- Introduction
- Materials and Methods
- Results
- Study participants and baseline characteristics.
- Accuracy of HRP2 and pLDH RDTs for initial diagnosis of malaria.
- Association of sensitivity of HRP2 and pLDH RDTs with parasite density.
- Association of specificity of HRP2 and pLDH RDTs with duration since last episode of malaria.
- Persistence of HRP2 and pLDH antigenemia during follow-up.
- Association of pretreatment parasite density with duration of antigenemia.
- Accuracy of HRP2 and pLDH RDTs for diagnosis of malaria in children with recurrent fever after treatment of uncomplicated malaria.
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Okello PE, Van Bortel W, Byaruhanga AM, Correwyn A, Roelants P, Talisuna A, D'Alessandro U, Coosemans M, 2006. Variation in malaria transmission intensity in seven sites throughout Uganda. Am J Trop Med Hyg 75: 219–225.
-
2.
World Health Organization, 2010. Guidelines for the treatment of malaria. Second edition. Geneva, World Health Organization. Report No: ISBN: 978 92 4 15 47925. Available at: http://www.who.int/malaria/publications/atoz/9789241547925/en/index.html. Accessed October 22, 2013.
-
3.
Nankabirwa J, Zurovac D, Njogu JN, Rwakimari JB, Counihan H, Snow RW, Tibenderana JK, 2009. Malaria misdiagnosis in Uganda–implications for policy change. Malar J 8: 66.
-
4.
Chandramohan D, Jaffar S, Greenwood B, 2002. Use of clinical algorithms for diagnosing malaria. Trop Med Int Health 7: 45–52.
-
5.
Kallander K, Nsungwa-Sabiiti J, Peterson S, 2004. Symptom overlap for malaria and pneumonia–policy implications for home management strategies. Acta Trop 90: 211–214.
-
6.
World Health Organization, 2006. The Use of Malaria Rapid Diagnostic Tests. Geneva: World Health Organization Library Cataloguing in Publication Data.
-
7.
Guthmann JP, Ruiz A, Priotto G, Kiguli J, Bonte L, Legros D, 2002. Validity, reliability and ease of use in the field of five rapid tests for the diagnosis of Plasmodium falciparum malaria in Uganda. Trans R Soc Trop Med Hyg 96: 254–257.
-
8.
Hopkins H, Bebell L, Kambale W, Dokomajilar C, Rosenthal PJ, Dorsey G, 2008. Rapid diagnostic tests for malaria at sites of varying transmission intensity in Uganda. J Infect Dis 197: 510–518.
-
9.
World Health Organization, 2011. Malaria Rapid Diagnostic Test Performance: Results of WHO Product Testing of Malaria RDTs: Round 3 (2010–2011). Geneva: World Health Organization. Report No: ISBN: 978 92 4 150472 0. Available at: http://www.who.int/tdr/publications/rapiddiagnostic/en/. Accessed October 18, 2013.
-
10.
Kyabayinze DJ, Tibenderana JK, Odong GW, Rwakimari JB, Counihan H, 2008. Operational accuracy and comparative persistent antigenicity of HRP2 rapid diagnostic tests for Plasmodium falciparum malaria in a hyperendemic region of Uganda. Malar J 7: 221.
-
11.
Swarthout TD, Counihan H, Senga RK, van den Broek I, 2007. Paracheck-Pf accuracy and recently treated Plasmodium falciparum infections: is there a risk of over-diagnosis? Malar J 6: 58.
-
12.
Tjitra E, Suprianto S, Dyer ME, Currie BJ, Anstey NM, 2001. Detection of histidine-rich protein 2 and panmalarial ICT Malaria Pf/Pv test antigens after chloroquine treatment of uncomplicated falciparum malaria does not reliably predict treatment outcome in eastern Indonesia. Am J Trop Med Hyg 65: 593–598.
-
13.
Singh N, Shukla MM, 2002. Short report: field evaluation of posttreatment sensitivity for monitoring parasite clearance of Plasmodium falciparum malaria by use of the Determine Malaria pf test in central India. Am J Trop Med Hyg 66: 314–316.
-
14.
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: 179–182.
-
15.
Gerstl S, Dunkley S, Mukhtar A, De Smet M, Baker S, Maikere J, 2010. Assessment of two malaria rapid diagnostic tests in children under five years of age, with follow-up of false-positive pLDH test results, in a hyperendemic falciparum malaria area, Sierra Leone. Malar J 9: 28.
-
16.
