• 1.

    Zambia Ministry of Health, 2006. A Road Map for Impact on Malaria in Zambia 2006–2010: A 5-Year Strategic Plan. Lusaka, Zambia: Zambia Ministry of Health.

    • Search Google Scholar
    • Export Citation
  • 2.

    Agha S, Van Rossem R, Stallworthy G, Kusanthan T, 2007. The impact of a hybrid social marketing intervention on inequities in access, ownership and use of insecticide-treated nets. Malar J 6: 13.

    • Search Google Scholar
    • Export Citation
  • 3.

    Chanda P, Masiye F, Chitah BM, Sipilanyambe N, Moonga H, Banda P, Okorosobo T, 2007. A cost-effectiveness analysis of artemether lumefantrine for treatment of uncomplicated malaria in Zambia. Malar J 6: 21.

    • Search Google Scholar
    • Export Citation
  • 4.

    Steketee RW, Sipilanyambe N, Chimumbwa J, Banda JJ, Mohamed A, Miller J, Basu S, Miti SK, Campbell CC, 2008. National malaria control and scaling up for impact: the Zambia experience through 2006. Am J Trop Med Hyg 79: 4552.

    • Search Google Scholar
    • Export Citation
  • 5.

    Roll Back Malaria, 2011. Focus on Zambia. Geneva, Switzerland: World Health Organization. Progress & Impact Series Country Reports No. 2.

    • Search Google Scholar
    • Export Citation
  • 6.

    Zurovac D, Ndhlovu M, Sipilanyambe N, Chanda P, Hamer DH, Simon JL, Snow RW, 2007. Paediatric malaria case-management with artemether-lumefantrine in Zambia: a repeat cross-sectional study. Malar J 6: 31.

    • Search Google Scholar
    • Export Citation
  • 7.

    Chizema-Kawesha E, Miller JM, Steketee RW, Mukonka VM, Mukuka C, Mohamed AD, Miti SK, Campbell CC, 2010. Scaling up malaria control in Zambia: progress and impact 2005–2008. Am J Trop Med Hyg 83: 480488.

    • Search Google Scholar
    • Export Citation
  • 8.

    Zambia Ministry of Health, 2010. Zambia National Malaria Programme Performance Review 2010. Lusaka, Zambia: Ministry of Health.

  • 9.

    Zambia Ministry of Health, 2015. National Malaria Control Programme Strategic Plan for FY 2011–2016: Consolidating Malaria Gains for Impact in National Malaria Strategic Plan. Lusaka, Zambia: Zambia Ministry of Health.

    • Search Google Scholar
    • Export Citation
  • 10.

    Zambia Ministry of Health, 2011. National Human Resources for Health Strategic Plan 2011–2015. Lusaka, Zambia: Ministry of Health.

  • 11.

    Chanda P, Hamainza B, Moonga HB, Chalwe V, Banda P, Pagnoni F, 2011, Relative costs and effectiveness of treating uncomplicated malaria in two rural districts in Zambia: implications for nationwide scale-up of home-based management. Malar J 10: 159.

    • Search Google Scholar
    • Export Citation
  • 12.

    Shelley KD, Belete YW, Phiri SC, Musonda M, Kawesha EC, Muleya EM, Chibawe CP, van den Broek JW, Vosburg KB, 2016. Implementation of the community health assistant (CHA) cadre in Zambia: a process evaluation to guide future scale-up decisions. J Community Health 41: 398408.

    • Search Google Scholar
    • Export Citation
  • 13.

    Lusaka Times, 2015. Construction of 650 Health Posts on Course for Completion Next Year. Lusaka, Zambia: Lusaka Times.

  • 14.

    Seidenberg PD, Hamer DH, Iyer H, Pilingana P, Siazeele K, Hamainza B, MacLeod WB, Yeboah-Antwi K, 2012. Impact of integrated community case management on health-seeking behavior in rural Zambia. Am J Trop Med Hyg 87 (Suppl 5): 105110.

    • Search Google Scholar
    • Export Citation
  • 15.

