Vitamin A supplementation in acute diarrhea.

BACKGROUND: Vitamin A supplementation reduces the severity of subsequent diarrheal episodes. This study was conducted to examine the effect of single oral high-dose vitamin A supplementation on the duration of acute diarrhea in 6- to 12-month-old infants who are not malnourished. METHOD: In this double-blind, randomized, placebo-controlled study, infants who were admitted to Hacettepe University Ihsan Dogramaci Children's Hospital Diarrheal Diseases Training and Treatment Unit with acute diarrhea were randomly assigned either to a group receiving a single oral dose of 100,000 IU vitamin A or placebo. There were 60 infants in each group. All infants were followed up until the diarrheal episode ended. Serum vitamin A levels were determined both at admission and 2 weeks later. RESULTS: No effect of vitamin A supplementation could be demonstrated on either the total duration of diarrhea (7.4 +/- 3.2 days in the treatment group vs. 7.8 +/- 3.1 days in the placebo group) or on its duration after intervention (3.8 +/- 2.3 days in the treatment group vs. 3.9 +/- 1.9 days in the placebo group; P > 0.05 for both comparisons). Serum vitamin A levels were not significantly different at admission (23.5 +/- 9.7 microg/dL in the treatment group vs. 24.1 +/- 9.7 microg/dL in the placebo group; P > 0.05) nor at the end of a follow-up period of 2 weeks (treatment: 33.3 +/- 13.7 microg/dL, placebo: 35.2 +/- 11.2 microg/dL; P > 0.05). However, the increase in serum vitamin A levels at the end of the 2-week follow-up interval for infants in both the treatment and placebo groups were found to be significant compared with levels at admission (P < 0.01). The mean weight gain in both groups were similar by the end of the first month (6.9 +/- 5.0% in the treatment group vs. 6.3 +/- 4.2% in the placebo group; P > 0.05). CONCLUSION: No effect of oral vitamin A supplementation on serum vitamin A levels, duration of diarrhea, or weight gain during an acute diarrheal episode could be demonstrated in our study group of infants between 6 and 12 months of age who had no malnutrition.

Clinical trial to evaluate immunogenicity and safety of inactivated hepatitis A vaccination starting at 2-month-old children.

Active immunization with hepatitis A vaccine has been shown to provide long-term protection against hepatitis A virus (HAV) infection. However, few data are available regarding use of the hepatitis A vaccine in children under two years of age. The present study was conducted to test the safety and immunogenicity of inactivated hepatitis A vaccine administered to infants, and to evaluate the correlation between mother and infant anti-HAV antibodies. A total of sixty healthy children, two months of age, were enrolled in this study and immunized with 360 EU of inactivated hepatitis A vaccine (Havrix) according to the two, four and six months of age schedule. Blood sampling was performed prior to the first vaccination and one month after the third vaccination at seven months. Venipuncture was also done on mother on admission. The reactogenicity was expressed as the percentage of reported local and systemic reactions. The most common side effects were erythema on the injection site and fever. Infants with passively transferred maternal anti-HAV antibodies had a reduced anti-HAV GMT after vaccination. On admission, only one infant and his mother were seronegative and seroconversion was only detected in this infant. One month after the third dose seven infants (12.3%) were found to be seronegative. The infant without passively acquired maternal anti-HAV had the protective levels with a GMT of 3176 mIU/ml one month following the third dose. There was a significant positive correlation between the titers of mother and infant anti-HAV antibodies (n = 0.96, p < 0.001) on admission. Hepatitis A vaccine showed no immunogenicity in infants with presence of maternal antibodies. Hepatitis A vaccine is safe but it should be used after the disappearance of maternal antibodies.

Short-term developmental outcome of iron prophylaxis in infants.

BACKGROUND: Previous studies on the cognitive effects of iron treatment have focused on anemic or non-anemic iron-deficient infants. The effect of iron supplementation on cognitive development among iron-sufficient infants has not been studied. The aim of the present study was to examine the effect of iron supplementation on performance in the Bayley Scales of Infant Development (BSID) and anthropometric measurement in 6-month-old iron-sufficient healthy infants. METHODS: Healthy, iron-sufficient infants who were 6 months of age and were attending the Well Baby Clinic were considered for enrollment. Infants were randomly assigned to take ferrous sulfate supplementation (1 mg/kg per day) or no supplementation and were followed for 3 months. Anthropometric measurement, hematologic status and BSID were evaluated on admission and after 3 months. RESULTS: Seven infants in the intervention group and nine in the control group completed the study. No significant differences were observed in anthropometric measurements and complete blood counts between the two groups after the 3 month study period. The mean transferrin saturation (TS) level decreased significantly in the control group during the study period (from 15.3+/-2.6 to 7.8+/-5.1%; P = 0.0117), but no such reduction was seen in the intervention group. At the end of the study, the TS of the control group was found to be significantly lower than that of the intervention group (7.8+/-5.1 vs. 19.9+/-7.9%, respectively; P = 0.0033). The BSID scores of infants in both groups were within the normal range on admission and at the end of the study period. CONCLUSIONS: Short-term iron supplementation did not change developmental test scores despite the hematologic response in iron-sufficient healthy infants. The high prevelance of iron-deficiency anemia and its relationship with adverse developmental outcome suggests that prevention of iron-deficiency anemia with prophylaxis needs to be emphasized, rather than treatment.

Immunogenicity study of a combined diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis vaccine used to reconstitute a freeze-dried Haemophilus influenzae type b vaccine (DTaP-IPV//PRP-T) administered simultaneously with a hepatitis B vaccine at two, three and four months of life.

This study was designed to assess the immunogenicity of a vaccine combining diphtheria and tetanus toxoids, acellular pertussis vaccine, and inactivated poliovirus vaccine reconstituting Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (DTaP-IPV//PRP-T; Pasteur Mérieux Connaught, Lyon, France) administered simultaneously in association with hepatitis B vaccine (RECOMBIVAX (¿trade mark omitted¿) Merck, Sharp & Dohme, West Point, PA, USA) for the primary immunization of infants. The vaccines were administered at two, three and four months of age. One hundred and sixty-two healthy infants, aged 8-10 weeks, were enrolled in the study. Blood samples were taken before the first dose and 4 weeks after the third dose. The infants were observed for 15 minutes after vaccination for any immediate reaction. Adverse events requiring a medical consultation were recorded by the parents in a diary over the 7 days following vaccination. Four weeks after the third immunization, the percentages of infants fulfilling seroconversion criteria were 98.9% for pertussis toxin, 95.9% for filamentous haemagglutinin, 100.0% for tetanus, 100.0% for diphtheria, 99.3% for poliovirus type 1, 100.0% for both poliovirus types 2 and 3, 98.0% for Haemophilus influenzae type b, and 100% for hepatitis B surface antigen. No vaccine-related serious adverse event was reported. The simultaneous administration of DTaP-IPV//PRP-T and hepatitis B vaccines at two, three and four months of age yielded clinically satisfactory immune responses to all antigens compared with historical controls and gave a good safety profile.

Clinical characteristics of transient glucose intolerance during acute diarrhoea.

