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At least 19 recordsLinked to original sources

PubMed2005

Efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, chloroquine-sulfadoxine-pyrimethamine combination, and amodiaquine-sulfadoxine-pyrimethamine combination in Central African children with noncomplicated malaria.

This paper reports a two-phase study in Bangui, Central African Republic (CAR): first, we assessed the clinical efficacy to chloroquine (CQ), sulfadoxine-pyrimethamine (SP), and amodiaquine (AQ), then we tested the efficacy of two combinations: CQ + SP and AQ + SP. We used the standard 14-day WHO 2001 protocol to compare therapeutic responses in children under 5 years of age with acute uncomplicated Plasmodium falciparum malaria in Bangui between February 2002 and March 2004. The overall treatment failure rates with CQ, AQ, SP, CQ + SP, and AQ + SP were 40.9%, 20.0%, 22.8%, 7.2%, and 0%. These findings suggest that the Ministry of Health should recommend an interim policy with AQ + SP combination as the first-line antimalarial drug in Bangui until best alternative treatments like artemisinin-based combination therapies (ACTs) become available at low prices in the CAR.

Amodiaquine↗

PubMed2000

Chloroquine or amodiaquine combined with sulfadoxine-pyrimethamine for treating uncomplicated malaria.

BACKGROUND: Amodiaquine and chloroquine give fast relief from malaria symptoms, particularly fever. When used alone in areas where there is some parasite resistance they do not completely clear parasites from the blood in all cases, and so not all patients are cured of infection. The major disadvantage of using sulfadoxine-pyrimethamine alone is that it takes a relatively long time to relieve fever. OBJECTIVES: To assess the effectiveness of chloroquine or amodiaquine given with sulfadoxine-pyrimethamine to treat uncomplicated falciparum malaria. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Science Citation Index, African Index Medicus and LILACS were searched. Experts in the field and drug companies were contacted. SELECTION CRITERIA: Randomised and quasi-randomised trials of chloroquine or amodiaquine given with sulfadoxine-pyrimethamine compared with either drug alone in adults or children with confirmed uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two people independently applied the inclusion criteria. Data were extracted by the reviewer and checked independently by another person. MAIN RESULTS: Five trials were included. Fever clearance time was reduced by combination therapy compared with sulfadoxine-pyrimethamine alone. Parasite clearance at day seven follow-up was not significantly different for chloroquine or amodiaquine treatment with or without sulfadoxine-pyrimethamine. Parasite clearance at day 28 was better with combination therapy compared with chloroquine or amodiaquine alone (odds ratio 14.28, 95% confidence interval 6.76 to 30.19), but not significantly better than sulfadoxine-pyrimethamine alone (odds ratio 3.17, 95% confidence interval 0.96 to 10.43). There was no evidence from the included trials of serious side effects with combination treatment. REVIEWER'S CONCLUSIONS: In areas where chloroquine or amodiaquine are still effective, despite some degree of resistance, using these drugs in combination with sulfadoxine-pyrimethamine, rather than sulfadoxine-pyrimethamine alone, may make people feel better faster and improve sustained parasites clearance.

Adult↗

PubMed2001

Therapy of uncomplicated falciparum malaria: a randomized trial comparing artesunate plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone in Irian Jaya, Indonesia.

Combining artesunate with existing antimalarial drugs may improve cure rates, delay emergence of resistance, and reduce transmission. We performed a randomized comparative trial to quantify the effect of adding artesunate to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in Indonesia. Using a modified 1997 World Health Organization protocol for assessment of therapeutic efficacy of antimalarial drugs, 105 patients (stratified by age/ethnic group) were randomized: 53 received artesunate orally, 4 mg/kg of body weight, a single daily dose for three days, plus sulfadoxine-pyrimethamine orally (1.25 mg of pyrimethamine/kg of body weight), a single dose on day 0, and 52 patients received sulfadoxine-pyrimethamine alone. Six from the combination group were withdrawn from analysis, as were six of the sulfadoxine-pyrimethamine group. Treatment failure rates on day 14 were 0% in the artesunate plus sulfadoxine-pyrimethamine group and 8.7% in the sulfadoxine-pyrimethamine group (P = 0.12). Treatment failure rates on day 28 were 4.4% and 15.2%, respectively (P = 0.16). Relative risk of treatment failure at 28 days was 0.3 (95% confidence interval [CI] = 0.1-1.3). Mean fever clearance time (1.3 versus 1.7 days) and mean parasite clearance time (1.4 versus 2.0 days) were both faster in the artesunate plus sulfadoxine-pyrimethamine group than in the sulfadoxine-pyrimethamine group (P = 0.08 and P < 0.0001, respectively). Only 20 (39.2%) of 51 patients treated with artesunate plus sulfadoxine-pyrimethamine were still parasitemic on day 1 compared with 45 (86.5%) of 52 patients treated with sulfadoxine-pyrimethamine alone (P = 0.000001, relative risk [RR] = 0.4, 95% CI = 0.3-0.6). Gametocyte carriage was lower following artesunate plus sulfadoxine-pyrimethamine than following sulfadoxine-pyrimethamine (RR = 0.5, 95% CI = 0.2-1.0 on day 7 and RR = 0.5, 95% CI = 0.2-1.1 on day 14). Mild diarrhea, rash, and itching resolved without treatment. Combined artesunate plus sulfadoxine-pyrimethamine resulted in more rapid fever and parasiteclearance, was well tolerated, reduced risk of treatment failure, and lowered gametocyte carriage.

Administration, Oral↗

PubMed2004

Sulfadoxine resistance in Plasmodium vivax is associated with a specific amino acid in dihydropteroate synthase at the putative sulfadoxine-binding site.

Sulfadoxine is predominantly used in combination with pyrimethamine, commonly known as Fansidar, for the treatment of Plasmodium falciparum. This combination is usually less effective against Plasmodium vivax, probably due to the innate refractoriness of parasites to the sulfadoxine component. To investigate this mechanism of resistance by P. vivax to sulfadoxine, we cloned and sequenced the P. vivax dhps (pvdhps) gene. The protein sequence was determined, and three-dimensional homology models of dihydropteroate synthase (DHPS) from P. vivax as well as P. falciparum were created. The docking of sulfadoxine to the two DHPS models allowed us to compare contact residues in the putative sulfadoxine-binding site in both species. The predicted sulfadoxine-binding sites between the species differ by one residue, V585 in P. vivax, equivalent to A613 in P. falciparum. V585 in P. vivax is predicted by energy minimization to cause a reduction in binding of sulfadoxine to DHPS in P. vivax compared to P. falciparum. Sequencing dhps genes from a limited set of geographically different P. vivax isolates revealed that V585 was present in all of the samples, suggesting that V585 may be responsible for innate resistance of P. vivax to sulfadoxine. Additionally, amino acid mutations were observed in some P. vivax isolates in positions known to cause resistance in P. falciparum, suggesting that, as in P. falciparum, these mutations are responsible for acquired increases in resistance of P. vivax to sulfadoxine.

Amino Acid Sequence↗

PubMed2006

Sulfadoxine-pyrimethamine plus artesunate versus sulfadoxine-pyrimethamine plus amodiaquine for treating uncomplicated malaria.

BACKGROUND: Artemisinin-based combination treatments are strongly advocated, but supplies are limited. Sulfadoxine combined with amodiaquine is an alternative non-artemisinin combination. OBJECTIVES: To compare sulfadoxine-pyrimethamine plus amodiaquine (SP plus AQ) with sulfadoxine-pyrimethamine plus artesunate (SP plus AS) for treating uncomplicated Plasmodium falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to October 2005), EMBASE (1988 to October 2005), LILACS (October 2005), and reference lists. We also contacted researchers and organizations working in this field. SELECTION CRITERIA: Randomized controlled trials comparing SP plus AS with SP plus AQ for treating uncomplicated P. falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria, extracted data, and assessed methodological quality. The primary outcome measure was treatment failure (parasitological or clinical evidence of treatment failure between start of treatment and day 28). We calculated the relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. MAIN RESULTS: Four trials (775 participants) met the inclusion criteria. All were from areas of high and seasonal malaria transmission in Africa. Fewer participants using SP plus AQ failed treatment by day 28 (RR 0.59, 95% CI 0.42 to 0.83; 652 participants, 3 trials). Even excluding new infections, SP plus AQ performed better (RR 0.62, 95% CI 0.40 to 0.96; 649 participants, 3 trials). There was no statistically significant difference between the two treatments for treatment failure at day 14 (RR 1.14, 95% CI 0.47 to 2.78; 775 participants, 4 trials). SP plus AS was more effective at reducing gametocyte carriage at day seven (RR 2.31, 95% CI 1.36 to 3.92; 220 participants, 1 trial). One trial reported that one person - in the SP plus AQ group - developed severe malaria. Adverse events were poorly reported, but did not seem to differ in type and number between the two treatment combinations. AUTHORS' CONCLUSIONS: SP plus AQ performed better at controlling treatment failure at day 28, but was not as good as SP plus AS at reducing gametocyte carriage at day seven. Careful consideration of local resistance patterns is required because resistance to sulfadoxine-pyrimethamine and amodiaquine are high in many areas. In order to delay development of resistance to artesunate, the combination with sulfadoxine-pyrimethamine should only be considered where both drugs are known to be effective. Data on adverse events are still lacking.

Amodiaquine↗

PubMedDate not supplied

A randomized safety and tolerability trial of artesunate plus sulfadoxine--pyrimethamine versus sulfadoxine-pyrimethamine alone for the treatment of uncomplicated malaria in Gambian children.

Artemisinin derivatives, such as artesunate, have a short half-life and very rapid anti-malarial activity. Theoretically, using such agents in conjunction with well-established anti-malarial drugs such as sulfadoxine-pyrimethamine may reduce the rate of drug resistance. Such a combination has not previously been used in Africa. We have conducted a pilot safety trial of artesunate (4 mg/kg for 3 days) given with a single dose of sulfadoxine-pyrimethamine (25 mg/kg sulfadoxine) compared to sulfadoxine-pyrimethamine alone among 40 Gambian children with uncomplicated malaria. Both regimens were safe and well tolerated and there were no adverse experiences attributed to the combination. The addition of artesunate resulted in a higher proportion of afebrile children and children with a negative blood film on Day 2, and a reduction in the proportion of gametocyte carriers, when compared to sulfadoxine-pyrimethamine alone.

Antimalarials↗

PubMed2002

Therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine and the sulfadoxine-pyrimethamine-amodiaquine combination against uncomplicated Plasmodium falciparum malaria in young children in Cameroon.

OBJECTIVE: To evaluate the therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine, and the sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated Plasmodium falciparum malaria in young children in Cameroon. METHODS: In a randomized study we evaluated the effectiveness and tolerance of (i) sulfadoxine-pyrimethamine (SP) (25 mg/kg body weight of sulfadoxine and 1.25 mg/kg of pyrimethamine in a single oral dose), (ii) amodiaquine (AQ) (30 mg/kg body weight in three divided daily doses), and (iii) the sulfadoxine-pyrimethamine-amodiaquine combination (SP+AQ) (same doses as in the other two treatment groups, given simultaneously on day 0) in young children in southern Cameroon. The parasitological and clinical responses were studied until day 28 in accordance with the modified 1996 WHO protocol for the evaluation of the therapeutic efficacy of antimalarial drugs. FINDINGS: Of 191 enrolled patients, 6 and 8 were excluded or lost to follow-up before day 14 and between day 14 and day 28, respectively. For the AQ-treated patients, parasitological and clinical evaluation on day 14 showed late treatment failure in 2 of 61 (3.3%) and adequate clinical response with parasitological failure in one (1.6%). There was an adequate clinical response in all patients treated with SP or SP+AQ. Therapeutic failure rates on day 28 were 13.6%, 10.2% and 0% in the SP, AQ, and SP+AQ groups, respectively. Anaemia improved in all three regimens. AQ produced faster fever clearance but was associated with more transient minor side-effects than SP. SP+AQ reduced the risk of recrudescence between day 14 and day 28 but increased the incidence of minor side-effects. CONCLUSION: SP+AQ can be recommended as a temporary means of slowing the spread of multidrug resistance in Plasmodium falciparum in Africa while the introduction of other combinations, including artemisinin derivatives, is awaited.