    Larsen DA, Winters A, Cheelo S, Hamainza B, Kamuliwo M, Miller JM, Bridges DJ, 2017. Shifting the burden or expanding access to care? Assessing malaria trends following scale-up of community health worker malaria case management and reactive case detection. Malar J 16: 441.

    • Search Google Scholar
    • Export Citation
  • 16.

    Strachan C, Wharton-Smith A, Sinyangwe C, Mubiru D, Ssekitooleko J, Meier J, Gbanya M, Tibenderana JK, Counihan H, 2014. Integrated community case management of malaria, pneumonia and diarrhoea across three African countries: a qualitative study exploring lessons learnt and implications for further scale up. J Glob Health 4: 020404.

    • Search Google Scholar
    • Export Citation
  • 17.

    Zambia Ministry of Health, 2010. Zambia National Malaria Indicator Survey 2010. Lusaka, Zambia: Ministry of Health.

  • 18.

    Zambia Ministry of Health, 2012. Zambia National Malaria Indicator Survey 2012. Lusaka, Zambia: Ministry of Health.

  • 19.

    Zambia Ministry of Health, 2008. Zambia National Malaria Indicator Survey 2008. Lusaka, Zambia: Ministry of Health.

  • 20.

    von Seidlein L, Dondorp A, 2015. Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance. Expert Rev Anti Infect Ther 13: 715730.

    • Search Google Scholar
    • Export Citation
  • 21.

    White NJ, 2016. Does antimalarial mass drug administration increase or decrease the risk of resistance? Lancet Infect Dis 17: e15e20.

  • 22.

    von Seidlein L, Greenwood BM, 2003. Mass administrations of antimalarial drugs. Trends Parasitol 19: 452460.

  • 23.

    Poirot E, Skarbinski J, Sinclair D, Kachur S, Slutsker L, Hwang J, 2013. Administration of antimalarial drugs to whole populations. Cochrane Database Syst Rev 12: CD008846.

    • Search Google Scholar
    • Export Citation
  • 24.

    Bretscher MT, Griffin JT, Ghani AC, Okell LC, 2017. Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment. Malar J 16: 341.

    • Search Google Scholar
    • Export Citation
  • 25.

    Brady OJ 2017. Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study. Lancet Glob Health 5: e680e687.

    • Search Google Scholar
    • Export Citation
  • 26.

    Larsen DA, Bennett A, Silumbe K, Hamainza B, Yukich JO, Keating J, Littrell M, Miller JM, Steketee RW, Eisele TP, 2015. Population-wide malaria testing and treatment with rapid diagnostic tests and artemether-lumefantrine in southern Zambia: a community randomized step-wedge control trial design. Am J Trop Med Hyg 92: 913921.

    • Search Google Scholar
    • Export Citation
  • 27.

    Cook J 2019. Mass screening and treatment on the basis of results of a Plasmodium falciparum-specific rapid diagnostic test did not reduce malaria incidence in Zanzibar. J Infect Dis 211: 14761483.

    • Search Google Scholar
    • Export Citation
  • 28.

    Stresman GH 2015. Focal screening to identify the subpatent parasite reservoir in an area of low and heterogeneous transmission in the Kenya highlands. J Infect Dis 212: 17681777.

    • Search Google Scholar
    • Export Citation
  • 29.

    Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJ, 2012. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun 3: 1237.

    • Search Google Scholar
    • Export Citation
  • 30.

    McMorrow ML, Aidoo M, Kachur SP, 2011. Malaria rapid diagnostic tests in elimination settings—can they find the last parasite? Clin Microbiol Infect 17: 16241631.

    • Search Google Scholar
    • Export Citation
  • 31.

    Eisele TP 2020. Impact of four rounds of mass drug administration with dihydroartemisinin-piperaquine implemented in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 718.

    • Search Google Scholar
    • Export Citation
  • 32.

    Silumbe K 2020. Assessment of the acceptability of testing and treatment during a mass drug administration trial for malaria in Zambia using mixed methods. Am J Trop Med Hyg 103 (Suppl 2): 2836.

