Factors associated with occurrence of salmonellosis among children living in Mukuru slum, an urban informal settlement in Kenya.
- 作者列表："Mbae C","Mwangi M","Gitau N","Irungu T","Muendo F","Wakio Z","Wambui R","Kavai S","Onsare R","Wairimu C","Ngetich R","Njeru F","Van Puyvelde S","Clemens J","Dougan G","Kariuki S
BACKGROUND:In Kenya, typhoid fever and invasive non-typhoidal salmonellosis present a huge burden of disease, especially in poor-resource settings where clean water supply and sanitation conditions are inadequate. The epidemiology of both diseases is poorly understood in terms of severity and risk factors. The aim of the study was to determine the disease burden and spatial distribution of salmonellosis, as well as socioeconomic and environmental risk factors for these infections, in a large informal settlement near the city of Nairobi, from 2013 to 2017. METHODS:Initially, a house-to-house baseline census of 150,000 population in Mukuru informal settlement was carried out and relevant socioeconomic, demographic, and healthcare utilization information was collected using structured questionnaires. Salmonella bacteria were cultured from the blood and faeces of children < 16 years of age who reported at three outpatient facilities with fever alone or fever and diarrhea. Tests of association between specific Salmonella serotypes and risk factors were conducted using Pearson Chi-Square (χ2) test. RESULTS:A total of 16,236 children were recruited into the study. The prevalence of bloodstream infections by Non-Typhoidal Salmonella (NTS), consisting of Salmonella Typhimurium/ Enteriditis, was 1.3%; Salmonella Typhi was 1.4%, and this was highest among children < 16 years of age. Occurrence of Salmonella Typhimurium/ Enteriditis was not significantly associated with rearing any domestic animals. Rearing chicken was significantly associated with high prevalence of S. Typhi (2.1%; p = 0.011). The proportion of children infected with Salmonella Typhimurium/ Enteriditis was significantly higher in households that used water pots as water storage containers compared to using water directly from the tap (0.6%). Use of pit latrines and open defecation were significant risk factors for S. Typhi infection (1.6%; p = 0.048). The proportion of Salmonella Typhimurium/ Enteriditis among children eating street food 4 or more times per week was higher compared to 1 to 2 times/week on average (1.1%; p = 0.032). CONCLUSION:Typhoidal and NTS are important causes of illness in children in Mukuru informal settlement, especially among children less than 16 years of age. Improving Water, Sanitation and Hygiene (WASH) including boiling water, breastfeeding, hand washing practices, and avoiding animal contact in domestic settings could contribute to reducing the risk of transmission of Salmonella disease from contaminated environments.
背景: 在肯尼亚，伤寒发热和侵袭性非 typhoidal 沙门氏菌病巨大的疾病负担，尤其是在贫穷的资源环境清洁供水和卫生条件不足.两种疾病流行病学在严重程度和危险因素方面知之甚少。这项研究的目的是确定沙门氏菌病的疾病负担和空间分布，以及这些感染的社会经济和环境危险因素，在内罗毕市附近的一个大型非正式定居点,从 2013 年到 2017 年。 方法: 最初，对 Mukuru 非正式定居点的 150,000 人进行了逐户基线普查，并使用结构化问卷收集相关的社会经济、人口和医疗保健利用信息。从 3 个门诊机构报告的仅发热或发热和腹泻的 <16 岁儿童的血液和粪便中培养出沙门氏菌。采用 Pearson 卡方 (χ 2) 检验对特定沙门菌血清型与危险因素的相关性进行检测。 结果: 共有 16,236 名儿童被招募到研究中。非伤寒沙门菌 (NTS)，包括鼠伤寒沙门菌/肠炎的血流感染率为 1.3%; 伤寒沙门菌为 1.4%,这在 <16 岁的儿童中最高。鼠伤寒沙门氏菌/肠炎的发生与饲养任何家畜无显著相关性。饲养鸡与 S 的高患病率显著相关。伤寒 (2.1%; P = 0.011)。使用水罐作为储水容器的家庭中感染鼠伤寒沙门氏菌/肠炎的儿童比例显著高于直接使用水龙头的水 (0.6%)。使用坑式厕所和露天排便是 S 的显著危险因素。伤寒感染 (1.6%; P = 0.048)。儿童每周吃 4 次或 4 次以上街头食物的鼠伤寒沙门氏菌/肠炎比例高于平均 1 ~ 2 次/周 (1.1%; P = 0.032)。 结论: 伤寒和 NTS 是 Mukuru 非正式聚居区儿童发病的重要原因，尤其是 16 岁以下儿童。改善水、环境卫生和个人卫生 (WASH)，包括沸水、母乳喂养、洗手做法,在家庭环境中避免动物接触可能有助于降低沙门氏菌病从污染环境中传播的风险。
