Adaptation of lymphadenopathy associated virus (LAV) to replication in EBV-transformed B lymphoblastoid cell lines.

A strain of lymphadenopathy associated retrovirus ( LAV ) passaged in vitro was used to infect a lymphoblastoid cell line obtained by transformation with Epstein-Barr virus of B lymphocytes from a healthy donor. The virus produced from this line (B- LAV ) was also able to grow at a high rate in some other lymphoblastoid lines and in a Burkitt lymphoma line. This adapted strain retained the biochemical, ultrastructural, and antigenic characteristics of the original strain, as well as its tropism for normal T4+ lymphocytes. It is thus possible to grow LAV in large quantities that can be used for the preparation of diagnostic reagents. The interaction between such a human retrovirus and Epstein-Barr virus, a DNA virus, may have some implication for the pathology of the acquired immunodeficiency syndrome and related diseases.

Surveillance of AIDS in the European Community: recent trends and predictions to 1991.

Statistical modelling is applied to routine AIDS surveillance data to assess recent trends and to provide a range of short-term predictions. Several alternative functions have been fitted to half-yearly incidence data reported by the countries of the European Community by 31 December 1989 and adjusted for reporting delays. Among homosexual/bisexual men, recent trends in AIDS incidence are more nearly linear than exponential. Higher though less than exponential rates of growth are observed among intravenous drug users and among those presumed infected by heterosexual contact. Extrapolations to the end of 1991 using each of five functions provide a range of forecasts. Projections of total cumulated cases to the end of 1991 lie in the range 60,000-78,000, with 24,000-30,000 projected cases among homosexual/bisexual men, 23,000-33,000 among intravenous drug users, and 6000-8000 in the heterosexual transmission group. With the possible exception of the latter group, the lower parts of these ranges appear more probable.

Seroepidemiology of HTLV-I/II in universal screening of blood donations in France.

OBJECTIVE: To evaluate the serological and epidemiological characteristics of HTLV-I/II-positive blood donors in continental France during the first 6 months of universal screening of blood donations (n = 1,816,927). METHOD: A collaborative investigation of all confirmed anti-HTLV-I/II-positive samples reported by blood transfusion centres was performed. Seventy-three out of 77 reported samples were retested at two reference laboratories. Epidemiological data on risk factors were compiled. RESULTS: Of the 73 retested samples, 66 were confirmed to be HTLV-I-positive and one to be HTLV-II-positive; six samples were designated false-positive, mainly because of non-specific reactivity to recombinant gp21 in Western blot. The overall prevalence of HTLV-I/II in continental France is 0.039 per thousand. The main risk factor identified for HTLV-I infection was directly (origin) or indirectly (heterosexual contact) linked to endemicity in the Caribbean. The cost per case of avoided contamination in the 6-month period of this study was 1.36 million French francs. CONCLUSIONS: Sixty-two per cent of HTLV-I/II-infected blood donations would not have been discarded through the previous targeted HTLV screening or through other mandatory tests, including anti-hepatitis B core. To avoid false-positive results, we propose a new algorithm of diagnosis.

AIDS in Europe: current trends and short-term predictions estimated from surveillance data, January 1981-June 1986.

European AIDS surveillance data, reported to the World Health Organization (WHO) Collaborating Centre on AIDS, Paris by 30 June 1986, have been analysed statistically to assess current trends and to provide short-term predictions. Reported case numbers were first adjusted to allow for the estimated time delays between diagnosis and reporting. The adjusted data (cases per half-year of diagnosis) were then fitted using exponential functions over selected time intervals to monitor and compare the evolution of the epidemic in individual countries and in the European Community (EC) as a whole. Predictions to mid-1988 were made by extrapolation. Results are presented for the EC and for the following individual countries: Belgium, Denmark, France, Federal Republic of Germany, Italy, The Netherlands, Spain, Sweden, Switzerland and the United Kingdom.

Misconceptions about transmission of AIDS and attitudes toward prevention in the French general public.

A survey of the social perception of AIDS and its prevention was carried out in December 1987 in a representative sample of the adult population of the Paris region (France). A significant part of the general public still holds misconceptions about transmission by casual contact and blood donation. Misbeliefs about modes of transmission clearly encourage individuals' willingness to stigmatize AIDS patients and to support the most coercive measures of prevention (such as quarantine). Advertizing efforts to promote use of condoms, sexual education in schools, and systematic HIV screening for pregnant women are the only measures which create a broad consensus independently of sociocultural differences. Socioeconomic status and even religious or political beliefs strongly influence public opinions toward other preventive measures.

Factors associated with tuberculosis at AIDS diagnosis in France.

OBJECTIVE: To identify factors associated with tuberculosis (TB) at AIDS diagnosis in France. DESIGN: Analysis of surveillance data. METHODS: Among all adult AIDS cases diagnosed since January 1988 and reported by December 1993 in France, the proportion diagnosed with AIDS-defining TB (extrapulmonary TB among cases diagnosed between 1988 and 1992, all forms of TB among cases diagnosed in 1993) was analysed by year of diagnosis, sex, age, nationality, profession, HIV transmission group and region of residence by multiple logistic regression. RESULTS: Between 1988 and 1992, 5.7% (1134 out of 19,968) of AIDS patients were diagnosed with AIDS-defining extrapulmonary TB. Presence of extrapulmonary TB was associated with male sex [adjusted odds ratio (AOR), 1.7], nationality from a sub-Saharan country (AOR, 4.8), heterosexual contact or injecting drug use (AOR, 2.4 and 2.7, respectively), residence in the Paris area (AOR, 1.7), and unemployment or factory work (AOR, 2.5 and 2.4, respectively). In 1993, 10.6% (393 out of 3721) of AIDS patients were diagnosed with TB (all forms). In multivariate analysis, three factors were independently associated with the risk of presenting TB at AIDS diagnosis: transmission category, nationality, and region of residence. CONCLUSIONS: Some factors associated with TB at AIDS diagnosis in France are known to be related to a high incidence of TB in industrialized countries (nationality, from a developing country, male sex, low socioeconomic status). The independent association with injecting drug use or residence in Paris suggests a contribution of recent TB infection in specific groups of HIV-infected persons. This contribution should be evaluated to implement appropriate preventive measures.

Reconstruction and prediction of the HIV/AIDS epidemic among adults in the European Union and in the low prevalence countries of central and eastern Europe.

OBJECTIVES: To reconstruct the HIV epidemic and to provide forecasts of AIDS incidence among adults in the European Union (EU) and in a group of low prevalence (LP) countries of central and eastern Europe (including the Asian republics of the former Soviet Union). METHODS: An empirical Bayesian back-calculation method was applied to AIDS incidence data reported by 31 March 1994. The HIV-infection curve was modelled as a yearly step function and a seven-stage Markov model of disease progression, incorporating effects of pre-AIDS treatment, was used. Estimation was by penalized maximum likelihood with empirical Bayesian smoothing. Data were analysed by transmission group and, within the EU, by country. Predictions of AIDS cases to 1998 were made assuming constant annual HIV incidence from 1993 onwards. RESULTS: Estimated HIV prevalences per 100,000 population aged 15-59 years were, at 31 December 1993, 198 (n = 447,800) in the EU and 2.7 (n = 6840) in the 22 LP countries, with increases of 41% (EU) and 71% (LP) between 1989 and 1993. Among homo/bisexual men in the EU, prevalence appears to have stabilized since 1989 and AIDS incidence appears to be reaching a peak. Among all prevalent HIV infections in the EU, 42% were estimated to be among injecting drug users, 25% among homo-/bisexual men and 18% among persons infected heterosexually, compared with 29%, 35% and 19%, respectively, in the LP countries. Without allowing for the 1993 revision of the case definition, annual AIDS incidence is predicted to increase, between 1994 and 1998, by 24% in the EU and by 48% in the LP countries, with the largest percentage increases among heterosexually-infected persons. CONCLUSION: The overall HIV prevalence rate is estimated to have been about 70-fold lower in the LP countries than in the EU in the early 1990s, but to be increasing much more rapidly in the former. Moreover, recent reports of rapidly increasing HIV infection rates suggest that back-calculation may seriously underestimate the size of the epidemic in the LP countries. Implementation of effective preventive measures is urgent if large-scale epidemics are to be avoided in the presently LP countries of the European region.

The HIV epidemic associated with injecting drug use in Europe: geographic and time trends.

OBJECTIVES: To evaluate the magnitude and trends of the HIV epidemic associated with injecting drug use in Europe. METHODS: AIDS cases associated with injecting drug users (IDU) diagnosed through 1995 were analysed, including IDU, homo-/bisexual IDU, heterosexual partners of IDU and children whose mothers were IDU. HIV seroprevalence studies among IDU were reviewed. RESULTS: Of the 171,932 cumulative AIDS cases, 73,119 (43%) were IDU-associated (IDU, 89.0%; homo-/bisexual IDU, 3.5%: heterosexual partners of IDU, 6.2%; children with IDU mothers, 1.4%). Over 90% of IDU-associated cases were concentrated in south-western European countries with considerably higher rates in Spain (124 cases per million in 1995) than elsewhere (Italy, 68 per million; Portugal, 42 per million; France, 38 per million). During 1990-1995, incidence increased at an average annual rate of 11% overall and > 23% in central and eastern Europe; overall, incidence increased in older persons (12%) while decreasing in those aged 13-24 years (by 6%). HIV prevalence in IDU showed considerable geographic variation across and within countries. In several countries of western Europe, prevalence decreased. In the former Soviet Union, large HIV outbreaks have recently been detected among IDU through systematic HIV testing (e.g., in Ukraine, 6750 HIV infections were diagnosed in IDU tested during 1995-1996). CONCLUSIONS: IDU have played a major role in the spread of HIV in Europe. In several western European countries, the incidence of HIV acquired through drug use has declined following high rates in mid-1980s. Studies to assess current transmission are needed and prevention efforts must be maintained. In eastern Europe, emerging epidemics reinforce the urgency for prevention.

Time trends in HIV infection among pregnant women in Europe.

OBJECTIVE: To estimate time trends in HIV prevalence among pregnant women delivering livebirths in 14 European countries using a uniform methodology. METHODS: A form of back-projection was used to estimate HIV prevalence among pregnant women based on reported cases of AIDS due to perinatally acquired HIV infection. The method used estimates the rate of progression to AIDS in children with HIV, and the rate of transmission of HIV from mother to child, derived from published studies. RESULTS: The prevalence of HIV among pregnant women delivering livebirths was estimated to be highest in Spain (2.61 per 1000 livebirths in 1992-1993), relatively high (> or = 0.3 per 1000 livebirths) throughout the period 1984-1993 in France, Italy and Switzerland, and low (< 0.2 per 1000 livebirths) in Germany, The Netherlands and Scandinavia. There were large and statistically significant increasing trends in the estimated HIV prevalence among pregnant women in Portugal (an estimated 77% increase per 2-year period), Spain (40% increase) and the United Kingdom (77% increase; all P < 0.001). Statistically significant increasing trends of a smaller magnitude were estimated for France (24% increase) and Italy (23% increase; both P < 0.001). CONCLUSIONS: Sharp increases in HIV prevalence among pregnant women were estimated for several European countries, whereas in other countries no trends in the estimated prevalence were detected.

Trends in HIV infection among sexually transmitted disease patients in Paris.

OBJECTIVE: To assess trends in HIV infection among sexually transmitted disease (STD) patients. DESIGN: Repeated unlinked anonymous survey, 1991-1993. SETTING: STD clinics in Paris, France. SUBJECTS: Patients (n = 4354) with a new suspected STD. METHODS: HIV antibody testing, using blood from syphilis samples. RESULTS: HIV prevalences were stable over time in all transmission groups. One-third of homo-/bisexual men were HIV-positive. Prevalence was 2.5 times higher among heterosexual patients from Africa or the Caribbean than among those from other countries. Among patients under 25 years of age prevalence significantly decreased from 4.3% in 1991 to 0.8% in 1993 (P = 0.01). Among homo-/bisexual men, despite a 50% reduction in the incidence of STD, the absolute number of those newly HIV-infected remained stable; median age increased from 28 years in 1991 to 32 years in 1993 (P = 0.02). Among heterosexuals, trends in HIV incidence were difficult to assess: recently infected patients were more likely to be identified in 1993 than in 1991, since the proportion of patients who reported a recent HIV-negative test increased over time. CONCLUSION: Prevalence studies contribute to define specific subgroups which should be targeted for prevention (HIV-positive or older homosexuals, heterosexuals from Africa and the Caribbean). Despite a decrease in both overall STD incidence and HIV prevalence among patients aged under 25 years, overall HIV incidence has not decreased, at least among homo-/bisexual men in whom recent HIV infections occurred at a high rate overall, and increased in those aged 35 years or more. Sentinel site-based HIV seroprevalence studies are best interpreted in the light of results obtained from different populations and through routine surveillance of STD.

Pregnancy and contraception in a French cohort of HIV-infected women. SEROCO Study Group.

OBJECTIVE: To describe the impact of HIV diagnosis on contraception, incidence of pregnancy and live-births among HIV-infected women in France. DESIGN: Follow-up of women included in a French cohort of HIV-infected adults (SEROCO). METHODS: In 17 hospital-based units and one private practitioners' network in the Paris area and south-east region of France, 412 HIV-infected women (volunteers) were enrolled from 1988 to 1993, shortly after HIV diagnosis (median, 3 months), and followed for a median of 3 years. The main outcome measures were incidence and outcome of pregnancy, proportions of women sexually active and methods of contraception. RESULTS: The incidence of pregnancy decreased significantly from 20.4 per 100 person-years in the year preceding HIV diagnosis to 7.9 per 100 person-years after HIV diagnosis (P < 0.001), whereas the proportion of pregnancies voluntarily interrupted doubled (63 versus 29%). The proportion of women who were sexually inactive increased from 5% before HIV diagnosis to 20% thereafter. During followup, 80% of sexually active women were using contraceptive methods. CONCLUSIONS: The study supports an association between the discovery of HIV infection and a decrease in the proportion of women who are sexually active, a decrease in the incidence of pregnancy in general and live-births in particular, and an increase in the proportion of pregnancies voluntarily interrupted. Nevertheless, 24% of the women became pregnant and around 20% of sexually active women were not using any contraception. The high rate of voluntary abortion may indicate that many of these pregnancies were unplanned and could have been prevented.

HIV-1 diversity in France, 1996-1998. The AC 11 laboratory network.

OBJECTIVE: To study the distribution of HIV-1 subtypes in France and to describe the characteristics of patients infected with non-B subtypes. METHODS: All adults who tested HIV-1 positive on Western blot for the first time in one of the participating laboratories between September 1996 and March 1998 were eligible, whether or not they had been diagnosed previously elsewhere. Data on age, sex, country of birth, HIV-transmission group, dates of the last negative and first positive HIV test and clinical stage were collected. Serotyping was performed with a peptide subtype-specific enzyme immunoassay on each plasma sample and genotyping with heteroduplex mobility assay on each non-B serotype-infected patient. Patients characteristics were compared in B and non-B subtypes. RESULTS: Of the 2168 HIV-positive patients included by 32 laboratories, subtype,results were available for 2042. Among those, 73.4% were men, 12.2% born in sub-Saharan Africa, 41.5% infected through heterosexual contact and 67.6% in CDC stage A. Among the 2042 patients, 1 725 (84.5%) were infected with B subtype. Among the 317 non-B subtypes, subtype A was predominant (66.9%); all other subtypes (C, D, E, F, G, H, O) were present. Factors independently associated with a non-B subtype were to be included in the Paris area [adjusted odds ratio (aOR), 1.6; 95% confidence interval (CI), 1.1-2.3], to be born in sub-Saharan Africa (aOR, 26.0; 95% CI, 17.5-37.8) and to be infected through heterosexual contact (aOR, 4.2; 95% CI, 2.8-6.4). CONCLUSIONS: In France, although B subtype is still predominant, all non-B subtypes are now present. The diversity of HIV strains may affect diagnostic tests and clinical practice, especially viral load measurements. Moreover, the decreased susceptibility of non-B subtypes to antiretroviral drugs emphasizes the importance of surveillance of HIV diversity.

Sexually transmitted infections in European HIV-infected women: incidence in relation to time from infection. European Study on the Natural History of HIV Infection in Women.

OBJECTIVES: To investigate the prevalence and incidence of sexually transmitted infections (STI) in HIV-infected women in relation to time from infection and sexual behaviour. DESIGN: The European study on the natural history of HIV infection in women is a prospective cohort study of 487 HIV-infected women with a known interval of seroconversion from 12 European countries. METHODS: Incidence was measured with person-time methods. Generalized estimating equations analysis was used to determine risk factors for STI. RESULTS: At entry, 15% of the women were diagnosed with at least one acute STI (chlamydial infection, trichomoniasis or gonorrhoea), 10% with at least one other STI (genital warts or genital ulcerations) and 13% with vaginal candidiasis. Although frequently diagnosed during follow-up, the occurrence of acute STI and vaginal candidiasis decreased, whereas the occurrence of other STI increased with ongoing time from HIV infection. Furthermore, women with a history of prostitution [relative risk (RR), 2.00; 95% confidence interval (95% CI), 1.20-3.33] and women with irregular condom use (RR, 7.74; 95% CI, 3.52-17.0) were at higher risk for an acute STI. CONCLUSIONS: Although STI diagnoses were frequent, the occurrence of acute STI declined with time from infection which might be explained by changed sexual behaviour over time. The occurrence of other STI increased with time from HIV infection, presumably due to reactivation as a result of immunosuppression.

Determinants of delayed diagnosis of HIV infection in France, 1993-1995.

OBJECTIVE: To describe the circumstances of the first HIV-positive test and to study the determinants of a delayed diagnosis of HIV infection. METHODS: In a retrospective study among adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts, data on socioeconomic characteristics, circumstances of first HIV-positive test and attitudes and behaviours regarding medical care were collected in a confidential interview and analysed for potential association with a late test, defined as a first HIV-positive test within 6 months of AIDS diagnosis. RESULTS: Of the 359 AIDS patients studied, 69 (19.2%) had a late test. Late testers were more likely than other patients to have had an HIV-positive test because of clinical symptoms (89.7 versus 38.9%, P < 0.001) and not to perceive themselves as being at risk of infection with HIV (53.6 versus 39.3%, P < 0.05). The proportion of late testers was 34.6% among heterosexually infected patients, 12.7% among homo-/ bisexual men and 9.6% among injecting drug users. Factors independently associated with a late test were male gender [adjusted odds ratio (aOR), 5.6; 95% confidence interval (CI), 1.7-18.9] and absence of earned income (aOR, 5.2; 95% CI, 1.4-19) among heterosexually infected patients; high education (aOR, 3.1; 95% CI, 1.0-9.6) and having consulted a person practising alternative medicine (aOR, 3.4; 95% CI, 1.2-10) in homo-/bisexual men. CONCLUSIONS: Despite incentives to be tested for HIV, many individuals in France are still tested too late, even if they are in known high-risk groups. Efforts to test HIV-infected people as early as possible should be made by increasing the perception of HIV risk and decreasing the level of missed opportunities for testing. Current case management approaches make this recommendation critically important from both public health and an individual perspective.

Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women.

OBJECTIVES: To assess the impact of HIV-related immunodeficiency and antiretroviral treatment on the occurrence and evolution of abnormal Papanicolaou tests. STUDY DESIGN: Cohort of 485 HIV-infected women with a known date of infection, enrolled during May 1993-April 1998 in 23 centres (gynaecology, infectious disease or STD clinics, or drug treatment centres) in 12 European countries; in 21 centres, follow-up was performed every 6 months (median follow-up: 2 years). METHODS: Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. The prevalence of squamous intraepithelial lesions (SIL), the incidence of SIL and regression from low-grade SIL were studied according to CD4 count after controlling for HPV detection results. RESULTS: Compared with women with CD4 cell counts > 500 x 10(6)/l, women with CD4 cell counts < 200 x 10(6)/l had a twofold increase in both prevalence and incidence of SIL and in non-regression from untreated low-grade SIL; in addition, these women had a lower response rate to treatment of high-grade cervical intraepithelial neoplasia. The increase in SIL incidence associated with a low CD4 cell count was significant in women not receiving antiretroviral treatment (relative risk, CD4 cell count 200-499 x 10(6)/l, 1.9; CD4 cell count < 200 x 10(6)/l, 2.9; CD4 cell count > 500 x 10(6)/l, reference), whereas it was less marked and not statistically significant in treated women. CONCLUSIONS: Severe HIV-related immunodeficiency strongly increases the risk of occurrence of SIL; antiretroviral treatment may reduce this risk, probably by restoring or at least preserving immune function.

Comparative prevalence, incidence and short-term prognosis of cervical squamous intraepithelial lesions amongst HIV-positive and HIV-negative women.

OBJECTIVE: To investigate the impact of HIV infection on the prevalence, incidence and short-term prognosis of squamous intraepithelial lesions (SIL), in a prospective study with 1-year follow-up. METHODS: Between 1993 and 1995, 271 HIV-positive and 171 HIV-negative women at high risk of HIV infection were recruited, 365 (82.6%) of whom completed the 1-year follow-up. The women underwent a Papanicolaou smear test at inclusion and at 6 and 12 months. Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. RESULTS: The SIL prevalence ranged from 7.5% for HIV-negative to 31.3% for HIV-positive women with CD4 cell counts < 500 x 10(6)/l (P < 0.001). Other factors associated independently and significantly with SIL prevalence were HPV-16, 18, 33 and related types, HPV-31, -35, -39 and related types, lifetime number of partners, younger age, past history of SIL and lack of past cervical screening. The SIL incidence ranged from 4.9% in HIV-negative women to 27% in HIV-positive women with CD4 cells < 500 x 10(6)/l (P < 0.001). Progression from low- to high-grade SIL during follow-up was detected in 38.1% of HIV-positive women with CD4 cells < or = 500 x 10(6)/l but in no HIV-negative nor HIV-positive women with CD4 cells > 500 x 10(6)/l. HPV-16, 18, 33 and related types were also associated with higher incidence of SIL and progression from low- to high-grade SIL. CONCLUSION: HIV-induced immunodeficiency is associated with high prevalence, incidence and persistence/progression of SIL. A pejorative influence of HIV infection without marked immunodeficiency is less clear. HIV-positive women with SIL may thus benefit from early treatment when a useful immune response is still present.

Transfusion-associated AIDS cases in Europe: estimation of the incubation period distribution and prediction of future cases.

European data on transfusion-associated (TA) AIDS cases reported by December 31, 1989 have been analyzed using both parametric and nonparametric methods. Parametric estimates of the median incubation period of TA AIDS in adults vary from 6.5 to 11 years according to the type of distribution assumed (Weibull or gamma) and the latest year of diagnosis included (1987 or 1988). The latter finding may reflect a lengthening of the incubation period due to increasing treatment of HIV-infected patients prior to the development of AIDS. It is predicted that, by the end of 1991, between 2,000 and 3,000 cases of AIDS will have been diagnosed in Europe among adults infected by transfusion between 1978 and 1985 (when systematic screening of donated blood was introduced in most western countries). It is not possible, however, to predict how many further cases may arise among those transfused more recently in countries in which screening was introduced at a later date.

Social change and HIV in the former USSR: the making of a new epidemic.

This paper describes the development of the recent HIV epidemic in countries of the former Soviet Union. It explores the socio-political and economic roots of an injection-drug-driven HIV epidemic associated with a drug culture that facilitates HIV transmission. This review, based on many unpublished reports, studies and field notes, discusses the new social and health context in which the epidemic is developing. The evidence of a growing number of drug users in the region is discussed and drug injection behaviour described. The authors present selected data on the heterosexual transmission of HIV and linkages between the drug-linked HIV epidemic and its further spread into the non-injecting population. The potential overlap with the still uncontrolled syphilis epidemic that began in 1990 is probably a key factor in the future of HIV spread in the region. Until now, HIV infection among STD patients has been extremely low. However, rapid changes in sexual norms and behaviours, the growing commercial sex industry, and increased mobility soon may affect the current situation. The huge economic and socio-political crises currently affecting the region have created a "risk situation" for the spread of HIV. Concerns are raised about the appropriateness and the scope of government and non-governmental approaches to the exploding HIV and STD epidemics.

Prevalence of HIV-2 infection in Europe.

The HIV/AIDS pandemic is primarily caused by HIV-1. Another type of virus, HIV-2, is found mainly in certain West African countries In Europe, most of the cases of HIV-2 infection described have been in people from Africa. The objective of this study was

AIDS trends in Europe: decrease in the west, increase in the east.

In 1996, 24 920 AIDS cases were reported in the WHO European Region, bringing the cumulative total to 185 808 cases including 6969 (4%) paediatric cases (<13 years). For the first time since the start of the epidemic, the annual number of cases reported d