Seroprevalence of hepatitis E and Helicobacter pylori in a low socioeconomic area of a metropolitan city in a developing country.

This study aims to determine the prevalence of coinfection of H. pylori and hepatitis E virus (HEV) in the paediatric age group in an urban slum area of Karachi and identify risk factors associated with co-infection. Five hundred and forty children aged one to 15 years were investigated. Blood samples were collected and questionnaires completed on socio-demographic characteristics. Anti-H. pylori, HEV IgG and IgM antibodies were analysed by enzyme immunoassays (EIAs). The seroprevalence of H. pylori antibody was 47.2%, while that of HEV IgG and IgM was 14.4% and 2.4%, respectively. 12.4% exhibited seroprevalence for both H. pylori and HEV (IgG). In 67 (26%) cases positive for H. pylori IgG, HEV IgG positivity was also seen (P < 0.001). Only 13 (5%) positive for H. pylori were also positive for HEV IgM (P < 0.001). Only 11 (4%) HEV IgG-positive cases were H. pylori antibody-negative (P < 0.001). Hepatitis E virus was common in children who had access to municipal piped water (P = 0.025). H. pylori was common in children who used a non-flush toilet system (P < 0.001). Children exposed to H. pylori infection were also exposed to the risk of HEV.

Risk factors associated with typhoid fever in children aged 2-16 years in Karachi, Pakistan.

We analysed the data from the control group in a typhoid vaccine trial in Karachi to assess the differences in individual-, household- and cluster-level characteristics for developing typhoid fever. The annual incidence of typhoid in children aged 2-16 years in the control arm of the vaccine trial was 151/100 000 population. After adjustment, the risk of typhoid was lower with increasing age [risk ratio (RR) 0·89, 95% confidence interval (CI) 0·83-0·95], was higher with an increase in population density (RR 1·13, 95% CI 1·05-1·21) and was lower in the households using a safe drinking-water source (RR 0·63, 95% CI 0·41-0·99). Typhoid fever affects younger children living in areas of high population density and lack of access to safe water in Pakistan. A combination of environmental and biological interventions is required to prevent the continued epidemiological and economic impact of typhoid fever in high-risk areas of Pakistan.

Helicobacter pylori infection in children: population-based age-specific prevalence and risk factors in a developing country.

AIM: We estimated the prevalence, age of acquisition and risk factors for Helicobacter pylori (H. pylori) seroprevalence in children aged 1-15 years. METHODS: Exposure was assessed using ELISA. Parents responded to a questionnaire regarding number of individuals sharing house, rooms, water source, latrines, housing and assessment of socioeconomic status (SES) by Hollingshead Index. RESULTS: Serum of 1976 children was tested. Helicobacter pylori seropositivity in children aged 11-15 years was 53.5% (OR: 2.0, 95% CI: 1.58-2.5). It increased with moderate crowding index (CRI) of 2-4 to 45.9% (OR: 1.23, 95% CI: 0.92-1.63) and to 51.2% with CRI >4 (OR: 1.52, 95% CI: 1.12-2.06). In middle SES, seropositivity was 50.5% (331/655) (OR: 1.7, 95% CI: 1.29-2.35), whereas in lower SES, it was 47.1% (500/1062) (OR: 1.5, 95% CI: 1.1-2.0). Multivariate analysis showed that Helicobacter pylori seroprevalence was high in children aged 6-10 and 11-15 years (OR: 1.5, 95% CI: 1.2-1.9 and OR: 1.9, 95% CI: 1.56-2.47 respectively), in lower-middle SES (OR: 1.6, 95% CI: 1.2-2.1 and OR: 1.5, 95% CI: 1.10-2.0 respectively) and in uneducated fathers (OR: 1.58, 95% CI: 1.27-1.95). CONCLUSION: Helicobacter pylori seropositivity increases with age, in low-middle SES and is related to father's educational status. Reducing H. pylori seroprevalence will require improvement in sanitary conditions and educational status of the population.

Enhanced detection rate of typhoid fever in children in a periurban slum in Karachi, Pakistan using polymerase chain reaction technology.

OBJECTIVE: Yield of blood culture in clinically suspected cases of typhoid fever is low, whereas indirect serological diagnostic tests are unreliable. Hence, polymerase chain reaction (PCR)-based detection of Salmonella enterica Serovar typhi was used as an aid for diagnosis of typhoid fever in addition to other diagnostic tests. Two periurban communities in Karachi were selected for an epidemiological study of typhoid fever. The aim of the study was to assess whether PCR increased the detection rate of typhoid fever in children in the community. MATERIAL AND METHODS: Children aged 2 to 14 years presenting with fever lasting for three or more days were selected. PCR using Hashimoto's protocol based on ViaB gene sequence was used in addition to blood culture and other serological tests. RESULTS: Of the 214 children included in the study, blood culture was found positive for S. enterica S. typhi in 26 (12.4%) cases, whereas 24 children (11.7%) were diagnosed as suffering from typhoid fever when the PCR-based method was used. Both tests were positive in only 10 (4.9%) children. The number of children found positive for either test was 40. PCR increased the rate of detection of typhoid fever by 51%. CONCLUSION: The sensitivity, specificity, +ve and -ve predictive values of PCR in this study were 40%, 93%, 45% and 92%, respectively.

Health care utilization for diarrhea and fever in 4 urban slums in Karachi.

OBJECTIVE: To estimate the fraction of fever and diarrhea patients making use of private practitioners, self-treatment, hospital care, drug vendors, community health centers and traditional healers. DESIGN: A cross-sectional survey. PLACE AND DURATION OF STUDY: Four slums in and around Karachi during October and November, 2001. PATIENTS AND METHODS: A sample of 1842 households was selected with probability proportional to size of the slum. The household head or a representative was asked regarding the treatment providers for diarrhea and cases of fever persistent for 3 days or more. Only households with an actual case of fever and/or diarrhea were included in the analysis. RESULTS: The study found that more than half of diarrhea and fever cases are seen by private practitioners. Self medication with medicines available in the home or specifically purchased for the disease episode from a drug vendor combined provides 13% to 18% of health care. Only between 11% and 13% of patients are seen by the public sector, hospitals and community health centers. There was no significant difference between the choice of health care provider for diarrhea and fever cases. CONCLUSION: In this survey, the majority of fever and diarrhea patients presented first to private practitioners and not to drug vendors or the public sector. Successful passive surveillance of febrile or diarrheal illness in these communities has to integrate private practitioners.

Status epilepticus in children: a five-year experience at Aga Khan University Hospital.

OBJECTIVE: Status epilepticus is an under diagnosed entity in Pakistan. It is a potentially reversible condition but has a high mortality, if it is not recognized and managed on time. The purpose of this study was to determine the clinical profile and the relationship of mortality of status epilepticus with its known risk factors. METHODS: This was a retrospective study. Medical records of all the patients admitted in the last five years (1998-2002) with a diagnosis of status epilepticus (ICDcode 345.30, 345.31) were reviewed. Data was recorded on a Performa and analyzed by using the statistical programme SPSS, chi square and Fischer exact test. RESULTS: The total number of patients were twenty-four. Sixteen patients were males (66.7%). Mean age was fifty-eight months and mean duration of hospital stay 5.5 days (range 2 to 22days). Eight patients were diagnosed to have epilepsy. Four (16.7%) had a previous history of status epilepticus. Three patients presented with status epilepticus for the first time without any previous history of seizures. Ten patients required midazolam infusion (41.7%) and out of these 3 (12.5%) were also given thiopentone infusion to control the seizures. Nine patients were shifted to the ICU for ventilation and control of seizures. Mortality in our study was 25%. Risk factors for mortality included age less than or equal to one year, abnormal MRI, type of the status epilepticus and the total duration of status epilepticus. No significant relationship was found with any of the known risk factors CONCLUSION: Status epilepticus is a neurological emergency. A very high mortality was seen in our study. No risk factors were identified for this high mortality.

Zinc supplementation in malnourished children with persistent diarrhea in Pakistan.

OBJECTIVE: To evaluate the potential benefit of dietary supplementation of a rice-lentil (Khitchri) and yogurt diet with 3 mg/kg/d of elemental zinc (as zinc sulfate) in hospitalized malnourished children (age 6-36 months) with persistent diarrhea for 14 days. METHODOLOGY: Randomized, double-blind placebo-controlled trial. SETTING: Nutrition Research Ward at the National Institute of Child Health, Karachi, Pakistan, where children were admitted for 14 days of inpatient supervised rehabilitation. PRIMARY OUTCOME: overall weight gain by day 14. SECONDARY OUTCOMES: overall energy intake, stool output, time to diarrheal recovery and weight gain (>/=3 days), plasma zinc, copper, prealbumin, and insulin-like growth factor-1. RESULTS: Of 87 children randomized for supplementation with either zinc or placebo, the two groups were comparable at admission in terms of severity and duration of diarrhea, as well as nutritional and anthropometric parameters. The overall weight gain, stool volume, stool frequency, as well as the time taken for diarrheal recovery or steady weight gain, were comparable for both supplemented children and controls. Supplemented children had a significant improvement in plasma zinc levels and serum alkaline phosphatase by day 14 of therapy in comparison with controls. Plasma copper levels were low in both groups at admission and although an increase was seen in control children, levels decreased further after zinc supplementation. There was no significant difference between the two groups for hemoglobin, serum albumin, prealbumin, and plasma insulin-like growth factor-1 increments during the course of therapy. Evaluation of primary and secondary outcome criteria among the subset of children with plasma zinc levels <60 microg/d at admission did not reveal any significant differences. CONCLUSIONS: Although there was satisfactory recovery in malnourished children with persistent diarrhea receiving the Khitchri-yogurt diet, there was no evidence of improved weight gain or acceleration of recovery from diarrhea with zinc supplementation. In contrast, the reduction in plasma copper levels in zinc-supplemented malnourished children suggests that caution should be exercised in supplementing severely malnourished children with zinc alone.

Insulin-like growth factor I response during nutritional rehabilitation of persistent diarrhoea.

OBJECTIVE: Evaluation of nutritional recovery, intestinal permeability, and insulin-like growth factor I (IGF-I) response in malnourished children with persistent diarrhoea and their relation to concomitant systemic infection(s). STUDY DESIGN: Open study of severely malnourished children (aged 6-36 months) with persistent diarrhoea (>/= 14 days) admitted for nutritional rehabilitation with a standardised rice-lentil and yogurt diet. Successful recovery was defined prospectively as overall weight gain (> 5 g/kg/day) with a reduction in stool output by day 7 of treatment. Data on coexisting infections and serum C reactive protein (CRP) were collected at admission. RESULTS: Of 63 children, 48 (group A) recovered within seven days of dietary treatment. These children had a significant increase in serum IGF-I (DeltaIGF-I%) and, in contrast to serum prealbumin and retinol binding protein, DeltaIGF-I% correlated with weight gain (r = 0.41). There was no correlation between the IGF-I response and intestinal permeability as assessed by urinary lactulose/rhamnose excretion. Treatment failures (group B) included more children with clinical (relative risk, 4.8; 95% confidence interval, 1.2 to 19.7) and culture proven sepsis at admission and higher concentrations of serum CRP (median (range), 36 (0-182) v 10 (0-240) mg/l) at admission. There was a negative correlation between admission CRP concentration and DeltaIGF-I% (r = -0.45). CONCLUSIONS: In comparison with serum albumin, prealbumin, and retinol binding protein, serum IGF-I increment is a better marker of nutritional recovery in malnourished children with persistent diarrhoea. The possible association of systemic infections, serum IGF-I response, and mucosal recovery needs evaluation in future studies.

Self-reported feeding advice by physicians for common childhood illnesses.

BACKGROUND: A nutritious diet is important for recovery during illnesses. Dietary advice by physicians and consumption of food by the patients are often based upon their hot and cold concepts and beliefs about various foods rather than on scientific basis. OBJECTIVES: To look at the food-advising behaviour of physicians during illnesses and to know the maternal concepts about various foods being hot or cold. METHODS: A questionnaire was served to the physicians participating in a continuous medical education session held at the Aga Khan University and Hospital, asking them to write the foods they advise or restrict during different illnesses such as fever, jaundice etc. Mothers of sick children suffering from diarrhea and other illnesses were also interviewed to know their concepts about various foods. RESULTS: Six (10%) out of sixty physicians believed in hot and cold concepts of the food. A variety of common foods were either restricted or strongly recommended by 10% to 50% of these physicians without any scientific basis, 23% physicians restricted fatty foods in jaundice, 17% physicians restricted in cough and cold. Although the interviewed mothers believed in hot-cold concepts of food but 55-63% of them were not sure what is meant by hot or cold food. In spite of that 70-80% of these mothers classified chicken, meat, egg, brinjal, masoor and mangoes are hot foods and rice, yogurt, moong, banana and orange as cold foods. CONCLUSION: Hot-Cold concept of food exists not only in mothers but also in physicians. Proper education regarding food intake is mandatory for both mothers and physicians to ascertain adequate intake of calories during sickness.

Maternal vitamin-D deficiency in Pakistan.

OBJECTIVE OF THE STUDY: This study was performed to assess the vitamin D status of healthy Pakistani nursing mothers and their breastfed infants. METHODS: Seventy-one nursing mothers and their breastfed infants belonging to upper and lower socio-economic class were examined 6 weeks to 11 months after delivery. Serum 25-hydroxy vitamin D [25(OH)D], serum calcium, phosphorus and alkaline phosphatase were measured. RESULTS: The mean serum 25(OH)D in mothers was 36.7+/-32.4 nmol/L and 41.25+/-35.4 nmol/ L in infants. Thirty-four (48%) mothers and 37 (52%) infants had levels less than 25 nmol/ L. Significantly higher levels were found in uneducated mothers (p=0.01), mothers of lower socio-economic class (p<0.001) and in those living in mud houses (p<0.001). A significant correlation was found between serum 25(OH)D levels of infants under three months of age and their mothers (p<0.01). CONCLUSIONS: High prevalence of vitamin D deficiency was found in nursing mothers and their infants predominantly in the upper socioeconomic class.

Cholera in children in Karachi from 1990 through 1995: a study of cases admitted to a tertiary care hospital.

Although cholera is an endemic disease in Bangladesh, India and other countries, it was never a significant cause of gastroenteritis in Pakistan before 1988. Since then, cases of cholera are identified each year, both in adults and children in Pakistan. In order to see the contribution of Vibrio cholerae as a cause of gastroenteritis in children, we reviewed the cases of cholera admitted in the pediatric ward of the Aga Khan University Hospital, Karachi, Pakistan. Of 4346 children hospitalized with gastroenteritis during 1990 through 1995, 348 children (8%) were confirmed to have cholera. The youngest child with cholera was seven days old. The mean age was 31 +/- 34 months. The cases of cholera were received from all over the city. Most cases were due to Vibrio cholerae Ogawa biotype ELTOR but the new strain, i.e., Vibrio cholerae 0139 was isolated in 14% cases in 1994. The sensitivity of Vibrio cholerae has also changed. In 1994, the organisms were resistant to commonly recommended antibiotics, i.e., tetracycline, ampicillin and erythrocin but sensitive to ceftrioxone, cefixime, ofloxacin and nalidixic acid. Adequate measures to improve hygiene and sanitation and supply of safe potable water is needed to prevent any future epidemic of cholera in the city.

Vitamin D status of breastfed Pakistani infants.

