Controlled Human Malaria Infection After Bites From Mosquitoes Infected With Two Novel P. Falciparum Strains
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional

Summary: 
      An effective vaccine against malaria is urgently needed to combat the scourge of this
      disease. Before candidate vaccines can be tested in endemic countries, they are first tested
      in human volunteers in so-called Controlled Human Malaria Infections (CHMI's). Ideally, a
      candidate vaccine should be tested against multiple strains of malaria, representative of the
      disease's global distribution. Recently we compared, for the first time, infections with the
      novel malaria strains NF135 and NF166 to those with the broadly-used and well-characterised
      strain NF54.

      The purpose of the current study is to optimise the course of infections with these novel
      strains by determining the minimum number of infectious bites necessary to reliably induce a
      malaria infection.
    

Detailed description: 
      Plasmodium falciparum (Pf) malaria remains responsible for an intolerable burden of morbidity
      worldwide and an effective vaccine is sorely needed to aid control efforts. Before candidate
      malaria vaccines can enter full-scale (phase IIb) field trials in endemic areas, they must
      first be tested under controlled circumstances in (phase IIa) Controlled Human Malaria
      Infection (CHMI) studies. Since Pf isolates display a wide genetic diversity across the
      globe, phase IIa challenge infections should be conducted with both homologous and
      heterologous strains.

      Since 1998 a highly successful Controlled Human Malaria Infection model at the UMC St
      Radboud, Nijmegen, The Netherlands, has been employed both to test candidate vaccines and to
      answer fundamental questions about pathophysiological and immunological mechanisms during
      early Pf infection in human volunteers. To date largely the NF54 strain of P. falciparum has
      been used in this Nijmegen model, with which extensive experience has meanwhile been
      acquired. In order to increase the portfolio of Pf strains available for future phase IIa
      studies, we recently compared NF54 to the novel candidate strains NF135.C10 and NF166.C8 with
      regards to parasitological, clinical and immunological characteristics during a Controlled
      Human Malaria Infection (TIP3 study, NCT01627951). The pre-patent period in all NF135- and
      NF166-infected subjects was markedly shorter than in NF54-infected subjects, following the
      bites of 5 infected mosquitoes on each subject. The current study will therefore assess
      whether NF135 and NF166 infections can still reliably be induced with fewer than 5 infected
      bites per subject. This will envisionably increase the tolerability of NF135 and NF166
      infections and render their dynamics more similar to those of NF54 infections, for better
      comparison in future heterologous challenge studies.
    

Intervention name(s): NF135 n=5; NF135 n=2; NF135 n=1; NF166 n=5; NF166 n=2; NF166 n=1
Intervention type(s): Other; Other; Other; Other; Other; Other
Intervention description(s): Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.; Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes.; Subjects will be infected with the NF135.C10 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito.; Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 5 infected Anopheline mosquitoes.; Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bites of 2 infected Anopheline mosquitoes.; Subjects will be infected with the NF166.C8 strain of Plasmodium falciparum through the bite of 1 infected Anopheline mosquito.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Plasmodium falciparum; malaria