Scandinavian journal of infectious diseases. Supplementum最新文献

In addition to cancer of the lower female genital tract, human papillomaviruses (HPV) are associated with a large number of benign, precancer and cancer lesions at different anatomic sites in both genders. Malignant tumours and their precursors are usually attributed to the oncogenic (high-risk, HR) HPV types, whereas benign lesions (papillomas) are associated with the low-risk (LR) HPV types, most notably with HPV6 and HPV11. Until recently, the main interest in HPV research has been focused on HR-HPV types and their associated pathology, and much less attention has been paid to the lesions caused by the LR-HPV types. With the recent licensing of an effective prophylactic vaccine against the 2 most important LR-HPV types (HPV6 and HPV11), it has become timely to make a systematic survey on the annual disease burden due to these 2 HPV genotypes in our country. These types of data should form the foundation for all calculations of the annual costs needed to treat these diseases by conventional means. Accurate estimates of disease burden are also mandatory for all modelling of the cost-effectiveness of prophylactic HPV6 and HPV11 vaccines. If proven useful for any of these purposes, this document will have fulfilled its purpose. In the first step, published HPV literature was used to create a list of benign, premalignant and malignant lesions associated with this virus at different anatomic sites. GLOBOCAN 2004 (IARC) database was used to derive the global numbers of incident cases for each of these malignancies in 2002, and the Finnish Cancer Registry (FCR) website for obtaining these (y 2005) numbers in Finland. The evidence linking HPV to each individual tumour category was classified as: 1) established, 2) emerging, and 3) controversial. All published evidence was weighted for each individual malignant, premalignant and benign lesion, anatomic region by region, while assessing the attributable fraction of HPV6/11 genotypes in each lesion. Because benign and most of the precancer lesions are not registered by FCR or GLOBOCAN, different approaches had to be used to derive the best estimates for their incidence, based on published literature or other registries (e.g. genital wart registry of the UK and Wales, and mass screening registry of FCR). With a lack of reasonable consensus, a lower and an upper limit was set for the range of estimates. In cases with different age-specific incidence (e.g. genital warts), the population pyramid of Finland was used to calculate the incident cases. Where well established, the different incidence rates among males and females were used to calculate the numbers of incident cases by gender. The malignant neoplasms with established or emerging evidence on the causal role of HPV are listed by their ICD-10 codes in Table I. Included in this list are also 2 controversial malignancies (colorectal cancer and endometrial cancer), of which the contradictory HPV data are critically discussed. The third major cancer

Apart from cancers of the lower female genital tract, human papillomaviruses (HPV) are associated with a large number of benign, premalignant and malignant lesions at different anatomic sites in both genders. Malignant tumours and their precursors are usually attributed to the oncogenic (high-risk, HR) HPV types, whereas benign lesions (mostly papillomas) are ascribed to the low-risk (LR) HPV types, most notably HPV6 and HPV11. To date, the main interest has been focused on HR-HPV types and their associated pathology, and much less attention has been paid to the lesions caused by the LR-HPV types. The recent licensing of an effective prophylactic vaccine against the 2 most important LR-HPV types (HPV6 and HPV11) has resulted in considerably increased interest in these LR-HPV types as well. This author recently conducted a systematic survey of the annual disease burden due to HPV6/11 infections in Finland. As a rational continuation, the present survey was conducted to estimate the annual disease burden due to HPV16 and HPV18 infections in our country. Together, these 2 documents form the foundation for calculations of the annual costs needed to treat the diseases caused by these 2 most common LR and HR HPV types. Similar to HPV6/11, accurate estimates of disease burden are also mandatory for all modelling of the cost-effectiveness of prophylactic HPV16/18 vaccines. In the first step, the published HPV literature was used to create a list of benign, premalignant and malignant lesions associated with this virus at different anatomic sites. The GLOBOCAN 2004 (IARC; International Agency for Research on Cancer) database was used to derive the global numbers of incident cases for each of these malignancies in 2002, and the Finnish Cancer Registry (FCR) website was used to obtain these numbers for Finland (y 2005). The evidence linking HPV to each individual tumour category was classified as: (1) established, (2) emerging, and (3) controversial. All published evidence was weighted for each individual malignant, premalignant and benign lesion, anatomic region-by-region, while assessing the attributable fraction of HPV16/18 genotypes in each lesion. Because benign and most of the precancer lesions are not registered by the FCR or GLOBOCAN, different approaches had to be used to derive the estimates for their incidence, based on published literature or other registries. In cases with no reasonable consensus, a lower and an upper boundary was set for the range of these estimates. Where well established, the different incidence rates among males and females were used to calculate the numbers of incident cases by gender. The present survey implicates that a minimum of 7859 to 8316 new cases of HPV16- or HPV18-associated clinical lesions would be detected each y in Finland, if all were registered. In other words, these numbers represent the annual disease burden due to these 2 most common HR-HPV genotypes. In the Finnish population, these lower and upper

