Plasmodium Gametocytes in Field Studies: Do We Measure Commitment to Transmission or Detectability?

Abstract

The proportion of Plasmodium spp. infections carrying gametocytes, and gametocyte densities, are often reported as surrogate markers for transmission potential. It remains unclear whether parasites under natural conditions adjust commitment to transmission depending on external factors. Population-based surveys comprising mostly asymptomatic low-density infections are always impacted by the sensitivity of the assays used to diagnose infections and detect gametocytes. Asexual parasite density is an important predictor for the probability of detecting gametocytes, and in many cases it can explain patterns in gametocyte carriage without the need for an adjustment of the gametocyte conversion rate. When reporting gametocyte data, quantification of blood-stage parasitemia and its inclusion as a confounder in multivariable analyses is essential.

Keywords: gametocyte conversion rate; gametocyte density; limit of detection; malaria transmission; molecular gametocyte detection; population gametocyte prevalence.

Figure 1

Population parasite and gametocyte prevalence in relation to the diagnostic method used to detect blood-stage infections (qPCR, nested PCR, or microscopy). In each bar, the number of asexual infections, the number of infections with gametocytes detected, and the proportion of gametocyte-positive infections are given. Gametocytes were detected by RT-qPCR of marker transcripts pfs25 and pvs25 among samples that tested positive for P. falciparum or P. vivax by qPCR, nested PCR, or microscopy. Data are from a cross-sectional survey in Papua New Guinea, involving 2083 individuals [14].

Figure 2

P. vivax pvs25 (A) and P. falciparum pfs25 (B) transcript density vs. genome density in cross-sectional surveys. Possible scenarios resulting in infections with above or below proportions of gametocytes among all parasites are indicated. As each gametocyte contains one genome, high pvs25 or pfs25 densities when genome copies are very low (top-left region in graphs) are not observed. Data are from two cross-sectional surveys conducted in Papua New Guinea (4,600 individuals surveyed, 766 positive for P. vivax, 611 positive for P. falciparum by qPCR) [20].