Characterization of capsular genes in Haemophilus influenzae isolates from H. influenzae type b vaccine recipients.
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Bacterial Capsules↗
Biomedical subjects
M Santosham
Publications and source records attributed to M Santosham.
Diarrhoeal diseases in the White Mountain Apaches: clinical studies.
Acute diarrhoeal diseases continue to be a major health problem in certain underprivileged populations in the United States, including native Americans living in reservations. To describe the features of patients with diarrhoeal diseases requiring medical care, those attending the medical facilities of the Fort Apache Indian Reservation, Whiteriver, Arizona, were studied during 1981-1985. Clinical and aetiological information was obtained on 535 patients which constitute a 20% sample of those attending the outpatient clinic and all 386 patients who required 550 hospitalizations. Rotavirus, enterotoxigenic Escherichia coli, and Shigella were the most common aetiologic agents, a pattern similar to that seen in the developing countries. The clinical features of diarrhoeal illness and the frequent associated occurrence of acute respiratory symptoms, however, were remarkably similar, regardless of aetiology.
Acute Disease↗
Diarrhoeal diseases in the White Mountain Apaches: epidemiologic studies.
Acute diarrhoeal disease in children is known to be a major public health problem among native Americans living in reservations in the southwestern part of the United States. This study was undertaken to describe the epidemiology and causative agents of diarrhoea more completely, with the expectation that this information may help in the ultimate control of the disease in this population. Three interrelated epidemiologic studies were carried out in the White Mountain Apache Tribe, Whiteriver, Arizona, during 1981-1985: a three-year longitudinal study on a cohort of 112 newborns, a longitudinal two-year study in a cohort of 200 families, and a case-control study on 1,072 children with diarrhoea attending a medical facility. Both epidemiologic and microbiological patterns of diarrhoeal disease were found to be very similar to those seen in developing countries, indicating the need for basic improvements in sanitation and hygiene in this population.
Acute Disease↗
Postlicensure effectiveness of the Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer-membrane protein complex conjugate vaccine among Navajo children.
The incidence of invasive Haemophilus influenzae type b (Hib) infection was decreased significantly among Navajo children since the licensure of Hib conjugate vaccines, even though two lots of Hib (polyribosylribitol phosphate)-meningococcal B outer-membrane protein conjugate vaccine (PRP-OMP) widely used among the Navajo were later found to be of low immunogenicity. We measured the effectiveness of all Hib conjugate vaccines combined, PRP-OMP alone, and the PRP-OMP lots with lower-than-expected immunogenicity among Navajo infants and children. This was a matched case-control study using active, laboratory-based surveillance for the ascertainment of Navajo children 2 1/2 to 59 months of age with invasive Hib infection; 45 patients with infection and 180 control subjects were enrolled. The effectiveness of one, two, and three doses, respectively, of all Hib conjugate vaccines combined was 96% (95% confidence interval (CI) 65%, 99%), 99% (95% CI, 69%, 100%), and 99% (95% CI - 57%, 100%). The effectiveness of one or more doses of PRP-OMP was 95% (95% CI, 66%, 99%). The effectiveness of a single dose of the lots of lower-than-expected immunogenicity was 89% (95% CI, -8%, 99%). The Hib conjugate vaccine coverage increased from 49% during 1991 to 94% during 1992; no control subjects younger than 18 months of age were enrolled during 1993. The occurrence of invasive Hib infections in this population after licensure of Hib conjugate vaccines was the result of gradual vaccine uptake, not poor vaccine effectiveness. The use of PRP-OMP has been highly effective despite concerns about the immunogenicity of several lots.
Bacterial Outer Membrane Proteins↗
Immunogenicity, safety and tolerability of varying doses and regimens of inactivated hepatitis A virus vaccine in Navajo children.
