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.     

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.     

A Comprehensive Approach to Identification of Surface-Exposed,Outer Membrane-Spanning Proteins of Leptospira interrogans

Leptospirosis is a zoonosis with worldwide distribution caused by pathogenic spirochetes belonging to the genus Leptospira. The leptospiral life cycle involves transmission via fresh water and colonization of the renal tubules of their reservoir hosts or infection of accidental hosts, including humans. Bacterial outer membrane proteins (OMPs), particularly those with surface-exposed regions, play crucial roles in virulence mechanisms of pathogens and the adaptation to various environmental conditions, including those of the mammalian host. Little is known about the surface-exposed OMPs in Leptospira, particularly those with outer membrane-spanning domains. Herein, we describe a comprehensive strategy for identification and characterization of leptospiral transmembrane OMPs. The genomic sequence of L. interrogans serovar Copenhageni strain Fiocruz L1–130 allowed us to employ the β-barrel prediction programs, PRED-TMBB and TMBETA-NET, to identify potential transmembrane OMPs. Several complementary methods were used to characterize four novel OMPs, designated OmpL36, OmpL37, OmpL47 and OmpL54. In addition to surface immunofluorescence and surface biotinylation, we describe surface proteolysis of intact leptospires as an improved method for determining the surface exposure of leptospiral proteins. Membrane integration was confirmed using techniques for removal of peripheral membrane proteins. We also demonstrate deficiencies in the Triton X-114 fractionation method for assessing the outer membrane localization of transmembrane OMPs. Our results establish a broadly applicable strategy for the elucidation of novel surface-exposed outer membrane-spanning proteins of Leptospira, an essential step in the discovery of potential virulence factors, diagnostic antigens and vaccine candidates.     

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.     

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.     

Growth retardation in weight and catch-up growth following infection by measles and whooping cough among babies of rural Zaire (Lake Tumba)

This study has shown that measles and whooping cough affect growth in weight among babies of rural Zaire (Lake Tumba). The average loss in weight due to measles, is more than twice the amount due to whooping cough. However, the time needed to regain the original growth channel after infection by measles, is about half the time needed to fully catch up after whooping cough. The amount of weight loss is proportional to the child's weight at the onset of the disease. There is no difference in the susceptibility to lose weight after measles or whooping cough, between boys and girls, nor between Oto and Twa. This study has also shown that the effect of measles and whooping cough on the growth in weight, is independent of the season of the hear, although the incidence of these diseases showed a significant seasonal pattern. Finally, this study gives evidence for the fact that the incidence of weight loss one month after the onset of measles or whooping cough is age-related.     

Analysis of Surface-Exposed Outer Membrane Proteins in Helicobacter pylori

More than 50 Helicobacter pylori genes are predicted to encode outer membrane proteins (OMPs), but there has been relatively little experimental investigation of the H. pylori cell surface proteome. In this study, we used selective biotinylation to label proteins localized to the surface of H. pylori, along with differential detergent extraction procedures to isolate proteins localized to the outer membrane. Proteins that met multiple criteria for surface-exposed outer membrane localization included known adhesins, as well as Cag proteins required for activity of the cag type IV secretion system, putative lipoproteins, and other proteins not previously recognized as cell surface components. We identified sites of nontryptic cleavage consistent with signal sequence cleavage, as well as C-terminal motifs that may be important for protein localization. A subset of surface-exposed proteins were highly susceptible to proteolysis when intact bacteria were treated with proteinase K. Most Hop and Hom OMPs were susceptible to proteolysis, whereas Hor and Hof proteins were relatively resistant. Most of the protease-susceptible OMPs contain a large protease-susceptible extracellular domain exported beyond the outer membrane and a protease-resistant domain at the C terminus with a predicted β-barrel structure. These features suggest that, similar to the secretion of the VacA passenger domain, the N-terminal domains of protease-susceptible OMPs are exported through an autotransporter pathway. Collectively, these results provide new insights into the repertoire of surface-exposed H. pylori proteins that may mediate bacterium-host interactions, as well as the cell surface topology of these proteins.     

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.     

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.     

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.     

Etiology, clinical manifestations, and epidemiology in community-acquired respiratory infection in children in the Khabarovsk region

Clinico-epidemiological analysis and etiological verification of the outbreak of respiratory infection among school children in a rural district of the Khabarovsk territory, registered in spring 1997, were made. According to clinical signs, one-third of the patients had whooping cough, while the rest of the children exhibited the signs of respiratory infection with the symptoms of longering bronchitis. A half of the children had not been vaccinated against whooping cough, as they had been given injections of adsorbed DT vaccine with reduced antigen content. Etiologically, the diagnosis of whooping cough was confirmed in 57% of the patients with 47.4% of them having Bordetella pertussis monoinfection and 52.6% having mixed infection, mainly in combination with chlamydiosis. Whooping cough took an abnormal course under these circumstances. Treatment with erythromycin produced a good effect.     

Prenatal immunization for the protection of infants against whooping cough

Summary Prenatal immunization against whooping cough could, in theory at least, save the lives of infants. With this in view the present report outlines the results obtained when a group of mothers were immunized with whooping cough vaccine during pregnancy. The immunization procedures followed resulted in low agglutination titres in the mother and subsequently in the infant. As a result, it was necessary to arrange a different schedule of immunizations.     

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.     

Severity of notified whooping cough.

An analysis was made of the severity of over 8000 cases of whooping cough notified from October 1974 to March 1975. Ten per cent of these patients were admitted to hospital and there were 10 deaths. Severity was directly related to age, the disease being most severe in children under 1 year, especially those under 6 months. There was some evidence that previous vaccination reduced the severity of the disease, but the vaccination programme does not cover very young children, and for them whooping cough is a dangerous disease.     

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.     

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.     

Inhibiting effect of ADP-ribosylation by pertussis toxin on passive transport of Ca2+ into the cell membrane of porcine myometrium]

ADP-ribosylation by whooping cough toxin of protein components of inside-out oriented vesicles of pig myometrium plasma membranes under conditions of their depolarization results in significant inhibition of passive transport of Ca2+ ions. The inhibiting effect is dose- and time-dependent. rho-Chloromercuribenzoate (0.5 mM) blocks the effect of whooping cough toxin, no such effect on Ca2+ transport being observed in control preparations.     

Identification of protective outer membrane antigens of Brucella ovis by passive immunization of mice with monoclonal antibodies

Outer membrane proteins (OMPs) and rough lipopolysaccharide (R-LPS), the main surface antigens of Brucella ovis, display surface-exposed epitopes. Mixtures of monoclonal antibodies (mAbs) to both antigens were previously shown to protect mice against a B. ovis challenge. To further identify the antigens involved, seven mAbs against Brucella OMPs (Omp10, Omp16, Omp19, Omp25, Omp31, Omp2b and Omp1) and three to R-LPS were tested for protection either individually or in combinations. Significant reduction in spleen infection in challenged mice, relative to controls, was used as the protection criteri. Controls included nonimmunized mice and mice given an irrelevant, anti-O-polysaccharide (OPS), mAb. For comparison, a group received a mouse serum containing antibodies to both OMPs and R-LPS; this serum was prepared by immunization with a B. ovis hot-saline extract which, as described previously, induces protective immunity in mice and rams. Significant protection was observed with both mAbs to OMPs and R-LPS. mAbs to Omp16, Omp19 and Omp31 afforded the highest protection and prevented the development of splenomegaly. The protective effect of mAb to Omp31 was not interfered with by nonprotective mAbs in different mixtures. The data presented confirm the protective role of antibodies to OMPs and R-LPS against B. ovis, and identify several OMPs, especially Omp31, which are promising candidates for a subunit vaccine against ram epididymitis.     

Interpretation of the contraindications to whooping cough vaccination.

The official recommendations on the contraindications to whooping cough immunisation are currently couched in general terms. The results of a simple inquiry made to directors of public health laboratories, general paediatriciains, paediatric neurologists, medical officers, general practitioners, and health visitors to see how they would interpret the contraindications in certain specific cases suggest that there is considerable uncertainty on how the contraindications should be interpreted. This is probably one factor responsible for the fall in the rate of whooping cough immunisation in the United Kingdom.     

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.