Correlation between pertussis toxin IgG antibodies in postvaccination sera and subsequent protection against pertussis

All acellular pertussis vaccines contain pertussis toxoid and induce protection against pertussis. This study investigated the relation between the postvaccination levels of pertussis toxin (PT) serum IgG and protection against pertussis. PT IgG was determined in sera obtained 21-77 days after the third vaccination from 813 children who received 3 doses of pertussis toxoid. The children were followed for 21-33 months after vaccination for the occurrence of pertussis. Of the children, 126 were exposed to pertussis in their households. The median PT IgG concentration was 79 U/mL in those who developed severe pertussis (>/=21 day of paroxysmal cough), 156 U/mL with mild pertussis (<21 days of paroxysmal cough), and 246 U/mL in those who did not develop pertussis (79 vs. 246, P<.0001). Corresponding values in the 687 children with no household exposure were 99, 124, and 155 U/mL, respectively (99 vs. 155, P<.0001). Thus, there is a highly significant correlation between the level of vaccine-induced serum PT IgG and protection against pertussis.     

Diphtheria in Latvia, 1986-1996

After nearly two decades without a diphtheria case in Latvia, the disease reappeared in 1986. From 1990 to 1996, case counts were highest among adults 40-49 years of age, school-aged children, and adolescents. Nonetheless, the average annualized incidence of disease was highest among infants and preschoolers. In August 1995, mass vaccination efforts began to provide adults 25-60 years of age with at least one dose of vaccine. By the end of the year, a 77% coverage rate was achieved, resulting in a decrease of reported diphtheria cases by 1996. From February to September 1997, special outreach efforts were focused on hard-to-reach populations; as a result, by June 1997, 55% of adults had received three doses of vaccine. While decreases in the incidence of and morbidity from diphtheria have occurred, additional efforts still need to be concentrated on improving vaccination coverage in adults and children <2 years of age and in reducing mortality from diphtheria.     

Epidemic diphtheria in the Kyrgyz Republic, 1994-1998

The Kyrgyz Republic experienced a widespread diphtheria epidemic during 1994-1998. National diphtheria surveillance and vaccination coverage information were used to describe the course of the epidemic. The epidemic began in August 1994, reached a peak in 1995 with 704 cases (incidence rate: 15.4/100,000 population) and 30 deaths, and declined to an incidence rate of 4.0/100,000 during the first 8 months of 1998. Age-specific incidence was highest in 1995 among persons 15-19 and 20-29 years old. Three rounds of mass vaccination with tetanus and diphtheria toxoids for adult use (Td) were conducted; reported coverage was 69% in 1995 and >95% in 1996 and 1997. Reported routine vaccination coverage with three doses of diphtheria toxoid by age 12 months increased from 62% in 1989 to 98% in 1997. Mass vaccination of the adult population with Td and improvements in childhood vaccination coverage played a major role in controlling the epidemic.     

Rubella in England, Scotland and Wales

Rubella vaccine was offered to schoolgirls in the United Kingdom (UK) from 1970, with antenatal testing and postpartum vaccination for susceptible women introduced during the 1970s. Mass vaccination with MMR of children aged 12-15 months was introduced in 1988; schoolgirl vaccination was discontinued in 1996 and replaced by a second dose of MMR for pre-school children; postpartum vaccination of susceptible women identified through antenatal testing continues. Rubella was made a notifiable disease in 1988, and is monitored through clinical and laboratory reports; data are available on rubella associated terminations and congenital rubella syndrome(CRS) births, rubella susceptibility in population subgroups, and vaccine uptake. Reported cases of CRS declined from about 50 a year 1971-75 to just over 20 a year 1986-90, and rubella associated terminations from an average of 750 to 50 a year. About 40 infants with CRS have been reported since 1991; about a third of their mothers were infected abroad, most in their country of origin (imported infections), a third were born abroad but acquired infection in the UK, and a third were UK-born. Women living in the UK who were born abroad have much higher rubella susceptibility rates than UK-born women. Although there is currently very little rubella infection circulating, uptake of MMR has dropped by over 10% since 1995. If rubella starts to circulate again, immigrant women will be at increased risk of acquiring infection in pregnancy.     