The Navajo are known to be at high risk for hepatitis A virus (HAV) infection. This study investigated the safety and immunogenicity of an investigational, alum-adjuvanted, formalin-inactivated HAV vaccine (VAQTA) developed by Merck Research Laboratories in Navajo children. One hundred two of 212 children, ages 4 to 12 years, were HAV-seronegative (< 10 mIU/ml by an enhanced sensitivity modification of the HAVAB; Abbott). Ninety of these children received the HAV vaccine. Study participants were given vaccines containing various viral protein concentrations: Group A (n = 18), 6 units; Group B (n = 36), 13 units; and Group C (n = 36), 25 units HAV protein (1 unit approximately 1 ng viral protein antigen). Three-dose (0, 8, 24 weeks) and two-dose (0, 24 weeks) regimens were compared in subgroups within B and C. The vaccine was well-tolerated and there were no serious adverse reactions; no vaccinee developed hepatitis A. After 1 dose 82 to 100% of children seroconverted (> or = 10 mIU/ml, modified HAVAB; Abbott) and 100% seroconverted after 2 doses. After 1 dose the geometric mean titer for antibody was: Group A, 22 mIU/ml; Group B, 18 mIU/ml; and Group C, 38 mIU/ml. After 3 doses geometric mean titers increased to 10,106 mIU/ml in Group A, 7258 mIU/ml in Group B and 11,856 mIU/ml in Group C. Further field studies are indicated to evaluate its use in high risk populations, such as the Navajo.
Age Factors↗
Hydrolyzed lactalbumin-based oral rehydration solution for acute diarrhoea in infants.
The addition of different organic substrates to standard glucose oral rehydration solution (G-ORS) has been shown to improve the intestinal absorption of sodium and water, and thereby decrease stool losses. Therefore, we evaluated, in infants with acute diarrhoea, the safety and efficacy of three oral rehydration solutions (ORS) which had the same concentrations of electrolytes (with sodium 60 mmol/l) but different substrates of proteins and carbohydrates. One solution (LAD-ORS) contained hydrolyzed lactalbumin (LAD) with maltodextrin and sucrose, a second (MS-ORS) was identical but without LAD and a third (G-ORS) was standard glucose ORS. The three solutions were compared in a double-blind, randomized trial in 74 hospitalized well-nourished children in Panama and the United States. All three oral rehydration solutions were equally efficacious and safe in these children, 54% of whom were infected with rotavirus. There was no suggestion that hydrolyzed lactalbumin or maltodextrin provided any advantage over glucose-ORS in terms of stool output or in duration of diarrhoea. We conclude that all three solutions are efficacious in the therapy of acute diarrhoea in infants.
Acute Disease↗
Evaluation of a maize-cowpea-palm oil diet for the dietary management of Nigerian children with acute, watery diarrhea.
A randomized clinical trial was carried out to compare a locally available maize-cowpea-palm oil diet (group MCP) with a commercially produced lactose-free, soy protein isolate formula (group SF) for the dietary management of 69 Nigerian boys, 6-24 months of age, hospitalized for acute, watery diarrhea. Although the treatment groups were generally similar initially, the children in group SF had slightly lower mean weight-for-age z scores (p = 0.08), lower serum bicarbonate levels (p = 0.04) and greater stool outputs during the period of rehydration before the diets were initiated (p = 0.01). Rates of treatment failure in group MCP (5.7%) and group SF (8.8%) were similar (p = 0.67). There were no significant differences in the adjusted mean stool outputs by study group on days 1-5, but the children in group SF had slightly lower fecal weights on day 6 (p = 0.05). Children in group MCP had a substantially reduced duration of liquid stool excretion (estimated median duration 42 h versus 140 h; p < 0.001). On the other hand, children in group SF consumed considerably more of their diet, had greater net absorption of macronutrients and greater rates of weight gain than those in group MCP. We conclude that children can safely consume the MCP diet during acute, watery diarrhea without increasing their risk of treatment failure or augmenting stool output. However, the diet may not be adequate as a sole source of nutrients beyond the period of acute illness.
Acute Disease↗
Barriers to use of oral rehydration therapy.
