Clinical risk factors, bacterial aetiology, and outcome of urinary tract infection in children hospitalized with diarrhoea in Bangladesh.

Urinary tract infection (UTI) is common in children aged <5 years with diarrhoea, but little is known about risk factors, aetiology and outcome of such children. We aimed to evaluate these knowledge gaps of UTI in children aged <5 years with diarrhoea. We enrolled all children aged <5 years with diarrhoea admitted to Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between May 2011 and April 2013, who had history of fever (⩾38 °C) and obtained a urine sample for culture. Diarrhoea with UTI (confirmed by culture) constituted cases (n = 26) and those without UTI constituted controls (n = 78). Threefold controls were randomly selected. The case-fatality rate was comparable in cases and controls (4% vs. 1%, P = 0·439). Escherichia coli (69%) and Klebsiella (15%) were the most commonly isolated pathogens. Persistent diarrhoea, pneumonia and prior antibiotics use were identified as risk factors for UTI in logistic regression analysis (P < 0·05 for all). Thus, children with diarrhoea presenting with persistent diarrhoea, pneumonia, and prior antibiotic use should be investigated for UTI for their prompt management that may reduce morbidity.

Lack of BCG vaccination and other risk factors for bacteraemia in severely malnourished children with pneumonia.

We sought to examine the factors associated with bacteraemia and their outcome in children with pneumonia and severe acute malnutrition (SAM). All SAM children of either sex, aged 0-59 months, admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh with radiologically confirmed pneumonia from April 2011 to July 2012 were enrolled (n = 405). Comparison was made between pneumonic SAM children with (cases = 18), and without (controls = 387) bacteraemia. The death rate was significantly higher in cases than controls (28% vs. 8%, P < 0·01). In logistic regression analysis, after adjusting for potential confounders, the SAM children with pneumonia and bacteraemia more often had a history of lack of bacillus Calmette-Guérin (BCG) vaccination (odds ratio 7·39, 95% confidence interval 1·67-32·73, P < 0·01). The results indicate the importance of continuation of BCG vaccination which may provide benefit beyond its primary purpose.

Changing patient population in Dhaka Hospital and Matlab Hospital of icddr,b.

The Diarrhoeal Disease Surveillance System of icddr,b noted increasing number of patients ≥60 years at urban Dhaka and rural Matlab from 2001 to 2012. Shigella and Vibrio cholerae were more frequently isolated from elderly people than children under 5 years and adults aged 5-59 in both areas. The resistance observed to various drugs of Shigella in Dhaka and Matlab was trimethoprim-sulphamethoxazole (72-63%), ampicillin (43-55%), nalidixic acid (58-61%), mecillinam (12-9%), azithromycin (13-0%), ciprofloxacin (11-13%) and ceftriaxone (11-0%). Vibrio cholerae isolated in Dhaka and Matlab was resistant to trimethoprim-sulphamethoxazole (98-94%), furazolidone (100%), erythromycin (71-53%), tetracycline (46-44%), ciprofloxacin (3-10%) and azithromycin (3-0%).

Co-morbidity: exploring the clinical overlap between pneumonia and diarrhoea in a hospital in Dhaka, Bangladesh.

