Acceptability of short message service (SMS) as a tool for malaria treatment adherence in the Brazilian Amazon: a qualitative study

Background: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. Methods: This cross-sectional study, with in-depth telephone interviews, analyzed participants’ perceptions of short message service (SMS) in adherence to treatment. Results: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. Conclusions: SMS could assist patients in adhering to prescribed antimalarials.Fil: Rodovalho, Sheila. Universidade do Estado do Amazonas; BrasilFil: Dias, Ádila Liliane Barros. Universidade do Estado do Amazonas; BrasilFil: Paz Ade, Maria. Pan American Health Organization; ArgentinaFil: Saint Gerons, Diego Macias. Pan American Health Organization; ArgentinaFil: Castro, Jose Luis. Pan American Health Organization; ArgentinaFil: Beratarrechea, Andrea Gabriela. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Murta, Felipe Leão Gomes. Universidade do Estado do Amazonas; BrasilFil: dos Santos, Alicia Cacau Patrine. Universidade do Estado do Amazonas; BrasilFil: Marques, Leonardo Lincoln Gomes. Universidade do Estado do Amazonas; BrasilFil: Sampaio, Vanderson Souza. Universidade do Estado do Amazonas; BrasilFil: Baia da Silva, Djane Clarys. Fundación Oswaldo Cruz; Brasil. Universidade do Estado do Amazonas; BrasilFil: Monteiro, Wuelton Marcelo. Universidade do Estado do Amazonas; Brasi

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

Early and Late Pathogenic Events of Newborn Mice Encephalitis Experimentally Induced by Itacaiunas and Curionópolis Bracorhabdoviruses Infection

In previous reports we proposed a new genus for Rhabdoviridae and described neurotropic preference and gross neuropathology in newborn albino Swiss mice after Curionopolis and Itacaiunas infections. In the present report a time-course study of experimental encephalitis induced by Itacaiunas and Curionopolis virus was conducted both in vivo and in vitro to investigate cellular targets and the sequence of neuroinvasion. We also investigate, after intranasal inoculation, clinical signs, histopathology and apoptosis in correlation with viral immunolabeling at different time points. Curionopolis and Itacaiunas viral antigens were first detected in the parenchyma of olfactory pathways at 2 and 3 days post-inoculation (dpi) and the first clinical signs were observed at 4 and 8 dpi, respectively. After Curionopolis infection, the mortality rate was 100% between 5 and 6 dpi, and 35% between 8 and 15 dpi after Itacaiunas infection. We identified CNS mice cell types both in vivo and in vitro and the temporal sequence of neuroanatomical olfactory areas infected by Itacaiunas and Curionopolis virus. Distinct virulences were reflected in the neuropathological changes including TUNEL immunolabeling and cytopathic effects, more intense and precocious after intracerebral or in vitro inoculations of Curionopolis than after Itacaiunas virus. In vitro studies revealed neuronal but not astrocyte or microglial cytopathic effects at 2 dpi, with monolayer destruction occurring at 5 and 7 dpi with Curionopolis and Itacaiunas virus, respectively. Ultrastructural changes included virus budding associated with interstitial and perivascular edema, endothelial hypertrophy, a reduced and/or collapsed small vessel luminal area, thickening of the capillary basement membrane, and presence of phagocytosed apoptotic bodies. Glial cells with viral budding similar to oligodendrocytes were infected with Itacaiunas virus but not with Curionopolis virus. Thus, Curionopolis and Itacaiunas viruses share many pathological and clinical features present in other rhabdoviruses but distinct virulence and glial targets in newborn albino Swiss mice brain

Transmission electron photomicrographs of ultrathin sections obtained from primary neuronal cultures.

<p>Control cultures of normal cells (A) and after Itacaiunas (B) and Curionopolis (C, D) infection at 4 and 5 days post-inoculation, respectively. Apoptotic cells (C) and virus budding (rectangle and arrows) (C, D) after Curionopolis infection. Itacaiunas virus particles (arrows) in culture at 5 days post-inoculation (B). N: nucleus; AN: apoptotic nucleus.</p

Transmission electron photomicrographs of ultrathin sections obtained from control (A) and mouse brain infected intracerebrally with Curionopolis for 36 (B,C), 60 (D) and 96 h (E), and with Itacaiunas for 24 (F), 60 (G), 72 (H), 96 (I) and 108 h (J).

