Infectivity of Microscopic and Submicroscopic Malaria Parasite Infections in Areas of Low Malaria Endemicity Free

To the Editor—The contribution of low-density, subpatent Plasmodium falciparum infection to mosquito infection and onward transmission of malaria has received much recent attention as a determinant of the success of malaria elimination strategies. The study by Lin et al [1] addresses this issue in the context of low malaria transmission intensity in Cambodia. The authors observed that 5.9% of adults with symptomatic malaria were infectious in mosquito feeding experiments and that the vast majority of these infections (96%) arose from patients whose blood had microscopically detectable gametocytes. The study provides valuable information on infectivity in this particular group (ie, adults with clinical malaria who have presented to the hospital). It also suggests that infectivity in areas where individuals seek medical care early in their infection, with fewer mature gametocytes, would be lower than in areas where clinic attendance is delayed, perhaps because symptoms take longer to develop and/or individuals postpone seeking treatment, and gametocyte levels have more time to increase.

Although these observations made in the Cambodian study are valuable, there are several important considerations when using these clinic-based observations to draw broader conclusions on the human infectious reservoir for malaria. In many settings, the majority of malaria parasite infections do not elicit effective care-seeking behavior but persist as asymptomatic infections. A recent large epidemiological study in Cambodia, Vietnam, and along the Thailand-Myanmar border showed that 20% of the population in these settings harbored falciparum or vivax infections, most of which were afebrile [2]. Imwong et al [3] recently demonstrated that the mean density of these asymptomatic infections is approximately 5 parasites/μL; the majority of infections are thereby present at densities that are unlikely to be detected by microscopy or rapid diagnostic tests [4, 5]. It is the contribution of these asymptomatic and often submicroscopic infections to the infectious reservoir that is poorly characterized.

The conclusion of Lin et al that ultrasensitive diagnostic assays are not required to identify individuals who are most infectious to mosquitoes is most probably correct. It is, however, still very much an open question what proportion of all mosquito infections is caused by individuals with clinical malaria who are seeking treatment and what proportion is caused by individuals with asymptomatic, chronic infections that may be submicroscopic. Indeed, in an earlier study in Thailand, Pethleart et al [6] concluded that the infectious reservoir was largely driven by the latter group (ie, infected individuals who did not present to clinics). That study also concluded that submicroscopic gametocytes were an important source of mosquito infections in this population. Moreover, the true relevance of the results from any of the artificial mosquito infections needs to be balanced by natural mosquito dynamics such as local abundance, biting rates, and species-specific susceptibility to infection [7].

Ultimately, where the health system is able to (or can be improved to be able to) rapidly identify and treat infections, it seems reasonable to assume that the duration of symptomatic infections will be shortened, resulting in fewer infectious individuals. This could have an important impact on overall malaria transmission, as suggested in the optimistic conclusions by Lin et al. However, in many settings in Africa and Asia, asymptomatically infected individuals vastly outnumber those with symptoms, and the lack of interaction with health systems means that many infections remain untreated. It is imperative that the identification and treatment of malaria by health facilities remain the cornerstone of malaria control programs, but specific targeting of asymptomatic infections is likely to accelerate the progress toward elimination. Further studies on the importance of asymptomatic and submicroscopic malaria parasite infections for onward transmission will facilitate this progress.

Notes

Financial support. This work was supported by the Bill and Melinda Gates Foundation (grant AFIRM OPP1034789) and the European Research Council (fellowship ERC-2014-StG 639776 to T. B.).

Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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