Transient glucose intolerance (TGI) is an important cause of WHO G-ORS (Glucose-Oral Rehydration Solution) treatment failure and hospitalization in dehydrated children during acute diarrhoea. This retrospective case-control study was designed to determine some risk and predictive factors for developing TGI among moderately dehydrated patients with acute diarrhoea while under G-ORS therapy. Among moderately dehydrated patients, files of 22 patients with TGI and 66 other dehydrated patients without intolerance were reviewed. Patients with TGI were younger (9.7+/-10.5 mo and 11.6+/-7.8 mo, respectively, p < 0.05), the median age being 6 mo in the TGI group and 10 mo in non-TGI group. There was no difference between groups for sex, admission season, history of fever or vomiting, frequency of vomiting, presence of blood, mucous or leukocyte in stool, presence of associated disease and duration of diarrhoea on admission. The admission haemoglobin, white blood cell, blood pH, sodium and potassium levels were similar in both groups. The mean serum chloride level (116.8+/-6.9, 109.6+/-7.9 mEq/l, respectively, p<0.05) was higher in the TGI group and the bicarbonate level was lower (12.9+/-3.8, 15.3+/-6.0, respectively, p < 0.05). Stool frequency was also higher in patients with TGI (11.2+/-5.3/24 h, 5.9+/-4.4/24 h, respectively, p < 0.05). No difference was found between the nutritional status of children in both groups. More children were breastfed in the group without TGI (34/56, 61%, 6/18, 33% respectively, p=0.079, OR=0.32, 95% CI [0.09-1.11]). It was concluded that patients with TGI are younger and have high stool frequency. Although statistical significance could not be shown, breastfeeding seems to protect children from TGI, as it protects from diarrhoea.

Priming effect, immunogenicity and safety of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis (DTaP) combination vaccine administered to infants in Belgium and Turkey.

To evaluate the priming effect, immunogenicity and safety of an Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular (two component) pertussis (DTaP) combination vaccine, a randomized, comparative study was conducted in two centers, one in Belgium and one in Turkey. A total of 410 healthy infants, 160 in Belgium and 250 in Turkey, randomly received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138) received DTaP and PRP-T vaccines reconstituted immediately prior to injection at 3, 4 and 5 months of age, and are referred to as the combined, short schedule group (Co-S). A second group (N = 135) received DTaP + PRP-T simultaneously but injected at different sites according to the same schedule, and are referred to as the associated, short schedule group (As-S). The third group (N = 137) also received DTaP + PRP-T at separate sites, but at 2, 4 and 6 months, and are referred to as the associated, long schedule group (As-L). The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial, using the same batch of DTaP vaccine. Children of both short-schedule groups (Co-S and As-S) received, at the age of 12-14 months, a booster dose of DTaP vaccine associated with unconjugated PRP vaccine. Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine. The immune response to Hib capsular polysaccharide, however, was significantly lower after combined administration (Co-S group) than after associated (As-S group) administration (P < 0.0001), with a similar trend among both countries (GMTs, 1.78 microg/ml and 6.19 microg/ml in Belgium, and 5.02 microg/ml and 11.67 microg/ml in Turkey). Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups. Belgian infants showed a significantly lower immune response to all antigens than Turkish infants (P < or = 0.001 for all antigens), with a similar trend among each study group. In all groups, the incidence of adverse events was lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of systemic reactions were observed in the Belgian population, possibly due to differences in reporting practice. Our results indicate (1) that the combination vaccine, DTaP//PRP-T, represents an important improvement over the existing uncombined vaccines; (2) that immunogenicity studies should include at least one booster injection to evaluate priming effects by combined vaccines; and (3) that it is feasible and valuable to co-randomize combination vaccine studies in sufficiently different geographical areas and child populations.

Rehydration of moderately dehydrated children with transient glucose intolerance using rice oral rehydration solution.

