WHO consultation on ETEC and Shigella burden of disease, Geneva, 6-7th April 2017: Meeting report.

According to the 2015 Global Burden of Disease Study, diarrhea ranked ninth among causes of death for all ages, and fourth among children under 5 years old, accounting for an estimated 499,000 deaths in this young age group. It was also the second most common cause of years lived with disability (2.39 billion YLDs). The goal of the WHO/UNICEF Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea (GAPPD) is to reduce deaths from diarrhea in children under 5 years of age to less than 1 per 1000 live births, by 2025. Development of new and improved vaccines against diarrheal infections is a fundamental element of the strategy towards achieving this goal. Enterotoxigenic Escherichia coli (ETEC) and Shigella are enteropathogens that cause significant global mortality and morbidity, particularly in low- and middle-income countries. In 2016, WHO's Product Development for Vaccines Advisory Committee (PDVAC) recommended that the WHO's Initiative for Vaccine Research (IVR) engage in this area, based on PDVAC's criteria of prioritizing the development of vaccines against pathogens that will address a major unmet public health need, and for which clinical candidates with a good probability of technical success are in the pipeline. As a first step, WHO's IVR convened global subject matter experts to discuss the current global ETEC and Shigella disease burden estimates, including the current understanding of the long-term indirect effects of ETEC and Shigella infection, and how these data may affect future decision making on vaccine development for both pathogens. The available global burden estimates for ETEC and Shigella differ with respect to the relative importance of these two pathogens. The mortality estimates vary between iterations published by the same group, as well as between estimates of different groups, although the uncertainty intervals are broad and overlapping. These variances are attributable to differences in the data available and incorporated in the models; the methods used to detect the pathogens; the modelling methodologies; and, to actual changes in the total number of diarrheal deaths over time. The changes in the most recently reported mortality estimates for these pathogens, as compared to previous iterations, has led to debate as to whether investment in development of stand-alone vaccines, rather than combined vaccines, is warranted from cost-effectiveness and vaccine impact perspectives. Further work will be needed to understand better the variances and uncertainties in the reported mortality estimates to support investment decision making, and ultimately policy recommendations for vaccine use. In addition, a comprehensive assessment of the value proposition for vaccines against these pathogens is needed and will be strengthened if the long-term health consequences associated with diarrhea and dysentery due to these pathogens are better defined.

Azithromycin Resistance in Shigella spp. in Southeast Asia.

Infection by Shigella spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment; however, antimicrobial resistance in Shigella spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian Shigella isolates and use these data to assess appropriate susceptibility breakpoints. Shigella isolates recovered in Vietnam and Laos were screened for susceptibility to azithromycin (15 µg) by disc diffusion and MIC. Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin-resistant Shigella sonnei isolates using whole-genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri isolates (3.3%, MIC ≥ 16 g/liter) and 16/294 S. sonnei isolates (5.4%, MIC ≥ 32 g/liter) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (mphA in 19 isolates and ermB in 3 isolates). The susceptibility data demonstrated the acceptability of the S. flexneri (MIC ≥ 16 g/liter, zone diameter ≤ 15 mm) and S. sonnei (MIC ≥ 32 g/liter, zone diameter ≤ 11 mm) breakpoints with a <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei isolates on at least seven occasions between 2000 and 2009 but failed to become established. While the proposed susceptibility breakpoints may allow better recognition of resistant isolates, additional studies are required to assess the impact on the clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative options for management of Shigella infections in countries where Shigella is endemic.

Aloe vera (Aloe barbadensis Miller) supplemented probiotic lassi prevents Shigella infiltration from epithelial barrier into systemic blood flow in mice model.

The aim of present work was to investigate preventive role of orally administered Aloe vera supplemented probiotic lassi (APL) on Shigella dysenteriae infection in mice. At the end of experimental period (2, 5 and 7 days of challenging), different organs such as spleen, liver, small intestine, large intestine, and peritoneal fluid were collected and assessed for Shigella colonization. Secretary IgA was estimated in intestinal fluid. Blood was collected in heparinized tubes for various haematological studies. Oral administration of APL showed a significant (p < 0.05) reduction in the Shigella counts (log cfu/mL) in all organs as compared to other treatment groups at different intervals after post feeding. Similarly, secretary IgA antibody levels (µg/mL) in intestinal fluid were significantly (p < 0.05) increased in case of APL fed mice. Further, feeding of APL also demonstrated a positive effect on different haematological parameters viz. Hb (gm %), RBC and WBC count. The results indicated the immunoprotective effects of APL against Shigella dysenteriae induced infection in mice.

