Lower risk of invasive meningococcal disease during pregnancy: national prospective surveillance in England, 2011-2014.

OBJECTIVE: To describe cases of invasive meningococcal disease (IMD) in women of childbearing age and to estimate the disease incidence and relative risk of IMD in pregnant compared with non-pregnant women. DESIGN: Prospective enhanced national surveillance for IMD. SETTING: England. POPULATION: Women of reproductive age (15-44 years) with laboratory-confirmed IMD. METHODS: Public Health England conducts enhanced national surveillance for IMD in England. Laboratory-confirmed cases are followed up with postal questionnaires to general practitioners. All cases confirmed in women of reproductive age from 1 January 2011 to 31 December 2014 were included. MAIN OUTCOME MEASURES: Annual IMD incidence and relative risk of IMD in pregnant compared with non-pregnant women of reproductive age. RESULTS: During the 4-year surveillance period, there were 1502 cases of IMD in females across England; of these, 310 (20.6%) cases were in women of reproductive age, including four women who were pregnant at the time of IMD confirmation (1.3%). Serogroup distribution of IMD cases in women of childbearing age was similar to the overall distribution. The four cases in otherwise healthy pregnant women were confirmed across all trimesters and all survived; one case in the first trimester had a septic miscarriage. The incidence of IMD was lower in pregnant than in non-pregnant women (0.16 compared with 0.76 per 100 000 pregnant and non-pregnant years, respectively), giving a lower risk of IMD in pregnant women (incidence rate ratio, IRR, 0.21; 95% confidence interval, 0.06-0.54). CONCLUSIONS: Pregnant women are nearly five times less likely to develop IMD compared with non-pregnant women, but the infection can be severe. TWEETABLE ABSTRACT: The risk of meningococcal disease is lower in pregnant women compared with non-pregnant women; the infection can occur across all trimesters and can be severe.

New treatments for hepatitis C virus (HCV): scope for preventing liver disease and HCV transmission in England.

New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact.

Current epidemiology of tetanus in England, 2001-2014.

Public Health England conducts enhanced national surveillance of tetanus, a potentially life-threatening vaccine-preventable disease. A standardized questionnaire was used to ascertain clinical and demographic details of individuals reported with clinically suspected tetanus. The 96 cases identified between 2001 and 2014 were analysed. The average annual incidence was 0·13/million (95% confidence interval 0·10-0·16) of which 50·0% were male. Where reported, 70·3% of injuries occurred in the home/garden (45/64). Overall, 40·3% (31/77) cases were in people who inject drugs (PWID), including a cluster of 22 cases during 2003-2004. Where known (n = 68), only 8·8% were age-appropriately immunized. The overall case-fatality rate was 11·0% (9/82). All tetanus-associated deaths occurred in adults aged >45 years, none of whom were fully immunized. Due to the success of the childhood immunization programme, tetanus remains a rare disease in England with the majority of cases occurring in older unimmunized or partially immunized adults. Minor injuries in the home/garden were the most commonly reported likely sources of infection, although cases in PWID increased during this period. It is essential that high routine vaccine coverage is maintained and that susceptible individuals, particularly older adults, are protected through vaccination and are offered timely post-exposure management following a tetanus-prone wound.

Retrospective cohort study of liver transplantation in the United Kingdom between 1994 and 2010: the impact of hepatitis C infection.

BACKGROUND: Liver transplantation is an important and established treatment option for chronic hepatitis C virus (HCV) related end-stage liver disease (HCV-related ESLD). This study describes trends in elective liver transplantation among persons with HCV-related ESLD. STUDY DESIGN: Retrospective cohort. METHODS: Analyses of United Kingdom (UK) Transplant Registry data for the period 1994 to 2010, with follow-up information extending to 2011. RESULTS: Annual registrations for liver transplantation increased linearly and alcoholic liver cirrhosis (2075, 24%) and HCV-related ESLD (1213, 14%) were the most common indications. HCV-related ESLD patients were mainly aged 40-49 years (32%) and 50-59 years (43%); males (76%); and of white ethnicity (74%). Overall, 75% (956/1213) received a liver transplant with a linear increase over the period (OR 1.11, 95% CI 1.08, 1.13). Pre transplant mortality was unchanged (adjusted OR 1.0, 95% CI 0.96, 1.05) and post-transplant mortality decreased in both HCV-related (adjusted OR 0.77, 95% CI 0.68, 0.88) and non-HCV-related ESLD (adjusted OR 0.82, 95% CI 0.75, 0.89) patients. CONCLUSION: The increase in demand for and receipt of liver transplants among persons with HCV-related ESLD requires coordinated efforts to increase not only organ donation, but investment in HCV prevention programmes and improved access to hepatitis C treatment services.

