Researchers compared standard vs. ultra sensitive malaria diagnostics
Study findings showed that standard molecular diagnostics detect most potentially transmissible malaria infections and cannot be replaced by rapid diagnostic testing to screen for potential Plasmodium falciparum transmitters, researchers reported in The Lancet Infectious Diseases.
“Submicroscopic malaria infections contribute to transmission in exposed populations but their extent is underestimated even by standard molecular diagnostics. Sophisticated sampling and ultra-sensitive molecular methods can maximize test sensitivity but are not feasible in routine surveillance,” Ingrid Felger, PhD, from the department of medical parasitology and infection biology at the Swiss Tropical and Public Health Institute in Basel, Switzerland, and colleagues wrote. “Here we investigate the gains achievable by using increasingly sensitive methods with the aim to understand what diagnostic sensitivity is necessary to guide malaria interventions.”
Felger and colleagues assessed the diagnostic sensitivity of standard quantitative PCR (qPCR), ultrasensitive qPCR (us-qPCR), rapid diagnostic tests (RDT) and ultrasensitive P. falciparum RDT.
In a cross-sectional survey conducted in the Madang province in Papua New Guinea, they collected venous blood samples from 300 participants in two coastal, medium-endemic villages. They collected samples during peak rainy season, between Dec. 5, 2016, and Feb. 24, 2017.
“We systematically validated the proportion of P. falciparum and P. vivax infections as well as gametocyte carriers detected in samples from a community survey using different blood volumes, different molecular diagnostics, standard RDT and a novel ultrasensitive RDT (us-RDT),” the researchers wrote.
Felger and colleagues screened participants’ finger-prick blood samples for detectable P. falciparum and P. vivax infections and gametocyte carriers, according to the study.
Of the 161 P. falciparum infections, standard qPCR identified 54% (n = 87) and us-qPCR identified an additional 7% (n = 11). Half of the P. falciparum infections detected by standard qPCR, including high gametocytemic infections, were missed by us-RDT. Standard qPCR identified 52% (n = 73) of the 141 P. vivax infections and us-qPCR identified an additional 10% (n = 14).
Additionally, us-qPCR detected 86% (n = 80) of the 93 P. falciparum gametocyte carriers and 91% (75) of the 82 P. vivax gametocyte carriers. Felger and colleagues observed that with increasing age, the prevalence of P. vivax decreased and infections undetectable by standard qPCR increased.
In finger-prick blood samples, us-qPCR identified nearly all potentially transmitting parasite carriers, they noted. Although the infections are unlikely to be transmitted, an analyses of larger blood volumes found a large pool of ultra-low-density P. falciparum and P. vivax infections.
“Gametocyte densities in infections undetected by standard molecular diagnostics were very low and potentially not infective,” they wrote. “The us-RDT did not achieve this level of sensitivity and missed infections with high gametocyte densities. Our findings reduce the pressure to identify the very last parasite and advocate against the need for venous sampling in malaria control and elimination interventions.”
In a related comment also published in The Lancet Infectious Diseases, Anna Rosanas-Urgell, PhD, and Johanna Helena Kattenberg, PhD, both of the department of biomedical sciences at the Institute of Tropical Medicine, Antwerp, Belgium, said the findings “provide reassurance for current monitoring and screening interventions, since they show that standard qPCR, which is feasible in population-based studies, detects the majority of potentially transmissible infections. Their paper also draws attention to the scarcity of information on exactly which infections contribute to transmission.” – by Marley Ghizzone