    • Search Google Scholar
    • Export Citation
  • 33.

    Finn TP 2020. Treatment coverage estimation for mass drug administration for malaria with dihydroartemisin-piperaquine in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 1927.

    • Search Google Scholar
    • Export Citation
  • 34.

    Finn TP 2020. Adherence to mass drug administration with dihydroartemisinin-piperaquine and Plasmodium falciparum clearance in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 3745.

    • Search Google Scholar
    • Export Citation
  • 35.

    Chishimba S 2020. Prevalence of Plasmodium falciparum and non-falciparum infections by photo-induced electron transfer–PCR in a longitudinal cohort of individuals enrolled in a mass drug administration trial in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 8289.

    • Search Google Scholar
    • Export Citation
  • 36.

    Bennett A 2020. A longitudinal cohort to monitor malaria infection incidence during mass drug administration in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 5465.

    • Search Google Scholar
    • Export Citation
  • 37.

    Daniels RF 2020. Evidence for reduced malaria parasite population after application of population-level antimalarial drug strategies in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 6673.

    • Search Google Scholar
    • Export Citation
  • 38.

    Porter TR 2020. Recent travel history and Plasmodium falciparum malaria infection in a region of heterogenous transmission in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 7481.

    • Search Google Scholar
    • Export Citation
  • 39.

    Chanda J 2020. Pyrethroid and carbamate resistance in Anopheles funestus giles along Lake Kariba in southern Zambia. Am J Trop Med Hyg 103 (Suppl 2): 9097.

    • Search Google Scholar
    • Export Citation
  • 40.

    Yukich JO 2020. Cost-effectiveness of focal mass drug administration and mass drug administration with dihydroartemisinin-piperaquine for malaria prevention in Southern Province, Zambia: results of a community-randomized controlled trial. Am J Trop Med Hyg 103 (Suppl 2): 4653.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

Moving from Malaria Burden Reduction toward Elimination: An Evaluation of Mass Drug Administration in Southern Province, Zambia

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  • 1 PATH Malaria Control and Elimination Partnership in Africa (MACEPA), Lusaka, Zambia;
  • 2 Department of Tropical Medicine, Center for Applied Malaria Research and Evaluation, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana;
  • 3 PATH MACEPA, Seattle, Washington;
  • 4 National Malaria Control Centre, Zambia Ministry of Health, Lusaka, Zambia

From December 2014 to February 2016, a cluster randomized controlled trial was carried out in 60 health facility catchment areas along Lake Kariba in Zambia’s Southern Province. The trial sought to evaluate the impact of four rounds of a mass drug administration (MDA) intervention with dihydroartemisinin–piperaquine (DHAP) or focal MDA with DHAP at the household level compared with a control population that received the standard of care. This study was the first randomized controlled trial with DHAP for MDA in sub-Saharan Africa and was conducted through a collaboration between the National Malaria Elimination Programme in the Zambian Ministry of Health, the PATH Malaria Control and Elimination Partnership in Africa, and the Center for Applied Malaria Research and Evaluation at Tulane University. This article serves as an introduction to a collection of articles designed to explore different aspects of the intervention. By describing the recent history of malaria control in Zambia leading up to the trial—from the scale-up of point-of-care diagnosis and treatment, vector control, and indoor residual spraying early in the twenty-first century, to the efforts made to sustain the gains achieved with that approach—it provides a rationale for the implementation of a trial that has informed a new national strategic plan and solidified malaria elimination as Zambia’s national goal.

INTRODUCTION

From December 2014 to February 2016, a cluster randomized controlled trial was carried out in 60 health facility catchment areas along Lake Kariba in Zambia’s Southern Province to evaluate the impact of four rounds of a mass treatment intervention with dihydroartemisinin–piperaquine (DHAP). The trial sought to evaluate the relative effectiveness of community-wide mass drug administration (MDA) or focal MDA (fMDA) at the household level (fMDA) with DHAP compared with a control population that received the standard of care (which included good access to case management, including community case management; high coverage of long-lasting insecticide-treated mosquito nets [LLINs] and indoor residual spraying [IRS] with pirimiphos-methyl; and robust surveillance, including rapid reporting and reactive case detection).

