View clinical trials related to Plasmodium Falciparum.
Filter by:The purpose of the study is to determine the safety and tolerability of ID administration of PfSPZ Challenge to volunteers taking chloroquine chemoprophylaxis (an approach called PfSPZ-CVac).
This is an open label, human pilot study to optimise controlled human malaria infection (CHMI) administered by Plasmodium falciparum sporozoites (PfSPZ. Volunteers will be inoculated with PfSPZ Challenge. The route of administration and dose will vary in order to identify the optimal regimen that achieves the greatest infection rate in volunteers with Plasmodium falciparum. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected for each of the regimens.
Malaria is one of the major infectious diseases in the world with a tremendous impact on the quality of life, significantly contributing to the ongoing poverty in endemic countries. It causes 800.000 deaths per year, the majority of which are children under the age of five. The malaria parasite enters the human body through the skin, by the bite of an infected mosquito. Subsequently, it invades the liver and develops and multiplies inside the hepatocytes. After a week, the hepatocytes burst open and the parasites are released in the blood stream, causing the clinical phase of the disease. As a unique opportunity to study malaria immunology and efficacy of immunisation strategies, a protocol has been developed in the past to conduct controlled human malaria infections (CHMIs). CHMIs generally involve small groups of malaria-naïve volunteers infected via the bites of P. falciparum infected laboratory-reared Anopheline mosquitoes. Although potentially serious or even lethal, P. falciparum malaria can be radically cured at the earliest stages of blood infection when risks of complications are virtually absent. The investigators have shown previously that healthy human volunteers can be protected from a malaria mosquito (sporozoite) challenge by immunization with sporozoites (by mosquito bites) under chloroquine prophylaxis (CPS immunization). Interestingly, sterile protection in 100% of the human CPS immunized volunteers was achieved by a relatively miniscule dose, i.e. a total of 45 infectious mosquito bites, strikingly 20-fold more potent than the 1000 bites needed in a model using irradiated mosquitoes. One possible explanation for this efficient induction of protective immunity, is the immune modulating effect of chloroquine. The investigators aim to assess this possible immune modulating effect in CPS immunization by comparing immunization with P. falciparum sporozoites under chloroquine with immunization under mefloquine prophylaxis, which has the same antimalarial effect, but not the immune modulating effects known from chloroquine.
Plasmodium falciparum malaria remains a global public health threat. Leading malaria vaccine candidates confer only partial short-lived protection at best. An understanding of the mechanisms by which humans acquire malaria immunity through repeated P. falciparum infections may aid the development of a malaria vaccine. This pilor study is designed to initiate the epidemiological groundwork for a future prospective cohort study of acquired malaria immunity in Kalifabougou, Mali, a rural village of approximately 5 000 individuals who are exposed to seasonal P. falciparum transmission each year from July through December. This study will estimate the age-stratified point prevalence of P. falciparum infection before the malaria season and at the peak of the 6-month malaria season, and it will estimate the age-stratified incidence of symptomatic p. falciparum infection during the 6-month malaria season. The spatial distribution of asymptomatic P. falciparum infections and incident malaria cases within the village of Kalifabougou will be determined by merging the prevalence and incidence data with census and Global Positioning System (GPS) data....
Plasmodium falciparum isolates display a wide genetic diversity with possibly different properties to induce immune responses. These properties could directly influence the ability to induce protective efficacy. Since 1998 an experimental human malaria infection model at the Radboud University Nijmegen Medical Center (RUNMC) has been very successful in answering questions with regards to immunological mechanisms of human Pf infection. To date only the NF54 strain of Pf has been deployed in this Nijmegen model. However, investigation of heterologous Pf challenge is not only highly informative for our basic understanding of induction of immune responses but also provides an essential model for protective capacity testing in the clinical development of candidate malaria vaccines. Recently, the parasite culture laboratory of the RUNMC has been able to overcome technical hurdles to produce infectious mosquitoes of two genetically different isolates from different geographical regions to increase the portfolio for Phase IIa trials. These isolates, PfA and PfB will be compared with the NF54 strain for parasitic, immunological and clinical features in humans.
