Plasmodium falciparum gametocyte sex ratios in children with acute, symptomatic, uncomplicated infections treated with amodiaquine

Abstract

Background: Amodiaquine is frequently used as a partner drug in combination therapy or in some setting as monotherapy, but little is known about its effects on gametocyte production and sex ratio and its potential influence on transmission in Africa. The effects of amodiaquine on sexual stage parasites and gametocyte sex ratio, and the factors associated with a male-biased sex ratio were evaluated in 612 children with uncomplicated Plasmodium falciparum malaria who were treated with amodiaquine during the period 2000 - 2006 in an endemic area.

Methods: Clinical, parasitological and laboratory parameters were evaluated before treatment and during follow-up for 28-42 days, and according to standard methods. Gametocyte sex ratio was defined as the proportion of peripheral gametocytes that are male.

Results: Clinical recovery from illness occurred in all children. Gametocytaemia was detected in 66 patients (11%) before treatment and in another 56 patients (9%) after treatment. Gametocyte densities were significantly higher by days 3-7 following treatment compared with pre-treatment (P < 0.0001). Overall, mean gametocyte sex ratio increased significantly during follow-up and over the study periods from 2000-2006 (P < 0.001 in both cases), but was female-biased at enrolment throughout the study periods. Absence of fever, a haematocrit < 25%, asexual parasitaemia > 20,000/microL, gametocytaemia < 18/microL, and enrolment in 2006 were associated with a male-biased sex ratio pre-treatment. Anaemia and high parasitaemia were independent predictors of gametocyte maleness 7 days post treatment.

Conclusion: Amodiaquine may significantly increase gametocyte carriage, density and sex ratio, and may potentially influence transmission. It is possible that anaemia could have contributed to the increased sex ratio. These findings may have implications for malaria control efforts in Africa.

Figure 1

Kaplan-Meier plot (survival curve) of cumulative probability of remaining gametocyte-free after amodiaquine treatment of malarious children in 2000 (thick broken line), 2004 (thin broken line) and 2006 (solid line) (Log rank statistic = 0.8, P = 0.23).

Figure 2

Variations in the packed cell volume, density of gametocyte, and gametocyte sex ratio over the course of treatment of malaria infections with amodiaquine in years 2000 (thick broken line), 2004 (thin broken line), and 2006 (solid line).

Figure 3

Kaplan-Meier plot (survival curve) of cumulative probability of remaining free of a male-biased gametocyte sex ratio (gsr) after amodiaquine treatment of malarious children in 2000 (thick broken line), 2004 (thin broken line) and 2006 (solid line) (Log rank statistic = 2, P = 0.37).