The acceptability of mass administrations of anti-malarial drugs as part of targeted malaria elimination in villages along the Thai–Myanmar border

Economic development, deforestation and on-going malaria control activities including the distribution of insecticide-treated bed nets (ITNs) and improved management have reduced malaria prevalence to historically low levels in the Greater Mekong Subregion (GMS). The recent emergence and spread of artemisinin resistance in Western Cambodia is a threat for the effective treatment of falciparum malaria [1]. In the absence of alternative first-line anti-malarial drugs increasing falciparum malaria related morbidity and mortality can be expected. The interruption of malaria transmission is the remaining best strategy to stop the spread of artemisinin-resistant Plasmodium falciparum, which requires the elimination of all falciparum infections including the submicroscopic parasite reservoir. The large majority of parasitaemia people in low transmission settings have no clinical signs or symptoms of malaria hence screening with rapid diagnostic tests, microscopy and even standard PCR misses a proportion of infections [2]. Targeted malaria elimination includes mass drug administrations (MDA) for the presumptive treatment of all residents in foci of high sub-microscopic infections in addition to improved case management by village health workers and the distribution of ITNs.

Mass administrations of anti-malarial drugs have been recorded and reported for more than a century [3]. Well-conducted campaigns have interrupted malaria transmission for extended periods [4] and permanently in an island setting (Aneityum, Vanuatu) [5]. Public health interventions depend on the goodwill and support of the community [6]. Mass administrations of anti-malarial drugs differ fundamentally from other interventions in that the participation of the entire community is essential for success. Non-participants can become a residual reservoir for infections, continue to transmit malaria and thus prevent elimination. There has been extensive research on the pharmacokinetics, dynamics, and efficacy of various anti-malarial drug regimens [7]. Less is known about the factors, which influence community acceptance or refusal to participate in mass administrations of anti-malarial drugs.

Newby and co-workers conducted a systematic literature review of mass administrations of anti-malarial drugs in 2014 [3]. Very few of the articles provided detailed descriptions of knowledge, attitudes and perceptions towards mass administrations or a description of efforts to engage the community and increase participation. Examples for continued research on the acceptance of anti-malarial mass drug administration campaigns come from Aneityum Island [8, 9] and The Gambia [10‐12]. One such report described a quantitative survey following a mass administration of anti-malarials conducted in The Gambia in 1998/99 [10]. Individuals who believed in the importance of the MDA and those who were aware that a high level of participation was needed for the MDA to be successful were more likely to participate.

Understanding that the purpose of the MDA was to reduce malaria, knowledge of the fact that malaria is transmitted by mosquitoes and awareness of the clinical signs of malaria were associated with participation. Individuals who discussed the MDA with other villagers and those who attended the sensitization meeting were also more likely to participate than those who did not. In The Gambia women were significantly more likely than men to participate in the mass drug administrations. The investigators concluded that better information could lead to increased participation in their target populations in rural West Africa. In 2013, 14 years after the campaign, social scientists re-visited the study site in The Gambia and interviewed the population about this and subsequent mass drug administrations targeting trachoma transmission [11]. This later qualitative study found that timing of the campaign, accurate information on the procedures, drug regimen, and possible side effects were critical for participation. The authors concluded that continuous sensitization meetings may be needed to achieve high coverage. In 2014 a second mass administration of anti-malarial drugs was conducted in The Gambia. A combined quantitative and qualitative study explored the motivations and circumstances for non-uptake and non-adherence [12]. This time the most frequently mentioned reasons for non-participation were mobility/travel, fear of drug reactions, inconvenience and insufficient information.

A targeted malaria elimination project is currently underway in villages along the Thailand–Myanmar border. Quantitative surveys were conducted to study reasons for participation or non-participation in the drug administration campaign with the aim to identify factors associated with acceptance of the complete drug administration, three rounds of three doses of anti-malarials, part of the drug administration or no participation at all.

In TOT the community is historically divided between two armed factions. The village has grown together from two separate villages but the population remains divided. Uniting the population in participating in the intervention has not been successful. In the absence of a cohesive community an intervention supported by one faction tends to be opposed by the other faction irrespective of potential benefits. The respondents from TOT gave different answers than the respondents from the other three villages suggesting different believes and perceptions. Their knowledge regarding the cause, signs and symptoms of malaria as well as their understanding of the intervention was significantly lower than in the other villages. The poor understanding of the disease as well as the rationale for the intervention to eliminate malaria has probably contributed to the low participation of respondents. The MDA in 2014 had been well tolerated and no severe adverse events attributable to the study drugs had been reported which should have diffused any safety concerns. But there were unconfirmed rumours about adverse events unfairly blamed on the anti-malarial drugs in some parts of the village. The investigators attributed the continued transmission of falciparum malaria after the MDA to the relatively poor participation resulting in a residual parasite reservoir. Hence the MDA was repeated at the end of the 2-year surveillance period in 2015. The study staff had a continued presence over the 2-year surveillance period. The increased knowledge of malaria in 2015 compared to 2014 may reflect the impact of the education efforts provided by the study team. Yet increased knowledge and understanding did not translate in higher participation rates during the second MDA in 2015 suggesting that in TOT the historical division and antagonism between fractions of the population played a more important role in non-participation than lack of understanding.

