ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization , 2015. Guidelines for the Treatment of Malaria. Third ed. Available at: https://www.afro.who.int/publications/guidelines-treatment-malaria-third-edition. Accessed November 12, 2023.
-
2.
World Health Organization , 2019. Response Plan to pfhrp2 Gene Deletions. Geneva, Switzerland: WHO.
-
3.
Gitonga CW , Karanja PN , Kihara J , Mwanje M , Juma E , Snow RW , Noor AM , Brooker S , 2010. Implementing school malaria surveys in Kenya: Towards a national surveillance system. Malar J 9: 306.
-
4.
Steinhardt LC et al., 2020. School-based serosurveys to assess the validity of using routine health facility data to target malaria interventions in the central highlands of Madagascar. J Infect Dis 223: 995–1004.
-
5.
Stevenson JC et al., 2013 Reliability of school surveys in estimating geographic variation in malaria transmission in the western Kenyan highlands. PloS One 8: e77641.
-
6.
Mathanga DP et al., 2015. The high burden of malaria in primary school children in southern Malawi. Am J Trop Med Hyg 93: 779–789.
-
7.
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: 1–11.
-
8.
Lee JH , Jang JW , Cho CH , Kim JY , Han ET , Yun SG , Lim CS , 2014. False-positive results for rapid diagnostic tests for malaria in patients with rheumatoid factor. J Clin Microbiol 52: 3784–3787.
-
9.
World Health Organization , 2017. False-Negative RDT Results and Implications of New Reports of P. falciparum Histidine-Rich Protein 2/3 Gene Deletions. Geneva, Switzerland: WHO.
-
10.
Chacky F et al., 2018. Nationwide school malaria parasitaemia survey in public primary schools, the United Republic of Tanzania. Malar J 17: 452.
-
11.
Martiáñez-Vendrell X , Skjefte M , Sikka R , Gupta H , 2022. Factors affecting the performance of HRP2-based malaria rapid diagnostic tests. Trop Med Infect Dis 7: 265.
-
12.
Nankabirwa JI , Yeka A , Arinaitwe E , Kigozi R , Drakeley C , Kamya MR , Greenhouse B , Rosenthal PJ , Dorsey G , Staedke SG , 2015. Estimating malaria parasite prevalence from community surveys in Uganda: A comparison of microscopy, rapid diagnostic tests and polymerase chain reaction. Malar J 14: 528.
-
13.
Iwuafor AA , Ita OI , Ogban GI , Udoh UA , Amajor CA , 2018. Evaluation of diagnostic accuracy of rapid diagnostic test for malaria diagnosis among febrile children in Calabar, Nigeria. Nigerian Med J 59: 64–69.
-
14.
Ishengoma DS , Francis F , Mmbando BP , Lusingu J , Magistrado P , Alifrangis M , Theander TG , Bygbjerg IC , Lemnge MM , 2011. Accuracy of malaria rapid diagnostic tests in community studies and their impact on treatment of malaria in an area with declining malaria burden in north-eastern Tanzania. Malar J 10: 1–13.
-
15.
Sendor R et al., 2023. Similar prevalence of Plasmodium falciparum and non-P. falciparum malaria infections among schoolchildren, Tanzania. Emerg Infect Dis 29: 1143–1153.
-
16.
Mitchell CL et al., 2022. Evaluating malaria prevalence and land cover across varying transmission intensity in Tanzania using a cross-sectional survey of school-aged children. Malar J 21: 80.
-
17.
Grignard L et al., 2020. A novel multiplex qPCR assay for detection of Plasmodium falciparum with histidine-rich protein 2 and 3 (pfhrp2 and pfhrp3) deletions in polyclonal infections. EBioMedicine 55: 102757.
-
18.
Makenga G , Menon S , Baraka V , Minja DT , Nakato S , Delgado-Ratto C , Francis F , Lusingu JP , Van Geertruyden J-P , 2020. Prevalence of malaria parasitaemia in school-aged children and pregnant women in endemic settings of sub-Saharan Africa: A systematic review and meta-analysis. Parasite Epidemiol Control 11: e00188.
-
19.
Ngasala B , Mutemi DD , Mwaiswelo RO , 2019. Diagnostic performance of malaria rapid diagnostic test and microscopy compared with PCR for detection of Plasmodium falciparum infections among primary schoolchildren in Kibiti District, Eastern Tanzania: An area with moderate malaria transmission. Am J Trop Med Hyg 101: 809–811.
-
20.
