Strengthening therapeutic adherence and pharmacovigilance to antimalarial treatment in Manaus, Brazil: a multicomponent strategy using mHealth

Abstract

Background Public health initiatives for improving adherence to primaquine based regimens and enhancing effective pharmacovigilance are needed to support the efforts for malaria elimination in real world conditions. Methods A multicomponent patient-oriented strategy using a Smart Safety Surveillance (3S) approach including: (1) educational materials for treatment counselling and identification of warning symptoms of haemolytic anaemia; (2) an mHealth component using Short Message Service (SMS) treatment reminders and (3) development and implementation of follow-up phone surveys three days after treatment completion, using a web-based platform linked to the local information system of malaria. Adherence was measured using the Morisky Medication Adherence Scale. Self-reported events were registered using a structured questionnaire and communicated to the Brazilian Health Regulatory Agency. Results Educational materials were disseminated to 5594 patients, of whom 1512 voluntarily entered the mHealth component through the local information system; 7323 SMS were sent, and 1062 participants completed a follow-up survey after treatment. The mean age of patients was 37.36 years (SD 13.65), 61.24% were male, 98.54% were infected with. Plasmodium vivax and 95.90% received a short regimen of chloroquine plus primaquine (CQ + PQ 7 days), as per malaria case management guidelines in Brazil. From the 1062 surveyed participants 93.31% were considered adherent to the treatment. Most of the patients (95.20%) reported at least one adverse event. Headache, lack of appetite and nausea/vomiting were the most frequently reported adverse events by 77.31%, 70.90% and 56.78% of the patients respectively. A quarter of the patients reported anxiety or depression symptoms; 57 (5.37%) patients reported 5 to 6 warning symptoms of haemolytic anaemia including jaundice and dark urine in 44 (4.14%). Overall, three patients presenting symptoms of haemolytic anaemia attended a hospital and were diagnosed with G6PD deficiency, and one had haemolysis. All of them recovered. Conclusions Under real world conditions, a multicomponent patient-oriented strategy using information and communication technologies allowed health care providers to reinforce treatment adherence and enhance safety surveillance of adverse events associated with regimens using primaquine. Active monitoring through phone surveys also reduced under-reporting of ADRs. This approach is low-cost, scalable and able to support prioritized activities of the national malaria programme.

Systematic Review of Psychiatric Adverse Effects Induced by Chloroquine and Hydroxychloroquine: Case Reports and Population Studies

“…When considering the studies that do specify the psychiatric adverse effects, the most common symptom is depressive mood, 14,17,21,22,27,40 followed by anxiety symptoms 7,21,22,40 and hallucination. 27,39,40 In less frequency, studies also mentioned that patients developed psychosis, 7,17,21 agitation, 7,40 disturbed/strange thoughts, 7,14 depressive psychosis, 7 manic psychosis, 7 restlessness, 7 irritable mood, 7 panic attack, 17 confusion, 16 post-traumatic stress disorder (PTSD), 22 delirium, 27 and emotional lability. 39…”

“…Among those studies that do specify the length of treatment, individuals took CQ for a mean of 6 days, ranging from 6 hours to 18 days. 7,11,16,19,20,39,40,80 Using a different approach, Petersen et al 14 classified individuals into short-term (ie, less than 8 weeks of treatment) and long-term (ie, more than 8 weeks). The authors found, however, no significant difference in the percentage of psychiatric adverse effects between them.…”

“…Most populational studies do not specify the dose in which individuals ingested CQ, especially survey-based and retrospective studies. The studies that addressed how much CQ was ingested reported a mean of 443 mg, ranging from 250 to 2700 mg. 7,11,16,19,26,39,80 Ursing et al 20 and Saint-Gerons et al 40 reported a more detailed dose, in which patients took 10 mg/kg on days 0 and 1 and 2 doses of 5 mg/kg on day 2, and 10 mg/kg on day 1 and 7.5 mg/kg on days 2 and 3, respectively.…”

“…One study also observed that 6.2% of patients reported visual hallucinations after CQ intake. 40 Results from the survey studies may need to be considered with caution, for some confounding variables may have been present (see the Discussion section). We also identified 2 nested case-control and 5 randomized control studies, which offered better control over possible confounds.…”

Adherence to 14-day radical cure for P. vivax malaria in Papua, Indonesia: a mixed- methods study

“…Studies about patient adherence to antimalarials yielded varied results related to patient characteristics, the nature of their consultation with the provider, and methodological variations of the study [12]. Assessment of adherence relied on subjective measures such as self-reporting or a combination of selfreporting and more objective measures such as pill count, presenting empty pill bags, or directly measuring the level of PQ in the blood [13][14][15][16]. Treatment supervision to improve adherence has been studied, including in the trial where this study is embedded [17,18].…”