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Biomedical subjects

M Santosham

Publications and source records attributed to M Santosham.

At least 37 records · Page 2Linked to original sources

Toward elimination of Haemophilus influenzae type B carriage and disease among high-risk American Indian children.

OBJECTIVES: This report describes the epidemiology of Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal colonization among Navajo and White Mountain Apache children younger than 7 years in an era of widespread immunization. METHODS: We conducted active surveillance for invasive H influenzae disease from 1992 to 1999 and an oropharyngeal carriage study from 1997 to 1999. The predominant vaccine used was PedvaxHib. RESULTS: The average annual incidence of invasive Hib disease among children younger than 24 months was 22 cases per 100,000. Of 381 children younger than 7 years, only 1 (0.3%; 95% confidence interval = 0.0%, 1.3%) was colonized with Hib; 370 (97%) had received 2 or more doses of Hib conjugate vaccine. CONCLUSIONS: Among Navajo and White Mountain Apache children, Hib conjugate vaccines have led to a sustained reduction in invasive Hib disease and a reduction in oropharyngeal Hib carriage. The disease incidence among children younger than 24 months remains 20 times higher than in the general US population. Hib elimination will require additional characterization of colonization and disease in these high-risk populations.

Carrier State↗

Comparison of soy-based formulas with lactose and with sucrose in the treatment of acute diarrhea in infants.

OBJECTIVE: To evaluate the effect of feeding infants a soy-based formula with lactose compared with a soy-based formula with sucrose during an acute diarrheal episode. PARTICIPANTS AND METHODS: Two hundred boys, aged 3 to 18 months, who were admitted to the hospital with acute diarrhea and signs of dehydration were randomly assigned to receive a soy-based formula with lactose or sucrose after initial rehydration. Intake and output (stool, urine, and vomit) were measured and recorded every 3 hours until diarrhea resolved. RESULTS: The stool output during the first 24 hours of maintenance therapy, the total stool output during maintenance therapy, and the stool output during the entire illness (measured in grams per kilograms) were significantly lower among patients who received the soy-based formula with sucrose (P<.05, P<.001, and P<.001, respectively) than among patients who received the soy-based formula with lactose. The duration of diarrhea was significantly shorter among patients who received the soy-based formula with sucrose (P<.001). The relative risk of being withdrawn from the study increased to 1.95 (95% confidence interval, 0.65-9.2) and the relative risk of recurrence of dehydration after feeding was initiated increased significantly to 3.49 (95% confidence interval, 1.1-9.6; P<.01) in the group receiving the soy-based formula with lactose. CONCLUSION: During diarrheal episodes, feeding infants a soy-based formula with sucrose has a better outcome (lower stool output, shorter duration of diarrhea, and lower failure rates) than feeding infants a soy-based formula with lactose.

Acute Disease↗

Severe respiratory syncytial virus disease in Alaska native children. RSV Alaska Study Group.

Hospitalization rates for respiratory syncytial virus (RSV) infection range from 1 to 20/1000 infants. To determine the rate and severity of RSV infections requiring hospitalization for infants in the Yukon-Kuskokwim (YK) Delta of Alaska, a 3-year prospective surveillance study was conducted. The annual rate of RSV hospitalization for YK Delta infants <1 year of age was 53-249/1000. RSV infection was the most frequent cause of infant hospitalization. RSV disease severity did not differ among non-high-risk infants in the YK Delta and at Johns Hopkins Hospital (JHH). On average, 1/125 infants born in the YK Delta required mechanical ventilation for RSV infection. During the peak season, approximately $1034/child <3 years of age was spent on RSV hospitalization in the YK Delta. In YK Delta infants </=6 months old, RSV microneutralizing antibody titers <1200 were associated with severe disease (odds ratio=6.2, P=.03). In the YK Delta and at JHH, newborns may be at greater risk for severe RSV illness than previously thought.

Age Factors↗

Simultaneous vitamin A administration at routine immunization contact enhances antibody response to diphtheria vaccine in infants younger than six months.

