Predictive Performance of Rapid Diagnostic Tests for Falciparum Malaria and Its Modeled Impact on Integrated Community Case Management of Malaria in Sub-Saharan African Febrile Children

Clin Infect Dis. 2021 Sep 7;73(5):e1158-e1167. doi: 10.1093/cid/ciaa1942.

Abstract

Background: Integrated community case management (iCCM) of malaria complements public health services to improve access to timely diagnosis and treatment of malaria. ICCM relies on standardized test-and-treat algorithms implemented by community health workers using malaria rapid diagnostic tests (RDTs). However, due to a changing epidemiology of fever causes in Africa, positive RDT results might not correctly reflect malaria. In this study, we modeled diagnostic predictive values for all malaria-endemic African regions as an indicator of the programmatic usefulness of RDTs in iCCM campaigns on malaria.

Methods: Positive predictive values (PPVs) and negative predictive values (NPVs) of RDTs for clinical malaria were modeled. Assay-specific performance characteristics stem from the Cochrane Library and data on the proportion of malaria-attributable fevers among African febrile children aged <5 years were used as prevalence matrix.

Results: Average country-level PPVs vary considerably. Ethiopia had the lowest PPVs (histidine-rich protein II [HRP2] assay, 17.35%; parasite lactate dehydrogenase [pLDH] assay, 39.73%), and Guinea had the highest PPVs (HRP2 assay, 95.32%; pLDH assay, 98.46%). On the contrary, NPVs were above 90% in all countries (HRP2 assay, ≥94.87%; pLDH assay, ≥93.36%).

Conclusions: PPVs differed considerably within Africa when used to screen febrile children, indicating unfavorable performance of RDT-based test-and-treat algorithms in low-PPV settings. This suggests that the administration of antimalarials alone may not constitute causal treatment in the presence of a positive RDT result for a substantial proportion of patients, particularly in low-PPV settings. Therefore, current iCCM algorithms should be complemented by information on other setting-specific major causes of fever.

Keywords: Africa; RDT; integrated community case management; malaria.

MeSH terms

  • Antigens, Protozoan
  • Case Management
  • Child
  • Diagnostic Tests, Routine
  • Ethiopia
  • Fever / diagnosis
  • Humans
  • Malaria* / diagnosis
  • Malaria* / drug therapy
  • Malaria* / epidemiology
  • Malaria, Falciparum* / diagnosis
  • Malaria, Falciparum* / drug therapy
  • Malaria, Falciparum* / epidemiology
  • Plasmodium falciparum
  • Protozoan Proteins
  • Sensitivity and Specificity

Substances

  • Antigens, Protozoan
  • Protozoan Proteins