Skip to main content Accessibility help
×
Home

Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment

  • MARTHA BETSON (a1), JOSÉ C. SOUSA-FIGUEIREDO (a2), AARON ATUHAIRE (a3), MOSES ARINAITWE (a3), MOSES ADRIKO (a3), GERALD MWESIGWA (a3), JUMA NABONGE (a4), NARCIS B. KABATEREINE (a3), COLIN J. SUTHERLAND (a2) and J. RUSSELL STOTHARD (a5)...

Summary

During a longitudinal study investigating the dynamics of malaria in Ugandan lakeshore communities, a consistently high malaria prevalence was observed in young children despite regular treatment. To explore the short-term performance of artemether-lumefantrine (AL), a pilot investigation into parasite carriage after treatment(s) was conducted in Bukoba village. A total of 163 children (aged 2–7 years) with a positive blood film and rapid antigen test were treated with AL; only 8·7% of these had elevated axillary temperatures. On day 7 and then on day 17, 40 children (26·3%) and 33 (22·3%) were positive by microscopy, respectively. Real-time PCR analysis demonstrated that multi-species Plasmodium infections were common at baseline, with 41·1% of children positive for Plasmodium falciparum/Plasmodium malariae, 9·2% for P. falciparum/ Plasmodium ovale spp. and 8·0% for all three species. Moreover, on day 17, 39·9% of children infected with falciparum malaria at baseline were again positive for the same species, and 9·2% of those infected with P. malariae at baseline were positive for P. malariae. Here, chronic multi-species malaria infections persisted in children after AL treatment(s). Better point-of-care diagnostics for non-falciparum infections are needed, as well as further investigation of AL performance in asymptomatic individuals.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment
      Available formats
      ×

Copyright

The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution licence http://creativecommons.org/licenses/by/3.0/

Corresponding author

*Corresponding author: Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. E-mail: jrstoth@liv.ac.uk

