Invasive Pneumococcal Disease in Neonates Prior to Pneumococcal Conjugate Vaccine Use in South Africa: 2003-2008.

BACKGROUND: Neonatal invasive pneumococcal disease (IPD) in developing countries is poorly described. We provide a baseline description of neonatal IPD in South Africa, before implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009. METHODS: Data from children (age ≤ 2 years) with IPD (pneumococcus identified from a normally sterile specimen) from January 2003 to December 2008 were extracted from a national laboratory-based surveillance database. Clinical and laboratory characteristics of IPD among neonates (0-27 days old) was compared with IPD among young children (≥ 28 days ≤ 2 years). Early-onset IPD (0-6 days old) was compared with late-onset IPD (≥ 7-27 days old). Isolates were serotyped using the Quellung reaction. RESULTS: Overall 27,630 IPD cases were reported. Of the 26,277 (95%) with known ages, 6583 (25%) were ≤ 2 years of age, of which 4.5% (294/6583) were neonates. The estimated annual incidence of neonatal IPD in 2008 was 5 per 100,000 live births. Fifty-one percent of neonates with IPD presented with early-onset IPD. Case fatality ratios (CFRs) were high in both groups, 31% (28/89) in neonatal IPD versus 26% (614/2383) in non-neonatal IPD (P = 0.18). Among neonates, the meningitis cases (15/37, 41%) were associated with the highest CFR. The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes accounted for 69% (134/194) of neonatal IPD isolates. CONCLUSIONS: Pneumococcal neonatal disease in South Africa was not uncommon before PCV introduction and is associated with a high CFR. The indirect effect on neonatal IPD of PCV rollout requires further evaluation.

Declining Incidence of Invasive Meningococcal Disease in South Africa: 2003-2016.

BACKGROUND: Invasive meningococcal disease (IMD) is endemic to South Africa, where vaccine use is negligible. We describe the epidemiology of IMD in South Africa. METHODS: IMD cases were identified through a national, laboratory-based surveillance program, GERMS-SA, from 2003-2016. Clinical data on outcomes and human immunodeficiency virus (HIV) statuses were available from 26 sentinel hospital sites. We conducted space-time analyses to detect clusters of serogroup-specific IMD cases. RESULTS: Over 14 years, 5249 IMD cases were identified. The incidence was 0.97 cases per 100 000 persons in 2003, peaked at 1.4 cases per 100 000 persons in 2006, and declined to 0.23 cases per 100 000 persons in 2016. Serogroups were confirmed in 3917 (75%) cases: serogroup A was present in 4.7% of cases, B in 23.3%, C in 9.4%; W in 49.5%; Y in 12.3%, X in 0.3%; Z in 0.1% and 0.4% of cases were non-groupable. We identified 8 serogroup-specific, geo-temporal clusters of disease. Isolate susceptibility was 100% to ceftriaxone, 95% to penicillin, and 99.9% to ciprofloxacin. The in-hospital case-fatality rate was 17% (247/1479). Of those tested, 36% (337/947) of IMD cases were HIV-coinfected. The IMD incidence in HIV-infected persons was higher for all age categories, with an age-adjusted relative risk ratio (aRRR) of 2.5 (95% confidence interval [CI] 2.2-2.8; P < .001) from 2012-2016. No patients reported previous meningococcal vaccine exposure. Patients with serogroup W were 3 times more likely to present with severe disease than those with serogroup B (aRRR 2.7, 95% CI 1.1-6.3); HIV coinfection was twice as common with W and Y diseases (aRRR W = 1.8, 95% CI 1.1-2.9; aRRR Y = 1.9, 95% CI 1.0-3.4). CONCLUSIONS: In the absence of significant vaccine use, IMD in South Africa decreased by 76% from 2003-2016. HIV was associated with an increased risk of IMD, especially for serogroup W and Y diseases.

Effectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine effectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the effectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. METHODS: Cases of invasive pneumococcal disease in children aged 5 years or younger were identified through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine effectiveness as a percentage, with the equation 1 - [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine effectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. FINDINGS: Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The effectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (-35 to 100) among three case-control sets of children with HIV infection. PCV13 effectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI -12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine effectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV. INTERPRETATION: Our results indicate that PCV13 in a 2 + 1 schedule is effective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine effectiveness in children infected with HIV was high, it did not reach significance, possibly because of the small sample size. These findings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries. FUNDING: Gavi, The Vaccine Alliance.

Epidemiology of Serotype 1 Invasive Pneumococcal Disease, South Africa, 2003-2013.

In South Africa, 7-valent pneumococcal conjugate vaccine (PCV) was introduced in April 2009 and replaced with 13-valent PCV in April 2011. We describe the epidemiology of serotype 1 Streptococcus pneumoniae disease during the pre- and post-PCV eras (2003-2013). Using laboratory-based invasive pneumococcal disease (IPD) surveillance, we calculated annual incidences, identified IPD clusters, and determined serotype 1-associated factors. Of 46,483 IPD cases, 4,544 (10%) were caused by serotype 1. Two clusters of serotype 1 infection were detected during 2003-2004 and 2008-2012, but incidence decreased after 2011. Among children <5 years of age, those who had non-serotype 1 IPD had shorter hospital stays, fewer cases of penicillin-nonsusceptible disease, and lower HIV prevalence and in-hospital death rates than did those with serotype 1 IPD; similar factors were noted for older patients. Serotype 1 IPD had distinctive clinical features in South Africa, and annual incidences fluctuated, with decreases noted after the introduction of PCV13.

Increased risk for and mortality from invasive pneumococcal disease in HIV-exposed but uninfected infants aged <1 year in South Africa, 2009-2013.

BACKGROUND: High antenatal human immunodeficiency virus (HIV) seroprevalence rates (∼ 30%) with low perinatal HIV transmission rates (2.5%), due to HIV prevention of mother-to-child transmission program improvements in South Africa, has resulted in increasing numbers of HIV-exposed but uninfected (HEU) children. We aimed to describe the epidemiology of invasive pneumococcal disease (IPD) in HEU infants. METHODS: We conducted a cross-sectional study of infants aged <1 year with IPD enrolled in a national, laboratory-based surveillance program for incidence estimations. Incidence was reported for 2 time points, 2009 and 2013. At enhanced sites we collected additional data including HIV status and in-hospital outcome. RESULTS: We identified 2099 IPD cases in infants from 2009 to 2013 from all sites. In infants from enhanced sites (n = 1015), 92% had known HIV exposure status and 86% had known outcomes. IPD incidence was highest in HIV-infected infants, ranging from 272 to 654 per 100,000 population between time points (2013 and 2009), followed by HEU (33-88 per 100,000) and HIV-unexposed and uninfected (HUU) infants (18-28 per 100,000). The case-fatality rate in HEU infants (29% [74/253]) was intermediate between HUU (25% [94/377]) and HIV-infected infants (34% [81/242]). When restricted to infants <6 months of age, HEU infants (37% [59/175]) were at significantly higher risk of dying than HUU infants (32% [51/228]; adjusted relative risk ratio, 1.76 [95% confidence interval, 1.09-2.85]). DISCUSSION: HEU infants are at increased risk of IPD and mortality from IPD compared with HUU children, especially as young infants. HEU infants, whose numbers will likely continue to increase, should be prioritized for interventions such as pneumococcal vaccination along with HIV-infected infants and children.