• 1.

    WHO, 2015. World Malaria Report. Available at: http://www.who.int/malaria/publications/world-malaria-report-2015/report/en/. Accessed November 13, 2018.

  • 2.

    WHO, 2016. World Malaria Report. Available at: http://www.who.int/malaria/publications/world-malaria-report-2016/report/en/. Accessed November 13, 2018.

  • 3.

    Searle KM, Hamapumbu H, Lubinda J, Shields TM, Pinchoff J, Kobayashi T, Stevenson JC, Bridges DJ, Larsen DA, Thuma PE, Moss WJ; Southern Africa International Centers of Excellence for Malaria Research, 2016. Evaluation of the operational challenges in implementing reactive screen-and-treat and implications of reactive case detection strategies for malaria elimination in a region of low transmission in southern Zambia. Malar J 15: 412.

    • Search Google Scholar
    • Export Citation
  • 4.

    Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L, 2013. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther 11: 623639.

    • Search Google Scholar
    • Export Citation
  • 5.

    Bousema JT, Gouagna LC, Drakeley CJ, Meutstege AM, Okech BA, Akim IN, Beier JC, Githure JI, Sauerwein RW, 2004. Plasmodium falciparum gametocyte carriage in asymptomatic children in western Kenya. Malar J 3: 18.

    • Search Google Scholar
    • Export Citation
  • 6.

    Lin JT, Saunders DL, Meshnick SR, 2014. The role of submicroscopic parasitemia in malaria transmission: what is the evidence? Trends Parasitol 30: 183190.

    • Search Google Scholar
    • Export Citation
  • 7.

    Bousema T, Okell L, Felger I, Drakeley C, 2014. Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nat Rev Microbiol 12: 833840.

    • Search Google Scholar
    • Export Citation
  • 8.

    de Mast Q, Brouwers J, Syafruddin D, Bousema T, Baidjoe AY, de Groot PG, van der Ven AJ, Fijnheer R, 2015. Is asymptomatic malaria really asymptomatic? Hematological, vascular and inflammatory effects of asymptomatic malaria parasitemia. J Infect 71: 587596.

    • Search Google Scholar
    • Export Citation
  • 9.

    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
  • 10.

    Okell LC, Ghani AC, Lyons E, Drakeley CJ, 2009. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis 200: 15091517.

    • Search Google Scholar
    • Export Citation
  • 11.

    Mharakurwa S, Thuma PE, Norris DE, Mulenga M, Chalwe V, Chipeta J, Munyati S, Mutambu S, Mason PR; Southern Africa International Centers of Excellence for Malaria Research, 2012. Malaria epidemiology and control in southern Africa. Acta Trop 121: 202206.

    • Search Google Scholar
    • Export Citation
  • 12.

    Laban NM, Kobayashi T, Hamapumbu H, Sullivan D, Mharakurwa S, Thuma PE, Shiff CJ, Moss WJ; Southern Africa International Centers of Excellence for Malaria Research, 2015. Comparison of a PfHRP2-based rapid diagnostic test and PCR for malaria in a low prevalence setting in rural southern Zambia: implications for elimination. Malar J 14: 25.

    • Search Google Scholar
    • Export Citation
  • 13.

    PMI, 2018. FY 2018 Zambia Malaria Operational Plan. Available at: https://www.pmi.gov/where-we-work/zambia. Accessed November 13, 2018.

  • 14.

    Kent RJ, Mharakurwa S, Norris DE, 2007. Spatial and temporal genetic structure of Anopheles arabiensis in southern Zambia over consecutive wet and drought years. Am J Trop Med Hyg 77: 316323.

    • Search Google Scholar
    • Export Citation
  • 15.

    WHO, 2017. Malaria Rapid Diagnostic Test Performance—Results of WHO Product Testing of Malaria RDTs: Round 7 (2015–2016). Available at: https://www.who.int/malaria/publications/atoz/978924151268/en/. Accessed November 13, 2018.

  • 16.

    Kain KC, Lanar DE, 1991. Determination of genetic variation within Plasmodium falciparum by using enzymatically amplified DNA from filter paper disks impregnated with whole blood. J Clin Microbiol 29: 11711174.

    • Search Google Scholar
    • Export Citation
  • 17.

    Steenkeste N et al. 2009. Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers. Malar J 8: 86.

  • 18.

    Mlambo G, Vasquez Y, LeBlanc R, Sullivan D, Kumar N, 2008. A filter paper method for the detection of Plasmodium falciparum gametocytes by reverse transcription polymerase chain reaction. Am J Trop Med Hyg 78: 114116.

    • Search Google Scholar
    • Export Citation
  • 19.

    Mayxay M, Pukrittayakamee S, Chotivanich K, Looareesuwan S, White NJ, 2001. Persistence of Plasmodium falciparum HRP-2 in successfully treated acute falciparum malaria. Trans R Soc Trop Med Hyg 95: 179182.

