African meningitis belt pneumococcal disease epidemiology indicates a need for an effective serotype 1 containing vaccine, including for older children and adults

<p>Abstract</p> <p>Background</p> <p>Pneumococcal conjugate vaccine strategies in GAVI-eligible countries are focusing on infant immunization but this strategy may not be optimal in all settings. We aimed to collect all available population based data on pneumococcal meningitis throughout life in the African meningitis belt and then to model overall meningitis risk to help inform vaccine policy.</p> <p>Methods</p> <p>After a systematic review of literature published from 1970 through the present, we found robust population-based <it>Streptococcus pneumoniae </it>(Sp) meningitis data across age strata for four African meningitis belt countries that included 35 surveillance years spanning from 1970 to 2005. Using these data we modeled disease risk for a hypothetical cohort of 100,000 persons followed throughout life.</p> <p>Results</p> <p>Similar to meningococcal meningitis, laboratory-confirmed pneumococcal meningitis was seasonal, occurring primarily in the dry season. The mean annual Sp meningitis incidence rates were 98, 7.8 to 14, and 5.8 to 12 per 100,000 among persons <1, 1 through 19, and 20 to 99 years of age, respectively, which (in the absence of major epidemics) were higher than meningococcal meningitis incidences for persons less than 1 and over 20 years of age. Mean Sp meningitis case fatality ratios (CFR) among hospitalized patients ranged from 36-66% depending on the age group, with CFR exceeding 60% for all age groups beyond 40 years; depending on the age group, Sp meningitis mortality incidences were 2 to 12-fold greater than those for meningococcal meningitis. The lifetime risks of pneumococcal meningitis disease and death were 0.6% (1 in 170) and 0.3% (1 in 304), respectively. The incidences of these outcomes were highest among children age <1 year. However, the cumulative risk was highest among persons age 5 to 59 years who experienced 59% of pneumococcal meningitis outcomes. After age 5 years and depending on the country, 59-79% of meningitis cases were caused by serotype 1.</p> <p>Conclusions</p> <p>In the African meningitis belt, Sp is as important a cause of meningitis as <it>Neisseria meningitidis</it>, particularly among older children and working age adults. The meningitis belt population needs an effective serotype 1 containing vaccine and policy discussions should consider vaccine use outside of early childhood.</p

From current vaccine recommendations to everyday practices: An analysis in five sub-Saharan African countries

AbstractBackgroundEstimates of WHO and UNICEF vaccination coverage may provide little insight into the extent to which vaccinations are administered on time. Yet, lack of adherence to the recommended age to receive a specific vaccination may have detrimental health consequences. For example, delays in receiving vaccination will prolong the risk of lack of protection, often when disease risk is highest, such as during early infancy. We estimated the reported age at vaccination, and vaccine coverage at different ages in children from five sub-Saharan African countries.MethodsWe analyzed data from the latest Demographic and Health Programme databases available for Burkina Faso 2010 (n=15,044 observations), Ghana 2008 (n=2992), Kenya 2008–9 (n=6079), Senegal 2010–11 (n=12,326), and Tanzania 2010 (n=8023). We assessed, amongst vaccinees, the exact age when vaccine was administered for the three infant doses of pentavalent vaccine (DTP) and the first dose of measles-containing-vaccine (MCV), as well as the proportion of children immunized with these antigens by a certain age. Vitamin A supplementation (VAS) coverage was evaluated as a potential contact visit for vaccine introduction.ResultsFor all DTP doses, the median intervals between recommended and actual ages of receiving vaccination ranged from 12, 17 and 23 days in Kenya, to 22, 33 and 45 days in Senegal. MCV was mostly given during the recommended age of 9 months. In each country, there was a large discrepancy in the median age at DTP vaccination between regions. VAS coverage in young children ranged from 30.3% in Kenya to 78.4% in Senegal, with large variations observed between areas within each study country.ConclusionIn the context of new vaccine introduction, age of children at vaccination should be monitored to interpret data on vaccine-preventable disease burden, vaccine effectiveness, and vaccine safety, and to adapt targeted interventions and messages

Vaccine-preventable haemophilus influenza type B disease burden and cost-effectiveness of infant vaccination in Indonesia.

