Genotype D4 Research Articles

Molecular epidemiology of hepatitis delta virus (HDV) in Iran: A preliminary report

To identify hepatitis delta virus (HDV) genetic variability and its circulating genotypes amongst infected Iranian patients, 25 patients with positive anti-HDV status from different parts of Iran were enrolled in this cross-sectional study. A portion of the HDV delta antigen was amplified, sequenced, and subjected to molecular and phylogenetic analysis. Clinical features and virological markers were evaluated. HDV RNA could be detected in 88% of anti-HDV positive cases (22 patients) with chronic hepatitis B virus (HBV) infection and liver cirrhosis. Phylogenetic analysis revealed that all Iranian patients were infected by genotype I (clade 1) of HDV, supported by a high bootstrap value (100%, 1,000 replicates). All HDV-positive patients were coinfected with genotype D1 of HBV. No significant association was determined between demographic, clinical, and virological variables in the population studied. In conclusion, the present molecular epidemiology survey reveals that clade 1 of HDV is predominant among coinfected HBV patients in Iran.

Clinical significance of precore and core promoter mutations in genotype D hepatitis B‐related chronic liver disease

The impact of mutations in the precore and basal core promoter (BCP) regions of the hepatitis B virus on the course of chronic liver disease is not well established. We sought to examine the relationship of these characteristics to the clinical expression of liver disease in patients infected with genotype D chronic hepatitis B (CHB). BCP and precore mutations in 110 patients with genotype D1 CHB were determined and correlated with clinical phenotype. Of 110 patients, 95 (86.5%) were HBeAg-negative. Compared with HBeAg-positive subjects, HBeAg-negative patients were over a decade older and had lower viral loads (3.70 +/- 0.98 vs 5.77 +/- 0.69 log copies/ml, P < 0.001). The double mutation A1762T-G1764A was more prevalent in patients with advanced liver disease (AdLD) and was associated with higher alanine aminotransferase and viral load. After adjusting for age, there was a more than fourfold increase in the risk of AdLD with this mutation (OR = 4.4; 95% CI: 1.13-16.92, P < 0.03). Conversely, the G1757A substitution was associated with protection, being 90% less frequent among patients with AdLD (P = 0.001). The results indicate that in genotype D CHB, the presence of the A1762T-G1764A mutation was associated with more aggressive liver disease while the G1757A substitution was associated with protection from advanced disease.

Cocirculation of genotypes D4 and D6 in Greece during the 2005 to 2006 measles epidemic

One of World Health Organization's proposed methods for the establishment of measles surveillance worldwide, to achieve the elimination of measles virus by 2010, is the genetic characterization of measles wild-type virus strains. In this study, 34 measles virus strains, isolated from clinical samples during the 2005 to 2006 measles outbreak in Greece, were genotyped and studied in terms of nucleotide variation and phylogeny. Interestingly, the cocirculation of 2 different genotypes, namely, D6 and D4, was revealed. In fact, the D4 genotype has never been previously reported in Greece. Finally, although the D4 Greek strains possessed identical nucleotide sequences, the D6 isolates segregated into 3 distinct subgroups, 2 of which differed genetically and phenotypically from all GenBank deposited measles sequences. It is, thus, important to continue the epidemiologic surveillance of measles in Greece to aid future studies of measles transmission, monitor the effectiveness of measles immunization, and eventually document the elimination of the virus in our country.

A set of reference sequences for the hepatitis C genotypes 4d, 4f, and 4k covering the full open reading frame.

