View clinical trials related to Malaria.
Filter by:This is a single-centre, open-label, dose finding study using induced blood stage malaria (IBSM) infection to characterize the pharmacodynamic interaction between OZ439 and DSM265, administered around 120 minutes apart for treatment of early Plasmodium falciparum blood stage infection. The study will be conducted in up to three cohorts (n=8 per cohort) using different doses of OZ439 and DSM265. The doses of OZ439 and DSM265 that will be investigated in the first cohort will be 200 mg of OZ439 and 100mg of DSM265, both administered as single doses around 120 minutes apart. Subsequent doses in subsequent cohort(s) will be determined following a review of observed OZ439 and DSM265 safety, and pharmacokinetic and pharmacodynamic interaction outcomes, particularly the antimalarial activity of the drugs given in combination as defined by parasite clearance kinetics. The doses used in Cohort 2 and 3 may be adjusted but will not exceed the maximum acceptable doses predefined for this study (which are 400 mg for DSM265 and 500mg for OZ439) as determined in previous safety and pilot efficacy studies. The dose will be determined by the funding sponsor and the principal investigator (PI) following Safety Review team (SRT) and scientific evaluation. If no safe alternative dose can be determined the option exists to curtail the study to less than three cohorts. Each participant in the cohort will be inoculated on Day 0 with ~1,800 viable parasites of Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. On an outpatient basis, participants will be monitored daily via phone call and then daily (AM) from day 4 (until PCR positive for presence of malaria parasites). Once PCR positive they will be monitored twice-daily morning (AM) and evening (PM) until treatment, for adverse events and the unexpected early onset of symptoms, signs or parasitological evidence of malaria. On the day designated for commencement of treatment, as determined by qPCR results, participants will be admitted to the study unit and monitored. The threshold for commencement of treatment will be when PCR quantification of all participants is = 1,000 parasites/mL. If the PCR quantification of any participant is = 5,000 parasites/mL and is accompanied by a clinical symptom score >5, or if clinical or parasitological evidence of malaria occurs in any participant before all participants have reached the treatment threshold (PCR quantification of = 1,000), then treatment of that participant will begin within a 24 h period. Following treatment with OZ439 and DSM265, participants will be followed up as inpatients for at least 48 hours to ensure tolerance of the treatment and clinical response, then if clinically well on an outpatient basis for safety and clearance of malaria parasites via PCR. Compulsory commencement of treatment with Riamet® (artemether-lumefantrine) will occur on study day 16 ±3 days post OZ439 and DSM265 treatment unless required earlier. Early standard anti-malarial drug intervention can occur if either poor responses or fast responses are seen following OZ439 and DSM265 treatment. This is to ensure participant safety and to avoid participant inconvenience if useful data cannot be obtained. A poor response is defined as a decrease in parasitaemia of less than 20% from baseline by 3 days post OZ439 and DSM265 treatment. A fast response occurs when, within the seven day period following the treatment, two consecutive PCR assessments in 48 hours are negative. However, pre-emptive treatment with Riamet® can commence whenever deemed necessary by the investigator. Participants will be monitored, either in clinic, or by telephone for three days to ensure adherence to Riamet® therapy. Participants will be treated with a single dose (45 mg) of primaquine as described in section 4.3 in this protocol at the end of their Riamet® treatment if gametocytes are identified, to ensure complete clearance of any gametocytes present. Adverse events will be monitored via telephone monitoring, within the clinical research unit, and on outpatient review after malaria challenge inoculation and antimalarial study drugs administration. Blood samples for safety evaluation, malaria monitoring, and red blood cell antibodies will be drawn at screening and/ or baseline and at nominated times after malaria challenge.
This is a single-centre, 2-part, randomised, single-dose parallel group study in healthy male subjects and female subjects of non-childbearing potential.
For more than a decade, Uganda's Ministry of Health has led a community health worker program model in which Village Health Teams (VHTs), cadres of unpaid volunteers, are assigned the task of delivering preventative health services and education to their local communities. Studies have demonstrated the effectiveness of Uganda's VHTs in improving certain health outcomes; however it is known that VHTs are not optimally supported, and there has been VHT attrition in recent years. The Ministry of Health has recognized the inadequate support of VHTs thus far and is aiming to "expand VHTs to all local governments and explore ways of sustaining VHTs." The objective of this study is to evaluate the extent to which material support is a deciding factor in the efficiency and durability of Uganda's VHT initiative. Material support may take the form of monetary stipends, regular payment, transportation assistance, or nonfinancial materials such as bicycles or mobile phone airtime. This study will review existing literature and gather novel data through surveys of VHT members and VHT stakeholders. The quantitative and qualitative survey data will be analyzed for trends that may point to a conclusion in the context of existing health policy discourse on community health worker remuneration. The purpose of this study is to strengthen the knowledge base on whether or not the current absence of material support significantly limits the potential for Uganda's VHTs to be sustained and expanded. This information can be used by governmental and non-governmental organizations in their work to strengthen and sustain VHTs throughout the country.
