Potential effect modification of RTS,S/AS01 malaria vaccine efficacy by household socio-economic status.

BACKGROUND: In the phase III RTS,S /AS01 trial, significant heterogeneity in efficacy of the vaccine across study sites was seen. Question on whether variations in socio - economic status (SES) of participant contributed to the heterogeinity of the vaccine efficacy (VE) remains unknown. METHODS: Data from the Phase III RTS,S /AS01 trial in children aged 5-17 months in Kintampo were re-analysed. SES of each child was derived from the Kintampo Health and Demographic Surveillance System, using principal component analysis of household assets. Extended Cox regression was used to estimate the interaction between RTS,S/AS01 VE and household SES. RESULTS: Protective efficacy of the RTS,S/AS0 vaccine significantly varied by participant's household SES, thus increase in household SES was associated with an increase in protective efficacy (P-value = 0.0041). Effect modification persisted after adjusting for age at first vaccination, gender, distance from community to the health facility, child's haemoglobin level, household size, place of residence and mothers' educational level. CONCLUSION: Household SES may be a proxy for malaria transmission intensity. The study showed a significant modification of the RTS,S/AS01 malaria vaccine efficacy by the different levels of child's household socio - economic status. TRIAL REGISTRATION: Efficacy of GSK Biologicals' candidate malaria vaccine (25049) against malaria disease in infants and children in Africa. NCT00866619 prospectively registered on 20 March 2009.

Longitudinal estimation of Plasmodium falciparum prevalence in relation to malaria prevention measures in six sub-Saharan African countries.

BACKGROUND: Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. METHODS: This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013. Participants were enrolled in a 2:1:1 ratio according to age category: 6 months-4 years, 5-19 years, and ≥ 20 years, respectively, per year and per centre. All sites carried out surveys 1-3 while survey 4 was conducted only in 3 sites. Surveys were usually performed during the peak malaria parasite transmission season, in one home visit, when medical history and malaria risk factors/prevention measures were collected, and a blood sample taken for rapid diagnostic test, microscopy, and haemoglobin measurement. PfPR was estimated by site and age category. RESULTS: Overall, 6401 (survey 1), 6411 (survey 2), 6400 (survey 3), and 2399 (survey 4) individuals were included in the analyses. In the 6 months-4 years age group, the lowest prevalence (assessed using microscopy) was observed in 2 Tanzanian centres (4.6% for Korogwe and 9.95% for Bagamoyo) and Lambaréné, Gabon (6.0%), while the highest PfPR was recorded for Nanoro, Burkina Faso (52.5%). PfPR significantly decreased over the 3 years in Agogo (Ghana), Kombewa (Kenya), Lilongwe (Malawi), and Bagamoyo (Tanzania), and a trend for increased PfPR was observed over the 4 surveys for Kintampo, Ghana. Over the 4 surveys, for all sites, PfPR was predominantly higher in the 5-19 years group than in the other age categories. Occurrence of fever and anaemia was associated with high P. falciparum parasitaemia. Univariate analyses showed a significant association of anti-malarial treatment in 4 surveys (odds ratios [ORs]: 0.52, 0.52, 0.68, 0.41) and bed net use in 2 surveys (ORs: 0.63, 0.68, 1.03, 1.78) with lower risk of malaria infection. CONCLUSION: Local PfPR differed substantially between sites and age groups. In children 6 months-4 years old, a significant decrease in prevalence over the 3 years was observed in 4 out of the 8 study sites. Trial registration Clinical Trials.gov identifier: NCT01190202:NCT. GSK Study ID numbers: 114001.

Estimating Annual Fluctuations in Malaria Transmission Intensity and in the Use of Malaria Control Interventions in Five Sub-Saharan African Countries.

RTS,S/AS01E malaria vaccine safety, effectiveness, and impact will be assessed in pre- and post-vaccine introduction studies, comparing the occurrence of malaria cases and adverse events in vaccinated versus unvaccinated children. Because those comparisons may be confounded by potential year-to-year fluctuations in malaria transmission intensity and malaria control intervention usage, the latter should be carefully monitored to adequately adjust the analyses. This observational cross-sectional study is assessing Plasmodium falciparum parasite prevalence (PfPR) and malaria control intervention usage over nine annual surveys performed at peak parasite transmission. Plasmodium falciparum parasite prevalence was measured by microscopy and nucleic acid amplification test (quantitative PCR) in parallel in all participants, and defined as the proportion of infected participants among participants tested. Results of surveys 1 (S1) and 2 (S2), conducted in five sub-Saharan African countries, including some participating in the Malaria Vaccine Implementation Programme (MVIP), are reported herein; 4,208 and 4,199 children were, respectively, included in the analyses. Plasmodium falciparum parasite prevalence estimated using microscopy varied between study sites in both surveys, with the lowest prevalence in Senegalese sites and the highest in Burkina Faso. In sites located in the MVIP areas (Kintampo and Kombewa), PfPR in children aged 6 months to 4 years ranged from 24.8% to 27.3%, depending on the study site and the survey. Overall, 89.5% and 86.4% of children used a bednet in S1 and S2, of whom 68.7% and 77.9% used impregnated bednets. No major difference was observed between the two surveys in terms of PfPR or use of malaria control interventions.

