Introduction Globally, a large number of under-five deaths have occurred from preventable and treatable common childhood illnesses. Therefore, early identification of general danger signs of common childhood illnesses and adhering to appropriate treatment helps to reduce morbidity and mortality. This study aimed to assess the knowledge of mothers and associated factors on general danger signs of common childhood illnesses of under-five children in Central Tigrai, Ethiopia. Methods A community-based cross-sectional study design was employed from February to March 2017. A total of 416 study participants were finally enrolled in the study using simple random sampling technique. A pretested and structured interviewer-based questionnaire was used. Data were entered, coded and analysed using SPSS 22.0. Multivariable logistic regression was used to control the effect of confounders. Results In this study, 44.7% of the mothers had good knowledge of the general danger signs of common childhood illnesses. Mothers' educational status (AOR=1.93, 95%CI=1.09-3.44, p=0.025), occupation of mothers (AOR=5.94, 95%CI=3.17-11.12, p<0.001), childbirth order (AOR=1.85, 95%CI=1.00-3.40, p=0.005) and source of information (AOR=2.19, 95%CI=1.23-3.87, p=0.007) were significantly associated with knowledge of mothers on general danger signs of common childhood illnesses. Conclusions Maternal knowledge of general danger signs of common childhood illnesses was low. Therefore, intervention modalities focusing on improving the educational level, behavioural change communication activities, and access of mothers to health visits are needed.
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