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Assessment of ultra-sensitive malaria diagnosis vs standard molecular diagnostics for malaria elimination: An in-depth molecular community cross-sectional study

The Lancet Infectious Diseases Oct 04, 2018

Hofmann NE, et al. - Authors gauged the gains achievable with regard to malaria elimination by using increasingly sensitive methods of testing in order to understand what diagnostic sensitivity (ultra-sensitive malaria diagnosis or standard molecular diagnostics) is needed to guide malaria interventions. us-qPCR on fingerprick blood volumes identified almost all potentially transmitting parasite carriers. A large pool of ultra-low-density Plasmodium falciparum and Plasmodium vivax infections, which are unlikely to be transmitted, was revealed by analyzing larger blood volumes. Hence, for identifying potential P falciparum transmitters, current RDTs cannot replace molecular diagnostics.

Methods

  • Experts collected the venous blood samples from participants in a cross-sectional survey in two coastal medium-endemic villages in Madang province, Papua New Guinea.
  • They quantified the proportion of P falciparum and P vivax infections and gametocyte carriers detectable in fingerprick blood volumes (200 μL) by standard 18S rRNA qPCR, us-qPCR, rapid diagnostic test (RDT), and ultra-sensitive P falciparum RDT using ultra-sensitive quantitative PCR (us-qPCR) on concentrated high-volume blood samples (2 mL) as reference.
  • They also compared the epidemiological patterns observed with each diagnostic approach in the study population.

Results

  • As per data, venous blood samples were collected from 300 participants between December 5, 2016 and February 24, 2017 (ie, peak rainy season).
  • A total of 87 (54%) of 161 P falciparum infections and 73 (52%) of 141 P vivax infections detected by the reference method were identified by standard qPCR.
  • An additional 11 (7%) P falciparum infections and 14 (10%) P vivax infections 80 (86%) of 93 P falciparum gametocyte carriers were identified by us-qPCR and 75 (91%) of 82 P vivax gametocyte carriers were found among infections detectable by us-qPCR.
  • Results demonstrated that half of P falciparum infections detected by standard qPCR, including high gametocytemic infections were missed by ultra-sensitive RDT.
  • Findings suggested that epidemiological patterns corresponded well between standard qPCR and the reference method.
  • With the decrease in the prevalence of P vivax with increasing age, there was an increase in the proportion of P vivax infections undetectable by standard qPCR.
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