key strategy to eliminating human deaths from dog-mediated rabies in Kenya by 2030. We assessed the availability, forecasting and supply chain logistics for rabies PEP in Kenya, compared with the system used for vaccines in the expanded program of immunization (routine vaccines). Semi-structured questionnaires capturing data on forecasting, procurement, distribution, cold chain and storage, monitoring and reporting for routine vaccines and rabies vaccines and RIG were administered to 35 key personnel at the national, county, sub-county and health facility levels in five counties. Results showed large variability in PEP availability (stockouts ranged from 3 to 36 weeks per year) with counties implementing rabies elimination activities having shorter stockouts. PEP is administered intramuscularly using the 5-dose Essen regimen (day 0, 3, 7, 14 and 28). PEP costs to bite patients were reported to range from 10 to 15 US dollars per dose; RIG was seldom available. A less robust supply and logistics infrastructure is used for rabies PEP compared to routine vaccines. Forecasting and monitoring mechanisms for rabies PEP was poor in the study counties. The supply of vaccines from the national to the sub-national level is mainly through two government agencies and a private agency. Since government decentralization, the National Vaccine and Immunization Program has remained as the main supplier of the routine vaccines, playing a lesser role in the supply of rabies biologicals. Adoption of the dose-saving intradermal route for PEP administration, reduction of PEP costs to patients, and placing rabies vaccines within the routine vaccines supply and logistics system would significantly improve PEP availability and accessibility to persons at risk of rabies; a critical step to achieving elimination of human deaths from rabies

Sustaining pneumococcal vaccination after transitioning from Gavi support: a modelling and cost-effectiveness study in Kenya

Background: In 2009, Gavi, the World Bank, and donors launched the pneumococcal Advance Market Commitment, which helped countries access more affordable pneumococcal vaccines. As many low-income countries begin to reach the threshold at which countries transition from Gavi support to self-financing (3-year average gross national income per capita of US$1580), they will need to consider whether to continue pneumococcal conjugate vaccine (PCV) use at full cost or to discontinue PCV in their childhood immunisation programmes. Using Kenya as a case study, we assessed the incremental cost-effectiveness of continuing PCV use. Methods: In this modelling and cost-effectiveness study, we fitted a dynamic compartmental model of pneumococcal carriage to annual carriage prevalence surveys and invasive pneumococcal disease (IPD) incidence in Kilifi, Kenya. We predicted disease incidence and related mortality for either continuing PCV use beyond 2022, the start of Kenya's transition from Gavi support, or its discontinuation. We calculated the costs per disability-adjusted life-year (DALY) averted and associated 95$15·8 million annually compared with discontinuing vaccination. We predicted that the incremental cost per DALY averted of continuing PCV would be $153 (95$1445, and in comparison to other vaccines, continued PCV use at full costs is cost-effective (on the basis of the assumption that any reduction in disease will translate to a reduction in mortality). Although affordability is likely to be a concern, our findings support an expansion of the vaccine budget in Kenya. Funding: Wellcome Trust and Gavi, the Vaccine Alliance

Cohort profile : the Kilifi vaccine monitoring study

The Kilifi Vaccine Monitoring Study (KiVMS) is a long-term continuous cohort study set up to investigate effectiveness, impact, coverage, safety and indirect vaccine effects by recruiting birth cohorts and, where applicable, cohorts of older and adults. It is based in the area covered by the Kilifi Health and Demographic Surveillance System, Kilifi, Kenya, and currently has records of 33 962 children in the birth cohort database. A major strength of KiVMS is its unique integration of a vaccine registry, a morbidity surveillance system and the largest health and demographic surveillance system (HDSS) in Africa

Assessment of missed opportunities for vaccination in Kenyan health facilities, 2016.

BACKGROUND: In November 2016, the Kenya National Vaccines and Immunization Programme conducted an assessment of missed opportunities for vaccination (MOV) using the World Health Organization (WHO) MOV methodology. A MOV includes any contact with health services during which an eligible individual does not receive all the vaccine doses for which he or she is eligible. METHODS: The MOV assessment in Kenya was conducted in 10 geographically diverse counties, comprising exit interviews with caregivers and knowledge, attitudes, and practices (KAP) surveys with health workers. On the survey dates, which covered a 4-day period in November 2016, all health workers and caregivers visiting the selected health facilities with children <24 months of age were eligible to participate. Health facilities (n = 4 per county) were purposively selected by size, location, ownership, and performance. We calculated the proportion of MOV among children eligible for vaccination and with documented vaccination histories (i.e., from a home-based record or health facility register), and stratified MOV by age and reason for visit. Timeliness of vaccine doses was also calculated. RESULTS: We conducted 677 age-eligible children exit interviews and 376 health worker KAP surveys. Of the 558 children with documented vaccination histories, 33% were visiting the health facility for a vaccination visit and 67% were for other reasons. A MOV was seen in 75% (244/324) of children eligible for vaccination with documented vaccination histories, with 57% (186/324) receiving no vaccinations. This included 55% of children visiting for a vaccination visit and 93% visiting for non-vaccination visits. Timeliness for multi-dose vaccine series doses decreased with subsequent doses. Among health workers, 25% (74/291) were unable to correctly identify the national vaccination schedule for vaccines administered during the first year of life. Among health workers who reported administering vaccines as part of their daily work, 39% (55/142) reported that they did not always have the materials they needed for patients seeking immunization services, such as vaccines, syringes, and vaccination recording documents. CONCLUSIONS: The MOV assessment in Kenya highlighted areas of improvement that could reduce MOV. The results suggest several interventions including standardizing health worker practices, implementing an orientation package for all health workers, and developing a stock management module to reduce stock-outs of vaccines and vaccination-related supplies. To improve vaccination coverage and equity in all counties in Kenya, interventions to reduce MOV should be considered as part of an overall immunization service improvement plan

