Active clinical trials for "Malaria, Falciparum"

The purpose of this study is to determine whether an investigational malaria vaccine is safe and induces an immune response against malaria when tested in adults living in the United States.

Malaria, a disease responsible for over one million deaths per year, is caused by a germ spread by mosquito bites. The purpose of this study is to evaluate a vaccine designed for the prevention of malaria caused by the parasite, Plasmodium falciparum, and to evaluate the device used to give the vaccine. This study will provide information on how safe, effective, and tolerable the vaccine is in healthy adults. The participants will be assigned, by chance, to receive 3 doses/shots of the vaccine or a placebo (substance that contains no medication) by injection in the upper arm. Study participants will include 39 healthy adults aged 18-40 years who have not been exposed to malaria and who will enroll at the Emory Vaccine and Treatment Evaluation Unit in Atlanta, Georgia. Study procedures include physical exams and several blood samples. Participants will be involved in the study for approximately seven and one half months.

In the 1950s, the WHO included mass drug administration (MDA) with antimalarial drugs as a tool for malaria control in 'exceptional conditions when conventional control strategies have failed'. Subsequently, MDA has received little attention until the introduction of artemisinin based combination therapy (ACT). The principle aim of MDA is to interrupt malaria transmission by clearing the population of sexual stage parasites, gametocytes, prior to the transmission season. Gametocytes are essential for propagation of the disease and elimination of gametocytes will result in a reduction in malaria transmission. As a consequence, a successful MDA will reduce the burden of disease in a population and is expected to have little influence on the development of protective immunity in areas of low transmission intensity. In Africa, only one large scale MDA study was conducted in the last 10 years. That study, conducted in The Gambia using sulphadoxine-pyrimethamine (SP) plus a single dose of artesunate (AS), failed to show a significant impact of MDA on malaria transmission. Possible reasons for this failure are the limited impact of the drug regimen (a single dose of AS) on malaria transmission, the incomplete coverage, the relatively high transmission intensity in the area and the migration of individuals between villages. Here, we propose to conduct an MDA study in an area of very low malaria transmission intensity in Tanzania. We use the highly active drug combination SP+AS (3 days) followed by a single dose of primaquine..

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.

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).

Phase I/II Trial of a Malaria Vaccine, FMP011/AS01B, in Adults Living in the United States of America.

Malaria is an illness caused by a parasite (an animal or plant that lives in or on a host) that enters the human body through the bite of an infected mosquito. The purpose of this study is to find out about the safety of an experimental malaria vaccine and whether the vaccine causes humans to produce antibodies (proteins made by the body's immune system to help control or prevent infection). Four strengths of the vaccine will be tested. The lowest strength of the vaccine will be tested before the next higher strength is tested. Each dosage (shot) of vaccine will be given to 18 people in 4 dosage groups on Day 0, at 1 month and at 6 months. Two people in each dosage group will receive injections of a placebo (contains no medication). Participants will include 80 healthy adults between 18 and 40 years of age. Multiple blood draws will occur over the duration of the study. Participants will be involved in study related procedures for approximately 13 months.

This is a dose-escalation, age de-escalation randomised double-blind controlled Phase Ib trial to assess the safety, tolerability and immunogenicity of ChAd63-RH5 administered with MVA-RH5 in a heterologous prime-boost regimen. Adults (18-35 years), young children (1-6 years) and infants (6-11 months) will be enrolled in the study. Safety data will be collected for each of the vaccination regimens. The humoral and cellular immune responses generated by each of these regimens will be assessed.

A double-blind, individual randomised trial will be undertaken in children under five years of age living in areas of Burkina Faso or Mali where the transmission of malaria is intense and highly seasonal to determine whether administration of further doses of the malaria vaccine RTS,S/AS01 at the beginning of the malaria transmission until children reach the age of five years is (a) as effective as SMC with SP + AQ in preventing clinical malaria (b) provides additional, useful protection when given together with SMC. The primary trial end-point will be the incidence of clinical episodes of malaria detected by passive case detection. This is a two year extension of the current RTS,S/AS01 + SMC trial to continue the trial until the study children reach the age of five years, the current age at which SMC is recommended until.

This study will consist of two phases and be aimed at assessing the safety and tolerability of the new genetically attenuated GA2 malaria parasite (Phase 1) and its preliminary protective efficacy against controlled human malaria infection (Phase 2) in healthy Dutch volunteers.