Patrones de sensibilidad y comportamiento clínico de la infección por Shiguella en pacientes pediátricos / Patterns of sensitivity and clinical behavior of Shigella infection in pediatric patients

Objetivos: Identificar los patrones de sensibilidad y el comportamiento clínico de la infección por Shigella en los pacientes pediátricos atendidos en el Hospital Nacional Docente Madre Niño San Bartolomé en el periodo comprendido entre Junio del 2010 a Mayo del 2013. Material y métodos: Se realizó un estudio observacional, descriptivo, retrospectivo y transversal. Se revisaron 82 historias clínicas de los pacientes con diagnóstico de infección por Shigella; en el periodo que corresponde al estudio. Resultados: La media de la edad global fue de 7.5+/-2.7 años. La media de la edad de los varones fue de 7.4+/-2.3 años y de las mujeres fue de 7.6+/-3.1 años. El 57.3 por ciento de los casos fueron de sexo masculino. El 32.9 por ciento de los niños consumían alimentos de riesgo. El 13.4 por ciento de los pacientes habían tenido contacto con diarrea. El 41.5 por ciento de los pacientes habían tenido varias patologías previas. El 32.9 por ciento de los pacientes habían tenido diarreas anteriores. El síntoma inicial fue la diarrea en el 64.6 por ciento de los casos. El 56.1 por ciento de los pacientes tuvo vómitos. El 45.1 por ciento de los pacientes cursó con fiebre (38-39 grados centígrados). El 52.4 por ciento de los pacientes tuvo dolor abdominal. La diarrea con moco se presentó en un 37.8 por ciento de los casos. El 79.3 por ciento de los paciente recibieron el plan A de rehidratación. La comorbilidad más frecuente fue la rinofaringitis en un 18.3 por ciento de los casos. El 50 por ciento de los pacientes tuvieron una reacción inflamatoria con más de 100 leucocitos por campo. Conclusiones: Hubo una mayor frecuencia de sensibilidad a la ciprofloxacina y azitromicina y hubo una mayor frecuencia de resistencia al cloranfenicol. La mayoría provenía del cercado de Lima, contaban con saneamiento en sus domicilios, contaban con sus vacunas y acudían a control CRED. Una minoría consumía alimentos de riesgo, habían tenido contacto con diarrea. El síntoma inicial fue la...

Goals: To identify the patterns of sensibility and clinical behavior of Shigella infection among pediatric patients attended at San Bartolome Hospital, between June 2010 and May 2013. Methods and materials: An observational, descriptive, retrospective and cross-sectional study was designed. Medical records of 82 patients with diagnosis of Shigella infection were checked; in the period of time corresponding to the study. Results: The mean global age was 7.5 +/- 2.7 years old. The boys mean age was 7.4 +/- 2.3 years old and girl’s was 7.6 +/- 3.1 years old. 57.3 por ciento of all cases were male, and 32.9 per cent consumed risky food. 13.4 per cent of patients have had contact with diarrhea. 41.5 per cent have had many other previous diseases. 32.9 per cent have had previous diarrheas. The main symptom was diarrhea in 64.6 per cent of all cases. 56.1 per cent of patients had vomits. 45.1 per cent had fever (38-39 grades centigrade). 52.4 per cent had abdominal pain. Diarrhea with mucus was present in 37.8 per cent of cases. 79.3 per cent of patients received A plan for rehydration. The most common comorbidity was rhinopharyngitis with 18.3 per cent of all cases. 50 per cent of patients had a positive inflammatory cells in stools, with more than one hundred of leukocytes. Conclusions: There was a predominant sensibility of Shigella to Ciprofloxacin and Azithromycin, and there was an important resistance to Chloramphenicol. Most of the patients were from Cercado de Lima, had sanitation at their homes, had their vaccines on time and came to CRED control. A minority consumed risk food and had contact with diarrhea. Initial symptom was diarrhea, most patients had vomiting, fever, abdominal pain, diarrhea with mucus. The most commonly used therapies were ciprofloxacin and azithromycin. Most patients had inflammatory reaction with more than 100 leukocytes per field.

Effects of Ocimum gratissimum L essential oil at subinhibitory concentrations on virulent and multidrug-resistant Shigella strains from Lagos, Nigeria.

