Pneumococcal Mortality Research Articles

Societal Cost of Racial Pneumococcal Disease Disparities in US Adults Aged 50 Years or Older.

This study aimed to estimate the societal cost of racial disparities in pneumococcal disease among US adults aged ≥ 50 years. In a model-based analysis, societal costs of invasive pneumococcal disease (IPD) and hospitalized nonbacteremic pneumococcal pneumonia (NBP) were estimated using (1) direct medical costs plus indirect costs of acute illness; (2) indirect costs of pneumococcal mortality; and (3) direct and indirect costs of related disability. Disparities costs were calculated as differences in average per-person pneumococcal disease cost between Black and non-Black adults aged ≥ 50 years multiplied by the Black population aged ≥ 50 years. Costs were in 2019 US dollars (US$), with future costs discounted at 3% per year. Total direct and indirect costs per IPD case were US$186,791 in Black populations and US$182,689 in non-Black populations; total hospitalized NBP costs per case were US$100,632 (Black) and US$96,781 (non-Black). The difference in population per-person total pneumococcal disease costs between Black and non-Black adults was US$47.85. Combined societal costs of disparities for IPD and hospitalized NBP totaled US$673.2 million for Black adults aged ≥ 50 years. Disease and disability risks, life expectancy, and case-fatality rates were influential in one-way sensitivity analyses, but the lowest cost across all analyses was US$194 million. The 95% probability range of racial disparity costs were US$227.2-US$1156.9 million in a probabilistic sensitivity analysis. US societal cost of racial pneumococcal disease disparities in persons aged ≥ 50years is substantial. Successful pneumococcal vaccination policy and programmatic interventions to mitigate these disparities could decrease costs and improve health.

Burden of pneumococcal disease in children in Cuba before the introduction of a novel pneumococcal conjugate vaccine

# Background The Cuban heptavalent conjugate pneumococcal vaccine will be introduced for children beginning in 2020. We estimated the burden of pneumococcal cases and deaths in children 1-59 months in 2015. # Methods Mortality and morbidity attributable to pneumococcus were estimated for each of the three primary syndromes commonly associated with pneumococcus: pneumonia, meningitis, and invasive non-pneumonia, non-meningitis (NPNM). Vaccine randomized clinical trial data were used to estimate the proportion of pneumonia deaths attributable to pneumococcus. Data from Cuba were obtained from two domestic sources: National Bacterial Meningitis Surveillance System and the laboratory register from the National Reference Laboratory. Syndrome-specific pneumococcal mortality proportions were applied to all-cause pneumonia and meningitis death estimates prepared by the World Health Organization Maternal Child Epidemiology Estimation (WHO/MCEE) collaboration. The proportion of pneumonia cases attributable to pneumococcus was applied to estimates of all-cause clinical and severe pneumonia also prepared by the WHO/MCEE collaboration. Pneumococcal NPNM morbidity and mortality estimates were prepared using the ratio pneumococcal meningitis to pneumococcal invasive disease. Estimates were adjusted for HIV prevalence and access to health care. # Results In 2015, pneumococcus was estimated to cause 970 severe cases (uncertainty range, UR=692-1209) and 39 deaths (UR=23-59) among children 1-59 months. The estimated incidence rate of severe pneumonia was 149 (UR=112-170) per 100,000 children 1-59 months. The estimated case fatality ratio (CFR) was 2% (UR=1-2%). Over a period of one year, 22 deaths were attributed to pneumococcal pneumonia (UR=16-23), 9 (UR=14-19) to pneumococcal meningitis, and 8 (UR=3-17) to pneumococcal bacteremia. The CFR due pneumococcal meningitis was 18% (UR= 8-37%) in 2015. # Conclusions Reduced morbidity and mortality due to pneumococcal disease in Cuba could be achieved with the accelerated introduction of a novel PCV product in children.