Jagannathan PM, Kakuru A, Arinaitwe E, Greenhouse B, Taperro J, Rosenthal P, Kahuruza F, Kamya M, Dorsey G, 2012. Increasing incidence of malaria in children despite insecticide-treated bed nets and prompt anti-malarial therapy in Tororo, Uganda. Malar J 11: 435.
-
17.
Arinaitwe E, Sandison TG, Wanzira H, Kakuru A, Homsy J, Kalamya J, Kamya MR, Vora N, Greenhouse B, Rosenthal PJ, Tappero J, Dorsey G, 2009. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis 49: 1629–1637.
-
18.
Buderer NM, 1996. Statistical methodology: incorporating the prevalence of disease into the sample size calculation for sensitivity and specificity. Acad Emerg Med 3: 895–900.
-
19.
Bell DR, Wilson DW, Martin LB, 2005. False-positive results of a Plasmodium falciparum histidine-rich protein 2-detecting malaria rapid diagnostic test due to high sensitivity in a community with fluctuating low parasite density. Am J Trop Med Hyg 73: 199–203.
-
20.
Mueller I, Betuela I, Ginny M, Reeder JC, Genton B, 2007. The sensitivity of the OptiMAL rapid diagnostic test to the presence of Plasmodium falciparum gametocytes compromises its ability to monitor treatment outcomes in an area of Papua New Guinea in which malaria is endemic. J Clin Microbiol 45: 627–630.
-
21.
Amel Abdel-Wahab A, Abdel-Muhsin AM, Ali E, Suleiman S, Ahmed S, Walliker D, Babiker HA, 2002. Dynamics of gametocytes among Plasmodium falciparum clones in natural infections in an area of highly seasonal transmission. J Infect Dis 185: 1838–1842.
-
22.
Abeku TA, Kristan M, Jones C, Beard J, Mueller DH, Okia M, Rapuoda B, Greenwood B, Cox J, 2008. Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands. Malar J 7: 202.
-
23.
Aydin-Schmidt B, Mubi M, Morris U, Petzold M, Ngasala BE, Premji Z, Bjorkman A, 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. Malar J 12: 349.
-
24.
Batwala V, Magnussen P, Hansen KS, Nuwaha F, 2011. Cost-effectiveness of malaria microscopy and rapid diagnostic tests versus presumptive diagnosis: implications for malaria control in Uganda. Malar J 10: 372.
-
25.
Zikusooka CM, McIntyre D, Barnes KI, 2008. Should countries implementing an artemisinin-based combination malaria treatment policy also introduce rapid diagnostic tests? Malar J 7: 176.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 470 | 382 | 33 |
| Full Text Views | 461 | 12 | 0 |
| PDF Downloads | 140 | 9 | 0 |
Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda
Phoebe Mbabazi
Phoebe Mbabazi
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Foundation for Innovative New Diagnostics (FIND), Kampala, Uganda; Infectious Diseases Research Collaboration, Kampala, Uganda; Infectious Diseases Institute, Kampala, Uganda
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Heidi Hopkins
Heidi Hopkins
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Foundation for Innovative New Diagnostics (FIND), Kampala, Uganda; Infectious Diseases Research Collaboration, Kampala, Uganda; Infectious Diseases Institute, Kampala, Uganda
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Emmanuel Osilo
Emmanuel Osilo
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Foundation for Innovative New Diagnostics (FIND), Kampala, Uganda; Infectious Diseases Research Collaboration, Kampala, Uganda; Infectious Diseases Institute, Kampala, Uganda
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Michael Kalungu
Michael Kalungu
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Foundation for Innovative New Diagnostics (FIND), Kampala, Uganda; Infectious Diseases Research Collaboration, Kampala, Uganda; Infectious Diseases Institute, Kampala, Uganda
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Pauline Byakika-Kibwika
Pauline Byakika-Kibwika
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Foundation for Innovative New Diagnostics (FIND), Kampala, Uganda; Infectious Diseases Research Collaboration, Kampala, Uganda; Infectious Diseases Institute, Kampala, Uganda
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Moses R. Kamya
Moses R. Kamya
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Foundation for Innovative New Diagnostics (FIND), Kampala, Uganda; Infectious Diseases Research Collaboration, Kampala, Uganda; Infectious Diseases Institute, Kampala, Uganda
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Malaria rapid diagnostic tests (RDTs) may improve fever management in areas without microscopy. We compared the accuracy of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as a gold standard, for initial diagnosis, treatment monitoring, and diagnosis of recurrent malaria in a cohort of children followed longitudinally in a high-transmission area in Uganda. For 305 initial fever episodes, sensitivity was 98% for HRP2 and 87% for pLDH, whereas specificity was 55% and 96%, respectively. The HRP2 gave 51% false-positive results on Day 28, whereas pLDH gave no false positives after Day 7. For 59 recurrent fever episodes during follow-up, sensitivity was 100% for HRP2 and 91% for pLDH, whereas specificity was 33% and 100%, respectively. The HRP2-based RDTs are useful for initial diagnosis of malaria caused by superior sensitivity; however, as a result of superior specificity, pLDH-based RDTs are more appropriate to monitor treatment and diagnose recurrent malaria.
