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Recommendations to Enhance P. vivax Research, Resources and Training (2005)

Participants attending the conference met in small break-out groups on the final day to draft recommendations to specifically enhance P. vivax research in the areas of transmission and epidemiology; pathology and morbidity; vaccines, antigens and immunity; drug treatment, resistance and development; and genomics, genetics and population studies.

Pathology and morbidity

  • Clinical epidemiological studies in different transmission settings to measure the spectrum, risk factors and magnitude of morbidity and mortality from P. vivax. Publication of existing data as soon as possible (high priority)
  • Socio-economic burden of vivax malaria needs to be measured, and cost-effectiveness of interventions to reduce vivax morbidity determined. (high priority)
  • Establish a network of sites/groups to undertake the above, including standardization of definitions, and sharing of protocols. [links in to sites for future vaccine studies] (high priority)
  • Molecular mechanisms involved in P. vivax-asssociated pathology and morbidity, especially those related to fever, anemia, pregnancy, coma and respiratory distress, including both host and parasite determinants of disease
  • Longitudinal studies examining interactions between P. vivax and P. falciparum, including effects of prior exposure as well as coinfection (i.e. cross-protection, additive effects on morbidity and effects on pathophysiology), including studies in high transmission areas
  • Relative contribution of drug resistance and relapse (vs new infection) to burden of disease, and development of methodologies to measure these

Epidemiology and transmission

  • The epidemiology of P. vivax malaria is poorly documented compared to P. falciparum. There is an urgent need to conduct studies on the epidemiology of P. vivax malaria at multiple sites to estimate the true burden of disease worldwide.
  • Systematic collation of the epidemiology of P. vivax in standardized databases
  • Host, parasite and mosquito determinants of P. vivax transmission, and their underlying mechanisms
  • Mathematical modelling of host, parasite and mosquito factors involved in transmission of P. vivax, in settings with different intensities of P. vivax and P. falciparum transmission, and the effects of interventions

Vaccines, antigens and immunity

  • There is increasing although limited evidence from a few clinical studies that P. vivax may cause severe pathology. There is a need to conduct clinical studies on the incidence and role of P. vivax malaria in severe disease. Studies on anemia, thrombocytopenia and P. vivax malaria in pregnancy need special attention to estimate impact of P. vivax malaria.
  • There is limited information on the development of immunity to P. vivax malaria in endemic areas. Epidemiology studies in P. vivax endemic areas need to be conducted to document development of immunity to P. vivax malaria following repeated exposure. Understanding the nature of naturally acquired immunity may provide new approaches to development of malaria vaccines. Epidemiology studies on P. vivax malaria at different geographical locations will not only provide useful information but may also provide the basis for development of sites for field trials of vaccines for P. vivax malaria.

Drug treatment, resistance and development

  • Improve diagnosis of P. vivax malaria through:
    • Microscopy training and quality control to improve differential diagnosis of P. falciparum and P. vivax.
    • Improve detection sensitivity for P. vivax: studies to identify vivax antigens that are expressed at high levels need to be undertaken.
  • Standardize methods to assess parasite susceptibility to antimalarial drugs in vitro which may be achieved by:
    • Methods reporting so results obtained may be compared.
    • Optimization and standardization of assay protocols
  • Determine the molecular mechanisms of resistance to antimalarial drugs in P. vivax:
    • Conduct comparative biology studies to investigate common or different mechanisms in emergence and spread of drug resistance between P. falciparum and P. vivax (e.g. CQR in P. falciparum and P. vivax: different determinant? different rate of spread?).
  • Expansion of the collection of P. vivax strains adapted to infection of non-human primates, representing a wider variety of geographic areas and drug resistance phenotypes
  • Studies of alternative therapy for CQR vivax
  • Establish a database incorporating in vivo efficacy, in vitro susceptibility and resistance mutations/gene modifications.
  • Improve methods for assessing primaquine efficacy and for measuring primaquine relapses.
  • Develop simple, rapid and inexpensive assays to identify individuals likely to suffer hemolysis to inform primaquine treatment decisions.
  • Increase drug discovery studies against liver stage parasites.

Genomics, genetics and population studies

Comparative genomics

  • Develop in vitro culture methods for P. vivax.
  • Sequence the following strains: P. cynomolgi, P. knowlesi, P. coatney, and P. simium.
  • Obtain additional isolates of P. vivax : chloroquine-resistant; from North Korea; more Chesson - like isolates; severe disease strains.
  • Generate a P. vivax HapMap: SNP ascertainment through sequencing (though concerns voiced regarding amount of DNA/purity of DNA from patient samples).

Population studies

  • Establish an informal network of researchers interested in population genetics and diversity of P. vivax.

Bioinformatics

  • More workshops to teach researchers how to analyze P. vivax genome sequence data
  • Population genetics, human genome, and vector genome analysis need also to be included

Reagents

  • Microarray platforms- an appeal for coordination of platform design
  • Proteomics: at least two projects ongoing - blood stages and ookinete stage planned