The interplay between determinism and stochasticity in childhood diseases

An important issue in the history of ecology has been the study of the relative importance of deterministic forces and processes noise in shaping the dynamics of ecological populations. We address this question by exploring the temporal dynamics of two childhood infections, measles and whooping cough, in England and Wales. We demonstrate that epidemics of whooping cough are strongly influenced by stochasticity; fully deterministic approaches cannot achieve even a qualitative fit to the observed data. In contrast, measles dynamics are extremely well explained by a deterministic model. These differences are shown to be caused by their contrasting responses to dynamical noise due to different infectious periods.     

Whooping-cough vaccine. Statement by Joint Committee on Vaccination and Immunization of the Central Health Services Council and the Scottish Health Service Planning Council.

In 1974 it was recommended that pertussis vaccine should continue to be offered in a triple vaccine together with diphtheria and tetanus vaccines. Further data on the prevalence of whooping cough and the incidence of adverse reactions have shown no reason to change this policy; the hazard of whooping cough remains greater than that of immunization.     

Transients and attractors in epidemics

Historical records of childhood disease incidence reveal complex dynamics. For measles, a simple model has indicated that epidemic patterns represent attractors of a nonlinear dynamic system and that transitions between different attractors are driven by slow changes in birth rates and vaccination levels. The same analysis can explain the main features of chickenpox dynamics, but fails for rubella and whooping cough. We show that an additional (perturbative) analysis of the model, together with knowledge of the population size in question, can account for all the observed incidence patterns by predicting how stochastically sustained transient dynamics should be manifested in these systems.     

Natural course of 500 consecutive cases of whooping cough: a general practice population study.

OBJECTIVE--To describe the natural course of whooping cough. DESIGN--Observational study of a general practice population. SETTING--Discrete semirural East Midlands practice of 11,500 patients. SUBJECTS--500 consecutive cases of whooping cough diagnosed clinically during 1977-92. MAIN OUTCOME MEASURES--Incidence of vomiting, whooping, apnoea, admission to hospital, and complications; duration and frequency of paroxysms. Pattern of spread. RESULTS--The incidence in the practice population was 4347/100,000 population compared with a notification rate for England and Wales of 717/100,000. Most cases were relatively mild. 284 patients vomited after paroxysms, 242 whooped, and 57 had apnoea. Duration and frequency of paroxysms varied widely. Female and unimmunised patients suffered more severe disease. Bordetella was isolated from fewer immunised patients (24/96 v 63/122 unimmunised). Infection was usually spread through contacts with someone with clinical whooping cough. Five patients developed pneumonia, three of whom had been immunised. Three patients required hospital admission. CONCLUSIONS--Most cases of whooping cough are relatively mild. Such cases are difficult to diagnose without a high index of suspicion because doctors are unlikely to hear the characteristic cough, which may be the only symptom. Parents can be reassured that a serious outcome is unlikely. Adults also get whooping cough, especially from their children, and get the same symptoms as children. The difficulty of early diagnosis and probability of missed cases reinforces the need to keep the incidence low through immunisation in order to protect infants, who are the most vulnerable.     

Whooping cough after stopping pertussis immunisation.

An epidemic of whooping cough occurred in a rural practice in Shetland, containing 144 children under 16. Before July 1974 all children were immunised against pertussis, but after that date immunisation was stopped. Of the 134 children studied, 93 had been immunised. Sixty-five of the children developed whooping cough. The incidence of infection was similar in those who had and had not been immunised. The incidence was also similar in those born before and after July 1974. There was no evidence to support the routine use of pertussis immunisation in rural Shetland.     

Attack rates of notified whooping cough in immunised and unimmunised children.

The incidence of whooping cough among immunised children under the age of six and among children of the same age who were not fully immunised was ascertained by analysing whooping-cough notifications from several health authorities. In the first three years of the study the results showed that attack rates were much higher in children who were not fully immunised than in those who were. This finding suggests that current vaccines provide young children with substantial protection against whooping cough.     

Study of intellectual performance of children in ordinary schools after certain serious complications of whooping cough. Swansea Research Unit of the Royal College of General Practitioners.

In a case-control study 27 index children from ordinary schools who had had convulsions or apnoea as a complication of whooping cough about eight years previously were compared with 27 children who had never had whooping cough and 15 who had had whooping cough without complications. Other factors likely to cause intellectual impairment after conception were considered. The index group had a significantly lower median intelligence quotient and poorer school attainment than either of the control groups. The results support the hypothesis that convulsions or apnoea as a complication of whooping cough may be associated with subsequent intellectual impairment.     

Impact of whooping cough on patients and their families.

The effects of whooping cough were studied in 21 children admitted to hospital with the disease and in their families. The illness caused considerable distress to both child and family. Parents suffered especially from fears for the life and health of their child and from serious loss of sleep. Two months after admission the child''s behaviour was still disturbed, but in most cases the rest of the family had returned to normal. There was much misunderstanding and misinformation about whooping cough among both parents and doctors.     

