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Featured researches published by Raymond Reid.


The Lancet | 2003

Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial

Katherine L. O'Brien; Lawrence H. Moulton; Raymond Reid; Robert Weatherholtz; Jane Oski; Laura Brown; Gaurav Kumar; Alan J. Parkinson; Diana Hu; Jill Hackell; Ih Chang; Robert Kohberger; George R. Siber; Mathuram Santosham

BACKGROUND Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years. Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world. We aimed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine (PnCRM7) against such disease. METHODS In a group-randomised study, we gave this vaccine to children younger than 2 years from the Navajo and White Mountain Apache Indian reservations; meningococcal type C conjugate vaccine (MnCC) served as the control vaccine. Vaccine schedules were determined by age at enrollment. We recorded episodes of invasive pneumococcal disease and serotyped isolates. Analyses were by intention to treat and per protocol. FINDINGS 8292 children enrolled in the trial. In the per protocol analysis of the primary efficacy group (children enrolled by 7 months of age) there were eight cases of vaccine serotype disease in the controls and two in the PnCRM7 group; in the intention-to-treat analysis we noted 11 cases of vaccine serotype disease in the MnCC control group and two in the PnCRM7 group. After group randomisation had been controlled for, the per protocol primary efficacy of PnCRM7 was 76.8% (95% CI -9.4% to 95.1%) and the intention-to-treat total primary efficacy was 82.6% (21.4% to 96.1%). INTERPRETATION PnCRM7 vaccine prevents vaccine serotype invasive pneumococcal disease even in a high risk population. Other regions with similar disease burden should consider including this vaccine in the routine childhood vaccine schedule.


The New England Journal of Medicine | 1991

The Efficacy in Navajo Infants of a Conjugate Vaccine Consisting of Haemophilus influenzae Type b Polysaccharide and Neisseria meningitidis Outer-Membrane Protein Complex

Mathuram Santosham; Mark Wolff; Raymond Reid; Matt Hohenboken; Massee Bateman; Julius G. Goepp; Margaret Mary Cortese; David A. Sack; Janné Hill; Wendy Newcomer; Linda Capriotti; Jeanne Smith; Marjorie Owen; Sheila Gahagan; Diana Hu; Renee Kling; Linda Lukacs; Ronald W. Ellis; Philip P. Vella; Gary B. Calandra; Holly Matthews; Vincent I. Ahonkhai

BACKGROUND AND METHODS Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo, controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. RESULTS Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P less than 0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P less than 0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P less than 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). CONCLUSIONS The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose.


JAMA Pediatrics | 2011

Maternal Influenza Vaccination and Effect on Influenza Virus Infection in Young Infants

Angelia A. Eick; Timothy M. Uyeki; Alexander Klimov; Henrietta Hall; Raymond Reid; Mathuram Santosham; Katherine L. O'Brien

OBJECTIVE To assess the effect of seasonal influenza vaccination during pregnancy on laboratory-confirmed influenza in infants to 6 months of age. DESIGN Nonrandomized, prospective, observational cohort study. SETTING Navajo and White Mountain Apache Indian reservations, including 6 hospitals on the Navajo reservation and 1 on the White Mountain Apache reservation. PARTICIPANTS A total of 1169 mother-infant pairs with mothers who delivered an infant during 1 of 3 influenza seasons. MAIN EXPOSURE Maternal seasonal influenza vaccination. MAIN OUTCOME MEASURES In infants, laboratory-confirmed influenza, influenza-like illness (ILI), ILI hospitalization, and influenza hemagglutinin inhibition antibody titers. RESULTS A total of 1160 mother-infant pairs had serum collected and were included in the analysis. Among infants, 193 (17%) had an ILI hospitalization, 412 (36%) had only an ILI outpatient visit, and 555 (48%) had no ILI episodes. The ILI incidence rate was 7.2 and 6.7 per 1000 person-days for infants born to unvaccinated and vaccinated women, respectively. There was a 41% reduction in the risk of laboratory-confirmed influenza virus infection (relative risk, 0.59; 95% confidence interval, 0.37-0.93) and a 39% reduction in the risk of ILI hospitalization (relative risk, 0.61; 95% confidence interval, 0.45-0.84) for infants born to influenza-vaccinated women compared with infants born to unvaccinated mothers. Infants born to influenza-vaccinated women had significantly higher hemagglutinin inhibition antibody titers at birth and at 2 to 3 months of age than infants of unvaccinated mothers for all 8 influenza virus strains investigated. CONCLUSIONS Maternal influenza vaccination was significantly associated with reduced risk of influenza virus infection and hospitalization for an ILI up to 6 months of age and increased influenza antibody titers in infants through 2 to 3 months of age.


