Establishment of a Sporozoite Challenge Model for Plasmodium Vivax in Human Volunteers

NCT01083095 | Completed Early Phase 1 DMC

• 2 other identifiers: MVDC-2003-003Reto II
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

A clinical trial aimed to standardize a vivax sporozoite infection model in human volunteers was conducted at the Malaria Vaccine and Drug Development Center (MVDC) in collaboration with the Immunology Institute at Valle State University and the Fundación Clínica Valle del Lili (FCVL) in Cali, Colombia. The primary objective was to determine if naïve human volunteers could be safely and reproducibly infected by the bite of An. albimanus mosquitoes carrying P. vivax sporozoites in their salivary glands and a secondary objective consisted in determining the minimal number of infected mosquitoes required to infect all volunteers, with a reproducible pre-patent period. The trial was divided into two steps: Step A directed to obtain human blood infected with P.vivax parasite used to infect anopheles mosquitoes and Step B to produce P. vivax sporozoites in Anopheles mosquitoes to determine the dose response of naive human volunteers exposed to 3 +/- 1, 6 +/- 1 y 9 +/- 1 mosquitoes bites. A total of 15 samples of P. vivax infected donors were used to infect different batches of mosquitoes.

Conditions

Malaria, Vivax

Keywords

Malaria; Sporozoite; Challenge Model; Plasmodium vivax; Human Volunteers

Outcome Measures

Primary Outcomes (1)

• Percentage of infected naïve human volunteers after different number of infected mosquito biting

  30 days

Secondary Outcomes (1)

• Minimal number of infected mosquitoes required to infect all volunteers with a reproducible prepatent period

  30 days

Study Arms (3)

3 +/- 1 bite

ACTIVE COMPARATOR

Volunteers were exposed to mosquito biting for 10 min

Biological: Sporozoite Challenge Model for Plasmodium vivax in Humans

6 +/- 1 bite

ACTIVE COMPARATOR

Volunteers were exposed to mosquito biting for 10 min

Biological: Sporozoite Challenge Model for Plasmodium vivax in Humans

9 +/- 1 bite

ACTIVE COMPARATOR

Volunteers were exposed to mosquito biting for 15 min

Biological: Sporozoite Challenge Model for Plasmodium vivax in Humans

Interventions

Sporozoite Challenge Model for Plasmodium vivax in Humans BIOLOGICAL

Eighteen naïve volunteers were exposed to the bite of carrying P. vivax sporozoites. Volunteers were randomly allocated to 1 of 6 groups and exposed to different numbers of mosquito biting, for 10 min. After feeding, dissection of all mosquitoes exposed in the cage was performed, to confirm the presence of a blood meal in their midguts and sporozoites in their salivary glands. If a volunteer did not get the number of infective bites assigned for his/her group, he/she was allowed to be bitten for a new group of mosquitoes until a total of 3±1, 6±1, or 9±1 mosquito bites were achieved.

Also known as: Controlled malaria vivax infection challenge

3 +/- 1 bite; 6 +/- 1 bite; 9 +/- 1 bite

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or non-pregnant female adults (18- 50 years of age).
• Use of adequate contraceptive method from the initiation of the study until two months after sporozoite challenge for females.
• No plans to travel to a malaria endemic area during the course of the study and agree to not travel outside the study area from Day 7 to Day 23 post-challenge (the high risk period for becoming parasitemic).
• Reachable by phone during the entire study period
• Duffy positive phenotype

You may not qualify if:

• Are \<18 or \>49 years of age.
• Any female who is pregnant at serum positive B-HCG screening or who is nursing.
• Duffy negative phenotype.
• G-6-PD deficiency or any other hemoglobinopathy.
• Current or past infection with any species of malaria
• History of allergy to antimalarial drugs or immediate type hypersensitivity reactions to mosquito bites.
• Clinical or laboratory evidence of significant systemic disease, including hepatic, renal, cardiac, immunologic or hematological disease. Are HIV positive or have any other known immunodeficiency (including receiving immunosuppressive therapy or a history of splenectomy); are infected with hepatitis B or C virus; have a history of autoimmune disease (including inflammatory bowel disease, hemolytic anemia, autoimmune hepatitis, rheumatoid arthritis, lupus, etc.) or connective tissue disease or have any other serious underlying medical condition.
• Clinically significant laboratory abnormalities as determined by the Investigator(s).
• Plan to have surgery between enrollment and the end of the challenge follow-up.
• Have any other conditions that are determined by at least two concurring investigators that may interfere with the capacity to provide free and willing informed consent.

Sponsors & Collaborators

• Malaria Vaccine and Drug Development Center: lead
• Ministerio de la Protección Social, Colombia.: collaborator

Study Sites (1)

Malaria Vaccine and Drug Testing Center

Cali, Valle del Cauca Department, Colombia

Location

Related Publications (27)

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  PMID: 9086149 RESULT

• Clyde DF, McCarthy VC, Miller RM, Hornick RB. Specificity of protection of man immunized against sporozoite-induced falciparum malaria. Am J Med Sci. 1973 Dec;266(6):398-403. doi: 10.1097/00000441-197312000-00001. No abstract available.

  PMID: 4590095 RESULT

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Related Links

• Related Info

MeSH Terms

Conditions

Malaria, Vivax; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Socrates Herrera, MD

  MVDC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 6, 2010
• First Posted: March 9, 2010
• Study Start: January 1, 2005
• Primary Completion: March 1, 2005
• Study Completion: December 1, 2006
• Last Updated: March 9, 2010

Record last verified: 2006-12

Locations

CO (1)