Clinical Trial for the Development of a Safe Malaria Challenge Model That Can be Reproduced in Humans (Pvivax)

This is an interventional prevention trial for Plasmodium Vivax Malaria focused on measuring Malaria, Plasmodium vivax Read More

Inclusion Criteria:

• Healthy adults (male or non-pregnant, non-lactating female) 18 to 55 years of age;
• Able to provide free and willing written informed consent to participate;
• A score at least 80% correct on a 10 question Assessment of Understanding;
• No plans to travel to a malaria endemic area during the course of the study;
• Duffy positive phenotype;
• Normal (non-deficient) G6PD phenotype (range : 4.6 to 13.5 u/gm hemoglobin);
• Free of significant health problems as established by medical history and clinical examination completed prior to the study;
• Available to participate and reachable by phone for duration of study (approximately 9 months starting from screening).
• Only subjects with no or low cardiac risk factors according to the Gaziano study and a normal EKG will be included in the study

Exclusion Criteria:

• Pregnant or nursing at screening or plans to become pregnant or nurse from the time of enrollment until 6 months after sporozoite challenge;
• Duffy negative phenotype;
• G6PD deficiency or have any hemoglobinopathy by history;
• Past infection with any species of malaria (as demonstrated by a positive thick smear) in the last 5 years;
• History of receipt of treatment or prophylaxis for malaria during the previous 6 months;
• History of receipt of malaria vaccine within the previous 5 years;
• History of receipt of malaria challenge (being bitten by experimentally infected mosquitoes) within the previous 5 years;
• Plans to travel to malarious areas during the study period;
• Allergy to antimalarials or significant (e.g. systemic) hypersensitivity reactions to mosquito bites (local hypersensitivity reactions at the site of a mosquito bite are not an exclusion criterion);
• History of psoriasis (given its interaction with chloroquine);
• Use of any investigational or non-registered drug or vaccine within 30 days preceding the challenge or planned use during the study period;
• Use or planned use of any drugs with significant anti-malarial activity, such as doxycycline, clindamycin, azithromycin, during the study period (volunteers can withhold the use of these medications during the study period, at the minimum starting from 4 weeks before the challenge until 4 weeks after becoming parasitemic);
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection and history of splenectomy;

• Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of challenge;

  • For corticosteroids, this is defined as prednisone, or equivalent, 0.5 mg/kg/day;
  • Inhaled and topical steroids are allowed;
• A family history of congenital or hereditary immunodeficiency;
• Chronic or active neurologic disease including seizure disorder;

• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination, or abnormal baseline laboratory screening tests:

  • ALT above normal range (table 9);
  • Creatinine above normal range (table 9);
  • Hemoglobin below normal range (table 10);
  • Platelet count below normal range (table 10);
  • Total white cell count below normal range (table 10);

• Acute disease at the time of enrollment

  • Acute disease is defined as the presence of a moderate or severe illness with or without fever;
  • Challenge can be administered to persons with a minor illness, such as diarrhea or mild upper respiratory infection without fever (i.e., oral temperature < 38°C/100.4°F);
• Hepatomegaly, right upper quadrant abdominal pain or tenderness;
• Seropositive for HIV, hepatitis C virus (antibodies to HIV and HCV), and/or HBsAg;
• Administration of immunoglobulins and/or any blood products within the 3 months preceding challenge or planned administration during the study period;
• Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination;
• Inability to make follow-up visits;
• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.