Following the successful rehydration of two moderately dehydrated patients with transient glucose intolerance (TGI) using rice-oral rehydration solution (R-ORS), R-ORS has been used in Hacettepe University Ihsan Dogramaci Children's Hospital Diarrhea Training and Treatment Unit (DTTU) to rehydrate moderately dehydrated children with TGI. The files of children with moderate dehydration and glucose intolerance admitted to the unit were reviewed retrospectively within two periods according to the availability of R-ORS. The clinical and laboratory findings were analysed where available. Before R-ORS became available (September 1993) 6 patients were admitted, all of whom deteriorated with glucose (G)-ORS treatment in 7.0 +/- 3.8 h and were hospitalized for i.v. fluid treatment. During the second period 22 moderately dehydrated children with TGI were admitted. The clinical and laboratory characteristics on admission of the children in the two periods were not statistically different (p > 0.05). Among the 22 patients admitted during the second period 10 were administered G-ORS in the unit and 12 had already received G-ORS at home. Clinical and laboratory deterioration was observed in these 10 patients while receiving G-ORS in the unit within 6.3 +/- 3.7 h and rehydration was continued with R-ORS. Clinical and laboratory improvement were demonstrated in 8 patients within 18.2 +/- 6.5 h. Overall, 17 patients were rehydrated successfully with R-ORS, with a mean time of 18.0 +/- 7.2 h. Five patients were hospitalized. The overall success rate of R-ORS was 77.3%. R-ORS may be considered as an alternative mode of therapy to i.v. treatment in the rehydration of moderately dehydrated children with TGI.

Cryptosporidium parvum prevalence in a group of Turkish children.

Stool samples from two hundred children with diarrhea and from 50 healthy children were examined, by modified Kinyoun's acid-fast staining (MAF), Giemsa staining and direct (DFA) and indirect immunofluorescence antibody (IFA) methods, in order to determine cryptosporidiosis prevalence under the age of 12 and to detect the most efficient identifying method for use in our country. Cryptosporidium oocysts were detected in seven (3.5%) of the cases. None of the samples from the control subjects was found to be positive for Cryptosporidium. Our results indicate that Cryptosporidial oocysts should be detected in children with diarrhea. Modified Kinyoun staining method is practical and reliable for this purpose. Immunofluorescence staining methods can be applied for conformation of the results, if available.

Safety, tolerability and immunogenicity of a Haemophilus influenzae type b vaccine containing aluminum phosphate adjuvant administered at 2, 3 and 4 months of age.

The primary aim of this study was to assess the tolerability and immunogenicity of a new Haemophilus influenzae type b (Hib)/AlPO4 (CHIRON, SpA) vaccine, in two-month-old healthy infants. Twenty-three subjects were enrolled and administered the new Hib vaccine containing AlPO4 adjuvant at two, three and four months of age concomitantly with diphtheria-pertussis-tetanus (DPT) and hepatitis B vaccines according to the local program. Children were observed for 30 minutes after each immunization for any immediate local and systemic reactions. An active surveillance for side effects was performed on the 2nd and 7th days following each immunization by telephone. Families also filled out diaries for the first seven days. From the 2nd day to the next immunization only data about adverse events necessitating a physician's visit or about serious adverse events were collected. Blood samples were obtained before the first immunization and one month after the third dose for evaluation of anti-polyribosylribitol phosphate (PRP) antibody response. Local reactions at the Hib site were mild and less frequent compared to those observed at the DPT site. Systemic reactions noted after the three immunizations were fever in 70 percent, irritability in 48 percent, persistent crying in 26 percent, change in eating habits in 22 percent, diarrhea in 17 percent, sleepiness in 17 percent, vomiting in 9 percent, and unusual crying in 4 percent of the cases. There was no serious adverse event. One hundred percent and 95 percent of children achieved an anti-PRP antibody response over 0.15 microg/ml and 1.0 microg/ml, respectively. The geometric mean titer was 15 microg/ml and the geometric mean ratio 84. It was concluded that the new (Hib)/AlPO4 vaccine is safe and well tolerated, and induced a good PRP antibody response in healthy two-month-old infants.

The effect of live measles vaccines on serum vitamin A levels in healthy children.