This groundbreaking study, the first randomized controlled trial with DHAP for MDA in sub-Saharan Africa, was the result of a collaboration between the National Malaria Control Programme in the Zambian Ministry of Health, the PATH Malaria Control and Elimination Partnership in Africa, and the Center for Applied Malaria Research and Evaluation at Tulane University. Because of the extensive data collection conducted for the trial, many different aspects of the intervention could be addressed in detail. Here, we present a collection of articles designed to explore these topics. This introductory article provides a history of malaria control in Zambia leading up to the trial, a rationale for its implementation, and a brief explanation of the articles found in the supplement.

ZAMBIA SCALES UP FOR IMPACT

Early in the twenty-first century, Zambia saw its malaria rates tripling over the previous three decades (from 121 per 1,000 population in 1976 to 428 per 1,000 population in 2003).1 With the global health and malaria community declaring ambitious malaria targets, the Zambian government identified malaria control as one of its main public health priorities. The country was not without existing prevention measures, but although LLIN distribution channels provided a solid base of coverage, they were disproportionately reaching those in urban areas and those with better access to healthcare facilities, rather than rural populations most affected by malaria.2 Thus, with an influx of additional resources planned by the Global Fund to Fight AIDS, Tuberculosis and Malaria and with renewed hope for progress in disease burden reduction, a strategic plan for 2006–2010 was developed emphasizing the scale-up of simplified point-of-care diagnosis with malaria rapid diagnostic tests (RDTs), artemisinin-based combination therapy, vector control with LLINs, and, in selected areas, IRS.1 Input from the Bill & Melinda Gates Foundation3,4 made mass distributions of LLINs possible, while support from Zambia’s traditional mining centers, the U.S. President’s Malaria Initiative (PMI), and the World Bank led to an increase in IRS coverage by the national program that expanded from the more urbanized rail corridor into more rural malarious districts. In addition, intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine for malaria prevention among expectant mothers was supported through antenatal clinics.

With this commitment came noticeable results. More than 6 million LLINs were distributed between 2007 and 2010, and more than 1 million households received IRS annually between 2008 and 2010. Between 2003 and 2010, IRS activities expanded from five districts to 54. By 2010, 73% of households in Zambia had either one or more LLINs or had received IRS in the previous year—a 41% increase in household availability of malaria prevention nationally between 2006 and 2010 and a 5-fold increase between 2001/2002 and 2008.5 In the early part of the decade, changes to Zambia’s case management treatment policy, from failing monotherapies to artemether–lumefantrine, were financed to support implementation, although progress in adoption in health facilities was slow.6 Between 2003 and 2008, malaria case management was supported by the increased availability of diagnostic tools, primarily through the expansion of RDTs, which were made available initially to rural health centers and health posts. In 2008, more than 2 million RDTs were distributed.7

In 2010, Zambia’s malaria focus shifted to sustaining the gains from the initial scale-up. As recommended by a program review in 20108 and adopted in the country’s 2011–2015 strategic plan,9 three broad malaria epidemiological strata were defined based on the latest prevalence information from national household surveys. Lusaka and environs were the lowest epidemiological burden, eastern and northern areas of Zambia the highest, and all other areas fell in the middle. Notable new activities during this period included the expansion of malaria testing and treatment services at the community level through integrated community case management (iCCM). The launch of the National Human Resources for Health Strategic Plan in 2011 focused on adding an additional 18,000 health workers in various cadres and 5,000 community health workers (CHWs).10 Early research had demonstrated the cost-effectiveness of engaging CHWs to supplement facility testing and treatment services.11 Integrated community case management training and funding for implementation ramped up during this period with support from the PMI, the Global Fund, and the Canada International Development Assistance. For the volunteering CHWs offering iCCM services, support was further provided nationally by the roll out of the community health assistant workforce and by increasing the number of health posts in underserved areas.12,13 Furthermore, the expansion of malaria case management to more rural, malarious areas through iCCM shifted coverage of care to trained CHWs,1416 addressing the most significant hurdle to diagnosis and treatment access.