BACKGROUND: There is limited information on risk factors for pneumonia and pneumonia-related deaths in children who also have diarrhoea. AIM: To identify risk factors for the above in order to improve strategies for case management and to develop appropriate public health messages. METHODS: All children under 5 years of age admitted to the Special Care Ward, Dhaka Hospital of the International Centre for Diarrhoeal Disease Research (ICDDR,B) from 1 September to 31 December 2007 were considered for enrollment if they also had diarrhoea. Of the 258 children with diarrhoea enrolled, those with (n=198) or without (n=60) WHO-defined pneumonia constituted the pneumonia and comparison groups, respectively. Among the 198 children with pneumonia, children who survived (n=174) were compared with those who died in hospital (n=24). RESULTS: After adjusting for socio-demographic factors, including low levels of literacy of either parent, low household income, not having a window or exhaust fan in the kitchen, household smoking and over-crowding, children with pneumonia were more likely to sleep on a bare wooden-slatted or bamboo bed (OR 2·7, 95% CI 1·40-5·21, p = 0·003) than on other bedding, and were also more likely to have a parent/care-giver with poor knowledge of pneumonia (OR 1·94, 95% CI 1·02-3·70, p=0·043). Independent risk factors for death include severe underweight (OR 5·2, 95% CI 1·2-22·0, p=0·03), hypoxaemia (OR 17·5, 95% CI I 1·9-160·0, p=0·01), severe sepsis (OR 8·7, 95% CI I 1·8-41·5, p=0·007) and lobar consolidation (OR 11·9, 95% CI 2·3-61·6, p=0·003). CONCLUSIONS: Increased public awareness of signs of pneumonia and severe sepsis in children under 5 is important to mitigate the risks of pneumonia and pneumonia-related deaths, and the importance of appropriate bedding for young children in reducing the risk of pneumonia needs to be addressed.

Influences of dehydration on clinical features of radiological pneumonia in children attending an urban diarrhoea treatment centre in Bangladesh.

BACKGROUND: As the signs of dehydration often overlap with those of pneumonia, it may be difficult for health workers in resource-poor settings to make a clinical diagnosis of pneumonia in children with dehydration. This issue has received very little attention. AIM: To compare the clinical features of pneumonia in children with and without dehydration caused by diarrhoea. METHODS: All children aged 2-59 months with diarrhoea and radiologically confirmed pneumonia admitted to the Special Care Ward (SCW) of Dhaka Hospital, ICDDR,B between September and December 2007 were enrolled for the study. Children with dehydration (67 cases) and those without (101 controls) were compared. RESULTS: Cases presented less frequently with fast breathing (60% vs 88%, p<0.001) and lower chest-wall indrawing (67% vs 82%, p=0.035) than did controls. In logistic regression analysis, cases more often had severe malnutrition (OR 2.31, CI 1.06-5.02, p=0.035) and cyanosis (OR 19.05, CI 1.94-186.68, p=0.011) and were abnormally sleepy (OR 372, CI 1.71-8.08, p=0.001). CONCLUSIONS: Fast breathing and lower chest-wall indrawing may be less reliable for the diagnosis of pneumonia in children with dehydration, especially when there is severe malnutrition.

Evidence of intra-familial transmission of Helicobacter pylori by PCR-based RAPD fingerprinting in Bangladesh.

Helicobacter pylori is a genetically diverse bacterial species, which has facilitated adaptation to new hosts and persists worldwide. The main objective of this study was to explore intra-familial transmission of H. pylori in Bangladesh. We characterized H. pylori in 35 families including 138 family members using random amplified polymorphic DNA (RAPD) fingerprinting. Forty-six percent of H. pylori isolated from the mother shared a related genotype with strains isolated from their children. Twenty-nine percent of H. pylori isolates of the mother are related to the youngest children. Only 6% of the parents shared related genotype of H. pylori. These findings suggest that mother-to-child transmission occurs in early childhood and is the most probable route of transmission of H. pylori in Bangladesh.

Micronutrients and anaemia.

Micronutrient deficiencies and anaemia remain as major health concerns for children in Bangladesh. Among the micronutrient interventions, supplementation with vitamin A to children aged less than five years has been the most successful, especially after distribution of vitamin A was combined with National Immunization Days. Although salt sold in Bangladesh is intended to contain iodine, much of the salt does not contain iodine, and iodine deficiency continues to be common. Anaemia similarly is common among all population groups and has shown no sign of improvement even when iron-supplementation programmes have been attempted. It appears that many other causes contribute to anaemia in addition to iron deficiency. Zinc deficiency is a key micronutrient deficiency and is covered in a separate paper because of its importance among new child-health interventions.

Immunopathological patterns in the rectal mucosa of patients with shigellosis: expression of HLA-DR antigens and T-lymphocyte subsets.

