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NEW: Gametocyte Carriage Study Group

5 March 2014

A pooled analysis of Plasmodium falciparum gametocyte carriage in regions of differing malaria endemicity.

Gametocytes are the precursors of male and female gametes of malaria parasites. They are triggered in the red cells of the human host by a switch from asexual replication to sexual development. If both male and female gametocytes are taken up by a mosquito in a blood meal, they develop into gametes and complete the cycle of fertilization in the mosquito gut. Although gametocytes are not responsible for clinical symptoms, their transfer to a mosquito vector allows the transmission of malaria to another mammalian host. [1]

Most antimalarial drugs target asexual blood-stage parasites, but the artemisinin components of artemisinin combination therapies (ACTs) can also specifically kill early stages of gametocyte development.  This property means that they could play a critical role in reducing the transmission of malaria and decreasing the spread of drug resistant parasites. However, the effectiveness of this activity against gametocytes varies depending on the drug regimen, the doses given, the local prevalence of drug resistance and host immunity.

The methods for detecting and measuring gametocytes vary considerably from the simple proportion of patients who have gametocytes during follow up of drug treatment, to quantitative measures of gametocyte density and the ultimate measure- the infectivity of a patient’s blood to mosquitos [2,3].

Whilst there is good evidence that ACT treatments are associated with a significant reduction in gametocyte carriage, Georgina Humphreys, WWARN’s Postdoctoral Researcher highlights “the crucial factor is the ability of patients to infect the mosquito vector. There is a need for us to better understand gametocyte carriage in a variety of endemic settings using standardised analytical approaches, controlling for confounding factors.”

To respond to this question, a new WWARN Gametocyte Carriage Study Group has been defined to assess the risk factors associated with gametocyte carriage and clearance. Data sets from over 120 studies with gametocyte information have been contributed previously to the WWARN repository, including more than 6000 patients who carried gametocytes when they presented for treatment of malaria. If contributors of those data sets choose to join this study group, that will be a significant start. However, additional data sets will also be solicited, so new members of the group will be welcome.

The goal will be to create a single database, of quality-assured individual patient data, in order to evaluate:

  • Risk factors for gametocyte carriage at enrolment
  • Gametocyte clearance dynamics during follow-up
  • Treatment success and risk of gametocyte carriage

Teun Bousema, Senior Lecturer at London School of Hygiene and Tropical Medicine, one of the leaders of the study group confirms ‘these data will allow us to clarify the public health benefit of different ACTs and their role in reducing malaria transmission in different endemic settings and with different treatments.’

The study group will be led by Teun Bousema and  Prof. Chris Drakely from the LSHTM with coordination support from Georgina Humphreys of WWARN. Find out more about the analysis and governance proposal and how to join this group. For further information, email Georgina Humphreys georgina.humphreys(at)wwarn.org

[1] Jongwutiwes S et al. Source for Simultaneous detection of Plasmodium vivax and Plasmodium falciparum gametocytes in clinical isolates by multiplex-nested RT-PCR. Malaria Journal 2012; 11:190  doi:10.1186/1475-2875-11-190  

[2] Stepniewska K, Price RN, Sutherland CJ, et al. Plasmodium falciparum gametocyte dynamics in areas of different malaria endemicity. Malar. J. 2008;7:249. doi:  10.1186/1475-2875-7-249

[3] Bousema T, Drakeley C. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin. Microbiol. Rev. 2011;24(2):377–410. doi:  10.1128/CMR.00051-10. Accessed October 23, 2013.