Clinical trial NCT02556242: Targeted Indoor Residual Spraying Against Malaria
Official title: From Malaria Control to Sustainable Elimination: Cluster Randomised Trial Comparing Targeted Versus Generalised Vector Control in South Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Keywords: vector control
insecticide
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: University of Witwatersrand, South Africa
name: National Department of Health, South Africa
name: Medical Research Council
name: National Institute for Communicable Diseases, South Africa
First posted: 2015-09-22
Enrollment: 393387
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Since 2000, annual numbers of malaria cases in South Africa have sharply declined to about 5,000, with case numbers fairly stable since 2007. The principal malaria prevention strategy has consisted of generalised Indoor Residual Spraying (IRS) of all houses in malaria endemic districts. As recent case data indicate that the levels of transmission in many districts have been reduced to very low levels, the continuation of untargeted IRS in areas where there is little or no evidence of recent transmission may be unwarranted. Efforts to eliminate malaria will only be sustainable if mass prevention efforts can be scaled down in an evidence-based manner, whilst maintaining or enhancing high sensitivity of the surveillance system of the disease. This trial will provide scientific evidence for targeted malaria prevention responding to localised transmission in pre-elimination settings, compared to continuation of generalised IRS of all houses.

Two methods of IRS delivery for community malaria prevention will be compared through an open-label cluster-randomised trial consisting of two study arms with 30 clusters per arm of approximately 8,000 inhabitants per cluster.

Comparison is on the basis of non-inferiority by showing that malaria incidence in the targeted IRS arm is no higher than malaria incidence in the generalised IRS arm within a specified margin of difference, and on the basis of superiority showing that the proportion of houses targeted for spraying is higher in the intervention than the reference arm. Neighbourhood investigation in response to each locally acquired case in the intervention arm, and comparison neighbourhoods in the reference arm, will include testing for antibody sero-conversion to malarial antigens to assess whether cases arise in communities with long term exposure to malaria parasites.

The trial will be carried out in the South African provinces of Limpopo and Mpumalanga, in localities which have average reported incidence of malaria of \<5 cases per 1000 per annum over the past five years.

Detailed description: Two methods of IRS delivery for malaria prevention, targeted spraying versus annual generalised spraying, will be compared through an open-label cluster randomised trial consisting of two trial arms with 30 clusters per arm. Clusters will be artificial constructs made up of groups of spray localities or complete wards to comprise populations of about 5,000 to 10,000 persons. The unit of randomisation will be the cluster.

The intervention arm of the trial will receive IRS delivery through targeted reactive spraying in the neighbourhood of recent local cases only; the reference (control) arm of the trial will receive IRS through generalised annual spraying of all structures as per standard current practice.

Comparison will be on the basis of non-inferiority by showing that malaria incidence in the targeted IRS arm is no higher than malaria incidence in the generalised IRS arm within a specified margin of difference, and on the basis of superiority showing that the proportion of houses sprayed, of those targeted for spraying, is higher in the intervention than the reference arm. Neighbourhood investigation in response to each locally acquired case in the intervention arm, and comparison neighbourhoods in the reference arm will include testing for antibody sero-conversion to malarial antigens to assess whether cases arise in communities with long term exposure to malarial parasites.

Eligibility criteria: Inclusion criteria

1. Entire communities of approximately 8000 persons
2. Residents in malaria endemic districts of Limpopo and Mpumalanga Province
3. Areas with local malaria incidence \<5 cases per 1000 per year on average over 5 years

Primary outcomes:
measure: Malaria incidence, by routine passive case detection, of clinical malaria (fever ≥37.5°C, or history of fever (48 hours), in the presence of parasitaemia confirmed by RDT or microscopy).
timeFrame: Communities will be followed for up to 20 months
Secondary outcomes:
measure: Intervention costs per 1,000 households and cost-effectiveness of reactive, targeted indoor residual spraying (TIRS) compared to generalised IRS (GIRS)
timeFrame: Up to 20 months
measure: Proportion of structures targeted for IRS unsprayed
timeFrame: Up to 20 months whenever reactive spraying is triggered
measure: Household compliance (not painting, washing, re-plastering )
timeFrame: By cross sectional household survey after 18 months
measure: Householder acceptability of IRS
timeFrame: By cross sectional household survey after 18 months
measure: If unsprayed, proportions due to refusals, spray teams not making contact and spray teams not calling back
timeFrame: By cross sectional household survey after 18 months
measure: Sero-prevalence of antibodies to malaria antigens AMA-1 and MSP-1-19
timeFrame: By cross sectional household survey after 18 months
Other outcomes:
Locations:
city: Tzaneen
country: South Africa
facility: Provincial Malaria Control Programme
state: Limpopo
city: Nelspruit
country: South Africa
facility: Provincial Malaria Control Programme
state: Mpumalnga
Study officials:
affiliation: University of Witwatersrand, South Africa
name: Maureen Coetzee, Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Immo Kleinschmidt, Phd
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bath D, Cook J, Govere J, Mathebula P, Morris N, Hlongwana K, Raman J, Seocharan I, Zitha A, Zitha M, Mabuza A, Mbokazi F, Machaba E, Mabunda E, Jamesboy E, Biggs J, Drakeley C, Moonasar D, Maharaj R, Coetzee M, Pitt C, Kleinschmidt I. Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa. Lancet. 2021 Feb 27;397(10276):816-827. doi: 10.1016/S0140-6736(21)00251-8.