Alternative and Novel Drug Based Prevention Approaches

About antimalarial drugs

A number of strategies use antimalarial drugs to reduce transmission by clearing the affected population of malaria parasites. To date, the most common approach is known as mass drug administration (MDA). MDA has been implemented as part of attempts to reduce or eliminate malaria from an area and to respond to malaria epidemics caused by P. falciparum, the most lethal of the malaria parasites, and P. vivax. MDA and related strategies that deploy antimalarials to reduce malaria transmission are described below.

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Mass Drug Administration (MDA)

MDA for malariais the administration of a full therapeutic course of an antimalarial medicine at approximately the same time and often at repeated intervals, to all age groups in a defined geographical area (except those for whom the medicine in contraindicated). In general, MDA is more effective with higher coverage, smaller population size, minimal risk of re-introduction of infection, and good access to treatment and vector control measures.

The World Health Organization currently conditionally recommends MDA for malaria in the following settings:

1. Use of MDA to reduce burden of falciparum malaria can be considered in areas of moderate to high transmission to provide short-term reductions in disease burden despite a waning of effect within 1 to 3 months.
2. Use of MDA to rapidly reduce falciparum malaria burden in emergency settings or periods of health service disruption despite a waning of effect within 1 to 3 months.
3. Use of MDA to reduce transmission of falciparum malaria in very low to low transmission settings despite a waning effect. MDA should be considered only in areas with limited risk of importation of malaria and sufficient resources available to not affect other components of malaria elimination.
4. Use of MDA to reduce transmission of vivax malaria despite a waning effect. MDA should be considered only in areas with limited risk of importation of malaria and sufficient resources available to not affect other components of malaria elimination. Programs will also need to consider how to safely and feasibly prevent relapses.

Variations of MDA are also recommended by WHO in the final phase of elimination or the prevention of reintroduction.

Targeted Drug Administration (TDA)

Use of targeted drug administration (TDA) to reduce transmission of malaria in very low to low transmission to post-elimination settings. TDA is a form of drug-based prevention involving the administration of a full therapeutic course of an antimalarial medicine to individuals at increased risk of malaria infection compared to the general population. Use of Reactive drug administration (RDA) to reduce malaria transmission in approaching elimination or post-elimination settings. RDA is the provision of antimalarial medicine to all people residing with or near a confirmed malaria case and all people who share the same risk of infection (e.g., co-travelers and co-workers).

Mass Test and Treatment (MTAT)

MTAT refers to testing all people in a population in a delimited geographical area with an appropriate malaria diagnostic test and providing treatment to those with a positive test result. This intervention is based on the assumption that most of the people who can serve to infect mosquitoes will have high enough levels of parasites or antigen in their blood to be detected at the time of screening. Targeted test and treat (TTaT) is a variation of an MTaT performed in individuals at increased risk of malaria infection and treatment of all positive cases with an appropriate antimalarial medicine. WHO does not currently recommend MTAT and TTAT as suitable interventions to reduce malaria transmission using current diagnostic tests.

Mass Fever Treatment (MFT)

MTF, like MDA, refers to the treatment of malaria with a curative dose of an antimalarial drug within a well-defined population without testing, but unlike MDA, only persons with a fever are treated. MFT is a rapid measure that can be considered as part of an outbreak response, especially if diagnostic tests are insufficient or the healthcare system is being overwhelmed. The criteria for choosing an antimalarial drug for MFT are the same as for the national policy for treating uncomplicated malaria (most likely an artemisinin-based combination therapy [ACT]). WHO states that mass treatment of fever cases with an ACT is appropriate as a strategy to reduce mortality once malaria has been established as the cause of the epidemic. This strategy aims to get treatment to people with probable malaria cases as quickly as possible to cure illness, avert death, and help contain the epidemic. After the outbreak response is more fully implemented in the community, laboratory confirmation of malaria parasites should precede treatment.

Monoclonal antibodies

Mononclonal antibodies (mAbs) are proteins that are cloned in the laboratory that can target specific disease antigens. To date, mAbs have been used successfully for prevention and treatment of certain kinds of auto-immune diseases, cancer, and more recently, infectious diseases such as COVID-19 and respiratory syncytial virus (RSV). Several anti-malaria mAbs, isolated from antibodies made by clinical trial participants in malaria vaccine trials are in early stages of clinical development. All target P. falciparum and specifically the circumsporozoite protein, which is abundantly expressed by the infectious sporozoite stage of the parasite once it is injected by mosquitoes into humans. Two mAbs developed by NIH, CIS43LS and L9LS, as well as one developed by the Gates Medical Research Institute, called MAM01, have been shown to be safe and well tolerated in early clinical trials. Trials to evaluate the safety and efficacy in African children are underway in several countries, and early results are promising.