Author Notes
Financial support: This research was funded by Uganda Malaria Clinical Operational and Health Services (COHRE) training program at Makerere University, Grant D43-TW00807701A1, from the Fogarty International Centre (FIC) at the National Institute of Health (NIH).
Authors' addresses: Phoebe Mbabazi, International Hospital Kampala, Kampala, Uganda, E-mail: phibsmm@gmail.com. Heidi Hopkins, ACT Consortium, London School for Tropical Medicine and Hygiene, London, United Kingdom, E-mail: heidi.hopkins@lshtm.ac.uk. Emmanuel Osilo, Infectious Disease Research Collaboration, Tororo, Uganda, E-mail: goodbeads@yahoo.co.uk. Michael Kalungu, School of Statistics and Planning, Makerere University, Kampala, Uganda, E-mail: kalungu_michaeal@yahoo.co.uk. Pauline Byakika-Kibwika and Moses R. Kamya, Makerere University College of Health Sciences, Kampala, Uganda, E-mails: pbyakika@gmail.com and mkamya@infocom.co.ug.
Reprint requests: Phoebe Mbabazi, International Hospital Kampala, P.O. Box, 8177, Kampala, Uganda, E-mail: phibsmm@gmail.com.
- Introduction
- Materials and Methods
- Results
- Study participants and baseline characteristics.
- Accuracy of HRP2 and pLDH RDTs for initial diagnosis of malaria.
- Association of sensitivity of HRP2 and pLDH RDTs with parasite density.
- Association of specificity of HRP2 and pLDH RDTs with duration since last episode of malaria.
- Persistence of HRP2 and pLDH antigenemia during follow-up.
- Association of pretreatment parasite density with duration of antigenemia.
- Accuracy of HRP2 and pLDH RDTs for diagnosis of malaria in children with recurrent fever after treatment of uncomplicated malaria.
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Okello PE, Van Bortel W, Byaruhanga AM, Correwyn A, Roelants P, Talisuna A, D'Alessandro U, Coosemans M, 2006. Variation in malaria transmission intensity in seven sites throughout Uganda. Am J Trop Med Hyg 75: 219–225.
-
2.
World Health Organization, 2010. Guidelines for the treatment of malaria. Second edition. Geneva, World Health Organization. Report No: ISBN: 978 92 4 15 47925. Available at: http://www.who.int/malaria/publications/atoz/9789241547925/en/index.html. Accessed October 22, 2013.
-
3.
Nankabirwa J, Zurovac D, Njogu JN, Rwakimari JB, Counihan H, Snow RW, Tibenderana JK, 2009. Malaria misdiagnosis in Uganda–implications for policy change. Malar J 8: 66.
-
4.
Chandramohan D, Jaffar S, Greenwood B, 2002. Use of clinical algorithms for diagnosing malaria. Trop Med Int Health 7: 45–52.
-
5.
Kallander K, Nsungwa-Sabiiti J, Peterson S, 2004. Symptom overlap for malaria and pneumonia–policy implications for home management strategies. Acta Trop 90: 211–214.
-
6.
World Health Organization, 2006. The Use of Malaria Rapid Diagnostic Tests. Geneva: World Health Organization Library Cataloguing in Publication Data.
-
7.
Guthmann JP, Ruiz A, Priotto G, Kiguli J, Bonte L, Legros D, 2002. Validity, reliability and ease of use in the field of five rapid tests for the diagnosis of Plasmodium falciparum malaria in Uganda. Trans R Soc Trop Med Hyg 96: 254–257.
-
8.
Hopkins H, Bebell L, Kambale W, Dokomajilar C, Rosenthal PJ, Dorsey G, 2008. Rapid diagnostic tests for malaria at sites of varying transmission intensity in Uganda. J Infect Dis 197: 510–518.
-
9.
