This controlled trial involving 39,836 children evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in South Africa. Vaccination decreased the frequency of invasive pneumococcal ...disease among both HIV-negative and HIV-positive children and reduced the number of first episodes of radiologically confirmed pneumonia.
In children a 9-valent conjugate vaccine prevents invasive disease.
Acute respiratory tract infections are a major cause of death in children under the age of five years.
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Streptococcus pneumoniae,
the leading bacterial pathogen,
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has become increasingly resistant to antibiotics.
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,
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Administration of a 7-valent vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197) reduced the incidence of invasive pneumococcal disease in children.
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The formulation lacks serotypes 1 and 5, which are important causes of invasive pneumococcal disease throughout the world.
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The efficacy of conjugate vaccine in the prevention of invasive pneumococcal disease among children infected with human immunodeficiency virus (HIV) is unknown. Therefore, we conducted a prospective, . . .
Highly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of ...developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research. Answers to the questions posed are likely to help prioritize and balance strategies to slow the progression of HIV infection, to address comorbidities and drug toxicity, and to enhance understanding about both HIV infection and aging.
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The safety, immunogenicity, and impact on carriage of a nonvalent pneumococcal vaccine given at ages 6, 10, and 14 weeks were examined in a double-blind, randomized, placebo-controlled trial in 500 ...infants in Soweto, South Africa. No serious local or systemic side effects were recorded. Significant antibody responses to all pneumococcal serotypes were observed 4 weeks after the third dose. Haemophilus influenzae type b polyribosylribitol phosphate (geometric mean titer, 11.62 μg/mL) and diphtheria (1.39 IU/mL) antibodies were significantly higher in children receiving pneumococcal conjugate, compared with placebo recipients (4.58 μg/mL and 0.98 IU/mL, respectively). Nasopharyngeal carriage of vaccine serotypes decreased in vaccinees at age 9 months (18% vs. 36%), whereas carriage of nonvaccine serotypes increased (36% vs. 25%). Carriage of penicillin-resistant pneumococci (21% vs. 41%) and cotrimoxazole-resistant pneumococci (23% vs. 35%) were significantly reduced 9 months after vaccination, compared with controls.
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The Tuberculin Skin Test Huebner, Robin E.; Schein, Maybelle F.; Bass, John B.
Clinical infectious diseases,
12/1993, Volume:
17, Issue:
6
Journal Article
Peer reviewed
The tuberculin skin test is one of the most widely used diagnostic tests ever developed and remains the only method of detecting infection due to M. tuberculosis. False-positive and false-negative ...reactions to tuberculin can make decisions about preventive therapy problematic. The development of more sensitive and specific skin-test antigens could result in a diagnostic test that distinguishes among infections with different species of mycobacteria. Clearly, much remains to be learned about tuberculin skin testing, particularly in the context of HIV infection.
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BACKGROUND.Haemophilus influenzae type b (Hib) conjugate vaccines have successfully reduced the burden of invasive Hib disease in developed countries; however, their effectiveness in countries with a ...high incidence of pediatric HIV-1 is unknown.
METHODS.The effectiveness of Hib conjugate vaccine was prospectively evaluated in South African children. The burden of invasive Hib disease in children <1 year old was compared in 2 cohorts. The first cohort included 22 000 African children born in 1997 969 (4.45%) of whom were estimated to be HIV-1-infected who were not vaccinated with Hib conjugate vaccine. This group was compared with 19 267 children 1162 (6.03%) of whom were estimated to be HIV-1-infected vaccinated at 6, 10 and 14 weeks of age with an Hib conjugate vaccine TETRAMUNE (polyribosylribitol phosphate-CRM197-diphtheria-tetanus toxoids-whole cell pertussis) between March, 1998, and June, 1999.
RESULTS.The estimated burden of invasive Hib disease in nonimmunized HIV-1-infected children <1 year of age was 5.9-fold 95% confidence interval (95% CI), 2.7 to 12.6 higher than in HIV-1-uninfected children. The overall estimated effectiveness of Hib conjugate vaccine in fully vaccinated children <1 year of age was 83.2% (95% CI 60.3 to 92.9). Vaccine effectiveness was significantly reduced in HIV-1- infected 43.9% (95% CI −76.1 to 82.1) compared with uninfected children 96.5% (95% CI 74.4 to 99.5);P < 10. Among three of the fully vaccinated HIV-1-infected children who developed invasive Hib disease, the anti-Hib polyribosylribitol phosphate serum antibody concentrations were 0.23, 0.25 and 0.68 μg/ml.
CONCLUSION.Although the Hib conjugate vaccine was less effective among HIV-1-infected than among uninfected children, it was 83% effective in preventing overall invasive Hib disease and therefore should be considered for inclusion in the routine vaccination schedule by other African countries.
BACKGROUND.Children <6 months of age are at increased risk of pneumococcal disease. The early immunogenicity of conjugate vaccines therefore may be important to prevent disease in young children.
...OBJECTIVES.To determine the immunogenicity of a nonavalent pneumococcal conjugate vaccine after one dose, two doses and three doses and its impact on the antibody response to coadministered antigens.
