An estimate of the contribution of HIV infection to the recent rise in tuberculosis in England and Wales.

BACKGROUND: The number of patients with tuberculosis has been increasing slowly in England and Wales since the late 1980s. HIV infection has been a contributory factor to increases in tuberculosis in a number of comparable industrialised countries. This study investigated the extent of tuberculosis and HIV co-infection in England and Wales in 1993 and 1998, and estimated its contribution to the increase in tuberculosis observed during this period. METHODS: Patients aged 16-54 years old at diagnosis on the 1993 and 1998 National Tuberculosis Survey databases were matched with those on the HIV/AIDS patient database. A coded process maintained patient confidentiality. Primary outcome measures were the increase between 1993 and 1998 in the numbers with both infections reported and an estimate of the proportion of the increase in tuberculosis during this period attributable to HIV co-infection. RESULTS: In 1993 61 (2.2%) tuberculosis patients aged 16-54 years matched with patients reported to the HIV database, increasing to 112 (3.3%) in 1998 (p=0.08; OR 1.35; 95% CI 0.97 to 1.87). Patients co-infected with HIV contributed an estimated 8.5% of the increase in number of tuberculosis patients between 1993 and 1998 nationwide (11% in London). In both years prevalence of co-infection was greatest in London and in patients of white and black African ethnic groups. CONCLUSIONS: In 1998 the number of tuberculosis patients co-infected with HIV in England and Wales, though still small, had nearly doubled since 1993, with most of the increase occurring in London. As HIV infection may be undiagnosed in patients with tuberculosis, and tuberculosis may be unreported in patients with diagnosed HIV infection, the true extent of co-infection will have been underestimated by this study. In addition, constraints in coded matching make it inevitable that some reported co-infections are missed. Routine HIV testing of all patients with tuberculosis should now be considered, particularly in patients of white or black African ethnic origin under 55 years of age.

The national CD4 surveillance scheme for England and Wales.

This paper describes a national surveillance scheme, began in 1995, designed to monitor immunosuppression associated with HIV infection in adults in England and Wales. Currently 60 out of 64 (94%) laboratories performing CD4 cell counts participate in the scheme. The database contains over 42,000 patient records with over 300,000 counts, taken between April 1984 and March 2000. Approximately half of the patient records in the CD4 database match with patient records in the UK database of diagnosed HIV infections; a large proportion of the unmatched patients in the CD4 database may not be HIV-infected. Close to 50% of both men who have sex with men and injecting drug users and two-thirds of those who acquired their infection heterosexually had CD4 cell counts below 350 cells/mm3 at the time of HIV diagnosis. The National CD4 Surveillance Scheme provides important information regarding the epidemiology of HIV infection such as the changes in patterns of early and late diagnosis. It should continue to be used in conjunction with the other HIV surveillance systems to present as complete a picture of the epidemic as possible.

Unusual HIV transmissions through blood contact: analysis of cases reported in the United Kingdom to December 1997.

It is important to establish the likely route of infection for all reported HIV infected individuals if the HIV epidemic is to be understood. Investigating routes of infection may bring unusual infection routes to light. Steps have been taken in the United Kingdom (UK) to establish the likely mode of HIV acquisition for everyone reported as infected. If an initial report is incomplete the clinician caring for the patient is asked for relevant information. If further information is needed, and an interview is feasible and acceptable to both the clinician and the patient, information is collected from the patient through face-to-face semistructured interview. Such follow up has identified 19 cases (among 34,000 records of individuals with HIV and/or AIDS for which probable routes of infection have established) who seem to have acquired HIV infection in unusual circumstances. Seven of the 19 cases described in this paper are thought to have acquired HIV infection in the UK, two in Spain, and ten in countries with a high prevalence of HIV infection. This paper describes the circumstances in which HIV transmission is believed to have occurred.

'Soundex' codes of surnames provide confidentiality and accuracy in a national HIV database.

