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Background: Human Immunodeficiency Virus (HIV)-exposed uninfected (HEU) infants have a higher burden of infectious diseases related morbidity and mortality compared with HIV-unexposed uninfected (HUU). Immunization of pregnant women living with HIV (PWLWH) could reduce the severity and burden of infectious diseases for HEU in early infancy. Methods: We conducted a systematic review of safety and immunogenicity of vaccines administered to PWLWH and meta-analyses to test the overall effect of immunogenicity comparing pregnant women without HIV (PWWH) to PWLWH. We searched MEDLINE, Embase, Web of Science, Virtual Health Library and Cochrane databases in accordance with PRISMA guidelines for randomized controlled trials and observational studies. Review articles, case series, conference abstracts, and animal studies were excluded. Studies were included from inception to 6th September 2023, with no language restrictions. Random effects meta-analyses were performed for immunogenicity using Review manager (RevMan) analysis software version 5.4.1, Geometric Mean Titer (GMT) values were transformed to obtain the mean and standard deviation within RevMan, the effect size was computed and reported as mean difference with respective 95% confidence intervals. The review was registered with PROSPERO CRD42021289081. Findings: We included 12 articles, comprising 3744 pregnant women, 1714 were PWLWH given either influenza, pneumococcal or an investigational Group B streptococcal (GBS) vaccine. Five studies described safety outcomes, and no increase in adverse events was reported in PWLWH compared to PWWH. The GMT increase from baseline to 28-35 weeks post vaccination in HA units ranged from 12.4 (95% CI: 9.84-14.9) to 238.8 (95% CI: 0.35-477.9). Meta-analyses of influenza vaccines showed the pooled geometric mean difference in Hemagglutination Inhibition (HAI) titers post vaccination was 56.01 (95% CI: 45.01-67.01), p < 0.001. The increase was less in PWLWH when compared with PWWH: -141.76 (95% CI: -194.96, -88.55), p < 0.001. Interpretation: There are limited data on the safety and immunogenicity of vaccines given to PWLWH making policy consideration in this group difficult when new vaccines are introduced. With new vaccines on the horizon, PWLWH need to be included in studies to promote vaccine confidence for this special population. Funding: This work was funded by Medical Research Council Joint Clinical Trials Round 9 [MR/T004983/1].
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Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda. Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy. Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.
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INTRODUCTION: Community and individual sociodemographic characteristics play an important role in child survival. However, a question remains how urbanisation and demographic changes in sub-Saharan Africa affect community-level determinants for child survival. METHODS: Longitudinal data from the Iganga/Mayuge Health and Demographic Surveillance Site was used to obtain postneonatal under-5 mortality rates between March 2005 and February 2015 in periurban and rural areas separately. Multilevel survival analysis models were used to identify factors associated with mortality. RESULTS: There were 43 043 postneonatal under-5 children contributing to 116 385 person years of observation, among whom 1737 died. Average annual crude mortality incidence rate (IR) differed significantly between periurban and rural areas (9.0 (8.1 to 10.0) per 1000 person-years vs 18.1 (17.1 to 19.0), respectively). In periurban areas, there was evidence for decreasing mortality from IR=11.3 (7.7 to 16.6) in 2006 to IR=4.5 (3.0 to 6.9) in 2015. The mortality fluctuated with no evidence for reduction in rural areas (IR=19.0 (15.8 to 22.8) in 2006; IR=15.5 (13.0 to 18.6) in 2015). BCG vaccination was associated with reduced mortality in periurban and rural areas (adjusted rate ratio (aRR)=0.45; 95% CI 0.30 to 0.67 and aRR=0.56; 95% CI 0.41 to 0.76, respectively). Maternal education level within the community was associated with reduced mortality in both periurban and rural sites (aRR=0.83; 95% CI 0.70 to 0.99; aRR=0.90; 95% CI 0.81 to 0.99). The proportion of households in the poorest quintile within the community was associated with mortality in rural areas only (aRR=1.08; 95% CI 1.00 to 1.18). In rural areas, a large disparity existed between the least poor and the poorest (aRR=0.50; 95% CI 0.27 to 0.92). CONCLUSION: We found evidence for a mortality decline in peri-urban but not rural areas. Investments in the known key health (eg, vaccination) and socio-economic interventions (education, and economic development) continue to be crucial for mortality declines. Focused strategies to eliminate the disparity between wealth quintiles are also warranted. There may be equitable access to health services in peri-urban areas but improved metrics of socioeconomic position suitable for peri-urban residents may be needed.