    • Search Google Scholar
    • Export Citation
  • 20.

    Marquart L, Butterworth A, McCarthy JS, Gatton ML, 2012. Modelling the dynamics of Plasmodium falciparum histidine-rich protein 2 in human malaria to better understand malaria rapid diagnostic test performance. Malar J 11: 74.

    • Search Google Scholar
    • Export Citation
  • 21.

    CIA, 2017. The World Factbook—Zambia. Available at: https://www.cia.gov/library/publications/the-world-factbook/geos/za.html. Accessed August 8, 2018.

  • 22.

    Gatton ML, Cheng Q, 2010. Interrupting malaria transmission: quantifying the impact of interventions in regions of low to moderate transmission. PLoS One 5: e15149.

    • Search Google Scholar
    • Export Citation
  • 23.

    Stresman GH, Stevenson JC, Ngwu N, Marube E, Owaga C, Drakeley C, Bousema T, Cox J, 2014. High levels of asymptomatic and subpatent Plasmodium falciparum parasite carriage at health facilities in an area of heterogeneous malaria transmission intensity in the Kenyan highlands. Am J Trop Med Hyg 91: 11011108.

    • Search Google Scholar
    • Export Citation
  • 24.

    Stevenson JC, Stresman GH, Baidjoe A, Okoth A, Oriango R, Owaga C, Marube E, Bousema T, Cox J, Drakeley C, 2015. Use of different transmission metrics to describe malaria epidemiology in the highlands of western Kenya. Malar J 14: 418.

    • Search Google Scholar
    • Export Citation
  • 25.

    Wu L, van den Hoogen LL, Slater H, Walker PG, Ghani AC, Drakeley CJ, Okell LC, 2015. Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature 2015 Dec 3 (7580): S86–S93. DOI: 10.1038/nature16039.

  • 26.

    Ouedraogo AL et al. 2016. Dynamics of the human infectious reservoir for malaria determined by mosquito feeding assays and ultrasensitive malaria diagnosis in Burkina Faso. J Infect Dis 213: 9099.

    • Search Google Scholar
    • Export Citation
  • 27.

    Nankabirwa J, Brooker SJ, Clarke SE, Fernando D, Gitonga CW, Schellenberg D, Greenwood B, 2014. Malaria in school‐age children in Africa: an increasingly important challenge. Trop Med Int Health 19: 12941309.

    • Search Google Scholar
    • Export Citation
  • 28.

    Walldorf JA et al. 2015. School-age children are a reservoir of malaria infection in Malawi. PLoS One 10: e0134061.

  • 29.

    Noor AM, Kirui VC, Brooker SJ, Snow RW, 2009. The use of insecticide treated nets by age: implications for universal coverage in Africa. BMC Public Health 9: 369.

    • Search Google Scholar
    • Export Citation
  • 30.

    Pinchoff J, Hamapumbu H, Kobayashi T, Simubali L, Stevenson JC, Norris DE, Colantuoni E, Thuma PE, Moss WJ; Southern Africa International Centers of Excellence for Malaria Research, 2015. Factors associated with sustained use of long-lasting insecticide-treated nets following a reduction in malaria transmission in southern Zambia. Am J Trop Med Hyg 93: 954960.

    • Search Google Scholar
    • Export Citation
  • 31.

    Kanyangarara M, Hamapumbu H, Mamini E, Lupiya J, Stevenson JC, Mharakurwa S, Chaponda M, Thuma PE, Gwanzura L, Munyati S, Mulenga M, Norris DE, Moss WJ; Southern Africa International Centers of Excellence for Malaria Research, 2018. Malaria knowledge and bed net use in three transmission settings in southern Africa. Malar J 17: 41.

    • Search Google Scholar
    • Export Citation
  • 32.

    Proietti C, Pettinato DD, Kanoi BN, Ntege E, Crisanti A, Riley EM, Egwang TG, Drakeley C, Bousema T, 2011. Continuing intense malaria transmission in northern Uganda. Am J Trop Med Hyg 84: 830837.

    • Search Google Scholar
    • Export Citation
  • 33.

    Koita OA et al. 2012. False-negative rapid diagnostic tests for malaria and deletion of the histidine-rich repeat region of the hrp2 gene. Am J Trop Med Hyg 86: 194198.

    • Search Google Scholar
    • Export Citation
  • 34.

    Wurtz N et al. 2013. Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests. Malar J 12: 34.

    • Search Google Scholar
    • Export Citation
  • 35.

    Parr JB et al. 2017. Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of the Congo: a national cross-sectional survey. J Infect Dis 216: 3644.

    • Search Google Scholar
    • Export Citation
  • 36.