Stochastic amplification in an epidemic model with seasonal forcing

We study the stochastic susceptible-infected-recovered (SIR) model with time-dependent forcing using analytic techniques which allow us to disentangle the interaction of stochasticity and external forcing. The model is formulated as a continuous time Markov process, which is decomposed into a deterministic dynamics together with stochastic corrections, by using an expansion in inverse system size. The forcing induces a limit cycle in the deterministic dynamics, and a complete analysis of the fluctuations about this time-dependent solution is given. This analysis is applied when the limit cycle is annual, and after a period doubling when it is biennial. The comprehensive nature of our approach allows us to give a coherent picture of the dynamics which unifies past work, but which also provides a systematic method for predicting the periods of oscillations seen in whooping cough and measles epidemics.     

Whooping cough in adults.

During the 1970s whooping cough returned in Sweden after an absence of more than 10 years and is now seen in all age groups, During a three-year period 174 adults with culture-verified whooping cough were identified in Gothenburg. Most of the patients had typical symptoms with whooping attacks and often vomiting. The disease was long lasting but complications were rare. Physicians should be aware that whooping cough may occur in adults, since adults may be an important source of infection for infants and erythromycin given in the catarrhal phase may modify the clinical course.     

Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease.

OBJECTIVE--To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease. DESIGN--Follow up study of men born during 1911-30 whose birth weights, weights at 1 year, and childhood illnesses were recorded at the time by health visitors. SETTING--Hertfordshire, England. SUBJECTS--5718 men born in the county during 1911-30 and a subgroup of 825 men born in the county during 1920-30 and still living there. MAIN OUTCOME MEASURES--Death from chronic obstructive airways disease, mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and respiratory symptoms. RESULTS--55 men died of chronic obstructive airways disease. Death rates fell with increasing birth weight and weight at 1 year. Mean FEV1 at age 59 to 70 years, adjusted for height and age, rose by 0.06 litre (95% confidence interval 0.02 to 0.09) with each pound (450 g) increase in birth weight, independently of smoking habit and social class. Bronchitis or pneumonia in infancy was associated with a 0.17 litre (0.02 to 0.32) reduction in adult FEV1 and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0.22 litre (0.02 to 0.42) reduction in adult FEV1. CONCLUSIONS--Lower birth weight was associated with worse adult lung function. Intrauterine influences which retard fetal weight gain may irrecoverably constrain the growth of the airways. Bronchitis, pneumonia, or whooping cough in infancy further reduced adult lung function. They also retarded infant weight gain. Consistent with this, death from chronic obstructive airways disease in adult life was associated with lower birth weight and weight at 1 year. Promoting lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of chronic obstructive airways disease in the next generation.     

Simulations of pertussis epidemiology in the United States: effects of adult booster vaccinations

An expanded pertussis (whooping cough) vaccination program which includes adult boosters every 10 yr is studied using computer simulations of two models. These age-structured pertussis transmission models include waning of both infection-acquired and vaccine-induced immunity, and vaccination of children corresponding to the vaccination coverage since 1940. Adult vaccinations cause a larger boost in the immunity level in the second model than in the first model. In the simulations the addition of adult pertussis booster vaccinations every 10 yr is beneficial in reducing adult incidence, but causes only modest reductions in the incidence in infants and young children. These simulations suggest that a careful cost effectiveness analysis is needed before implementation of an adult pertussis vaccination program.     

Injury by hypertonic phosphate enema.

Over a 2-year period 67 strains of Bordetella pertussis were identified in 231 single specimens of nasopharyngeal secretions submitted from patients suspected to have whooping cough in the National Capital Region; 89.5% of the identifications were made by culture. Serotype 1,3 was predominant. At least 75% of the patients with bacteriologically confirmed whooping cough had not been fully immunized. There was no evidence that adenoviruses or other viruses played any important etiologic role in the 204 cases of whooping cough or whooping cough syndrome studied virologically.     

Intensity of the epidemic process of whooping cough under conditions of mass immunization over a period of many years

On the basis of analysis of whooping cough incidence in 1959 to 1975 in Moscow the authors present characteristics of the epidemic process under conditions of planned many-year immunization of children against this infection. Whooping cough morbidity proved to undergo significant changes-from sharp falls the first 8 years of immunization to a relative stabilization with a gradual reduction the last 5 years. Marked seasonal and periodic elevations persist against the background of reduction of morbidity. Preschool- and schoolchildren are equally involved in the epidemic process; the most frequently involved are nonvaccinated children aged 1 year and 4 to 10 years, which lost postvaccinal immunity. Further reduction of the severity of whooping cough and increase in the number of unimanifested forms of the infection was noted. This was apparently connected not only with immunization, but also with the reduction of the virulence of H. pertusis detected in studying the cultures isolated in Moscow from 1967 to 1974. The intensity indices of the epidemic process in whooping cough pointed to the necessity of using a more effective vaccine for the protection of children from whooping cough, despite the noted reduction of morbidity, and diminished severity of the course of the disease, and of the causative agent virulence.     

Immunological surveys of antibodies against B. pertussis and B. parapertussis in some African and Asian countries.

