Optimized rat models better mimic patients with irinotecan-induced severe diarrhea.

Irinotecan-induced severe diarrhea (IISD) not only limits irinotecan's application but also significantly affects patients' quality of life. However, existing animal models often inadequately represent the dynamics of IISD development, progression, and resolution across multiple chemotherapy cycles, yielding non-reproducible and highly variable response with limited clinical translation. Our studies aim to establish a reproducible and validated IISD model that better mimics the pathophysiology progression observed in patients, enhancing translational potential. We investigated the impact of dosing regimens (including different dose, infusion time, and two cycles of irinotecan administration), sex, age, tumor-bearing conditions, and irinotecan formulation on the IISD incidence and severity in mice and rats. Lastly, we investigated above factors' impact on pharmacokinetics of irinotecan, intestinal injury, and carboxylesterase activities. In summary, we successfully established a standard model establishment procedure for an optimized IISD model with highly reproducible severe diarrhea incidence rate (100%) and a low mortality rate (11%) in F344 rats. Additionally, the rats tolerated at least two cycles of irinotecan chemotherapy treatment. In contrast, the mouse model exhibited suboptimal IISD incidence rates (60%) and an extremely high mortality rate (100%). Notably, dosing regimen, age and tumor-bearing conditions of animals emerged as critical factors in IISD model establishment. In conclusion, our rat IISD model proves superior in mimicking pathophysiology progression and characteristics of IISD in patients, which stands as an effective tool for mechanism and efficacy studies in future chemotherapy-induced gut toxicity research.

Genomic characterization of the rotavirus G3P[8] strain in vaccinated children, reveals possible reassortment events between human and animal strains in Manhiça District, Mozambique.

Mozambique introduced the rotavirus vaccine (Rotarix®; GlaxoSmithKline Biologicals, Rixensart, Belgium) in 2015, and since then, the Centro de Investigação em Saúde de Manhiça has been monitoring its impact on rotavirus-associated diarrhea and the trend of circulating strains, where G3P[8] was reported as the predominant strain after the vaccine introduction. Genotype G3 is among the most commonly detected Rotavirus strains in humans and animals, and herein, we report on the whole genome constellation of G3P[8] detected in two children (aged 18 months old) hospitalized with moderate-to-severe diarrhea at the Manhiça District Hospital. The two strains had a typical Wa-like genome constellation (I1-R1-C1-M1-A1-N1-T1-E1-H1) and shared 100% nucleotide (nt) and amino acid (aa) identities in 10 gene segments, except for VP6. Phylogenetic analysis demonstrated that genome segments encoding VP7, VP6, VP1, NSP3, and NSP4 of the two strains clustered most closely with porcine, bovine, and equine strains with identities ranging from 86.9-99.9% nt and 97.2-100% aa. Moreover, they consistently formed distinct clusters with some G1P[8], G3P[8], G9P[8], G12P[6], and G12P[8] strains circulating from 2012 to 2019 in Africa (Mozambique, Kenya, Rwanda, and Malawi) and Asia (Japan, China, and India) in genome segments encoding six proteins (VP2, VP3, NSP1-NSP2, NSP5/6). The identification of segments exhibiting the closest relationships with animal strains shows significant diversity of rotavirus and suggests the possible occurrence of reassortment events between human and animal strains. This demonstrates the importance of applying next-generation sequencing to monitor and understand the evolutionary changes of strains and evaluate the impact of vaccines on strain diversity.

A Rare Case of Severe Diarrhea: Gastrocolic Fistula Caused by Migration of Percutaneous Endoscopic Gastrostomy Tube.

Gastrocolic fistula is a rare complication of the percutaneous endoscopic gastrostomy (PEG) placement procedure. This complication occurs due to penetration of interposed colon when a PEG tube is placed into the stomach. It can go unrecognized, becoming evident only when a tube replacement is performed or tube migration occurs. We report a case of severe, intractable diarrhea occurring about one month after the PEG procedure in a patient with severe traumatic brain injury. We present our case and discuss its significance with the aim of raising clinicians' awareness of this rare condition.

Anthropometric Indices of Giardia-Infected Under-Five Children Presenting with Moderate-to-Severe Diarrhea and Their Healthy Community Controls: Data from the Global Enteric Multicenter Study.