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effect of simultaneous vitamin A supplementation and diphtheria, pertussis and tetanus (DPT) vaccination on the antibody levels. Infants aged 6-17 wk (n = 56) were randomly given 15 mg oral vitamin A or placebo at the time of their DPT immunization. Three such doses were given at monthly intervals. Immunoglobulin (Ig) G antibodies to diphtheria, pertussis and tetanus were assayed on enrollment and 1 mo after the third dose. Baseline antibody concentrations to diphtheria, pertussis and tetanus did not differ between the vitamin A-supplemented and placebo-treated groups. The postdose antibody to diphtheria level was significantly greater in the vitamin A than in the placebo-treated group. The geometric mean +/- SEM antibody levels (mg/L) were 22.9 +/- 1.2 and 11.0 +/- 1.3 in the vitamin A and placebo groups, respectively (P = 0.029). The postsupplementation concentrations of antibodies to pertussis and tetanus did not differ between the two groups. These results suggest that antibody response to diphtheria vaccination was potentiated by simultaneous vitamin A administration and DPT immunization.

Antibodies, Bacterial↗

A case-control study of risk factors for Haemophilus influenzae type B disease in Navajo children.

To understand the potential risk factors and protective factors for invasive Haemophilus influenzae type b (Hib) disease, we conducted a case-control study among Navajo children less than two years of age resident on the Navajo Nation. We analyzed household interview data for 60 cases that occurred between August 1988 and February 1991, and for 116 controls matched by age, gender, and geographic location. The Hib vaccine recipients were excluded from the analyses. Conditional logistic regression models were fit to examine many variables relating to social and environmental conditions. Risk factors determined to be important were never breast fed (odds ratio [OR] = 3.55, 95% confidence interval [CI] = 1.52, 8.26), shared care with more than one child less than two years of age (OR = 2.32, 95% CI = 0.91, 5.96); wood heating (OR = 2.14, 95% CI = 0.91, 5.05); rodents in the home (OR = 8.18, 95% CI = 0.83, 80.7); and any livestock near the home (OR = 2.18, 95% CI = 0.94, 5.04).

Analysis of Variance↗

The protective effectiveness of natural rotavirus infection in an American Indian population.

The degree of protection conferred by natural rotavirus infection was estimated through analyses of data gathered as part of a 2-year rotavirus vaccine study of 1185 Native American infants. In 292 placebo recipients with complete serum sample sets, rotavirus IgA antibody indicative of infection before 2 months of age was associated with a 58% decrease in symptomatic infections throughout the trial. In all 391 placebo recipients, the preventive effectiveness of an initial symptomatic infection was 72% overall and 94% within 6 months following the infection. In contrast to studies conducted at other sites in the United States, serotype G3 was the predominant serotype associated with gastrointestinal episodes (80%). The effectiveness of an initial serotype G3 episode with respect to preventing subsequent serotype G3 episodes was 91%.

Antibodies, Viral↗

Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations.

OBJECTIVES: We compared the efficacy, safety, and immunogenicity of a rhesus rotavirus tetravalent vaccine (RRV-TV), a rhesus rotavirus monovalent (serotype 1) vaccine (RRV-S1), and placebo in healthy American Indian infants for two rotavirus seasons. STUDY DESIGN: Infants aged 6 to 24 weeks were enrolled in a randomized, double-blind efficacy study. Infants were orally administered RRV-TV (4 x 10(5) plaque-forming units per dose), RRV-S1 (4 x 10(5) plaque-forming units per dose), or placebo at 2, 4, and 6 months of age. Stools collected during episodes of gastroenteritis were tested for detection of rotavirus antigen. A total of 1185 infants received at least one dose of a study vaccine or placebo, and 1051 received all three doses according to the protocol. RESULTS: During the first year of surveillance, the estimates of vaccine efficacy (with 95% confidence interval) for preventing rotaviral gastroenteritis were 50% (26, 67) for RRV-TV and 29% (-1, 50) for RRV-S1. In this population only 6% of rotaviral gastroenteritis episodes among placebo recipients were associated with type G1 disease. For severe disease the estimates of vaccine efficacy were higher: 69% (29, 88) for RRV-TV and 48% (-4, 75) for RRV-S1. CONCLUSIONS: These data indicate that RRV-TV is moderately efficacious in preventing all episodes of gastroenteritis caused by rotavirus and is most efficacious against the severe disease characteristic of rotaviral illness.

Double-Blind Method↗

Comparison of two regimens of feeding and oral electrolyte solutions in infants with diarrhea.

BACKGROUND: Glucose-based oral rehydration solutions (ORS) available in the United States do not appear to reduce the severity or duration of diarrhea. The use of cereal-derived ORS and cereal-based feedings appears to diminish the severity of illness in studies conducted in the developing world. To our knowledge, no controlled trials of cereal-derived ORS or cereal-based feedings have been performed in the United States. METHODS: We performed a randomized, double-blind trial of two ORS feeding regimens in outpatients with diarrhea. Patients aged 2-13 months with acute watery diarrhea were enrolled. Subjects received standard glucose-based ORS in alternation with soy-based, lactose-free infant formula (Group 1) or rice syrup solid containing ORS in alternation with rice-based, lactose-free infant formula (Group 2). Subjects were visited at home daily to determine the severity of illness and characteristics of the stool. RESULTS: After the first 2 days, significantly more Group 1 subjects continued to have diarrhea than did Group 2 subjects (median duration of diarrhea 3 vs. 2 days) as demonstrated by Kaplan-Meier survival curves (p = 0.04). CONCLUSION: We conclude that infants fed a regimen consisting of rice syrup solid containing ORS and rice formula resolved their diarrhea sooner than did infants fed a regimen of standard glucose-based ORS and formula. The relative contributions of ORS and formula to this more rapid recovery can be elucidated by further studies.

Diarrhea, Infantile↗

Oral rehydration therapy for diarrhea: an example of reverse transfer of technology.

On November 13 and 14, 1996, a scientific symposium on oral rehydration therapy (ORT) was held at the Johns Hopkins University School of Hygiene and Public Health in Baltimore, MD. The purpose of the meeting was to review the current treatment practices for the treatment of this disease in the United States. The group noted that diarrhea resulted in 300 to 400 deaths per year among children, approximately 200 000 hospitalizations, 1.5 million outpatient visits, and costs >$1 billion in direct medical costs. ORT is well established therapy for the treatment and prevention of dehydration due to diarrhea. The principles of ORT treatment include early adequate rehydration therapy using an appropriate oral rehydration solution (ORS), replacement of ongoing fluid losses from vomiting and diarrhea with ORS, and frequent feeding of appropriate foods as soon as dehydration is corrected. The effective use of ORT has saved millions of lives around the world. However, in the United States, ORT is grossly underused. Contrary to the recommendations of the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC), health care providers overuse intravenous hydration, prolong rehydration, delay reintroduction of feeding, and inappropriately withhold ORT, especially with children who are vomiting. The expert panel noted that the majority of deaths, hospitalization, and visits to emergency departments could be prevented by the appropriate use of ORT. They generated guidelines for the treatment and prevention of dehydration secondary to diarrhea. These measures, together with training providers, could substantially reduce diarrhea mortality and decrease hospitalizations of children by 100 000 per year in the next 5 years.

Dehydration↗

Oral prednisone as a risk factor for infections in children with asthma.

OBJECTIVE: To determine whether the frequency of acute infections in children with asthma is associated with the number of doses of prednisone received for asthma attacks. DESIGN: A cohort study. SETTING: Primary care clinic and emergency department of an inner-city teaching hospital from March 31, 1992, to May 31, 1993. PATIENTS: Convenience sample of clinic enrollees aged 2 to 14 years who had made two or more outpatient visits for acute asthma in the preceding year. Eighty-six children were enrolled. Seventy-eight (91%) completed the study. MAIN OUTCOME MEASURES: The independent variable was cumulative prednisone dose received during the study period. Outcome variables were episodes of acute infections. RESULTS: The mean (+/-SD) number of doses of prednisone (2 mg/kg to a maximum of 60 mg) received was 9.5 +/- 11.8 doses (range, 0 to 57 doses). Ninety-four episodes of acute infection occurred in 50 children. No difference was observed in the mean number of doses of prednisone received by those with the infection compared with those without the infection. No correlation was observed between the number of doses of prednisone received and the number of episodes of each infection. CONCLUSIONS: The administration of prednisone as short courses for acute asthma is not associated with an increase in the number of episodes of common acute infections.

Acute Disease↗

A double-blind clinical trial comparing World Health Organization oral rehydration solution with a reduced osmolarity solution containing equal amounts of sodium and glucose.

OBJECTIVE: To compare the safety and efficacy of an oral rehydration solution (ORS) containing 75 mmol/L of sodium and glucose each with the standard World Health Organization (WHO) ORS among Egyptian children with acute diarrhea. METHODS: One hundred ninety boys, aged 1 to 24 months, who were admitted to the hospital with acute diarrhea and signs of dehydration were randomly assigned to receive either standard ORS (311 mmol/L) or a reduced osmolarity ORS (245 mmol/L). Intake and output were measured every 3 hours. RESULTS: In the group treated with reduced osmolarity ORS, the mean stool output during the rehydration phase was 36% lower (95% confidence interval, 1%, 100%) than in those treated with WHO ORS. The relative risk of vomiting during the rehydration phase was significantly lower in children treated with reduced osmolarity ORS (relative risk, 2.4; 95% confidence interval, 1.2, 4.8). During the maintenance phase, stool output, mean intake of food and ORS, duration of diarrhea, and weight gain were similar in the treatment groups. The relative risk of treatment failure (need for unscheduled administration of intravenous fluids) was significantly increased in children receiving standard WHO ORS (relative risk, 7.9; 95% confidence interval, 1.1, 60.9). The mean serum sodium concentration at 24 hours was significantly lower in children receiving the reduced osmolarity ORS solution (134 +/- 6 mEq/L) than in children receiving the standard WHO ORS (138 +/- 7 mEq/L) (p < 0.001). The relative risk of the development or worsening of hyponatremia was not increased in children given the reduced osmolarity ORS, and urine output was similar in the treatment groups. CONCLUSION: The reduced osmolarity ORS has beneficial effects on the clinical course of acute diarrhea in children by reducing stool output, and the proportion of children with vomiting during the rehydration phase, and by reducing the need for supplemental intravenous therapy. These results provide support for the use of a reduced osmolarity ORS in children with acute noncholera diarrhea.

Acute Disease↗

How valid are clinical signs of dehydration in infants?

Our objective was to determine the ability of several clinical signs of dehydration to distinguish among degrees of dehydration in infants with acute diarrhea. The design was a prospective cohort study in a pediatric referral hospital in Cairo, Egypt. Infant boys, 3-18 months old, with a history of acute diarrhea (5 or more watery stools per day for no more than 7 days) were eligible, except those with frank protein-energy malnutrition, serious nongastrointestinal illness, or being exclusively breast-fed. Several clinical signs of dehydration were assessed upon study entry. Subjects were then rehydrated with an oral rehydration solution and fed a standardized diet until diarrhea ceased (no watery or loose stools for 16 h). The main outcome measure was percent body weight gain at rehydration and at resolution of illness. Data from 135 subjects were available for analysis. Average (SD) rehydration phase duration was 5.2 (2.1) h, and average (SD) duration of illness was 54.5 (38) h. Multiple regression analysis selected prolonged skinfold, altered neurologic status, sunken eyes, and dry oral mucosa as the clinical signs that correlated best with percent dehydration (R2 for model 0.244, p < 0.001). Mean weight gain for the two assessment systems was 3.6-3.9% for mild, 4.9-5.3% for moderate, and 9.5-9.8% for severe dehydration. The most valid clinical signs of dehydration include prolonged skinfold, altered neurologic status, sunken eyes, and dry oral mucosa. Children with clinical signs of mild or moderate dehydration have fluid deficits on the order of 3 or 5% body weight, respectively.

Acute Disease↗

Effect of diarrhea on the humoral response to oral polio vaccination.