METHODS:Shigella species cause diarrheal disease globally. Shigellosis is typically characterized by bloody stools and colitis with mucosal damage and is the leading bacterial cause of diarrheal death worldwide. After the pathogen is orally ingested, it invades and replicates within the colonic epithelium through mechanisms that rely on its type III secretion system (T3SS). Currently, oral infection-based small animal models to study the pathogenesis of shigellosis are lacking. Here, we found that orogastric inoculation of infant rabbits with Shigella flexneri resulted in diarrhea and colonic pathology resembling that found in human shigellosis. Fasting animals prior to S. flexneri inoculation increased the frequency of disease. The pathogen colonized the colon, where both luminal and intraepithelial foci were observed. The intraepithelial foci likely arise through S. flexneri spreading from cell to cell. Robust S. flexneri intestinal colonization, invasion of the colonic epithelium, and epithelial sloughing all required the T3SS as well as IcsA, a factor required for bacterial spreading and adhesion in vitro Expression of the proinflammatory chemokine interleukin 8 (IL-8), detected with in situ mRNA labeling, was higher in animals infected with wild-type S. flexneri versus mutant strains deficient in icsA or T3SS, suggesting that epithelial invasion promotes expression of this chemokine. Collectively, our findings suggest that oral infection of infant rabbits offers a useful experimental model for studies of the pathogenesis of shigellosis and for testing of new therapeutics.IMPORTANCEShigella species are the leading bacterial cause of diarrheal death globally. The pathogen causes bacillary dysentery, a bloody diarrheal disease characterized by damage to the colonic mucosa and is usually spread through the fecal-oral route. Small animal models of shigellosis that rely on the oral route of infection are lacking. Here, we found that orogastric inoculation of infant rabbits with S. flexneri led to a diarrheal disease and colonic pathology reminiscent of human shigellosis. Diarrhea, intestinal colonization, and pathology in this model were dependent on the S. flexneri type III secretion system and IcsA, canonical Shigella virulence factors. Thus, oral infection of infant rabbits offers a feasible model to study the pathogenesis of shigellosis and to develop and test new therapeutics.
METHODS:PURPOSE:To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. METHODS:Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8 weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50 Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. RESULTS:Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9 Gy) and those that decreased their functional burden (35 Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. CONCLUSIONS:Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15 Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.
METHODS:NLRP3 inflammasome may serve as a potential target for the development of novel therapeutics for inflammatory bowel diseases. In this study, we found that Libertellenone M (Lib M), a secondary metabolite from the endophytic fungus Phomopsis sp. S12, has anti-inflammatory potential both in vitro and in vivo. Lib M selectively inhibited the expression of proinflammatory cytokine IL-1β and IL-18 in LPS-activated macrophages. The cleavage of pro-caspase 1 was remarkably reduced by Lib M in macrophages stimulated with three NLRP3 inflammasome activators. Administering Lib M attenuated dextran sulfate sodium-induced experimental acute colitis in mice and significantly reduced the production of these cytokines and cleaved caspase 1 in colon tissues. Apart from inhibition of NLRP3 inflammasome assembly, Lib M also suppressed NF-κB nuclear translocation in macrophages. Taken together, these findings suggest that Lib M-mediated inhibition of NLRP3 inflammasome activation could protect against colitis-like inflammatory diseases, and that this compound derived from a plant-associated fungus might inspire the exploration of novel immunosuppressive agents.