Among all intestinal parasitosis, giardiasis has been reported to be associated with delayed growth in malnourished children under 5 living in low- and middle-income countries. Relevant data on the nutritional status of children aged 0-59 months presenting with moderate-to-severe diarrhea (MSD) and giardia infection were collected from sentinel health facilities of the Global Enteric Multicenter Study's (GEMS) seven field settings, placed in diverse countries of Sub-Saharan Africa and South Asia between, December 2007 and February 2011. Then, this study analyzed a robust dataset of study participants (n = 22,569). Children having giardiasis with MSD constituted as cases (n = 1786), and those without MSD constituted as controls (n = 3470). Among the seven field sites, symptomatic giardiasis was 15% and 22% in Asian and African sites, respectively, whereas asymptomatic giardia infection (healthy without MSD) in Asian and African sites was 21.7% and 30.7%, respectively. Wasting and underweight were more frequently associated and stunting less often associated with symptomatic giardiasis (for all, p < 0.001). Symptomatic giardiasis had a significant association with worsening of nutritional status in under-five children. Improved socio-economic profile along with proper sanitation and hygienic practices are imperative to enhance child nutritional status, particularly in resource limited settings.

Characteristics of Salmonella Recovered From Stools of Children Enrolled in the Global Enteric Multicenter Study.

BACKGROUND: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of nontyphoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. METHODS: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole-genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk-diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing, and whole-genome sequencing was performed to assess the phylogeny of ST313. RESULTS: Of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java, and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar among both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone, but African isolates were susceptible to these antibiotics. CONCLUSIONS: Our data confirm that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multidrug-resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa.

Application value of self-made perianal skin nursing strategy of device in the severe diarrhea or fecal incontinence / 中国实用护理杂志

Objective@#To explore the application effect of self-made nursing strategy of device in the severe diarrhea or fecal incontinence.@*Methods@#A total of 60 patients with severe diarrhea or fecal incontinence were randomly divided into study group and control group according to the order of admission, each with 30 patients. The control group received traditional nursing strategy, while the study group was applied self-made perianal skin nursing strategy of device. The change of perianal skin injury, nursing workload and patients′ pain index of two groups were compared.@*Results@#The study group perianal skin injury, nursing workload and patients pain index were (0.40±0.11) points, (2.14±0.22) times/day, (1.36±0.40) points, which were better than (0.84±0.14) points, (3.58±0.29) times/day, (3.28±0.60) points in the control group (t=2.475, 3.934, 2.652, P<0.05).@*Conclusion@#self-made perianal skin nursing strategy of device could reduce the incidence of perianal skin injury, liberation of nursing work, reduce the pain of patients. Which is worthy of clinical application for its convenience.

Risk factors for death among children 0-59 months of age with moderate-to-severe diarrhea in Manhiça district, southern Mozambique.

BACKGROUND: Despite major improvements in child survival rates, the number of deaths due to diarrhea remains unacceptably high. We aimed to describe diarrhea-associated mortality and evaluate risk factors for death among Mozambican children with moderate-to-severe diarrhea (MSD). METHODS: Between December 2007 and November 2012, children under-five with MSD were enrolled in Manhiça district, as part of the Global Enteric Multicenter study (GEMS). Clinical, epidemiological, and socio-demographic characteristics were collected. Anthropometric measurements were performed and stool samples collected upon recruitment. A follow-up visit ~ 60 days post-enrolment was conducted and verbal autopsies performed in all death cases. RESULTS: Of the 916 MSD-cases analyzed; 90% (821/916) completed 60 days follow-up and 69 patients died. The case fatality rate at follow-up was 8% (69/821), and the mortality rate 10.2 (95%CI: 7.75-13.59) deaths per 1000 persons-week at risk. Nearly half of the deaths 48% (33/69) among study participants clustered within 2 weeks of the onset of diarrhea. Typical enteropathogenic Escherichia coli (typical EPEC) and Cryptosporidium were the two pathogens associated to an increased risk of death in the univariate analysis with (HR = 4.16, p = 0.0461) and (H = 2.84, p = 0.0001) respectively. Conversely, Rotavirus infection was associated to a decreased risk of death (HR = 0.52, p = 0.0198). According to the multivariate analysis, risk factors for death included co-morbidities such as malnutrition (HR = 4.13, p <  0.0001), pneumonia/lower respiratory infection (HR = 3.51, p <  0.0001) or invasive bacterial disease (IBD) (HR = 6.80, p = 0.0009), presenting on arrival with lethargy or overt unconsciousness (HR = 1.73, p = 0.0302) or wrinkled skin (HR = 1.71, p = 0.0393), and cryptosporidium infection (HR = 2.14, p = 0.0038). When restricting the analysis to those with available HIV results (n = 191, 22% of the total study sample), HIV was shown to be a significant risk factor for death (HR = 5.05, p = 0.0009). Verbal autopsies were conducted in 100% of study deaths, and highlighted diarrhea as the main underlying cause of death 39%, (27/69); followed by HIV/AIDS related deaths 29.0% (20/69) and sepsis 11.6% (8/69). CONCLUSION: Preventive strategies targeting Cryptosporidium, malnutrition and early identification and treatment of associated co-morbidities could contribute to the prevention of the majority of diarrhea associated deaths in Mozambican children.