Pertussis complications in Germany— 3 years of hospital-based surveillance during the introduction of acellular vaccines

Summary  Between 1 November 1993 and 31 October 1996, admissions to paediatric departments forBordetella pertussis complications were reported to a nationwide, hospitalbased active surveillance system. The case definition included pertussis complicated by pneumonia, apnoea requiring assisted ventilation, seizures, encephalopathy or a combination of these. Two hundred sixteen cases of pertussis complications were registered. 57.4% of them were in infants, 50.9% of them less than 6 months old. There were five deaths, three previously healthy children died. At the time of hospital admission, 106 cases would have been eligible for at least three doses of pertussis vaccine, only four (3.8%) had received the recommended number of immunisations From the second quarter of 1995, the reported number of cases declined. The decrease coincides with an improvement of pertussis vaccination coverage between 1992 and 1995 due to an increased use of acellular vaccines. The reduction of complicated pertussis was observed even in age-groups too young for the recommended vaccinations. The observed decrease could be due to the increase in vaccination coverage with interuption of the chain of transmission to the younger age-groups, to a cyclic decrease in pertussis cases, or to a combination of both. Continued surveillance will provide information on the epidemiological trend of hospitalisations for pertussis complications in the first European country to have introduced vaccination with acellular vaccines on a large scale.     

Safety and immunogenicity of combined Dtpa-IPV vaccine for primary and booster vaccination

This study evaluated the safety and immunogenicity of combined diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis vaccine (DTPa-IPV) given as primary immunization at ages 3, 4.5 and 6 months and a booster dose between the ages of 18 and 27 months to healthy children. The acellular pertussis tricomponent vaccine contains pertussis toxoid (PT), filamentous haemaglutinin (FHA) and 69 kDa outer membrane protein (PRN). Serum immune responses to the administered antigens were measured before and after the primary and the booster vaccination series. The safety of the vaccine was evaluated based on diary cards completed by parents within 4 d following each vaccination. A total of 237 and 150 children completed the primary and booster vaccination series, respectively. A total of 483 (66.5%) and 111 (74%) local and 317 (43.7%) and 98 (65.3%) general adverse events were reported after 726 doses of the primary series and 150 of the booster doses, respectively. Compared with primary vaccination, the incidence of all adverse symptoms was greater after the booster dose and a previous severe reaction was a risk factor for a severe reaction after the booster dose (OR = 5.11). All but 1 child, who failed to have antibodies to diphtheria toxoid after the booster dose, responded to all administered antigens with antibody titres greater than the assay cut-off points. The combined DTPa-IPV used for primary and booster immunization induced good immunity, but was associated with large local reactions in 21.3% of children after the booster dose.     

Hospitalización por tos ferina en España (1997-2011)

IntroductionPertussis incidence has increased in recent years in countries with high vaccination coverage. The aim of this study was to determine the health impact of pertussis in Spain in the period 1997-2011 in relation to hospitalizations, mortality, and associated costs.MethodsWe retrospectively analyzed hospital discharges included in the Minimum Data Set (MDS) in Spain for the period 1997-2011, with a primary or secondary diagnosis related to pertussis. We calculated incidence rates of hospitalization for pertussis (per 100,000) per year, by age group and by Autonomous Region, along with the mortality and lethality rates.ResultsA total of 8,331 hospital discharges with a diagnosis of pertussis were recorded in Spain between 1997 and 2011. The overall incidence of pertussis hospitalizations was 1.3 cases per 100,000 inhabitants. The large majority (92%) of hospitalizations occurred in children under one year of age, with an incidence of 115.2 hospitalizations per 100,000. There were 47 deaths, 37 (79%) in the group of children under 1 year and 6 (13%) in the group older than 65 years. The estimated cost of hospitalization for pertussis was 1,841 euros.ConclusionThe epidemiology of severe cases of pertussis, and its clinical and economic impact, confirms the need to modify the vaccination strategies for Spain to achieve more effective control in the most vulnerable groups.     

