Immunogenicity and Efficacy of Pneumococcal Conjugate Vaccine (Prevenar13®) in Preventing Acquisition of Carriage of Pneumococcal Vaccine Serotypes in Tanzanian Children With HIV/AIDS.

In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear to have higher rates of pneumococcal carriage and invasive disease. Successful immunity is dependent on mounting a sufficient immune response to the vaccine. We conducted a double blinded crossover randomised controlled trial to determine the serum antibody response (≥4-fold and geometric mean concentration) to pneumococcal vaccine (PCV13) serotypes at 3 months after second vaccination. We also determined the number and proportion of children carrying new (not present at baseline) vaccine serotypes of S. pneumoniae isolated from nasopharynx at 6 months post initial vaccination in recipients of Prevenar13® compared with those given Haemophilus influenzae-type b (Hib) vaccine (control). The study was conducted at St Augustine's also known as Teule Hospital in Muheza, Tanga Tanzania. 225 HIV infected children aged 1-14 years were enrolled from Jan 2013 to Nov 2013 and randomised to Prevenar13® or Hib vaccines each given at baseline and 2-3 months later. Nasopharyngeal and serum samples were collected at baseline and 4-6 months later. Serotyping was done by Quellung Reaction using Staten antisera. Serum antibodies were ELISA quantified. The study revealed a non-significant reduction in the acquisition of new vaccine serotypes of S. pneumoniae in the recipients of PCV13 by nearly a third compared to those who received Hib vaccine. The vaccine efficacy was 30.5% (95% confidence interval [CI] -6.4-54.6%, P = 0.100)]. The antibody response was not enough to induce a 4-fold rise in GMC in 7 of the 13 vaccine serotypes. When combining the effects of preventing new acquisition and clearing existing vaccine type carriage, the overall efficacy was 31.5% (95% CI 1.5-52.4%, P = 0.045). In the PCV13 group, the proportion of participants carrying vaccine serotype was significantly lower after 2 doses of PCV13 (30%; 32/107), compared with the baseline proportion (48%; 51/107). The introduction of PCV13 targeting HIV-positive children in a setting similar to Tanzania is likely to be associated with appreciable decrease in the acquisition and carriage of pneumococci, which is an important marker of the likely effect of the vaccine on pneumococcal disease. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335579, identifier ACTRN12610000999033.

Nasopharyngeal carriage of Streptococcus pneumoniae: prevalence and risk factors in HIV-positive children in Tanzania.

BACKGROUND: Pneumococcal colonization of the nasopharynx is especially common in young children and is a pre-requisite for pneumococcal disease. Those with immunosuppression, such as HIV, are at higher risk of colonization and disease, especially at older ages. Currently, vaccination schedules are only offered to children under 6 months of age, despite the large impact of pneumococcal disease in older unvaccinated children with HIV. We conducted a study to assess the prevalence of, and risk factors for, pneumococcal carriage in HIV-positive children aged <15 years. METHODS: We collected a single nasopharyngeal swab from 142 HIV-infected children aged 1-14 years over a 2-month period. To detect carriage of pneumococcus, these samples were cultured and serotyped; PCR was performed on negative samples. We also collected epidemiological data via survey and medical records. RESULTS: The overall carriage rate was 81% and was at least 76% in those aged 5-14 years. The 7-, 10-, and 13-valent pneumococcal vaccines would cover 37%, 37%, and 49% of children with carriage, respectively. In the multivariate analysis, we identified increase in weight since last visit (p=0.028) and the existence of care-givers who had respiratory symptoms in the past week (p=0.022) as risk factors for carriage. Weight gain was also significantly associated with antiretroviral use (p=0.002). CONCLUSIONS: These data illuminate the little known area of pneumococcal carriage in older HIV-infected children as well as finding novel risk factors for pneumococcal carriage, namely the association with household members who have respiratory symptoms and with an increase in the child's weight prior to swabbing. Weight gain may be due to an increase in health enabling more mobility and increasing the risk of acquiring carriage. The carriage rate observed (81%) is one of the highest recorded. Further research should address whether vaccination can prevent the acquisition of carriage and so protect against disease.