OBJECTIVE: To identify potential barriers to the use of oral rehydration therapy (ORT) by pediatric practitioners. DESIGN: Cross-sectional, anonymous, self-administered survey of physicians' ORT knowledge, attitudes, and practice. SETTING: A national continuing medical education conference. PARTICIPANTS: One hundred four general pediatricians primarily in private practice (66%) who completed training after 1980 (76%). MEASUREMENTS AND RESULTS: Most respondents (83%) reported that ORT plays an important role in their management of dehydration. However, compliance with guidelines from the American Academy of Pediatrics for use of oral therapy is limited: 30% withhold ORT in children with vomiting or moderate dehydration, 50% fail to advise prompt refeeding, and only 3% advise use of a spoon or syringe. The degree of importance of ORT in physicians' practice was negatively associated with reported lack of convenience of ORT administration in the practice setting (P < .001), support staff preference for intravenous versus ORT (P < .001), need for additional training of support staff to implement ORT (P < .01), and likelihood of reimbursement for intravenous versus ORT (P = .07). Notably, degree of importance of ORT was not associated with physician ORT knowledge. CONCLUSION: Efforts to improve use of ORT should be expanded beyond physician education and focus on such barriers as support staff limitations and financial constraints.
Acute Disease↗
Comparative efficacy of rice-based and glucose-based oral rehydration salts plus early reintroduction of food.
The use of oral rehydration salts (ORS) to restore fluid balance in children with diarrhoea is universally accepted. However, there is uncertainty about whether glucose-based ORS or ORS based on precooked rice powder is more effective. In a randomised trial we compared the two types of ORS in children who were given food immediately after completion of rehydration. 460 boys aged 3-18 months, admitted to hospital with acute diarrhoea and signs of dehydration, were randomly assigned to groups receiving rice-based and glucose-based ORS solution (230 to each group). After full rehydration (4-12 h), a weaning food consisting of rice and mixed vegetables was given until the diarrhoea stopped. Continuing losses of liquid stool and vomitus were replaced with the assigned ORS solution. There were no differences between the groups during the rehydration phase in stool volume, volume of ORS solution taken, duration of rehydration phase, or weight gain. However, after initiation of feeding, the glucose-based ORS group had significantly lower stool volumes than the rice-based ORS group (142 [95% CI 117-173] vs 96 [77-120] g/kg); they also took a smaller amount of ORS solution (153 [127-185] vs 111 [90-136] mL/kg) and had a shorter duration of diarrhoea (55 [SD 35] vs 44 [35] h). Glucose-based ORS solution was more effective than rice-based ORS solution for the treatment of diarrhoea in children when feeding with a rice-based diet was started soon after correction of dehydration. These results support the continued recommendation of glucose-based ORS solution as standard therapy for treatment of children with acute diarrhoea and emphasize the importance of resuming feeding as soon as dehydration has been corrected.
Acute Disease↗
Inactivated hepatitis A vaccine in childhood: implications for disease control.
The experience to date with the Merck inactivated hepatitis A vaccine in healthy children 2-16 years old is reviewed. Comparison of response to increasing doses indicates that an intramuscular dose of 25 units results in seroconversion of 99% of children by week 4 following a single dose. Antibody persistence rate is nearly 100% six months later, whether or not a second priming dose is given at week 8. This vaccine has proven highly immunogenic in children and has a favourable safety/tolerability profile. It should be useful for pre-exposure prophylaxis and control of hepatitis A, and should eventually replace immune globulin (Ig) for this indication.
Adolescent↗
Prevention of Haemophilus influenzae type b disease.
Haemophilus influenzae type b (Hib) is the leading cause of meningitis in children < 5 years of age. The majority of cases of Hib occur in infants < 2 years of age. Until recently the only vaccine available against this disease contained the pure polysaccharide (PRP) of Hib (Hib-PRP vaccine). The Hib-PRP vaccine was demonstrated to be efficacious in infants > 18 months of age but not below that age. This product was licensed for routine use in the USA for children aged 24 months or more. Recently a hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIg) was prepared by immunizing adult donors with Hib-PRP, meningococcal and pneumococcal vaccines. BPIg has been demonstrated to prevent Hib infections when it is administered to infants at 4-month intervals. However, BPIg has not been licensed for routine use in the USA. A number of new Hib conjugate vaccines have also been developed in the last few years by convalently linking the Hib-PRP to different carrier proteins. Four different Hib conjugate vaccines have undergone clinical trials in the USA. Two of these vaccines, HbOC (Hib capsular oligosaccharide linked to CRM197) and Hib-OMPC (Hib capsular polysaccharide linked to Neisseria meningitidis outer membrane protein complex) have been demonstrated to protect infants aged 2 months or more from Hib disease. Both HbOC and Hib-OMPC are currently licensed for routine use in the USA. The widespread use of these vaccines should have a substantial impact in reducing morbidity and mortality from Hib disease.
