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Anticipating rotavirus vaccines: hospital-based surveillance for rotavirus diarrhea and estimates of disease burden in Bangladesh.

OBJECTIVES: Rotavirus is the most common cause of severe diarrhea in children worldwide, and a vaccine may soon be licensed and available for use in immunization programs. To assess the need for a rotavirus vaccine in Bangladesh, we estimated the disease burden of rotavirus diarrhea from national vital statistics for births and diarrheal deaths, together with hospital surveillance data on the proportion of severe childhood diarrhea attributed to rotavirus. METHODS: From 1990 through 1993, hospital surveillance was conducted of a systematic, random 4% sample of >80,000 patients with diarrhea who sought care each year at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). RESULTS: Rotavirus was detected in 20% (1561 of 7709) of fecal specimens from children with diarrhea <5 years of age; 92% of all cases (1436) occurred in children <2 years of age, but only 3% (50) of cases occurred in infants <3 months of age. Children infected with rotavirus were more likely to have watery stools (P < 0.001), severe vomiting (P < 0.001) but less severe dehydration (P = 0.007) than children infected with other enteropathogens. CONCLUSIONS: We estimate that in this setting, where 18% of children die by age 5 and about 25% of these succumb to diarrhea, between 14,850 and 27,000 of the 3 million Bangladeshi children born in 1994 will die of rotavirus by the age of 5 years, equivalent to 1 rotavirus death per 111 to 203 children. The estimated burden of rotavirus diarrhea in Bangladesh is sufficiently great to warrant field testing of rotavirus vaccines for possible inclusion in the current immunization program.

Bangladesh↗

[Seroprevalence of hepatitis B virus markers in pregnant women attending a public hospital in Navarra].

OBJECTIVE: To design efficient massive immunization programs for newborns it is essential to know the prevalence of HBV infection in pregnant women. As a contribution to this knowledge the prevalence of HBV markers was studied in pregnant women attended at a public hospital in Navarra. An assessment was also made of the relationship between prevalence of HBV markers and other epidemiological factors. METHODS: The gestational history was reviewed of 2,499 pregnant women aged 14-45 years attended at the hospital during 1991. The following factors were investigated: age, profession, job, and educational level of the woman and her partner, residence, Health Area, risk factors and serological markers (HbsAG, anti-HBs, anti-HBc, and, when appropriate, HBeAg/anti-Hbe. RESULTS: The screening rate of HBsAg in the group of pregnant women was 70%; the prevalence of positive HbsAg was 0.70%. The respective prevalence rates of anti-HBs, anti-HBc, and AMP were 6%, 7.5% and 8.6%. The type of residence, social class and risk exposure had influence on the prevalence of positive markers. CONCLUSIONS: The 70% of screening rate in the group of pregnant women is still far from reaching the goal of 95% intended in the Plan de Salud Infantil in Navarra for 1993. A prevalence of 0.70 for positive HBsAg was observed. No geographical differences were observed in the distribution of HBV markers, but its prevalence was influenced by the type of residence, social class and risk exposure. A discussion follows whether a massive immunization program form newborns in Navarra is warranted.

Adolescent↗

Hepatitis B vaccination among children in inner-city public housing, 1991-1997.