Infection with genotype 4 of the Hepatitis C virus is common in Africa and the Mediterranean area, but has also been found at increasing frequencies in injection drug users in Europe and North America. Full length viral sequences to characterize viral diversity and structure have recently become available mostly for subtype 4a, and studies in Egypt and Saudi Arabia, where high proportions of subtype 4a infected patients exist, have begun to establish optimized treatment regimens. However knowledge about other subtype variants of genotype 4 present in less developed African states is lacking. In this study the full coding region from so far poorly characterized variants of HCV genotype 4 was amplified and sequenced using a long range PCR technique. Sequences were analyzed with respect to phylogenetic relationship, possible recombination and prominent sequence characteristics compared to other known HCV strains. We present for the first time two full-length sequences from the HCV genotype 4k, in addition to five strains from HCV genotypes 4d and 4f. Reference sequences for accurate HCV genotyping are required for optimized treatment, and a better knowledge of the global viral sequence diversity is needed to guide vaccines or new drugs effective in the world wide epidemic.

Increasing incidence of acute hepatitis C in individuals diagnosed with primary HIV in the United Kingdom

Hepatitis C virus (HCV) is increasingly identified in HIV-positive individuals [1,2]. In a recent study, high-risk sexual behaviour but not intravenous drug use was implicated in HCV acquisition in men who have sex with men (MSM) [3]. The acquisition of HCV in HIV-positive individuals is predominantly asymptomatic [1] and has a deleterious impact on morbidity [4,5]. UK guidelines recommend hepatitis C antibody screening at HIV diagnosis and subsequently according to risk, although risk is not defined [6]. This approach may delay the diagnosis of incident infection permitting unknowing transmission and missed opportunities for early intervention. Primary HIV-1 infection (PHI) is associated with high-risk sexual behaviour and a high frequency of concomitant sexually transmitted infections (STI) [7]. We hypothesized that those diagnosed with PHI may be particularly vulnerable to HCV acquisition. A total of 155 HIV-1-positive MSM (average age 30 years, range 22–77) identified with PHI (evidence of HIV acquisition within 6 months) were recruited at St Mary's Hospital, London, between1999 and 2006 [8]. Sexual behaviour histories and blood for alanine aminotransferase (ALT) and HCV serology were taken at 3-monthly intervals. Retrospective HCV-RNA polymerase chain reaction testing was carried out on stored serum to determine the approximate time of HCV acquisition. We found that 11 out of 155 of the men (7%) seroconverted to HCV within this period. The average age of those who acquired HCV was 36 years (range 32–46) (Table 1). The acquisition of HCV occurred year on year from 0/20 in 1999, 0/40 in 2000, 0/65 in 2001, 0/72 in 2002, 0/90 in 2003, 1/40 (2.5%) in 2004, 4/130 (3.1%) in 2005 and 6/155 (3.9%) in 2006.Table 1: Details of patients in study.The median time from PHI diagnosis to the detection of HCV antibody was 23 months (range 8–42); three HCV seroconversions occurred during the first year after PHI, four during the second, two in the third, one in the fourth and one in the fifth. Nine out of 11 individuals were identified with acute HCV after symptoms or having a raised ALT. Two individuals, with admitted high-risk sexual behaviour but normal ALT measurements, were identified by HCV serology. Retrospective sampling showed that all individuals were HCV-RNA negative at PHI, HCV RNA was detected before antibody detection in four cases and the HCV were of genotypes 1a (eight) and 4d (two). Seven out of 11 individuals had an increase in HIV RNA at HCV seroconversion. There was no association between the HIV-RNA increase and ALT at HCV diagnosis (P = 0.55). Six out of 11 individuals acquired an STI after PHI, which is significantly higher than in the whole PHI cohort (6/11 versus 26/155; P = 0.004). All acts of unprotected sex occurred with partners of unknown HCV status, whose HIV status was either HIV positive or unknown. All transmissions occurred within the United Kingdom. In the 3 months preceding HCV seroconversion, all denied intravenous drug use, 10 out of 11 had taken recreational drugs, eight reported fisting and four had shared sex toys with casual partners. Two individuals cleared HCV spontaneously, whereas nine out of 11 remained chronically infected and were offered a one-year course of pegylated interferon α and ribavirin. We show that individuals with PHI have higher rates of HCV acquisition than other HIV-positive cohorts [1,2], that HCV acquisition can occur soon after acquiring HIV, and that the incidence of HCV infection is increasing. Consistent with previous studies, the acquisition of HCV was associated with a rise in HIV RNA [9]. The higher incidence of STI acquisition in those acquiring HCV highlights the importance of safe sex counselling in HIV-positive individuals. Unprotected sexual contact has grave implications for both the ongoing HIV and the emerging HCV epidemics in MSM. This emphasizes the need for prevention efforts and HCV education among HIV-infected individuals, particularly those reporting high-risk sexual behaviour and recreational drug use. Although ‘HIV serosorting’ did play a role in the decision to have unprotected sex, serosorting for HCV did not. This study supports the enhanced surveillance of high-risk groups to identify new HCV cases to prevent the onward transmission of both HCV and HIV and to allow the opportunity for early treatment intervention to enhance HCV clearance rates [8–10]. We recommend the use of targeted sexual behaviour histories in conjunction with regular serum ALT and directed HCV testing. The latter may be particularly valuable to allow early detection in high-risk individuals. Conflicts of interest: None.