Risk factors for death among children 0-59 months of age with moderate-to-severe diarrhea in Manhiça district, southern Mozambique

In spite of very significant decreasing trends in the last three decades, childhood mortality remains unacceptably high globally, with 5.6 million children dying every year before reaching their 5th birthday, the majority of which in low and middle-income countries (LMIC) [1]. Diarrheal diseases still represent a major cause of morbidity and mortality in childhood, and are believed to account for 499,000­526,000 annual child deaths, nearly 9% of all under five global mortality [2, 3], in spite of the good intake of life-saving interventions such as oral rehydration solution (ORS) [3] and the rotavirus vaccine [4]. Deaths in sub-Saharan Africa and Southeast Asia account for ~ 78% of deaths due to diarrhea worldwide [5, 6], underscoring the inequities related to this particular syndrome. The Global Enteric Multi-center Study (GEMS) reported that most episodes of moderate-to-severe diarrhea (MSD) among children under 5 years old were primarily due to four pathogens: Rotavirus, Cryptosporidium, Enterotoxigenic Escherichia coli (ST-ETEC), and Shigella [7]. The risk of dying from diarrheal disease was reported to be higher among children younger than 2 years of age, albeit with relatively different rates from one region to another [7]. The advent of the HIV/AIDS pandemic has also changed the incidence [8], clinical presentation and outcome of diarrheal diseases, as the immunosuppression derived from the infection favors a higher incidence of gastrointestinal infections, not only from "classical" diarrhea pathogens, but also from more aggressive opportunistic infections, typical of the immunocompromised host. This has resulted in significant changes in the last decades in the spectrum, clinical presentation, duration and prognosis of diarrheal episodes in those countries where HIV is highly prevalent [9, 10].

Cryptosporidium Infection: Epidemiology, Pathogenesis, and Differential Diagnosis.

Cryptosporidium is a protozoan that infects a wide variety of vertebrates, including humans, causing acute gastroenteritis. The disease manifests with abdominal pain and diarrhea similar to that of choleric infection. In the immunocompromised hosts, the parasite causes prolonged infections that can also be fatal. For this reason, cryptosporidiosis is considered one of riskiest opportunistic infections for patients with acquired immunodeficiency syndrome. The best way to control the infection in these patients is setting up sensitive and specific diagnostic tests for epidemiological surveillance and morbidity reduction. Here, we summarized the general aspects of Cryptosporidium infection focusing on available diagnostic tools used for the diagnosis of cryptosporidiosis. Molecular methods currently available for its detection and progress in the development of new diagnostics for cryptosporidiosis are also discussed.

Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use, health-related quality of life, safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP. METHODS: A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1 mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS). RESULTS: Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p = .0181) or for IBS-D (p = .0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported. CONCLUSIONS: Alosetron 1 mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP.

Clinical features, risk factors, and impact of antibiotic treatment of diarrhea caused by Shigella in children less than 5 years in Manhiça District, rural Mozambique.