Immunological surveys in African and Asian countries showed a different degree of herd immunity in the respective countries and the circulation of various types of B. pertussis. Antibodies against B. parapertussis, the second aertiological agent of whooping cough, were found in all countries in all age groups. Before planning any vaccination program, attention should be paid to the vaccine concerning the content of all types of B. pertussis, as was shown in the results of the testing of different vaccines used in Mongolia and Algeria. It is also possible to estimate the age limit for vaccination and thus economic use of the vaccine. The contemporary state of reporting whooping cough cases is very unsatisfactory.     

Expanded program on immunization and its implementation in the Czech Socialist Republic

National immunization programs carried out in the CSR are here confronted with the EPI regional targets for Europe, a component of the WHO global program "Health for all by the year 2000". The EPI target diseases to be brought under control in Europe by 1990 include measles, poliomyelitis, diphtheria and neonatal tetanus; control of congenital rubella infection is to be achieved by the year 2000. The presented data show that Czechoslovakia has succeeded in implementing this program much ahead of the WHO time schedule. The elimination of measles infection was achieved in 1982, poliomyelitis was brought under control in 1961, and the effective diphtheria control has been in effect since the mid-1960s. Cases of neonatal tetanus are absent in the CSR since 1965, the annual incidence of postnatal tetanus is permanently 0.1-0.2 per 100,000 population. The goal of achieving the rubella-free status and thus the elimination of congenital rubella cases at country level is expected to be reached in the early 1990s. Implementation of the remaining WHO recommendations pertinent to infections other than EPI target diseases appears also satisfactory. Regular immunization against whooping cough, one of the oldest immunization programs in Czechoslovakia, succeeded in effectively eliminating this infection in the early 1970s. Selective immunization campaigns against influenza infection, introduced many years ago, help protect, together with a large-scale use of available chemoprophylactics, some 200,000 individuals every year in CSR. The hepatitis B immunization program was started in 1983 and is primarily limited to health service staff, which is in line with the existing WHO recommendations. Inception of the regular immunization program against mumps is planned for the beginning of 1987.     

Duration of effectiveness of pertussis vaccine: evidence from a 10 year community study

A 10 year study of whooping cough in a discrete general practice community was performed to assess longitudinally the efficacy of pertussis vaccine from one to seven years after immunisation. Of the 436 cases of whooping cough over 10 years, 326 occurred in children aged 1-7 years. The rate of immunisation was known for each cohort of children born during each year, and the attack rate of whooping cough was thus calculated for those immunised and unimmunised. The attack rates were highest in those cohorts exposed to the epidemics of 1977-9, 1981-3, and 1985-7. The efficacy of the vaccine was calculated as a percentage as (attack rate in unimmunised group—attack rate in immunised group) × 100/attack rate in unimmunised group. It fell from 100% in the first year to 46% in the seventh, being 84% in the fourth and only 52% in the fifth.Thus the pertussis vaccine or its schedule of use does not seem to provide sufficient herd immunity to prevent outbreaks of whooping cough. Matters might be improved if vaccination against pertussis were included in the preschool immunisation programme.     

The duration and strength of postvaccinal measles immunity

A prolonged immunoepidemiological follow-up of a large group of children immunized against measles revealed a high epidemiological efficacy of a single vaccination. Cases of measles were registered only among those vaccinees in whose blood sera no specific hemagglutinins were detectable by titration with 4 hemagglutinating units of measles antigen prior to the disease. The study showed that groups of children seronegative with respect to measles appeared, as a rule, after unsatisfactory immunization and not due to loss of postvaccinal immunity with time. Properly immunized children in whom the formation of antimeasles antibodies had occurred in response to the injection of live measles vaccine retained postvaccinal immunity for more that 15 years (the term of observation).     

Domiciliary immunisation for preschool child defaulters.

A selective domiciliary immunisation service has been introduced for preschool children living in the Central Manchester Health District. The service is provided for the children of parents who have given written consent for immunisation but have subsequently failed to bring their children to the clinic or their general practitioner''s surgery to start or complete the basic course of immunisation against diphtheria, tetanus, whooping cough, poliomyelitis, and measles. This failure has occurred despite at least two written invitations for each injection and several reminders from the health visitor. Many additional children have been protected by this scheme.     

Effect of vaccination on severity and dissemination of whooping cough.

A study was undertaken in general practice to clarify those factors, especially vaccinations, that influence the clinical picture and infectivity of whooping cough in the community. Although the range of the disease encountered was fairly mild, its duration was notable (mean +/- SD 50.9 +/- 32.1 days). By using multiway contingency table analysis it was found that in the more severe cases of whooping cough vaccination significantly shortened the illness (p less than 0.005) and reduced the number of coughing spasms (p less than 0.025). The protective effect of the vaccine was most notable in modifying infectivity within the family: 19% of vaccinated family contacts of index patients in whom the disease had been confirmed bacteriologically developed the disease when exposed to it compared with 72% of non-vaccinated contacts (p less than 0.001). These results show that whooping cough vaccination modifies the clinical illness and offers a worthwhile degree of protection to children exposed to the disease.