title: Serology reveals heterogeneity of Plasmodium falciparum transmission in northeastern South Africa: implications for malaria elimination.
abstract: It is widely acknowledged that modifications to existing control interventions are required if South Africa is to achieve malaria elimination. Targeting indoor residual spraying (IRS) to areas where cases have been detected is one strategy currently under investigation in northeastern South Africa. This seroprevalence baseline study, nested within a targeted IRS trial, was undertaken to provide insights into malaria transmission dynamics in South Africa and evaluate whether sero-epidemiological practices have the potential to be routinely incorporated into elimination programmes.
  
  
  
  Filter-paper blood spots, demographic and household survey data were collected from 2710 randomly selected households in 56 study wards located in the municipalities of Ba-Phalaborwa and Bushbuckridge. Blood spots were assayed for Plasmodium falciparum apical membrane antigen-1 and merozoite surface protein-119blood-stage antigens using an enzyme linked immunosorbent assay. Seroprevalence data were analysed using a reverse catalytic model to determine malaria seroconversion rates (SCR). Geospatial cluster analysis was used to investigate transmission heterogeneity while random effects logistic regression identified risk factors associated with malaria exposure.
  
  
  
  The overall SCR across the entire study site was 0.012 (95% CI 0.008-0.017) per year. Contrasting SCRs, corresponding to distinct geographical regions across the study site, ranging from <0.001 (95% CI <0.001-0.005) to 0.022 (95% CI 0.008-0.062) per annum revealed prominent transmission heterogeneity. Geospatial cluster analysis of household seroprevalence and age-adjusted antibody responses detected statistically significant (p < 0.05) spatial clusters of P. falciparum exposure. Formal secondary education was associated with lower malaria exposure in the sampled population (AOR 0.72, 95% CI 0.56-0.95, p = 0.018).
  
  
  
  Although overall transmission intensity and exposure to malaria was low across both study sites, malaria transmission intensity was highly heterogeneous and associated with low socio-economic status in the region. Findings suggest focal targeting of interventions has the potential to be an appropriate strategy to deploy in South Africa. Furthermore, routinely incorporating sero-epidemiological practices into elimination programmes may prove useful in monitoring malaria transmission intensity in South Africa, and other countries striving for malaria elimination.
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Joseph
authors.identifier: 0000-0001-7273-874X
authors.initials: J
authors.lastname: Biggs
authors.affiliation: Centre for Opportunistic Tropical and Hospital Infections, National Institute for Communicable Diseases, Johannesburg, South Africa. jaishreer@nicd.ac.za.|Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. jaishreer@nicd.ac.za.|Institute for Sustainable Malaria Control, University of Pretoria, Pretoria, South Africa. jaishreer@nicd.ac.za.
authors.forename: Jaishree
authors.initials: J
authors.lastname: Raman
authors.affiliation: Tropical Epidemiology Group, Department of Infectious Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Cook
authors.affiliation: School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Khumbulani
authors.initials: K
authors.lastname: Hlongwana
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.affiliation: Health GIS Centre, South Africa Medical Research Council, Durban, South Africa.
authors.forename: Natashia
authors.initials: N
authors.lastname: Morris
authors.affiliation: Health GIS Centre, South Africa Medical Research Council, Durban, South Africa.
authors.forename: Ishen
authors.initials: I
authors.lastname: Serocharan
authors.affiliation: Centre for Opportunistic Tropical and Hospital Infections, National Institute for Communicable Diseases, Johannesburg, South Africa.|Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Eunice
authors.initials: E
authors.lastname: Agubuzo
authors.affiliation: Limpopo Provincial Malaria Control Programme, Polokwane, South Africa.
authors.forename: Philip
authors.initials: P
authors.lastname: Kruger
authors.affiliation: Mpumalanga Provincial Malaria Control Programme, Nelspruit, South Africa.
authors.forename: Aaron
authors.initials: A
authors.lastname: Mabuza
authors.affiliation: Mpumalanga Provincial Malaria Control Programme, Nelspruit, South Africa.
authors.forename: Alpheus
authors.initials: A
authors.lastname: Zitha
authors.affiliation: Limpopo Provincial Malaria Control Programme, Polokwane, South Africa.
authors.forename: Elliot
authors.initials: E
authors.lastname: Machaba
authors.affiliation: Centre for Opportunistic Tropical and Hospital Infections, National Institute for Communicable Diseases, Johannesburg, South Africa.|Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Maureen
authors.initials: M
authors.lastname: Coetzee
authors.affiliation: Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Tropical Epidemiology Group, Department of Infectious Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Immo
authors.initials: I
authors.lastname: Kleinschmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015994:Incidence; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology / Q000635:transmission*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000502:physiology*; D015995:Prevalence; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D013019:South Africa / Q000453:epidemiology; D055815:Young Adult
keywords: Elimination; Heterogeneity; Hotspot; Malaria; PfAMA-1; PfMSP-119; Serology; South Africa; Transmission