References

Hide All
Achan, J., Tibenderana, J. K., Kyabayinze, D., Wabwire Mangen, F., Kamya, M. R., Dorsey, G., D'Alessandro, U., Rosenthal, P. J. and Talisuna, A. O. (2009). Effectiveness of quinine versus artemether-lumefantrine for treating uncomplicated falciparum malaria in Ugandan children: randomised trial. British Medical Journal 339, b2763.
Arinaitwe, E., Sandison, T. G., Wanzira, H., Kakuru, A., Homsy, J., Kalamya, J., Kamya, M. R., Vora, N., Greenhouse, B., Rosenthal, P. J., Tappero, J. and Dorsey, G. (2009). Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clinical Infectious Diseases 49, 16291637.
Aydin-Schmidt, B., Mubi, M., Morris, U., Petzold, M., Ngasala, B. E., Premji, Z., Bjorkman, A. and Martensson, A. (2013). Usefulness of Plasmodium falciparum-specific rapid diagnostic tests for assessment of parasite clearance and detection of recurrent infections after artemisinin-based combination therapy. Malaria Journal 12, 349.
Baliraine, F. N. and Rosenthal, P. J. (2011). Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria with artemether-lumefantrine in Uganda. Journal of Infectious Diseases 204, 11201124.
Bassat, Q., Mulenga, M., Tinto, H., Piola, P., Borrmann, S., Menendez, C., Nambozi, M., Valea, I., Nabasumba, C., Sasi, P., Bacchieri, A., Corsi, M., Ubben, D., Talisuna, A. and D'Alessandro, U. (2009). Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial. PLoS One 4, e7871.
Batwala, V., Magnussen, P. and Nuwaha, F. (2010). Challenges to implementation of artemisinin combination therapy policy in Uganda. International Health 2, 262268.
Beshir, K. B., Sutherland, C. J., Sawa, P., Drakeley, C. J., Okell, L., Mweresa, C. K., Omar, S. A., Shekalaghe, S. A., Kaur, H., Ndaro, A., Chilongola, J., Schallig, H. D., Sauerwein, R. W., Hallett, R. L. and Bousema, T. (2013). Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. Journal of Infectious Diseases 208, 20172024.
Betson, M., Sousa-Figueiredo, J. C., Rowell, C., Kabatereine, N. B. and Stothard, J. R. (2010). Intestinal schistosomiasis in mothers and young children in Uganda: investigation of field-applicable markers of bowel morbidity. American Journal of Tropical Medicine and Hygiene 83, 10481055.
Borrmann, S., Sasi, P., Mwai, L., Bashraheil, M., Abdallah, A., Muriithi, S., Fruhauf, H., Schaub, B., Pfeil, J., Peshu, J., Hanpithakpong, W., Rippert, A., Juma, E., Tsofa, B., Mosobo, M., Lowe, B., Osier, F., Fegan, G., Lindegardh, N., Nzila, A., Peshu, N., Mackinnon, M. and Marsh, K. (2011). Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast. PLoS One 6, e26005.
Bruce, M. C., Macheso, A., Kelly-Hope, L. A., Nkhoma, S., McConnachie, A. and Molyneux, M. E. (2008). Effect of transmission setting and mixed species infections on clinical measures of malaria in Malawi. PLoS One 3, e2775.
Bukirwa, H., Yeka, A., Kamya, M. R., Talisuna, A., Banek, K., Bakyaita, N., Rwakimari, J. B., Rosenthal, P. J., Wabwire-Mangen, F., Dorsey, G. and Staedke, S. G. (2006). Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clinical Trials 1, e7.
Collins, W. E. and Jeffery, G. M. (2005). Plasmodium ovale: parasite and disease. Clinical Microbiology Reviews 18, 570581.
Collins, W. E. and Jeffery, G. M. (2007). Plasmodium malariae: parasite and disease. Clinical Microbiology Reviews 20, 579592.
Dinko, B., Oguike, M. C., Larbi, J. A., Bousema, T. and Sutherland, C. J. (2013). Persistent detection of Plasmodium falciparum, P. malariae, P. ovale curtisi and P. ovale wallikeri after ACT treatment of asymptomatic Ghanaian school-children. International Journal for Parasitology: Drugs and Drug Resistance 3, 4550.
Dlamini, S. V., Beshir, K. and Sutherland, C. J. (2010). Markers of anti-malarial drug resistance in Plasmodium falciparum isolates from Swaziland: identification of pfmdr1-86F in natural parasite isolates. Malaria Journal 9, 68.
Dondorp, A. M., Nosten, F., Yi, P., Das, D., Phyo, A. P., Tarning, J., Lwin, K. M., Ariey, F., Hanpithakpong, W., Lee, S. J., Ringwald, P., Silamut, K., Imwong, M., Chotivanich, K., Lim, P., Herdman, T., An, S. S., Yeung, S., Singhasivanon, P., Day, N. P., Lindegardh, N., Socheat, D. and White, N. J. (2009). Artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine 361, 455467.
