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[Treatment of whooping cough and whooping cough syndrome by cefoperazone (author's transl)].

Clinical trial of cefoperazone (CPZ) for the treatment of whooping cough and whooping cough syndrome was performed and the following results were obtained. 1) In 18 cases suffering from whooping cough, CPZ was given 47 approximately 106 mg/kg/day (average 72 mg/kg/day) by intravenous route. The clinical efficacy rates judged by doctors in charge were 44% on the 3 rd day, 75% on the 7 th day, 86% on the period day. And in these cases, the clinical efficacy rates judged by committee members were 56%, 83% and 86%. 2) In 6 cases diagnosed as whooping cough syndrome, CPZ was given 49 approximately 96 mg/kg/day (average 59 mg/kg/day) by the same route. The clinical efficacy rates judged by doctors in charge were 67% on the 3 rd day, 80% on the 7 th day and 75% on the period day. And in these cases, those judged by committee members were 83%, 80% and 100%. 3) In 1 case, Bordetella pertussis was searched and showed 0.012 mcg/ml of MIC. It was eliminated on the 1 st day after administration. 4) Doctors in charge judged the utility of CPZ for whooping cough. Twelve cases were useful and 6 cases were slightly useful. 5) No side effects were observed except for elevation of GOT and LDH. These results suggest that CPZ might be useful drug against whooping cough.

Bordetella pertussis

Evidence of whooping-cough-vaccine efficacy from the 1978 whooping-cough epidemic in Hertfordshire.

The question of the efficacy of whooping-cough immunisation was central to the controversy that started in 1974. Definitive answers were not possible at the time because of the very low levels of whooping-cough in the preceding years and the absence of up-to-date information. The widespread abandonment of whooping-cough immunisation and the subsequent epidemic of whooping-cough have provided a natural epidemiological experiment. Figures from Hertfordshire in 1978 show that for children aged 4 years and under whooping-cough immunisation conferred 92% protection.

Child Health Services

[Whooping cough epidemiology in Denmark prior to and after the introduction of whooping cough vaccination. Protective effect of the vaccine and herd immunity].

The epidemiology of whooping cough in Denmark is described on the basis of the notified cases of the disease. The frequency of whooping cough has decreased to approximately one sixteenth of the previous level in children following the introduction of vaccination for whooping cough in 1961. Following change to a programme with only three vaccinations with a weaker, non-aluminium-adsorbed pure whooping cough vaccine in 1970, whooping cough became again slightly more frequent in the nineteen seventies and eighties. No definite reduction in the proportion of cases of whooping cough among infants could be detected although this was what the 1970 programme was particularly aimed at. Isolated deaths from whooping cough still occurred in the eighties, all of these among unvaccinated infants. The risk of whooping cough in an unvaccinated child is approximately one sixth of the risk prior to introduction of vaccination. In a vaccinated child, the risk, as judged from the notified cases, is one twentieth of the risk during the time prior to introduction of vaccination. In all age groups "herd immunity" is considered to have contributed considerably to the reduced incidence. The incidence in Denmark is, however, high compared with the incidence in some other industrialized countries. A vaccination programme with more numerous whooping cough vaccinations and possibly with a more immunogenic vaccine may be recommended on the basis of the strategy aimed at keeping the incidence of whooping cough, and thus the risk of exposure, as low as possible.

Cross-Sectional Studies

[Monitoring of a whooping cough epidemic 1994/95 in Switzerland using the sentinel notification system. Sentinella Registry].

Since June 1991 pertussis cases have been reported in the Swiss Sentinel Network (Sentinella). A total of 150-200 general practitioners, physicians specialized in internal medicine, and pediatricians participate in this system on a voluntary basis. Of the three specialties involved, this non-randomized sample represents 3.0%-3.5% of all physicians registered in Switzerland. The objective of this surveillance system is to monitor clinical pertussis over time. The case definition included all patients with a cough illness lasting at least 14 days with one of the following: paroxysms of cough, inspiratory "whoop", post-tussive vomiting (sporadic cases), or an epidemiological link to a pertussis case (epidemic cases). A laboratory diagnosis based on the polymerase chain reaction technique (PCR) was available for 82.7% of cases reported in 1994 and 1995. Of these, 27.7% had a positive PCR result. Reports of epidemic pertussis tested for Bordetella pertussis by PCR were confirmed by the laboratory in 46.5% of cases. The laboratory confirmation rate was more than twice as high among epidemic cases than among sporadic cases (20.7%). The crude incidence rate of whooping cough was 70 cases per 100,000 population per year in 1992 and 1993. Compared to previous years, pertussis incidence was significantly higher in 1994 and 1995 (370 cases per 100,000 population and 280 cases per 100,000 population respectively). The increase in reports was especially marked between July and October 1994 and whooping cough became epidemic in the third trimester of 1994 and at the beginning of 1995. In these 2 years, Switzerland experienced an estimated 40,000 clinical pertussis cases. Based on the proportion of PCR-positive pertussis cases in the sentinel sample, 12,500 of these would have been laboratory-confirmed. Most cases were observed in infants and in children up to 6 years of age. Assuming a vaccination coverage of 90%, the global efficacy of vaccination (3 or more doses versus less than 3) for 1994 and 1995 among children aged 12 to 47 months and not born before 1991 was 0.74 (0.59 and 0.88 for a vaccination coverage of 85% and 95% respectively). Vaccine efficacy was higher in PCR-positive cases (0.87; 0.79; 0.94) than in PCR-negative cases (0.54; 0.27; 0.78). Vaccination efficacy estimates on the basis of surveillance data are certainly less precise than those inferred from clinical trials. However, our results indicate that the efficacy of vaccination in children significantly declined with increasing age. Whooping cough still has the potential to cause epidemics in Switzerland in spite of a high vaccination coverage. With the introduction of acellular pertussis vaccines and new vaccination schemes in Switzerland, the Swiss Sentinel Network fulfills an important task as a monitoring system and contributes to the evaluation of new vaccination strategies.

