Artemisinin combination therapy mass drug administration in a setting of low malaria endemicity: programmatic coverage and adherence during an observational study in Zanzibar

Malaria was the leading cause of morbidity and mortality in Zanzibar prior to 2003, with malaria endemicity being classified as moderate to high (i.e. parasitaemia among symptomatic patients tested was 35–40%) [1]. In response to the malaria burden, the Zanzibar Malaria Control Programme—in collaboration with bilateral, multilateral and non-governmental partners—scaled up prevention and control efforts, including: artemisinin-based combination therapy (ACT); insecticide-treated nets (ITNs); indoor residual spraying of households with insecticide (IRS); and intermittent preventive treatment for pregnant women (IPTp) with sulfadoxine–pyrimethamine (SP) [2‐4]. Over the past decade these efforts changed malaria endemicity in Zanzibar from hyper- to hypo-endemic, with parasite prevalence dropping to and being maintained at <1% for the previous 3 years [1, 4].

Building on the success of these efforts and in alignment with global guidance [5], Zanzibar is now targeting malaria elimination on both Unguja and Pemba islands: the goal is to achieve zero locally acquired cases by 2018 by achieving and maintaining 100% coverage with appropriate prevention measures [6]. While malaria elimination relies upon a similar mix of interventions as during the malaria control phase (i.e. case management, vector control, and surveillance), it requires more intensified, rapid, and targeted responses, especially for targeting transmission hotspots and specific high-risk populations [7‐9]. The Zanzibar Malaria Elimination Programme (ZAMEP) is able to identify hotspots through its malaria case notification (MCN) (“Coconut”) surveillance system, which tracks daily facility-based malaria cases for real-time decision-making and active case detection through household screening and treatment (HSaT).

One potential strategy for targeted interventions in a malaria elimination setting is focal mass drug administration (MDA) in high-risk populations. Although falling out of favour due to efficacy concerns during the eradication era in the 1960s, MDA has re-emerged as a potential strategy for malaria elimination and eradication [10, 11]. Use of MDA since the eradication era has mainly been preventative therapy and seasonal chemoprevention; however, an argument for MDA is that diagnosis can be hampered by lack of biomarkers of the liver stage of malaria and limitations of currently available detection methods for lower density blood stage infections [12, 13]. A recent systematic literature review found that: (1) MDA has been used in large-scale malaria control, elimination and outbreak response efforts, with community participation and at least 80% coverage of the target population being important factors for a successful MDA campaign; (2) MDA and mass chemoprophylaxis probably contributed to reducing parasite prevalence in certain intervention settings; and (3) select MDA programmes have been considered successful based on qualitative assessments other than efficacy [14]. Renewed interest in MDA as an approach for interrupting transmission is based on the availability of effective anti-malarial drugs with transmission reducing characteristics as well as mathematic modeling studies showing the epidemiological impact of the intervention in settings with low transmission intensity and during periods of low vector densities [15]. However, there is evidence to suggest that effectiveness of MDA is often not sustained beyond 6 months [16].

This study presents findings on the community’s acceptability, completion and perceptions after focal MDA with ACT intended to mitigate increased seasonal malaria transmission in Zanzibar. MDA was conducted within communities as a response to an increase in malaria cases in the four shehias defined as hotspots where MDA was recommended because—although MSaT had been done a few weeks prior—the number of malaria cases in these shehias continued to increase. The rationale for MDA was to provide appropriate treatment to clear malaria parasites in the population so as to prevent on-going transmission in malaria hotspots with intense transmission. The findings of the pilot presented here showed high MDA participation (97.1%) and acceptance by the communities targeted, with high completion of ACT doses (90.2%) among participants who received the medication. This finding was most likely attributed to the intensive community sensitization and mobilization activities that took place prior to the MDA, including the house-to-house approach as well as the post-MDA public announcements to remind people to complete subsequent doses. The findings also suggest that community sensitization was effective, as the majority (94.2%) of survey participants reporting that they would take part in future MDAs. This suggests that MDA can be considered as a practical intervention in persisting malaria hotspots, particularly if active case detection efforts such as MSaT and HSaT fail to adequately curb transmission.

The post-MDA survey findings showed that the reasons for failure to complete the ACT doses were fear of side-effects such as abdominal pain, headaches, vomiting, dizziness, sneezing, muscular aches, fever, nausea and body malaise. Similar findings were observed in studies conducted in The Gambia where barriers of the MDA campaign included the perception and fear of the community members on the side-effects of the drugs and procedures [20, 21]. These misconceptions by the participants and misunderstandings about the medication can contribute greatly to the lack of adherence to an MDA [22]. Similarly, fear of side-effects from the drugs leading to decreased MDA coverage has also been reported in MDA for other parasitic diseases, e.g. lymphatic filariasis [23‐27]. Other reasons for non-compliance reported by participants in Zanzibar included: forgetting to take treatment; insufficient information about MDA; reluctance to take drugs without malaria symptoms; fasting; and busy with daily chores. The number of pills required for a full ACT regimen has also been shown to discourage adherence to the MDA programme [28]. Single dose treatment, possibly under DOT, could enhance compliance for malaria MDA.

As neglected tropical disease MDAs have shown in multiple countries [29‐31], in order to maximize MDA participation, misconception and fears of side-effects within the target population need to be addressed at the start of the activity and frequent communication should be maintained throughout the MDA period through community education and training of health care workers [14, 26, 32]. This is particularly salient if several rounds of MDA were to be conducted in order to have a more lasting impact on malaria transmission. In addition, community sensitization should involve village leaders to enhance participation from community members [20]. The importance of educating the target community with correct information regarding the drug, procedures to be taken and the possible side-effects helps to enhance adherence. The results of this study show that MDA is a practical response intervention in low transmission settings; however, further research is needed to investigate the effectiveness of MDA in the four shehias.

This study demonstrates that MDA for malaria was feasible and highly accepted by communities at high risk of malaria in Zanzibar, with high participation and completion rates, even though they had recently been targeted for MSaT. Together with other preventative measures, MDA has the potential to contribute to interrupting transmission of malaria and accelerate ZAMEP’s efforts towards malaria elimination.