Hepatitis B virus transmission in pre-adolescent schoolchildren in four multi-ethnic areas of England.

The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7-11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The estimated average annual incidence of hepatitis B was estimated to be 29.26/100 000 children (95% CI 16.00-49.08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5.00 and 12.49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.

Improved hepatitis C treatment response in younger patients: findings from the UK HCV National Register cohort study.

In a cohort of 272 treatment-naive individuals with chronic hepatitis C infection acquired on a known date who were enrolled in the UK HCV National Register, a progressive improvement in response to treatment was found with the evolution of antiviral therapies from 20% (25/122) for interferon monotherapy to 63% (55/88) for pegylated interferon+ribavirin therapy. Multivariable analysis results showed increasing age to be associated with poorer response to therapy [odds ratio (OR) 0·84, 95% confidence interval (CI) 0·72-0·99, P=0·03] whereas time since infection was not associated with response (OR 0·93, 95% CI 0·44-1·98, P=0·85). Other factors significantly associated with a positive response were non-type 1 genotype (P<0·0001) and combination therapies (P<0·0001). During the first two decades of chronic HCV infection, treatment at a younger age was found to be more influential in achieving a sustained viral response than treating earlier in the course of infection.

Using automated extraction of hepatitis B tests for surveillance: evidence of decreasing incidence of acute hepatitis B in England.

Surveillance of acute hepatitis B in England is necessary to estimate incidence, determine routes of transmission and inform public health actions. Here we describe an automated process to extract information on testing for markers of hepatitis B infection in English sentinel laboratories between 2002 and 2008. The resulting data were used to identify individuals with acute infections, describe their characteristics and estimate the incidence of infection. Two-thirds of acute infections were in males. Heterosexual exposure and injecting drug use were the main risks reported. Annual incidence was estimated at 1.3/100 000 person-years overall (1.7 and 0.6 for males and females, respectively) and declined each year. Automated extraction of hepatitis B markers, including quantitative results where available, can help to classify HBV status more accurately for surveillance. HBV incidence in England is at its lowest level in recent years.

Hepatitis C in ethnic minority populations in England.

The aim of the study was to investigate the differing epidemiology of hepatitis C-related end-stage liver disease in ethnic minorities in England. We used Hospital Episode Statistics from 1997/98 to 2004/05 to directly age-standardize numbers of episodes and deaths from hepatitis C-related end-stage liver disease in ethnic groups using the white English population as standard and the age-structured population by ethnic group from the 2001 Census. We estimated the odds of having a diagnosis of end-stage liver disease amongst hepatitis C-infected individuals in each ethnic group compared with whites using logistic regression. The main outcome measures were age-standardized morbidity and mortality ratios and morbidity and mortality odds ratios. Standardized ratios (95% confidence interval) for hepatitis C-related end-stage liver disease ranged from 73 (38-140) in Chinese people to 1063 (952-1186) for those from an 'Other' ethnic group. Amongst individuals with a diagnosis of hepatitis C infection, the odds ratios (95% CI) of severe liver disease were 1.42 (1.13-1.79), 1.57 (1.36-1.81), 2.44 (1.85-3.22), 1.73 (1.36-2.19) and 1.83 (1.08-3.10) comparing individuals of Black African, Pakistani, Bangladeshi, Indian and Chinese origin with whites, respectively. Ethnic minority populations in England are more likely than whites to experience an admission or to die from severe liver disease as a result of hepatitis C infection. Ethnic minority populations may have a higher prevalence of hepatitis C or they may experience a poorer prognosis because of differential access to health services, longer duration of infection or the prevalence of co-morbidities.

Where are people being tested for anti-HCV in England? Results from sentinel laboratory surveillance.

SUMMARY: Many people infected with hepatitis C virus (HCV) are unaware of their infection and are, therefore. potentially infectious to others. To enable effective case-finding policies to be developed, an understanding of where people, and injecting drug users (IDUs) in particular, are accessing HCV antibody testing is needed. HCV antibody testing data were collected electronically from 21 sentinel laboratories in England between 2002 and 2006 in this cross-sectional study. Service types of the physician requesting the HCV test were identified and classified. Differences in people being tested in each service type and over time were investigated. Over half a million people were tested in 5 years. Whilst most testing took place in hospital, a large proportion of people were tested in community care, particularly in general practice surgeries and genito-urinary medicine clinics. Younger people were more likely to be tested in community care, and there was evidence that testing differed according to ethnic status. IDUs were tested in all parts of the health services, although the highest proportion positive were from prisons and specialist services for drug users. Testing increased between 2002 and 2005 whilst the proportion of people testing positive declined. Routine laboratory data can provide valuable information on where people are being tested for HCV. Risk exposures should be investigated and testing targeted to people at higher risk for infection. Local laboratories should review data on testing locations and proportion positive to inform local initiatives to improve testing and yield.