Transmitted human immunodeficiency virus (HIV) resistance to antiretrovirals (i.e. resistance in antiretroviral naive patients) emerged during the 1990s as a potentially relevant public health problem. HIV variants resistant to all classes of approved antiretroviral agents have been identified in significant proportions antiretroviral naive patients, and this phenomenon appears as a potential threat to the effectiveness of highly active antiretroviral therapy. Available data from surveys conducted between 1996 and 2001 show the prevalence of drug resistance among newly HIV-infected individuals to range from 3%, to above 20% in North America, and from 5% to 15% in Europe. Increases in prevalence observed during the late 1990s in some studies are not confirmed by most recent data. Transmission of multidrug resistance still appears to be an uncommon occurrence. However, methodological heterogeneity and problems in study design make it difficult to compare results between different surveys and to draw firm conclusions from the results. There is a clear need to improve surveillance systems aimed at identifying patients at the time of primary infection and to standardize laboratory methods for the identification of genetic markers of resistance to be used for epidemiological purposes.

Single withess: Drug resistance is one of the main factors limiting the success of antiretroviral therapy. Some other factors, such as individual enzymatic pattern and immune system function, play a role in the outcome of therapy in HIV infection. Moreover, adherence to treatment could also be a pivotal factor. Thus, there is a complex network that influences patients' response and ultimately contributes to the development of drug resistance. A particular situation among HIV-infected individuals is the finding of a 'discordant' response, which means a virological failure with the maintenance of an optimal immune function. In these subjects, the mere determination of the genotypic pattern of drug resistance is not necessary. Rather, the quantification of phenotypic drug resistance together with the measurement of viral fitness and/or CD4+ T-cell dynamics will help in defining further therapeutic strategies.

Single witness: The current development of guidelines for antiretroviral therapy in resource-limited settings raised the issues of the possible use of drug resistance testing (DRT) in middle- and low-income countries, especially in the context of prevention of mother-to-child transmission (MTCT) programmes. Although resource limitation make it clear that DRT cannot be recommended as an essential part of clinical management of HIV-infected pregnant women in Africa, it is important to monitor the prevalence and incidence of drug resistance on a population basis as ART is scaled up worldwide and programmes for the prevention of MTCT will be implemented. Moreover, even in low-resource countries there are some special settings where DRT may be available for patient care and its use may be considered.

This article describes the major changes in the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) epidemic in Italy, using data from the National AIDS Registry and from 5 local surveillance systems for new HIV diagnoses. From 1982 to 2001, 49,063 adults with AIDS were reported to the AIDS Registry. From 1988 to 2000, the 5 local systems reported 23,252 new HIV diagnoses. The AIDS incidence increased until 1995, followed by a progressive decrease. A decrease was also observed for the incidence of new HIV diagnoses after 1989, with an apparent stabilization after 1998. Most AIDS cases have been represented by intravenous drug users (IDU), yet since 1999 the percentage of cases attributable to sexual transmission has exceeded that for IDUs. Similarly, among new HIV diagnoses, the percentage of cases attributable to sexual transmission increased from 23.6% before 1993 to 58.5% in 2000. The percentage of people with AIDS who discovered their seropositivity no earlier than 6 months before AIDS diagnosis increased from 20.6% in 1996 to 48.8% in 2001. Although the incidence of both AIDS and new HIV diagnoses has declined, a possible resurgence of the epidemic cannot be ruled out, in light of various factors that could lead to an increasing number of living infected people.

Resistance is the inherent capacity of a living being to resist untoward circumstances (disease, malnutrition or toxic agents). Resistance has developed to nearly all specific and effective antiviral agents, including all drugs against human immunodeficiency virus (HIV). Resistance develops rapidly when viral replication is not maximally suppressed. Drug-resistant viruses may be transmitted at the moment of primary infection. Assays to measure drug resistance are available in specialized laboratories and warnings are related to possible expanded use of these assays in the absence of randomized studies with prolonged clinical endpoints. Randomized clinical trials to allow general recommendations for the use of resistance assays in clinical practice are still urgently required.

The tropism of human immunodeficiency virus type 1 (HIV-1) for the central nervous system (CNS) develops early during the course of the infection. Potent antiretroviral therapy has been demonstrated to be effective in controlling the replication of HIV-1 in cerebrospinal fluid (CSF), even though a variable response in this compartment compared with that in plasma has been observed. Different concentrations of antiretroviral drugs are found in CSF and the use of antiretroviral drugs penetrating across the blood-brain barrier is considered to be required for controlling CNS infection in advanced patients, particularly in those with neurological disorders. The compartmentalization of HIV-1 infection in the CNS may affect the treatment response, which may cause a different evolution of viral drug resistance in the 2 compartments. Although HIV-1 resistance testing in CSF is not recommended for the routine management of patients with virological failure, treatment decisions in patients with neurological disorders may require knowledge of the resistance profile of the virus in the CSF.