Vaccine immunity to diphtheria: a 20-year follow-up study.

A cohort of close to 70 children born in 1967-68 was followed for estimations of serum antitoxin levels against diphtheria. During the first 3-year-period after vaccination the mean level declined from 0.05 international units (IU) to 0.03. From the year before to the year after the booster of 0.5 LF of toxoid was given at the age of 8 years, the mean level raised from 0.01 to 0.06 IU. At 18 years the mean was again down to 0.01. Between 18 and 23 years of age a difference between the sexes was seen (higher levels in men). The explanation of this phenomenon must be the extra booster given to those young men who have done their compulsory military service.     

How best to estimate the global burden of pertussis?

In most countries, pertussis surveillance is inadequate for accurately estimating numbers of cases or deaths. Good estimates are needed to help set priorities for vaccination programmes. We aimed to develop a simple, reliable, and explicit method for estimating pertussis cases and deaths for children under 15 years to calculate the global disease burden in 1999. We estimated the proportion of susceptible children becoming infected in countries with poor vaccination coverage (<70%) in 1999 at 30% by 1 year, 80% by 5 years, and 100% by 15 years of age and for countries with good coverage (> or =70%) at 10% by 1 year, 60% by 5 years, and 100% by 15 years. Vaccine efficacy was estimated at 80% for preventing infection and 95% for preventing deaths. We used UN population estimates and vaccination coverage reported to WHO (adjusted for specific survey data if available). Case fatality ratios for countries with high and low child mortality were derived from published and unpublished work. For some countries with good vital events registration we used reported deaths adjusted for underascertainment. In 1999 there were an estimated 48.5 million pertussis cases in children worldwide. Deaths from pertussis were estimated at 390000 and at 295000 after adjustment for local data sources. Based on this approach, disability-adjusted life years from pertussis (12.7 million) in 2000 exceeded those of other preventable diseases such as lung cancer (11.4 million) and meningitis (5.8 million). This simple approach yields estimates that can be used for setting vaccination programme priorities. Better data are needed on the public health importance of pertussis in high mortality countries, the benefits of incomplete vaccination, and the harm from delayed vaccination.     

Response to Vaccination against Mumps in Medical Students: Two Doses Are Needed

Mumps is a vaccine-preventable infectious disease diffuse worldwide. The implementation of mumps vaccination reduced largely the spread of infection. On 11,327 Medical School students the prevalence of mumps positive antibodies was evaluated according to dose/doses of vaccine, year of birth and sex. Compliance to mumps vaccine was low in students born before 1990 but increased consistently after this year, above all compliance to two doses, due to the implementation of the vaccine offer. Positivity of mumps antibodies is significantly (p < 0.0001) lower in students vaccinated once (71.2%) compared to those vaccinated twice (85.4%). In addition, students born after 1995, largely vaccinated twice, showed a seropositivity near to 90%. Further, females had a significantly (p < 0.0001) higher proportion of positive antibodies after vaccination than males, both one (74.6% vs. 64.7%) and two doses (86.8% vs. 82.9%). Finally, seropositivity after two vaccine doses remains high (86.1%) even 15 years after the second dose. In conclusion, the research highlighted that vaccination against mumps reaches a good level of coverage only after two doses of vaccine persisting at high levels over 15 years and induces a more significant response in females.     

Magnitude of interference after diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b capsular polysaccharide-tetanus vaccination is related to the number of doses administered.

We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after 1, 2, or 3 doses of a diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine combined with a PRP-tetanus conjugate (PRP-T) vaccine, followed by separate injections of DTaP and PRP-T vaccines for the last 1 or 2 doses. Healthy infants were recruited from pediatric practices and were immunized according to recommended schedules. A significant decrease in the mean anti-PRP (from 5.25 to 2.68 microg/mL) and anti-tetanus toxoid antibody responses (from 0.13 to 0.09 Eq/mL) was observed as the number of doses of the DTaP/PRP-T combination vaccine increased (P<.02 and P=.01, respectively). In contrast, the mean anti-diphtheria toxoid antibody response increased with increasing numbers of DTaP/PRP-T doses (P=.0001). The effects of interference were not eliminated by the completion of the primary series with 1 or 2 doses of the DTaP and PRP-T vaccines given separately.     

