205071 - A phase IV, longitudinal, cross-sectional, retrospective, ancillary epidemiology study of the EPI-MAL-005 study to evaluate the genetic diversity in the Plasmodium falciparum parasite circumsporozoite sequences before and after the implementation of the RTS,S/AS01E vaccine in malaria-positive subjects ranging from 6 months to less than 5 years of age (EPI-MALARIA-010 VS AME)

Study type

• Study topic:
  Other
• Study topic, other:
  Genetic
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cross-sectional

Study drug and medical condition

• Medical condition to be studied:
  Malaria

Population studied

• Short description of the study population:
  Subjects aged 6 months to <5 years of age, enrolled in the EPI-MAL-005 study at the two sites ; before and after the start of RTS,S/AS01E vaccination, may be included in the EPI-MAL-010 study
• Age groups:
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
• Estimated number of subjects:
  5600

Study design details

• Study design:
  Longitudinal, retrospective, epidemiological, cross-sectional study, ancillary to the EPI-MAL-005 study.
• Main study objective:
  To monitor the genetic diversity in circumsporozoite sequences in the P. falciparum parasite population before and after vaccine implementation in children aged 6 months to <5 years.
• Setting:
  The two pre-selected sites for the EPI-MAL-010 study are Kintampo in Ghana (Western Africa) and Kombewa in Kenya (Eastern Africa). The sites are located in the planned RTS,S/AS01E pilot implementation areas of Ghana and Kenya, which are moderate-to-high transmission areas as recommended by the WHO for the MVIP. Based on the results from MALARIA-066, selecting one site situated in Western Africa and the other in Eastern Africa will allow further exploring the already observed P. falciparum strain diversity differences between Western and Eastern Africa, as well as giving to EPI-MAL-010 a certain level of continental diversity in terms of human populations.
• Outcomes:
  Prevalence of P. falciparum haplotype infections among subjects infected or not with P. falciparum and frequency of P. falciparum haplotype infections among the individual malaria clones in subjects vaccinated or not with RTS,S/AS01E per study site. Prevalence and frequency of P.falciparumhaplo type infections by age group, gender and RTS,S/AS01Evaccinationstatusper study site, Trends in longitudinal prevalence of specific P.falciparumhaplotypesamongsubjectsinfectedornotwith P.falciparum,vaccinatedornotwith RTS,S/AS01E,Trends inlongitudinalfrequencyofspecific P.falciparum haplotypes among the individualmalariaclonesinsubjectsvaccinatedornotwithRTS,S/AS01E.
• Data analysis plan:
  - The haplotype prevalence will be estimated by site, as the number of subjects infected with a specific P. falciparum haplotype, divided by the total number of subjects. Thus, the denominator will be all the subjects aged 6 months to <5 years included in the EPI-MAL-010 study for each of the 2 sites considered: malaria positive and negative subjects based on malaria blood reading and/or NAAT. ; - The haplotype frequency will be estimated by site, as the number of occurrences of a specific P. falciparum haplotype, divided by the total number of clones. Thus, in case of multiple infections with P. falciparum malaria, the same subject will contribute multiple times in the denominator. The frequency will be estimated using data only from subjects aged 6 months to <5 years, measured malaria positive by microscopy and/or NAAT, included in the EPI-MAL-010 study for each of the 2 sites considered.