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

Abstract

BackgroundPneumococcal 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.MethodsAfter a systematic review of literature published from 1970 through the present, we found robust population-based Streptococcus pneumoniae (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.ResultsSimilar 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.ConclusionsIn the African meningitis belt, Sp is as important a cause of meningitis as Neisseria meningitidis, 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.

Impact of the hajj on pneumococcal transmission

“…Serotypes with higher invasive indices can cause endemic disease, for example in the African meningitis belt [28][29][30], as well as localized outbreaks [31][32][33]. We identified only nine total pneumococci with serotypes associated with a higher invasiveness index (three at the beginning of the Hajj and six at the end).…”

Lack of formyl peptide receptor 1 and 2 leads to more severe inflammation and higher mortality in mice with of pneumococcal meningitis

“…Fpr1 encodes murine Fpr1, which is considered the murine orthologue of human FPR, whereas Fpr-rs2 (mFPR2) encodes a receptor that is most similar to human formyl peptide receptor like 1 (FPRL1) or FPR2. 10,11 It is known that the receptor interacts with a menagerie of structurally diverse ligands including some from bacterial origins beside fMLF, such as Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), derived from Helicobacter pylori, HIV envelope peptides, or is associated with different neurodegenerative disorders, including Alzheimer's and prion disease. 12 Previous works revealed the expression of FPRs in the brain by glial cells.…”

Inflammasome-Dependent IFN-γ Drives Pathogenesis inStreptococcus pneumoniaeMeningitis

“…The Gram-positive extracellular bacterium Streptococcus pneumoniae (pneumococcus) is the most common pathogen in adults and, despite antibiotic therapy, it has the highest mortality of all meningitis-causing agents: 4-16% in children and up to 60% in adults (2)(3)(4). Furthermore, pneumococcal meningitis causes the highest rates of neurologic sequelae (5), with long-term disabilities reported in 27-57% of survivors (6)(7)(8).…”