In 2011, Zambia began using the District Health Information System, or DHIS2, an open-source health management information system platform that enabled the ministry of health to strengthen their routine health information systems, harmonize reporting across partners, and introduce a weekly malaria rapid reporting system via mobile phone–based data entry. The increasing timeliness and quality of data facilitated the ability to make strategic, data-driven decisions to improve service delivery. In 2011, Zambia initiated CHW-based passive and reactive case detection, expanding care and treatment access to communities and introducing a case investigation intervention to find additional malaria infections in the community.

SUSTAINING MALARIA CONTROL

Despite often achieving high coverage with vector control and other interventions, by 2014, Zambia had not achieved the reduction in transmission it had expected. Malaria indicators surveys in 2010 and 2012 showed that 16% and 15% of children tested positive by microscopy, respectively, an increase from the 10% documented in 2008.1719 Of note, many of these infections were in asymptomatic individuals likely because of acquired immunity; thus, passive case detection methods seemed unlikely to substantially reduce the parasite reservoir in the population. These challenges to the “control-only” approach and rising global interest in malaria elimination helped move Zambia toward setting an ambitious malaria elimination target date of 2021. To achieve this, new tools were needed and various approaches to population-based drug strategies were considered and tested.

Although MDA had been used in many different countries for malaria control in past decades, it had largely fallen out of favor because of concerns about the transient impact and drug resistance. However, as the global progress began to stagnate between 2000 and 2010, the malaria community began looking for alternative tools. Mass drug administration and related activities—mass test and treat (MTAT), mass screen and treat, and fMDA—began to be re-examined as potential solutions. Mass drug administration had a long, successful history of control and elimination for some neglected tropical diseases, and the advent of artemisinin-based combination therapies meant that resistance was less likely.20,21 However, the evidence surrounding these solutions was incomplete, having mostly been generated decades ago using nonexperimental study designs that limited the evidence generated. In addition, many MDA interventions were one-off research exercises that did not include robust malaria prevention and control activities after cessation of the study.22 A 2013 Cochrane review concluded that MDA was likely safe but noted the lack of high-quality evidence and called for studies that looked at how the effects of MDA could be sustained past 6 months after administration.23 Early modeling results also suggested that MDA could have a significant impact when coupled with other interventions such as robust vector control.24,25

A PIVOT TOWARD ELIMINATION

The decision to launch an MDA trial stemmed from the new focus on elimination and the realization that MTAT, a mass treatment strategy the country had already experimented with, was inadequate to achieve substantial transmission reduction. An MTAT randomized controlled trial conducted in Southern Province, Zambia, from 2011 to 2013 showed a statistically significant effect but one far too small to provide major gains toward elimination.26 A similar study conducted in Zanzibar showed no effect.27 At the same time, reports from several studies showed that HRP2 RDTs were missing a significant number of low-density infections, meaning that a substantial component of the parasite reservoir would not be detected by a test-and-treat strategy.2830 In this context, therefore, MDA was a promising malaria elimination acceleration strategy to test.

This supplement presents the results of the main trial evaluating four rounds of MDA or fMDA with DHAP, compared with a control of no MDA or fMDA.31 We also report the findings of several studies conducted concurrently that investigated various aspects of the trial. These include studies on the acceptability of treatment,32 MDA coverage,33 DHAP efficacy and adherence to the treatment regimen,34 RDT performance,35 infection incidence,36 parasite genotypes before and after the intervention,37 human movement and the relationship between travel history and malaria infection status,38 insecticide resistance and parasite infection in Anopheles funestus mosquitoes in the study area,39 and the cost-effectiveness of adding an MDA or fMDA strategy to the standard-of-care malaria control in Southern Province.40 Although specific to the trial and study area, many of the issues explored in these articles are germane to consideration of the potential usefulness of population-based drug strategies in other settings. Moreover, the gains in knowledge from this trial helped usher Zambia into a new era of its malaria efforts, providing key evidence to inform a new national strategic plan and solidifying elimination as the national goal.