OBJECTIVE: Serum retinol levels have been shown to be depressed during measles infection. This study aims to demonstrate whether there is any decrease in serum vitamin A level following immunization with live viral vaccine and its relation with vaccine seroconversion in children with measles. Since many children receive measles vaccine alone or in combination with measles-mumps-rubella vaccine, we studied serum vitamin A levels and antibody levels in healthy, well-nourished children before and after immunization with monovalent and combined live attenuated measles vaccine. METHODS: The first group included 21 healthy children between the ages of 9-11 months who received live measles (Schwarz) vaccine. There were also 21 healthy children (range 14-20 months of age) who received measles-mumps-rubella Trimovax (Pasteur Merieux) vaccine. All children were tested for serum vitamin A levels before vaccination, on days 9-14 and 30-42 following both vaccinations. Measles specific antibody levels were also measured on admission and 30-42 days following vaccinations. RESULTS: In both vaccination groups, mean serum vitamin A levels reduced significantly on days 9-14, but increased slightly on days 30-42 in the measles-mumps-rubella vaccinated group (P < 0.05). The baseline and follow-up levels of mean serum vitamin A did not differ between seroconverted and nonseroconverted cases within the measles vaccinated group. CONCLUSION: Serum vitamin A levels are reduced following vaccination with monovalent and combined live attenuated measles vaccines.

Salmonella gastroenteritis in children.

Among 20,100 children with gastroenteritis admitted to Hacettepe University Ihsan Dogramaci Children's Hospital Diarrhea Training and Treatment Unit between April 1987 and December 1994, 508 Salmonella strains were isolated. Epidemiology, clinical pictures, laboratory findings, and outcome of these patients are discussed. Salmonella gastroenteritis represented 2.5 percent of all diarrheal cases during the study period. The highest number of isolations of Salmonella strains were reported between June and October. Salmonella serogroup B was the most common isolated strain (77%) followed by serogroup D (21%) and serogroup C (2%). Progressive decrease among group B isolations were noted between 1991-1994 with a concomitant increase in group D isolations. S. typhimurium was the most common serotype and overall represented 52 percent of the strains. Bloody diarrhea was found to be present in 27 percent of all cases. It is noted that the patients infected with group B strains had a higher rate of bloody diarrhea than the patients infected with group D strains (30% versus 15%, p < 0.05). Dehydration was present in 14 percent of the cases. We noted that severe dehydration (0.2%) and electrolyte disturbances (1.5%) were rare among our patients. None of these cases had a complication or an extraintestinal manifestation of Salmonella gastroenteritis. No deaths were reported.

Experience with oral rehydration therapy in moderately dehydrated children due to diarrhea.

Additional reports on oral rehydration therapy (ORT) in the management of moderately dehydrated patients may convince practitioners to convert from high-cost intravenous treatment to low-cost and efficient ORT in moderately dehydrated patients. Therefore, the failure rate and its association with admission serum sodium, potassium and bicarbonate levels of 162 moderately dehydrated children with diarrhea treated with ORT were analyzed retrospectively. The overall failure rate was found to be 17.6 percent. This rate did not differ significantly among normonatremic, hyponatremic and hypernatremic patients (16%, 25% and 28%, respectively; p > 0.05), nor did the rate differ among normokalemic, hypokalemic and hyperkalemic patients (16%, 33% and 25%, respectively; p > 0.05). Only moderately and severely acidotic patients had higher failure rates than non-acidotic and mildly acidotic cases (21%, 38%, 4% and 14% respectively; p < 0.05). Severely acidotic patients were also rehydrated over a longer time (10.4 +/- 6.6 hours) than were nonacidotic patients (6.7 +/- 2.3 hours, p < 0.001). Thus the degree of acidosis, which is closely related to the clinical severity of dehydration, was found to be much more predictive of ORT failure and the duration of rehydration than were other electrolyte disturbances. Besides correcting dehydration, ORT was safe and effective in treating various electrolyte disturbances.

Immunogenicity and safety of Haemophilus influenzae type b capsular polysaccharide tetanus conjugate vaccine (PRP-T) presented in a dual-chamber syringe with DTP.

