Impact of insecticide resistance in Anopheles arabiensis on malaria incidence and prevalence in Sudan and the costs of mitigation

Significance Emerging insecticide resistance in malaria vectors could presage a catastrophic rebound in malaria morbidity and mortality. In areas of moderate levels of resistance to pyrethroids, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) with a carbamate insecticide were significantly more effective than IRS with pyrethroid insecticide. The impact on the effectiveness of LLINs could not be quantified. The incremental cost of using a carbamate insecticide to which vectors are susceptible was US $0.65 per person protected per year, which is considered acceptable by international standards. While the WHO recommends that different interventions, where possible, should use different insecticide classes, these data alone should not be used as the basis for a policy change in vector control interventions. Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact of resistance on malaria disease burden is limited. A cluster randomized trial was conducted in Sudan with pyrethroid-resistant and carbamate-susceptible malaria vectors. Clusters were randomly allocated to receive either long-lasting insecticidal nets (LLINs) alone or LLINs in combination with indoor residual spraying (IRS) with a pyrethroid (deltamethrin) insecticide in the first year and a carbamate (bendiocarb) insecticide in the two subsequent years. Malaria incidence was monitored for 3 y through active case detection in cohorts of children aged 1 to <10 y. When deltamethrin was used for IRS, incidence rates in the LLIN + IRS arm and the LLIN-only arm were similar, with the IRS providing no additional protection [incidence rate ratio (IRR) = 1.0 (95% confidence interval [CI]: 0.36–3.0; P = 0.96)]. When bendiocarb was used for IRS, there was some evidence of additional protection [interaction IRR = 0.55 (95% CI: 0.40–0.76; P < 0.001)]. In conclusion, pyrethroid resistance may have had an impact on pyrethroid-based IRS. The study was not designed to assess whether resistance had an impact on LLINs. These data alone should not be used as the basis for any policy change in vector control interventions.

[1]  I. Kleinschmidt,et al.  A cluster randomized trial comparing deltamethrin and bendiocarb as insecticides for indoor residual spraying to control malaria on Bioko Island, Equatorial Guinea , 2016, Malaria Journal.

[2]  David Weetman,et al.  Identification, Validation, and Application of Molecular Diagnostics for Insecticide Resistance in Malaria Vectors. , 2016, Trends in parasitology.

[3]  H. Ranson,et al.  Insecticide Resistance in African Anopheles Mosquitoes: A Worsening Situation that Needs Urgent Action to Maintain Malaria Control. , 2016, Trends in parasitology.

[4]  G. Killeen,et al.  Incremental impact upon malaria transmission of supplementing pyrethroid-impregnated long-lasting insecticidal nets with indoor residual spraying using pyrethroids or the organophosphate, pirimiphos methyl , 2016, Malaria Journal.

[5]  U. Dalrymple,et al.  The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015 , 2015, Nature.

[6]  I. Kleinschmidt,et al.  Design of a study to determine the impact of insecticide resistance on malaria vector control: a multi-country investigation , 2015, Malaria Journal.

[7]  J. Morgan,et al.  When a discriminating dose assay is not enough: measuring the intensity of insecticide resistance in malaria vectors , 2015, Malaria Journal.

[8]  K. Lindblade,et al.  A cohort study of the effectiveness of insecticide-treated bed nets to prevent malaria in an area of moderate pyrethroid resistance, Malawi , 2015, Malaria Journal.

[9]  Bradley J. Main,et al.  Adaptive introgression in an African malaria mosquito coincident with the increased usage of insecticide-treated bed nets , 2015, Proceedings of the National Academy of Sciences.

[10]  Magnus Manske,et al.  Adaptive introgression between Anopheles sibling species eliminates a major genomic island but not reproductive isolation , 2014, Nature Communications.

[11]  I. Kleinschmidt,et al.  Indoor Residual Spraying in Combination with Insecticide-Treated Nets Compared to Insecticide-Treated Nets Alone for Protection against Malaria: A Cluster Randomised Trial in Tanzania , 2014, PLoS medicine.

[12]  O. Mayans,et al.  Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae , 2014, PloS one.

