ABSTRACT
Shigella species account for the second-leading cause of deaths due to diarrheal diseases among children of less than 5 years of age. The emergence of multi-drug-resistant Shigella isolates and the lack of availability of Shigella vaccines have led to the pertinence in the efforts made for the development of new therapeutic strategies against shigellosis. Consequently, designing small-interfering RNA (siRNA) candidates against such infectious agents represents a novel approach to propose new therapeutic candidates to curb the rampant rise of anti-microbial resistance in such pathogens. In this study, we analyzed 264 conserved sequences from 15 different conserved virulence genes of Shigella sp., through extensive rational validation using a plethora of first-generation and second-generation computational algorithms for siRNA designing. Fifty-eight siRNA candidates were obtained by using the first-generation algorithms, out of which only 38 siRNA candidates complied with the second-generation rules of siRNA designing. Further computational validation showed that 16 siRNA candidates were found to have a substantial functional efficiency, out of which 11 siRNA candidates were found to be non-immunogenic. Finally, three siRNA candidates exhibited a sterically feasible three-dimensional structure as exhibited by parameters of nucleic acid geometry such as: the probability of wrong sugar puckers, bad backbone confirmations, bad bonds, and bad angles being within the accepted threshold for stable tertiary structure. Although the findings of our study require further wet-lab validation and optimization for therapeutic use in the treatment of shigellosis, the computationally validated siRNA candidates are expected to suppress the expression of the virulence genes, namely: IpgD (siRNA 9) and OspB (siRNA 15 and siRNA 17) and thus act as a prospective tool in the RNA interference (RNAi) pathway. However, the findings of our study require further wet-lab validation and optimization for regular therapeutic use for treatment of shigellosis.
Subject(s)
Dysentery, Bacillary , Shigella , Child , Diarrhea/drug therapy , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/genetics , Humans , RNA Interference , RNA, Small Interfering/metabolism , Shigella/geneticsABSTRACT
OBJECTIVE: To compare the health and nutrition of children younger than 5 years admitted to hospital during and before the coronavirus disease 2019 (COVID-19) pandemic in Bangladesh. METHODS: We collected data from hospital records of children 0-59 months admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh in March 2020-February 2021 (COVID-19 period; n = 2552) and March 2019-February 2020 (pre-COVID-19 period; n = 6738). Data collected included sociodemographic, anthropometric, clinical and biochemical characteristics. We compared these data for child admissions in the COVID-19 and pre-COVID-19 periods, including infants 0-11 months born during and before the pandemic and admitted to hospital. FINDINGS: Admissions of children as a percentage of total admissions were lower in March 2020 (2.47%; 63/2552) than March 2019 (8.30%; 559/6738), but increased to 20.61% (526/2552) in February 2021, three times greater than in the pre-COVID-19 period (6.69%; 451/6738). Children admitted during the COVID-19 period were significantly more likely to have dehydration, severe sepsis or septic shock, convulsions, hypernatraemia and raised creatinine than children admitted before the pandemic (P < 0.05). In infants < 6 months and those born during the pandemic, stunting and wasting were significantly higher than in infants in the pre-COVID-19 period (P < 0.05). The risk of death was higher in infants < 6 months during the pandemic (odds ratio: 1.66; 95% confidence interval: 0.95-2.92). CONCLUSION: During the pandemic, children presented with more severe illness and poorer nutrition. Efforts are needed to reduce the adverse effects of the pandemic on the health and well-being of children.