Measures of Malaria Burden after Long-Lasting Insecticidal Net Distribution and Indoor Residual Spraying at Three Sites in Uganda: A Prospective Observational Study.
BACKGROUND
Long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are the primary vector control interventions used to prevent malaria in Africa. Although both interventions are effective in some settings, high-quality evidence is rarely available to evaluate their effectiveness following deployment by a national malaria control program. In Uganda, we measured changes in key malaria indicators following universal LLIN distribution in three sites, with the addition of IRS at one of these sites.


RESULTS
Comprehensive malaria surveillance was conducted from October 1, 2011, to March 31, 2016, in three sub-counties with relatively low (Walukuba), moderate (Kihihi), and high transmission (Nagongera). Between 2013 and 2014, universal LLIN distribution campaigns were conducted in all sites, and in December 2014, IRS with the carbamate bendiocarb was initiated in Nagongera. High-quality surveillance evaluated malaria metrics and mosquito exposure before and after interventions through (a) enhanced health-facility-based surveillance to estimate malaria test positivity rate (TPR), expressed as the number testing positive for malaria/number tested for malaria (number of children tested for malaria: Walukuba = 42,833, Kihihi = 28,790, and Nagongera = 38,690); (b) cohort studies to estimate the incidence of malaria, expressed as the number of episodes per person-year [PPY] at risk (number of children observed: Walukuba = 340, Kihihi = 380, and Nagongera = 361); and (c) entomology surveys to estimate household-level human biting rate (HBR), expressed as the number of female Anopheles mosquitoes collected per house-night of collection (number of households observed: Walukuba = 117, Kihihi = 107, and Nagongera = 107). The LLIN distribution campaign substantially increased LLIN coverage levels at the three sites to between 65.0% and 95.5% of households with at least one LLIN. In Walukuba, over the 28-mo post-intervention period, universal LLIN distribution was associated with no change in the incidence of malaria (0.39 episodes PPY pre-intervention versus 0.20 post-intervention; adjusted rate ratio [aRR] = 1.02, 95% CI 0.36-2.91, p = 0.97) and non-significant reductions in the TPR (26.5% pre-intervention versus 26.2% post-intervention; aRR = 0.70, 95% CI 0.46-1.06, p = 0.09) and HBR (1.07 mosquitoes per house-night pre-intervention versus 0.71 post-intervention; aRR = 0.41, 95% CI 0.14-1.18, p = 0.10). In Kihihi, over the 21-mo post-intervention period, universal LLIN distribution was associated with a reduction in the incidence of malaria (1.77 pre-intervention versus 1.89 post-intervention; aRR = 0.65, 95% CI 0.43-0.98, p = 0.04) but no significant change in the TPR (49.3% pre-intervention versus 45.9% post-intervention; aRR = 0.83, 95% 0.58-1.18, p = 0.30) or HBR (4.06 pre-intervention versus 2.44 post-intervention; aRR = 0.71, 95% CI 0.30-1.64, p = 0.40). In Nagongera, over the 12-mo post-intervention period, universal LLIN distribution was associated with a reduction in the TPR (45.3% pre-intervention versus 36.5% post-intervention; aRR = 0.82, 95% CI 0.76-0.88, p < 0.001) but no significant change in the incidence of malaria (2.82 pre-intervention versus 3.28 post-intervention; aRR = 1.10, 95% 0.76-1.59, p = 0.60) or HBR (41.04 pre-intervention versus 20.15 post-intervention; aRR = 0.87, 95% CI 0.31-2.47, p = 0.80). The addition of three rounds of IRS at ~6-mo intervals in Nagongera was followed by clear decreases in all outcomes: incidence of malaria (3.25 pre-intervention versus 0.63 post-intervention; aRR = 0.13, 95% CI 0.07-0.27, p < 0.001), TPR (37.8% pre-intervention versus 15.0% post-intervention; aRR = 0.54, 95% CI 0.49-0.60, p < 0.001), and HBR (18.71 pre-intervention versus 3.23 post-intervention; aRR = 0.29, 95% CI 0.17-0.50, p < 0.001). High levels of pyrethroid resistance were documented at all three study sites. Limitations of the study included the observational study design, the lack of contemporaneous control groups, and that the interventions were implemented under programmatic conditions.


CONCLUSIONS
Universal distribution of LLINs at three sites with varying transmission intensity was associated with modest declines in the burden of malaria for some indicators, but the addition of IRS at the highest transmission site was associated with a marked decline in the burden of malaria for all indicators. In highly endemic areas of Africa with widespread pyrethroid resistance, IRS using alternative insecticide formulations may be needed to achieve substantial gains in malaria control.
Infectious Diseases Research Collaboration, Kampala, Uganda.
Agaba
A
Katureebe
HealthMap, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Kate
K
Zinszer
Infectious Diseases Research Collaboration, Kampala, Uganda.
Emmanuel
E
Arinaitwe
Infectious Diseases Research Collaboration, Kampala, Uganda.
John
http://orcid.org/0000-0003-4063-0763
J
Rek
Infectious Diseases Research Collaboration, Kampala, Uganda.
Elijah
http://orcid.org/0000-0001-9532-5710
E
Kakande
IMS Brogan Health, Montreal, Quebec, Canada.
Katia
K
Charland
Infectious Diseases Research Collaboration, Kampala, Uganda.|Uganda Malaria Surveillance Project, Kampala, Uganda.
Ruth
R
Kigozi
Infectious Diseases Research Collaboration, Kampala, Uganda.
Maxwell
M
Kilama
Infectious Diseases Research Collaboration, Kampala, Uganda.|School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Joaniter
J
Nankabirwa
Infectious Diseases Research Collaboration, Kampala, Uganda.|Uganda Malaria Surveillance Project, Kampala, Uganda.
Adoke
A
Yeka
Infectious Diseases Research Collaboration, Kampala, Uganda.
Henry
H
Mawejje
Uganda Malaria Surveillance Project, Kampala, Uganda.|Child Health & Development Centre, Makerere University College of Health Sciences, Kampala, Uganda.
Arthur
A
Mpimbaza
Uganda Ministry of Health, Kampala, Uganda.
Henry
http://orcid.org/0000-0002-8347-6922
H
Katamba
Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Martin J
MJ
Donnelly
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, United States of America.
Philip J
PJ
Rosenthal
London School of Hygiene and Tropical Medicine, London, United Kingdom.
Chris
http://orcid.org/0000-0003-4863-075X
C
Drakeley
School of Biological and Biomedical Sciences, Durham University, Durham, United Kingdom.
Steve W
SW
Lindsay
London School of Hygiene and Tropical Medicine, London, United Kingdom.
Sarah G
SG
Staedke
Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, United States of America.
David L
DL
Smith
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, United States of America.
Bryan
http://orcid.org/0000-0003-0287-9111
B
Greenhouse
Infectious Diseases Research Collaboration, Kampala, Uganda.|School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Moses R
MR
Kamya
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, United States of America.
Grant
G
Dorsey
D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D057148:Insecticide-Treated Bednets / Q000706:statistics & numerical data*; D007306:Insecticides; D008288:Malaria / Q000453:epidemiology* / Q000469:parasitology / Q000517:prevention & control / Q000635:transmission; D008297:Male; D009032:Mosquito Control; D011159:Population Surveillance; D011446:Prospective Studies; D014454:Uganda / Q000453:epidemiology
D007306:Insecticides