Bordetella pertussis

Whooping cough: Christchurch 1982.

Whooping cough continues to be a major health problem in New Zealand. In a twelve month period, 64 cases were admitted to the paediatric wards of Christchurch Hospital. Of these 64 patients, 24 (37.5%) were fully immunised. The possible explanations for the large number of children contracting whooping cough, who have been immunised according to the schedule used in New Zealand, is discussed.

Child

Specific immunoglobulin for treatment of whooping cough.

Immunoglobulin treatment for whooping cough (pertussis) is widely believed to be ineffective although there are sound reasons for regarding the condition as a toxin-induced disease. We wondered whether the lack of success with pertussis immunoglobulins might be attributable to inadequate dose, so we designed a randomised, double-blind, placebo-controlled trial of two immunoglobulin preparations. The study was conducted at three Swedish hospitals. We enrolled 73 children aged less than 36 months who were admitted with a clinical diagnosis of whooping cough. On admission they were assigned to one of three groups: (a) monocomponent pertussis toxoid vaccine; (b) two-component acellular vaccine also containing filamentous haemagglutinin; or (c) 20% albumin solution (placebo). The immunoglobulins had a high antitoxin content and had been raised with acellular pertussis vaccines. Diagnosis of pertussis was confirmed by laboratory tests and the follow-up was completed in 67 children. The main study group consisted of 47 children with less than or equal to 14 days of disease before therapy. Duration of whoops post-treatment was 8.7 days (95% Cl 4.8, 12.6) in the 33 children receiving immunoglobulin vs 20.6 (95% Cl 11.9, 29.3) in the 14 receiving placebo (p = 0.0041). Mean number of whoops during the first week of follow-up was also significantly reduced (p = 0.0196). We found that early treatment was important, since the effect on duration of whoops was most pronounced when disease duration before treatment was less than or equal to 7 days. There were no significant differences between the two immunoglobulin preparations. High-dose specific pertussis immunoglobulin with a high antitoxin concentration has a beneficial effect in the treatment of whooping cough.

Child, Preschool

Efficacy of whooping-cough vaccines used in the United Kingdom before 1968. A preliminary report to the Director of the Public Health Laboratory service by the Public Health Laboratory Service Whooping-Cough Committee and Working Party.

In a large survey of the efficacy of pertussis vaccines made in 33 areas in the United Kingdom during the period 1 November 1966 to 31 October 1967 a total of 3,564 households were investigated. Nine hundred and seventy-seven strains of Bordetella pertussis and 6 strains of Bord. parapertussis were isolated from persons in 792 households.After contact in the home 56% of fully vaccinated children under 5 years of age developed a paroxysmal cough, and in more than two-thirds of these patients the diagnosis was confirmed bacteriologically. This suggests that pertussis vaccination was not very effective. A comparison with the attack rate in unvaccinated children also indicates a poor protection from vaccination.NONE OF THE FOLLOWING FACTORS APPEARED TO BE RESPONSIBLE FOR THE POOR PROTECTION AFFORDED BY VACCINATION: vaccination in early infancy, a long interval since vaccination, and the absence of booster doses.Almost all the children in the survey had been given vaccines from a single manufacturer, and therefore a comparison of the efficacy of vaccines prepared by different manufacturers was inconclusive. All the vaccinated children in the survey had been vaccinated before or during 1967. The efficacy of current preparations will require to be assessed by continuing surveillance.

Age Factors

A search for subclinical infection during a small outbreak of whooping cough: implications for clinical diagnosis.

The transmission of whooping cough in a general practice community was followed after the identification of the first case for nearly three years. Intensive case-finding was undertaken to detect contacts of known cases of whooping cough and to take pernasal swabs from those with any cough; 102 swabs were taken. In three months 39 cases of whooping cough were clinically diagnosed, 17 (44%) of which were confirmed bacteriologically. All had a prolonged paroxysmal cough, one-third reported a catarrhal phase, 18 (46%) vomited with paroxysms and nine (23%) whooped. No isolations of Bordetella pertussis were obtained from the 84 contacts with non-paroxysmal coughs. There was no evidence that subclinical bordetella infection (showing none of the signs of whooping cough) is a common occurrence.It is probable that many recognizable cases of whooping cough are missed because it can be a milder illness than is often realized and commonly exhibits neither whooping, vomiting nor a catarrhal phase. Paroxysms may be infrequent. The diagnosis of whooping cough should be suspected from a prolonged paroxysmal cough alone.

Adolescent

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.

Adult

Progress towards the development of new vaccines against whooping cough.

Acellular vaccines against whooping cough are in the final stage of clinical testing and are likely to become available for mass immunization in the near future. Over a dozen vaccines of similar composition have been developed by vaccine companies and research laboratories; all of them contain a detoxified form of pertussis toxin (PT) that may be present alone or combined with one or more other non-toxic proteins, such as filamentous haemagglutinin (FHA), pertactin (69 kDa), and the agglutinogens (AGG). Most of the vaccines contain a PT that has been inactivated by chemical treatment, a process that reduces the immunogenicity of the molecule and may not completely eliminate the risk of reversion to toxicity. To avoid these problems, we have constructed by genetic manipulation a mutant of Bordetella pertussis that produces a non-toxic form of PT. This molecule (PT-9K/129G) contains two amino acid substitutions in the S1 subunit (Arg9-->Lys and Glu129-->Gly) which abolish the enzymatic activity of the S1 subunit and all the toxic properties of PT, without changing the immunological properties of the wild-type toxin. Following extensive preclinical studies, which have shown that PT-9K/129G is safe and more antigenic than the toxin treated with chemical agents, this molecule was tested for safety and immunogenicity in adult volunteers, 18-month-old children and 2-month-old infants. The molecule has been tested alone, combined with FHA and pertactin and also combined with diphtheria and tetanus toxoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Cerebellar ataxia following whooping cough.

Bordetella pertussis (BP), the agent of whooping cough, has not been recognized so far as a cause of permanent cerebellar ataxia in human. We describe three patients who developed a disabling and permanent cerebellar syndrome soon after whooping cough. In two patients, diagnosis of BP infection was confirmed by culture of nasopharyngeal secretions. The infection occurred between the age of 13 and 15 years, with neurological symptoms beginning after a delay varying from 3 weeks to 3 months. In our three patients, the cerebellar syndrome was characterized by dysmetria of ocular saccades, scanning speech and ataxic gait. Brain MRI demonstrated a pancerebellar atrophy. The pathogenesis of this cerebellar degeneration is not established. Experimental studies have demonstrated that the cerebellum is particularly vulnerable to lymphocytosis-promoting factor (LPF), one of the exotoxins from BP. The mechanism of this toxicity might be a marked increase in the cellular levels of 3',5'cyclic guanosine monophosphate (cGMP). Since whooping cough is a bacterial exotoxin-mediated disease, this is the first report of a cerebellar syndrome triggered by a bacterial exotoxin.

Adult

Whooping-cough vaccination: historical, social and political controversies.

New acellular whooping cough vaccines may have the effect of leading us to forget that infectious diseases such as whooping cough have declined in the context of particular historical, social conditions and persist in the context of particular types of social inequalities. The debates over the existence of damage from whole-cell whooping cough vaccine, and the respective risks of the vaccine and the disease are still unresolved owing to methodological limitations of studies on both sides of the argument. One-sided health 'education' campaigns on whooping cough vaccine have questionable ethics, and suppression of dissenting views is counterproductive. Health professionals and parents have a right to know the political context of the debate.

Ethics, Medical

Quantitation of circulating T and B lymphocytes in children with whooping cough.

The numbers of circulating T and B lymphocytes in seven children with whooping cough due to Bordetella pertussis and eight control subjects were determined. All the children with whooping cough had an absolute lymphocytosis (mean 29,142/mm3vs. 5,225/mm3) and by surface marker criteria both T cells and B cells were increased (mean T cells, whooping cough 15,794/mm3 vs. 3,516/mm3 controls; mean B cells, 13,393/mm3 whooping cough vs. 1,706/mm3 controls). However, the ratios of T cells to B cells in the whooping cough (1.4) and control group (1.9) did not differ significantly. This proportional increase in both T and B lymphocytes indicates that whatever mechanism are responsible for lymphocytosis in B. pertussis infection affect both populations in a similar manner.

B-Lymphocytes