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

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.Fil: Macías Saint Gerons, Diego. Universidad de Valencia; EspañaFil: Rodovalho, Sheila. Universidad Federal del Amazonas.; BrasilFil: Barros Dias, Ádila Liliane. Universidad Federal del Amazonas.; BrasilFil: Lacerda Ulysses de Carvalho, André. Pan American Health Organization; BrasilFil: Beratarrechea, Andrea Gabriela. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monteiro, Wuelton Marcelo. Universidad Federal del Amazonas.; BrasilFil: Barata Machado, Myrna. State of Amazonas Health Surveillance Foundation; BrasilFil: Fernandes da Costa, Cristiano. State of Amazonas Health Surveillance Foundation; BrasilFil: Yoshito Wada, Marcelo. No especifíca;Fil: Maximiano Faria de Almeida, Márcia Helena. No especifíca;Fil: Silva de Matos Fonseca, Rayanne. Fundação de Medicina Tropical Dr. Heitor Vieira Dourado; BrasilFil: Mota Cordeiro, Jady Shayenne. Fundação de Medicina Tropical Dr. Heitor Vieira Dourado; BrasilFil: Rodrigues Antolini, Alinne Paula. No especifíca;Fil: Nepomuceno, João Altecir. No especifíca;Fil: Fleck, Karen. Brazilian Health Regulatory Agency; BrasilFil: Simioni Gasparotto, Fernanda. Brazilian Health Regulatory Agency; BrasilFil: Lacerda, Marcus. Fundação de Medicina Tropical Dr. Heitor Vieira Dourado; BrasilFil: Rojas Cortés, Robin. Pan American Health Organization; Estados UnidosFil: Pal, Shanthi Narayan. No especifíca;Fil: Porrás, Analía I.. Pan American Health Organization; Estados UnidosFil: Ade, María de la Paz. Pan American Health Organization; Estados UnidosFil: Castro, José Luis. Pan American Health Organization; Estados Unido

Growth, sporulation and production of bioactive compounds by Bacillus subtilis R14

The physiology of B. subtilis R14 was investigated in minimal medium under excess-oxygen and oxygen-limited conditions. Growth and efficient sporulation could be achieved in excess-oxygen culture on medium with readily metabolizable carbon and nitrogen sources, which allowed high growth rate and high biomass yield. A short transition phase between the exponential growth and sporulation could be attained by formulating a medium with a well-balanced C/N ratio. Under oxygen-limitation, but in the presence of essential nutrients (i.e. excess-nutrient cultivation), B. subtilis R14 produced bioactive compounds, which showed activity against several phytopathogenic bacteria. Under anaerobic condition, the organism did not grow neither through fermentation nor anaerobic respiration. However, addition of pyruvate to the medium allowed its growth through fermentation and anaerobic respiration. The knowledge acquired in this work could be relevant both for the design of a production process as well as for the formulation of an effective commercial biocontrol product