Impact of vaccination delay on deaths averted by pneumococcal conjugate vaccine: Modeled effects in 8 country scenarios

Delay in vaccination from schedule has been frequently documented and varies by vaccine, dose, and setting. Vaccination delay may result in the failure to prevent deaths that would have been averted by on-schedule vaccination.We constructed a model to assess the impact of delay in vaccination with pneumococcal conjugate vaccine (PCV) on under-five mortality. The model accounted for the week of age-specific risk of pneumococcal mortality, direct effect of vaccination, and herd protection. For each model run, a cohort of children were exposed to the risk of mortality and protective effect of PCV for each week of age from birth to age five. The model was run with and without vaccination delay and difference in number of deaths averted was calculated. We applied the model to eight country-specific vaccination scenarios, reflecting variations in observed vaccination delay, PCV coverage, herd effect, mortality risk, and vaccination schedule. As PCV is currently being scaled up in India, we additionally evaluated the impact of vaccination delay in India under various delay scenarios and coverage levels.We found deaths averted by PCV with and without delay to be comparable in all of the country scenarios when accounting for herd protection. In India, the greatest relative difference in deaths averted was observed at low coverage levels and greatest absolute difference was observed around 60% vaccination coverage. Under moderate delay scenarios, vaccination delay had modest impact on deaths averted by PCV in India across levels of coverage or vaccination schedule. Without accounting for herd protection, vaccination delay resulted in much greater failure to avert deaths.Our model suggests that realistic vaccination delay has a minimal impact on the number of deaths averted by PCV when accounting for herd effect. High population coverage can largely over-ride the deleterious effect of vaccination delay through herd protection.

Global Pneumococcal Disease and Policies for Control

Global Pneumococcal Disease and Policies for Control

Genome Analysis of a Highly Virulent Serotype 1 Strain of Streptococcus pneumoniae from West Africa

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia, estimated to cause 2 million deaths annually. The majority of pneumococcal mortality occurs in developing countries, with serotype 1 a leading cause in these areas. To begin to better understand the larger impact that serotype 1 strains have in developing countries, we characterized virulence and genetic content of PNI0373, a serotype 1 strain from a diseased patient in The Gambia. PNI0373 and another African serotype 1 strain showed high virulence in a mouse intraperitoneal challenge model, with 20% survival at a dose of 1 cfu. The PNI0373 genome sequence was similar in structure to other pneumococci, with the exception of a 100 kb inversion. PNI0373 showed only15 lineage specific CDS when compared to the pan-genome of pneumococcus. However analysis of non-core orthologs of pneumococcal genomes, showed serotype 1 strains to be closely related. Three regions were found to be serotype 1 associated and likely products of horizontal gene transfer. A detailed inventory of known virulence factors showed that some functions associated with colonization were absent, consistent with the observation that carriage of this highly virulent serotype is unusual. The African serotype 1 strains thus appear to be closely related to each other and different from other pneumococci despite similar genetic content.

Mortality reductions for older adults differ by race/ethnicity and gender since the introduction of adult and pediatric pneumococcal vaccines.

We determined the effectiveness of a 23-valent-polysaccharide pneumococcal vaccine (PPV-23) and pneumococcal conjugate vaccine (PCV-7) in reducing adult pneumococcal mortality by comparing historically predicted declines in pneumococcal disease mortality with observed patterns since the introduction of PPV-23 and PCV-7, including analyses of age, gender, and racial/ethnic subgroups. We analyzed all deaths registered on U.S. death certificates reporting any site of pneumococcal infection (e.g., meningitis, sepsis, pneumonia, bacteremia, and peritonitis) from 1968 to 2006. We used time-series dynamic linear regression on annual pneumococcal mortality rates to determine the percentage reduction in post-1983 mortality rates for a given increase in PPV-23 vaccination rates and post-2000 mortality rates for a given increase in PCV-7 vaccination rates. Pneumococcal mortality decreased well before the introduction of PPV-23 in 1983 and again before the introduction of PCV-7 in 2000. The level of PPV-23 vaccination was associated with a direct and significant reduction in adult mortality, especially white female adults > or = 65 years of age. In contrast, the level of PCV-7 vaccination in the population was not associated with an indirect and significant reduction in pneumococcal mortality beyond the historical pace of decline. PPV-23 introduction was associated with a reduction in pneumococcal mortality among older adults > or = 65 years of age beyond levels predicted by secular trends, whereas PCV-7 introduction was not. Mortality reduction was not uniformly experienced across the population, revealing the need for additional strategies to reduce pneumococcal mortality in older adults.