Understanding pre-hospital disease management of fever and diarrhoea in children-Care pathways in rural Tanzania.

OBJECTIVE: Many children in sub-Saharan Africa die from infectious diseases like malaria, pneumonia, and diarrhoea that can be prevented by early diagnosis, effective and targeted treatment. This study aimed to gain insights into case management practices by parents before they present their children to hospital. METHODS: We conducted a cross-sectional study among 332 parents attending a district hospital with their under-fives symptomatic with fever and/or diarrhoea between November 2019 and July 2020 in rural Tanzania. Timely and targeted treatment was defined as seeking health care within 24 h of fever onset, and continued fluid intake in case of diarrhoea. RESULTS: The main admission diagnoses were acute respiratory infections (61.8%), malaria (25.3%), diarrhoea (18.4%) and suspected sepsis (8.1%). The majority of children (91%) received treatment prior to admission, mostly antipyretics (75.6%), local herbal medicines (26.8%), and antibiotics (17.8%)-half of them without prescription from a clinician. For diarrhoea, the use of oral rehydration solution was rare (9.0%), although perceived as easily accessible and affordable. 49.4% of the parents presented their children directly to the hospital, 23.2% went to a pharmacy/drug shop and 19.3% to a primary health facility first. Malaria symptoms began mostly 3 days before the hospital visit; only 25.4% of febrile children visited any health facility within 24 h of disease onset. Prior use of local herbal medicine (AOR = 3.2; 95% CI 1.4-7.3), visiting the pharmacy (adjusted Odds Ratio [AOR] = 3.1; 95% confidence interval [CI]: 1.0-9.8), the dispensary being the nearest health facility (AOR = 3.0; 95% CI: 1.5-6.2), and financial difficulties (AOR = 2.2; 95% CI 1.1-4.5) were associated with delayed treatment. CONCLUSION: This study suggests that antipyretics and antibiotics dispensed at pharmacies/drug shops, as well as use of local herbal medicines, delay early diagnosis and treatment, which can be life-threatening. Pharmacies/drug shops could be integrated as key focal points for sensitising community members on how to respond to paediatric illnesses and encourage the use of oral rehydration solutions.

Trained immunity in the pathogenesis of vitiligo.

Vitiligo is caused by an autoimmune reaction against melanocytes leading to melanocyte loss. The cause of vitiligo is an interaction between genetic susceptibility and environmental factors. Both the adaptive immune system-through cytotoxic CD8+ T cells and melanocyte specific antibodies-and the innate immune system are involved in these immune processes in vitiligo. While recent data stressed the importance of innate immunity in vitiligo, the question remains why vitiligo patients' immune response becomes overly activated. Could a long-term increase in innate memory function, described as trained immunity after vaccination and in other inflammatory diseases, play a role as an enhancer and continuous trigger in the pathogenesis of vitiligo? After exposure to certain stimuli, innate immune system is able to show an enhanced immunological response to a secondary trigger, indicating a memory function of the innate immune system, a concept termed trained immunity. Trained immunity is regulated by epigenetic reprogramming, including histone chemical modifications and changes in chromatin accessibility that cause sustained changes in the transcription of specific genes. In responses to an infection, trained immunity is beneficial. However, there are indications of a pathogenic role of trained immunity in inflammatory and autoimmune diseases, with monocytes presenting features of a trained phenotype, resulting in increased cytokine production, altered cell metabolism through mTOR signaling, and epigenetic modifications. This hypothesis paper focusses on vitiligo studies that have shown these indications, suggesting the involvement of trained immunity in vitiligo. Future studies focusing on metabolic and epigenetic changes in innate immune cell populations in vitiligo could help in elucidating the potential role of trained immunity in vitiligo pathogenesis.