The Journal of Infectious Diseases | 2007

Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial

Katherine L. O'Brien; Eugene Millar; Elizabeth R. Zell; Melinda Bronsdon; Robert Weatherholtz; Raymond Reid; Jocelyn Becenti; Sheri Kvamme; Cynthia G. Whitney; Mathuram Santosham

BACKGROUND Pneumococcal conjugate vaccines (PCVs) prevent vaccine serotype (VT) invasive disease; nonvaccine serotype (NVT) disease increases modestly. The impact of PCV on nasopharyngeal (NP) colonization is essential to understanding disease effects. METHODS We conducted a community-randomized controlled trial with catch-up vaccination through age 2 years investigating the effect of 7-valent PCV (PnCRM7) on NP colonization among American Indian infants and their unvaccinated contacts. Infants receiving blinded vaccine at 2, 4, 6, and 12-15 months of age had NP cultures obtained at age 7, 12, and 18 months. Serotype-specific colonization was detected by immunoblot. RESULTS We enrolled 566 vaccinated and 286 unvaccinated children from 511 households and collected 5157 specimens, of which 3525 (68.4%) had pneumococcus. PnCRM7 vaccinees were less likely to be colonized with VT (odds ratio [OR], 0.40 [95% confidence interval {CI}, 0.23-0.67]) but were more likely to be colonized with NVT pneumococci (OR, 1.67 [95% CI, 1.02-2.78]). PnCRM7 vaccinees were less densely colonized with VT strains than control vaccinees (OR, 0.61 [95% CI, 0.38-0.99]). Day care-attending unvaccinated children in PnCRM7 communities were less likely to have VT colonization than those in control communities (OR, 0.27 [95% CI, 0.07-1.07]). CONCLUSIONS PnCRM7 reduces the risk of VT acquisition and colonization density but increases the risk of NVT acquisition among vaccinees and their household contacts.


The Journal of Pediatrics | 1997

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

Mathuram Santosham; Lawrence H. Moulton; Raymond Reid; Janné Croll; Robert Weatherholt; Richard L. Ward; John Forro; Edward T. Zito; Michael E. Mack; George Brenneman; Bruce L. Davidson

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.


Clinical Infectious Diseases | 2008

Indirect Effect of 7-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Colonization among Unvaccinated Household Members

Eugene Millar; James Watt; Melinda A. Bronsdon; Jean Dallas; Raymond Reid; Mathuram Santosham; Katherine L. O'Brien

BACKGROUND Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, rates of invasive pneumococcal disease have decreased in both vaccinated and unvaccinated age groups. Reduction of invasive pneumococcal disease in unvaccinated groups has been attributed to reduced transmission of vaccine-type pneumococci in the community. Understanding the impact of PCV7 on carriage among vaccinated and unvaccinated community members is critical to interpreting, predicting, and understanding the impact of PCV7 on disease. METHODS A group-randomized, phase III efficacy trial of PCV7 was conducted among southwestern American Indian communities. Meningococcal conjugate vaccine against serogroup C was used as the control. After the trial was unblinded, we conducted a carriage study of participating communities to evaluate the impact of PCV7 on colonization among trial participants and their unvaccinated household members. RESULTS Adults and unvaccinated children aged <5 years living in households with a PCV7 vaccinee were less likely to be colonized with vaccine-type pneumococci (odds ratio [OR] for adults, 0.57; 95% confidence interval [CI], 0.33-0.99; OR for children, 0.57; 95% CI, 0.26-0.98) than were those living in a household with a control vaccinee. There was no difference for children aged 5-17 years. Decreases in vaccine-type carriage were offset by increases in carriage of nonvaccine types. Among adults living with a trial participant colonized with vaccine-type pneumococcus, those in the households randomized to receive PCV7 were less likely to be colonized with the same serotype than were those in the households randomized to receive the control vaccine (OR, 0.34; 95% CI, 0.11-0.99). CONCLUSIONS Vaccine-type pneumococcal carriage was lower among adults and unvaccinated children living with a PCV7 vaccinee. This is attributable to reduced exposure and reduced transmission when exposure occurs.


The New England Journal of Medicine | 1987

Prevention of Haemophilus influenzae Type b Infections in High-Risk Infants Treated with Bacterial Polysaccharide Immune Globulin

Mathuram Santosham; Raymond Reid; Ambrosino Dm; Wolff Mc; Janné Almeido-Hill; Priehs C; Aspery Km; Garrett S; Croll L; Foster S

Apache Indian infants have a high frequency of Haemophilus influenzae type b (Hib) and pneumococcal infections. Forty percent of Hib infections in these infants occur before the age of six months, when active immunization may not be protective. To evaluate the efficacy of passive immunization with a human hyperimmune globulin (bacterial polysaccharide immune globulin [BPIG]) prepared from the plasma of immunized adult donors, we randomly assigned 703 infants in a double-blind fashion to receive 0.5 ml of BPIG per kilogram of body weight (n = 353) or 0.5 ml of saline (n = 350) intramuscularly at 2, 6, and 10 months of age. Hib-antibody levels were significantly higher in BPIG recipients than in placebo recipients at 4, 6, and 10 months of age (P less than 0.001). During the first 90 days after BPIG or placebo injection, no Hib or pneumococcal infections were detected in the BPIG group, whereas seven Hib infections (six cases of bacteremia and one of meningitis) and four pneumococcal infections (bacteremia) were detected in the placebo group (P = 0.007 and 0.06, respectively). During the fourth month, one case of Hib meningitis and two cases of pneumococcal bacteremia developed in the BPIG group, whereas there were no Hib or pneumococcal infections in the placebo group. We conclude that BPIG given at four-month intervals provided significant protection against serious Hib disease for three months, and that in high-risk infants it might be used alone, perhaps at three-month intervals, or together with active immunization.