Acknowledgments:

We express our gratitude to the study respondents in Southern Province for participating in this study. We also express our gratitude to the Zambia Ministry of Health at all levels. At the Provincial Health Office, we are especially grateful for the support of Jelita Chinyonga, provincial medical officer, and her staff for moving this effort forward. We would like to thank Chris Lungu, Muleba Matafwali, Kedrick Katonga, Sosenna Assefa, Juliana Ngalande, Hazel Chabala, and Elisabeth Wilhem for their enduring support during study implementation. We also acknowledge the support of Daniel J. Bridges, Conceptor Mulube, Brenda Mambwe, Rachel Kasaro, and Mirriam Chibalabala for their support in laboratory sample management and analyses. We also thank the Bill & Melinda Gates Foundation for their financial support.

REFERENCES

  • 1.

    Zambia Ministry of Health, 2006. A Road Map for Impact on Malaria in Zambia 2006–2010: A 5-Year Strategic Plan. Lusaka, Zambia: Zambia Ministry of Health.

    • Search Google Scholar
    • Export Citation
  • 2.

    Agha S, Van Rossem R, Stallworthy G, Kusanthan T, 2007. The impact of a hybrid social marketing intervention on inequities in access, ownership and use of insecticide-treated nets. Malar J 6: 13.

    • Search Google Scholar
    • Export Citation
  • 3.

    Chanda P, Masiye F, Chitah BM, Sipilanyambe N, Moonga H, Banda P, Okorosobo T, 2007. A cost-effectiveness analysis of artemether lumefantrine for treatment of uncomplicated malaria in Zambia. Malar J 6: 21.

    • Search Google Scholar
    • Export Citation
  • 4.

    Steketee RW, Sipilanyambe N, Chimumbwa J, Banda JJ, Mohamed A, Miller J, Basu S, Miti SK, Campbell CC, 2008. National malaria control and scaling up for impact: the Zambia experience through 2006. Am J Trop Med Hyg 79: 4552.

    • Search Google Scholar
    • Export Citation
  • 5.

    Roll Back Malaria, 2011. Focus on Zambia. Geneva, Switzerland: World Health Organization. Progress & Impact Series Country Reports No. 2.

    • Search Google Scholar
    • Export Citation
  • 6.

    Zurovac D, Ndhlovu M, Sipilanyambe N, Chanda P, Hamer DH, Simon JL, Snow RW, 2007. Paediatric malaria case-management with artemether-lumefantrine in Zambia: a repeat cross-sectional study. Malar J 6: 31.

    • Search Google Scholar
    • Export Citation
  • 7.

    Chizema-Kawesha E, Miller JM, Steketee RW, Mukonka VM, Mukuka C, Mohamed AD, Miti SK, Campbell CC, 2010. Scaling up malaria control in Zambia: progress and impact 2005–2008. Am J Trop Med Hyg 83: 480488.

    • Search Google Scholar
    • Export Citation
  • 8.

    Zambia Ministry of Health, 2010. Zambia National Malaria Programme Performance Review 2010. Lusaka, Zambia: Ministry of Health.

  • 9.

    Zambia Ministry of Health, 2015. National Malaria Control Programme Strategic Plan for FY 2011–2016: Consolidating Malaria Gains for Impact in National Malaria Strategic Plan. Lusaka, Zambia: Zambia Ministry of Health.

    • Search Google Scholar
    • Export Citation
  • 10.

    Zambia Ministry of Health, 2011. National Human Resources for Health Strategic Plan 2011–2015. Lusaka, Zambia: Ministry of Health.

  • 11.

    Chanda P, Hamainza B, Moonga HB, Chalwe V, Banda P, Pagnoni F, 2011, Relative costs and effectiveness of treating uncomplicated malaria in two rural districts in Zambia: implications for nationwide scale-up of home-based management. Malar J 10: 159.

    • Search Google Scholar
    • Export Citation
  • 12.