Markwalter CF et al., 2021. Direct comparison of standard and ultrasensitive PCR for the detection of Plasmodium falciparum from dried blood spots in Bagamoyo, Tanzania. Am J Trop Med Hyg 104: 1371–1374.
-
21.
Gatton M , Dunn J , Chaudhry A , Ciketic S , Cunningham J , Cheng Q , 2017. Use of PfHRP2-only RDTs rapidly select for PfHRP2-negative parasites with serious implications for malaria case management and control. J Infect Dis 215: 1156–1166.
-
22.
Golassa L , Messele A , Amambua-Ngwa A , Swedberg G , 2020. High prevalence and extended deletions in Plasmodium falciparum hrp2/3 genomic loci in Ethiopia. PLoS One 15: e0241807.
-
23.
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: 36–44.
-
24.
Kaaya RD , Kavishe RA , Tenu FF , Matowo JJ , Mosha FW , Drakeley C , Sutherland CJ , Beshir KB , 2022. Deletions of the Plasmodium falciparum histidine-rich protein 2/3 genes are common in field isolates from north-eastern Tanzania. Sci Rep 12: 5802.
-
25.
Rogier E et al., 2022. Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions from persons with symptomatic malaria infection in Ethiopia, Kenya, Madagascar, and Rwanda. Emerg Infect Dis 28: 608–616.
-
26.
Watson OJ , Sumner KM , Janko M , Goel V , Winskill P , Slater HC , Ghani A , Meshnick SR , Parr JB , 2019. False-negative malaria rapid diagnostic test results and their impact on community-based malaria surveys in sub-Saharan Africa. BMJ Glob Health 4: e001582.
-
27.
Feleke SM et al., 2021. Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia. Nat Microbiol 6: 1289–1299.
-
28.
World Health Organization , 2020. Template Protocols to Support Surveillance and Research for pfhrp2/pfhrp3 gene deletions. Available at: https://www.who.int/publications/i/item/9789240002036. Accessed November 23, 2023.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1432 | 1432 | 223 |
| Full Text Views | 272 | 272 | 45 |
| PDF Downloads | 87 | 87 | 12 |
Evaluation of Malaria Rapid Diagnostic Test Performance and pfhrp2 Deletion in Tanzania School Surveys, 2017
Billy Ngasala
Billy Ngasala
Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;
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Frank Chacky
Frank Chacky
National Malaria Control Programme, Dodoma, Tanzania;
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Ally Mohamed
Ally Mohamed
National Malaria Control Programme, Dodoma, Tanzania;
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Fabrizio Molteni
Fabrizio Molteni
Swiss Tropical and Public Health Institute, Basel, Switzerland;
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Ssanyu Nyinondi
Ssanyu Nyinondi
RTI International, Dar es Salaam, Tanzania;
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Bilali Kabula
Bilali Kabula
RTI International, Dar es Salaam, Tanzania;
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Humphrey Mkali
Humphrey Mkali
RTI International, Dar es Salaam, Tanzania;
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Kyaw Thwai
Kyaw Thwai
Institute for Global health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
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Zachary R. Popkin-Hall
Zachary R. Popkin-Hall
Institute for Global health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
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Cedar Mitchell
Cedar Mitchell
Institute for Global health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
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Jonathan B. Parr
Jonathan B. Parr
Institute for Global health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;
Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;
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Jonathan J. Juliano
Jonathan J. Juliano
Institute for Global health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;
Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;
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Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;
Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;
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Jessica T. Lin
Jessica T. Lin
Institute for Global health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;
Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina
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Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;
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ABSTRACT.
As part of malaria nationwide monitoring and evaluation initiatives, there is an increasing trend of incorporating malaria rapid diagnostic tests (mRDTs) in surveys conducted within primary schools to detect malaria parasites. However, mRDTs based on the detection of histidine-rich protein 2 (HRP2) are known to yield false-positive results due to persistent antigenemia, and false-negative results may result from low parasitemia or Plasmodium falciparum hrp2/3 gene deletion. We evaluated diagnostic performance of an HRP2 and pan-parasite lactate dehydrogenase (HRP2/pLDH) mRDT against polymerase chain reaction (PCR) for detection of P. falciparum among 17,051 primary school–age children from eight regions of Tanzania in 2017. According to PCR, the prevalence of P. falciparum was 19.2% (95% CI: 18.6–19.8). Using PCR as reference, the sensitivity and specificity of mRDT was 76.2% (95% CI: 74.7–77.7) and 93.9% (95% CI: 93.5–94.3), respectively. Test agreement was lowest in low transmission areas, where true-positive mRDTs were outnumbered by false-negatives due to low parasitemia. Discordant samples (mRDT-negative but PCR-positive) were screened for pfhrp2/3 deletion by real-time PCR. Among those with a parasite density sufficient for analysis, pfhrp2 deletion was confirmed in 60 samples, whereas pfhrp3 deletion was confirmed in two samples; one sample had both pfhrp2 and pfhrp3 deletions. The majority of samples with gene deletions were detected in the high-transmission Kagera region. Compared with mRDTs, PCR and other molecular methods offer increased sensitivity and are not affected by pfhrp2/3 deletions, making them a useful supplement to mRDTs in schools and other epidemiological surveys.
