Association of house spraying with suppressed levels of drug resistance in Zimbabwe.
BACKGROUND
Public health strategies are needed to curb antimalarial drug resistance. Theoretical argument points to an association between malaria transmission and drug resistance although field evidence remains limited. Field observations, made in Zimbabwe, on the relationship between transmission and multigenic drug resistance, typified by chloroquine, are reported here.


METHODS
Periodic assessments of the therapeutic response of uncomplicated falciparum malaria to chloroquine in two selectively sprayed or unsprayed health centre catchments, from 1995 - 2003. Cross-sectional analysis of in vivo chloroquine failure events for five sites in relation to natural endemicity and spraying history.


RESULTS
During selective house spraying, the chloroquine failure rate for the sprayed catchment decreased, such that, after four years, the odds of chloroquine failure were 4x lower than before start of spraying in the area (OR 0.2, 95% CI 0.07 - 0.75, p = 0.010, n = 100). Chloroquine failure odds for the sprayed area became 4x lower than contemporaneous failure odds for the unsprayed area (OR 0.2 95% CI 0.08 - 0.65, p = 0.003, n = 156), although the likelihood of failure was not significantly different for the two catchments before selective spraying started (OR 0.5, 95% CI 0.21 - 1.32; p = 0.170, n = 88). When spraying ended, in 1999, the drug failure odds for the former sprayed area increased back 4 fold by 2003 (OR 4.2, 95%CI 1.49 - 11.78, p = 0.004, n = 146). High altitude areas with naturally lower transmission exhibited a 6x lower likelihood of drug failure than low-lying areas (OR 0.16 95% CI 0.068 - 0.353, -2 log likelihood change 23.239, p < 0.001, n = 465). Compared to sites under ongoing annual spraying, areas that were last sprayed 3-7 years ago experienced a 4-fold higher probability of chloroquine failure (OR 4.1, 95%CI 1.84 - 9.14, -2 log likelihood change 13.956, p < 0.001).


CONCLUSIONS
Reduced transmission is associated with suppressed levels of resistance to chloroquine and presumably other regimens with multigenic drug resistance. It seems the adoption of transmission control alongside combination chemotherapy is a potent strategy for the future containment of drug-resistant malaria.
Mharakurwa
Sungano
S
Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N, Wolfe Street, Baltimore, MD 21205, USA. smharaku@jhsph.edu
Mutambu
Susan L
SL
Mudyiradima
Robert
R
Chimbadzwa
Tawanda
T
Chandiwana
Steven K
SK
Day
Karen P
KP
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D018432:Drug Resistance, Multiple; D019450:Genes, MDR / Q000235:genetics; D005838:Genotype; D006798:Housing; D006801:Humans; D015994:Incidence; D007306:Insecticides; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology* / Q000517:prevention & control; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009032:Mosquito Control / Q000379:methods*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011110:Polymorphism, Genetic; D011336:Probability; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000235:genetics; D017211:Treatment Failure; D015030:Zimbabwe / Q000453:epidemiology
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D007306:Insecticides; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine