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.

A pilot study of faecal volatile organic compounds in faeces from cholera patients in Bangladesh to determine their utility in disease diagnosis.

The aim of this pilot study was to analyse the volatile organic compounds in faecal samples collected from cholera patients in Bangladesh to determine biomarkers that could be used for disease diagnosis. Samples were collected from patients at the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh and also from healthy controls at the same institution. The volatile organic compounds were extracted from the headspace above the sample using solid phase microextraction and analysed using gas chromatography-mass spectrometry. A biomarker was identified in the cholera samples that could be used for disease diagnosis.

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.

Partially hydrolysed guar gum supplemented comminuted chicken diet in persistent diarrhoea: a randomised controlled trial.

BACKGROUND: Partially hydrolysed guar gum (Benefiber) added to a diet is fermented in the colon, producing short chain fatty acids, which improve intestinal function, including colonic salt and water absorption. AIMS: To evaluate the effect of Benefiber supplemented comminuted chicken diet in the treatment of persistent diarrhoea. METHODS: One hundred and sixteen children (aged 5-24 months), presenting to Dhaka Hospital with a history of watery diarrhoea for more than 14 days (persistent diarrhoea), were randomised to receive either: (1) comminuted chicken diet with Benefiber (study diet); or (2) comminuted chicken diet without Benefiber (control diet). The study period was seven days. RESULTS: Of 116 children, 57 received the study diet and 59 received the control diet. Diarrhoea resolved in a greater number of children with the study than with the control diet (46/55 (84%) v 36/58 (62%); odds ratio 3.12, 95% CI 1.19 to 8.4). Survival analysis for the duration of diarrhoea also showed a reduced duration of diarrhoea in children receiving the study diet. There was also a trend in daily stool reduction in children receiving the study diet, significant on days 4-7. CONCLUSION: Results show that Benefiber supplemented comminuted chicken diet enhances recovery of children with persistent diarrhoea, indicating its therapeutic potential.

High prevalence of cagA and vacA seropositivity in asymptomatic Bangladeshi children with Helicobacter pylori infection.

AIM: To evaluate the prevalence of antibodies against two major markers of virulence of Helicobacter pylori--cytotoxin-associated gene A (cagA) and the vacuolating cytotoxin gene (vacA)--among children in a peri-urban community of Bangladesh, and to evaluate Western blot (WB) assay for detection of H. pylori infection diagnosed by 13C urea breath test (UBT) in such children. METHODS: One hundred and eighty-two children aged 18-60 mo, of the peri-urban community of Dhaka, were screened for H. pylori infection using UBT, and the serum samples were analysed for antibody against cagA and vacA by Western blot. RESULTS: The overall prevalence of H. pylori infection by 13C-urea breath test was 80%. The seroprevalence of cagA with or without vacA, vacA with and without cagA, and both cagA and vacA were 82%, 82% and 81%, respectively. Among children with a positive UBT, 95% were seropositive for both cagA and vacA, indicating that the products of these genes are frequently co-expressed in H. pylori infection in this community. The sensitivity, specificity, positive and negative predictive value of the Western blot test for H. pylori infections, compared to UBT, were 94%, 68%, 92% and 76%, respectively. CONCLUSION: Compared to UBT, Western blot test is reliable for the detection of H. pylori infection. The high seroprevalence of cagA- and vacA-positive virulent H. pylori strains in an asymptomatic paediatric population indicate that such strains are common in this population and may cause characteristic H. pylori infection in Bangladesh.

Recrudescence and reinfection with Helicobacter pylori after eradication therapy in Bangladeshi adults.

BACKGROUND & AIMS: In developing countries where Helicobacter pylori infection is widespread, posttherapeutic recurrence rates may be high. Many of the limited studies available have methodological problems and show varied recurrence rates. We determined late recrudescence rates, true reinfection, and ulcer recurrence. METHODS: One hundred five Bangladeshi patients with H. pylori infection and duodenal ulcer disease were treated with a triple therapy. Follow-up included 13C-urea breath tests, endoscopy, and biopsy-based tests. In reinfected patients, genomic typing compared pretherapeutic and posttherapeutic strains. RESULTS: Recrudescence, associated with nitroimidazole-based treatment, occurred in 15 of 105 patients (14%) within the first 3 months, but only 8 of 105 patients tested positive 4 weeks after therapy ended. True reinfection was diagnosed in 11 of 105 patients between 3 and 18 months after therapy. The annual reinfection rate was 13%, based on a total follow-up of 84.7 patient years. Ulcer relapse occurred in 2 of 15 (13%) recrudescence cases and in 6 of 11 (55%) reinfection cases, but also in 4 of 73 (5%) H. pylori-negative patients. CONCLUSIONS: In Bangladesh, late recrudescence of H. pylori after eradication therapy occurs within the first 3 months. The reinfection rate is high and might influence cost-benefit analyses for determining diagnostic and therapeutic procedures.

Urinary choloyl-PABA excretion in diagnosing small intestinal bacterial overgrowth: evaluation of a new noninvasive method.

The synthetic substrate cholyl-PABA, developed by conjugating cholic acid with paraaminobenzoic acid, is hydrolyzed by the bacterial enzyme cholyl hydrolase to release free PABA. This study aimed to evaluate whether quantitating urinary excretion of PABA after oral administration of cholyl-PABA can detect small intestinal bacterial overgrowth. In the first phase, investigations were performed on 10 healthy volunteers to study the dynamics of urinary excretion of PABA and any adverse reactions after oral administration of 1.2 g of cholyl-PABA. Another 10 healthy volunteers and 25 adult patients with various gastrointestinal disorders participated in the second phase, where the urinary cholyl-PABA test was compared to the [14C]xylose breath test (XBT). The upper limit of normal levels of urinary PABA excretion at the end of 4 h was 1.1% of the administered dose of cholyl-PABA. The urinary PABA excretion after 4 hr [median (range), in percentage] in the XBT-positive group was 1.6 (0.6-35.0), which was significantly higher than those in the XBT-negative group [0.7 (0.4-1.8)] and the healthy controls [0.7 (0.2-1.1)]. The agreement between the XBT and the urinary cholyl-PABA test was 85.7% (P < 0.01). No adverse effect was noted. In conclusion, the urinary cholyl-PABA test offers a simple, safe, noninvasive, and rapid method for diagnosing small intestinal bacterial overgrowth and warrants further clinical evaluation.

Screening of patients with acute infectious diarrhoea: evaluation of clinical features, faecal microscopy, and faecal occult blood testing.

BACKGROUND: For optimal management of acute infectious diarrhoeal diseases, it is necessary to utilize a screening process to distinguish between invasive and non-invasive diarrhoeas. The aim of this study was to compare the diagnostic utilities of clinical features, faecal microscopy (FM), and faecal occult blood testing (FOBT) in distinguishing invasive diarrhoeas from non-invasive ones. METHODS: A total of 1008 patients with acute diarrhoea were evaluated. Rectal swabs were cultured for Salmonella, Shigella, and Vibrio species; rectal swabs from 109 of these patients were also examined for Campylobacter, enterotoxigenic Escherichia coli, and rotavirus species. Isolation of faecal enteropathogens served as the gold standard. FOBT was performed with a commercial modified guaiac test. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and likelihood ratio were compared. RESULTS: Among the 1008 patients 402 with a single identified enteropathogen were available for analysis. Invasive and non-invasive enteropathogens were isolated from 262 (65.2%) and 140 (34.8%) cases, respectively. The presence of visible blood in faeces was almost a pathognomonic sign of invasive diarrhoea but had poor sensitivity. Clinical features were useful but inadequate in differentiating patients with non-bloody diarrhoea (74% of patients) into invasive and non-invasive categories. The sensitivities, specificities, PPVs, and NPVs of FM and FOBT were 75%, 77%, 58%, 88%, and 85%, 68%, 53%, and 91%, respectively. CONCLUSION: The presence of visible blood in faeces is a highly specific clinical feature of invasive diarrhoea but suffers from low sensitivity. In non-bloody diarrhoea FOBT is a valuable screening test and is comparable to FM, particularly when interpreted in the clinical context.

