Evaluation of the Safety and Immunogenicity of the RTS,S/AS01E Malaria Candidate Vaccine When Integrated in the Expanded Program of Immunization

Background. The RTS,S/AS01E malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). Methods. This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01E when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01E at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and wholecell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01E at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. Results. The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01E coadministration groups. RTS,S/AS01E generated high anti-circumsporozoite protein and anti- hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01E at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. Conclusion. RTS,S/AS01E integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007. GlaxoSmithKline study ID number: 106369 (Malaria-050

Malaria risk and access to prevention and treatment in the paddies of the Kilombero Valley, Tanzania

Background: The Kilombero Valley is a highly malaria-endemic agricultural area in south-eastern Tanzania. Seasonal flooding of the valley is favourable to malaria transmission. During the farming season, many households move to distant field sites (shamba in Swahili) in the fertile river floodplain for the cultivation of rice. In the shamba, people live for several months in temporary shelters, far from the nearest health services. This study assessed the impact of seasonal movements to remote fields on malaria risk and treatment-seeking behaviour. Methods: A longitudinal study followed approximately 100 randomly selected farming households over six months. Every household was visited monthly and whereabouts of household members, activities in the fields, fever cases and treatment seeking for recent fever episodes were recorded. Results: Fever incidence rates were lower in the shamba compared to the villages and moving to the shamba did not increase the risk of having a fever episode. Children aged 1-4 years, who usually spend a considerable amount of time in the shamba with their caretakers, were more likely to have a fever than adults (odds ratio = 4.47, 95 confidence interval 2.35-8.51). Protection with mosquito nets in the fields was extremely good (98 antimalarials was uncommon. Despite the long distances to health services, 55.8 health facility, while home-management was less common (37 17.4-50.5). Conclusion: Living in the shamba does not appear to result in a higher fever-risk. Mosquito nets usage and treatment of fever in health facilities reflect awareness of malaria. Inability to obtain drugs in the fields may contribute to less irrational use of drugs but may pose an additional burden on poor farming households. A comprehensive approach is needed to improve access to treatment while at the same time assuring rational use of medicines and protecting fragile livelihoods

Obstacles to prompt and effective malaria treatment lead to low community-coverage in two rural districts of Tanzania

BACKGROUND\ud \ud Malaria is still a leading child killer in sub-Saharan Africa. Yet, access to prompt and effective malaria treatment, a mainstay of any malaria control strategy, is sub-optimal in many settings. Little is known about obstacles to treatment and community-effectiveness of case-management strategies. This research quantified treatment seeking behaviour and access to treatment in a highly endemic rural Tanzanian community. The aim was to provide a better understanding of obstacles to treatment access in order to develop practical and cost-effective interventions.\ud \ud METHODS\ud \ud We conducted community-based treatment-seeking surveys including 226 recent fever episodes in 2004 and 2005. The local Demographic Surveillance System provided additional household information. A census of drug retailers and health facilities provided data on availability and location of treatment sources.\ud \ud RESULTS\ud \ud After intensive health education, the biomedical concept of malaria has largely been adopted by the community. 87.5% (78.2-93.8) of the fever cases in children and 80.7% (68.1-90.0) in adults were treated with one of the recommended antimalarials (at the time SP, amodiaquine or quinine). However, only 22.5% (13.9-33.2) of the children and 10.5% (4.0-21.5) of the adults received prompt and appropriate antimalarial treatment. Health facility attendance increased the odds of receiving an antimalarial (OR = 7.7) but did not have an influence on correct dosage. The exemption system for under-fives in public health facilities was not functioning and drug expenditures for children were as high in health facilities as with private retailers.\ud \ud CONCLUSION\ud \ud A clear preference for modern medicine was reflected in the frequent use of antimalarials. Yet, quality of case-management was far from satisfactory as was the functioning of the exemption mechanism for the main risk group. Private drug retailers played a central role by complementing existing formal health services in delivering antimalarial treatment. Health system factors like these need to be tackled urgently in order to translate the high efficacy of newly introduced artemisinin-based combination therapy (ACT) into equitable community-effectiveness and health-impact

Women and ARVâ based prevention: opportunities and challenges

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138349/1/jia29419.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Introducing insecticide-treated nets in the Kilombero Valley, Tanzania: the relevance of local knowledge and practice for an information, education and communication (IEC) campaign.

Since 1997 the WHO has been recommending an integrative strategy to combat malaria including new medicines, vaccines, improvements of health care systems and insecticide-treated nets (ITNs). After successful controlled trials with ITNs in the past decade, large-scale interventions and research now focus on operational issues of distribution and financing. In developing a social marketing approach in the Kilombero Valley in south-east Tanzania in 1996, a combination of qualitative and quantitative methods was employed to investigate local knowledge and practice relating to malaria. The findings show that the biomedical concept of malaria overlaps with several local illness concepts, one of which is called malaria and refers to mild malaria. Most respondents linked malaria to mosquitoes (76%) and already used mosquito nets (52%). But local understandings of severe malaria differed from the biomedical concept and were not linked to mosquitoes or malaria. A social marketing strategy to promote ITNs was developed on the basis of these findings, which reinforced public health messages and linked them with nets and insecticide. Although we did not directly evaluate the impact of promotional activities, the sharp rise in ownership and use of ITNs by the population (from 10 to > 50%) suggests that they contributed significantly to the success of the programme. Local knowledge and practice is highly relevant for social marketing strategies of ITNs

Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization.

BACKGROUND: The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). METHODS: This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and whole-cell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01(E) at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. RESULTS: The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01(E) coadministration groups. RTS,S/AS01(E) generated high anti-circumsporozoite protein and anti-hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01(E) at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. CONCLUSION: RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050)