View clinical trials related to Malaria, Falciparum.
Filter by:The purpose of this study is to determine the efficacy of pyrimethamine/sulfdoxine (Fansidar®) for the treatment of uncomplicated falciparum malaria in the Peruvian Amazon. Reports in the mid 1990s indicated that Fansidar was failing to cure patients with confirmed falciparum malaria. The study design was based on accepted WHO parasitological and clinical outcomes to determine the overall efficacy of Fansider and inform the Peruvian National Malaria Control authorities as to the continued wisdom of recommending Fansidar as first line treatment for uncomplicated falciparum malaria in the Peruvian Amazon.
It has now been demonstrated clearly that in Western Cambodia parasitological responses to artesunate and artemether containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world. Median parasite clearance time (PCT) in patients treated with artesunate 4 mg/kg/day was 78 hours and with 2 mg/kg/day 82 hours, compared to 54 and 48 hours, respectively, in Western Thailand; at 72hours peripheral blood parasitaemia was still detectable in 55% of patients in Western Cambodia, compared to 7.5% in Western Thailand. Although occasional poor responses to artesunate have been described previously the current reports suggest a consistent problem. These antimalarials are central to current treatment strategies, and so spread of parasites with reduced artemisinin susceptibility outside this area would be a disaster. A recent consensus meeting Pnomh Penh agreed that this should indeed be termed resistance, and represented a major threat to malaria control. Radical containment measures would be needed. This study aims to address whether a semi-synthetic or fully synthetic peroxide antimalarial would be more effective than artesunate and could therefore be used in Cambodia as part of the elimination strategy. Artemisone is a semisynthetic derivative of dihydroartemisinin, which importantly changes its tertiary structure. This drug has also shown promising efficacy for the treatment of uncomplicated falciparum malaria in phase II trials in Thailand and seems to be at least as efficacious as artesunate. No significant toxicity has been reported for artemisone and it is very well tolerated. If sensitivity for artemisone has remained intact in Western Cambodia, this will have important implications for the strategies available for containment of the threatening problem of artesunate resistance in Western Cambodia. It will also have important implications for further development of these drugs for the use in artemisinin combination therapies (ACTs).
OZ439 is a synthetic trioxolane that has potential value as a peroxide antimalarial agent. This was a Phase I, single-centre, multi-component, double-blind, randomised, placebo-controlled study in healthy male and female subjects. The study was conducted in 3 parts: - Part A investigated the safety, tolerability and pharmacokinetics (PK) of single oral escalating doses of OZ439. Up to 6 dose levels will be investigated to estimate dose proportionality. - Part B, the effect of food on a single oral dose of OZ439 was investigated in a 2-way crossover design. - Part C investigated the safety, tolerability and PK profile of multiple oral doses of OZ439. The starting oral dose was 50 mg and the maximum single dose to be administered did not exceed 1600 mg per subject. The maximum duration of dosing proposed was 3 days.
Antimalarial drug resistance is increasing nearly everywhere in the tropical world, confounding global attempts to "Roll Back Malaria." South East Asia has the most resistant malaria parasites in the world. This has limited the options for treatment in this region. Artemisinin-based combination therapy is now the recommended treatment for uncomplicated falciparum malaria. The success of this policy change in practice will depend on the efficacy of the components of the combination used, the population coverage achieved, high levels of adherence to treatment, low cost of the drugs, and preferably the drugs in a combination treatment should be formulated in a single tablet, to prevent one drug being taken without the partner drug. Until recently there were only two artemisinin-based fixed combinations available, artemether-lumefantrine and dihydroartemisinin-piperaquine; and only the former has international registration. More fixed combinations are needed urgently.
The study will determine if amodiaquine tablet (Pfizer), an antimalaria agent, is pharmaceutically equivalent to a comparator product (Arsuamoon-Guilin China).
The study will determine if artesunate tablet (Pfizer), an antimalarial agent, is pharmaceutically equivalent to Arsuamoon® tablets (Guilin-China).
