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Malaria, a disease caused by the parasite Plasmodium, is one of the world's major infectious diseases. With approximately 627.000 deaths a year, it is both a chief cause of morbidity and mortality as well as a significant contribution to ongoing poverty in endemic countries. Ultimately, the key to malaria control, and hopefully eradication, would be an effective vaccine. Though a number of vaccine-candidates have entered the pipeline of pre-clinical and clinical development, they have yet to achieve the level of efficacy necessary for effective malaria prevention. It has been shown previously that if healthy human volunteers taking chloroquine chemoprophylaxis are repeatedly exposed to Plasmodium parasites through the bites of infected mosquitoes, they are fully protected against a later challenge infection with a 'homologous' (genetically similar) Plasmodium parasite. This process is known as ChemoProphylaxis and Sporozoites, or CPS-immunization. One of the obstacles to developing an effective vaccine is the genetic heterogeneity of malaria parasites. To further consider the development of whole-parasite based vaccines against malaria and in order to better understand the protective immunity induced by CPS-immunization, it is essential to investigate whether heterologous protection against genetically diverse (heterologous) P. falciparum clones can be induced.
This is a single center, randomized, double-blind study to determine whether healthy volunteers immunized with P. falciparum NF54 parasites under chloroquine prophylaxis are protected against a challenge infection with the genetically distinct NF135.C10 or NF166.C8 P. falciparum clones.
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Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following.
1.1 Body weight <50 kg or Body Mass Index (BMI) <18.0 or >30.0 kg/m2 at screening.
1.2 A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.
1.3 A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD deficiency.
1.4 History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
1.5 Positive Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) screening tests.
1.6 Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.
1.7 History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
1.8 Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
1.9 History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset, positive urine toxicology test for cocaine or amphetamines at screening or prior to infection or positive urine toxicology test for cannabis at inclusion or prior to infection.
For female subjects: positive urine pregnancy test at screening or prior to infection.
Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study.
Known hypersensitivity to or contra-indications (including co-medication) for use of chloroquine, Malarone or artemether-lumefantrine, or history of severe (allergic) reactions to mosquito bites.
Receipt of any vaccinations in the 3 months prior to the start of the study or plans to receive any other vaccinations during the study period or up to 8 weeks thereafter.
Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
Being an employee or student of the department of Medical Microbiology of the Radboudumc or the department of Internal Medicine.
Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
Primary purpose
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40 participants in 6 patient groups
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Data sourced from clinicaltrials.gov
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