Comparative Efficacy of Chloroquine and Sulfadoxine-Pyrimethamine for Uncomplicated Plasmodium Falciparum Malaria and Impact on Gametocyte Carriage Rates in the East Nusatenggara Province of Indonesia

Abstract

The efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) was evaluated in 89 subjects greater than one year of age with uncomplicated P. falciparum malaria in the East Nusatenggara Province of Indonesia. Fever clearance time was longer in the SP group than in the CQ group. However, parasite clearance time was extended in subjects who received CQ compared with those who received SP. Major adverse events were not observed in either group, and no hospitalizations were required during the study. Treatment failure rates at day 28 were 69% for CQ and 8.5% for SP. In both treatment groups, gametocytemia developed during the follow-up period, but was more pronounced in the SP group, peaking at 94% on day 7. Regardless of treatment group, children < 10 years of age had significantly higher treatment failure rates than subjects >/=10 years of age (relative risk = 2.49), suggesting that acquired immunity influenced treatment outcomes in the presence of parasite drug resistance. Although a highly effective alternative to CQ for clearing infection, SP treatment also presented some potential drawbacks (e.g., increased and persistent gametocytemia). Replacement of CQ with SP as a first-line therapy, either alone or in combination with CQ, in those areas of Indonesia with high levels of CQ resistance should significantly improve treatment outcomes, particularly in vulnerable populations lacking clinical immunity. More efficacious and rapidly acting asexual stage treatments are generally associated with increased gametocyte clearance and combination therapy in areas where drug resistance is high or emerging may provide an additional means for reducing transmission.

A High-Throughput Screen Targeting Malaria Transmission Stages Opens New Avenues for Drug Development

“…The observed differential in vitro activity against early gametocyte stages confirms data from field studies: for susceptible parasites, treatment with artemsinin and derivatives as well as chloroquine significantly reduces the prevalence and density of malaria transmission stages [31–34]. Emergence of resistance, however, is usually paralleled by increased transmission rates [35].…”

The efficacy of sulfadoxine–pyrimethamine alone and in combination with chloroquine for malaria treatment in rural Eastern Sudan: the interrelation between resistance, age and gametocytogenesis

“…The upsurge of gametocytemia following treatment with SP compared with treatment with other antimalarial drugs like CQ (Sutanto et al 2004), quinine (Coosemans et al 1988), or artemisinin (our unpublished data), is a consistent finding worthy meticulous examination. The fast propagation in SP resistance was assumed to be multi-factorial, as it could be due to intrinsic parasite/drug properties, to crossresistance with drugs like septrin (Sibley et al 2001) and/or due to a linkage between CQ and SP resistance (unpublished data).…”

“…The upsurge of gametocytemia following treatment with SP compared with treatment with other antimalarial drugs like CQ (Sutanto et al. 2004), quinine (Coosemans et al.…”

Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu

“…Six cases of P. falciparum had detectable parasitaemia on day two but not beyond and only one persisted until day 3 at low density (120/μl). Gametocytaemia was common in P. falciparum infections throughout the follow-up period, as neither SP nor CQ are effective gametocidal agents[37] and SP is frequently associated with increasing gametocytaemia following therapy, an observation supported in this study on days six through 20 (Figure 3) [38]. Although CQ+SP was an effective treatment for asexual P. falciparum parasitaemia, this combination has the potential to increase transmission in the early post-treatment period.…”