Partially hydrolyzed guar gum-supplemented oral rehydration solution in the treatment of acute diarrhea in children.

BACKGROUND: Partially hydrolyzed guar gum (Benefiber; Novartis Nutrition, Minneapolis, MN, U.S.A.) is fermented by colonic bacteria liberating short-chain fatty acids (SCFAs), which accelerate colonic absorption of salt and water. The purpose of this study was to evaluate the effect of Benefiber (BF)-supplemented World Health Organization Oral Rehydration Solution (WHO ORS) in the treatment of acute noncholera diarrhea in children. METHODS: A double-blind, randomized, controlled clinical trial was performed at ICDDR,B in 150 male children aged 4 to 18 months who had watery diarrhea of less than 48 hours' duration. After admission, children were assigned to receive either WHO ORS or BF-supplemented WHO ORS until recovery. Major outcome measures, such as duration of diarrhea and amount of stool output, were compared between the treatment groups. RESULTS: Patients receiving BF-supplemented WHO ORS had significantly reduced duration of diarrhea compared with the control group (mean +/- SD, 74 +/- 37 vs. 90 +/- 50 hours, P = 0.03). Survival analysis for duration of diarrhea also showed a reduction the BF-supplemented WHO ORS-treated group (P = 0.025, log rank test). There was also less stool output daily from days 2 through 7 in the patients treated with BF-supplemented WHO ORS compared with that in the children treated with WHO ORS; the reduction was significant on day 7 only. CONCLUSION: Benefiber added to standard WHO ORS substantially reduces the duration of diarrhea and modestly reduced stool output in acute noncholera diarrhea in young children, indicating its potential as a new antidiarrheal therapy for acute diarrhea in children.

Intestinal immune responses in patients infected with enterotoxigenic Escherichia coli and in vaccinees.

Immune responses against enterotoxigenic Escherichia coli (ETEC) were examined in Bangladeshi adults with naturally acquired disease and compared to responses in age-matched Bangladeshi volunteers who had been orally immunized with a vaccine consisting of inactivated ETEC bacteria expressing different colonization factor antigens (CFs) and the B subunit of cholera toxin. B-cell responses in duodenal biopsy samples, feces, intestinal washings, and blood were determined. Because most of the patients included in the study were infected with ETEC expressing CS5, immune responses to this CF were studied most extensively. Vaccinees and patients had comparable B-cell responses against this antigen in the duodenum: the median numbers of antibody-secreting cells (ASC) were 3,300 immunoglobulin A (IgA) ASC/10(7) mononuclear cells (MNC) in the patient group (n = 8) and 1,200 IgA ASC/10(7) MNC in the vaccinees (n = 13) (not a significant difference). Similarly, no statistically significant differences were seen in the levels of duodenal B cells directed against enterotoxin among vaccinees and patients. A comparison of the capacities of the various methods used to assess mucosal immune responses revealed a correlation between numbers of circulating B cells and antibody levels in saponin extracts of duodenal biopsy samples (r = 0.58; n = 13; P = 0.04) after vaccination. However, no correlation was seen between blood IgA ASC and duodenal IgA ASC after two doses of vaccine. Still, a correlation between numbers of CF-specific B cells in blood sampled from patients early during infection and numbers of duodenal B cells collected 1 week later was apparent (r = 0.70; n = 10; P = 0.03).

Helicobacter pylori colonization in infants and young children is not necessarily associated with diarrhoea.