Diagnosis of acute hepatitis C virus infection and estimated incidence in low- and high-risk English populations.

The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward; few people exhibit clinical symptoms and genome/antigen detection techniques do not indicate when infection had occurred. Here, a strategy to detect HCV RNA in the absence of antibody ('window-period') for diagnosis of acute infection is assessed. The sentinel surveillance of hepatitis testing study was used to retrospectively identify anti-HCV negative samples from high-risk individuals (2002-2003), for testing singly for HCV RNA. Additional samples were identified prospectively (2005) and tested in pools for HCV RNA. Positive samples were genotyped. Incidence and costs of adopting the pooling strategy were estimated. In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive, anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five positive pools identified four confirmed HCV RNA positive patients (one false positive). Estimated incidence was 12.9 per 100 person-years in injecting drug users (IDUs) (retrospective study) and 3.7 per 100 person-years among drug/alcohol services and prison attendees (prospective study). Estimated costs were pound 850 per positive sample, in areas of higher risk. The yield from a window-period strategy depends upon the population tested. Pooled HCV RNA testing of anti-HCV negative samples from the current IDUs is realistic and relatively inexpensive to identify recently infected individuals.

Antibody response and viral excretion after live polio vaccine or a combined schedule of live and inactivated polio vaccines.

A randomized controlled trial was performed in infants undergoing routine immunization in North Hertfordshire. Ninety-six children received a single dose of inactivated polio vaccine, followed by two doses of live attenuated oral polio vaccine and 97 children received three doses of live attenuated oral polio vaccine at 2, 3 and 4 months of age. Blood samples were taken by study nurses 6 weeks after vaccination and stool samples were collected by parents weekly for 4 weeks after each dose of vaccine. Follow-up was completed for 92 of 96 (96%) children in the combined schedule group and 92 of 97 (95%) in the control group. After vaccination the proportions of children with detectable antibody to poliovirus serotypes 1, 2 and 3 were high and similar between groups and geometric mean titers (95% confidence interval) to poliovirus types 1, 2 and 3 were 264 (200 to 347), 375 (311 to 450) and 189 (144 to 250) in the combined schedule group and 369 (290 to 469), 401 (321 to 498) and 206 (145 to 293) in the live vaccine group, respectively. The only significant difference between groups in rates of viral excretion was observed after the second dose of live attenuated oral polio vaccine, when excretion of type 3 poliovirus was reduced in those children who had received prior inactivated polio vaccine (P = 0.05). This study suggests that, compared with the current schedule, a combined schedule of inactivated and live poliovaccines is likely to produce equivalent individual protection against poliomyelitis and is unlikely to substantially alter circulation of poliovirus in the community.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced surveillance of invasive Haemophilus influenzae disease in England, 1990 to 1996: impact of conjugate vaccines.

We report an enhanced prospective survey of invasive Haemophilus influenzae infections that has defined the pattern of invasive disease in five English regions for 2 years before and 4 years after the introduction of the H. influenzae type b (Hib) vaccination program. During the prevaccination period the majority of cases of invasive H. influenzae were caused by type b; most (89%) of these infections occurred in children <5 years of age and the most common presentation was meningitis. Since the introduction of routine immunization of infants with conjugate Hib vaccine, there has been a 16-fold reduction in the annual attack rate of invasive Hib disease recorded in children <5 years of age. This reduction is of a magnitude similar to that observed in other countries with Hib vaccination programs. The number of infections caused by non-type b H. influenzae has shown a small but progressive increase over the same period, emphasizing the need for continued surveillance. There was no increase in the number of infections caused by other serotypes. Diagnostic category varied with both age and serotype but was not affected by vaccine introduction; meningitis was the most common presentation overall but pneumonia and bacteremia were more common in adults and with noncapsulated isolates.

Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era.

BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib) disease caused by the widespread use of conjugate vaccines, non-type b H. influenzae will become a more important cause of H. influenzae (Hi) disease. Characterization of the clinical and epidemiologic features of non-b Hi disease is needed in the Hib vaccine era. METHODS: A prospective active surveillance study of invasive Hi disease involving pediatricians in the United Kingdom and Republic of Ireland. For the first phase of the study (October 1, 1992, to October 31, 1995) pediatricians were asked to report any child who had invasive Hi disease and who had received Hib conjugate vaccine. For the second phase of the study (November 1, 1995. To December 31, 1998) pediatricians were asked to report any child with invasive Hi disease regardless of vaccination status. RESULTS: During the study period 102 cases of invasive non-type b Hi disease and 106 cases of invasive Hib disease were reported in children who had been fully vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22 months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than children with type b disease. For the last 2 years of the study invasive Hi disease occurring in a fully vaccinated child was more likely to be caused by a non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi is a rare cause of disease in children, but in the Hib vaccine era it has become more common than type b as a cause of Hi disease in fully vaccinated children.

The prevalence of hepatitis C in England and Wales.

OBJECTIVES: To estimate the background population prevalence of hepatitis C in England and Wales, observe the prevalence over time and assess the extent of infection outside of known risk groups. METHODS: Sera from residual specimens from adult patients submitted to laboratories in England and Wales were tested for anti-HCV. Testing was carried out using a cost-effective pooling strategy. RESULTS: Although the prevalence of anti-HCV was highest in 1986 (1.07%), in the multivariable analysis, prevalence did not vary significantly between the 3 periods 1986, 1991 and 1996 (P=0.14). The prevalence of infection was higher in males than in females (P=0.0013). An age-period-cohort analysis revealed a cohort effect due to a lower HCV prevalence in the most recent birth cohorts, that is, those born between the calendar years 1971-1975 and 1976-1980. CONCLUSIONS: The majority of HCV infections in England and Wales were probably acquired before 1986. Infections in younger males identified in 1996 may signify more recent acquisition by injecting drug use.

Evaluation of patients' knowledge about anticoagulant treatment.

OBJECTIVE: To develop a questionnaire to evaluate patients' knowledge of anticoagulation. DESIGN: Anonymous self completed questionnaire study based on hospital anticoagulant guidelines. SETTING: Anticoagulant clinic in a 580 bed district general hospital in London. SUBJECTS: 70 consecutive patients newly referred to the anticoagulant clinic over six months. MAIN MEASURES: Information received by patients on six items of anticoagulation counselling (mode of action of warfarin, adverse effects of over or under anticoagulation, drugs to avoid, action if bleeding or bruising occurs, and alcohol consumption), the source of such information, and patients' knowledge about anticoagulation. RESULTS: Of the recruits, 36 (51%) were male; 38(54%) were aged below 46 years, 22(31%) 46-60, and 10(14%) over 75. 50 (71%) questionnaires were returned. In all, 40 respondents spoke English at home and six another language. Most patients reported being clearly advised on five of the six items, but knowledge about anticoagulation was poor. Few patients could correctly identify adverse conditions associated with poor control of anticoagulation: bleeding was identified by only 30(60%), bruising by 23(56%), and thrombosis by 18(36%). Only 26(52%) patients could identify an excessive level of alcohol consumption, and only seven (14%) could identify three or more self prescribed agents which may interfere with warfarin. CONCLUSION: The questionnaire provided a simple method of determining patients' knowledge of anticoagulation, and its results indicated that this requires improvement. IMPLICATIONS: Patients' responses suggested that advice was not always given by medical staff, and use of counselling checklists is recommended. Reinforcement of advice by non-medical counsellors and with educational guides such as posters or leaflets should be considered. Such initiatives are currently being evaluated in a repeat survey.

The epidemiology of meningococcal disease in England and Wales, 1996 and 1997.

Surveillance of meningococcal infection in England and Wales relies on three sources of data. Doctors are required by statute to notify clinically diagnosed cases of meningococcal meningitis and, since 1989, cases of meningococcal septicaemia (in the abse

Viral meningitis in Cyprus and England : summer 1996.

An outbreak of viral meningitis began in Cyprus on 5 July 1996. By 28 August a total of 316 cases had been admitted to hospital, most of whom were infants and young children; 55 (17%) were less than 1 year of age, 117 (37%) were aged 1 to 4 years, 103 (33

Symptoms after accelerated immunisation.