This study was conducted to evaluate the vitamin D status of healthy breastfed Pakistani infants and their nursing mothers. Sixty-two breastfed healthy infants and their nursing mothers belonging to the upper and lower socioeconomic classes were examined. Serum 25-hydroxy vitamin D [25(OH)D], serum calcium, phosphorus and alkaline phosphatase were measured. The mean serum 25(OH)D in infants was 34.59 +/- 26.56 nmol/l. Fifty-five percent of infants and 45% of mothers had very low serum 25(OH)D levels (<25 nmol/l). Significantly higher levels were found in infants of lower socioeconomic class (p < 0.001) and in those living in mud houses (p = 0.002) and infants >6 months (p < 0.001). A high prevalence of vitamin D deficiency was found in breastfed infants and nursing mothers, predominantly among those belonging to the upper socioeconomic class. Infants of the lower socioeconomic class had comparatively higher serum 25(OH)D levels, but even these levels were below the normal range for infants (90 +/- 27.5 nmol/l).

Factors determining recovery during nutritional therapy of persistent diarrhoea: the impact of diarrhoea severity and intercurrent infections.

The recovery pattern and outcome were analysed in 261 consecutive children (age 6-36 months) with persistent diarrhoea who underwent inpatient nutritional rehabilitation with a rice-lentil (Khitchri) and yoghurt-based diet. Overall, 217 (83%) recovered successfully, as judged by a reduction in stool output and weight gain for a consecutive 3 d. Failures were more commonly febrile at admission [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.1-4.8] and a greater number had culture-proven sepsis (Fisher's exact test, p < 0.001). Logistic regression analysis identified significantly increased risk of treatment failure with several admission characteristics, including stool frequency > 5 d(-1) (OR 2.9, 95% CI 1.6-5.2), vomiting (OR 2.5, 95% CI 1.1-5.7) and sepsis (OR 2.8, 95% CI 1.1-7.5). Survival analysis revealed significantly longer time-to-recovery among children with stool frequency > 5 d(-1) at admission (p < 0.001), suspected sepsis necessitating intravenous antibiotics (p < 0.001) or oral candidiasis (p < 0.05). These findings suggest that severity of diarrhoea and coexisting systemic infections are key determinants of the response to nutritional therapy in children with persistent diarrhoea.

Lactose intolerance in persistent diarrhoea during childhood: the role of a traditional rice-lentil (Khitchri) and yogurt diet in nutritional management.

Lactose intolerance is frequently encountered in children with persistent diarrhoea (PD). Selection of an appropriate milk-based formulation is a major management problem in the developing world. In a consecutive series of studies, we evaluated the role of feeding a traditional rice-lentil (khitchri) diet alone (KY) or in combination with either soy formula (KY-Soy) a dilute buffalo milk (KY-B), in children (age 6 months-3 years) with PD. Serial observations of stool output, caloric intake and weight gain of these children over a 14 day period indicated satisfactory tolerance of the KY diet with adequate weight gain. The weight gain and stool output was however higher in lactose intolerant children, with the worst results seen with K-Y and buffalo milk combination. While lactose intolerant children with PD do have higher. rates of therapeutic failure, our data indicates that a traditional diet and yogurt combination can be used satisfactorily for nutritional rehabilitation in over 80% of such children.

Paediatric prescribing in Karachi.

To assess amount of drug overuse we studied drug prescribing for common childhood problems by 65 general practitioners (GPs) and 29 paediatricians. A total of 2433 encounters between GPs or paediatricians and children under five years of age were observed. The presenting complaints were fever in 18%, cough in 9%, both fever and cough in 21%, vomiting in 20% and diarrhoea in 41% of encounters. Antibacterials were prescribed in 49% of encounters, analgesics and antipyretics in 29%, antiemetics in 8% and injectables in 15%. Antidiarrhoeals were prescribed in 41% encounters with children reported to have diarrhoea. Ampicillin and cotrimoxazole were the two common antibacterials prescribed by both GPs and paediatricians. Antibacterials were prescribed in significantly larger number of encounters with GPs than in those with paediatricians. Mean encounter time of patients with GPs was 3.4+/-2.7 minutes and with paediatricians 9.7+/-4.1 minutes.