- Supplemental Materials (PDF 1149.6 KB)
Author Notes
Financial support: The School Malaria Parasite Survey was supported by
Conflicts of interest: J. B. Parr reports research support from Gilead Sciences, nonfinancial support from Abbott Laboratories, and consulting for Zymeron Corporation, all outside the scope of the submitted work.
Authors’ addresses: Billy Ngasala, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, E-mail: bngasala70@gmail.com. Frank Chacky and Ally Mohamed, National Malaria Control Programme, Dodoma, Tanzania, E-mails: chackyfa@gmail.com and allykayaga@gmail.com. Fabrizio Molteni, Swiss Tropical and Public Health Institute, Basel, Switzerland, E-mail: fabrizio.molteni@netcell.org. Ssanyu Nyinondi, Bilali Kabula, and Humphrey Mkali, RTI International, Dar es Salaam, E-mails: ssanyu@gmail.com, bika72@gmail.com, and hrmkali@omdm.rti.org. Kyaw Thwai, Zachary R. Popkin-Hall, Cedar Mitchell, and Jonathan B. Parr, Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC, E-mails: thwai@email.unc.edu, zach_popkin-hall@med.unc.edu, and cdr.mit@gmail.com. Jonathan B. Parr, Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC, Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC, and Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, NC, E-mail: jonathan_parr@med.unc.edu. Jonathan J. Juliano, Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC, Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC, Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, NC, and Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, E-mail: jonathan_juliano@med.unc.edu. Jessica T. Lin, Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC, Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC, and Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, E-mail: jessica_lin@med.unc.edu.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization , 2015. Guidelines for the Treatment of Malaria. Third ed. Available at: https://www.afro.who.int/publications/guidelines-treatment-malaria-third-edition. Accessed November 12, 2023.
-
2.
World Health Organization , 2019. Response Plan to pfhrp2 Gene Deletions. Geneva, Switzerland: WHO.
-
3.
Gitonga CW , Karanja PN , Kihara J , Mwanje M , Juma E , Snow RW , Noor AM , Brooker S , 2010. Implementing school malaria surveys in Kenya: Towards a national surveillance system. Malar J 9: 306.
-
4.
Steinhardt LC et al., 2020. School-based serosurveys to assess the validity of using routine health facility data to target malaria interventions in the central highlands of Madagascar. J Infect Dis 223: 995–1004.
-
5.
Stevenson JC et al., 2013 Reliability of school surveys in estimating geographic variation in malaria transmission in the western Kenyan highlands. PloS One 8: e77641.
-
6.
Mathanga DP et al., 2015. The high burden of malaria in primary school children in southern Malawi. Am J Trop Med Hyg 93: 779–789.
-
7.
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: 1–11.
-
8.
Lee JH , Jang JW , Cho CH , Kim JY , Han ET , Yun SG , Lim CS , 2014. False-positive results for rapid diagnostic tests for malaria in patients with rheumatoid factor. J Clin Microbiol 52: 3784–3787.
-
9.
World Health Organization , 2017. False-Negative RDT Results and Implications of New Reports of P. falciparum Histidine-Rich Protein 2/3 Gene Deletions. Geneva, Switzerland: WHO.
-
10.
Chacky F et al., 2018. Nationwide school malaria parasitaemia survey in public primary schools, the United Republic of Tanzania. Malar J 17: 452.
-
11.
Martiáñez-Vendrell X , Skjefte M , Sikka R , Gupta H , 2022. Factors affecting the performance of HRP2-based malaria rapid diagnostic tests. Trop Med Infect Dis 7: 265.
-
12.