Dorsey, G., Staedke, S., Clark, T. D., Njama-Meya, D., Nzarubara, B., Maiteki-Sebuguzi, C., Dokomajilar, C., Kamya, M. R. and Rosenthal, P. J. (2007). Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. Journal of the American Medical Association 297, 22102219.
Drakeley, C. and Reyburn, H. (2009). Out with the old, in with the new: the utility of rapid diagnostic tests for malaria diagnosis in Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene 103, 333337.
Felger, I. and Snounou, G. (2008). Recommended Genotyping Procedures (RGPs) to Identify Parasite Populations. Medicine for Malaria Venture and World Health Organization, Geneva, Switzerland.
Fogg, C., Bajunirwe, F., Piola, P., Biraro, S., Checchi, F., Kiguli, J., Namiiro, P., Musabe, J., Kyomugisha, A. and Guthmann, J. P. (2004). Adherence to a six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Uganda. American Journal of Tropical Medicine and Hygiene 71, 525530.
Gadalla, N. B., Adam, I., Elzaki, S. E., Bashir, S., Mukhtar, I., Oguike, M., Gadalla, A., Mansour, F., Warhurst, D., El-Sayed, B. B. and Sutherland, C. J. (2011). Increased pfmdr1 copy Number and sequence polymorphisms in Plasmodium falciparum isolates from Sudanese malaria patients treated with artemether-lumefantrine. Antimicrobial Agents and Chemotherapy 55, 54085411.
Houzé, S., Hubert, V., Cohen, D. P., Rivetz, B. and Le Bras, J. (2011). Evaluation of the Clearview(R) malaria pLDH malaria rapid diagnostic test in a non-endemic setting. Malaria Journal 10, 284.
Humphreys, G. S., Merinopoulos, I., Ahmed, J., Whitty, C. J., Mutabingwa, T. K., Sutherland, C. J. and Hallett, R. L. (2007). Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria. Antimicrobial Agents and Chemotherapy 51, 991997.
Juliano, J. J., Gadalla, N., Sutherland, C. J. and Meshnick, S. R. (2010). The perils of PCR: can we accurately ‘correct’ antimalarial trials? Trends in Parasitology 26, 119124.
Kamya, M. R., Yeka, A., Bukirwa, H., Lugemwa, M., Rwakimari, J. B., Staedke, S. G., Talisuna, A. O., Greenhouse, B., Nosten, F., Rosenthal, P. J., Wabwire-Mangen, F. and Dorsey, G. (2007). Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial. PLoS Clinical Trials 2, e20.
Katz, N., Chaves, A. and Pellegrino, J. (1972). A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Revista do Instituto de Medicina Tropical de Sao Paulo 14, 397400.
Maltha, J., Gillet, P. and Jacobs, J. (2013 a). Malaria rapid diagnostic tests in endemic settings. Clinical Microbiology and Infection 19, 399407.
Maltha, J., Gillet, P. and Jacobs, J. (2013 b). Malaria rapid diagnostic tests in travel medicine. Clinical Microbiology and Infection 19, 408415.
Mombo-Ngoma, G., Kleine, C., Basra, A., Wurbel, H., Diop, D. A., Capan, M., Adegnika, A. A., Kurth, F., Mordmuller, B., Joanny, F., Kremsner, P. G., Ramharter, M. and Belard, S. (2012). Prospective evaluation of artemether-lumefantrine for the treatment of non-falciparum and mixed-species malaria in Gabon. Malaria Journal 11, 120.
Mueller, I., Zimmerman, P. A. and Reeder, J. C. (2007). Plasmodium malariae and Plasmodium ovale – the “bashful” malaria parasites. Trends in Parasitology 23, 278283.
Mueller, I., Galinski, M. R., Baird, J. K., Carlton, J. M., Kochar, D. K., Alonso, P. L. and del Portillo, H. A. (2009). Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infectious Diseases 9, 555566.
Noedl, H., Se, Y., Schaecher, K., Smith, B. L., Socheat, D. and Fukuda, M. M. (2008). Evidence of artemisinin-resistant malaria in western Cambodia. New England Journal of Medicine 359, 26192620.
Nyunt, M. H., Kyaw, M. P., Win, K. K., Myint, K. M. and Nyunt, K. M. (2013). Field evaluation of HRP2 and pan pLDH-based immunochromatographic assay in therapeutic monitoring of uncomplicated falciparum malaria in Myanmar. Malaria Journal 12, 123.
Oguike, M. C., Betson, M., Burke, M., Nolder, D., Stothard, J. R., Kleinschmidt, I., Proietti, C., Bousema, T., Ndounga, M., Tanabe, K., Ntege, E., Culleton, R. and Sutherland, C. J. (2011). Plasmodium ovale curtisi and Plasmodium ovale wallikeri circulate simultaneously in African communities. International Journal for Parasitology 41, 677683.
Owusu-Agyei, S., Asante, K. P., Owusu, R., Adjuik, M., Amenga-Etego, S., Dosoo, D. K., Gyapong, J., Greenwood, B. and Chandramohan, D. (2008). An open label, randomised trial of artesunate+amodiaquine, artesunate+chlorproguanil-dapsone and artemether-lumefantrine for the treatment of uncomplicated malaria. PLoS ONE 3, e2530.