Risk factors for mortality among hospitalized children with persistent diarrhoea in Pakistan.

We evaluated factors associated with mortality among a cohort of malnourished children with persistent diarrhoea (PD) admitted for nutritional rehabilitation with a defined rice-lentil (Khitchri) and yoghurt diet. Of 302 children consecutively admitted with PD, 13 (4 per cent) died, mostly (62 per cent) within 72 h of admission. Univariate analysis of risk factors at admission associated with mortality indicated significantly increased risk of death with severe stunting [relative risk (RR) 3.1, 95 per cent confidence interval (CI) 1.1-9.0], hypoalbuminaemia (RR 4.3, 95 per cent CI 1.5-12.3), stool frequency > 12/day (RR 6.0, 96 per cent CI 2.0-17.6), stool volume > 100 g/kg/day (RR 10.7, 95 per cent CI 3.0-37.6) and severe dehydration (RR 7.5, 95 per cent CI 2.6-21.8). Children who died also had comparatively shorter duration of diarrhoea at admission, and were also associated with higher rate of bacteremia at admission (Fisher's exact test P < 0.01). The logistic regression model evaluating multivariate risk of mortality identified weight-for-age z-score and sepsis as significant risk factors. Our data suggest that severe malnutrition and sepsis are associated with significantly increased risk of mortality in children with PD. Stringent screening for infections and recognition of subgroups with severe malnutrition and severe diarrhoea may improve screening and case management strategies for this disorder.

Self-reported concepts about oral rehydration solution, drug prescribing and reasons for prescribing antidiarrhoeals for acute watery diarrhea in children.

Sixty-seven general practitioners (GPs) and 27 paediatricians practising in Karachi were interviewed to evaluate their knowledge and attitude towards use of oral rehydration solution (ORS) and management of acute watery diarrhoea (AWD) in children and to define factors for their self-reported prescribing of antidiarrhoeals. Whilst nearly 50% of them reported ORS to be palatable and acceptable by children, 80% reported that ORS was not accepted by parents as sole treatment. Eighty per cent of GPs and 37% of paediatricians reported prescribing antidiarrhoeals for AWD in children, and 'parental pressure' and 'use as placebo' were the commonest reasons. In addition 45% of GPs believed in the efficacy of antidiarrhoeals and thought these drugs necessary for the control of diarrhoea.

Efficacy of traditional rice-lentil-yogurt diet, lactose free milk protein-based formula and soy protein formula in management of secondary lactose intolerance with acute childhood diarrhoea.

Secondary lactose intolerance is often a cause of prolongation of diarrhoeal episodes. As appropriate management of lactose intolerance is elimination of lactose from diet, expansive lactose free formulae are often prescribed in acute childhood diarrhoea without establishing diagnosis of lactose intolerance. Since cheap weaning diets made from locally available cereals have been found effective in management of persistent diarrhoea, we postulated that same weaning diet made of rice lentil and yogurt (K-Y diet) could be effectively used in management of acute childhood diarrhoea associated with secondary lactose intolerance. We compared this K-Y diet with milk protein-based lactose free and soy-protein formula. Thirty children between 3-18 months of age completed dietary trial for 72 h. Of these nine children received K-Y diet (Group A), four children received milk protein-based formula (Group B) and 11 children received soy protein formula (Group C). Stool frequency was significantly reduced in children in Group A (13 +/- 6 on day 1 to 6 +/- 5 on day 3) and in Group B (13 +/- 5 on day 1 to 7 +/- 4 on day 3), but not in Group C (13 +/- 4 on day 1 to 10 +/- 8 on day 3). No significant difference was observed in intake of diet, total calories intake, and fluid intake among the three groups. It is concluded that cheap weaning diet made of locally available cereals and yogurt can be used effectively in management of secondary lactose intolerance associated with acute childhood diarrhoea.