Administration, Oral↗

PubMed1985

Prospective double-blind trial of two different doses of mefloquine plus pyrimethamine-sulfadoxine compared with pyrimethamine-sulfadoxine alone in the treatment of falciparum malaria.

This double-blind study is based on the treatment of 75 adult male patients suffering from Plasmodium falciparum malaria in Medellín, Colombia, a city in which there is no malaria transmission. The patients, who came from regions with high resistance to antimalarials, were divided into three groups receiving single-dose treatment as follows: a combination of 280 mg mefloquine, 800 mg sulfadoxine and 40 mg pyrimethamine; a combination of 420 mg mefloquine, 1200 mg sulfadoxine and 60 mg pyrimethamine; and a combination of 1500 mg sulfadoxine and 75 mg pyrimethamine. After treatment, follow-up examination was performed daily for I week and then weekly for another 3 weeks. The cure rate in the mefloquine groups (within the study period of 28 days) was 100%, and in the third group 75%. Normal blood levels of the administered drugs were found in 6 patients of the third group who were not cured; they were subsequently cured with a single dose of 1000 mg of mefloquine. Drug tolerance was good and no toxic effects were demonstrated in blood and urine examinations. While the doses in the drug combinations (containing mefloquine) gave very good results, we would recommend a slightly higher dose combination of mefloquine with sulfadoxine-pyrimethamine for the treatment of falciparum malaria in areas with a high prevalence of chloroquine resistance.

Adolescent↗

PubMed1989

Sulfadoxine specific lymphocyte transformation in a patient with eosinophilic pneumonia induced by sulfadoxine-pyrimethamine (Fansidar).

A patient developed eosinophilic peripheral pulmonary infiltrates while receiving malaria prophylaxis with sulfadoxine-pyrimethamine (Fansidar). Withdrawal of Fansidar and treatment with corticosteroids led to rapid recovery. No exacerbation occurred after cessation of corticosteroids. Lymphocyte transformation testing gave a positive result in the presence of sulfadoxine but not pyrimethamine. It is concluded that drug hypersensitivity to sulfadoxine was the cause of the eosinophilic pneumonia in this patient.

Adult↗

PubMed1990

[Comparative study of sulfadoxine-pyrimethamine and amodiaquine + sulfadoxine-pyrimethamine for the treatment of malaria caused by chloroquine-resistant Plasmodium falciparum in Maputo, Mozambique].

To compare the efficacy and side-effects of two therapeutic regimens for chloroquine-resistant falciparum malaria, a randomized study was carried out in 69 patients in Maputo Central Hospital in 1986-1987. The two treatments were sulfadoxine 25 mg/kg + pyrimethamine 1.25 mg/kg as a single dose (S + P) and amodiaquine 10 + 10 + 5 mg/kg over three days with sulfadoxine + pyrimethamine on the third day (A + S + P). The cure rate was 25/29 (86%) with S + P and 27/30 (90%) with A + S + P. No serious side-effects were observed. The probably slightly higher cure rate with the triple combination is hardly of clinical importance in semi-immune patients, but may theoretically help retard the development of resistance to sulfadoxine-pyrimethamine. This point and the question of the incidence of side-effects with the two regimens should be made the object of an epidemiological study.

Adult↗

PubMed1996

High-performance liquid chromatography determination of pyrimethamine, dapsone, monoacetyldapsone, sulfadoxine, and N-acetyl-sulfadoxine after rapid solid-phase extraction.