Clinical Infectious Diseases | 2006

Effect of Community-Wide Conjugate Pneumococcal Vaccine Use in Infancy on Nasopharyngeal Carriage through 3 Years of Age: A Cross-Sectional Study in a High-Risk Population

Eugene Millar; Katherine L. O'Brien; James Watt; Melinda A. Bronsdon; Jean Dallas; Cynthia G. Whitney; Raymond Reid; Mathuram Santosham

BACKGROUND A 7-valent pneumococcal conjugate vaccine (PnCRM7) has been shown to be highly effective in preventing invasive pneumococcal disease. Pneumococcal conjugate vaccines also protect against nasopharyngeal carriage of vaccine serotypes, but the duration of protection against nasopharyngeal carriage is not known. METHODS A group-randomized efficacy trial of PnCRM7 (vaccine serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) was conducted on the Navajo and White Mountain Apache reservations from April 1997 to October 2000. A group C meningococcal conjugate vaccine was used as the control vaccine. Infants enrolled between 6 weeks and 7 months of age received 3 doses of vaccine 2 months apart and a fourth dose at 12-15 months of age. Vaccinees were enrolled in a nasopharyngeal carriage study from February 2001 to January 2002 to assess the duration of protection against pneumococcal carriage induced by PnCRM7. RESULTS We included 749 children in the analysis, including 468 children vaccinated with PnCRM7 and 281 children vaccinated with group C meningococcal conjugate vaccine. The median age was 3.3 years (range, 1-7 years), and the median time since last dose of study vaccine was 27 months (range, 12-48 months). Frequencies of overall pneumococcal carriage were similar among PnCRM7 and group C meningococcal conjugate vaccine recipients (63.9% vs. 60.5%, respectively). The absolute frequency of vaccine-type pneumococcal carriage was lower among PnCRM7 recipients (10.3%) than among controls (17.1%; P = .01). This reduction was offset by an increase of nonvaccine-type pneumococcal carriage among PnCRM7 recipients (39.2% vs. 29.8%; P = .01). CONCLUSION Community-wide PnCRM7 vaccination in infancy reduces the prevalence of vaccine-type carriage and increases the prevalence of nonvaccine-type carriage through at least 3 years of age.


Pediatric Infectious Disease Journal | 1993

Vaccination with Haemophilus influenzae type b meningococcal protein conjugate vaccine reduces oropharyngeal carriage of Haemophilus influenzae type b among American Indian children.

Aion K. Takala; Mathuram Santosham; Janné Almeido-Hill; Mark Wolff; Wendy Newcomer; Raymond Reid; Helena Käyhty; E. Esko; P. H. Mäkelä

The effect of Haemophilus influenzae type b (Hib) meningococcal protein conjugale 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


Journal of Clinical Microbiology | 2007

Association of the Pneumococcal Pilus with Certain Capsular Serotypes but Not with Increased Virulence

Alan Basset; Krzysztof Trzciński; Christina Hermos; Katherine L. O'Brien; Raymond Reid; Mathuram Santosham; Alexander J. McAdam; Marc Lipsitch; Richard Malley

ABSTRACT The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pneumococcal collection and isolates of S. pneumoniae from blood cultures collected at Childrens Hospital Boston. Overall, 21.4% of strains in the American Indian collection had the rrgC gene, but there was no difference between isolates obtained from the nasopharynx and those obtained from sterile sites (blood or cerebrospinal fluid). Vaccine-type strains were significantly more likely than non-vaccine-type strains to have this pilus gene (P < 0.001). Among isolates with identical multilocus sequence types, there was a high concordance (95%) between the multilocus sequence type and the presence or the absence of rrgC. Finally, in the era of the pneumococcal conjugate vaccine, the frequency of rrgC in isolates from Childrens Hospital Boston has decreased significantly (42.8% before 2000 versus 21.3% after 2000; P = 0.019). Therefore, our data show that the pilus is present in a minority of strains and is associated with certain serotypes and that its frequency has been reduced by the conjugate pneumococcal vaccine.

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James Watt

Johns Hopkins University

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Eugene Millar

Johns Hopkins University

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Janné Croll

Johns Hopkins University

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Cynthia G. Whitney

Centers for Disease Control and Prevention

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Allison Barlow

Johns Hopkins University

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