A cohort of 151 infants and young children aged 1-23 months from a poor peri-urban community of Bangladesh was studied to determine the relationship between Helicobacter pylori colonization and morbidity due to diarrhoea. A 13C urea breath test was performed to detect the presence of H. pylori. Children were followed up at home every alternate day for 6 months and diarrhoeal morbidity data were collected. Diarrhoeal morbidity was compared between H. pylori-positive and H. pylori-negative children. Sixty-eight (45 per cent) children were H. pylori positive and 83 (55 per cent) were H. pylori negative. During the first 1-month period following the breath test, three (4.4 per cent) H. pylori-positive and four (4.8 per cent) H. pylori-negative children had diarrhoea. Thirty-two (47 per cent) of the children in the positive group and 43 (52 per cent) in the negative group had one or more episodes of diarrhoea during the 6-month follow-up period. Median number of diarrhoeal episodes was 1.0 (range 1.0-4.0) in the H. pylori-positive children and 2.0 (range 1.0-5.0) in the H. pylori-negative children (p = 0.19). No significant difference was observed in the cumulative days with diarrhoea. The results of this study suggest that H. pylori colonization is not associated with diarrhoeal morbidity in infants and young children.

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.

Small bowel and fecal microbiology in children suffering from persistent diarrhea in Bangladesh.

BACKGROUND: The etiology of persistent diarrhea in children is multifactorial. The objective of the current study was to ascertain the role of microorganisms in the etiology and pathogenesis of persistent diarrhea in a group of children in Bangladesh. METHODS: Enteric pathogens and total aerobic microflora were studied in the duodenal aspirates of 100 children with persistent diarrhea and compared with those in aspirates of 30 children with acute diarrhea, and those in aspirates of 15 healthy control children. The enteric pathogens in the stools of these children and in stools of an additional 38 patients with persistent diarrhea and 12 with acute diarrhea were also studied. RESULTS: Approximately two thirds of the patients with acute diarrhea and persistent diarrhea, and half of the control subjects had more than 10(5) organisms per milliliter of duodenal fluid. Significantly, more patients with persistent diarrhea had a greater variety of flora than did patients with acute diarrhea and control subjects. The predominant organisms in patients with acute diarrhea and in those with persistent diarrhea were Gram-negative rods, whereas those in control subjects were Gram-positive cocci. Significantly more acute diarrhea patients and persistent diarrhea patients had enteric pathogens isolated from stool than did control subjects. Diarrheagenic Escherichia coli, as a whole, were present in significantly more persistent diarrhea patients than in acute diarrhea patients and control subjects. Among diarrheagenic E. coli, enteroaggregative E. coli were significantly associated only with persistent diarrhea. Other organisms significantly associated with persistent diarrhea were Aeromonas spp. and Klebsiella spp. Some patients in the acute diarrhea and the persistent diarrhea groups had the same pathogens isolated from both the duodenal fluid and stool. CONCLUSIONS: In accordance with results of other studies, an association between enteroaggregative E. coli and persistent diarrhea was found in the present study. This suggests that therapy directed against enteroaggregative E. coli can be evaluated for management of some cases of persistent diarrhea.

Helicobacter pylori infection in infants and children of Bangladesh.

Helicobacter pylori is an important cause of chronic gastritis and plays important roles in the etiology of peptic ulcer disease, gastric cancer and non-ulcer dyspepsia. While H. pylori infections occur worldwide, the great majority of information is from the developed countries, and little is known about the epidemiology of H. pylori in the developing countries, particularly in children.

Epidemiological features of Helicobacter pylori infection in developing countries.

Helicobacter pylori infection has a worldwide distribution, and it has distinct epidemiological features in developing countries. In contrast to that in developed countries, H. pylori infection in developing countries seems to be nearly universal, beginning in early childhood. Children become infected in the first few months of life; in some communities as many as 50% of the children are infected by the age of 5 years, and up to 90% are infected by the time they reach adulthood. In some developing countries with improvements in industrialization, socioeconomic conditions, and hygiene, infection rates are lower. The incidence of H. pylori infection, determined indirectly, also suggests a rate several times higher than that in developed countries. Marked differences in H. pylori seroprevalence have been observed between various ethnic and racial groups. Although the mode of transmission of H. pylori remains uncertain, evidence suggests person-to-person transmission occurs.