    Shelley KD, Belete YW, Phiri SC, Musonda M, Kawesha EC, Muleya EM, Chibawe CP, van den Broek JW, Vosburg KB, 2016. Implementation of the community health assistant (CHA) cadre in Zambia: a process evaluation to guide future scale-up decisions. J Community Health 41: 398408.

    • Search Google Scholar
    • Export Citation
  • 13.

    Lusaka Times, 2015. Construction of 650 Health Posts on Course for Completion Next Year. Lusaka, Zambia: Lusaka Times.

  • 14.

    Seidenberg PD, Hamer DH, Iyer H, Pilingana P, Siazeele K, Hamainza B, MacLeod WB, Yeboah-Antwi K, 2012. Impact of integrated community case management on health-seeking behavior in rural Zambia. Am J Trop Med Hyg 87 (Suppl 5): 105110.

    • Search Google Scholar
    • Export Citation
  • 15.

    Larsen DA, Winters A, Cheelo S, Hamainza B, Kamuliwo M, Miller JM, Bridges DJ, 2017. Shifting the burden or expanding access to care? Assessing malaria trends following scale-up of community health worker malaria case management and reactive case detection. Malar J 16: 441.

    • Search Google Scholar
    • Export Citation
  • 16.

    Strachan C, Wharton-Smith A, Sinyangwe C, Mubiru D, Ssekitooleko J, Meier J, Gbanya M, Tibenderana JK, Counihan H, 2014. Integrated community case management of malaria, pneumonia and diarrhoea across three African countries: a qualitative study exploring lessons learnt and implications for further scale up. J Glob Health 4: 020404.

    • Search Google Scholar
    • Export Citation
  • 17.

    Zambia Ministry of Health, 2010. Zambia National Malaria Indicator Survey 2010. Lusaka, Zambia: Ministry of Health.

  • 18.

    Zambia Ministry of Health, 2012. Zambia National Malaria Indicator Survey 2012. Lusaka, Zambia: Ministry of Health.

  • 19.

    Zambia Ministry of Health, 2008. Zambia National Malaria Indicator Survey 2008. Lusaka, Zambia: Ministry of Health.

  • 20.

    von Seidlein L, Dondorp A, 2015. Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance. Expert Rev Anti Infect Ther 13: 715730.

    • Search Google Scholar
    • Export Citation
  • 21.

    White NJ, 2016. Does antimalarial mass drug administration increase or decrease the risk of resistance? Lancet Infect Dis 17: e15e20.

  • 22.

    von Seidlein L, Greenwood BM, 2003. Mass administrations of antimalarial drugs. Trends Parasitol 19: 452460.

  • 23.

    Poirot E, Skarbinski J, Sinclair D, Kachur S, Slutsker L, Hwang J, 2013. Administration of antimalarial drugs to whole populations. Cochrane Database Syst Rev 12: CD008846.

    • Search Google Scholar
    • Export Citation
  • 24.

    Bretscher MT, Griffin JT, Ghani AC, Okell LC, 2017. Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment. Malar J 16: 341.

    • Search Google Scholar
    • Export Citation
  • 25.

    Brady OJ 2017. Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study. Lancet Glob Health 5: e680e687.

    • Search Google Scholar
    • Export Citation
  • 26.

    Larsen DA, Bennett A, Silumbe K, Hamainza B, Yukich JO, Keating J, Littrell M, Miller JM, Steketee RW, Eisele TP, 2015. Population-wide malaria testing and treatment with rapid diagnostic tests and artemether-lumefantrine in southern Zambia: a community randomized step-wedge control trial design. Am J Trop Med Hyg 92: 913921.

    • Search Google Scholar
    • Export Citation
  • 27.

    Cook J 2019. Mass screening and treatment on the basis of results of a Plasmodium falciparum-specific rapid diagnostic test did not reduce malaria incidence in Zanzibar. J Infect Dis 211: 14761483.

    • Search Google Scholar
    • Export Citation
  • 28.