Background: - Globally, the Plasmodium falciparum parasite is responsible for at least 247 million acute cases of malaria each year, resulting in about 1 million deaths. Approximately 90 percent of these deaths, the majority in children under 5 years of age, occur in Africa due to infection with P. falciparum. - People living in endemic areas develop natural immunity to P. falciparum as a result of repeated infection. Consequently, children who survive to 5 years of age rarely succumb to life-threatening disease despite frequent infection. This acquired immunity is mediated in part by blood-stage parasite-specific antibodies. Thus, parasite proteins expressed during the blood-stage have been proposed as good candidates for inclusion in a vaccine. - A number of P. falciparum merozoite antigens have been identified as promising blood-stage vaccine candidates, including Merozoite Surface Protein 1 (MSP 1) and Apical Membrane Antigen 1 (AMA 1). This Phase I study is the first time that the combination vaccine (BSAM-2/Alhydrogel +CPG 7909) will be given to humans. The vaccine will be administered in a randomized, open-label (U.S.)/single-blinded (Mali), dose-escalating trial. Objectives: - To assess safety and reactogenicity of the combination vaccine (BSAM-2/Alhydrogel +CPG 7909) in malaria-naive U.S. adults and semi-immune Malian adults. - To determine the antibody response of the combination vaccine to the AMA 1 and MSP 142 proteins, as measured by antibody levels and parasite growth inhibition. - To determine the extent to which the antibody response to the individual antigens (AMA 1 and MSP 142) is correlated when the combination vaccine is given, and to determine T and B cell responses to vaccination. Eligibility: - United States: Healthy volunteers between 18 and 50 years, inclusive. Available for the 52 weeks of the trial and willing to participate in the study as evidenced by signing the informed consent document. - Mali: Healthy volunteers between 18 and 45 years, inclusive, and a known resident of the village of Bancoumana. Available for the 52 weeks of the trial; willing to participate in the study as evidenced by signing the informed consent document or by fingerprinting the consent document with the signature of a witness. - Potential participants must meet extensive health and screening requirements to participate in this study. Good general health is required as a result of review of medical history and clinical testing at the time of screening. - Women who are pregnant or breastfeeding are not eligible. Design: - During the 52-week study, participants will receive the first vaccine and complete the following: - Physical examination and patient education regarding the signs and symptoms of potential adverse effects. - Blood and urine testing, and vital signs (blood pressure, temperature, heart rate, and respiratory rate). - United States: Education on the use of digital thermometer, injection-site reaction measurement, and malaria vaccine side-effect memory enhancement tool (daily symptom diaries). - Mali: Additional blood draws for malaria smear and urine test for chloroquine testing. - U.S. and Mali participants will return to the study site on specified days throughout the 52 weeks to receive two additional vaccines, record vital signs, complete additional blood and urine testing, and review patient education. - U.S. participants will record oral temperature once during the day, as well as pain, tenderness, redness, swelling at the injection site and any systemic signs or symptoms for 6 days following each immunization. - Participants will receive financial compensation (United States) or food (Mali) to compensate for their time.
As HIV/AIDS is spreading in malaria-endemic countries, many patients here will need concomitant treatment for both infections. Effective combination treatments are available for both malaria (artemisinin-based combination treatments, ACTs) and HIV/AIDS (antiretroviral combination treatments, ARTs), and these treatments are presently recommended for concomitant use by ministries of health in many endemic countries, including Tanzania. However, theoretically some of these drugs may be involved in harmful interactions with each other, as they share common cytochrome enzymes involved in their metabolism. Such interactions could lead to less effective treatments and/or adverse effects, as a consequence of reduced or increased drug levels, respectively. Only little clinical and pharmacological information is however yet available to guide clinicians and policy-makers on this issue. The main aim of the InterACT study in Tanzania is to conduct a series of detailed observational studies of clinical and paraclinical safety, therapeutic efficacy and pharmacokinetic interactions between the currently nationally recommended first-line treatment for malaria, artemether-lumefantrine, and first-line antiretroviral treatments, primarily nevirapine-based combinations, for HIV/AIDS. The studies will be conducted among patients with uncomplicated malaria, who attend the HIV/AIDS Care and Treatment Clinic and Muheza Designated District Hospital in Muheza, north-eastern Tanzania, which is an area characterized by intense transmission of Plasmodium falciparum malaria and with a prevalence of HIV around 8-10%. The study is expected to inform guidelines for the treatment of malaria in patients with HIV/AIDS in Tanzania, and elsewhere.
The purpose of this study is to determine bioequivalence of amodiaquine suspension ( Pfizer) and the WHO approved reference product Flavoquine® tablet ( Sanofi Aventis).
In the EHMI-8 study (CMO 2006/207) the investigators induced sterile protection against P. falciparum challenge in healthy Dutch volunteers by repeated exposure to infected mosquitoes whilst under chloroquine prophylaxis. The surprisingly efficient induction of protection in this study strongly supports the development of whole parasite vaccines and is therefore an important finding to malaria vaccine development. In this study (EHMI8B) the investigators would like to explore the longevity of the protective immune response and simultaneously further characterise immune mechanisms responsible for protection by re-exposing EHMI-8 volunteers to infected mosquito bites.