The purpose of this pre-licensure cohort study is to estimate the incidence of adverse events of special interest (AESI), other adverse events (AE) leading to hospitalisation or death, meningitis and malaria in sub-Saharan African children under 5 years of age. The outcomes of this study will provide the baseline data for the post-licensure EPI-MALARIA-003 (115056) study that will evaluate the safety, effectiveness and impact of the RTS,S/AS01E vaccine. An interim analysis was performed on a sub-group of study participants enrolled in active surveillance from sites where the vaccine is currently implemented, having 6 months of follow-up following the administration of dose 3 of DTP/HepB/Hib vaccine (6-12 weeks group), or 6 months after Visit 3 (mimicking the RTS,S/AS01E primary vaccination schedule) for the 5-17 months group; corresponding to Visit 5. The interim analysis concerned primary safety endpoints and the main secondary endpoints.
Worldwide, approximately 2 billion people live in areas at risk for malaria with morbidity surpassing 250 million cases, with approximately 800,000 deaths, per year. Of the four species of malaria parasites that cause human infection, P. falciparum is responsible for the majority of severe malaria cases followed by P. vivax. Early and accurate diagnosis is essential for prompt and correct treatment, which can reduce the death rate and interrupt transmission. Currently, conventional methods for the diagnosis of malaria include microscopic examination of thin and thick blood smears and rapid diagnostic tests (RDTs). Light microscopy in practice typically detects parasitemia as low as 100 parasites/µl and it can differentiate species. The advantage of microscopy includes the ability to estimate parasitemia, the possibility to identify parasite stages, including gametocytes, and its low cost. However, this method is labor intensive, difficult to standardize, and requires well-trained microscopists. The majority of RDTs are based on detection of P. falciparum histidine-rich protein 2 (HRP-2) antigen and do not detect all malaria species. RDTs that detect lactose dehydrogenase (LDH) and aldolase generally broadly react with all four species of malaria parasites and therefore cannot differentiate among the species although efforts are underway to improve their performance for species detection. In settings where multiple malaria species co-circulate, molecular methods may be more reliable than microscopy and RDTs in accurately diagnosing the species of malaria parasites with low parasitemias. However, conventional molecular methods, such as nested polymerase chain reaction (nested PCR) or real-time PCR, are technically challenging and resource intensive and are generally restricted to reference laboratories due to the need for well-equipped laboratories. Recently, new molecular methods that can be used in field settings have been developed and this opens up new opportunities for exploring molecular tools for malaria diagnosis in endemic countries. With the objective of facilitating use of molecular tools for malaria control programs, the malaria laboratory at the Centers for Disease Control and Prevention (CDC) in Atlanta, USA developed a simple isothermal molecular method called Real-Time Fluorescence Loop-Mediated Isothermal Amplification (RealAmp) for the diagnosis of malaria. Currently, RealAmp primers exist for detecting the Plasmodium genus and the detection of P. falciparum and P. vivax species. The RealAmp method has great potential as a molecular tool for the diagnosis of malaria in the field (and other infections of major public health impact, such as HIV and tuberculosis). It can provide an alternative to conventional PCR-based diagnostic methods for field use in clinical and operational programs. The objective of this proposal is to validate the sensitivity of RealAmp for detection of malaria parasites in blood spots from patients with clinical diagnosis of malaria in two endemic states of Brazil with co-circulation of P. falciparum and P. vivax. In this evaluation, RealAmp and microscopic examination will be compared to a real-time PCR method as a reference test.
This is an observational safety and efficacy study on dihydroartemisinin-piperaquine in Timika, Indonesia with a 42 day follow up period.
Background: - Malaria is a severe infection caused by a parasite. People can get malaria if a mosquito that carries the parasite bites them. Malaria infection does not happen in the United States, but many people in Africa, Asia, and South America are at risk for it. Researchers want to test two vaccines that may help decrease malaria infection. Objective: - To see if two vaccines (Pfs25M-EPA/Alhydrogel and Pfs230DIM-EPA/Alhydrogel ) are safe in humans and cause an immune response that will prevent malaria parasites from correctly growing in the mosquito. Eligibility: - Healthy adults ages 18 50. Design: - There are several groups in this study. Each group will receive a different dose of the vaccine and some groups will received both vaccines. - Vaccinations will be given on two days about 4 weeks apart. - Participants will receive each vaccine as an injection into the arm. Blood will be drawn on the day of vaccination. - In the 4 weeks after receiving a vaccination, participants will have at least 3 clinic visits and 1 phone contact. They will have at least 3 more visits and 3 phone contacts over the next 6 months. - At each visit, participants will be evaluated for side effects to the vaccine and any new health changes or problems. They will be asked how they are feeling and if they have taken any medicine. Blood and urine samples may be taken at the visit. More follow-up visits may be needed to follow up on changes or problems.
To quantify the relative effectiveness, cost, and cost-effectiveness of fMDA and MDA with DHAp against no mass treatment for reducing P. falciparum parasite prevalence, confirmed OPD malaria case incidence and cohort infection incidence in areas of high and low malaria transmission and in a program-relevant manner that will permit adoption and adaptation for wider-scale deployment.
This is a prospective, open label, randomised controlled trial to assess the safety and efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria infection. Molecular markers for antimalarial resistance will also be assessed and the presence of molecular markers in the parasites will be associated with treatment outcomes.
This is a cluster randomised controlled trial comparing the impact of two community based malaria interventions: reactive case detection (RACD) vs reactive targeted presumptive treatment (focal mass drug administration, fMDA) on the incidence of malaria in Swaziland.