Measles cases in highly vaccinated population of Novosibirsk, Russia, 2000–2005

While the proportion of measles cases in vaccinees is expected to increase as vaccine coverage increases, such cases must be carefully investigated. The present study was conducted to examine possible contributions to vaccine failures (VFs) and to genetically characterize measles virus (MV) strains circulating in Novosibirsk, Russia during 2000-2005. Totally, 27 adult measles patients admitted to a regional hospital were prospectively enrolled in our study. Genetic characterization of the MV strains revealed circulation of genotypes A, D4 and D6 between 2000 and 2003 years; a genotype D6 MV was associated with the 2005 measles outbreak. Based on IgG avidity testing, half of the vaccinated patients demonstrated evidence of secondary vaccine failure (SVF). Patients, representing both levels of vaccine failure in our study were characterized by the lack of protective titers of neutralizing antibodies against circulating MVs, despite high IgG levels in many cases and high IgG avidity in SVF cases.

High genetic diversity of measles virus, World Health Organization European Region, 2005-2006.

During 2005-2006, nine measles virus (MV) genotypes were identified throughout the World Health Organization European Region. All major epidemics were associated with genotypes D4, D6, and B3. Other genotypes (B2, D5, D8, D9, G2, and H1) were only found in limited numbers of cases after importation from other continents. The genetic diversity of endemic D6 strains was low; genotypes C2 and D7, circulating in Europe until recent years, were no longer identified. The transmission chains of several indigenous MV strains may thus have been interrupted by enhanced vaccination. However, multiple importations from Africa and Asia and virus introduction into highly mobile and unvaccinated communities caused a massive spread of D4 and B3 strains throughout much of the region. Thus, despite the reduction of endemic MV circulation, importation of MV from other continents caused prolonged circulation and large outbreaks after their introduction into unvaccinated and highly mobile communities.

The dopamine D4 receptor polymorphism affects the canine fearfulness

The canine fearfulness is a behavioral trait known to have a genetic basis. This research analyzed genetic effects of the dopamine D4 receptor polymorphism on this behavior by postulating a mixed model of inheritance. Genotyping for the three different repeat polymorphism found in the third exon of the receptor gene was carried out for the population of the Korean native dogs. Four hundred fifty eight dogs with known pedigree were genotyped, and 264 individuals were tested for their fear responses to an experimenter, in which four different behavioral paradigms were adopted. Since the results assessed by principal factor analysis revealed a major factor explaining 69% of the total phenotypic variance, the subsequent analyses were conducted for this quantity. Analyses of the factor scores by estimating their posterior means indicated that there is a fixed effect exerted by the three different repeat polymorphism found in the D4 receptor as well as sex, in addition to unidentified polygenic effects. The phenotypic contribution of the D4 genotype was roughly estimated to be about 2%, which is a fraction of the total genetic effects responsible for more than 20% of the total phenotypic variance.