<p>Normal tissue with intact neuronal soma and appendages (A); viral particles (arrow), interstitial edema (stars) and cellular rarefaction (lozenge) are seen 36 h post-inoculation (p.i.) (B, C); necrotic cells were observed at 60 h p.i. (D); intense perivascular edema (stars), hyperplastic endotheliocytes and reduced vessel luminal area (E); well-preserved brain parenchyma and vessels at 24 h p.i. (F); viral particles, endotheliocyte hyperplasia, and mild interstitial edema (stars) at 60 h p.i. (G); membrane viral budding in rich polyribosomes oligodendrocyte-like cell at 72 h p.i. (H); brain parenchyma at 96 h p.i. presenting a large number of viral particles (I); apoptotic features were more marked at 108 h p.i. (J). AC = apoptotic cell, M = mitochondria, OL = oligodendrocyte, EC = endothelial cells, VL = vascular lumen, N = cell nucleus, NC = necrotic cells.</p

Combined interferential contrast and fluorescent photomicrographs of positive and negative controls (A, B) and Curionopolis- (C, D) or Itacaiunas (E,F)-infected neurons after TUNEL immunolabeling.

<p>Apoptotic nuclei (arrows) are observed in control cultures exposed to UV light (A) and after Curionopolis (D) and Itacaiunas (F) virus inoculation at 4 and 5 days post-inoculation, respectively. Negative control cultures (B) and infected cultures at 1 day post-inoculation (C, E) present few stained nuclei.</p

Bright-field (A, D, F) and interferential contrast (B, C, E, G) photomicrographs of Itacaiunas virus-infected mouse brain at 4 (A–C), 6 (D, E) and 8 (F, G) days post-inoculation.

<p>Low (A) and medium (B) power photomicrographs of the olfactory neuronal group (smaller rectangle). Details of immunolabeled neurons of the frontal cortex (C) (arrows and arrowheads). Low (D) (rectangle) and medium (E) power photomicrographs of a group (arrows) of hippocampal neurons showing low viral antigen condensation (arrowhead). TUNEL-positive midbrain neurons of infected brain sections (TUNEL POD procedure) 12 days after inoculation with Itacaiunas virus (F, G). The arrows indicate immunostained neuronal nuclei.</p

Phase-contrast (A, C, E) and fluorescence photomicrographs (B, D, F) of primary neuronal cultures to illustrate normal noninfected cell morphology (A, B) and cytopathic effects 3 days after inoculation of Curionopolis virus (C, D) and 4 days after inoculation of Itacaiunas virus (E, F).

<p>Arrows point to neurite fragmentation and circles indicate refringent points probably corresponding to apoptotic nuclei (A, C). Arrows and arrowheads indicate infected soma and dendrites, respectively (D, F). Neurons were stained by indirect immunofluorescence for anti-neurofilament antibodies. Secondary antibodies were conjugated with fluorescein isothiocyanate.</p

Bright-field (A, G) and interferential contrast (B–F, H) photomicrographs of infected mouse brain sections illustrating viral antigen-immunolabeled cells 2 (A–D) and 4 (E–G) days after inoculation with Curionopolis virus and TUNEL immunolabeling at 6 days (G, H).

<p>Low (square) (A), medium (B) and high (C) power photomicrographs of labeled olfactory bulb neurons. High power images illustrating isolated neurons of the olfactory bulb with immunolabeled soma (arrow) and other neuronal appendages (arrowheads) (C); immunolabeled meningeal cells are also indicated (arrow) (D); cortical (E) and thalamic (F) neurons immunostained with viral antigens distributed in the cell appendages. TUNEL-positive neurons in infected brain sections (TUNEL POD procedure) 6 days after inoculation with Curionopolis virus into the ventral olfactory bulb (G, H). The arrows indicate immunostained neuronal nuclei.</p