Epidemic diphtheria in Belarus, 1992-1997

In 1990, epidemic diphtheria reemerged in Russia and spread to Belarus in 1992, when 66 cases were reported. Diphtheria cases doubled each year in 1993 and 1994 and peaked in 1995, when 322 cases were reported. Intensified routine immunization of young children and mass vaccination of older children and selected groups of adults were conducted in 1995 and were followed by mass vaccination campaigns targeting all adults in 1996. By the end of 1996, full immunization of >95% of children and coverage of>87% of adults with >/=1 dose resulted in a rapid decline in diphtheria cases. In 1998, only 36 cases of diphtheria were reported. More than 70% of the 965 cases and 26 fatalities reported during 1990-1998 occurred among persons >14 years of age. High levels of immunity among the entire population are needed for rapid control of diphtheria epidemics in the vaccine era.     

Epidemiology of varicella hospitalizations in the United States, 1995-2005

To describe the impact of the varicella vaccination program on varicella-related hospitalizations (VRHs) in the United States, data from the Varicella Active Surveillance Project (VASP) were used to compare rates of hospitalization and rates of complications among patients hospitalized for varicella-related conditions from 1995 to 2005. Of the 26,290 varicella cases reported between 1995 and 2005, 170 cases resulted in VRHs, including 1 case that resulted in death. Both VRH rates per 100,000 population and complications during VRH per 100,000 population decreased significantly between the early vaccination period (1995-1998) and the middle/late vaccination period (1999-2005). Infants and adults were at highest risk for VRH, and having been vaccinated against varicella was a protective factor. Varicella vaccination may have prevented a significant number of VRHs. The fact that 4 vaccinated children required hospitalization for varicella-related complications demonstrates that 1 dose of varicella vaccine does not prevent serious disease in all cases, even among previously healthy children.     

Serum IgG antibody responses to pertussis toxin and filamentous hemagglutinin in nonvaccinated and vaccinated children and adults with pertussis.

Levels of IgG antibody to pertussis toxin (PT) and filamentous hemagglutinin (FHA) were measured in paired serum samples from 781 patients fulfilling at least one laboratory criterion for pertussis that was suggested by an ad hoc committee sponsored by the World Health Organization. The patients were participants or family members of participants in a double-blind efficacy trial of a monocomponent pertussis toxoid vaccine. Of 596 nonvaccinated children, 90% had significant (two-fold or more) rises in PT IgG and FHA IgG levels. Only 17 (32%) of 53 children previously vaccinated with three doses of pertussis toxoid had rises in PT IgG levels because they already had elevated PT IgG levels in their acute-phase serum samples. PT IgG and FHA IgG levels were significantly higher in acute-phase serum samples from 29 adults than in acute-phase serum samples from the nonvaccinated children. Nevertheless, significant rises in levels of PT IgG (79% of samples) and FHA IgG (90%) were demonstrated in adults. In conclusion, assay of PT IgG and FHA IgG in paired serum samples is highly sensitive for diagnosing pertussis in nonvaccinated individuals. Assay of PT IgG levels in paired sera is significantly less sensitive for diagnosis of pertussis for children vaccinated with pertussis toxoid.     

