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

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.