Effectiveness of monovalent rotavirus vaccine against hospitalization with acute rotavirus gastroenteritis in Kenyan children

Rotavirus remains a leading cause of diarrheal illness and death among children worldwide. Data on rotavirus vaccine effectiveness in sub-Saharan Africa are limited. Kenya introduced monovalent rotavirus vaccine (RV1) in July 2014. We assessed RV1 effectiveness against rotavirus-associated hospitalization in Kenyan children. Between July-2014 and December-2017, we conducted surveillance for acute gastroenteritis (AGE) in three hospitals across Kenya. We analysed data from children age-eligible for ≥1 RV1 dose, with stool tested for rotavirus and confirmed vaccination history. We compared RV1 coverage among those who tested rotavirus-positive (cases) versus rotavirus-negative (controls) using multivariable logistic regression; effectiveness was 1-adjusted odds ratio for vaccination x100%. Among 677 eligible children, 110 (16%) were rotavirus-positive. Vaccination data were available for 91 (83%) cases; 51 (56%) had received 2 RV1 doses and 33 (36%) 0 doses. Among 567 controls, 418 (74%) had vaccination data; 308 (74%) had 2 doses and 69 (16%) 0 doses. Overall 2-dose effectiveness was 64% (95% confidence interval [CI]: 35-80%); for children aged <12 months 67% (95%CI: 30-84%) and children aged ≥12 months 72% (95%CI: 10-91%). Significant effectiveness was seen in children with normal weight-for-age (84% [95%CI: 62-93%]), length/height-for-age (75% [95%CI: 48-88%]) and weight-for-length/height (84% [95%CI: 64-93%]); however, no protection was found among underweight, stunted nor wasted children. RV1 in the routine Kenyan immunization program provides significant protection against rotavirus AGE hospitalization. Protection was sustained beyond infancy. Malnutrition appears to diminish vaccine effectiveness. Efforts to improve rotavirus vaccine uptake and nutritional status are important to maximize vaccine benefit. [Abstract copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Impact of the Introduction of Rotavirus Vaccine on Hospital Admissions for Diarrhea Among Children in Kenya: A Controlled Interrupted Time-Series Analysis.

BACKGROUND: Monovalent rotavirus vaccine, Rotarix (GlaxoSmithKline), was introduced in Kenya in July 2014 and is recommended to infants as oral doses at ages 6 and 10 weeks. A multisite study was established in 2 population-based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalizations (RVHs). METHODS: Hospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhea hospitalizations among children aged <5 years in 2 health facilities in Kenya. A controlled interrupted time-series analysis was undertaken to compare RVH pre- and post-vaccine introduction using rotavirus-negative cases as a control series. The change in incidence post-vaccine introduction was estimated from a negative binomial model that adjusted for secular trend, seasonality, and multiple health worker industrial actions (strikes). RESULTS: Between January 2010 and June 2017 there were 1513 and 1652 diarrhea hospitalizations in Kilifi and Siaya; among those tested for rotavirus, 28% (315/1142) and 23% (197/877) were positive, respectively. There was a 57% (95% confidence interval [CI], 8-80%) reduction in RVHs observed in the first year post-vaccine introduction in Kilifi and a 59% (95% CI, 20-79%) reduction in Siaya. In the second year, RVHs decreased further at both sites, 80% (95% CI, 46-93%) reduction in Kilifi and 82% reduction in Siaya (95% CI. 61-92%); this reduction was sustained at both sites into the third year. CONCLUSIONS: A substantial reduction in RVHs and all-cause diarrhea was observed in 2 demographic surveillance sites in Kenya within 3 years of vaccine introduction

Population-Based Incidence of Typhoid Fever in an Urban Informal Settlement and a Rural Area in Kenya: Implications for Typhoid Vaccine Use in Africa

Background: High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene. Methods: During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated. Results: In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5–9 years old (596 per 100,000 pyo) and 2–4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2–4 and 5–9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2–4 year old urban children (2,243 per 100,000 pyo) which were.15-fold higher than rates in the rural site for the same age group

Differing Burden and Epidemiology of Non-Typhi Salmonella Bacteremia in Rural and Urban Kenya, 2006–2009

BACKGROUND: The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change. METHODS: As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006-2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0°C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured. RESULTS: NTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman's correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy. CONCLUSIONS: NTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa

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