CONTEXT: In 1991, the Advisory Committee on Immunization Practices recommended universal vaccination of infants against hepatitis B virus (HBV), with series initiation within days of birth. OBJECTIVE: To determine HBV vaccine coverage in a low-income urban population and to examine whether HBV immunization within the first month of life affects subsequent vaccine receipt. DESIGN: Cohort study based on immunization records collected in the Pediatric Immunization Program. Setting Large public housing development in Chicago, Ill. PARTICIPANTS: All 1143 children who were born between 1991 and 1997 and enrolled between 1993 and mid-1998, with follow-up to age 35 months. MAIN OUTCOME MEASURES: On-time vaccine receipt of HBV vaccine doses, diphtheria-tetanus-pertussis vaccine (DTP) dose 1, and the 4:3:1 series (4 doses of DTP vaccine, 3 doses of poliomyelitis vaccine, and 1 dose of measles-containing vaccine), analyzed by year. RESULTS: On-time HBV vaccination increased quickly following new guidelines and reached a plateau of about 50% coverage for those born in or after 1995. Since 1994, more children (64%) received the first HBV vaccine dose on time than any other vaccine. Children who received a dose of HBV vaccine during their first month of life were more likely to receive the first DTP vaccine dose on time (60.1%) than those who did not get an HBV vaccine dose during the first month (36.4%; chi2 = 53.7; P<.001). Children who received the first HBV vaccine dose during their first month were more likely than those receiving it at age 1 to 2 months to complete 3 HBV doses by 19 months (70.6% vs 51.1%; chi2 = 11.6; P = .001) and to complete the 4:3:1 series by age 19 months (49.8% vs 37.9%; chi2 = 4.0; P = .05). CONCLUSIONS: In this inner-city population, HBV vaccine has been received at rates similar to those of other vaccines within 3 years of issuance of new recommendations. Of note, immunization with HBV vaccine at birth was associated with timely receipt of other vaccines and, therefore, may have the potential to increase vaccination among groups less likely to be up-to-date on early childhood vaccines.

Chicago↗

Progress toward integrating hepatitis B vaccine into routine infant immunization schedules in the United States, 1991 through 1994. Connecticut Hepatitis B Project Group.

OBJECTIVE: We assessed progress toward universal infant immunization against hepatitis B, which was first recommended in November 1991. METHODS: Multiple data sources were used to describe vaccination policies and trends in infant hepatitis B vaccine coverage. RESULTS: As of June 1993, 51% of the 63 local, state, and territorial immunization programs recommended hepatitis B vaccination of all newborns shortly after birth. The number of first dosages of hepatitis B vaccine administered to infants in public sector clinics increased rapidly from late 1992 to 1993, and at the end of 1993 was approximately two thirds the number of first dosages of other infant antigens. In a nationwide survey of hospital nurseries 47% offered hepatitis B vaccine to all newborns. Of 3982 sampled newborns in these hospitals, 36.2% had been vaccinated before discharge. In San Francisco and Connecticut, where public health officials encouraged hospitals to offer hepatitis B vaccination, first-dose coverage at discharge was 82.3% in 1994 and 69.1% in 1993, respectively. Coverage was higher in healthier infants and lower in infants of older or better-educated mothers. Results from the National Health Interview Survey demonstrate that three-dose completion at 12 months of age increased form less than 1% of children born in 1989 to 40% of children born in the fourth quarter of 1992. Vaccination at birth increased from less than 1% of infants born in 1989 to 32% of infants born in the second half of 1993. CONCLUSIONS: Infant hepatitis B vaccination has expanded rapidly since national recommendations were made; however, universal coverage has not been achieved.

Connecticut↗

[Introduction of a conjugate vaccine against Hib in Chile and Uruguay].

In some countries, the invasive disease caused by Haemophilus influenzae type b (Hib) has been practically eliminated thanks to vaccination. However, in much of the developing world, meningitides and pneumonias caused by these bacteria continue to be a major cause of childhood morbidity and mortality, as well as high hospitalization costs. Because safe and effective conjugate vaccines are now available, the Special Program for Vaccines and Immunization of the Pan American Health Organization has recommended introducing them into the regular vaccination regimen of as many countries as possible. This has been done in Chile and Uruguay, where the Hib vaccine now forms part of the regular vaccination routine. When the vaccine was being introduced, both countries had difficulties they could have avoided if they had known of the experiences of other nations. Therefore, these two countries now offer the lessons they learned to other nations considering introducing the vaccine into their immunization programs. The most important lessons were to: strengthen the epidemiological surveillance system sufficiently in advance of introducing the vaccine; with the support of scientific societies, present the technical information that justifies introducing the vaccine; seek community backing and acceptance; precisely establish in advance the presentation and dosage of the vaccine that is most appropriate for the country; and be certain to have the political and legal decisions needed to ensure the continuity of Hib vaccination in the future.