    Menegon M, L’Episcopia M, Nurahmed AM, Talha AA, Nour BYM, Severini C, 2017. Identification of Plasmodium falciparum isolates lacking histidine-rich protein 2 and 3 in Eritrea. Infect Genet Evol 55: 131134.

    • Search Google Scholar
    • Export Citation
  • 37.

    Berhane A et al. 2018. Major threat to malaria control programs by Plasmodium falciparum lacking histidine-rich protein 2, Eritrea. Emerg Infect Dis 24: 462470.

    • Search Google Scholar
    • Export Citation
  • 38.

    Kozycki CT, Umulisa N, Rulisa S, Mwikarago EI, Musabyimana JP, Habimana JP, Karema C, Krogstad DJ, 2017. False-negative malaria rapid diagnostic tests in Rwanda: impact of Plasmodium falciparum isolates lacking hrp2 and declining malaria transmission. Malar J 16: 123.

    • Search Google Scholar
    • Export Citation
  • 39.

    Wampfler R, Mwingira F, Javati S, Robinson L, Betuela I, Siba P, Beck HP, Mueller I, Felger I, 2013. Strategies for detection of Plasmodium species gametocytes. PLoS One 8: e76316.

    • Search Google Scholar
    • Export Citation
  • 40.

    Bousema T, Drakeley C, 2011. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev 24: 377410.

    • Search Google Scholar
    • Export Citation
 
 
 

 

 
 
 

 

 

 

 

 

 

Characteristics of Subpatent Malaria in a Pre-Elimination Setting in Southern Zambia

View More View Less
  • 1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
  • | 2 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
  • | 3 Macha Research Trust, Choma, Zambia;
  • | 4 Ministry of Fisheries and Livestock, Nchelenge, Zambia;
  • | 5 W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

To achieve and sustain malaria elimination, identification and treatment of the asymptomatic infectious reservoir is critical. Malaria rapid diagnostic tests (RDTs) are frequently used to identify asymptomatic, Plasmodium-infected individuals through test-and-treat strategies, but their sensitivity is low when used in low transmission settings. Characteristics of individuals with subpatent (RDT-negative but polymerase chain reaction [PCR]–positive) Plasmodium parasitemia were evaluated in southern Zambia where malaria transmission has declined and efforts to achieve malaria elimination are underway. Simple random sampling based on satellite imagery was used to select households for participation in community-based, cross-sectional surveys between 2008 and 2013. Questionnaires were administered to collect information on age, gender, recent history of malaria symptoms, and recent antimalarial drug use. Blood samples were collected by finger prick for Plasmodium falciparum histidine-rich protein 2 RDT, blood smears for microscopy, and dried blood spots for molecular analysis to detect malaria parasites and their sexual stage. Of 3,863 participants with complete data, 102 (2.6%) were positive by microscopy, RDT, or PCR. Of these, 48 (47%) had subpatent parasitemia. Most individuals with subpatent parasitemia were asymptomatic (85%). Compared with individuals without parasitemia, individuals with subpatent parasitemia were significantly more likely to be aged 5–25 years. Approximately one quarter (27%) of those with subpatent parasitemia had detectable gametocytemia. These findings suggest that strategies based on active or reactive case detection can identify asymptomatic individuals positive by RDT, but more sensitive diagnostic tests or focal drug administration may be necessary to target individuals with subpatent parasitemia to achieve malaria elimination.

    • Supplemental Materials (PDF 145 KB)

Author Notes

Address correspondence to Tamaki Kobayashi, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St. W4612, Baltimore, MD 21205. E-mails: tkobaya2@jhu.edu

Conflicts of interest: P. T. reports grants from NIH/NIAID during the conduct of the study.

Authors’ addresses: Tamaki Kobayashi, Kelly M. Searle, and William J. Moss, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mails: tkobaya2@jhu.edu, ksearle1@jhu.edu, and wmoss1@jhu.edu. Mufaro Kanyangarara, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: mkanyan1@jhu.edu. Natasha M. Laban, Harry Hamapumbu, Jennifer C. Stevenson, and Philip E. Thuma, Macha Research Trust, Choma, Zambia, E-mails: natasha.laban1@gmail.com, harry.hamapumbu@macharesearch.org, jennyc.stevenson@macharesearch.org, and phil.thuma@macharesearch.org. Masiliso Phiri, Ministry of Fisheries and Livestock, Nchelenge, Zambia, E-mail: masilisophiri@gmail.com.

The Southern Africa International Centers of Excellence for Malaria Research includes: Biomedical Research and Training Institute, Zimbabwe; Johns Hopkins Malaria Research Institute, Baltimore, MD; Macha Research Trust, Zambia; National Institute of Health Research, Zimbabwe; Tropical Diseases Research Centre, Zambia; University of the Witwatersrand, South Africa; and the University of Zambia, Zambia.

Save