Hepatitis A outbreaks: the effect of a mass vaccination programme

A Hepatitis A vaccination programme of people belonging to risk groups begun in Catalonia in 1995 and a universal vaccination programme of pre-adolescents 12 years of age with the hepatitis A + B vaccine was added in 1998. The aim of the study was to investigate the characteristics of hepatitis A outbreaks occurring in Catalonia between 1991 and 2007 to determine the associated risk factors and optimize the use of vaccination. Incidence rates of outbreaks, cases and hospitalizations associated with outbreaks and the rate ratios (RR) of person-to-person transmission outbreaks between the periods before and after mass vaccination and their 95% confidence intervals (CI) were calculated. A rate of 2.45 outbreaks per million persons per year was found. The rate of cases affected in these outbreaks was 1.28 per 10(5) persons per year and the rate of hospitalizations was 0.45 per million persons per year. In person-to-person outbreaks, the highest incidence rate (5.26 and 6.33 per million persons per year) of outbreaks according to the age of the index case was in the 5 to 14 year age group in both periods (RR:0.83; 95% CI:0.48-1.43). A significant increase was observed in the 25 to 44 year age group (RR: 0.35; 95% CI 0.14-0.77). Hepatitis A vaccination has made an important impact on burden and characteristics of outbreaks and could provide greater benefits to the community if the vaccine was administrated to children during their first years of life.     

The expanding national burden of heart failure in the United States: the influence of heart failure in women

Background

Although some studies have shown that hospital admissions for heart failure doubled between 1973 and 1995, other data suggest that the heart failure hospitalization epidemic has stabilized in the United States. We sought to describe trends in heart failure hospitalizations over the past decade using data from the National Hospital Discharge Survey (NHDS).

Methods

The NHDS provides annual estimates of hospitalization discharges from a sample of hospitals in the United States. We combined the heart failure hospitalization frequencies with census estimates to calculate age and gender-specific annual hospitalization rates.

Results

Hospitalizations with a primary diagnosis of heart failure among adults (age ≥35) increased from 810,624 in 1990 to 989,500 in 1995 (annual increase 36,088, R² = 0.816, P = .014), and to 1,088,349 in 1999 (annual increase 31,091, R² = 0.780, P = .047). The age-adjusted hospitalization rate (per 1000 persons) increased from 7.186 in 1990 to 8.554 in 1999 for women (annual increase 0.14/year, R² = 0.731, P = .002) and from 6.892 in 1990 to 7.372 in 1999 for men (annual increase 0.011/year, R² = 0.008, P = 0.80). For women, the annual hospitalization rate increased from 1990 to 1999 in each age group (35-64, 65-74, 75-84, and ≥85), while the age-specific rates did not change in men.

Conclusions

Heart failure hospitalizations have continued to increase from 1990 to 1999. Although aging and growth of the US population contribute to this trend, the increases are substantially influenced by changes in hospitalization rates in women.     

Postvaccine genetic structure of Streptococcus pneumoniae serotype 19A from children in the United States

BACKGROUND: The introduction of the 7-valent conjugate pneumococcal vaccine (PCV7) in children may result in serotype replacement. We estimated the rate of increase of invasive pneumococcal disease (IPD) caused by serotype 19A in children <5 years old and determined the genetic composition of these isolates. METHODS: Cases of IPD between July 1999 and June 2004 were identified through the Active Bacterial Core Surveillance. Serotype 19A isolates obtained from children <5 years old between January 2003 and June 2004 were characterized by serotyping, antibiotic susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Select isolates representing homologous PFGE clusters were subjected to multilocus sequence typing, and eBURST was used to delineate clonal groups. RESULTS: Between July 1999 and June 2004, the overall rate of IPD decreased from 23.3 to 13.1 cases/100,000 population (P<.00001). In children <5 years old, the rate decreased from 88.7 to 22.4 cases/100,000 population (P<.00001), whereas the rate in persons > or =5 years old decreased from 18.4 to 12.4 cases/100,000 population (P<.0001). The rate of serotype 19A IPD in children <5 years old increased significantly from 2.6 cases/100,000 population in 1999-2000 to 6.5 cases/100,000 population in 2003-2004; this was accompanied by significant increases in penicillin nonsusceptibility (P=.008) and multidrug resistance (P=.002) among serotype 19A isolates. As was observed during the pre-PCV7 era, clonal complex (CC) 199 predominated within serotype 19A, representing approximately 70% of invasive serotype 19A isolates from children <5 years old during 2003-2004. New serotype 19A genotypes were observed during 2003-2004, including 6 CCs that were not found among pneumococcal serotype 19A isolates during surveillance in 1999. CONCLUSION: Serotype 19A is, at present, the most important cause of IPD by replacement serotypes, and it is increasingly drug resistant. CC199 is the predominant CC among type 19A serotypes in children <5 years old. Our data suggest that some of the increase in rates of infection with serotype 19A may be due to serotype switching within certain vaccine type strains.     