METHODS.A total of 500 infants from Soweto were immunized at 6, 10 and 14 weeks of age with either placebo (n = 250) or 9-valent pneumococcal conjugate vaccine (n = 250) containing serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F conjugated to CRM197 mutant diphtheria protein. Blood was taken for determination of serotype-specific IgG before the first dose and 1 month after each dose.
RESULTS.Before the first dose at 6 weeks of age >80% of infants had >0.15 μg/ml antibody to six of the nine antigens, >70% to serotypes 18C and 23F and >50% to serotype 4. Geometric mean concentrations (GMCs) after one dose ranged from 0.27 μg/ml for serotype 23F to 2.98 μg/ml for serotype 1; >90% of infants had serotype-specific antibody >0.15 μg/ml except for serotypes 23F (70%) and 6B (80%). After two doses GMCs ranged from 1.14 μg/ml for serotype 23F to 5.68 μg/ml for serotype 1; >95% of infants had serotype-specific antibody >0.15 μg/ml and >75% had >0.5 μg/ml for all nine serotypes. GMCs after three doses ranged from 2.73 μg/ml for serotype 23F to 6.18 μg/ml for serotype 5; >98% of infants had serotype-specific antibody >0.15 μg/ml and >92% had >0.5 μg/ml for all nine serotypes. Antibody concentrations after three doses were significantly higher to Haemophilus influenzae type b-polyribosylribitol phosphate vaccine in children who received pneumococcal conjugate vaccine, but they had lower antibodies to pertussis toxin than controls.
CONCLUSIONS.A single dose of this pneumococcal conjugate vaccine produces a potentially protective antibody response to most serotypes in the majority of children in this population.
High vaccine cost has limited use of conjugate vaccines in the developing world where the disease burden is greatest. Fixed fractional doses of Haemophilus influenzae type b (Hib) vaccines have been ...shown to be immunogenic, but dose responses of these vaccines in humans are needed to determine the lowest immunogenic dose as an option for lowering vaccine cost. We randomized children to receive one of five doses (0.625, 1.25, 2.5, 5.0 and 10 microg) of either a diphtheria CRM197 or tetanus toxoid-conjugated Hib vaccine. The children received a primary three-dose series at 6, 10, and 14 weeks of age and a booster dose at 9 months. Anti-PRP IgG antibodies were measured at each vaccination, at 18 weeks, and at one week following the booster dose. Concentrations of > or =1.25 microg of HibCRM197 vaccine produced mean anti-PRP responses at 18 weeks of > or =5.72 microg/ml and > or =0.15 microg/ml was achieved in >98% of the children with at least 79% reaching anti-PRP concentrations of > or =1.0 microg/ml. Concentrations of > or =1.25 microg of Hib-tetanus vaccine produced mean anti-PRP responses at 18 weeks of > or =8.63 microg/ml and > or =0.15 microg/ml was achieved in 100% of the children with at least 88.9% reaching anti-PRP concentrations of > or =1.0 microg/ml. While mean antibody concentrations after either vaccine decreased over time, the proportion of children with antibody levels of > or =0.15 microg/ml had not changed significantly at the 9 month measurement. Immunologic memory was demonstrated by significant increases in mean antibody concentrations one week after the booster dose for doses > or =1.25 microg of HibCRM197 and Hib-tetanus to mean concentrations > or =37.71 and 16.07 microg/ml, respectively. There were no differences in antibody responses for vaccine doses > or =1.25 microg of the same vaccine or between the same concentrations of the two different vaccines. Our data suggest that doses of these vaccines of > or =1.25 microg may be sufficient to stimulate an immune response that offers both short and longer term protection from invasive Hib disease.
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Abstract This study compared the characteristics of infants hospitalized with apnea that participated in a vaccine trial compared with two control groups which consisted of 100 infants randomly ...selected from the same vaccine trial and 52 consecutively born very low birth weight (VLBW) infants. A total of 23 infants were admitted with apnea of whom 19 weighed <1500 g at birth and all were born at <37 weeks gestation. More of the VLBW infants in the apnea group had neonatal neurological complications compared with the VLBW control group ( p = 0.005). Ten of 11 children with apnea within 72 h of immunization were possibly related to vaccination.
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Treatment of malaria with sulfadoxine/pyrimethamine and of presumed bacterial infections with trimethoprim/sulfamethoxazole (cotrimoxazole) was assessed to see if either increases the carriage of ...cotrimoxazole-resistant Streptococcus pneumoniae in Malawian children. Children <5 years old treated with sulfadoxine/pyrimethamine, cotrimoxazole, or no antimicrobial agent were enrolled in a prospective observational study. Nasopharyngeal swabs were taken before treatment and 1 and 4 weeks later. Pneumococci were tested for antibiotic susceptibility by broth microdilution. In sulfadoxine/pyrimethamine-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 38.1% at the initial visit to 44.1% at the 4-week follow-up visit (P = .048). For cotrimoxazole-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 41.5% at the initial visit to 52% at the 1-week follow-up visit (P = .0017) and returned to 41.7% at the 4-week follow-up. Expanding use of sulfadoxine/pyrimethamine to treat chloroquine-resistant malaria may have implications for national pneumonia programs in developing countries where cotrimoxazole is widely used.
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