Ocimum gratissimum leaf extracts have been extensively demonstrated to be effective against the various aetiologic agents of diarrhoea, including Shigellae. However, the mechanism of the shigellocidal action of this plant remains to be understood. This study investigated the effects of O. gratissimum essential oil (EO) at subinhibitory concentrations of 0.75 and 1.0 microg/ml on virulence and multidrug-resistant strains of 22 Shigella isolates from Nigeria. Compared with untreated Shigella strains, O. gratissimum EO caused significant decreases (p<0.01) in extracellular protease activity, o-lipopolysaccharide rhamnose content and incidence of invasiveness mediated as keratoconjunctivitis in guinea pig. The disparity in extracellular protease activity and o-lipopolysacharide rhamnose between the two treatment groups was also found to be significant (p<0.05), suggesting greater anti-virulent effects of O. gratissimum oil at 1.0 microg/ml. Antibiotic susceptibility testing revealed that the EO of O. gratissimum reduced the MICs of antibiotics to which Shigellae showed resistance by 9.8-53.1% and fluoroquinolones by 18.2-45.5%. The results of this study strongly suggest inhibition of extracellular protease and expression of O-LPS rhamnose in Shigellae by O. gratissimum EO. The future use of O. gratissimum- antibiotic combinations as a therapeutic measure against shigellosis is discussed.

Death from multi-resistant shigellosis in Fiji Islands.

Death from Shigellosis is rare in developed countries, however it causes over a million deaths in developing countries worldwide annually. Death from shigellosis is rare in Fiji. However, the global problem of emerging multidrug resistance raises some issues about the management of Shigellosis in this country. Within Fiji, Shigella is a notifiable disease. The Fiji Ministry of Health recorded 68 cases of Shigella in 1996, 173 cases in 1997 and 334 cases in 1998 (no data available for 1999). There was only one recorded death during this time--in 1998. Resistance to chloramphenicol occurred in 82% of cases. Shigella flexneri in Fiji remains sensitive to cephalothin and cefaclor. The current antibiotic guidelines in Fiji, recommend that antibiotics be used only for cases of moderate and severe dysentery. Shigellosis was suspected soon after presentation however the patient was unable to take oral antibiotics and was treated with intravenous antibiotics (chloramphenicol and ampicillin), which were ineffective due to resistance of the organism. The current antibiotic guidelines for severe dysentery recommend chloramphenicol or nalidixic acid--the later not available in Fiji. However the only intravenous drugs that retain their sensitivity to Shigella-ceftriaxone and cephalothin, are expensive ($F 45.00 per vial of ceftriaxone) and these are only available in large regional hospitals.

Diarrea aguda: tratamiento nutricional / Acute diarrhea: nutrtional treatment

El tratamiento de la diarrea aguda consistirá básicamente en rehidratación oral si existiera deshidratación, realimentación precoz y excepcionalmente farmacológico. La rehidratación debe durar 4-6 horas, que se prolonga a 8-12 horas si la deshidratación es hipernatrémica, pasando posteriormente a la fase de mantenimiento. Las soluciones de rehidratación oral son las recomendadas, usándose en países en vías de desarrollo la solución de la OMS por las pérdidas importantes de sodio en las heces y soluciones con menor contenido de sodio en los países industrializados al ser las pérdidas de sodio menores. La realimentación debe ser lo mas precoz y equilibrada posible, recoméndandose la lactancia materna si es la forma de alimentación o la fórmula sin diluir si realiza lactancia artificial. No es aconsejable sistemáticamente las fórmulas sin lactosa. El uso de probióticos mejora el cuadro. No se precisa tratamiento farmacológico y los antibióticos sólo están indicados en pacientes inmunodeprimidos, cólera, lactantes menores de 3 meses con coprocultivos bacterianos positivos, enfermedad sistémica, infección por amebas, giardias, clostridium difficile y shigella que permanece sintomática (AU)

Human milk secretory immunoglobulin A to Shigella virulence plasmid-coded antigens.

Although antibodies to the lipopolysaccharide antigens of Shigella have been demonstrated in human milk, such antibodies do not explain the putative protective effect of breast-feeding against symptomatic Shigella infection. Shigella species do not share related lipopolysaccharides, but they do possess closely related virulence plasmids that code for the proteins essential for cell invasion. We therefore sought to determine the frequency, amount, and duration of excretion of human milk antibodies to these shared virulence plasmid-associated antigens in populations of different rates of Shigella infection frequency (Mexico City, high; Houston, low). Such antibodies were present in the milk of virtually all the Mexican women but also were present in a large proportion of milk samples from the women living in Houston. The amounts of these antibodies were highest in colostrum but after 2 weeks of lactation fell to stable levels. The frequency and persistence of these antibodies in the milk of the women from Houston suggest that the memory and drive for secretion of these antibodies is extremely long lived.