The purpose of this study is to determine the safety and tolerability of a non-replicating, metabolically active Plasmodium falciparum sporozoite (PfSPZ) vaccine in malaria-naïve healthy volunteers following multiple-dose subcutaneous (SC) or intradermal (ID) administration. In addition, the investigators wish to evaluate PfSPZ vaccine-mediated protection against P. falciparum challenge in the following 4 groups (see below) and compare protective efficacy of the PfSPZ vaccine when given by SC v ID administration in all these groups: - Group 1: 4 doses of 7,500 PfSPZ/immunization, - Group 2: 4 doses of 30,000 PfSPZ/immunization, - Group 3: 4 doses of 135,000 PfSPZ/immunization - Group 4: 4 or 6 doses of 135,000 PfSPZ/immunization. If > 80% protective efficacy is not achieved in Groups 1, 2, or 3, volunteers in Group 4 will receive a fifth and sixth dose.
In many areas of the world most severely affected by the HIV/AIDS pandemic, insect and water-borne diseases such as malaria and diarrheal disease are common causes of illness and death. In addition, diarrhea and malaria are more common and more severe among adults and children infected with HIV. These infections may modulate the immune system, affect the replication of the HIV virus and could result in more rapid HIV disease progression in co-infected individuals. Access to practical, inexpensive and easy to use interventions to prevent these diseases may be effective in delaying HIV progression. Current Kenya government and World Health Organization guidelines recommend the use of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP/SMX]) to prevent co-infections, including malaria. Despite the provision of TMP/SMX to HIV-infected adults, infections with malaria and pathogens causing diarrhea remain common causes of morbidity and mortality in many resource-limited settings. In addition, TMP/SMX may not prevent all infections with malaria or other pathogens due to alternative mechanisms of action, antimicrobial resistance and non-compliance due to adverse events or other reasons. We propose a study to evaluate the impact of providing insecticide treated bednets and a simple water filtration device on markers of HIV disease progression among a cohort of ART naïve, HIV infected adults prescribed TMP/SMX in Kenya. In addition, we propose to evaluate the effect of these interventions on malaria and diarrheal disease incidence and on compliance with TMP/SMX.
The malaria parasite Plasmodium falciparum remains at sub-patent level throughout the dry season in areas of seasonal malaria transmission. Targeting this parasite reservoir before the transmission season could be a good strategy for malaria control. We are conducting a randomized double blind placebo controlled mass drug administration trial in eight village to clear the dry season low level parasitaemia with an ultimate aim of controlling malaria in eastern Sudan.
The purpose of this study is to determine whether a new investigational malaria vaccine is safe, well tolerated and effective against experimental exposure to malaria when given to healthy people with no previous exposure to malaria. The vaccine consists of a modified form of a relatively common virus, adenovirus, that has been rendered incapable of replicating itself and modified to deliver the malaria gene of interest to the body's cells allowing the cell to manufacture the protein encoded by the gene and present it to the body's immune system in a more natural and presumably effective way.
This study, conducted at Johns Hopkins University Center for Immunization Research in Washington DC, will test the safety and immune response of healthy volunteers to two experimental malaria vaccines. Malaria is a disease of red blood cells caused by a parasite that spreads from person to person by mosquitoes. It affects people of all ages, but is particularly severe in children. Patients may have a high fever, chills and muscle aches. They sometimes can have severe complications that may even result in death. The vaccines in this study are called "transmission blocking" vaccines. These vaccines stimulate the person's immune system to produce antibodies against malaria. When a mosquito bites a vaccinated person, it ingests some of the person's blood. The antibodies in the ingested blood stop the malaria parasite from developing inside the mosquito. The mosquito would not be able to transmit malaria to other people. PpPfs25/ISA51 (Vaccine A) stimulates production of antibodies against the malaria parasite Plasmodium falciparum, and ScPvs25/ISA51 (Vaccine B) stimulates antibodies against the malaria parasite Plasmodium vivax. The vaccines also contain a substance called Montanide ISA51, which boosts the immune response to the vaccine. Healthy volunteers between 18 and 50 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests. Women who are able to become pregnant have a urine pregnancy test before each immunization. Participants are randomly assigned to receive two injections, spaced 4 months apart, of either Vaccine A or Vaccine B at one of three doses-high, medium, or low. Two subjects in each dose group additionally serve as "controls" and receive only Montanide ISA51 mixed with saline. The vaccine is injected into the muscle of the upper arm. Subjects are monitored for 30 minutes after each injection for possible side effects and take home a diary card to record their temperature and any symptoms that may appear over the next 13 days. A blood sample is drawn before and on several occasions after each vaccination to check the subject's health and to evaluate the immune response to the vaccine. At 1, 3, 7, 14, and 21 days after each vaccination, participants come to the clinic for a check of vital signs (temperature, pulse, respiration, and blood pressure), brief physical examination, and history of symptoms since the previous visit.