Expression of HLA-DR antigens and infiltration of T-lymphocyte subsets (CD4, CD8), cell activation marker (CD25), B cells (CD20), macrophages (CD68 and Ber-Mac 3) and natural killer cells (CD56) in the rectal mucosa of patients with bacillary dysentery and in healthy controls were studied in an effort to interpret the immunopathological changes taking place in the rectal mucosa during the acute phase of shigellosis. The epithelium of the rectal mucosa from 21 of 32 patients was HLA-DR+. Conventional histology showed acute inflammation in 16 of these patients, chronic inflammation in 3, and in 2 histology was normal. In 7 of 20 controls the epithelium was HLA-DR+; 4 of these 7 were found to suffer from chronic inflammation, whilst in 3 the mucosa was normal. The number of HLA-DR+ intraepithelial lymphocytes in biopsies from patients with Shigella infection was significantly higher (p = 0.005) than in controls. The infiltration of CD8+ cells in the surface epithelium and in the lamina propria, and of CD4+ cells in the lamina propria alone, was significantly higher (p < 0.001) in patients than in controls. The results demonstrate that infiltration of T cells with suppressor/cytotoxic or helper/inducer phenotype in the epithelium and in the lamina propria in Shigella-infected patients may be related to the induction of HLA-DR expression in non-lymphoid cells during acute Shigella infection.

Astrovirus infection in association with acute, persistent and nosocomial diarrhea in Bangladesh.

BACKGROUND: Diarrhea is an important public health concern in developing countries such as Bangladesh. Diarrhea in children that persists for 14 days or more occurs in 7% of patients in Bangladesh and frequently results in death. Astrovirus has been demonstrated as a cause of acute and nosocomial diarrhea and can be excreted for prolonged periods, yet its importance as a cause of diarrhea among children in a developing country like Bangladesh has not been investigated. METHODS: We tested 629 stool specimens from patients with acute diarrhea, 153 from patients with persistent diarrhea, 175 specimens from 76 patients hospitalized for diarrhea who were sampled repeatedly to detect nosocomial infection and 428 from nonhospitalized healthy children (controls). All children enrolled in the study were <5 years of age. Astrovirus was detected by enzyme immunoassay and other enteropathogens were detected by standard techniques. RESULTS: The detection of astrovirus increased significantly with the duration of diarrhea. Astrovirus was found in 23 (15%) specimens from patients with persistent diarrhea, 26 (4%) patients with acute diarrhea, but only 8 (2%) healthy controls. This trend remained when we limited our analysis to infants <12 months of age and to episodes in which astrovirus was the sole pathogen. Among patients with nosocomial diarrhea, 16% of postadmission specimens were positive for astrovirus when the admission specimen was negative. CONCLUSION: The observation that astrovirus is detected more frequently with diarrhea of increasing duration suggests the need for further studies to determine whether astrovirus plays a causative role in persistent diarrhea or is a secondary agent.

Helicobacter pylori infection in the young in Bangladesh: prevalence, socioeconomic and nutritional aspects.

BACKGROUND: The gastric acid barrier, an important host defence against small bowel infection, may be compromised by infection with Helicobacter pylori. In developing countries, H. pylori infection occurs early in life and prevalence of hypochlorhydria is high particularly in the malnourished, which may predispose a child to repeated gastrointestinal infection and diarrhoea. Diarrhoea being a leading cause of childhood mortality and morbidity in developing countries, we investigated the prevalence of H. pylori infection in children in a poor Bangladeshi community and explored its association with socioeconomic and nutritional status. METHODS: The study was conducted in a poor periurban community among 469 children aged 1-99 months. Parents were interviewed using a questionnaire. To detect active infection with H. pylori a 13C-urea breath test was performed and weight was recorded on a beam balance with a sensitivity of 20 g. RESULTS: In all, 61% of 36 infants aged 1-3 months were positive for H. pylori; this rate dropped steadily with increasing age and was 33% in 10-15 month old children and then rose to 84% in 6-9 year olds. Overall H. pylori infection had no association with nutritional state of the child, or family income but the infection rate was 2.5 times higher in children of mothers with no schooling. CONCLUSIONS: The H. pylori infection rate is very high in early infancy in a poor periurban community of Bangladesh. The reason for a drop in the infection rate in late infancy is unclear but could be due to initial clearance of the infection by the body's defence mechanisms but with possible alteration of the gastric mucosa which sustains infection. Maternal education may be protective and may operate through some unidentified proximate behavioural determinants. The rate of H. pylori infection in infants and young children may predispose them to repeated gastrointestinal infection and diarrhoea.

