Operational strategies of anti-malarial drug campaigns for malaria elimination in Zambia’s southern province: a simulation study

BackgroundMalaria elimination requires reducing both the potential of mosquitoes to transmit parasites to humans and humans to transmit parasites to mosquitoes. To achieve this goal in Southern province, Zambia a mass test and treat (MTAT) campaign was conducted from 2011–2013 to complement high coverage of long-lasting insecticide-treated nets (LLIN). To identify factors likely to increase campaign effectiveness, a modelling approach was applied to investigate the simulated effect of alternative operational strategies for parasite clearance in southern province.MethodsOpenMalaria, a discrete-time, individual-based stochastic model of malaria, was parameterized for the study area to simulate anti-malarial drug administration for interruption of transmission. Simulations were run for scenarios with a range of artemisinin-combination therapies, proportion of the population reached by the campaign, targeted age groups, time between campaign rounds, Plasmodium falciparum test protocols, and the addition of drugs aimed at preventing onward transmission. A sensitivity analysis was conducted to assess uncertainty of simulation results. Scenarios were evaluated based on the reduction in all-age parasite prevalence during the peak transmission month one year following the campaign, compared to the currently-implemented strategy of MTAT 19 % population coverage at pilot and 40 % coverage during the first year of implementation in the presence of 56 % LLIN use and 18 % indoor residual spray coverage.ResultsSimulation results suggest the most important determinant of success in reducing prevalence is the population coverage achieved in the campaign, which would require more than 1 year of campaign implementation for elimination. The inclusion of single low-dose primaquine, which acts as a gametocytocide, or ivermectin, which acts as an endectocide, to the drug regimen did not further reduce parasite prevalence one year following the campaign compared to the currently-implemented strategy. Simulation results indicate a high proportion of low-density infections were missed by rapid diagnostic tests that would be treated and cleared with mass drug administration (MDA).ConclusionsThe optimal implementation strategy for MTAT or MDA will vary by background level of prevalence, by rate of infections imported to the area, and by ability to operationally achieve high population coverage. Overall success with new parasite clearance strategies depends on continued coverage of vector control interventions to ensure sustained gains in reduction of disease burden.

[1]  Katya Galactionova,et al.  Modeling the Cost Effectiveness of Malaria Control Interventions in the Highlands of Western Kenya , 2014, PloS one.

[2]  Kevin C. Kobylinski,et al.  Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors , 2010, Malaria Journal.

[3]  Busiku Hamainza,et al.  Population-Wide Malaria Testing and Treatment with Rapid Diagnostic Tests and Artemether-Lumefantrine in Southern Zambia: A community Randomized Step-Wedge Control Trial Design , 2015, The American journal of tropical medicine and hygiene.

[4]  Massamba Sylla,et al.  The effect of oral anthelmintics on the survivorship and re-feeding frequency of anthropophilic mosquito disease vectors. , 2010, Acta tropica.

[5]  Teun Bousema,et al.  Factors determining the occurrence of submicroscopic malaria infections and their relevance for control , 2012, Nature Communications.

[6]  Thomas A. Smith,et al.  Importance of factors determining the effective lifetime of a mass, long-lasting, insecticidal net distribution: a sensitivity analysis , 2012, Malaria Journal.

[7]  Thomas Smith,et al.  Comparing the Effectiveness of Malaria Vector-Control Interventions Through a Mathematical Model , 2010, The American journal of tropical medicine and hygiene.

[8]  Bernhards Ogutu,et al.  A controlled, parallel, cluster-randomized trial of community-wide screening and treatment of asymptomatic carriers of Plasmodium falciparum in Burkina Faso , 2013, Malaria Journal.

[9]  T. Bousema,et al.  Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double-blind, dose-ranging trial. , 2014, The Lancet. Infectious diseases.

[10]  Jaline Gerardin,et al.  Mass campaigns with antimalarial drugs: a modelling comparison of artemether-lumefantrine and DHA-piperaquine with and without primaquine as tools for malaria control and elimination , 2015, BMC Infectious Diseases.

[11]  D. Terlouw,et al.  Optimizing the programmatic deployment of the anti-malarials artemether-lumefantrine and dihydroartemisinin-piperaquine using pharmacological modelling , 2014, Malaria Journal.

[12]  C. Lengeler,et al.  Adherence to and acceptability of artemether-lumefantrine as first-line anti-malarial treatment: evidence from a rural community in Tanzania , 2010, Malaria Journal.