    Stresman GH 2015. Focal screening to identify the subpatent parasite reservoir in an area of low and heterogeneous transmission in the Kenya highlands. J Infect Dis 212: 17681777.

    • Search Google Scholar
    • Export Citation
  • 29.

    Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJ, 2012. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun 3: 1237.

    • Search Google Scholar
    • Export Citation
  • 30.

    McMorrow ML, Aidoo M, Kachur SP, 2011. Malaria rapid diagnostic tests in elimination settings—can they find the last parasite? Clin Microbiol Infect 17: 16241631.

    • Search Google Scholar
    • Export Citation
  • 31.

    Eisele TP 2020. Impact of four rounds of mass drug administration with dihydroartemisinin-piperaquine implemented in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 718.

    • Search Google Scholar
    • Export Citation
  • 32.

    Silumbe K 2020. Assessment of the acceptability of testing and treatment during a mass drug administration trial for malaria in Zambia using mixed methods. Am J Trop Med Hyg 103 (Suppl 2): 2836.

    • Search Google Scholar
    • Export Citation
  • 33.

    Finn TP 2020. Treatment coverage estimation for mass drug administration for malaria with dihydroartemisin-piperaquine in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 1927.

    • Search Google Scholar
    • Export Citation
  • 34.

    Finn TP 2020. Adherence to mass drug administration with dihydroartemisinin-piperaquine and Plasmodium falciparum clearance in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 3745.

    • Search Google Scholar
    • Export Citation
  • 35.

    Chishimba S 2020. Prevalence of Plasmodium falciparum and non-falciparum infections by photo-induced electron transfer–PCR in a longitudinal cohort of individuals enrolled in a mass drug administration trial in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 8289.

    • Search Google Scholar
    • Export Citation
  • 36.

    Bennett A 2020. A longitudinal cohort to monitor malaria infection incidence during mass drug administration in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 5465.

    • Search Google Scholar
    • Export Citation
  • 37.

    Daniels RF 2020. Evidence for reduced malaria parasite population after application of population-level antimalarial drug strategies in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 6673.

    • Search Google Scholar
    • Export Citation
  • 38.

    Porter TR 2020. Recent travel history and Plasmodium falciparum malaria infection in a region of heterogenous transmission in Southern Province, Zambia. Am J Trop Med Hyg 103 (Suppl 2): 7481.

    • Search Google Scholar
    • Export Citation
  • 39.

    Chanda J 2020. Pyrethroid and carbamate resistance in Anopheles funestus giles along Lake Kariba in southern Zambia. Am J Trop Med Hyg 103 (Suppl 2): 9097.

    • Search Google Scholar
    • Export Citation
  • 40.

    Yukich JO 2020. Cost-effectiveness of focal mass drug administration and mass drug administration with dihydroartemisinin-piperaquine for malaria prevention in Southern Province, Zambia: results of a community-randomized controlled trial. Am J Trop Med Hyg 103 (Suppl 2): 4653.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to John M. Miller, PATH Malaria Control and Elimination Partnership in Africa, Mikwala House, Stand 11059, off Brentwood Lane, Longacres, Lusaka, Zambia. E-mail: jmiller@path.org

Disclosure: All authors had full access to all the data in the study.

Disclaimer: The funding source had no role in the conduct, analysis, or interpretation of results of the study.

Financial support: The trial was an investigator-initiated study supported by a grant from the Bill & Melinda Gates Foundation.

Authors’ addresses: John M. Miller, Maya S. Fraser, Manuel T. Lewis, and Laurence Slutsker, PATH Malaria Control and Elimination Partnership in Africa (MACEPA), Lusaka, Zambia, E-mails: jmiller@path.org, mfraser@path.org, mtlewis@path.org, and lslutsker@path.org. Thomas P. Eisele, Department of Tropical Medicine, Center for Applied Malaria Research and Evaluation, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, E-mail: teisele@tulane.edu. Elizabeth Chizema Kawesha, National Malaria Control Centre, Zambia Ministry of Health, Lusaka, Zambia, E-mail: e.chizema5@gmail.com.

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