PHLS work on the surveillance and epidemiology of tuberculosis

The re-emergence worldwide of tuberculosis as a major threat to public health and continuing and changing challenges in the control of tuberculosis in England and Wales provide the basis for the designation, by the PHLS, of tuberculosis as a priority area. In addition to the mycobacteriology reference services provided by the PHLS in England and Wales (summarised in an accompanying article) the PHLS contributes to the control of tuberculosis through its surveillance and other epidemiological work. This article summarises the range of this work, emphasising the collaborative nature of the effort required for surveillance, prevention, and control of tuberculosis.     

The loss of immunity in directly transmitted infections modeling: effects on the epidemiological parameters

When directly transmitted infectious diseases are modeled assuming an everlasting induced immunity (and constant contact rate), there are well-established formulas to deal with, which is not true if we include the loss of induced immunity. In general, the immunity induced by the disease is everlasting. We propose a model considering the loss of immunity and present methods for the estimation of two epidemiological parameters: the force of infection and the basic reproduction ratio. We also analyze the effects of the loss of immunity on these parameters. Based on these results, we concluded that reinfection can play an important role in highly vaccinated populations.     

Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease

Previously we have formulated transmission models of untreated tuberculosis epidemics (Blower et al., Nature, Medicine 1 (1995), 815-821); in this paper, we present time-dependent uncertainty and sensitivity analyses in order to quantitatively understand the transmission dynamics of tuberculosis epidemics in the absence of treatment. The time-dependent uncertainty analysis enabled us to evaluate the variability in the epidemiological outcome variables of the model during the progression of a tuberculosis epidemic. Calculated values (from the uncertainty analysis) for the disease incidence, disease prevalence, and mortality rates were approximately consistent with historical data. The time-dependent sensitivity analysis revealed that only a few of the model's input parameters significantly affected the severity of a tuberculosis epidemic; these parameters were the disease reactivation rate, the fraction of infected individuals who develop tuberculosis soon after infection, the number of individuals that an infectious individual infects per year, the disease death rate, and the population recruitment rate. Our analysis demonstrates that it is possible to improve our understanding of the behavior of tuberculosis epidemics by applying time-dependent uncertainty and sensitivity analysis to a transmission model.     

Prevention of nosocomial transmission of Mycobacterium tuberculosis

The recent resurgence of TB together with the ongoing HIV epidemic has resulted in a larger number of infectious TB patients being admitted to US health care facilities. These patients have become a source for both nosocomial (patient-to-patient) and occupational (patient-to-health care worker) M. tuberculosis transmission. Infectious MDR-TB patients serve as even greater potential infectious sources because they often remain AFB smear and culture positive for months to years. The keys to the prevention of nosocomial and occupational transmission of M. tuberculosis is conducting a risk assessment for each area of the facility and instituting appropriate control measures, having a high index of suspicion by clinicians for infectious TB in those who present with consistent signs and symptoms, rapid triage of such patients to isolation areas and their appropriate clinical work-up, and the institution of effective antituberculous therapy. Infection control personnel should ensure that infectious TB patients are isolated in appropriate isolation rooms (i.e., negative pressure, greater than or equal to 6 ACH, and direct external exhaust of the room air). Health care workers with infectious TB patient contact should be instructed in the epidemiology of M. tuberculosis transmission, the role of respirators in protecting the health care worker from airborne inoculation, and the importance of periodic health care worker TST. The nosocomial TB outbreaks in the 1980s and 1990s document that M. tuberculosis can be transmitted to both patients and health care workers in US health care facilities when appropriate infection control measures are not fully implemented. Follow-up studies at some of these institutions, however, document that when infection control measures similar to the 1990 or 1994 CDC TB Guidelines are fully implemented, M. tuberculosis transmission to both patients and health care workers can be reduced or eliminated. Protection of both patients and health care workers from M. tuberculosis infection is dependent on an understanding and full implementation of the 1994 CDC TB Guidelines.     