[13]  I. Hastings,et al.  Development, Evaluation, and Application of an In Silico Model for Antimalarial Drug Treatment and Failure , 2011, Antimicrobial Agents and Chemotherapy.

[14]  W. Hawley,et al.  The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South sumatra, Western indonesia: an open-label, randomized, controlled trial. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  Busiku Hamainza,et al.  Assessing the effectiveness of household-level focal mass drug administration and community-wide mass drug administration for reducing malaria parasite infection prevalence and incidence in Southern Province, Zambia: study protocol for a community randomized controlled trial , 2015, Trials.

[16]  Teun Bousema,et al.  The potential impact of adding ivermectin to a mass treatment intervention to reduce malaria transmission: a modelling study. , 2014, The Journal of infectious diseases.

[17]  T. Bousema,et al.  The gametocytocidal efficacy of primaquine in malaria asymptomatic carriers treated with dihydroartemisinin-piperaquine in The Gambia (PRINOGAM): study protocol for a randomised controlled trial , 2015, Trials.

[18]  S. P. Kachur,et al.  Mass drug administration for malaria , 2013, The Cochrane database of systematic reviews.

[19]  D. Norris,et al.  Seasonality, blood feeding behavior, and transmission of Plasmodium falciparum by Anopheles arabiensis after an extended drought in southern Zambia. , 2007, The American journal of tropical medicine and hygiene.

[20]  Richard W Steketee,et al.  Single low-dose primaquine to reduce malaria transmission. , 2014, The Lancet. Infectious diseases.

[21]  Thomas Smith,et al.  A Periodically-Forced Mathematical Model for the Seasonal Dynamics of Malaria in Mosquitoes , 2012, Bulletin of mathematical biology.

[22]  Q. Bassat,et al.  Ivermectin to reduce malaria transmission: a research agenda for a promising new tool for elimination , 2013, Malaria Journal.

[23]  Nicolas Maire,et al.  What Should Vaccine Developers Ask? Simulation of the Effectiveness of Malaria Vaccines , 2008, PloS one.

[24]  M. Tanner,et al.  Towards a comprehensive simulation model of malaria epidemiology and control , 2008, Parasitology.

[25]  Kevin C. Kobylinski,et al.  Ivermectin mass drug administration to humans disrupts malaria parasite transmission in Senegalese villages. , 2011, The American journal of tropical medicine and hygiene.

[26]  J. Utzinger,et al.  The economic payoffs of integrated malaria control in the Zambian copperbelt between 1930 and 1950 , 2002, Tropical medicine & international health : TM & IH.

[27]  J. Guthmann,et al.  Adherence to the combination of sulphadoxine–pyrimethamine and artesunate in the Maheba refugee settlement, Zambia , 2004, Tropical medicine & international health : TM & IH.

[28]  Teun Bousema,et al.  Epidemiology of subpatent Plasmodium falciparum infection: implications for detection of hotspots with imperfect diagnostics , 2013, Malaria Journal.

[29]  Elizabeth L. Turner,et al.  Impact of Intermittent Screening and Treatment for Malaria among School Children in Kenya: A Cluster Randomised Trial , 2014, PLoS medicine.

[30]  F. Checchi,et al.  Adherence to a six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Uganda. , 2004, The American journal of tropical medicine and hygiene.

[31]  Andrew J Tatem,et al.  Integrating rapid risk mapping and mobile phone call record data for strategic malaria elimination planning , 2014, Malaria Journal.

[32]  Thomas Smith,et al.  Ensemble Modeling of the Likely Public Health Impact of a Pre-Erythrocytic Malaria Vaccine , 2012, PLoS medicine.

[33]  M. Coleman,et al.  Malaria Journal Integrated Vector Management: the Zambian Experience , 2022 .

[34]  Gregory E. Glass,et al.  Analysis of Anopheles arabiensis blood feeding behavior in southern Zambia during the two years after introduction of insecticide-treated bed nets. , 2010, The American journal of tropical medicine and hygiene.

[35]  F. Nosten,et al.  Randomized, Double-Blind, Placebo-Controlled Trial of Monthly versus Bimonthly Dihydroartemisinin-Piperaquine Chemoprevention in Adults at High Risk of Malaria , 2012, Antimicrobial Agents and Chemotherapy.

[36]  Kevin C. Kobylinski,et al.  Endectocides for malaria control. , 2011, Trends in parasitology.

[37]  C. Dolea,et al.  World Health Organization , 1949, International Organization.