Gametocyte sex ratios in children with asymptomatic, recrudescent, pyrimethamine-sulfadoxine-resistant, Plasmodium falciparum malaria

Abstract The clinical features of the primary Plasmodium falciparum infections in 25 children, and of the recrudescent infections that emerged after pyrimethamine-sulfadoxine (PS) treatment of the children had failed, were evaluated. In addition, the gametocyte sex ratios in these children and in age- and gender-matched controls who had PS-sensitive (PS-S) infections were also examined. Compared with the primary infections, the recrudescent infections were accompanied by significantly fewer symptoms and lower levels of parasitaemia but significantly higher gametocytaemia:parasitaemia ratios. Although the mean gametocyte sex ratio was female-biased pre-treatment, in both the PS-resistant (PS-R) and PS-S infections it became male-biased on days 7 and 14 post-treatment. The times taken to attain a sex ratio of 1 were similar in both groups. The predominance of macrogametocytes seen 'early' post-treatment (on day 3) was later replaced by a predominance of microgametocytes (on days 7 and 14). Analysis of the disposition of gametocytaemia, from the time to attain a sex ratio of 1, showed that the area under the curve of the plot of the level of microgametocytaemia υ. time and the mean half-life of the microgametocytaemia were significantly greater and microgametocytaemia clearance was significantly slower than the corresponding values for macrogametocytaemia. Although sex ratios in Plasmodium may naturally become more male-biased as the infection progresses, it is possible that PS treatment may have contributed to the male-biased sex ratios observed post-treatment.

[1]  A. Sowunmi,et al.  Asymptomatic, recrudescent, chloroquine-resistant Plasmodium falciparum infections in Nigerian children: clinical and parasitological characteristics and implications for the transmission of drug-resistant parasites , 2003, Annals of tropical medicine and parasitology.

[2]  A. Sowunmi A randomized comparison of chloroquine and chloroquine plus ketotifen in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children , 2003, Annals of tropical medicine and parasitology.

[3]  C. Drakeley,et al.  Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes. , 2002, The American journal of tropical medicine and hygiene.

[4]  A. Sowunmi A randomized comparison of chloroquine, amodiaquine and their combination with pyrimethamine-sulfadoxine in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children , 2002, Annals of tropical medicine and parasitology.

[5]  Todd G. Smith,et al.  FERTILITY INSURANCE AND THE SEX RATIOS OF MALARIA AND RELATED HEMOSPORORIN BLOOD PARASITES , 2002, The Journal of parasitology.

[6]  P. Brey,et al.  Plasmodium sex determination and transmission to mosquitoes. , 2002, Trends in parasitology.

[7]  J. E. Hyde,et al.  Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? , 2001, Trends in parasitology.

[8]  S. West,et al.  Evolution of gametocyte sex ratios in malaria and related apicomplexan (protozoan) parasites. , 2001, Trends in parasitology.

[9]  X. Su,et al.  A molecular marker for chloroquine-resistant falciparum malaria. , 2001, The New England journal of medicine.

[10]  J. Trape The public health impact of chloroquine resistance in Africa. , 2001, The American journal of tropical medicine and hygiene.

[11]  J. Wootton,et al.  Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. , 2000, Molecular cell.

[12]  J. Trape,et al.  Gametocytemia and infectivity to mosquitoes of patients with uncomplicated Plasmodium falciparum malaria attacks treated with chloroquine or sulfadoxine plus pyrimethamine. , 2000, The American journal of tropical medicine and hygiene.

[13]  S. West,et al.  Sex ratio and virulence in two species of lizard malaria parasites , 2000 .

[14]  T. Coulson,et al.  Sex determination in malaria parasites. , 2000, Science.

[15]  A. Dicko,et al.  Pyrimethamine-sulfadoxine efficacy and selection for mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase in Mali. , 1999, The American journal of tropical medicine and hygiene.

[16]  C. Mendis,et al.  The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector. , 1998, The American journal of tropical medicine and hygiene.

[17]  O. Doumbo,et al.  Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. , 1997, The Journal of infectious diseases.

[18]  W. Jelkmann,et al.  Decreased erythropoietin response in Plasmodium falciparum malaria‐associated anaemia , 1997, European journal of haematology.

[19]  J. E. Hyde,et al.  Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins. , 1997, Molecular and biochemical parasitology.

[20]  C. Manyando,et al.  Enhanced gametocyte production in Fansidar‐treated Plasmodium falciparum malaria patients: implications for malaria transmission control programmes , 1997, Tropical medicine & international health : TM & IH.

[21]  J. Verhave,et al.  Effect of gametocyte sex ratio on infectivity of Plasmodium falciparum to Anopheles gambiae. , 1996, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[22]  K. Mendis,et al.  Features of recrudescent chloroquine-resistant Plasmodium falciparum infections confer a survival advantage on parasites and have implications for disease control. , 1996, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[23]  A. Sowunmi Renal function in acute falciparum malaria. , 1996, Archives of disease in childhood.

[24]  B. Kendall,et al.  Brain swelling and ischaemia in Kenyans with cerebral malaria. , 1994, Archives of disease in childhood.

[25]  K. Dechering,et al.  Experimental infections of Anopheles gambiae with Plasmodium falciparum of naturally infected gametocyte carriers in Cameroon: factors influencing the infectivity to mosquitoes. , 1993, Tropical medicine and parasitology : official organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft fur Technische Zusammenarbeit.

[26]  A. Sowunmi,et al.  Malaria in Nigeria: a revisit. , 1990, Annals of tropical medicine and parasitology.

[27]  U. Hellgren,et al.  Plasma concentrations of sulfadoxine-pyrimethamine and of mefloquine during regular long term malaria prophylaxis. , 1990, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[28]  J. Schall The sex ratio of Plasmodium gametocytes , 1989, Parasitology.

[29]  W. Wernsdorfer,et al.  Plasma concentrations of sulfadoxine in healthy and malaria infected Thai subjects. , 1988, Acta tropica.

[30]  J H Meuwissen,et al.  Synchronization of Plasmodium falciparum gametocytes using an automated suspension culture system , 1986, Parasitology.

[31]  R. Sinden,et al.  Plasmodium falciparum gametocytes: their longevity and infectivity , 1977, Parasitology.

[32]  S. Kitchen,et al.  On the Relative Susceptibility of Anopheles Quadrimaculatus to Plasmodium Vivax and Plasmodium Falciparum1 , 1935 .

[33]  D. Thomson I.—A Research into the Production, Life and Death of Crescents in Malignant Tertian Malaria, in Treated and Untreated Cases, by an Enumerative Method , 1911 .