Child↗

Innate immune molecular landscape following controlled human influenza virus infection.

Viral infections can induce prolonged changes in innate immunity. Here, we use blood samples from a human influenza H3N2 challenge study (NCT03883113) to perform comprehensive multi-omics analyses. We detect remodeling of immune programs in circulating innate immune cells that persist after resolution of the infection. We find changes associated with suppressed inflammation, including decreased cytokine and AP-1 gene expression as well as decreased accessibility at AP-1 targets and interleukin-related gene promoter regions. We also find decreased histone deacetylase gene expression, increased MAP kinase gene expression, and increased accessibility at interferon-related gene promoter regions. Genes involved in inflammation and methylation remodeling show modulation of gene-chromatin site regulatory circuit activity. These results reveal a coordinated rewiring of the molecular landscape in innate immune cells induced by mild influenza virus infection.

Humans↗

A simplified schedule to integrate the hepatitis B vaccine into an expanded program of immunization in endemic countries.

OBJECTIVE: To investigate the safety, immunogenicity, and efficacy of a simplified hepatitis B vaccination schedule. METHODS: The second dose of hepatitis B vaccine and the first dose of diphtheria-tetanus-pertussis (DTP) vaccine were given simultaneously at age 6 weeks. The second dose of DTP vaccine was given at age 3.5 months. The third dose of DTP vaccine and the third dose of hepatitis B vaccine were given at age 5.5 months. One hundred three infants (group A) born to mothers without hepatitis B surface antigen (HBsAg) received DTP with whole-cell pertussis vaccine. Fifty-five infants (group B) born to mothers with HBsAg and hepatitis B e antigen received DTP with acellular pertussis vaccine. RESULTS: By age 9 months, none of group A and 4 (7%) group B infants were sero-positive for HBsAg. The protective efficacy against the hepatitis B carrier state in these infants at high risk was 92%. Antibody to hepatitis B surface antigen was 10 mlU/ml or greater in 99 (96%) of group A infants and in 50 (91%) of group B infants. Both the acellular and whole-cell DTP vaccines were immunogenic, and the incidences of adverse reactions were within an expected and acceptable range. CONCLUSIONS: The simplified vaccination schedule to integrate the hepatitis B vaccine into the Expanded Programme of Immunization was safe, Immunogenic, and effective. This schedule may improve vaccine compliance and be applied to DTP and hepatitis B combination vaccines now under investigation.

Antigens↗

Effect of vitamin A administered at Expanded Program on Immunization contacts on antibody response to oral polio vaccine.

OBJECTIVE: Vitamin A supplementation to mothers in the postpartum period and to their infants at routine immunization contacts is being considered to reduce vitamin A deficiency in infancy. This study was conducted to determine the impact of maternal and infant vitamin A supplementation on antibody response to oral polio vaccine (OPV). DESIGN: Randomized, double blind, placebo-controlled trial. INTERVENTIONS: Mothers in the intervention group received 60 mg retinol equivalent (RE) vitamin A 3-4 weeks after delivery and their infants 7.5 mg RE with each OPV dose at 6, 10 and 14 weeks of age. The control group mothers and their infants received a placebo at each of these contacts. MAIN OUTCOMES: Geometric mean (GM) titer of neutralizing antibodies and proportion of children with protective titer to the three polioviruses at 26 weeks of age. RESULTS: Vitamin A supplementation increased the proportion of infants with protective antibody titer against poliovirus type 1 (relative risk (RR) 1.15, 95% confidence interval (CI) 1.03-1.28) and the GM antibody titer (ratio of GM 1.55, 95% CI 1.03-2.31) following immunization. The proportion of infants with protective antibody titer against poliovirus type 2 (RR 0.99, 95% CI 0.94-1.05) or type 3 (RR 1.05, 95% CI 0.96-1.15) was not significantly different in vitamin A and placebo groups. The GM antibody titer for poliovirus type 2 (ratio of GM 0.99, 95% CI 0.64-1.54) or poliovirus type 3 (ratio of GM 1.10, 95% CI 0.69-1.75) also did not differ across groups. CONCLUSIONS: Vitamin A given to the mothers in the postpartum period and their infants with OPV did not interfere with the antibody response to any of the three polioviruses and enhanced the response to poliovirus type 1.