PIP: The gastric acid barrier is an important host defense against small bowel infection. The integrity of that barrier, however, may be compromised by infection with Helicobacter pylori. The authors investigated the prevalence of H. pylori infection among 469 children aged 1-99 months in a poor, periurban, Bangladeshi community and explored its association with socioeconomic and nutritional status. The children's parents were interviewed via questionnaire, while a C-urea breath test was conducted and weight recorded on a beam balance with a sensitivity of 20 g to detect active infection with H. pylori. 61% of 36 infants aged 1-3 months tested positive for H. pylori. However, the rate of infection declined steadily with increasing age to reach 33% among children aged 10-15 months. The rate of infection then rose to 84% in 6-9 year olds. Overall, H. pylori infection had no association with the nutritional state of the child or family income, but the infection rate was 2.5 times higher among children of mothers with no schooling. It is unclear why the infection rate dropped in late infancy. Initial clearance of the infection by the body's defence mechanisms could be responsible, albeit with the possible alteration of the gastric mucosa which sustains infection. Maternal education may be protective and may operate through some unidentified proximate behavioral determinants. The rate of H. pylori infection in infants and young children may predispose them to repeated gastrointestinal infection and diarrhea.

Quantitative assessment of IgG and IgA subclass producing cells in rectal mucosa during shigellosis.

AIMS: To assess quantitatively both the morphological changes in the rectal mucosa and the changes in the relative frequency of IgA and IgG subclass producing cells found in the rectal mucosa during the acute phase of shigellosis and at convalescence. METHODS: Rectal biopsies from 25 Shigella dysenteriae 1 infected patients, 10 Shigella flexneri infected patients, and 40 uninfected controls were studied. Morphological changes in the mucosa were graded. The frequency of IgA and IgG subclass producing cells was assessed. In addition, immunostaining for secretory component in epithelial cells was analysed. RESULTS: Using morphological grading, 20% of the 35 patients studied had advanced inflammation (grade 3) in the acute phase of the disease. At convalescence, grade 1 inflammation was seen in 37% of the patients and in 10% of the controls. In the acute phase, as well as at convalescence, the number of IgA1, IgA2, and IgG2 positive cells was significantly higher than in the controls. The results were related to the histopathological degree of inflammation. CONCLUSIONS: In shigellosis, there is evidence for a prolonged humoral response residing in the mucosa long after the clinical symptoms have resolved, suggesting that shigellosis induces persisting mucosal humoral immune and inflammatory responses, remaining at least until 30 days after the infection.

Comparative trial of five antimicrobial compounds in the treatment of cholera in adults.

To compare the efficacy of ciprofloxacin, erythromycin, nalidixic acid and pivmecillinam in the treatment of tetracycline-resistant strains of Vibrio cholerae O1 in adults, a randomized, open, clinical trial was conducted. A tetracycline group was used for comparison. Seventy-five adult men infected with V. cholerae O1 were randomly assigned to receive either 400 mg pivmecillinam or 500 mg of one of each of the other drugs. Ciprofloxacin was given every 12 h and the others every 6 h for 3 d. The mean total stool volume per kg was 155 mL for the ciprofloxacin group, 212 mL for the erythromycin and pivmecillinam groups, 246 mL for nalidixic acid, and 293 mL for tetracycline. The difference between ciprofloxacin and tetracycline was significant (P = 0.045). After 72 h, diarrhoea had stopped in 14 patients (93%) in the ciprofloxacin group and 12 (80%) in the erythromycin group, compared to 5 (42%) of those receiving tetracycline (P = 0.006 and 0.049, respectively). Bacteriological clearance was 100% at 24 h in patients treated with ciprofloxacin compared to 20% and 8.3% (P < 0.001 for both comparisons) in the erythromycin and tetracycline groups. Ciprofloxacin in conjunction with appropriate fluid therapy was the most effective treatment for cholera in adults; erythromycin was the next best.