The other village with low participation rates was HKT. HKT shares with TOT a fragmented community. The population of HKT has rapidly increased over the last decade and many of the recent arrivals consider themselves temporary visitors and hold different believes than the indigenous residents. Because they plan to stay only for a limited period the newcomers don’t consider themselves necessarily as part of the community and see little reason to participate in a campaign, which does not provide direct benefits. In HKT the relatively high refusal rate in the MDA was associated with Burman ethnicity. Specifically Burman shopkeepers felt little need to participate in the MDA. Participating in the campaign requires closing the shop for nine mornings to come to the healthcare centre. The absence of a direct benefit is hence potentially compounded by a loss of income. The members of the Burman minority in these tribal areas see themselves at low risk for malaria, are generally more affluent and should they become sick with malaria will have easier access to appropriate healthcare than the indigenous villagers.

An alternative, more universal reason for non-participation in the MDA independent of village was related to an inadequate understanding of the intervention. Respondents who felt that they had received sufficient information were significantly more likely to participate than responds who felt that they didn’t know enough about the campaign. The perception of being well informed about the intervention has been shown to play a critical role in other mass drug administrations against malaria [10] and other infectious diseases including lymphatic filariasis [14]. But there was no direct correlation between understanding and willingness to participate in the campaign. Many community members had limited understanding of the intervention or knowledge of malaria but still participated. On the other hand relatively well informed and educated community members such as the shopkeepers in HKT refused to participate.

The study relied on recollection and opinions, which may be biased and inaccurate. The most frequent response to the question why they did not participate in the MDA was “I was travelling/I was not in the village at the time.” This reply is more polite than stating “I distrust the institution conducting the campaign” even though distrust could have played a role in the decision to be absent from the campaign. To get a more detailed understanding of the true reasons for incomplete or non-participation including deeper motivations, fears and apprehension, in-depth interviews and focus group discussions will be needed.

The biologic principles underlying the drug administrations are complex and require a relatively sophisticated understanding of the pathogenesis of malaria, the concept of a parasite reservoir and the treatment of subclinical infections. These concepts are not easy to communicate especially over a short time period in a field setting to semi-literate communities few of whom have a secondary education. In the absence of a comprehensive understanding of the risks and benefits of the campaigns many villagers have to decide whether or not to participate in the campaign based on their trust in the study staff who have explained the intervention, the potential risks and benefits. Several researchers have explored the concept of trust in decisions whether or not to participate in public health interventions including clinical trials [15‐18]. Qualitative research has shown time and again that trust plays a central role in the uptake of public health interventions. Trust relationships tend to be complex. In some settings it is not the promised indirect benefit of intervention such as the elimination of a disease but the tangible direct benefits such as free appropriate primary health care and free transport to a hospital in an emergency at least for the duration of the surveillance period [15]. In the absence of tangible benefits and limited comprehension of the broader indirect benefits for the community it is essential for the potential participant to be able to believe that the intervention team will act in the best interest of the participant. To gain such trust requires time and persistent good will from both sides. The repeated campaigns in TOT illustrate in a fragmented community 2 years of permanent presence, primary health care provision and successful health education were not enough to increase participation.

The study found excellent participation in two cohesive communities. In contrast in fragmented communities attempts to mobilise the entire community were less successful. The findings suggest several approaches how community participation in anti-malarial mass drug administrations can be increased. Understanding the purpose and the reasons underlying the intervention is a helpful but perhaps not essential pre-condition for participation. Time invested in information campaigns is a productive investment to increase coverage. Not only is the information provided critical but how this information is communicated is essential. A sincere effort to provide honest information to community members can be one of several steps to build trust with the community. Building trust in a community is a complex, time consuming undertaking but only if all community members are convinced that they will ultimately benefit from the campaign can the very high participation rates achieved required for the elimination of infectious diseases like malaria. Based on the experience in one fragmented village overcoming internal divisions within a village is an extraordinary challenge requiring additional time, engagement and repeated campaigns.