Adult↗

A successful program of immunizing Rh-negative male volunteers for anti-D production using frozen/thawed blood.

Individually matched (rhesus-D) Rh-positive frozen/thawed red blood cells were used to immunize 28 Rh-negative male volunteers. The immunizing schedule consisted of a single unit (200 ml) of frozen/thawed red blood cells, followed by six monthly booster doses (0.5 to 1.0 ml) after a rest period of six months. A final response rate of 93 percent (26 of 28) was achieved. All responders had produced anti-D before the second booster injection (mean detection time 4.25 months). Retrospective analysis indicated that the final response rate and the level of anti-D response could be predicted as early as seven to eight months from the start of immunization. These findings have practical implications for deciding when to discontinue immunization. The Rh genotype of the immunizing cells did not appear to be an important factor in determining the anti-D response, and with the matching system used, antibodies other than anti-C, D, and/or E were not produced. The use of frozen/thawed red blood cells for immunization has the advantage of permitting optimum matching for undesirable red blood cell antigens and minimizing the risk of transmitting disease to the recipients.

Antibody Formation↗

Invasive pneumococcal infections in Canadian children, 1991-1998: implications for new vaccination strategies. Canadian Paediatric Society/Laboratory Centre for Disease Control Immunization Monitoring Program, Active (IMPACT).

We reviewed 2040 consecutive cases of invasive pneumococcal infection that were seen at 11 pediatric centers across Canada during 1991-1998 to determine if such infections could be prevented by new conjugate vaccines. Isolates from 1528 cases were serotyped. Most cases (61.5%) occurred in patients aged >2 years. Underlying medical conditions were present in 23.2% of case patients. Serotypes in the 7-valent conjugate vaccine matched isolates as follows: 85.8% of tested isolates from children aged 6 months to 5 years, but significantly fewer isolates in younger and older children; 72.9% of isolates from non-healthy children, but 83.9% of isolates from previously healthy children; and 95.4% of isolates with high-level penicillin resistance, but only 72.7% of those with intermediate-level resistance. Significant natural variation in the proportion of isolates matching 7-valent vaccines occurred from year to year and among centers. New conjugate vaccines have great potential but their effectiveness and limitations require ongoing study.

Bacteremia↗

Impaired T helper 1 function of nonstructural protein 3-specific T cells in Japanese patients with encephalitis with neurological sequelae.

Japanese encephalitis virus (JEV) is the principal cause of viral encephalitis. The predominance of children among patients with encephalitis in areas where JEV is endemic that do not have immunization programs suggests that acquired immunity is critical in protecting adults against symptomatic JEV encephalitis. We characterized and compared the T cell response to nonstructural (NS) protein 3 between healthy individuals naturally exposed to JEV and patients in the convalescent phase of JEV encephalitis. The NS3 protein, used as a fusion to the 11-amino acid protein transduction domain of human immunodeficiency virus Tat, elicited CD4(+) and T helper-dependent CD8(+) T cell responses. The production of interferon (IFN)- gamma by responding T cells was significantly higher in healthy donors than in patients, correlating strongly with acquired protective immunity to JEV. Furthermore, a striking inverse association between IFN- gamma levels and the severity of postencephalitic sequelae in patients implicated a role of IFN- gamma in recovery.

Antibody Formation↗

The use of diclazuril in extended withdrawal anticoccidial programs: 2. Immunity to Eimeria tenella challenge after drug withdrawal.

