Evaluation of Malaria Rapid Diagnostic Test Performance and pfhrp2 Deletion in Tanzania School Surveys, 2017

Author:

Ngasala Billy1,Chacky Frank2,Mohamed Ally2,Molteni Fabrizio3,Nyinondi Ssanyu4,Kabula Bilali4,Mkali Humphrey4,Thwai Kyaw5,Popkin-Hall Zachary R.5,Mitchell Cedar5,Parr Jonathan B.567,Juliano Jonathan J.5678,Lin Jessica T.569

Affiliation:

1. Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;

2. National Malaria Control Programme, Dodoma, Tanzania;

3. Swiss Tropical and Public Health Institute, Basel, Switzerland;

4. RTI International, Dar es Salaam, Tanzania;

5. Institute for Global health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;

6. Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;

7. Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;

8. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;

9. Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina

Abstract

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.

Publisher

American Society of Tropical Medicine and Hygiene

Reference28 articles.

1. Response Plan to pfhrp2 Gene Deletions,2019

2. Implementing school malaria surveys in Kenya: Towards a national surveillance system;Gitonga,2010

3. School-based serosurveys to assess the validity of using routine health facility data to target malaria interventions in the central highlands of Madagascar;Steinhardt,2020

4. Reliability of school surveys in estimating geographic variation in malaria transmission in the western Kenyan highlands;Stevenson,2013

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