World Health Organization, 2011. Malaria Rapid Diagnostic Test Performance: Results of WHO Product Testing of Malaria RDTs: Round 3 (2010–2011). Geneva: World Health Organization. Report No: ISBN: 978 92 4 150472 0. Available at: http://www.who.int/tdr/publications/rapiddiagnostic/en/. Accessed October 18, 2013.
-
10.
Kyabayinze DJ, Tibenderana JK, Odong GW, Rwakimari JB, Counihan H, 2008. Operational accuracy and comparative persistent antigenicity of HRP2 rapid diagnostic tests for Plasmodium falciparum malaria in a hyperendemic region of Uganda. Malar J 7: 221.
-
11.
Swarthout TD, Counihan H, Senga RK, van den Broek I, 2007. Paracheck-Pf accuracy and recently treated Plasmodium falciparum infections: is there a risk of over-diagnosis? Malar J 6: 58.
-
12.
Tjitra E, Suprianto S, Dyer ME, Currie BJ, Anstey NM, 2001. Detection of histidine-rich protein 2 and panmalarial ICT Malaria Pf/Pv test antigens after chloroquine treatment of uncomplicated falciparum malaria does not reliably predict treatment outcome in eastern Indonesia. Am J Trop Med Hyg 65: 593–598.
-
13.
Singh N, Shukla MM, 2002. Short report: field evaluation of posttreatment sensitivity for monitoring parasite clearance of Plasmodium falciparum malaria by use of the Determine Malaria pf test in central India. Am J Trop Med Hyg 66: 314–316.
-
14.
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: 179–182.
-
15.
Gerstl S, Dunkley S, Mukhtar A, De Smet M, Baker S, Maikere J, 2010. Assessment of two malaria rapid diagnostic tests in children under five years of age, with follow-up of false-positive pLDH test results, in a hyperendemic falciparum malaria area, Sierra Leone. Malar J 9: 28.
-
16.
Jagannathan PM, Kakuru A, Arinaitwe E, Greenhouse B, Taperro J, Rosenthal P, Kahuruza F, Kamya M, Dorsey G, 2012. Increasing incidence of malaria in children despite insecticide-treated bed nets and prompt anti-malarial therapy in Tororo, Uganda. Malar J 11: 435.
-
17.
Arinaitwe E, Sandison TG, Wanzira H, Kakuru A, Homsy J, Kalamya J, Kamya MR, Vora N, Greenhouse B, Rosenthal PJ, Tappero J, Dorsey G, 2009. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis 49: 1629–1637.
-
18.
Buderer NM, 1996. Statistical methodology: incorporating the prevalence of disease into the sample size calculation for sensitivity and specificity. Acad Emerg Med 3: 895–900.
-
19.
Bell DR, Wilson DW, Martin LB, 2005. False-positive results of a Plasmodium falciparum histidine-rich protein 2-detecting malaria rapid diagnostic test due to high sensitivity in a community with fluctuating low parasite density. Am J Trop Med Hyg 73: 199–203.
-
20.
Mueller I, Betuela I, Ginny M, Reeder JC, Genton B, 2007. The sensitivity of the OptiMAL rapid diagnostic test to the presence of Plasmodium falciparum gametocytes compromises its ability to monitor treatment outcomes in an area of Papua New Guinea in which malaria is endemic. J Clin Microbiol 45: 627–630.
-
21.
Amel Abdel-Wahab A, Abdel-Muhsin AM, Ali E, Suleiman S, Ahmed S, Walliker D, Babiker HA, 2002. Dynamics of gametocytes among Plasmodium falciparum clones in natural infections in an area of highly seasonal transmission. J Infect Dis 185: 1838–1842.
-
22.
Abeku TA, Kristan M, Jones C, Beard J, Mueller DH, Okia M, Rapuoda B, Greenwood B, Cox J, 2008. Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands. Malar J 7: 202.
-
23.
Aydin-Schmidt B, Mubi M, Morris U, Petzold M, Ngasala BE, Premji Z, Bjorkman A, 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. Malar J 12: 349.
-
24.
Batwala V, Magnussen P, Hansen KS, Nuwaha F, 2011. Cost-effectiveness of malaria microscopy and rapid diagnostic tests versus presumptive diagnosis: implications for malaria control in Uganda. Malar J 10: 372.
-
25.
Zikusooka CM, McIntyre D, Barnes KI, 2008. Should countries implementing an artemisinin-based combination malaria treatment policy also introduce rapid diagnostic tests? Malar J 7: 176.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 470 | 382 | 33 |
| Full Text Views | 461 | 12 | 0 |
| PDF Downloads | 140 | 9 | 0 |