The effect of diclazuril medication on the development of natural immunity to Eimeria tenella was determined. Birds in two treatments, nonexposed, non-challenged (NENC) and nonexposed, challenged (NEC), were from a holding group raised under conditions designed to prevent coccidial infection. Birds in five other treatments, from the same hatch and source as birds in the first two treatments, were from a floor pen study involving a natural exposure to Eimeria spp. These birds were assigned to the current study based on their respective treatments in the original floor pen study as follows: unmedicated (UNM), 66 ppm salinomycin (SAL) + 50 ppm roxarsone in the starter and grower diets to Day 28 (SAL 28), 66 ppm SAL + 50 ppm roxarsone in the starter diet and 1 ppm diclazuril (DIC) in the grower diet to Day 28 (DIC 28) or to Day 35 (DIC 35), or in the grower and finisher diets to Day 42 (DIC 42). Each treatment comprised three floor pens of 10 birds (female) in a randomized complete block design. All birds were fed an UNM finisher diet during the 7-d challenge study. Birds in each treatment, except NENC, were individually inoculated (p.o.) with 1 x 10(5) Eimeria tenella sporulated oocysts on Day 1. Based on bird performance and cecal lesion scores, birds in the DIC 35 and 42 treatments had a low immunity to the challenge infection, birds in the DIC 28 treatment were partially immunized, and the highest levels of immunity were observed in the UNM and SAL 28 treatments.

Animal Nutritional Physiological Phenomena↗

Hepatitis B immunization among adolescents.

Prior to this year, little has been written regarding the immunization of the adolescent population against hepatitis B. Most studies have focused on the immunization of infants, children, and adults, highlighting concerns about adolescent compliance with such an immunization program. The body of literature about hepatitis B immunization among adolescents has grown, and there is much to learn in preparation for the implementation of the immunization Practices Advisory Committee's most recent recommendation to immunize all 11- and 12-year-old children in the United States who have not previously been immunized against hepatitis B.

Adolescent↗

Predictions of the epidemiologic impact of introducing a pre-erythrocytic vaccine into the expanded program on immunization in sub-Saharan Africa.

We predict the effects of introduction of a pre-erythrocytic vaccine against Plasmodium falciparum into a malaria-endemic population in Africa. We use a stochastic simulation model that includes components of transmission, parasitology, and clinical epidemiology of malaria and was validated using the results of field trials of the RTS,S/AS02A vaccine. The results suggest that vaccines with efficacy similar to that of RTS,S/AS02A have a substantial impact on malaria morbidity and mortality during the first decade after their introduction, but have negligible effects on malaria transmission at levels of endemicity typical for sub-Saharan Africa. The main benefits result from prevention of morbidity and mortality in the first years of life. Vaccines with very short half-life or low efficacy may have little overall effect on incidence of severe malaria. A similar approach can be used to make predictions for other strategies for deployment of the vaccine and to other types of malaria vaccines and interventions.

Adolescent↗

The influence of an arduous military training program on immune function and upper respiratory tract infection incidence.

The effects of the first 19 weeks of U.K. Parachute Regiment (PARA) training on upper respiratory tract infection (URTI) incidence and immune function (circulating leukocyte counts, lymphocyte subsets, lipopolysaccharide-stimulated neutrophil degranulation, and salivary immunoglobulin A concentrations) were investigated for 14 PARA recruits and 12 control subjects. No significant differences were reported between groups for the number or duration of URTIs, lymphocyte subsets, or salivary immunoglobulin A concentrations during training. URTI incidence was greater in the PARA group at weeks 2 and 3 (p < 0.05), coinciding with a decrease in circulating leukocyte and lymphocyte counts (p < 0.05). Neutrophil degranulation was similar in the PARA and control groups at weeks 0 and 19. Decreases in saliva flow rate occurred in the PARA group at week 15 and weeks 18 to 20 (p < 0.05). These results show a limited effect of PARA training on URTI incidence and immune function. The progressive decrease in saliva flow rate during PARA training may indicate an ensuing state of hypohydration.

Adult↗