A solid-phase extraction procedure and a corresponding high-performance liquid chromatographic technique based on methods previously published by Edstein et al. (Edstein M. Quantification of antimalarial drugs. I. Simultaneous measurement of sulphadoxine, N4acetylsulphadoxine and pyrimethamine in human plasma. J Chromatogr 1984;305:502-7; Edstein M. Quantification of antimalarial drugs. II. Simultaneous measurement of dapsone, monoacetyldapsone and pyrimethamine in human plasma. J Chromatogr 1984;307:426-31) were developed for simultaneous determination of either dapsone (DDS), monoacetyldapsone (MADDS), and pyrimethamine (PYR) or sulfadoxine (SDX), N-acetyl-sulfadoxine (NAS) and pyrimethamine in plasma. Solid-phase extraction was achieved using C-18 extraction columns. An ionpair chromatography was performed on a C-18 analytical column (mu Bondapak C-18, 300 x 3.9 mm I.D.). Gradient elution with methanol, acetonitrile, PIC B6 reagent (1-hexanesulphonic acid), and water as mobile phase was applied. Ultraviolet detection was done at 210 nm for PYR, at 254 nm for SDX and NAS, and at 295 nm for DDS and MADDS. The extraction recoveries averaged 92.1% for PYR, 87.6% for DDS, 87.5% for MADDS, 91.2% for SDX, and 92.4% for NAS. The limit of quantification using 1.0-ml plasma samples was 15 ng/ml for PYR, DDS, MADDS, NAS, and 25 ng/ml for SDX (precision < 15%).

Anti-Infective Agents↗

PubMed2002

Therapeutic efficacies of artesunate-sulfadoxine-pyrimethamine and chloroquine-sulfadoxine-pyrimethamine in vivax malaria pilot studies: relationship to Plasmodium vivax dhfr mutations.

Artemisinin-derivative combination therapies (ACT) are highly efficacious against multidrug-resistant Plasmodium falciparum malaria. Few efficacy data, however, are available for vivax malaria. With high rates of chloroquine (CQ) resistance in both vivax and falciparum malaria in Papua Province, Indonesia, new combination therapies are required for both species. We recently found artesunate plus sulfadoxine-pyrimethamine (ART-SP) to be highly effective (96%) in the treatment of falciparum malaria in Papua Province. Following a preliminary study of CQ plus sulfadoxine-pyrimethamine (CQ-SP) for the treatment of Plasmodium vivax infection, we used modified World Health Organization criteria to evaluate the efficacy of ART-SP for the treatment of vivax malaria in Papua. Nineteen of 22 patients treated with ART-SP could be evaluated on day 28, with no early treatment failures. Adequate clinical and parasitological responses were found by day 14 in all 20 (100%) of the patients able to be evaluated and by day 28 in 17 patients (89.5%). Fever and parasite clearance times were short, with hematological improvement observed in 70.6% of the patients. Double (at positions 58 and 117) and quadruple (at positions 57, 58, 61, and 117) mutations in the P. vivax dihydrofolate reductase (PvDHFR) were common in Papuan P. vivax isolates (46 and 18%, respectively). Treatment failure with SP-containing regimens was significantly higher with isolates with this PvDHFR quadruple mutation, which included a novel T-->M mutation at residue 61 linked to an S-->T (but not an S-->N) mutation at residue 117. ART-SP ACT resulted in a high cure rate for both major Plasmodium species in Papua, though progression of DHFR mutations in both species due to the continued use of SP monotherapy for clinically diagnosed malaria threatens the future utility of this combination.

Adolescent↗

PubMed2005

Efficacy and tolerability of artesunate plus sulfadoxine-pyrimethamine and sulfadoxine-pyrimethamine alone for the treatment of uncomplicated Plasmodium falciparum malaria in Peru.

To assist the Peruvian Ministry of Health in modifying the malaria treatment policy for their north Pacific coastal region, we conducted an in vivo efficacy trial of sulfadoxine-pyrimethamine (SP) and SP plus artesunate (SP-AS) for the treatment for uncomplicated Plasmodium falciparum infections. A total of 197 patients were randomized to therapy with either SP (25 mg/kg of the sulfadoxine component in a single dose on day 0) or a combination of SP plus AS (4 mg/kg on days 0, 1, and 2) and were followed for 28 days for symptoms and recurrence of parasitemia. No statistically significant differences between the two groups were observed on enrollment with respect to age, sex, history of malaria, or geometric mean parasite density. A total of 185 subjects completed the 28-day follow-up. Of the 91 subjects treated with SP alone, two had recurrences of parasitemia on day 7 and one on day 21. Of the 94 subjects treated with SP-AS, one had a recurrence of parasitemia on day 21. Fever and asexual parasite density decreased significantly more rapidly and the proportion of patients with gametocytemia on days 3-28 was significantly lower in subjects treated with combination therapy than in those who received SP alone. No severe adverse drug reactions were observed; however, self-limited rash and pruritus were significantly more common and an exacerbation of nausea, vomiting, and abdominal pain were observed significantly more frequently among patients who had received SP-AS. These results have contributed to a National Malaria Control Program decision to change to SP-AS combination therapy as the first-line treatment for uncomplicated P. falciparum malaria in northern coastal Peru in November 2001, making Peru the first country in the Americas to recommend this combination therapy.

Adolescent↗

PubMed1987

A double-blind trial of a fixed combination of mefloquine plus sulfadoxine-pyrimethamine compared with sulfadoxine-pyrimethamine alone in symptomatic falciparum malaria.

A total of 100 male Zambian patients with symptomatic falciparum malaria were treated with either two tablets of mefloquine plus sulfadoxine-pyrimethamine (Fansimef) or three tablets of sulfadoxine-pyrimethamine (Fansidar) as a single dose. The patients were kept under observation from day 0 (day of treatment) to day 28 and all were cured. An S-type of response was seen in all patients; one patient in the Fansimef group inexplicably remained positive for Plasmodium falciparum trophozoites until day 6. There were no cases of recrudescence.The rate of clearance of parasitaemia was similar in both groups. The rate of clearance of fever was marginally faster in the Fansimef group. Side-effects such as pruritus, diarrhoea and abdominal pain occurred after both drugs but were mild and transient; tolerance was slightly better with Fansimef. Severe orthostatic hypotension occurred in 20% of the Fansidar patients and in only 2% of the Fansimef patients; this was reversed by bed rest. Haematological and biochemical parameters were generally not modified in an undesirable manner by the administration of these drugs.

Administration, Oral↗

PubMed2005

Antimalarial efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, and the combinations of amodiaquine + artesunate and sulfadoxine-pyrimethamine + artesunate in Huambo and Bie provinces, central Angola.

We studied three antimalarial treatments in Caala and Kuito, Angola, in 2002 and 2003. We tested chloroquine (CQ), amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) in Caala, and AQ, SP and the combinations AQ+artesunate (AQ+AS) and SP+artesunate (SP+AS) in Kuito. A total of 619 children (240 in Caala, 379 in Kuito) with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days, with PCR genotyping to distinguish recrudescence from reinfection. PCR-corrected failure proportions at day 28 were very high in the CQ group (83.5%, 95% CI 74.1-90.5), high in the SP groups (Caala: 25.3%, 95% CI 16.7-35.8; Kuito: 38.8%, 95% CI 28.4-50.0), around 20% in the AQ groups (Caala: 17.3%, 95% CI 10.0-27.2; Kuito: 21.6%, 95% CI 14.3-30.6) and very low in the artemisinin-based combination groups (1.2%, 95% CI 0.0-6.4 for each combination AQ+AS and SP+AS). These results show that CQ and SP are no longer efficacious in Caala and Kuito and that the moderate efficacy of AQ is likely to be compromised in the short term if used as monotherapy. We recommend the use of AQ with AS, though this combination might not have a long useful therapeutic life because of AQ resistance.

Amodiaquine↗

PubMedDate not supplied

Higher gametocyte prevalence following failure of treatment of Plasmodium falciparum malaria with sulfadoxine-pyrimethamine and the combination of chloroquine plus sulfadoxine-pyrimethamine: implications for progression of anti-folate resistance.

Chloroquine (CQ) treatment of CQ-resistant Plasmodium falciparum is associated with a significantly higher prevalence of post-treatment gametocytaemia which has been linked to the preferential transmission of CQ-resistant parasites. It is not known whether treatment failure (TF) with sulfadoxine-pyrimethamine (SP) is associated with the same higher prevalence of gametocytaemia as that seen with CQ TF. Using 1997 WHO in-vivo drug efficacy protocols for malaria, we therefore compared (in a study in 1999) the frequency of gametocytaemia in those with TF to the frequency seen in those with an adequate clinical and parasitological response (ACPR) following treatment with one of 3 regimens in Papua, Indonesia: SP monotherapy (n = 87; TF 20.7%), CQ monotherapy (n = 48; TF 83.3%), and the combination of CQ plus SP (n = 34; TF 38.2%). Following SP, day 7 prevalence was significantly higher in those with TF (67%) than with ACPR (38%, P = 0.03). Following combination treatment with CQ + SP, the day 14 gametocyte prevalence was significantly higher in those with TF (100% vs 38%, P = 0.016). The higher prevalence of SP TF-associated gametocytaemia may contribute to increased transmission of antifolate-resistant strains, and further cautions against the use of SP as monotherapy. Adding SP to CQ, after significant resistance has emerged to both drugs, may not prevent enhanced transmission of dual-resistant strains and progression of anti-folate resistance.

Adolescent↗

PubMed2004

Antimalarial efficacy of sulfadoxine-pyrimethamine, amodiaquine and a combination of chloroquine plus sulfadoxine-pyrimethamine in Bundi Bugyo, western Uganda.

We report below an in vivo antimalarial efficacy study conducted in 2002 in Bundi Bugyo, a district of western Uganda housing a large displaced population. We tested sulfadoxine-pyrimethamine (SP), amodiaquine (AQ) and the combination chloroquine plus SP (CQ + SP). A total of 268 children with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescences from re-infections. PCR-adjusted failure proportions at day 28 were 37.0% (34/92, 95% CI 27.1-47.7) in the SP group, 20.6% (14/68, 95% CI 11.7-32.1) in the AQ group and 22.8% (18/79, 95% CI 14.1-33.6) in the CQ + SP group. Early failures were particularly frequent in the SP group (15.2%). Clearance of gametocytes was slower in the SP and CQ + SP groups than in the AQ group. This study suggests that, in Bundi Bugyo, CQ + SP (Uganda's first-line regimen) will need to be replaced by a more efficacious regimen. Across Uganda, the deployment of SP containing combinations may not be a feasible long-term strategy. For Bundi Bugyo, we recommend a combination of artesunate and AQ. Our study also confirms previous findings that resistance is considerably underestimated by 14-day follow-ups. Antimalarial policy decisions should therefore be based on 28-day studies, with PCR adjustment to distinguish re-infections.

Amodiaquine↗

PubMed2005

A comparison of the efficacy of artesunate plus sulfadoxine-pyrimethamine with that of sulfadoxine-pyrimethamine alone, in the treatment of uncomplicated, Plasmodium falciparum malaria in eastern Sudan.

In an open, randomized, clinical trial, conducted in New Halfa, eastern Sudan, in September-October 2004, the efficacies and adverse effects of artesunate plus sulfadoxine-pyrimethamine (SP), in the treatment of uncomplicated, Plasmodium falciparum malaria, were compared with those of SP alone. Patients were randomized to receive either artesunate (4 mg/kg. day) on days 0-2 plus SP (25 mg sulfadoxine/kg) on day 0 or the SP alone, and then followed-up for 28 days. Sixty patients completed follow-up. Compared with the 30 given artesunate plus SP (ASP), the 30 given SP alone were much more likely to be febrile (30% v. 3.3%; P=0.006) and parasitaemic (50% v. 6.7%; P<00001) on day 1. By day 3, 16.7% of the patients given SP alone were still febrile and 6.7% of them were still parasitaemic, although all the patients given ASP were then afebrile (P=0.02) and aparasitaemic (P=0.1). Five (16.7%) of the patients treated with SP alone but none of those given ASP appeared to be treatment failures (P<0.05). Parasite genotyping revealed that four of the five apparent treatment failures were true recrudescences but the other represented a re-infection detected on day 28. The true frequencies of cure by day 28 were therefore 100% for ASP and 86.7% for SP alone (P=0.02). Adverse effects of treatment (nausea, itching and giddiness) were observed with similar frequencies in the two treatment arms (10.0% of the patients given ASP v. 13.3% of the patients given SP alone; P>0.05). The frequencies of gametocytaemia during follow-up were, however, much lower in the ASP arm than in the SP-only (0.0% v. 23.3%; P=0.005).Thus, although the problems posed by adverse effects were similar in the two treatment arms, ASP appeared markedly better, in terms of fever- and parasite-clearance times and the prevalence of post-treatment gametocytaemia, than SP alone.

Adolescent↗