Interruption of indigenous measles transmission in Bolivia since October 2000

Measles incidence in Bolivia declined after the introduction of campaign strategies in the 1980s. From 1990 to 1993, the peak incidence of measles (59 cases/100,000 population) was in 1992. In 1994, after the goal of interruption of measles transmission was adopted, a national vaccination campaign targeting children <15 years old was conducted and achieved 96% coverage. During 1995-1997, cases declined, although routine coverage was <90% in most years. During 1998-2000, a nationwide epidemic occurred among 2567 case-patients, most of whom were unvaccinated. A national vaccination campaign, with strong supervision, was conducted during November and December 1999 and targeted areas with low coverage. Only 122 cases were confirmed in 2000, with the last confirmed case occurring in October. Crucial to the control of the outbreak were sufficient resources and political support, intensive local planning, door-to-door vaccination with strict supervision, and rapid house-to-house coverage monitoring that improved accountability at the local level and timely and thorough outbreak investigations.     

Impacto de la vacunación de las embarazadas frente a la tosferina en las hospitalizaciones de menores de un año en un hospital de tercer nivel de Cataluña

IntroductionThe recommendation for pertussis vaccination in pregnancy was established in Catalonia in February 2014. The objective of this study was to compare the hospitalization rate for pertussis in children under one year of age before and after the implementation of the vaccination program.MethodsObservational and retrospective study of patients under one year of age admitted to hospital with a diagnosis of pertussis. The hospitalization rate of patients under one year of age of the period prior to the vaccination program (2008-2013) was compared with the period with vaccination program (2014-2019) in the total of children under one year of age and in 2 subgroups: children under 3 months and between 3-11 months.ResultsHospitalization rate was significantly lower in the period with vaccination program in children under one year of age and specifically in children under 3 months (2.43 vs. 4.72 per 1,000 person-years and 6.47 vs. 13.11 per 1,000 person-years, respectively). The rate ratios were: 0.51 (95% CI 0.36-0.73) for children under one year of age; 0.49 (95% CI 0.32-0.75) for those younger than 3 months and 0.56 (95% CI 0.30-1.03) for those with 3-11 months. No statistically significant differences were observed in the clinical severity between both periods.ConclusionThe introduction of the pertussis vaccination program in pregnancy was associated with a global lower hospitalization rate for pertussis in children under one year of age and specifically in those under 3 months of age.     

Diphtheria toxoid vaccine effectiveness: A case-control study in Russia

Prior to the completion of this and other studies, low effectiveness of diphtheria toxoid-containing vaccine was suspected to be a major contributing factor to the diphtheria epidemic that began in the Russian Federation in 1990. A vaccine effectiveness study was done in Moscow by enrolling physician-diagnosed cases and 10 control subjects per case. Controls were matched to cases by age (+/-3 months) and clinic registration. Vaccination history was abstracted from a standardized form for case-patients and from clinic vaccination records for control subjects. Two hundred seventeen case-patients and 2169 matched controls were included in the study. Most controls (92%) had received three or more doses of a diphtheria toxoid vaccine, compared with 72% of case-patients. The vaccine effectiveness for three or more doses was 97% (95% confidence interval: 94.3-98.4). Low vaccine effectiveness was not a contributing factor to the diphtheria epidemic in the Russian Federation. To control and prevent diphtheria epidemics, it is necessary to achieve and maintain high vaccination coverage with three or more doses of diphtheria toxoid among adults and children.