Plasmodium falciparum gametocyte carriage, sex ratios and asexual parasite rates in Nigerian children before and after a treatment protocol policy change instituting the use of artemisinin-based combination therapies

Abstract

The effects of artemisinin-based combination therapies (ACTs) on transmission of Plasmodium falciparum were evaluated after a policy change instituting the use of ACTs in an endemic area. P. falciparum gametocyte carriage, sex ratios and inbreeding rates were examined in 2,585 children at presentation with acute falciparum malaria during a 10-year period from 2001-2010. Asexual parasite rates were also evaluated from 2003-2010 in 10,615 children before and after the policy change. Gametocyte carriage declined significantly from 12.4% in 2001 to 3.6% in 2010 (@@&#967;2 for trend = 44.3, p < 0.0001), but sex ratios and inbreeding rates remained unchanged. Additionally, overall parasite rates remained unchanged before and after the policy change (47.2% vs. 45.4%), but these rates declined significantly from 2003-2010 (@@&#967;2 for trend 35.4, p < 0.0001). Chloroquine (CQ) and artemether-lumefantrine (AL) were used as prototype drugs before and after the policy change, respectively. AL significantly shortened the duration of male gametocyte carriage in individual patients after treatment began compared with CQ (log rank statistic = 7.92, p = 0.005). ACTs reduced the rate of gametocyte carriage in children with acute falciparum infections at presentation and shortened the duration of male gametocyte carriage after treatment. However, parasite population sex ratios, inbreeding rates and overall parasite rate were unaffected

A review of the effects of artemether-lumefantrine on gametocyte carriage and disease transmission

“…The above data are supported by other observations in children and adults, as detailed in Table 1[28,30,37,47,53,54,62,64,68,70]. …”

“…Studies that report the effects of AL (in the absence of a comparator treatment) on gametocyte carriage/clearance are reviewed below and summarized in Table 1[28,30,37,47,53,54,62,64,68,70] (and Additional file 2[28,30,37,47,53,54,62,64,68,70]). Unless otherwise stated, all data discussed relate to patients with uncomplicated P. falciparum malaria.…”

A Male and Female Gametocyte Functional Viability Assay To Identify Biologically Relevant Malaria Transmission-Blocking Drugs

“…We have recently shown that male gametocytes are generally more sensitive to antimalarial drugs than female gametocytes (28). This is highly significant as males may only represent ϳ20% of the total gametocyte population, and so assays without a sex-specific readout are not likely to identify male-targeted transmission-blocking compounds as they fall below the threshold of detection (31,32). As both gametocyte sexes are required for transmission, a combined male and female gametocyte readout is essential to maximize the screening potential of a gametocyte assay.…”

Sub-microscopic gametocyte carriage in febrile children living in different areas of Gabon

“…Although ACT shortens the duration of post-treatment circulation of mature gametocytes, a low density of mature sexual forms can persist after apparently complete clearance of trophozoites [14,35]. On day 28 after ACT treatment, a proportion of 12-40% of cured patients was found to be still gametocytaemic; a status which allows post-treatment malaria transmission [9,14,36,37]. Therefore, it can be assumed that the rebound of P .…”