Immunogenicity and safety of the RTS,S/AS01 malaria vaccine co-administered with measles, rubella and yellow fever vaccines in Ghanaian children: A phase IIIb, multi-center, non-inferiority, randomized, open, controlled trial.

BACKGROUND: To optimize vaccine implementation visits for young children, it could be efficient to administer the first RTS,S/AS01 malaria vaccine dose during the Expanded Programme on Immunization (EPI) visit at 6 months of age together with Vitamin A supplementation and the third RTS,S/AS01 dose on the same day as yellow fever (YF), measles and rubella vaccines at 9 months of age. We evaluated the safety and immunogenicity of RTS,S/AS01 when co-administered with YF and combined measles-rubella (MR) vaccines. METHODS: In this phase 3b, open-label, controlled study (NCT02699099), 709 Ghanaian children were randomized (1:1:1) to receive RTS,S/AS01 at 6, 7.5 and 9 months of age, and YF and MR vaccines at 9 or 10.5 months of age (RTS,S coad and RTS,S alone groups, respectively). The third group received YF and MR vaccines at 9 months of age and will receive RTS,S/AS01 at 10.5, 11.5 and 12.5 months of age (Control group). All children received Vitamin A at 6 months of age. Non-inferiority of immune responses to the vaccine antigens was evaluated 1 month following co-administration versus RTS,S/AS01 or EPI vaccines (YF and MR vaccines) alone using pre-defined non-inferiority criteria. Safety was assessed until Study month 4.5. RESULTS: Non-inferiority of antibody responses to the anti-circumsporozoite and anti-hepatitis B virus surface antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus RTS,S/AS01 alone was demonstrated. Non-inferiority of antibody responses to the measles, rubella, and YF antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus YF and MR vaccines alone was demonstrated. The safety profile of all vaccines was clinically acceptable in all groups. CONCLUSIONS: RTS,S/AS01 can be co-administered with Vitamin A at 6 months and with YF and MR vaccines at 9 months of age during EPI visits, without immune response impairment to any vaccine antigen or negative safety effect.

Opinions of Health Professionals on Tailoring Reproductive Health Services to the Needs of Adolescents.

INTRODUCTION: Tailoring sexual and reproductive health programs and services to the needs of adolescents will help adolescents make informed decisions and choices regarding their sexual and reproductive health. OBJECTIVE: To assess the opinions of service providers on tailoring sexual and reproductive health services to the needs of adolescents. METHOD: A qualitative study using indepth interviews was held among eight decision-makers and service providers in two hospitals within the Kintampo North Municipality and Kintampo South District as well as the Municipal and District Health Directorates in Kintampo North and South between April and May 2011. RESULTS: All respondents expressed the opinion that it is a good idea to tailor sexual and reproductive health services to the needs of adolescents. They admitted that very limited sexual and reproductive health programs targeting adolescent needs were available in the study area. Service providers also reported very low levels of health facilities use by adolescents for sexual and reproductive health information and services. Health professionals attributed the poor sexual and reproductive health services utilization by adolescents to stigma from the society and attitudes of service providers. CONCLUSION: There are no targeted sexual and reproductive health programmes and services for adolescents. Services providers indicated that it is important to tailor sexual and reproductive health services to the needs of adolescents to prevent stigma, unwanted pregnancy, abortion, and sexually transmitted infections.

Epidemiology of soil transmitted Helminth infections in the middle-belt of Ghana, Africa.

BACKGROUND: Helminths are among the most widespread infectious agents prevalent in tropical and sub-tropical regions of the developing world defined by inadequate sanitation, poverty and unsafe water sources. This study was carried out to describe the distribution of helminth and malaria parasite infections in the middle-belt of Ghana in sub-Saharan Africa where disease burden, including anaemia is rife and helminths are perceived to be significant contributors of the burden. METHODS: A cross-sectional survey involving 1826 residents located in the middle belt of Ghana where no or very little previous community-based helminth work had been carried out. The participants randomly recruited at household level provided biological samples collected over a 12-month period following a rigorous consenting process and these were analysed to describe the different types and seasonal distribution of helminths. FINDINGS: Overall, 19.3% intestinal helminth infection prevalence was documented. Also based on parasites targeted for elimination, 12.1% Hookworm, 4.0% Hymenolepis nana/Hymenolepis dimunita, 1.5% Ascaris lumbricoides, 1.5% Taenia species, 0.9% Strongyloides stercoralis and 0.8% Trichuris trichiura, with about 1.0% polyphelminthiasis were recorded in the survey. About 55.4% and 44.4% of the participants had heavy hookworm and Trichuris infections respectively. Most of the Ascariasis (83.3%) infections were light in intensity. Hookworm infection was identified with significant odds considering decreasing age (OR = 2.09, p = 0.03), inappropriate footwear use (OR = 1.88, p = 0.021), malaria parasite co-infection (OR = 1.62, p = 0.018), not scrubbing nails during hand washing (OR = 0.68, p = 0.048), source of drinking water (OR = 2.51, p = 0.027) and religion (OR = 4.36, p = 0.002). CONCLUSIONS: Hookworm infection was significantly higher in younger age groups and among those who did not have safe drinking water. Proper sanitation, protective footwear, religion and good personal hygiene practices were found to influence helminth and hookworm prevalence in the area. Malaria parasite coinfection with helminths, especially hookworm infections increased 2-fold.