Bacterial Capsules↗
Anti-PRP antibody levels after a primary series of PRP-OMPC and persistence of antibody titres following primary and booster doses.
The Haemophilus influenzae capsular polysaccharide-outer membrane protein conjugate, PRP-OMPC (PedvaxHIB) elicits very good antibody responses in infants > or = 2 months of age after the first dose. Increasing age at time of first vaccination correlates with higher antibody responses. Anti-PRP responses are consistently high with the first injection among all population groups studied. Booster doses stimulate anamnestic antibody responses after one year of age. Among US children (excluding Navajo and Apache children) given a primary injection at 14-18 months of age, the geometric mean titre (GMT) after 2 to 3 years was > 1 micrograms/ml. US children (excluding Navajo and Apache children) given a primary series at 2 and 4 months of age and a booster at 18 months of age also had an anti-PRP GMT > 1 micrograms/ml 2.5 years later. Navajo and Apache children given a primary series at 2 and 4 months of age and a booster at 12-15 months had antibody levels of 1.50 micrograms/ml one year later. Antibody persistence data suggest there will be long-term protection against Haemophilus influenzae b disease following immunization with PRP-OMPC.
Antibodies, Bacterial↗
Rehydration and nutritional management.
Diarrhoea remains a leading worldwide cause of morbidity and mortality. In developing countries alone, 1.5 billion episodes of diarrhoea occur per year in children under 5 years of age and approximately 4,000,000 of these result in death. Early, appropriate therapy decreases the risk of complications and death due to diarrhoea. Regardless of the causative agent, oral rehydration and nutritional management are the mainstays of good management of infants, children and adults with diarrhoea. Diarrhoeal disease control programmes throughout the developing world have adopted the WHO case management plan as a standard. In this chapter, we review the history, successes and shortcomings of various oral rehydration therapies and recommend a case management approach that is similar to the WHO plan. Although ORT is safe, effective, convenient and economical, this therapy has not been universally implemented in health care settings. The challenge for clinical and public health practitioners in developing and developed countries is to identify and overcome the barriers that exist so that all patients with diarrhoea will have the opportunity to receive optimal care.
Administration, Oral↗
Interference of immune globulin with measles and rubella immunization.
Passively acquired antibody may interfere with the active antibody response to live viral vaccines such as measles and rubella. To evaluate the duration of this inhibitory effect, we measured the measles and rubella antibody responses of Apache children immunized with measles, mumps, and rubella vaccine at varying intervals after administration of an immune globulin termed bacterial polysaccharide immune globulin (BPIG). This specific immune globulin contained measles and rubella antibody titers similar to those in standard intramuscularly and intravenously administered immune globulins. Antibody responses to measles vaccine were inhibited for up to 5 months after a BPIG dose of 80 mg IgG per kilogram of body weight, but responses to rubella vaccine were inhibited for only 2 months. Most children who had a decreased measles antibody response to primary measles, mumps, and rubella immunization given 1 1/2 to 4 months after BPIG administration responded to a booster immunization given 6 months after their last BPIG dose. We conclude that high doses of immune globulin (> 10 mg/kg) may inhibit the antibody response to measles for more than 3 months. We propose that the interval between administration of immune globulin and measles and rubella immunization be adjusted on the basis of the dose of immune globulin.
Antibodies, Viral↗
Vaccination with Haemophilus influenzae type b meningococcal protein conjugate vaccine reduces oropharyngeal carriage of Haemophilus influenzae type b among American Indian children.
