Recall and decay of consent information among parents of infants participating in a randomized controlled clinical trial using an audio-visual tool in The Gambia.

Communicating essential research information to low literacy research participants in Africa is highly challenging, since this population is vulnerable to poor comprehension of consent information. Several supportive materials have been developed to aid participant comprehension in these settings. Within the framework of a pneumococcal vaccine trial in The Gambia, we evaluated the recall and decay of consent information during the trial which used an audio-visual tool called 'Speaking Book', to foster comprehension among parents of participating infants. The Speaking Book was developed in the 2 most widely spoken local languages. Four-hundred and 9 parents of trial infants gave consent to participate in this nested study and were included in the baseline assessment of their knowledge about trial participation. An additional assessment was conducted approximately 90 d later, following completion of the clinical trial protocol. All parents received a Speaking Book at the start of the trial. Trial knowledge was already high at the baseline assessment with no differences related to socio-economic status or education. Knowledge of key trial information was retained at the completion of the study follow-up. The Speaking Book (SB) was well received by the study participants. We hypothesize that the SB may have contributed to the retention of information over the trial follow-up. Further studies evaluating the impact of this innovative tool are thus warranted

Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial

Background Neonates born to women infected with HIV are at increased risk for invasive group B streptococcus (GBS) disease. We aimed to compare safety and immunogenicity of trivalent glycoconjugate GBS vaccine in pregnant women with and without HIV in Malawi and South Africa. Methods In our non-randomised phase 2, open-label, multicentre study, we recruited pregnant women attending two antenatal clinics, one in Blantyre, Malawi, and one in Soweto, Johannesburg, South Africa. Participants were divided into three groups on the basis of their HIV infection status (no infection, infection and high CD4 cell count [>350 cells per mu L], and infection and low CD4 cell count [>50 to <= 350 cells per mu L]) and received a 5 mu g dose of glycoconjugate GBS vaccine (serotypes Ia, Ib, and III, with CRM197 [Novartis Vaccines, Siena, Italy]) intramuscularly at 24-35 weeks' gestation. GBS serotype-specific antibody concentrations were measured before vaccination (day 1), day 15, day 31, and at delivery, and in infants at birth and day 42 of life. The primary outcomes were safety in mothers and infants and the amount of placental transfer of GBS serotype-specific antibodies from mothers to their infants. All immunogenicity and safety analyses were done on the full analysis set, including participants who, or whose mother, correctly received the vaccine and who provided at least one valid assessable serum sample. This study is registered with ClinicalTrials.gov, number NCT01412801. Findings 270 women and 266 infants were enrolled between Sept 26, 2011, and Dec 4, 2012 (90 women and 87 infants without HIV, 89 and 88 with HIV and high CD4 cell counts, and 91 and 91 with HIV and low CD4 cell counts, respectively). Seven women were lost to follow-up, six withdrew consent, one died, and two relocated. Eight infants died or were stillborn and two were lost to follow-up. Across serotypes, fold change in antibody concentrations were higher for the HIV-uninfected group than the HIV-infected groups. Transfer ratios were similar across all three groups (0.49-0.72; transfer ratio is infant geometric mean antibody concentration in blood collected within 72 h of birth divided by maternal geometric mean antibody concentration in blood collected at delivery); however, at birth, maternally derived serotype-specific antibody concentrations were lower for infants born to women infected with HIV (0.52-1.62 mu g/mL) than for those born to women not infected with HIV (2.67-3.91 mu g/mL). 151 (57%) of 265 women reported at least one solicited adverse reaction: 39 (45%) of 87 women with HIV and low CD4 cell counts, 52 (59%) of 88 women with HIV and high CD4 cell counts, and 60 (67%) of 90 women in the HIV-uninfected group. 49 (18%) of 269 women had at least one adverse event deemed possibly related to the vaccine (six [7%] in the HIV and low CD4 cell count group, 12 [13%] in the HIV and high CD4 cell count group, and 21 [23%] in the HIV-uninfected group), as did three (1%) of 266 neonates (zero, two [1%], and one [1%]); none of these events was regarded as serious. Interpretation The vaccine was less immunogenic in women infected with HIV than it was in those not infected, irrespective of CD4 cell count, resulting in lower levels of serotype-specific maternal antibody transferred to infants, which could reduce vaccine protection against invasive GBS disease. A validated assay and correlate of protection is needed to understand the potential protective value of this vaccine. Copyright (C) Heyderman et al. Open Access article distributed under the terms of CC BY

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) formulated with 2-phenoxyethanol in multidose vials given with routine vaccination in healthy infants: An open-label randomized controlled trial.