Nankabirwa JI , Yeka A , Arinaitwe E , Kigozi R , Drakeley C , Kamya MR , Greenhouse B , Rosenthal PJ , Dorsey G , Staedke SG , 2015. Estimating malaria parasite prevalence from community surveys in Uganda: A comparison of microscopy, rapid diagnostic tests and polymerase chain reaction. Malar J 14: 528.
-
13.
Iwuafor AA , Ita OI , Ogban GI , Udoh UA , Amajor CA , 2018. Evaluation of diagnostic accuracy of rapid diagnostic test for malaria diagnosis among febrile children in Calabar, Nigeria. Nigerian Med J 59: 64–69.
-
14.
Ishengoma DS , Francis F , Mmbando BP , Lusingu J , Magistrado P , Alifrangis M , Theander TG , Bygbjerg IC , Lemnge MM , 2011. Accuracy of malaria rapid diagnostic tests in community studies and their impact on treatment of malaria in an area with declining malaria burden in north-eastern Tanzania. Malar J 10: 1–13.
-
15.
Sendor R et al., 2023. Similar prevalence of Plasmodium falciparum and non-P. falciparum malaria infections among schoolchildren, Tanzania. Emerg Infect Dis 29: 1143–1153.
-
16.
Mitchell CL et al., 2022. Evaluating malaria prevalence and land cover across varying transmission intensity in Tanzania using a cross-sectional survey of school-aged children. Malar J 21: 80.
-
17.
Grignard L et al., 2020. A novel multiplex qPCR assay for detection of Plasmodium falciparum with histidine-rich protein 2 and 3 (pfhrp2 and pfhrp3) deletions in polyclonal infections. EBioMedicine 55: 102757.
-
18.
Makenga G , Menon S , Baraka V , Minja DT , Nakato S , Delgado-Ratto C , Francis F , Lusingu JP , Van Geertruyden J-P , 2020. Prevalence of malaria parasitaemia in school-aged children and pregnant women in endemic settings of sub-Saharan Africa: A systematic review and meta-analysis. Parasite Epidemiol Control 11: e00188.
-
19.
Ngasala B , Mutemi DD , Mwaiswelo RO , 2019. Diagnostic performance of malaria rapid diagnostic test and microscopy compared with PCR for detection of Plasmodium falciparum infections among primary schoolchildren in Kibiti District, Eastern Tanzania: An area with moderate malaria transmission. Am J Trop Med Hyg 101: 809–811.
-
20.
Markwalter CF et al., 2021. Direct comparison of standard and ultrasensitive PCR for the detection of Plasmodium falciparum from dried blood spots in Bagamoyo, Tanzania. Am J Trop Med Hyg 104: 1371–1374.
-
21.
Gatton M , Dunn J , Chaudhry A , Ciketic S , Cunningham J , Cheng Q , 2017. Use of PfHRP2-only RDTs rapidly select for PfHRP2-negative parasites with serious implications for malaria case management and control. J Infect Dis 215: 1156–1166.
-
22.
Golassa L , Messele A , Amambua-Ngwa A , Swedberg G , 2020. High prevalence and extended deletions in Plasmodium falciparum hrp2/3 genomic loci in Ethiopia. PLoS One 15: e0241807.
-
23.
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: 36–44.
-
24.
Kaaya RD , Kavishe RA , Tenu FF , Matowo JJ , Mosha FW , Drakeley C , Sutherland CJ , Beshir KB , 2022. Deletions of the Plasmodium falciparum histidine-rich protein 2/3 genes are common in field isolates from north-eastern Tanzania. Sci Rep 12: 5802.
-
25.
Rogier E et al., 2022. Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions from persons with symptomatic malaria infection in Ethiopia, Kenya, Madagascar, and Rwanda. Emerg Infect Dis 28: 608–616.
-
26.
Watson OJ , Sumner KM , Janko M , Goel V , Winskill P , Slater HC , Ghani A , Meshnick SR , Parr JB , 2019. False-negative malaria rapid diagnostic test results and their impact on community-based malaria surveys in sub-Saharan Africa. BMJ Glob Health 4: e001582.
-
27.
Feleke SM et al., 2021. Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia. Nat Microbiol 6: 1289–1299.
-
28.
World Health Organization , 2020. Template Protocols to Support Surveillance and Research for pfhrp2/pfhrp3 gene deletions. Available at: https://www.who.int/publications/i/item/9789240002036. Accessed November 23, 2023.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1432 | 1432 | 223 |
| Full Text Views | 272 | 272 | 45 |
| PDF Downloads | 87 | 87 | 12 |