Plasma secretin determination as a test of gastric acid secretion: effect of a marker perfusion technique on validation.

OBJECTIVE: To examine whether plasma secretin levels can be used as a diagnostic measure of gastric acid output. METHODS: A marker perfusion technique was used to quantify gastric acid output. Blood samples were drawn for secretin radioimmunoassay at specified intervals before and after pentagastrin stimulation in six healthy volunteers and six patients suspected of having abnormal gastric acid secretion. RESULTS: Linear relationships were found between integrated secretin response and maximal acid output as well as between peak acid output and acid output at 2 h (P < 0.01). Similar correlations were also observed with secretin levels 52, 60 and 68 min after pentagastrin stimulation. Discrimination between low, average and high gastric acid secretors was possible at 52 and 60 min after stimulation. Plasma secretin did not increase after pentagastrin stimulation in the 12 subjects when acid was continually aspirated, nor did correction for gastric acid loss improve the correlation or discrimination. CONCLUSION: One or two measurements of plasma secretin about 1 h after pentagastrin administration may provide a useful quantitative estimate of gastric secretory capacity for epidemiological or clinical purposes.

Octreotide (SMS 201-995) as an antisecretory agent in cholera toxin & bile acid induced intestinal secretion in an in vivo animal study.

The effect of Octreotide (SMS 201-995), synthetic somatostatin analogue on small intestinal and colonic fluid secretion induced respectively by cholera toxin (CT) and deoxycholic acid (DCA) was investigated in rabbits using in vivo isolated loops. After exposure to CT and DCA, marked fluid accumulation was observed in the small intestinal and colonic loops, along with elevation of jejunal and colonic mucosal cyclic AMP concentrations. Octreotide inhibited CT and DCA induced small intestinal and colonic secretion, dose-dependently. This anti-secretory effect was observed after both intramuscular and oral administration of octreotide. In contrast, octreotide did not affect the elevated mucosal cyclic AMP concentrations. These results suggest that octreotide inhibits CT and DCA induced intestinal secretion, and this anti-secretory effect is produced by affecting processes beyond cyclic AMP formation.

Effects of tropisetron, a 5-hydroxytryptamine type 3 receptor blocker, on intestinal secretion induced by cholera toxin or deoxycholic acid in rabbits in vivo.

It has been suggested that 5-hydroxytryptamine is involved in the pathogenesis of various intestinal hypersecretory states including cholera. In this study, the effect of tropisetron (ICS 205-930), a specific 5-hydroxytryptamine type-3 receptor blocker, on jejunal and colonic fluid secretion induced respectively by cholera toxin and deoxycholic acid was investigated in rabbits using isolated loops of intestine in vivo. Marked fluid accumulation in both the jejunal and colonic loops was observed after exposure to cholera toxin and deoxycholic acid respectively. Elevation of jejunal and colonic mucosal cyclic adenosine monophosphate concentrations was also noted. Intraperitoneal administration of tropisetron dose-dependent inhibited jejunal secretion induced by cholera toxin. In contrast, no significant anti-secretory effect of tropisetron was observed against colonic secretion induced by deoxycholic acid. Tropisetron did not affect elevated mucosal cyclic adenosine monophosphate concentrations. The inhibitory effect of tropisetron on intestinal secretion induced by cholera toxin, which was independent of cyclic adenosine monophosphate formation, suggests that 5-hydroxytryptamine plays an important role in this type of secretion.