Malaria Vaccine in Children in Mali
Malaria Vaccine in Children in Mali
This study will test an experimental vaccine called AMA1-C1 in children to see if it is safe
 and if it reduces episodes of malaria parasitemia (parasites in the blood) in children
 exposed to malaria. Malaria affects about 300 million to 500 million people worldwide each
 year, causing from 2 million to 3 million deaths, mostly among children less than 5 in
 sub-Saharan Africa. It is the leading cause of death and illness among the general population
 of Mali in West Africa. Increasing drug resistance to the malaria parasite and widespread
 resistance of mosquitoes (the insects that transmit the parasite) to pesticides are reducing
 the ability to control malaria through these strategies. A vaccine that could reduce illness
 and death from malaria would be a valuable new resource in the fight against this disease.
 AMA1-C1 is an experimental vaccine developed by the NIAID. Tests of AMA1-C1 in 87 healthy
 people in the United States and in Mali found no serious harmful side effects of the vaccine.

 Two- and three-year-old children who live in Don gu bougou or Bancoumana, Mali, and are in
 general good health may be eligible for this study. Candidates are screened with a medical
 history, physical examination, and blood and urine tests.

 Participants are randomly assigned to receive two injections (shots) of either AMA1-C1 or a
 Haemophilus influenzae type B vaccine called Hiberix® (Registered Trademark), which is
 approved and used in Mali. All shots are given in the thigh muscle. Before the first shot, a
 small blood sample is obtained to make sure the child is well and to see if he or she has
 antibodies to the malaria parasite. The second shot is given 4 weeks after the first. After
 each shot, participants are observed in the clinic for 30 minutes. They return to the clinic
 1, 2, 3, 7 and 14 days after each shot for a physical examination. Blood samples are drawn at
 some visits to check for side effects of the vaccine and to measure the response to it.

 During the rainy season after the second vaccination, subjects come to the clinic once a
 month for an examination. Any child who has been ill with a disease that could be malaria has
 a blood sample collected by fingerstick to test for malaria and to learn about the malaria
 parasites causing the infection. Every fourth visit a fingerstick sample is taken regardless
 of whether the child has been sick. If a child becomes sick at any time during the study, he
 or she will be brought to the clinic for examination a...
Apical membrane antigen-1 (AMA1) is a surface protein expressed during the asexual blood
 stage of P. falciparum. It is produced as an 83-kDa polypeptide by mature schizonts in
 infected erythrocytes. In clinical studies in malaria-unexposed adults in the USA and in
 malaria-exposed adults in Mali, AMA1-C1/Alhydrogel was safe and immunogenic. This study will
 evaluate its safety and immunogenicity in malaria-exposed children living in an area of
 seasonal malaria transmission.
-  INCLUSION CRITERIA:

 Males or females aged 2 to less than 4 years old. Children must be born no earlier than
 September 1, 2002 and must have had their second birthday prior to first vaccination.

 Known residents of the village of Doneguebougou, Mali or Bancoumana.

 Good general health as determined by means of the screening procedures.

 Available for the duration of the trial (52 weeks).

 Willingness to participate in the study as evidenced by parents/legal guardians signing or
 fingerprinting the informed consent document.

 EXCLUSION CRITERIA:

 Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic,
 autoimmune, chronic infectious or renal disease by history, physical examination, and/or
 laboratory studies including urinalysis.

 Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
 affects the ability of the volunteer or the parent/legal guardian to understand and
 cooperate with the study protocol.

 Laboratory evidence of liver disease (alanine aminotransferase (ALT) greater than 1.25
 times the upper limit of normal of the testing laboratory).

 Laboratory evidence of renal disease (serum creatinine greater than the upper limit of
 normal of the testing laboratory, or more than trace protein or blood on urine dipstick
 testing).

 Laboratory evidence of hematologic disease (absolute leukocyte count less than 3000/mm(3)
 or greater than 14,500/mm(3), absolute lymphocyte count less than 1000/mm(3), platelet
 count less 120,000/mm(3), or hemoglobin less than 8.5 g/dL).

 Other condition that in the opinion of the investigator would jeopardize the safety or
 rights of a volunteer participating in the trial or would render the subject unable to
 comply with the protocol.

 Participation in another investigational vaccine or drug trial within 30 days of starting
 this study, or while this study is ongoing.

 History of a severe allergic reaction or anaphylaxis.

 Severe asthma (emergency room visit or hospitalization within the last 6 months).

 Positive ELISA for HCV.

 Positive HBsAg by ELISA.

 Known immunodeficiency syndrome.

 Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30
 days of starting this study.

 Receipt of a live vaccine within past 4 weeks (e.g. measles/mumps/rubella (MMR)) or a
 non-live vaccine (e.g. diphtheria/pertussis/tetanus (DPT)) within past 2 weeks prior to
 entry into the study.

 History of a surgical splenectomy.

 Receipt of a blood transfusion within the past 6 months.

 Previous receipt of an investigational malaria vaccine.

 History of a known allergy to nickel.

 History of known allergy to yeast.

 Known hypersensitivity to any component of the Hib vaccine (tetanus toxoid, lactose).

 Previous administration of Hib vaccines.

 Known thrombocytopenia or bleeding disorders.