BACKGROUND: This open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS). METHODS: Gambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35μg/mL (primary endpoint) was greater than -10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected. RESULTS: 500 participants were randomized and vaccinated; 489 (MDV: n=245; SDS: n=244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35μg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups. CONCLUSIONS: PCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716

Accuracy of Xpert Ultra in Diagnosis of Pulmonary Tuberculosis among Children in Uganda: a Substudy from the SHINE Trial.

Childhood tuberculosis (TB) presents significant diagnostic challenges associated with paucibacillary disease and requires a more sensitive test. We evaluated the diagnostic accuracy of Xpert MTB/RIF Ultra (Ultra) compared to other microbiological tests using respiratory samples from Ugandan children in the SHINE trial. SHINE is a randomized trial evaluating shorter treatment in 1,204 children with minimal TB disease in Africa and India. Among 352 samples and one cervical lymph node fine needle aspirate, one sample was randomly selected per patient and tested with the Xpert MTB/RIF assay (Xpert) and with Lowenstein-Jensen medium (LJ) and liquid mycobacterial growth indicator tube (MGIT) cultures. We selected only uncontaminated stored sample pellets for Ultra testing. We estimated the sensitivity of Xpert and Ultra against culture and a composite microbiological reference standard (any positive result). Of 398 children, 353 (89%) had culture, Xpert, and Ultra results. The median age was 2.8 years (interquartile range [IQR], 1.3 to 5.3); 8.5% (30/353) were HIV infected, and 54.4% (192/353) were male. Of the 353, 31 (9%) were positive by LJ and/or MGIT culture, 36 (10%) by Ultra, and 16 (5%) by Xpert. Sensitivities (95% confidence intervals [CI]) were 58% (39 to 65% [18/31]) for Ultra and 45% (27 to 64% [14/31]) for Xpert against any culture-positive result, with false positives of <1% and 5.5% for Xpert and Ultra. Against a composite microbiological reference, sensitivities were 72% (58 to 84% [36/50]) for Ultra and 32% (20 to 47% [16/50]) for Xpert. However, there were 17 samples that were positive only with Ultra (majority trace). Among children screened for minimal TB in Uganda, Ultra has higher sensitivity than Xpert. This represents an important advance for a condition which has posed a diagnostic challenge for decades

SARS-CoV-2 seroprevalence in pregnant women in Kilifi, Kenya from March 2020 to March 2022

BackgroundSeroprevalence studies are an alternative approach to estimating the extent of transmission of SARS-CoV-2 and the evolution of the pandemic in different geographical settings. We aimed to determine the SARS-CoV-2 seroprevalence from March 2020 to March 2022 in a rural and urban setting in Kilifi County, Kenya.MethodsWe obtained representative random samples of stored serum from a pregnancy cohort study for the period March 2020 to March 2022 and tested for antibodies against the spike protein using a qualitative SARS-CoV-2 ELISA kit (Wantai, total antibodies). All positive samples were retested for anti-SARS-CoV-2 anti-nucleocapsid antibodies (Euroimmun, ELISA kits, NCP, qualitative, IgG) and anti-spike protein antibodies (Euroimmun, ELISA kits, QuantiVac; quantitative, IgG).ResultsA total of 2,495 (of 4,703 available) samples were tested. There was an overall trend of increasing seropositivity from a low of 0% [95% CI 0–0.06] in March 2020 to a high of 89.4% [95% CI 83.36–93.82] in Feb 2022. Of the Wantai test-positive samples, 59.7% [95% CI 57.06–62.34] tested positive by the Euroimmun anti-SARS-CoV-2 NCP test and 37.4% [95% CI 34.83–40.04] tested positive by the Euroimmun anti-SARS-CoV-2 QuantiVac test. No differences were observed between the urban and rural hospital but villages adjacent to the major highway traversing the study area had a higher seroprevalence.ConclusionAnti-SARS-CoV-2 seroprevalence rose rapidly, with most of the population exposed to SARS-CoV-2 within 23 months of the first cases. The high cumulative seroprevalence suggests greater population exposure to SARS-CoV-2 than that reported from surveillance data

COVID-19 disease and vaccination in pregnancy: understanding knowledge, perceptions and experiences among pregnant women and community leaders in Uganda.