Renal, intestinal, and adrenal responses to sodium loading in Dahl-Iwai salt-sensitive and salt-resistant rats

Following the introduction of an improved surveillance system for infectious intestinal disease outbreaks in England and Wales, the Public Health Laboratory Service Communicable Disease Surveillance Centre received reports of 26 outbreaks between 1 January 1992 and 31 December 1995 in which there was evidence for waterborne transmission of infection. In these 26 outbreaks, 1756 laboratory confirmed cases were identified of whom 69 (4%) were admitted to hospital. In 19 outbreaks, illness was associated with the consumption of drinking water from public supplies (10 outbreaks) or private supplies (9 outbreaks). The largest outbreak consisted of 575 cases. In 4 of the remaining 7 outbreaks, illness was associated with exposure to swimming pool water. Cryptosporidium was identified as the probable causative organism in all 14 outbreaks associated with public water supplies and swimming pools. Campylobacter was responsible for most outbreaks associated with private water supplies. This review confirms a continuing risk of cryptosporidiosis from chlorinated water supplies in England and Wales, and reinforces governmental advice to water utilities that water treatment processes should be rigorously applied to ensure effective particle removal. High standards of surveillance are important for prompt recognition of outbreaks and institution of control measures. As microbiological evidence of water contamination may be absent or insufficient to implicate a particular water supply, a high standard of epidemiological investigation is recommended in all outbreaks of suspected waterborne disease.     

Tuberculosis in England and Wales in 1993: results of a national survey. Public Health Laboratory Service/British Thoracic Society/Department of Health Collaborative Group

BACKGROUND: A national survey of tuberculosis notifications in England and Wales was carried out in 1993 to determine the notification rate of tuberculosis and the trends in the occurrence of disease by ethnic group in comparison with the findings of similar surveys in 1978/79, 1983, and 1988. The prevalence of HIV infection in adults notified with tuberculosis in the survey period was also estimated. METHODS: Clinical, bacteriological, and sociodemographic information was obtained on all newly notified cases of tuberculosis in England and Wales during the six months from 2 January to 2 July 1993. The prevalence of HIV infection in 16-54 year old patients with tuberculosis notified throughout 1993 was assessed using "unlinked anonymous" testing supplemented by matching of the register of patients with tuberculosis with that of patients with AIDS reported to the PHLS AIDS centre. Annual notification rates were calculated using population estimates from the 1993 Labour Force Survey. RESULTS: A total of 2706 newly notified patients was eligible for inclusion in the survey of whom 2458 were previously untreated the comparable figures for 1988 were 2408 and 2163. The number of patients of white ethnic origin decreased from 1142 (53%) in 1988 to 1088 (44%) in 1993 whereas those of patients of Indian, Pakistani, or Bangladeshi (Indian subcontinent (ISC)) ethnic origin increased from 843 (39%) in 1988 to 1014 (41%) and those of "other" (non-white, non-ISC) ethnic origins increased from 178 (8%) to 356 (14%). The largest increase was seen in the black African ethnic group from 37 in 1988 to 171 in 1993. Forty nine per cent of patients had been born abroad and the highest rates were seen in those who had recently arrived in this country. The overall annual notification rate for previously untreated tuberculosis in England and Wales increased between 1988 and 1993 from 8.4 to 9.2 per 100,000 population. The rate declined in the white, Indian, and black Caribbean ethnic groups and increased in all other groups. In the white group the rate of decline has slowed since the last survey: in several age groups the rates were higher in 1993 than 1988 but the numbers in these groups were small. Thirty six (4.1%) of the 882 previously untreated respiratory cases were resistant to isoniazid and three (0.3%) to isoniazid and rifampicin. Sixty two (2.3%) adults aged 16-54 years were estimated to be HIV-infected. Evidence of under-reporting of HIV positive tuberculosis patients was found. CONCLUSIONS: The number of cases and annual notification rate for previously untreated tuberculosis increased between 1988 and 1993. Although the decline in rates in the white population has continued, the rate of decline has slowed. The high rates in the ISC ethnic group population have continued to decline since 1988 whereas rates in the black African group have increased. An increased proportion of cases were found among people born abroad, particularly those recently arrived in this country. In previously untreated cases the level of drug resistance remains low and multi-drug resistance is rare. A small proportion of adults with tuberculosis were infected with HIV but there may be selective undernotification of tuberculosis in these patients.     

Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli

BACKGROUND: The microscopic examination of sputum for acid-fast bacilli, is a simple and rapid test that is used to provide a presumptive diagnosis of infectious tuberculosis. While patients with tuberculosis with sputum smears negative for acid-fast bacilli are less infectious than those with positive smears, both theoretical and empirical evidence suggest that they can still transmit Mycobacterium tuberculosis. We aimed to estimate the risk of transmission from smear-negative individuals. METHODS: As part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, patients with tuberculosis with mycobacterial isolates with the same DNA fingerprint were assigned to clusters that were assumed to have involved recent transmission. Secondary cases with tuberculosis, whose mycobacterial isolates had the same DNA, were linked to their presumed source case to estimate transmission from smear-negative patients. Sensitivity analyses were done to assess potential bias due to misclassification of source cases, unidentified source cases, and HIV-1 co-infection. FINDINGS: 1574 patients with culture-positive tuberculosis were reported and DNA fingerprints were available for 1359 (86%) of these patients. Of the 71 clusters of patients infected with strains that had matching fingerprints, 28 (39% [95% CI 28-52]) had a smear-negative putative source. There were 183 secondary cases in these 71 clusters, of whom a minimum of 32 were attributed to infection by smear-negative patients (17% [12-24]). The relative transmission rate of smear-negative compared with smear-positive patients was calculated as 0.22 (95% CI 0.16-0.32). Sensitivity analyses and stratification for HIV-1 status had no impact on these estimates. INTERPRETATION: In San Francisco, the acid-fast-bacilli smear identifies the most infectious patients, but patients with smear-negative culture-positive tuberculosis appear responsible for about 17% of tuberculosis transmission.     

The fall in household size and the rise of the primary individual in the United States

The long-term fall in household size in the United States is discussed within the framework of the aging of the population, continuing as the effects of fertility and mortality decline accumulate. Using distributions of households by size from U.S. census data 1790-1970 and a components of change analysis on primary individuals for 1950-1974, household changes are related to demographic change for the periods 1790-1900, 1900-1950, and 1950-1974. Fertility and mortality declines have unambiguous impact on household size until the increases in primary individuals begin. But these, too, have a theoretically interesting, if indirect relationship to population structure.     

Assessment of the acrosome reaction in Bufo arenarum spermatozoa by immunostaining: comparison with other methods

Data from the surveillance scheme of general outbreaks of infectious intestinal disease in England and Wales were used to describe the epidemiology of outbreaks of salmonellosis in hospitals from 1992-1994. Outbreaks of infectious intestinal disease in hospitals accounted for 15% (189/1275) of all outbreaks. A salmonella was the implicated pathogen in 12% (22/189). The mode of transmission was described as mainly person to person in 12 outbreaks, mainly foodborne in eight and equal or unknown proportions of foodborne and person to person in two. The most common strain involved was Salmonella enteritidis PT4 (11 outbreaks). The mean duration of outbreaks was 16 days. The mean attack rate in patients was 25% but varied from 2-67%. Illness was reported in 260 patients, of whom 130 had a laboratory confirmed infection. Eight hundred and twenty-six asymptomatic patients were tested, 31 of whom were positive. The salmonella infection was believed to have contributed to the deaths of five patients. Ill staff (115) were tested and 68 were positive; 1508 well staff were tested and 33 were positive. Outbreaks of salmonellosis in hospitals are preventable. Attack rates can be high and outbreaks are often prolonged, with high morbidity and associated disruption of hospital services. There is need for effective infection control policies, appropriate training of staff, simple surveillance systems and readily available expert advice to ensure outbreaks are rapidly controlled.     

Micro-methods for serial determinations of elastin metabolism parameters in blood plasma and serum

Micro-methods are described for the serial determinations of elastin metabolism related parameters in human serum or plasma samples: serum elastase activity, elastase inhibitor titers and elastin peptide conc-s. These methods were used in an epidemiological study (the EVA study, " Etude du vieillissement vasculaire") carried out in Nantes, west of France on several thousand individuals. Blood samples obtained from the first-1389 individuals (574 males, 815 females) were used for the determinations. In order to carry out this large number of determinations previously described procedures had to be modified. These methods used for the large serial determinations of the above mentioned three elastin metabolism related serum (or plasma) parameters are described because of their potential interest for serial clinical investigations.     

Population dynamic interference among childhood diseases

Epidemiologists usually study the interaction between a host population and one parasitic infection. However, different parasite species effectively compete, in an ecological sense, for the same finite group of susceptible hosts, so there may be an indirect effect on the population dynamics of one disease due to epidemics of another. In human populations, recovery from any serious infection is normally preceded by a period of convalescence, during which infected individuals stay at home and are effectively shielded from exposure to other infectious diseases. We present a model for the dynamics of two infectious diseases, incorporating a temporary removal of susceptibles. We use this model to explore population-level consequences of a temporary insusceptibility in childhood diseases, the dynamics of which are partly driven by differences in contact rates in and out of school terms. Significant population dynamic interference is predicted and cannot be dismissed in the limited case-study data available for measles and whooping cough in England before the vaccination era.     

DNA fingerprinting of Mycobacterium tuberculosis complex culture isolates collected in Brazil and spotted onto filter paper

The usefulness of filter paper for preservation of bacterial cells was shown by mixed-linker DNA fingerprint analysis of Mycobacterium tuberculosis isolates from 77 Brazilian patients. DNA fingerprints of samples spotted onto filter paper and conventional culture material were identical. Thus, filter paper specimens analyzed by an amplification-based typing method provide a new resource for epidemiological studies of infectious diseases.     

Results from the 1995 survey of prevalent clinically diagnosed HIV infection in England, Wales, and Northern Ireland

Health districts in England, Wales, and Northern Ireland were surveyed in 1996 to collect summary information about people with diagnosed HIV infection who received care under the statutory services in 1995. The survey provided demographic and epidemiological information about the prevalent caseload by area of residence, and the extent to which patients with diagnosed HIV infection travelled to obtain care related to it. A total of 13362 people with diagnosed HIV infection were reported to be resident and treated in England, Wales, or Northern Ireland in 1995. Forty-four per cent of these were treated outside the health district where they lived, with regional specialist centres attracting patients from wider areas. At least 13% received care from more than one treatment centre. This national survey of prevalent diagnosed HIV infections provided public health specialists with information relevant to their own localities without compromising confidentiality. This information complements surveillance data from confidential AIDS case diagnosis reports, laboratory reports of HIV infections, and the unlinked anonymous HIV prevalence monitoring programme, all of which contribute to the assessment and projection of demands on health and social services, and provide evidence on which to develop and direct national and local health campaigns.     

Measures of concurrency in networks and the spread of infectious disease

An investigation is made into the impact of concurrent partnerships on epidemic spread. Starting from a definition of concurrency on the level of individuals, the authors define ways to quantify concurrency on the population level. An index of concurrency based on graph theoretical considerations is introduced, and the way in which it is related to the degree distribution of the contact graph is demonstrated. Then the spread of an infectious disease on a dynamic partnership network is investigated. The model is based on a stochastic process of pair formation and separation and a process of disease transmission within partnerships of susceptible and infected individuals. Using Monte Carlo simulation, the spread of the epidemic is compared for contact patterns ranging from serial monogamy to situations where individuals can have many partners simultaneously. It is found that for a fixed mean number of partners per individual the distribution of these partnerships over the population has a major influence on the speed of the epidemic in its initial phase and consequently in the number of individuals who are infected after a certain time period.     

Two-dimensional transferred-echo double resonance study of molecular motion in a fluorinated polycarbonate

A case-control study was undertaken to provide information about the role of some husbandry practices and farm characteristics in the epidemiology of bovine tuberculosis in the Veneto Region. Twenty-seven breeding herds where a positive result to the single intradermal cervical tuberculin test was confirmed by post-mortem examination were compared with seventy-four herds which had been free of the disease for at least three years. Epidemiological information was collected on farms. The factors taken into account in the study were chosen on the basis of their epidemiological plausibility and of the local livestock characteristics. Multiple logistic regression was applied to analyse the data. Factors identified as possibly involved in increasing the risk of bovine tuberculosis in the Veneto Region were the presence of mixed (dairy and beef) enterprises (OR = 4.9, P = 0.001) and of cattle purchase (OR = 5.8; P = 0.003). Other factors (such as herd size, housing system, summer mountain pasture, possible contact with wild animals, and indirect contacts with other herds) did not appear to significantly contribute to tuberculosis presence in this area. The results of this case-control study support the hypothesis that in the Veneto Region bovine tuberculosis infection is still associated with classical risk factors both (directly or indirectly) related to cattle movements.     

Tuberculosis trends in Barcelona (1987-1995). Impact of the human immunodeficiency virus and control measures

BACKGROUND: To study the epidemiology to tuberculosis (TB) in Barcelona, Spain from 1987 to 1995, analyzing the influence of HIV infection and the impact of control measures. PATIENTS, MATERIAL AND METHODS: All cases detected by the Barcelona Tuberculosis Prevention and Control Program were included in the study of the evolution of TB incidence according to different variables. The impact of HIV infection was analyzed through the attributable risk per cent (AR), and control measures through the evolution of the rate of treatment compliance, contact studies, and diagnostic delay. RESULTS: We detected 8,942 patients, 23.2% of whom were found through the active epidemiological surveillance system, representing an average annual incidence of 60.4/100,000. The incidence peaked in 1991 (68.7/100,000) and slowly declined to 55.7/100,000 in 1995. Men showed higher incidence (RR: 2.74; CI 95%: 2.62-2.87), particularly among the young (25-34 years olds), 53.3% of whom were HIV (+). The AR for HIV was 92.7%. In this period there was an increase in TB HIV (+), IVDU, and prisoners. Treatment compliance (80.8% in 1987 to 93.8% in 1995) and contact studies (3.2 studies/case in 1995) evolved favorably, unlike but diagnostic delay (35 days in 1995) did not. CONCLUSIONS: The Active Epidemiological Surveillance System has affored us a clear view of the actual situation regarding TB in Barcelona, Spain. Despite the HIV epidemics and the high number of IVDU, the evolution of TB has shown a steady decline due to improvement in control measures.     

The basic reproduction ratio for sexually transmitted diseases. Part 2. Effects of variable HIV infectivity

In this paper we investigate the effects of variable infectivity on the spread of HIV in a heterosexual population where pair formation and separation are taken into account. We calculate the basic reproduction ratio as a function of the number of new partners during the infectious period, keeping the total number of contacts fixed. Numerical evidence suggests that the basic reproduction ratio decreases for variable infectivity if the average infectivity is kept constant.     

Suboptimal compliance with periconceptual folic acid in an Irish hospital population

A time-series study of homicide and suicide rates by each method in England and Wales from 1950 to 1985 showed that the sociological correlates of these rates depended upon the method used for killing. This raises the possibility that murder and suicide may not be unitary phenomena, but rather that murder and suicide by particular methods are distinct deviant acts and should be studied separately.     

Molecular epidemiology and the new tuberculosis

DNA fingerprinting techniques now exist which identify specific strains of Mycobacterium tuberculosis. These techniques may be integrated with conventional epidemiologic approaches to better understand tuberculosis in its modern form. This paper reviews the lessons learned from this approach about the pathogenesis and epidemiology of tuberculosis. In addition, it speculates about the potential future applications of molecular epidemiology, including its use as an adjunct to conventional public health measures.