Efficacy of mobile phone short message service (SMS) on malaria treatment adherence and post-treatment review

The project will be conducted in 3 phases at 4 sites (2 rural and 2 urban) in Western Kenya. In phase I-Pilot phase, we will collect and collate primary and secondary data on cell phone coverage and use to demonstrate the feasibility of the intervention. We will also carry out facility based surveys to validate mobile phone ownership statistics among care givers attending health facilities for malaria and determine access, ownership and use of mobile phones. Further, we will pilot the SMS intervention, which will be one-way communication of SMS reminders on treatment adherence and post-treatment review sent to caregivers' personal mobile phones. The development process will involve malaria epidemiologists, social scientists, mobile health programmers, as well as clinicians and patients from the study areas. Phase II will be a multi-centre randomized controlled trial (RCT). Eligible caregivers of children < 5 years old with uncomplicated malaria will be randomly assigned (1:1) to two different arms: 1) the current standard of care based on provider counselling and health education alone, and 2) the current standard of care plus SMS reminders. Within each arm participants will be further equally randomly assigned to 3 different categories for the measurement of adherence. In the first category, 260 caregivers will be visited at home on day 1 of follow up to measure appropriate timing of the second artemether-lumefantrine (AL) dose. In category 2, 260 caregivers will be visited at home on day 2 to measure adherence of AL doses 2, 3 and 4. While, in category 3, another 260 caregivers will be visited at home on day 3 after they have completed the full treatment course to measure adherence for the full course of AL. The 520 caregivers per arm in category 1 and 2 that will be visited before completion of the full dose will not be visited again to avoid biases in the subsequent measures of adherence. These patients will also present the study group for the day 3 post treatment review. AL will be administered according to weight bands, directly observed for the first dose, and the remaining 5 doses self administered at home. Caregivers will receive standard instructions about how to administer AL at home, will be instructed to store used blister packs and to return for review if unwell. Eligible caregivers with mobile phones will be asked to key in a toll free number when the first dose is administered or their number will be registered and input into the automated system. The toll-free signal will generate a programme to randomly assign caregivers to either the intervention or control arm and to the 3 categories of home visits. In the intervention arm the signal will also generate a programme to automate SMS reminders from a central server depending on pilot investigative and development work, timed to when the next dose should be administered. Category 1 and 2 caregivers in the intervention arm will in addition to the adherence SMS reminders also receive a morning SMS reminder for the appointment for review at the health facility on day 3. While category 3 participants (intervention and control) will be reviewed at home on day 3. During the second week post treatment, weekly SMS reminders prompting caregivers to visit the health facility if the child is unwell will be sent to participants in the intervention arm. Finally, participants in the intervention arm will be sent a final SMS reminder for the appointment for review on day 28. The primary outcome are twofold: Adherence to a complete AL course (doses 2-6) measured in category 3 only and the proportion of patients reporting to the health facility for post treatment review and subsequent evaluation of clinical and parasitological cure at day 3 (category 1 and 2) and at day 28 (all categories). We will conduct individual patient level pooled analysis, according to CONSORT standards for reporting RCTs. In phase III, we will carry out a cost-effectiveness analysis for scale up.

The study will be conducted in three phases. In phase I, we will collect/collate primary and secondary data on mobile phone network coverage, access, cell phone ownership and use in relation to malaria risk to demonstrate the feasibility of the intervention. In addition we will develop, refine and finalize the SMS intervention as well as pilot the automated message delivery system. In phase II, we will conduct a randomized controlled trial (RCT) to assess the efficacy of the SMS intervention. In phase III, we will carry out a cost-effectiveness analysis of the intervention with respect to the primary outcomes of the intervention - adherence and post treatment review. Costs will be measured under the trial conditions, from the provider's perspective and will include costs that would be required for the Kenya ministry of health ( MoH) to expand the delivery of the intervention, if successful, to all facilities in Bondo district and nationally.

Artemisinin resistant falciparum malaria has emerged in Western Cambodia and has now been detected in Western Thailand. This is an ominous repetition of the spread of resistance to chloroquine and later to sulfadoxine-pyrimethamine several decades ago. Artemisinin resistance poses a major global public health threat, with the greatest potential effects in sub-Saharan Africa where the disease burden is the greatest and systems for resistance monitoring and containment are the weakest. The World Health Organization (WHO) Global Plan for Artemisinin Resistance Containment (GPARC) has, as one if its pillars, to increase monitoring and surveillance to evaluate the artemisinin resistance threat." In this study we propose to investigate an innovative malaria treatment adherence model profiting from widespread availability of mobile phones and use of text-messaging in malaria endemic areas as well as test the feasibility of an enhanced malaria drug resistance surveillance model to mitigate the threat of artemisinin resistance in Africa. The project we plan is in line with the recommendations of the WHO GPARC to increase surveillance for drug resistance and improve treatment outcomes for malaria. Locally, this trial is likely to benefit the Kenyan Ministry of Health, but could be extrapolated to other ministries of health in Africa. Improved adherence is likely to improve cure rates for malaria and prolong the useful therapeutic life of the current gold standard treatment for malaria-the artemisinin combination therapy. In addition the surveillance system that we plan to investigate, if successful could serve as an early warning signal for emerging drug resistance, that could lead to clinical investigations to confirm resistance and once confirmed facilitate the establishment of containment measures. The current WHO guidelines for malaria treatment recommend universal parasite-based diagnostic testing for all suspected cases of malaria. Moving away from presumptive to parasite-based diagnosis and treatment offers a new opportunity to test the feasibility of early warning tools that might be incorporated into routine health information systems (HIS). Our operational research is around simple models of treatment failure detection including the feasibility of institutionalizing post-treatment review. The loss of ACT would have huge economic costs to the global malaria community because presently there are no other alternatives. Drug resistance was associated with increased child mortality in the late 1990s in Africa and our research if successful could avert this disaster.
Application and exploitation: During the trial phase we will work closely with mobile phone service providers and mobile health programmers and will explore the feasibility of scale up. There are already existing mechanisms for collaborations with ministries of health and we will enhance these to facilitate the reach and potential up-take of the research to shape policy and practice. Communications and engagement: Once the trial is completed and found to be successful, we will summarize the results for uptake by research partners, policy makers and wider audiences including the provision of feedback to research participants and related communities. We have a long-standing working relationship with the Division of Malaria Control (DOMC) of the Kenyan Ministry of Health which is critical to maximize the influence of research findings on malaria policy and practice. Following the trial we envisage utilizing these channels within the Ministry to translate research findings into the policy and raise international donor support to fund a national scale-up.