The effect of Haemophilus influenzae type b (Hib) meningococcal protein conjugate vaccine (Hib-OMPC; Merck, Sharp & Dohme) on oropharyngeal (OP) carriage of Hib was evaluated in Navajo and Apache Indian children, who are known to be at high risk for invasive Hib disease. We obtained 1423 OP swabs at well child visits from 1321 children 3 months to 4 years of age: 293 of the swabs were obtained from children before the administration of any Hib-OMPC; 1119 were taken after the primary vaccination series; and 11 after the booster dose. Swabs were tested for the presence of Hib capsular polysaccharide antigen by enzyme-linked immunosorbent assay. Forty of 1423 swabs were positive for Hib. Among the 40 positive swabs 5 (13%) were obtained from children who had received Hib-OMPC vaccine appropriate for age at swabbing, compared with 500 of 1383 (36%) of negative swabs. Children who were OP carriers of Hib were older than noncarriers (mean age, 13 and 9 months, respectively) and a greater proportion of carriers (48%) had symptoms of respiratory infection at the time of swabbing than noncarriers (30%). These variables were significantly related to increased risk of OP carriage of Hib when incorporated jointly in a logistic regression model: not vaccinated according to age (odds ratio 2.7, 95% confidence interval 1.00 to 7.05); increase of age in months (odds ratio 1.1, 95% confidence interval 1.02-1.10); and respiratory infection symptoms present (odds ratio 2.0, 95% confidence interval 1.06-3.77). Thus besides preventing invasive Hib disease, appropriate vaccination with Hib-OMPC appears to reduce OP carriage of Hib.
Bacterial Outer Membrane Proteins↗
Antibody response of Navajo children primed with PRP-OMP vaccine to booster doses of PRP-OMP vs. HbOC vaccine.
We compared in 12- to 15-month-old American Indian infants the safety and immunogenicity of two licensed Haemophilus influenzae type b (Hib) conjugate vaccines, PRP-OMP (PedvaxHib) and HbOC (HibTITER), administered as booster vaccinations. All infants previously received PRP-OMP for their primary Hib vaccinations at 2 and 4 months of age. The geometric mean Hib antibody concentrations (microgram/ml) measured by radioactive antigen-binding assay for those receiving PRP-OMP (n = 17) or HbOC (n = 18) were 0.593 and 0.449, respectively, before boosting (P not significant) and 7.46 and 29.5 micrograms/ml, respectively, after boosting (P < 0.05). PRP-OMP recipients also had lower geometric mean IgG anti-Hib antibody concentrations than HbOC recipients (7.21 vs 28 micrograms/ml, P = 0.003) and lower bactericidal titers (3.18 vs. 15.4, not significant). We conclude that HbOC vaccine produced a significantly greater booster response than PRP-OMP vaccine when given at 12 to 15 months of age to children primed with two doses of PRP-OMP vaccine at 2 and 4 months of age.
Antibodies, Bacterial↗
Immunogenicity of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer membrane protein complex conjugate vaccine in infants and children with sickle cell disease.
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Anemia, Sickle Cell↗
The management of acute diarrhea in children: oral rehydration, maintenance, and nutritional therapy. Centers for Disease Control and Prevention.
Worldwide, diarrhea remains one of the most common illnesses among children. In the United States, children < 5 years of age experience > 20 million episodes of diarrhea each year, leading to several million doctor visits, 200,000 hospitalizations, and approximately 400 deaths. Much of this morbidity is due to the dehydration associated with acute watery diarrhea. Consequently, the proper management of children with acute diarrhea is important for all practitioners as well as for parents of small children. The development of oral therapy for the rehydration and maintenance of children with dehydrating diarrhea has become the worldwide mainstay of national diarrheal control programs. More recently, proper nutrition for children with diarrhea is viewed as an important adjunct to therapy, whereas antibiotics and other drugs play only a limited role. Intravenous therapy remains essential for diarrheal episodes associated with severe dehydration. This document reviews the proper management of diarrhea among children. Particular attention is given to the use of oral therapy for rehydration and maintenance therapy for the dehydrated child and nutritional management. In the United States, the improved management of children with diarrhea could lead to a noticeable decrease in the number of children who are hospitalized or die as a result of diarrheal illness. This report contains recommendations prepared by the Centers for Disease Control and Prevention (CDC), with input from a panel of pediatric and diarrheal management experts, which are consistent with recommendations endorsed by the American Academy of Pediatrics.
Acute Disease↗