Performance evaluation of a prototype rapid diagnostic test for combined detection of gambiense human African trypanosomiasis and malaria

PLoS Negl Trop Dis. 2020 Apr 6;14(4):e0008168. doi: 10.1371/journal.pntd.0008168. eCollection 2020 Apr.

Abstract

Background: Malaria is endemic in all regions where gambiense or rhodesiense human African trypanosomiasis (HAT) is reported, and both diseases have similarities in their symptomatology. A combined test could be useful for both diseases and would facilitate integration of the screening for gambiense HAT (gHAT) and malaria diagnosis. This study aimed to evaluate a combined prototype rapid diagnostic test (RDT) for gHAT and malaria.

Methods: Blood samples were collected in the Democratic Republic of the Congo and in Uganda to evaluate the performance of a prototype HAT/Malaria Combined RDT in comparison to an individual malaria RDT based on Plasmodium falciparum (P.f.) Histidine Rich Protein II (HRP-II or HRP2) antigen (SD BIOLINE Malaria Ag P.f. RDT) for malaria detection and an individual gHAT RDT based on recombinant antigens, the SD BIOLINE HAT 2.0 RDT for HAT screening. Due to the current low prevalence of gHAT in endemic regions, the set of blood samples that were collected was used to evaluate the specificity of the RDTs for gHAT, and additional archived plasma samples were used to complete the evaluation of the HAT/Malaria Combined RDT in comparison to the HAT 2.0 RDT.

Results: Frozen whole blood samples from a total of 486 malaria cases and 239 non-malaria controls, as well as archived plasma samples from 246 gHAT positive and 246 gHAT negative individuals were tested. For malaria, the sensitivity and specificity of the malaria band in the HAT/Malaria Combined RDT were 96.9% (95% CI: 95.0-98.3) and 97.1% (95% CI: 94.1-98.8) respectively. The sensitivity and specificity of the SD BIOLINE malaria Ag P.f. RDT were 97.3% (95% CI: 95.5-98.6) and 97.1% (95% CI: 94.1-98.8) respectively. For gHAT, using archived plasma samples, the sensitivity and specificity were respectively 89% (95% CI: 84.4-92.6) and 93.5% (95% CI: 89.7-96.2) with the HAT/Malaria Combined RDT, and 88.2% (95% CI: 83.5-92) and 94.7% (95% CI: 91.1-97.2) with the HAT 2.0 RDT. Using the whole blood samples that were collected during the study, the specificity of the HAT/Malaria Combined RDT for gHAT was 95.8% (95% CI: 94.3-97.0).

Conclusion: The HAT/Malaria Combined prototype RDT was as accurate as the individual malaria or gHAT RDTs. The HAT/Malaria Combined prototype RDT is therefore suitable for both malaria diagnosis and gHAT screening. However, there is a need to assess its accuracy using fresh samples in prospective clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Protozoan / blood
  • Antigens, Protozoan / immunology
  • Democratic Republic of the Congo
  • Diagnostic Tests, Routine / methods*
  • Female
  • Humans
  • Malaria / blood
  • Malaria / diagnosis*
  • Male
  • Plasmodium falciparum
  • Prospective Studies
  • Protozoan Proteins / blood
  • Protozoan Proteins / immunology
  • Sensitivity and Specificity
  • Trypanosoma brucei gambiense
  • Trypanosomiasis, African / blood
  • Trypanosomiasis, African / diagnosis*
  • Uganda
  • Young Adult

Substances

  • Antigens, Protozoan
  • HRP-2 antigen, Plasmodium falciparum
  • Protozoan Proteins

Grant support

Standard Diagnostics did not provide any funding to support this study. FIND is not a funding agency, but a non-profit organization that is funded by multiple donors. This work was funded by the Bill and Melinda Gates Foundation (www.gatesfoundation.org; grant OPP1033712), the Swiss Agency for Development and Cooperation (www.eda.admin.ch/sdc; grants No. 81019551 and 81050188) and the Department for International Development of the United Kingdom (www.gov.uk/government/organisations/department-for-international-development; grant No. 204074-101). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.