Separate injections of Haemophilus influenzae type b capsular polysaccharide-tetanus conjugate (PRP-T) vaccine and diphtheria-tetanus-pertussis (DTP) reconstitution of freeze-dried PRP-T vaccine with liquid DTP vaccine have been shown to be safe and immunogenic in infants. The present study was conducted to test the safety and immunogenicity of the liquid combination vaccine administered to young infants in the dual-chamber syringe. The study was a monocenter, open clinical trial of 3 month-old infants receiving PRP-T and DTP vaccines in the dual-chamber syringe reconstituted prior to injection. Healthy infants were immunized according to a 3, 4 and 5 months-of-age schedule. The vaccine was administered in a dual-chamber syringe, ready to use with two chambers. The proximal chamber contained freeze-dried PRP-T and the distal chamber contained liquid combination-vaccine DTP. The freeze-dried PRP-T vaccine was reconstituted with the liquid DTP vaccine in the same unidose dual-chamber syringe (0.5 mL) and was injected intramuscularly into the deltoid region. Blood sampling was performed prior to vaccination at 3 months of age and after the third vaccination at 6 months. The primary end-point was the serological response to PRP-T vaccine as expressed by the percentage of infants with an antibody titer greater than or equal to 1 microgram/mL. The reactogenicity was expressed as the percentage of reported local and systemic reactions. A total of 108 infants were included in the study and received the dual-chamber syringe vaccine. After the third injection, all the infants had a PRP antibody titer greater than or equal to 0.15 microgram/mL and 94.4% of infants had a PRP antibody titer greater than or equal to 1 microgram/mL; the pertussis agglutinin titers were over the threshold 40 and 80 in all infants and 98.1% were over the threshold 320. After the third injection, all the infants had diphtheria antibody titers greater than 0.1 IU/mL and 83.3% had titers greater than 1 IU/mL; all the infants had tetanus antibody titers greater than 0.1 IU/mL and 97.2% had results over 1 IU/mL. Thirty-seven infants (34.6%) had local reactions and 64.5% had systemic reactions. The dual-chamber syringe may reduce the cost of vaccine delivery, as well as the workload, and increase the vaccine acceptability and coverage rate of vaccines.

Shigella gastroenteritis: clinical and epidemiological aspects, and antibiotic susceptibility.

The epidemiology and antibiotic sensitivity of Shigella species is changing worldwide. The present study surveyed the changing clinical and epidemiological characteristics and antibiotic susceptibility of Shigella gastroenteritis in Hacettepe University Ihsan Dogramaci Children's Hospital Diarrhoea Training and Treatment Unit between 1987 and 1994. Among 19,812 diarrheal admissions, 618 (3.2%) patient files with Shigella gastroenteritis were reviewed retrospectively. Shigella soneii has been the commonest isolate (64%) since 1987 followed by S. flexineri (30%), S. boydii (5%) and S. dysenteriae (1%), the latter having not been isolated since 1990. The isolate rate of S. sonnei has increased whereas the isolation rate of S. flexineri has decreased concomitantly since 1987 (r = -0.94; P < 0.001). The majority of cases (365/618, 59%) were between 1 and 5 years of age. On admission bloody diarrhea was present in 36%, seizures in 3% and mild-moderate dehydration in 11% of cases. No case had severe dehydration. Only six patients (1%) were hospitalized. No deaths were recorded. The resistance rate for trimethoprim-sulfamethoxazole has increased from 27% in 1990 to 66% in 1994 (P < 0.05) while the resistance rate for ampicillin has decreased from 81% in 1987 to 32% in 1993 (P < 0.001). Shigella flexineri was found to have higher resistance rates to ampicillin, sulbactam-ampicillin, chloramphenicol and gentamicin than S. sonnei. Changing Shigella sp. over the years may be the reason for the mild course of Shigella gastroenteritis. Further regional epidemiological studies are necessary to develop more appropriate management guidelines, especially in developing countries.