BACKGROUND: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia. METHODS: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and$3.75 per dose. RESULTS: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and$8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and$74, respectively, versus $4438 and$102 for monovalent vaccine. CONCLUSIONS: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks

Afriflu2—Second international workshop on influenza vaccination in the African continent—8 November 2012, Cape Town (South Africa)

AbstractThe second meeting of the Afriflu conferences took place in Cape Town, South Africa, with over 60 participants from 15 countries in Africa and also outside the continent. Significant progress in surveillance has been made in better understanding the illness burden of influenza on the continent, which limited evidence suggests is greater than that in the developed world. In southern Africa HIV and TB coinfections play a major role in increasing hospitalisation and mortality, while elsewhere in Africa other cofactors still need to be determined.There is currently no indigenous vaccine production in sub-Saharan Africa and only one facility, based in South Africa, capable of filling imported bulk. Innovative vaccine strategies will need to be explored, such as maternal immunisation, and also the possibility of other influenza vaccine options, such as live attenuated influenza vaccine for young children. Sustained indigenous vaccine production is essential for the continent to have vaccine security in the event of a pandemic even though establishing local production faces considerable challenges especially ensuring adequate markets on the continent. There is an urgent need to develop effective communication messages for decision makers as well as healthcare workers addressing the importance of influenza even in the face of the major competing health burdens of the continent

Adjusting for case under-ascertainment in estimating RSV hospitalisation burden of older adults in high-income countries:a systematic review and modelling study

Abstract Introduction Previous studies suggest diagnostic testing characteristics (i.e. variations in clinical specimens and diagnostic tests) can contribute to underestimation of RSV disease burden. We aimed to improve the understanding of RSV hospitalisation burden in older adults (aged ≥ 65 years) in high-income countries through adjusting for case under-ascertainment. Methods We conducted a systematic review to include data on RSV-associated acute respiratory infection (ARI) hospitalisation burden in older adults in high-income countries. To adjust for case under-ascertainment, we developed a two-step framework that incorporated empirical data on the RSV detection proportion of different clinical specimens and testing approaches as well as their statistical uncertainty. We estimated the unadjusted and adjusted RSV-associated hospitalisation burden through multilevel random-effects meta-analysis. We further explored RSV-associated in-hospital mortality burden. Results We included 12 studies with eligible RSV hospitalisation burden data. We estimated that pooled unadjusted hospitalisation rate was 157 per 100,000 (95% CI 98–252) for adults aged ≥ 65 years; the rate was adjusted to 347 per 100,000 (203–595) after accounting for under-ascertainment. The adjusted rate could be translated into 787,000 (460,000–1,347,000) RSV-associated hospitalisations in high-income countries in 2019, which was about 2.2 times the unadjusted estimate. Stratified analysis by age group showed that the adjusted rate increased with age, from 231 per 100,000 in adults aged 65–74 years to 692 per 100,000 in adults aged > 85 years. The in-hospital case fatality ratio of RSV was 6.1% (3.3–11.0) and the total RSV-associated in-hospital deaths in high-income countries in 2019 could be between 22,000 and 47,000. Conclusion This study improves the understanding of RSV-associated hospitalisation burden in older adults and shows that the true RSV-associated hospitalisation burden could be 2.2 times what was reported in existing studies. This study has implications for calculating the benefit of interventions to treat and prevent RSV-associated disease

Incidence of acute lower respiratory tract disease hospitalisations, including pneumonia, among adults in Bristol, UK, 2019, estimated using both a prospective and retrospective methodology

OBJECTIVES: To determine the disease burden of acute lower respiratory tract disease (aLRTD) and its subsets (pneumonia, lower respiratory tract infection (LRTI) and heart failure) in hospitalised adults in Bristol, UK. SETTING: Single-centre, secondary care hospital, Bristol, UK. DESIGN: We estimated aLRTD hospitalisations incidence in adults (≥18 years) in Bristol, UK, using two approaches. First, retrospective International Classification of Diseases 10th revision (ICD-10) code analysis (first five positions/hospitalisation) identified aLRTD events over a 12-month period (March 2018 to February 2019). Second, during a 21-day prospective review (19 August 2019 to 9 September 2019), aLRTD admissions were identified, categorised by diagnosis and subsequently annualised. Hospital catchment denominators were calculated using linked general practice and hospitalisation data, with each practice’s denominator contribution calculated based on practice population and per cent of the practices’ hospitalisations admitted to the study hospital. PARTICIPANTS: Prospective review: 1322 adults screened; 410 identified with aLRTD. Retrospective review: 7727 adult admissions. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence of aLRTD and its subsets in the adult population of Southmead Hospital, Bristol UK. RESULTS: Based on ICD-10 code analysis, annual incidences per 100 000 population were: aLRTD, 1901; pneumonia, 591; LRTI, 739; heart failure, 402. aLRTD incidence was highest among those ≥65 years: 65–74 (3684 per 100 000 adults), 75–84 (6962 per 100 000 adults) and ≥85 (11 430 per 100 000 adults). During the prospective review, 410/1322 (31%) hospitalised adults had aLRTD signs/symptoms and annualised incidences closely replicated retrospective analysis results. CONCLUSIONS: The aLRTD disease burden was high, increasing sharply with age. The aLRTD incidence is probably higher than estimated previously due to criteria specifying respiratory-specific symptoms or radiological change, usage of only the first diagnosis code and mismatch between case count sources and population denominators. This may have significant consequences for healthcare planning, including usage of current and future vaccinations against respiratory infection