OBJECTIVES: During the period from December 2007 to November 2012, the epidemiology of diarrhea caused by Shigella was studied among children <5 years of age residing in Manhiça District, Southern Mozambique. MATERIALS AND METHODS: Children from 0 to 5 years with moderate-to-severe diarrhea (MSD) and less severe diarrhea (LSD) were enrolled along with matched controls (by age, gender, and neighborhood). Age-stratified logistic regression analyses were conducted to identify clinical features and risk factors associated with Shigella positivity in cases of diarrhea. The impact of antibiotic treatment was assessed for patients with known outcome. RESULTS: A total of 916 cases of MSD and 1979 matched controls, and 431 cases of LSD with equal number of controls were enrolled. Shigella was identified as significant pathogen in both cases of MSD and LSD compared to their respective controls. Shigella was detected in 3.9% (17/431) of LSD compared to 0.5% (2/431) in controls (P=0.001) and in 6.1% (56/916) of MSD cases compared to 0.2% (4/1979) in controls (P<0.0001), with an attributable fraction of 8.55% (95% CI: 7.86-9.24) among children aged 12-23 months. Clinical symptoms associated to Shigella among MSD cases included dysentery, fever, and rectal prolapse. Water availability, giving stored water to child, washing hands before preparing baby's food, and mother as caretaker were the protective factors against acquiring diarrhea caused by Shigella. Antibiotic treatment on admission was associated with a positive children outcome. CONCLUSION: Shigella remains a common pathogen associated with childhood diarrhea in Mozambique, with dysentery being a significant clinical feature of shigellosis. Adherence to the basic hygiene rules and the use of antibiotic treatment could contribute to the prevention of most of diarrhea due to Shigella.

The role of HIV infection in the etiology and epidemiology of diarrheal disease among children aged 0­59 months in Manhiça District, Rural Mozambique

The Global Enteric Multicenter Study enrolled children with moderate-to-severe diarrhea (MSD) and less-severe diarrhea (LSD) between December 2007 and November 2012. One to three controls for MSD cases and one per LSD case were enrolled and matched by age, sex, and neighborhood. All children were tested for HIV. Clinical data, anthropometric data, and stool samples were collected. Follow-up was performed at 60 days. Results Two hundred and fourteen MSD cases and 418 controls, together with 349 LSD cases and 214 controls were tested. HIV prevalence was 25% among MSD cases (4% for matched controls) and 6% among LSD cases (6% among matched controls). HIV-infected children were more likely to have MSD (odds ratio 5.6, p < 0.0001). Mortality rates were higher among HIV-infected children than among the uninfected (34 vs. 5 per 1000 child-weeks at risk; p = 0.0039). Cryptosporidium, Giardia, and enteroaggregative Escherichia coli (aatA only) were more prevalent among HIV-infected MSD cases than among uninfected ones.

The role of HIV infection in the etiology and epidemiology of diarrheal disease among children aged 0-59 months in Manhiça District, Rural Mozambique.

BACKGROUND: Diarrhea is an important health problem among HIV-infected patients. This study evaluated the role of HIV in the epidemiology, etiology, and severity of diarrheal disease among children. METHODS: The Global Enteric Multicenter Study enrolled children with moderate-to-severe diarrhea (MSD) and less-severe diarrhea (LSD) between December 2007 and November 2012. One to three controls for MSD cases and one per LSD case were enrolled and matched by age, sex, and neighborhood. All children were tested for HIV. Clinical data, anthropometric data, and stool samples were collected. Follow-up was performed at 60 days. RESULTS: Two hundred and fourteen MSD cases and 418 controls, together with 349 LSD cases and 214 controls were tested. HIV prevalence was 25% among MSD cases (4% for matched controls) and 6% among LSD cases (6% among matched controls). HIV-infected children were more likely to have MSD (odds ratio 5.6, p<0.0001). Mortality rates were higher among HIV-infected children than among the uninfected (34 vs. 5 per 1000 child-weeks at risk; p=0.0039). Cryptosporidium, Giardia, and enteroaggregative Escherichia coli (aatA only) were more prevalent among HIV-infected MSD cases than among uninfected ones. CONCLUSION: HIV is an important risk factor for MSD. The high mortality rate implies that children with MSD should be screened for HIV and managed accordingly.

A 9-year evaluation of temporal trends in alosetron postmarketing safety under the risk management program.

