Objective: To examine the frequency and profile of spontaneous reports of adverse drug reactions (ADRs) sent to Ethiopia’s pharmacovigilance (PV) database system. Methods: The descriptive and retrospective study analysed spontaneous ADR complaints reported to the PV database by healthcare professionals between 2013 and 2018. Spontaneous ADR reports that reached the PV center and met the minimum reporting criteria were identified and assessed in terms of reporting rate, patient characteristics, type of ADRs, suspected drugs, report sources, and reporters’ profession. Results: A total of 657 spontaneous ADR reports were filed to the PV center between 2013 and 2018. During the study period, the reporting pattern of ADRs changed dramatically. The number of reports increased from 2013 (n=12) and peaked in 2015 (n=205), and then declined from 2016 to 2018 (n=144, 142 and 65 in 2016, 2017 and 2018, respectively). Females had a higher percentage of reported cases (56.3%) than males (43.7%). The highest number of ADRs was reported in the age categories of 15-64 years (475, 72.3%), followed by 0-14 years (154, 23.4%), and 65 years and above (21, 3.2%). Pharmacists reported the majority of ADRs (81.7%), followed by health officers (7.2%), nurses (5.8%), and physicians (5.2%). Skin and subcutaneous tissue abnormalities were the most commonly reported ADRs. The anatomical therapeutic chemicals code class “anti-infective for systemic use” was the most usually suspected medication. Trimethoprim with sulfamethoxazole as a combination ADRs was the most commonly reported drug that cause ADRs (14.2%). Conclusions: The number of ADRs reported in Ethiopia was small and unpredictable compared to developed countries, indicating the performance of PV system and level of awareness of health care professionals towards ADR reporting was not satisfactory. In order to increase the frequency of spontaneous reports, more efficient PV methods and public policies must be implemented.

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Objective: To identify the residue determinants of the serospecificity and sero-cross-reactivity of dengue virus (DENV) envelope protein domain 3 (ED3), which contains two major putative epitopes of DENV. Methods: We constructed ED3 from DENV3 (3ED3) and DENV4 (4ED3), and six epitope-grafted variants, where we transferred epitope 1 (L³⁰⁴I, K³⁰⁵D, V³⁰⁹M, and S³¹⁰A) and/or epitope 2 (D³⁸³N, K³⁸⁴S, K³⁸⁷T, and N³⁸⁹H) of 4ED3 onto 3ED3 and vice-versa. Swiss albino mice aged 3-4 weeks were immunized against wildtype and epitope-grafted ED3 variants and anti-ED3 IgG antibody responses were determined using ELISA. Results: Mouse immunization using 3ED3 and 4ED3 generated serotype-specific antisera, as expected. Similarly, most epitope- grafted ED3s produced antisera serospecific to the template ED3 with little or no cross-recognition of ED3 of the serotype from which the epitopes were taken. These indicated that a mere grafting of the epitope was not sufficient to transfer serospecificity, contrary to our expectations. However, one epitope-grafted ED3 mutant, where epitope 1 of 3ED3 was grafted onto 4ED3 (4ED3^epi1), generated antisera that was serospecific to both 4ED3 and 3ED3. Conclusions: The 4ED3^epi1 is a chimeric ED3 that produces antisera possessing serospecificity to both 3ED3 and 4ED3 onto a common 4ED3 scaffold. The 4ED3^epi1, therefore, provides a unique tool for analyzing serospecificity and sero-cross-reactivity in dengue. We believe that chimeric ED3 may provide a template for future recombinant ED3 possessing serospecificity of multiple DENVs onto a single scaffold and may pave a way developing tri-and/or tetravalent anti-DENV antisera.

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Objective: To evaluate 11 Cuban native Bacillus (B.) thuringiensis isolates in order to select one with the best larvicidal activity against Aedes (Ae.) aegypti and low cytotoxicity. Methods: The cry and cyt genes of the isolates (A21, A51, L95, L910, M29, R84, R85, R87, R89, U81 and X48) were amplified by PCR. The influence of organic matter and NaCl on the larvicidal activity was tested by bioassays. Cytotoxicity was assayed on peritoneal macrophages of BALB/c mice. Results: The cyt1 (Aa, Ab, Ba), cyt2, cry4aA, cry4Ba, cry11 (Aa, Ba, Bb) and cry10 genes were identified in all native Cuban isolates. The larvicidal activity (LC₉₀) of seven isolates was affected by the presence of organic matter in the water, while A21, A51, L910, R84, U81 and X48 had better LC₅₀, LC₉₀, LC₉₅ than the 266/2 9-VII-98 control strain. The LC₅₀ of two isolates was affected by the presence of NaCl and A21, A51, R85 isolate had better larvicidal activity than the 266/2 9-VII-98 control strain. In terms of toxicity against macrophages, the extracts of nine isolates were less cytotoxic than the control strains. Conclusions: Native isolate A21 had the main virulence factors against Ae. aegypti larvae, displayed a good larvicidal activity in presence of different factors related with Ae. aegypti breeding sites, and had low citotoxicity against macrophages. These results can contribute to the improvement of existing biological control strategies and the development of new biolarvicides.

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Rationale: Human myiasis is the invasion of tissue or organs by fly larvae. This could be obligatory, facultative, or accidental. Patient concerns: A 4-year-old Saudi boy complained of fever over the past three days with multiple inflamed painful dermal furuncles and worms-like discharge. Diagnosis: Furuncular obligatory myiasis caused by Wohlfahrtia magnifica. Interventions: Maggots were removed for identification. The wounds were cleaned with antiseptic dressings. Topical and oral antibiotics were applied. Outcomes: Seven days later, the wounds completely healed. Lessons: Although several reports correlated human myiasis with old age, low health status, mental retardation, and low socioeconomic status, but the patient in our case was a healthy child from a family with good socioeconomic status, good hygiene, no history of diseases or mental disability, but traveled to a village where the climate is suitable for fly breeding.

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Objective: To investigate the morphological structure of ovarian follicular cells and biochemical parameters of both ovaries and fat bodies (sites of vitellogenesis) from Rhodnius (R.) prolixus infected with Trypanosoma (T.) rangeli. Methods: Adult virgin females of R. prolixus were fed upon a membrane apparatus containing heat-inactivated citrated rabbit blood and a suspension of T. rangeli epimastigotes (Macias strain). Females from the control group and all the males received parasite- free blood. Transmission electron microscopy was used to reveal the morphological aspects of ovarian follicle cells in both control and parasite-infected groups. Protein profile, proteolytic activities and Western blotting analyses were performed in either ovary or fat body samples of control and parasite-infected groups. Results: According to the ultrastructural data, T. rangeli infection elicited a degeneration process in the ovarian follicular cells of R. prolixus. Proteolytic assays indicated a reduction in the activity of aspartic peptidases in the ovary and fat body from parasite-infected group, while a significant increase in the cysteine peptidase activity was measured in both insect organs. Additionally, immunoblotting revealed that vitellogenin was overexpressed in the ovary of parasite-infected insects. Conclusions: T. rangeli infection seems to elicit an early programmed cell death in the ovarian follicle cells as well as induces the modulation on the activities of different peptidase classes in either ovaries or fat bodies and the overexpression of the vitellogenin in the ovary of R. prolixus.

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