[13]  A. Enayati,et al.  The Impact of Pyrethroid Resistance on the Efficacy of Insecticide-Treated Bed Nets against African Anopheline Mosquitoes: Systematic Review and Meta-Analysis , 2014, PLoS medicine.

[14]  C. Rogier,et al.  Entomological and parasitological impacts of indoor residual spraying with DDT, alphacypermethrin and deltamethrin in the western foothill area of Madagascar , 2014, Malaria Journal.

[15]  I. Kleinschmidt,et al.  Epidemiology of malaria in South Africa: from control to elimination. , 2013, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[16]  Anand P. Patil,et al.  Malaria Risk Mapping for Control in the Republic of Sudan , 2012, The American journal of tropical medicine and hygiene.

[17]  H. Ranson,et al.  Multiple-Insecticide Resistance in Anopheles gambiae Mosquitoes, Southern Côte d’Ivoire , 2012, Emerging infectious diseases.

[18]  Grant Dorsey,et al.  Indoor Residual Spraying of Insecticide and Malaria Morbidity in a High Transmission Intensity Area of Uganda , 2012, PloS one.

[19]  A. Egyir-Yawson,et al.  Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana , 2012, Proceedings of the National Academy of Sciences.

[20]  E. Walker,et al.  Spatial and temporal variation in the kdr allele L1014S in Anopheles gambiae s.s. and phenotypic variability in susceptibility to insecticides in Western Kenya , 2011, Malaria Journal.

[21]  R. Hayes,et al.  Restricted randomization of ZAMSTAR: a 2 × 2 factorial cluster randomized trial , 2008, Clinical trials.

[22]  R. Hunt,et al.  Insecticide susceptibility and vector status of natural populations of Anopheles arabiensis from Sudan. , 2008, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[23]  Hong Chen,et al.  Short report: permethrin and DDT resistance in the malaria vector Anopheles arabiensis from eastern Sudan. , 2007, The American journal of tropical medicine and hygiene.

[24]  John Vontas,et al.  Detection of knockdown resistance (kdr) mutations in Anopheles gambiae: a comparison of two new high-throughput assays with existing methods , 2007, Malaria Journal.

[25]  I. Kleinschmidt,et al.  Factors influencing the effectiveness of malaria control in Bioko Island, equatorial Guinea. , 2007, The American journal of tropical medicine and hygiene.

[26]  Rajendra Maharaj,et al.  Seven years of regional malaria control collaboration--Mozambique, South Africa, and Swaziland. , 2007, The American journal of tropical medicine and hygiene.

[27]  E. Ahmed,et al.  From chloroquine to artemisinin-based combination therapy: the Sudanese experience , 2006, Malaria Journal.

[28]  I. Kleinschmidt,et al.  Reduction in infection with Plasmodium falciparum one year after the introduction of malaria control interventions on Bioko Island, Equatorial Guinea. , 2006, The American journal of tropical medicine and hygiene.

[29]  B. Sharp,et al.  Impact of DDT re-introduction on malaria transmission in KwaZulu-Natal. , 2005, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[30]  Weltgesundheitsorganisation World malaria report , 2005 .

[31]  A. Rothberg Making Choices in Health: WHO Guide to Cost Effectiveness Analysis , 2008 .

[32]  Rob Baltussen,et al.  Making Choices in Health: WHO Guide to Cost Effectiveness Analysis , 2003 .

[33]  T. Theander,et al.  A marked seasonality of malaria transmission in two rural sites in eastern Sudan. , 2002, Acta tropica.

[34]  R. Hunt,et al.  Anopheles funestus resistant to pyrethroid insecticides in South Africa , 2000, Medical and veterinary entomology.

[35]  M. Coluzzi,et al.  Cytogenetics of the Anopheles gambiae complex in Sudan, with special reference to An. arabiensis: relationships with East and West African populations , 2000, Medical and veterinary entomology.

[36]  F. Collins,et al.  Identification of single specimens of the Anopheles gambiae complex by the polymerase chain reaction. , 1993, The American journal of tropical medicine and hygiene.

[37]  A. Scott,et al.  A simple method for the analysis of clustered binary data. , 1992, Biometrics.