OBJECTIVES: Adverse events (AEs) of ischemic colitis (IC) and complications of constipation (CoC) associated with alosetron are rare and have been adjudicated during the first 5.5 years of the risk management program (RMP); however, changes in incidence rates relative to reductions in AE reports and increases in alosetron prescriptions over the 9-year RMP have not been evaluated. The authors aim to evaluate temporal trends in alosetron postmarketing safety over the 9-year RMP. METHODS: The alosetron safety database was searched to identify cases of IC, CoC, and related AEs from 20 November 2002 to 31 December 2011. Adjudication of IC and CoC cases were based on US Food and Drug Administration-defined criteria. Incidence rates were calculated using the number of AEs and alosetron prescriptions (expressed as cases/1000 patient-years exposure). RESULTS: A total of 29 cases were adjudicated as probable/possible IC and 7 cases were adjudicated as CoC. Cumulative adjudicated incidence rate of IC (1.03 cases/1000 patient-years) is low and stable, while that of CoC (0.25 cases/1000 patient-years) is low, declining progressively over time. Decreases in the incidence rates of potential symptoms of IC (abdominal pain with bloody diarrhea/hematochezia) and CoC (constipation) were also observed. CONCLUSIONS: Over the 9-year RMP period, incidence rates of IC and CoC remain rare. Substantial reductions over time were observed in the incidence of CoC and in symptoms suggestive of IC or CoC, while IC incidence has been stable at approximately 1.0 case/1000 patient-years. Decreases in AEs and serious outcomes associated with IC and CoC since the reintroduction of alosetron are likely attributable to the RMP.

Case-control studies and risk factors for cataract in two population studies in Nigeria.

PURPOSE: The aim of this study was to determine and investigate the risks associated with cataract in South Western and North Central Nigeria. MATERIALS AND METHODS: A hospital-based, case-control study was conducted in Lagos (Lagos group), South Western Nigeria, and Kano (Kano group), North Central Nigeria. In this study, 530 subjects with visually impairing cataracts (study group) and 530 age(-) and sex-matched controls (control group) were recruited from patients aged 40 to 89 years attending the ophthalmology clinics at the same hospital. All subjects were examined for the presence/absence of cataract and interviewed about their educational achievements, diarrhea/dehydration crises, urban/rural residence, and ophthalmological conditions. A standardized questionnaire was administered to all subjects. Logistic regression analysis with age adjustment, literacy, outdoor work, body mass index, crowding, regular vegetable intake, heavy alcohol, and cigarette intake was performed. P < 0.05 was considered statistically significant. RESULTS: Using multivariate regression analysis, after adjustment for age and other demographics factors, low education and no education [adjusted odds ratios (OR) = 2.42 for the Lagos group and 4.10 for Kano group] and a positive history of diarrhea or dehydration crises (adjusted OR = 1.31 for the Lagos group and 2.12 for Kano group) were associated with an increased risk for cataract. Senile cataracts were more common among the Fulani ethnic group (adjusted OR = 2.21) of North Central Nigeria. However, rural or urban residence did not reveal any positive risk for cataract. CONCLUSION: The risk of cataract in North Central Nigeria is similar to that in South Western Nigeria. Cataracts were strongly associated with increasing age, with peak age of 55 years and were more common in those with lower education, severe diarrhea and among the members of Fulani in North Central Nigeria.

A Case with Short Bowel Syndrome Successfully Treated with Shigyakuto-kagen / 日本東洋医学雑誌

We present a patient with short bowel syndrome (SBS), successfully treated with the Kampo medicine, shigyakuto-kagen. The patient was a 74 year old female complaining of severe diarrhea, abdominal distention, and abdominal pain. She was diagnosed as having tuberculous peritonitis when she 23 years of age. A partial resection of the small bowel and colon was performed for ileus, secondary to her tuberculous peritonitis, eventually causing her short bowel syndrome (SBS). Severe abdominal distention and pain had persisted even after the resection surgery. She consulted our clinic at 60 years of age in order to receive Kampo therapy. Bukuryoshigyakuto was prescribed, and her condition markedly improved. Zanthoxylum piperitum was added to bukuryoshigyakuto, and the regimen had the reactivity of daikenchuto. She regained her pre-operation body weight. It is significant that this case was followed for 14 years with therapy based on Kampo diagnosis, without remarkable complications, although patients with SBS often tend to have poor prognosis.