A comparative study of Lapudrine® (chlorproguanil) and Maloprim® (pyrimethamine and dapsone) as chemoprophylactics against malaria in Gambian children

Greenwood, Brian; Greenwood, A.M.; Smith, A.; Menon, A.; Bradley, A. K.; Snow, Robert W.; Sisay, F.; Bennett, Steve; Watkins, William M.; Njie, Alpha

doi:10.1016/0035-9203(89)90635-4

Cited by 22 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed Menendez et al 1997 [7] showed that reduced severe anaemia and clinical malaria in the first year was followed in the second year by an increased rebound risk for both conditions. Similar findings were previously reported from the Gambia [8]. Thus the overall efficacy of chemoprophylaxis as a public health intervention is substantially reduced.…”

Section: Introductionsupporting

confidence: 89%

Clinical Immunity to Malaria

Schofield

Müeller²

2006

CMM

109

View full text Add to dashboard Cite

Under appropriate conditions of transmission intensity, functional immunity to malaria appears to be acquired in distinct stages. The first phase reduces the likelihood of severe or fatal disease; the second phase limits the clinical impact of 'mild' malaria; and the third provides partial but incomplete protection against pathogen burden. These findings suggest clinical immunity to mortality and morbidity is acquired earlier, with greater ease, and via distinct mechanisms as compared to anti-parasite immunity, which is more difficult to achieve, takes longer and is only ever partially efficacious. The implications of this view are significant in that current vaccination strategies aim predominantly to achieve anti-parasite immunity, although imparting clinical immunity is the public health objective. Despite enormous relevance for global public health, the mechanisms governing these processes remain obscure. Four candidate mechanisms might mediate clinical immunity, namely immunity to cytoadherence determinants, tolerance to toxins, acquired immunity to toxins, and immunoregulation. This review addresses the targets and determinants of clinical immunity, and considers the implications for vaccine development.

show abstract

Section: Introductionsupporting

confidence: 89%

Clinical Immunity to Malaria

Schofield

Müeller²

2006

CMM

109

View full text Add to dashboard Cite

show abstract

“…Of these, only nine covered a study period of 12 months or multiple thereof in under‐5s (but not necessarily covering the full age‐range). After adjusting for study duration and age, 13 studies were included for analysis (Greenwood et al. 1987, 1989; Mbogo et al.…”

Section: Resultsmentioning

confidence: 99%

“…Of these, only nine covered a study period of 12 months or multiple thereof in under-5s (but not necessarily covering the full age-range). After adjusting for study duration and age, 13 studies were included for analysis (Greenwood et al 1987(Greenwood et al , 1989Mbogo et al 1993;Alonso et al 1994;Kitua et al 1996;Lemnge et al 1997;McGuinness et al 1998;Ijumba et al 2002;Massaga et al 2003) (11 from rural and 2 from urban areas), representing 3493 episodes of slide confirmed malarial fevers during 5636 person-years of follow-up.…”

Section: Non-severe Malariamentioning

confidence: 99%

Estimates of the burden of malaria morbidity in Africa in children under the age of 5 years

Roca-Feltrer

Carneiro

Schellenberg

2008

Tropical Med Int Health

View full text Add to dashboard Cite

Summaryobjective To estimate the direct burden of malaria among children younger than 5 years in subSaharan Africa (SSA) for the year 2000, as part of a wider initiative on burden estimates.methods A systematic literature review was undertaken in June 2003. Severe malaria outcomes (cerebral malaria, severe malarial anaemia and respiratory distress) and non-severe malaria data were abstracted separately, together with information on the characteristics of each study and its population. Population characteristics were also collated at a national level. A meta-regression model was used to predict the incidence of malaria fevers at a national level. For severe outcomes, results were presented as median rates as data were too sparse for modelling.results For the year 2000, an estimated 545 000 (uncertainty interval: 105 000-1 750 000) children under the age of 5 in SSA experienced an episode of severe malaria for which they were admitted to hospital. A total of 24 000 (interquartile range: 12 000-37 000) suffered from persistent neurological deficits as a result of cerebral malaria. The number of malaria fevers associated with high parasite density in under-5s in SSA in 2000 was estimated as 115 750 000 (uncertainty interval: 91 243 000-257 957 000).conclusion Our study predicts a lower burden than previous estimates of under-5 malaria morbidity in SSA. As there is a lack of suitable data to enable comprehensive estimates of annual malaria incidence, we describe the information needed to improve the validity of future estimates.

show abstract

“…Dapsone had been used in malaria and leprosy for many years with no major safety concerns [32]–[34]. Thus, previous studies of CPG−DDS without artesunate did not prospectively include G6PD genotyping or phenotyping.…”

Section: Discussionmentioning

confidence: 99%

Chlorproguanil−Dapsone−Artesunate versus Artemether−Lumefantrine: A Randomized, Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum Malaria

et al. 2009

View full text Add to dashboard Cite

BackgroundChlorproguanil−dapsone−artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether−lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients.Methods and FindingsThe trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (≥1 to <15 years old, median age 3 years) with acute uncomplicated P. falciparum malaria were randomized (2∶1) to receive CDA 2/2.5/4 mg/kg once daily for three days (N = 914) or six-doses of AL over three days (N = 458). Non-inferiority of CDA versus AL for efficacy was evaluated in the Day 28 per-protocol (PP) population using parasitological cure (polymerase chain reaction [PCR]-corrected). Cure rates were 94.1% (703/747) for CDA and 97.4% (369/379) for AL (treatment difference –3.3%, 95%CI –5.6, −0.9). CDA was non-inferior to AL, but there was simultaneous superiority of AL (upper 95%CI limit <0). Adequate clinical and parasitological response at Day 28 (uncorrected for reinfection) was 79% (604/765) with CDA and 83% (315/381) with AL. In patients with a G6PD-deficient genotype (94/603 [16%] hemizygous males, 22/598 [4%] homozygous females), CDA had the propensity to cause severe and clinically concerning hemoglobin decreases: the mean hemoglobin nadir was 75 g/L (95%CI 71, 79) at Day 7 versus 97 g/L (95%CI 91, 102) for AL. There were three deaths, unrelated to study medication (two with CDA, one with AL).ConclusionsAlthough parasitologically effective at Day 28, the hemolytic potential of CDA in G6PD-deficient patients makes it unsuitable for use in a public health setting in Africa.Trial RegistrationClinicalTrials.gov NCT00344006

show abstract

A comparative study of Lapudrine® (chlorproguanil) and Maloprim® (pyrimethamine and dapsone) as chemoprophylactics against malaria in Gambian children

Cited by 22 publications

References 20 publications

Clinical Immunity to Malaria

Clinical Immunity to Malaria

Estimates of the burden of malaria morbidity in Africa in children under the age of 5 years

Chlorproguanil−Dapsone−Artesunate versus Artemether−Lumefantrine: A Randomized, Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum Malaria

Contact Info

Product

Resources

About