Piola, P., Fogg, C., Bajunirwe, F., Biraro, S., Grandesso, F., Ruzagira, E., Babigumira, J., Kigozi, I., Kiguli, J., Kyomuhendo, J., Ferradini, L., Taylor, W., Checchi, F. and Guthmann, J. P. (2005). Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 365, 14671473.
Price, R. N., Uhlemann, A. C., van Vugt, M., Brockman, A., Hutagalung, R., Nair, S., Nash, D., Singhasivanon, P., Anderson, T. J., Krishna, S., White, N. J. and Nosten, F. (2006). Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria. Clinical Infectious Diseases 42, 15701577.
Proietti, C., Pettinato, D. D., Kanoi, B. N., Ntege, E., Crisanti, A., Riley, E. M., Egwang, T. G., Drakeley, C. and Bousema, T. (2011). Continuing intense malaria transmission in northern Uganda. American Journal of Tropical Medicine and Hygiene 84, 830837.
Schoepflin, S., Lin, E., Kiniboro, B., DaRe, J. T., Mehlotra, R. K., Zimmerman, P. A., Mueller, I. and Felger, I. (2011). Treatment with coartem (artemether-lumefantrine) in Papua New Guinea. American Journal of Tropical Medicine and Hygiene 82, 529534.
Shokoples, S. E., Ndao, M., Kowalewska-Grochowska, K. and Yanow, S. K. (2009). Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. Journal of Clinical Microbiology 47, 975980.
Sousa-Figueiredo, J. C., Oguttu, D., Adriko, M., Besigye, F., Nankasi, A., Arinaitwe, M., Namukuta, A., Betson, M., Kabatereine, N. B. and Stothard, J. R. (2010). Investigating portable fluorescent microscopy (CyScope) as an alternative rapid diagnostic test for malaria in children and women of child-bearing age. Malaria Journal 9, 245.
Stothard, J. R., Sousa-Figueiredo, J. C., Betson, M., Seto, E. Y. and Kabatereine, N. B. (2011). Investigating the spatial micro-epidemiology of diseases within a point-prevalence sample: a field applicable method for rapid mapping of households using low-cost GPS-dataloggers. Transactions of the Royal Society of Tropical Medicine Hygiene 105, 500506.
Stothard, J. R., Sousa-Figueiredo, J. C., Betson, M., Bustinduy, A. and Reinhard-Rupp, J. (2013). Schistosomiasis in African infants and preschool children: let them now be treated! Trends in Parasitology 29, 197205.
The Four Artemisinin-Based Combinations (4ABC) Study Group (2011). A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial. PLoS Medicine 8, e1001119.
WHO (2001). Iron Deficiency Anaemia: Assessment, Prevention and Control. World Health Organization, Geneva, Switzerland.
WHO (2006). Preventive Chemotherapy in Human Helminthiasis. World Health Organization, Geneva, Switzerland.
WHO (2007). Methods and Techniques for Clinical Trials on Antimalarial Drug Efficacy: Genotyping to Identify Parasite Populations. Medicines for Malaria Venture and World Health Organization, Geneva, Switzerland.
WHO (2008). Malaria Rapid Diagnostic Test Performance. World Health Organization, Geneva, Switzerland.
WHO (2010 a). Guidelines for the Treatment of Malaria. World Health Organization, Geneva, Switzerland.
WHO (2010 b). Working to Overcome the Global Impact of Neglected Tropical Diseases. First WHO Report on Neglected Tropical Diseases. World Health Organization, Geneva, Switzerland.
WHO (2012). Malaria Rapid Diagnostic Test Performance. Results of WHO Product Testing of Malaria RDTs: Round 4 (2012). World Health Organization, Geneva, Switzerland.
Yeka, A., Dorsey, G., Kamya, M. R., Talisuna, A., Lugemwa, M., Rwakimari, J. B., Staedke, S. G., Rosenthal, P. J., Wabwire-Mangen, F. and Bukirwa, H. (2008). Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS One 3, e2390.
Yeka, A., Gasasira, A., Mpimbaza, A., Achan, J., Nankabirwa, J., Nsobya, S., Staedke, S. G., Donnelly, M. J., Wabwire-Mangen, F., Talisuna, A., Dorsey, G., Kamya, M. R. and Rosenthal, P. J. (2012). Malaria in Uganda: challenges to control on the long road to elimination I. Epidemiology and current control efforts. Acta Tropica 121, 184195.

Keywords

Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment

  • MARTHA BETSON (a1), JOSÉ C. SOUSA-FIGUEIREDO (a2), AARON ATUHAIRE (a3), MOSES ARINAITWE (a3), MOSES ADRIKO (a3), GERALD MWESIGWA (a3), JUMA NABONGE (a4), NARCIS B. KABATEREINE (a3), COLIN J. SUTHERLAND (a2) and J. RUSSELL STOTHARD (a5)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed