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1.
Parasit Vectors ; 17(1): 279, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943214

ABSTRACT

BACKGROUND: Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis. METHODS: This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment. RESULTS: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported. CONCLUSIONS: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.


Subject(s)
Anthelmintics , Artemisinins , Artesunate , Drug Therapy, Combination , Praziquantel , Pyrimethamine , Schistosoma haematobium , Schistosoma mansoni , Schistosomiasis haematobia , Schistosomiasis mansoni , Humans , Child , Praziquantel/administration & dosage , Praziquantel/adverse effects , Praziquantel/therapeutic use , Pyrimethamine/administration & dosage , Pyrimethamine/therapeutic use , Pyrimethamine/adverse effects , Animals , Adolescent , Artesunate/administration & dosage , Artesunate/therapeutic use , Female , Male , Schistosomiasis mansoni/drug therapy , Schistosoma haematobium/drug effects , Schistosomiasis haematobia/drug therapy , Schistosoma mansoni/drug effects , Kenya , Artemisinins/administration & dosage , Artemisinins/therapeutic use , Artemisinins/adverse effects , Treatment Outcome , Anthelmintics/administration & dosage , Anthelmintics/adverse effects , Anthelmintics/therapeutic use , Sulfalene/administration & dosage , Sulfalene/therapeutic use , Sulfalene/adverse effects , Drug Combinations , Parasite Egg Count
2.
Lancet Infect Dis ; 10(9): 603-11, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20705516

ABSTRACT

BACKGROUND: Schistosomiasis is an important parasitic disease in Kenya. Decreasing susceptibility of schistosomes to praziquantel, the major drug used to reduce disease morbidity, has made assessment of new antischistosomal drugs a priority. We aimed to assess the safety and efficacy of an artesunate-based combination drug in the treatment of schistosomiasis. METHODS: In this open-label randomised trial in Rarieda district of western Kenya, we enrolled school children (aged 6-15 years) who had Schistosoma mansoni infection according to duplicate Kato-Katz thick smears from a stool sample. Computer-generated block randomisation was used to assign children (1:1) to receive artesunate (100 mg) with sulfalene (also known as sulfamethoxypyrazine; 250 mg) plus pyrimethamine (12.5 mg) as one dose every 24 h for 3 days or one dose of praziquantel (40 mg/kg per day). The primary efficacy endpoint was the number of participants cured 28 days after treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01054651. RESULTS: Between October and December, 2009, 212 children were enrolled and assigned to receive artesunate with sulfalene plus pyrimethamine (n=106) or praziquantel (n=106). 69 patients (65%) were cured in the praziquantel treatment group compared with 15 (14%) in the artesunate with sulfalene plus pyrimethamine treatment group (p<0.0001). Adverse events were less common in patients taking artesunate with sulfalene plus pyrimethamine than in those taking praziquantel (22% [n=23] vs 49% [n=52], p<0.0001), and no drug-related serious adverse events occurred. INTERPRETATION: The standard treatment with praziquantel is more effective than artesunate with sulfalene plus pyrimethamine in the treatment of children with S mansoni infection in western Kenya. Whether artemisinin-based combination therapy has a role in the treatment of schistosomiasis is unclear.


Subject(s)
Artemisinins/therapeutic use , Pyrimethamine/therapeutic use , Schistosomiasis mansoni/drug therapy , Sulfalene/therapeutic use , Adolescent , Amebicides/adverse effects , Amebicides/therapeutic use , Animals , Antiprotozoal Agents/adverse effects , Antiprotozoal Agents/therapeutic use , Artemisinins/adverse effects , Artesunate , Child , Child, Preschool , Drug Therapy, Combination , Female , Humans , Infant , Kenya , Male , Pyrimethamine/adverse effects , Schistosoma mansoni , Schistosomiasis mansoni/classification , Sulfalene/adverse effects
3.
Malar J ; 9: 378, 2010 Dec 31.
Article in English | MEDLINE | ID: mdl-21194422

ABSTRACT

BACKGROUND: Several studies have demonstrated the efficacy of artemisinin-combination therapy (ACT) across malaria zones of the world. Fixed dose ACT with shorter courses and fewer tablets may be key determinants to ease of administration and compliance. METHODS: Children aged one year to 13 years presenting with uncomplicated Plasmodium falciparum malaria were recruited in Ibadan, south-western Nigeria. A total of 250 children each were randomly assigned to receive three doses of artesunate/sulphamethoxypyrazine/pyrimethamine (AS + SMP) (12 hourly doses over 24 hours) or three doses of artesunate/amodiaquine (AS + AQ) (daily doses over 48 hours). Efficacy and safety of the two drugs were assessed using a 28-day follow-up and the primary outcome was PCR- corrected parasitological cure rate and clinical response. RESULTS: There were two (0.4%) early treatment failures, one in each treatment arm. The PCR corrected cure rates for day 28 was 97.9% in the AS + AQ arm and 95.6% in the AS + SMP arm (p = 0.15). The re-infection rate was 1.7% in the AS + AQ arm and 5.7% in the AS + SMP arm (p = 0.021). The fever clearance time was similar in the two treatment groups: 1 - 2 days for both AS + SMP and AS + AQ (p = 0.271). The parasite clearance time was also similar in the two treatment groups with 1 - 7 days for AS + SMP and 1 - 4 days for AS + AQ (p = 0.941). The proportion of children with gametocytes over the follow-up period was similar in both treatment groups. Serious Adverse Events were not reported in any of the patients and in all children, laboratory values (packed cell volume, liver enzymes, bilirubin) remained within normal levels during the follow-up period but the packed cell volume was significantly lower in the AS + SMP group. CONCLUSIONS: This study demonstrates that AS + SMP FDC given as three doses over 24 hours (12-hour intervals) has similar efficacy as AS + AQ FDC given as three doses over 48 hours (24-hour interval) for the treatment of uncomplicated Plasmodium falciparum malaria in children in Nigeria. Both drugs also proved to be safe. Therefore, AS + SMP could be an alternative to currently recommended first-line ACT with continuous resistance surveillance.


Subject(s)
Antimalarials/administration & dosage , Artemisinins/administration & dosage , Malaria, Falciparum/drug therapy , Adolescent , Amodiaquine/administration & dosage , Amodiaquine/adverse effects , Antimalarials/adverse effects , Artemisinins/adverse effects , Artesunate , Child , Child, Preschool , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Female , Humans , Infant , Male , Nigeria , Pyrimethamine/administration & dosage , Pyrimethamine/adverse effects , Sulfalene/administration & dosage , Sulfalene/adverse effects , Time Factors , Treatment Outcome
4.
Malar J ; 8: 63, 2009 Apr 14.
Article in English | MEDLINE | ID: mdl-19366448

ABSTRACT

BACKGROUND: The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance. METHODS: Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP) three-day (once daily for 3 days) regimen (N = 476) or AS-SMP 24-hour (0 h, 12 h, 24 h) regimen (N = 458) or artemether-lumefantrine (AL), the regular 6 doses regimen (N = 450). The primary objective was to demonstrate non-inferiority (using a margin of -6%) of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate. RESULTS: The PCR corrected 28-day cure rate on the intention to treat (ITT) analysis population were: 96.0%(457/476) in the AS-SMP three-day group, 93.7%(429/458) in the AS-SMP 24-hour group and 92.0%(414/450) in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437) in the AS-SMP three-day group, 99.5%(416/419) in the AS-SMP 24-hour group and 99.7(391/394)% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea) which were slightly higher in the AS-SMP 24-hour group. CONCLUSION: AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated. TRIAL REGISTRATION: NCT00484900 http://www.clinicaltrials.gov.


Subject(s)
Antimalarials/therapeutic use , Artemisinins/therapeutic use , Ethanolamines/therapeutic use , Fluorenes/therapeutic use , Malaria, Falciparum/drug therapy , Plasmodium falciparum/drug effects , Pyrimethamine/therapeutic use , Sulfalene/therapeutic use , Animals , Antimalarials/administration & dosage , Antimalarials/adverse effects , Artemether, Lumefantrine Drug Combination , Artemisinins/administration & dosage , Artemisinins/adverse effects , Artesunate , Child , Child, Preschool , Drug Administration Schedule , Drug Combinations , Drug Therapy, Combination , Ethanolamines/administration & dosage , Ethanolamines/adverse effects , Female , Fluorenes/administration & dosage , Fluorenes/adverse effects , Humans , Infant , Malaria, Falciparum/epidemiology , Male , Plasmodium falciparum/isolation & purification , Pregnancy , Prospective Studies , Pyrimethamine/administration & dosage , Pyrimethamine/adverse effects , Sulfalene/administration & dosage , Sulfalene/adverse effects , Tablets , Treatment Outcome
5.
Am J Trop Med Hyg ; 75(4): 630-6, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17038684

ABSTRACT

The choice of artemisinin-based combination that is being adopted for malaria treatment in sub-Saharan Africa may depend on several factors, including cost, efficacy, side effects, and simplicity of administration. We tested the hypothesis that artesunate-sulfamethoxypyrazine-pyrimethamine is as efficacious as the four-dose regimen of artemether-lumefantrine for treatment of Plasmodium falciparum malaria. The study was carried out during two transmission seasons (2003 and 2004) in Sotuba, Mali. Participants at least 6 months of age with uncomplicated P. falciparum malaria were randomly assigned to receive artesunate-sulfamethoxypyrazine-pyrimethamine or artemether-lumefantrine. Treatment efficacy was assessed using the World Health Organization 28-day protocol. A total of 606 (303 in each arm) patients were enrolled. The cure rate was higher for artesunate-sulfamethoxypyrazine-pyrimethamine than for artemether-lumefantrine (98.7% versus 89.6%; P < 0.0001). After correction for cases of re-infection, the cure rates were 100% and 99.0%, respectively (P = 0.08). No serious adverse events occurred. Artesunate-sulfamethoxypyrazine-pyrimethamine is well-tolerated and effective against P. falciparum malaria. It showed an additional benefit of preventing new infections.


Subject(s)
Antimalarials/therapeutic use , Artemisinins/therapeutic use , Malaria, Falciparum/drug therapy , Pyrimethamine/therapeutic use , Sesquiterpenes/therapeutic use , Sulfalene/therapeutic use , Adolescent , Adult , Anemia/prevention & control , Antimalarials/adverse effects , Artemether , Artemisinins/adverse effects , Artesunate , Carrier State/drug therapy , Child , Child, Preschool , Drug Combinations , Drug Therapy, Combination , Ethanolamines/adverse effects , Ethanolamines/therapeutic use , Female , Fluorenes/adverse effects , Fluorenes/therapeutic use , Humans , Infant , Lumefantrine , Male , Middle Aged , Pyrimethamine/adverse effects , Sesquiterpenes/adverse effects , Sulfalene/adverse effects , Treatment Outcome
6.
Antimicrob Agents Chemother ; 49(2): 663-7, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15673749

ABSTRACT

We conducted a multicenter, randomized, open-label trial to compare mefloquine with a 3-day quinine plus sulphalene-pyrimethamine (SP) regimen for the treatment of imported uncomplicated malaria acquired in Africa. The end points of the study were efficacy, tolerability, and length of hospital stay. From July 1999 to February 2003, 187 patients were enrolled in five centers in Italy, of whom 93 were randomized to receive mefloquine (the M group) and 94 were randomized to receive quinine plus SP (the QSP group). Immigrants and visiting relatives and friends represented 90% of the cases and were mainly from western African countries. A slightly increased proportion of cases in the QSP group had abnormal alanine aminotransferase levels at the baseline. The early cure rate was similar in the two groups: 98.9% (confidence interval [CI] = 97 to 100%) in the M group and 96.8% (CI = 93 to 100%) in the QSP group. The extended follow-up was completed by 135 subjects (72.2%), and no case of recrudescence was detected. There were no differences in the parasite clearance time, but patients in the M group had shorter mean fever clearance time (35.9 h versus 44.4 h for the QSP group; P = 0.05) and a shorter mean hospital stay (3.9 days versus 4.6 days for the QSP group; P = 0.007). The overall proportions of reported side effects were similar in the two groups, but patients in the M group had a significantly higher rate of central nervous system disturbances (29.0% versus 9.6% for the QSP group; P < 0.001).


Subject(s)
Antimalarials/therapeutic use , Malaria, Falciparum/drug therapy , Mefloquine/therapeutic use , Pyrimethamine/therapeutic use , Quinine/therapeutic use , Sulfalene/therapeutic use , Adult , Africa , Antimalarials/adverse effects , Double-Blind Method , Drug Combinations , Drug Therapy, Combination , Endpoint Determination , Female , Follow-Up Studies , Humans , Italy , Malaria, Falciparum/parasitology , Male , Mefloquine/adverse effects , Middle Aged , Prospective Studies , Pyrimethamine/adverse effects , Quinine/adverse effects , Sulfalene/adverse effects
8.
Ann Acad Med Singap ; 18(3): 307-10, 1989 May.
Article in English | MEDLINE | ID: mdl-2549841

ABSTRACT

We report a case of prolonged fever, agranulocytosis, and anaemia associated with the long acting sulphametopyrazine-trimethoprim combination (Kelfiprim). A woman of 23 years took an overdose of 13 tablets over five days for presumed cystitis. One day after the last dose the patient developed fever and a generalised rash. The fever persisted and her previously normal leukocyte count decreased to 1.8 x 10(9)/1. After treatment with paracetamol the fever settled briefly, and then recurred for another 16 days. A later peripheral blood leukocyte count of 0.77 x 10(9)/1, haemoglobin of 10.8 g/dl, and a hypocellular bone marrow with depressed granulopoiesis and haemopoiesis suggested marrow suppression induced by sulfametopyrazine. Since the IgM antibody against the Epstein-Barr virus capsid antigen was detected, the adverse drug reaction might have been aggravated by this virus. The case highlights the risk of severe haematological adverse reactions associated with sulphonamide treatment, and argues for the use of trimethoprim alone for uncomplicated cystitis.


Subject(s)
Agranulocytosis/chemically induced , Anemia/chemically induced , Capsid Proteins , Sulfalene/adverse effects , Sulfanilamides/adverse effects , Trimethoprim/adverse effects , Adult , Agranulocytosis/immunology , Anemia/immunology , Antigens, Viral/analysis , Cystitis/drug therapy , Drug Combinations/adverse effects , Female , Herpesvirus 4, Human/immunology , Humans
11.
Curr Med Res Opin ; 8(5): 338-44, 1983.
Article in English | MEDLINE | ID: mdl-6340974

ABSTRACT

Sixty-eight patients with urinary infection were allocated at random to receive treatment with either 500 mg ampicillin 4-times daily or a trimethoprim (250 mg)/sulfamethopyrazine (200 mg) combination given once daily after a double, loading dose on the first day. All patients complained of urinary symptoms and showed significant bacteriuria, E. coli being the pathogen most frequently recovered. Clinical and microbiological assessments were carried out on entry and, as a rule, after 3 to 4 days and 1 to 2 weeks of treatment. In the 35 patients receiving trimethoprim/sulfamethopyrazine, 40 (95%) of the 42 original infecting organisms were eradicated. In the 33 patients on ampicillin, the eradication rate was 32 (89%) out of 36 organisms. The course of urinary symptoms was similarly favourable in the two groups. Overall response was considered as 'excellent' or 'good' in 89% of the patients receiving the combination preparation and in 82% of those given ampicillin. Clinical and biological tolerance was satisfactory under both regimens. A longer follow-up control should confirm the value of the new combination in the treatment of urinary infections.


Subject(s)
Ampicillin/therapeutic use , Anti-Infective Agents, Urinary/therapeutic use , Sulfalene/therapeutic use , Sulfanilamides/therapeutic use , Trimethoprim/therapeutic use , Urinary Tract Infections/drug therapy , Adult , Aged , Ampicillin/adverse effects , Clinical Trials as Topic , Double-Blind Method , Drug Administration Schedule , Drug Combinations/adverse effects , Drug Combinations/therapeutic use , Female , Humans , Male , Middle Aged , Sulfalene/adverse effects , Trimethoprim/adverse effects , Urinary Tract Infections/microbiology
13.
Br J Dis Chest ; 72(3): 231-4, 1978 Jul.
Article in English | MEDLINE | ID: mdl-359024

ABSTRACT

From a double-blind randomized controlled trial by 32 general practitioners on 218 patients with chronic bronchitis it appeared that sulfametopyrazine given once a week over one winter reduced the number of respiratory illnesses and the loss of time from work to about half that of a control group. It had no effect on time off work in individual spells of illness nor on the amount and purulence of sputum. Side-effects were few and mild.


Subject(s)
Bronchitis/prevention & control , Sulfalene/therapeutic use , Sulfanilamides/therapeutic use , Adult , Aged , Chronic Disease , Clinical Trials as Topic , Double-Blind Method , Female , Humans , Male , Middle Aged , Random Allocation , Sulfalene/adverse effects
15.
Br J Haematol ; 32(2): 183-91, 1976 Feb.
Article in English | MEDLINE | ID: mdl-1247492

ABSTRACT

A technique to investigate drugs which could cause haemolysis in subjects deficient in glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase; G6PD) has been developed. The method is based on the technique of 14CO2 evolution during the incubation of normal erythrocytes in the presence of [I-14C]glucose and their own serum, the latter containing the active metabolites of the drugs received by normal subjects. By this method agents causing a stimulation of the hexosemonophosphate pathway of normal erythrocytes should be regarded as potentially haemolytic for G6PD-deficient subjects. Two sulphonamides, sulphormethoxine and sulphalene, of which until now no haemolytic effects have been reported, together with chloroquine, have been investigated. While chloroquine does not affect the hexosemonophosphate shunt of normal erythrocytes, the two sulphonamides stimulate this pathway. THE RESULTS ARE CONFIrmed by the reduction of the half-life of 51Cr-labelled G6PD-deficient red cells (Mediterranean variant), after administration of the two sulphonamides.


Subject(s)
Erythrocytes/metabolism , Glucosephosphate Dehydrogenase Deficiency/blood , Hemolysis , Sulfadoxine/adverse effects , Sulfalene/adverse effects , Sulfanilamides/adverse effects , Chloroquine/pharmacology , Erythrocytes/drug effects , Humans , In Vitro Techniques
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