BACKGROUND: We investigated pregnant women and community leaders' knowledge, perceptions and experiences of the coronavirus disease 2019 (COVID-19) vaccination program during pregnancy in Uganda and how this changed over the course of the pandemic. METHODS: We conducted 20 in-depth interviews (IDIs) and two group discussions (GDs) with pregnant women and four GDs with community leaders in Kawempe division of Kampala, Uganda. The first round of IDIs/GDs were carried out in March 2021. In July 2021, telephone IDIs were conducted with 7 pregnant women and 10 community leaders randomly selected from first-round interview participants. Themes were analysed deductively drawing codes from the topic guides. RESULTS: In the first round, the majority of participants thought COVID-19 was not real because of misconceptions around government messaging/motivation and beliefs that Africans would not be affected. In the second round, participants recognised COVID-19 disease, because of rising case numbers and fatalities. There was increased awareness of the benefits of the vaccine. However, pregnant women remained unsure of vaccine safety and quality, citing side effects like fevers and general body weakness. Role models and coherent public health messaging and healthcare workers were key enablers of vaccine uptake. CONCLUSIONS: Targeted and sustained COVID-19 communication and engagement strategies are needed, especially for pregnant women and others in their communities, to improve vaccine confidence during outbreaks

Acceptance of multiple injectable vaccines in a single immunization visit in The Gambia pre and post introduction of inactivated polio vaccine.

BACKGROUND: As the World Health Organization (WHO) currently recommends that children be protected against 11 different pathogens, it is becoming increasingly necessary to administer multiple injectable vaccines during a single immunization visit. In this study we assess Gambian healthcare providers' and infant caregivers' attitudes and practices related to the administration of multiple injectable vaccines to a child at a single immunization visit before and after the 2015 introduction of inactivated polio vaccine (IPV). IPV introduction increased the number of injectable vaccines recommended for the 4-month immunization visit from two to three in The Gambia. METHODS: We conducted a cross-sectional questionnaire-based survey before and after the introduction of IPV at 4months of age in a representative sample of all health facilities providing immunizations in The Gambia. Healthcare providers who administer vaccines at the selected health facilities and caregivers who brought infants for their 4month immunization visit were surveyed. FINDINGS: Prior to IPV introduction, 9.9% of healthcare providers and 35.7% of infant caregivers expressed concern about a child receiving more than 2 injections in a single visit. Nevertheless, 98.8% and 90.9% of infants received all required vaccinations for the visit before and after IPV introduction, respectively. The only reason why vaccines were not received was vaccine stock-outs. Infant caregivers generally agreed that vaccinators could be trusted to provide accurate information regarding the number of vaccines that a child needed. CONCLUSION: Healthcare providers and infant caregivers in this resource limited setting accepted an increase in the number of injectable vaccines administered at a single visit even though some expressed concerns about the increase

Malaria in Children with Sickle Cell Anaemia in Areas with Low, Moderate and High Transmission in Uganda

Background. Few large prospective studies have evaluated burden and outcomes of malaria in children with sickle cell anaemia (SCA) in malaria endemic countries. We evaluated the incidence, complications and outcome of malaria in three cohorts of Ugandan children with SCA in three areas with differing malaria transmission. Methods. Cohort 1 were SCA aged 3-9 years, enrolled in the hydroxyurea therapy for neurological and cognitive protection in Uganda (BRAINSAFE II) trial at Mulago Hospital, a low transmission area, while cohort 2 and 3 aged 6 months to 15 years, were enrolled in the dihydroartemisinin-piperaquine (DP) or sulphadoxine-pyrimethamine (SP) for the chemoprevention of malaria in SCA (CHEMCHA) trial at Jinja Hospital (moderate transmission) and Kitgum Hospital (high transmission). In cohort 1, all received SP for malaria chemoprophylaxis and hydroxyurea at 20-30mg/kg/day, while cohorts 2 and 3, received either DP or SP for malaria chemoprevention, and a proportion (10%) received hydroxyurea in the study. Results. A total of 706 participants were enrolled: 267, 249 and 190 at Mulago, Jinja and Kitgum respectively. The mean age was 6.5 (SD 3.4) years; 5.1 (1.7), 7.9 (4.3) and 6.8 (3.5) years for Mulago, Jinja, and Kitgum respectively. Incidence of malaria was 13 (95% CI 6, 20) per 100 child years in low, 38 (95% CI 26, 51) in moderate and 104 (95% CI 64, 144) in the high transmission area, p<0.001. Adjusting for hydroxyurea treatment, incidence of malaria was 33 (95%CI 14, 52) per 100 child year on hydroxyurea and 51 (95%CI 40, 62) per 100 child years without hydroxyurea, p=0.001. The most common SCA-related complications were anaemia (39.6%, 133/336), and pain (27.7%, 93/336) among children with malaria. Over a period of 1042.8 person years, there were 115 admissions for malaria, with an overall incidence of 11 per 100 child year (95% CI 9, 13), and this differed across sites, p<0.001. Overall, 1.5% (11/706) children died, and 18.2% (2/11) deaths were directly related to malaria infection. Conclusion. Malaria incidence remains high among Ugandan children with SCA, and differs by transmission patterns. Prevention strategies should be strengthened, especially in high transmission areas