OBJECTIVE: The purpose of this study was to measure the effect of concurrent diarrheal illness on seroconversion to trivalent oral polio vaccine (OPV). METHODS: Six- to 16-week-old infants with acute diarrhea and age-matched controls received single doses of OPV at enrollment, 4 weeks after enrollment and 8 weeks after enrollment. Serum specimens were obtained at enrollment, before the second OPV dose and 4 weeks after the third OPV dose for measurement of antibody titers to polio virus by the microneutralization assay. RESULTS: Four weeks after the first OPV dose, the serologic responses to poliovirus types 2 and 3 in the case cohort were lower by 26 and 34%, respectively, than in the control cohort (P < 0.002 for both comparisons). Poliovirus type 2 and 3 geometric mean antibody titers in the diarrhea cohort were approximately 50% of the geometric mean antibody titers in the control cohort (235 (95% confidence interval (CI) 154 to 359) vs. 446 (95% CI 350 to 569) and 64 (95% CI 45 to 90) vs. 112 (95% CI 88 to 143), respectively, P < 0.01 for both comparisons). After the third OPV dose the seroconvertion rates to poliovirus types 2 and 3 each remained about 10% lower in the case cohort than in the control cohort, but the differences were not statistically significant. CONCLUSION: Concurrent acute diarrhea adversely affects seroconvertion rates of type 2 and 3 polioviruses among infants in Bangladesh receiving the first dose of trivalent OPV.

Acute Disease↗

Wood-burning stoves and lower respiratory illnesses in Navajo children.

BACKGROUND: Acute lower respiratory illnesses (ALRI) have been associated with exposure to domestic smoke. To examine further this association, a case-control study was conducted among Navajo children seen at the Public Health Service Indian Hospital at Fort Defiance, AZ. METHODS: Cases, children hospitalized with an ALRI (n = 45), were ascertained from the inpatient logs during October, 1992, through March, 1993. Controls, children who had a health record at the same hospital and had never been hospitalized for ALRI, were matched 1:1 to cases on date of birth and gender. Home interviews of parents of subjects during March and April, 1993, elicited information on heating and cooking fuels and other household characteristics. Indoor air samples were collected for determination of time-weighted average concentrations of respirable particles (i.e. < 10 microns in diameter). RESULTS: Age of cases at the time of admission ranged from 1 to 24 months (median, 7 months); 60% of the cases were male. Matched pair analysis revealed an increased risk of ALRI for children living in households that cooked with any wood (odds ratio (OR), 5.0; 95% confidence interval (CI), 0.6 to 42.8), had indoor air concentrations of respirable particles > or = 65 micrograms/m3 (i.e. 90th percentile) (OR 7.0, 95% CI 0.9 to 56.9), and where the primary caretaker was other than the mother (OR 9, 95% CI 1.1 to 71.4). Individual adjustment for potential confounders resulted in minor change (i.e. < 20%) in these results. Indoor air concentration of respirable particles was positively correlated with cooking and heating with wood (P < 0.02) but not with other sources of combustion emissions. CONCLUSIONS: Cooking with wood-burning stoves was associated with higher indoor air concentrations of respirable particles and with an increased risk of ALRI in Navajo children.

Acute Disease↗

The cost effectiveness of oral rehydration therapy for U.S. children with acute diarrhea.

Diarrheal disease is a common cause of morbidity among U.S. children under five years of age and exerts a heavy burden on the health care system. Oral rehydration therapy (ORT), a simple, inexpensive treatment modality that can prevent most diarrhea-related complications, is grossly underutilized in the United States. Using a decision-analysis model, this article describes the financial burden of childhood diarrhea in the United States for children under five years of age and discusses the substantial economic benefits of ORT programs. If fully implemented, such programs would save our health care system close to $1 billion annually.

Acute Disease↗

Case-cohort analysis of case-coverage studies of vaccine effectiveness.

Evaluation of vaccine field effectiveness may be performed by combining surveillance data on incident cases with an immunization coverage survey. Although many methods have been used for the analysis of studies of similar design, they are not always desirable or optimal. The authors discuss these approaches and propose use of a case-cohort analysis for such a study design when appropriate. The case-cohort analytic approach is illustrated with data from studies of a vaccine for Haemophilus influenzae type b (Hib) disease in children living on a southwestern Native American reservation during 1988-1993.

Bacterial Outer Membrane Proteins↗