OBJECTIVE: To document the incidence of symptoms after accelerated immunisation with diphtheria-tetanus-pertussis vaccine. DESIGN: Controlled study of children immunised with adsorbed diphtheria-tetanus-pertussis vaccine at accelerated and standard schedules. SETTING: Colchester and north Hertfordshire. SUBJECTS: 107 children scheduled to receive immunisation at 2, 3, and 4 months of age and 115 children scheduled to receive immunisation at 3, 4 1/2 to 5, and 8 1/2 to 11 months of age. MAIN OUTCOME MEASURES: Parentally recorded symptoms, axillary temperatures, and size of local redness and swelling at the injection site during the seven days after immunisation. RESULTS: In general symptoms occurred less frequently with the accelerated schedule. Proportions of parents reporting axillary temperatures greater than 37.2 degrees C or local redness or swelling greater than 2.5 cm after the third dose of vaccine were significantly reduced in the accelerated schedule group. CONCLUSION: Immunisation at 2, 3, and 4 months of age is likely to cause fewer reactions than immunisation at 3, 4 1/2 to 5, and 8 1/2 to 11 months of age.

Salivary diagnosis of measles: a study of notified cases in the United Kingdom, 1991-3.

OBJECTIVES: To validate a method for salivary diagnosis of measles and to assess the diagnostic accuracy of notified cases of measles. DESIGN: Blood and saliva samples were collected within 90 days of onset of symptoms from patients clinically diagnosed as having measles and tested for specific IgM by antibody capture radioimmunoassay. SETTING: 17 districts in England and one in southern Ireland during August 1991 to February 1993. SUBJECTS: 236 children and adults with measles notified by a general practitioner. RESULTS: Specific IgM was detected in serum in only 85 (36%) of the 236 cases. In cases associated with outbreaks and tested within six weeks of onset, 53/57 (93%) of samples were IgM positive, thereby confirming the sensitivity of serum IgM detection as a marker of recent infection. The serological confirmation rate was lower in cases with a documented history of vaccination (13/87; 15%) than in those without (70/149; 47%) and varied with age, being lowest in patients under a year, of whom only 4/36 (11%) were confirmed. Measles specific IgM was detected in 71/77 (92%) of adequate saliva samples collected from patients with serum positive for IgM. In cases where measles was not confirmed, 6/101 had rubella specific IgM and 5/132 had human parvovirus B19 specific IgM detected in serum. CONCLUSIONS: The existing national surveillance system for measles, which relies on clinically diagnosed cases, lacks the precision required for effective disease control. Saliva is a valid alternative to serum for IgM detection, and salivary diagnosis could play a major role in achieving measles elimination. Rubella and parvovirus B19 seem to be responsible for a minority of incorrectly diagnosed cases of measles in the United Kingdom and other infectious causes of measles-like illness need to be sought.

Persistence of antibody after accelerated immunisation with diphtheria/tetanus/pertussis vaccine.

OBJECTIVE: To determine the persistence of antibody to diphtheria, tetanus, and pertussis in children receiving an accelerated schedule of primary immunisation. DESIGN: Controlled study of antibody testing of blood samples from children immunised according to various schedules: three doses of triple vaccine completed at 8-13 calendar months, 6-7 calendar months, before 6 calendar months, or three doses followed by diphtheria/tetanus before age 2. SETTING: Plymouth Health Authority. SUBJECTS: 129 children aged 4 years who had received three doses of diphtheria/tetanus/pertussis vaccine with or without a diphtheria/tetanus booster. MAIN OUTCOME MEASURES: Diphtheria and tetanus antitoxin concentrations and antibody titres to pertussis toxin, filamentous haemagglutinin, and agglutinogens 2 and 3. RESULTS: All children had protective concentrations of antitoxin to diphtheria and tetanus (greater than or equal to 0.01 IU/ml). There was no evidence of a significant difference in diphtheria or tetanus antitoxin concentrations and pertussis antibody titres in children immunised with an accelerated course (third dose of triple vaccine before 6 months) compared with those who received a longer course (third dose at 8-13 months) with no booster (geometric mean antitoxin concentration 0.411 (95% confidence interval 0.273 to 0.618) v 0.426 (0.294 to 0.616) for diphtheria and 0.358 (0.231 to 0.556) v 0.299 (0.197 to 0.453) for tetanus; geometric mean antibody titres 903 (500 to 1631) v 1386 (848 to 2266) for pertussis filamentous haemagglutinin, 179 (130 to 248) v 232 (167 to 322) for pertussis toxin, and 2002 (1276 to 3142) v 3591 (2220 to 5809) for agglutinogens 2 and 3). CONCLUSION: Immunisation with three doses of triple vaccine at monthly intervals completed before 6 months of age probably provides adequate protection against diphtheria, tetanus, and whooping cough which will persist until the age of the preschool booster.