Clinicians and microbiologists will participate in voluntary national reporting of HIV infections and AIDS only if they have confidence in the scheme's confidentiality. At the same time, if the data are to be accurate, it must be possible to recognise reports that refer to the same individual. The use of surname 'soundex' code in combination with date of birth meets both requirements. We describe its use in the database of reported HIV infections held at the PHLS AIDS Centre. By the end of 1994 over 93% of the 20,407 reports on the database were soundex coded, and 70% of AIDS reports were linked to independent reports of HIV infection from microbiologists. In 1994, 22% of the reports of HIV infection were recognised as duplicating earlier reports of infection. Coding surnames using soundex is an acceptable and practical tool in surveillance of an infection for which confidentiality is a prime concern.

People who travel to be treated for HIV infection: keeping track for care management.

An HIV information exchange was established to provide district health authorities (DHAs) with current demographic and epidemiological data on residents infected with HIV. Reporters in each DHA in the Thames regions were asked to collect information about all HIV infected individuals treated within their districts during 1993. The information was collated at the PHLS AIDS Centre and summary tables were distributed to the DHAs involved describing their residents. We received reports of 7760 people infected with HIV and who were treated in the Thames regions in 1993. Thirty-five per cent were treated outside the region where they lived, 22% were treated within their region but outside their district of residence, and 43% were treated in the DHA where they lived. For 30 of the 38 DHAs the number of resident patients exceeded the number treated within the district. This exchange of information between DHA of treatment and DHA of residence showed that it is possible to provide summaries of current HIV case loads based on place of residence without compromising confidentiality. It also confirmed that many patients choose to be treated away from their area of residence.

Sexually transmitted diseases and HIV-1 infection among homosexual men in England and Wales.

OBJECTIVE: To examine surveillance data for evidence of changing sexual behaviour and continuing transmission of HIV-1 among men who have sex with men. DESIGN: Analytic study of surveillance data on sexually transmitted diseases. SETTING: England and Wales. MAIN OUTCOME MEASURES: Number of cases of rectal gonorrhoea and newly diagnosed HIV infection in homosexual men. RESULTS: New cases of gonorrhoea among men attending genitourinary medicine clinics increased by 7.7% in 1989 and by 4.2% in 1990. Reports of rectal isolates of Neisseria gonorrhoeae also rose and the male to female ratio for patients with rectal gonorrhoea changed from 0.3:1 during 1988-9 to 2.6:1 in 1990-1. Although the overall number of cases of acute hepatitis B fell during 1988-91, 81 and 82 homosexual men were infected in 1990 and 1991 respectively compared with 50 and 42 in 1988 and 1989. 1526 men had HIV-1 infection diagnosed in 1991, the largest number since 1987. Twenty eight of the 97 (29%) men who seroconverted between January 1989 and December 1991 were aged less than 25. The proportion of men aged 15-19 who were found to be infected with HIV-1 at their first test increased from an average of 2.4% up to 1990 to 4.7% in the first nine months of 1991. The prevalence of HIV infection in men under 25 attending genitourinary medicine clinics in London was 17% compared with 7.8% outside London. CONCLUSION: Unsafe sexual behaviour and HIV transmissions have increased among homosexual men after a period of decline. Recent HIV transmissions may disproportionately affect younger men.

Is the IEMA combined incubator/shaker device preferable to a waterbath for incubating enzyme immunoassays?

An incubator/shaker device proved to be a convenient alternative to a waterbath for the incubation of enzyme immunoassays (EIA). The device achieved effective and even heat transfer. In two of five EIAs it increased reactivity and in three of five EIAs it slightly increased the discrimination between seronegative and seropositive specimens though, for the samples investigated, extra sensitivity was not thereby achieved. At a high shaking frequency (1400 rpm) there was cross-contamination between wells, but this did not occur at 900 rpm. The relative contributions of heating and of shaking to the incubation of EIAs deserve further investigation.

Heterosexually acquired HIV-1 infection: cases reported in England, Wales and Northern Ireland, 1985 to 1991.

By the end of 1991, there had been 417 reports of AIDS and 1620 reports of HIV-1 infection in persons in England, Wales and Northern Ireland who probably acquired their infection through sexual intercourse between men and women. Between 1986 and 1991, the proportion of AIDS cases attributable to heterosexual transmission increased from 2% to 14% and of diagnosed HIV-1 infections from 4% to 23%. Reported HIV-1 infections inadequately reflect the extent of infection as only individuals choosing to be tested can be reported. HIV-1 infection acquired during heterosexual intercourse may be the result of transmission from partners who were infected by routes other than heterosexual transmission (first generation transmission) or of transmission from infected partners who were themselves infected through heterosexual intercourse (second generation transmission). Of the 417 cases in which AIDS was acquired through heterosexual intercourse, 42 (10%) were categorised as due to first generation transmission, 328 (79%) as second generation transmission--abroad, and 47 (11%) as second generation transmission--UK. Transmission categories could be allocated to 1438 of the 1620 reports of HIV infection: 17% were categorised as first generation, 74% as second generation--abroad, and 9% as second generation--UK. Heterosexual transmission of HIV infection is increasing, both in individuals acquiring their infection abroad as well as those who become infected in the United Kingdom.

Second generation heterosexual transmission of HIV-1 infection.

Reports of 217 HIV-1 infected persons have been investigated. Initially, 122 were described as having no identified risk of HIV infection and 95 were described as probably infected through heterosexual intercourse. The sexual partners of 34 of these 95 cases were reported as having acquired their infection heterosexually in the UK but information on the risk status of the sexual partners of the remaining 61 cases was lacking. Telephone follow-up through microbiologists and clinicians resulted in the recategorisation of 132 cases. Interviews were conducted with 22 HIV infected heterosexuals without a major risk for HIV infection, either in themselves or their sexual partners, and who had no evidence of heterosexual exposure outside the UK. Interviews confirmed the categorisation of 15 cases (9 male, 6 female) as due to second generation HIV-1 infection ie, infection acquired through heterosexual intercourse in the UK with a partner who also became infected through heterosexual intercourse. A possible chain of transmission is described involving three of these 15 cases.

Voluntary testing to measure HIV prevalence in sexually transmitted disease clinics.

Voluntary HIV testing was used to study the extent of HIV-1 infection in patients attending sexually transmitted disease (STD) clinics in England and Wales between 1985 and 1990. Homosexual and bisexual men and 10-20% of heterosexual men and women were invited to complete a study record and have an HIV-1 antibody test. The rate of newly diagnosed HIV-1 infection was higher in homosexual and bisexual men than in heterosexual clinic attenders. It was also higher in patients attending clinics in the South East compared with those attending clinics in other regions. From 1988 onwards, HIV infection was identified in heterosexual men and women who did not report behavioural risk factors associated with increased risk of HIV transmission. In the early years of the study, the proportion that agreed to complete a study record and have an HIV-1 antibody test was high in all groups. This proportion declined in those attending clinics in the South East, particularly among heterosexual men and women, less than 50% of whom agreed to take part in the study in 1989 and 1990. The decline in acceptance rate made voluntary testing unsuitable for monitoring trends in HIV infection. Unlinked anonymous HIV testing, which minimises the effect of participation bias, has become the method of choice for monitoring the prevalence of HIV infection.

The influence of assay sensitivity and specificity on error rates in three anti-HIV testing strategies.

Tests for anti-HIV can be used (1) to establish for clinical or other reasons whether an individual has developed antibody to the virus, (2) to screen donated blood for evidence of infection and (3) to provide estimates of the prevalence of infection in a population. It is suggested that different testing strategies, using one or more distinct anti-HIV assays, are appropriate in these three situations. This paper examines the expected accuracy of the results that would arise if these strategies were implemented to test populations with various anti-HIV prevalences using assays with selected sensitivities and specificities. The expected outcomes are shown in tabular form for chosen values of the variables.

Which anti-HTLV III/LAV assays for screening and confirmatory testing?

In preparation for routine anti-HTLV-III/LAV testing in the UK five commercial assays (A-E) were evaluated using 360 sera selected on clinical and epidemiological grounds. These comprised 220 specimens from blood donors, 83 specimens from patients in high-risk groups, and 57 specimens with features likely to produce false-positive results. Probably erroneous positive results arose from assay A in all three categories and assay B in the second and third categories. These reactions were much more common after specimens had been heated to 56 degrees C for 30 min. Except that an anti-HLA DR4,B5-containing serum was repeatedly positive by C, assays C, D, and E apparently did not give rise to false-positive results. Results by these three assays were also highly reproducible. In tests on serum dilutions the highest titres were obtained by assays A and D, but assays C and E discriminated most clearly between anti-HTLV-III/LAV positive and negative sera. These two assays were rapid and convenient and seemed particularly suitable for testing blood donations. Assay D was almost comparable with them in performance but more difficult to use. The commercial assays C, D and E, an antibody capture assay, and a simple immunofluorescence test could be the basis for a methodologically diverse national system of primary and confirmatory testing for anti-HTLV-III/LAV.

Post-vaccination symptoms following DTP and DT vaccination.

Post-vaccination symptoms in 6,004 infants given adsorbed Diphtheria Tetanus and Pertussis (DTP) vaccine and 4,024 infants given adsorbed Diphtheria and Tetanus (DT) vaccine have been compared. Although crying, screaming and fever were slightly more frequent after adsorbed DTP than adsorbed DT, attacks of high-pitched screaming, episodes of pallor and hypotonia, convulsions, other neurological disorders and sudden infant death occurred with similar frequency in the two groups. No specific neurological effect attributable to the pertussis component was found.

Symptoms after primary immunisation with DTP and with DT vaccine.

Symptoms after routine primary immunisation of 6004 infants with diphtheria/tetanus/pertussis (DTP) vaccine and 4024 infants with diphtheria/tetanus (DT) vaccine have been compared. After each dose, crying, screaming, and feverishness were more frequent with adsorbed DTP than adsorbed DT, but the difference was small. Attacks of high-pitched screaming, episodes of pallor or cyanosis with limpness, convulsions, and local reactions occurred with similar frequency after both vaccines. There was a considerable increase in local reactions after the 3rd dose with both vaccines. Over 1000 doses of plain DTP (with no aluminium hydroxide adjuvant) were given during the study. Post-vaccination symptoms were more common after the plain than after the 2 adsorbed preparations.

Virus diarrhoea associated with pale fatty faeces.

Steatorrhoea was a significant feature in an outbreak of rotavirus gastroenteritis which affected adults and infants in hospital. Fat globules or fatty acid crystals were obvious by light microscopy (LM) in faeces from 14 of 25 patients examined. Ten of the fatty stools and two of the remainder were very pale. By electron microscopy (EM) a rotavirus was seen in 11 of the 14 fatty faeces and in only two of 11 specimens without visible fat. In a further study of pale or fatty faeces 20 such specimens sent for laboratory examination from patients not involved in the hospital outbreak were compared microbiologically with a similar number which were neither pale nor fatty. Viruses were found by EM in 11 (55%) of the pale or fatty stools; eight rotaviruses, two astroviruses and an uncultivable adenovirus were seen; one further patient had acute jaundice. In contrast, no viruses were seen by EM in the twenty specimens which were normally pigmented and without evident fat. Steatorrhoea was significantly associated with rotavirus infection of the alimentary tract which usually presented as a fatty enteritis. We conclude that rotaviruses certainly, and other viruses possibly, can impede both the digestion of fat and the pigmentation of the faeces. Inspection and LM of faeces are easy. In acute enteritis a fatty or pale stool is an indication for virological examination.