A wide range of NS3/4A protease catalytic efficiencies in HCV-infected individuals

The hepatitis C virus (HCV) NS3/4A protease acts as an antagonist of virus-induced interferon (IFN) regulatory factor (IRF)-3 activation and IFN-β expression. The NS3/4A protease performs this function by cleaving Cardif and TRIF proteins to block retinoic-acid-inducible gen I (RIG-I) and toll-like receptor (TLR)-3 signaling, respectively. NS3/4A protease inhibition can prevent Cardif and/or TRIF inactivation during HCV infection, thereby maintaining the innate immune response. Thus, differences in NS3/4A protease catalytic efficiency could be related to viral pathogenicity. In this study, we analyzed the catalytic efficiency of the most abundant NS3/4A protease isolated from each of 12 individuals infected with HCV genotypes 1b, 1a, 3a, 4a or 4d. A diversity of NS3/4A protease catalytic efficiencies (up to a six-fold difference) was found in the analyzed samples. The genotype 1b NS3/4A proteases displayed the highest catalytic efficiencies. However, within this genotype up to three-fold differences were observed. Cross-genotypic interactions between the NS3 protease domain and the NS4A cofactor peptide were also investigated. Overall, catalytic efficiencies of NS3 proteases cross-interacting with NS4A cofactors from heterologous genotypes were as efficient as the homologous NS3/4A interactions. Of the 28 heterologous interactions tested, only 6 resulted in deleterious or nonfunctional enzymes. Nonfunctional interactions were not genotype-specific, suggesting that enhancement of NS3 catalytic efficiency by the NS4A cofactor depends on a few specific amino acid residues. Characterization of the proteolytic activities of individual NS3/4A proteases should provide clues for understanding HCV-host interactions, as well as assisting in the development of new classes of NS3/4A protease inhibitors.

Large Measles Outbreak at a German Public School, 2006

In 2006, a large measles outbreak (n = 614) occurred in Duisburg city, Germany, with 54% of cases aged >9 years. An investigation was launched to determine reasons for the resurgence of measles, assess vaccination coverage and vaccine effectiveness (VE). A retrospective cohort-study was undertaken at a Duisburg public school affected early in the outbreak. We distributed questionnaires to all 1250 students aged 10-21 years and abstracted vaccination records. Cases were identified according to a standard clinical case definition. Questionnaires were returned by 1098 (88%) students. Vaccination records were abstracted from 859 students, of whom 820 (95.4%) had received at least one, 605 (70.4%) 2, and 39 (4.5%) no dose(s) of measles-containing vaccine (MCV). Coverage with 2 doses was higher in younger students. We identified 53 cases (attack rate = 5%). Measles-virus sequencing revealed genotype D6. After excluding students vaccinated in 2006 and those with a history of measles, the attack rate was 53% in unvaccinated students, 1.0% in students with one, and 0.4% in those with 2 MCV-doses. VE was 98.1% (95% CI: 92-100%) in students with one and 99.4% (95% CI: 97-100%) with 2 MCV-doses. Based on observed attack rates in vaccinated and unvaccinated students with vaccination records and in students without vaccination records, one-dose-coverage among all participating students was estimated at 91%. VE was high. Vaccination coverage was, however, insufficient to prevent the outbreak. Immunization gaps were found especially in older students. To prevent further outbreaks and to achieve the goal of measles elimination in Germany, vaccination coverage must be increased.

Molecular characterization of measles virus circulating in the Indian Ocean Islands during 2005–2006 and in France in 2006

Despite the availability of safe and immunogenic vaccines, measles still causes significant morbidity and mortality especially in Africa. In this study, two measles outbreaks in the Indian Ocean Islands; Mayotte in 2005-2006 and Seychelles in 2006 were studied. Nasopharyngeal swabs, urine and/or blood samples were collected from patients with clinically diagnosed measles. Measles viruses were isolated in four cases from patients in Mayotte. Measles strains circulating in both outbreaks were determined to be genotype D4 when compared to the WHO reference strains. During this time, measles virus was isolated from patients in France and they were also found to belong to the same genotype. The viruses clustered into two distinct D4 subgroups; The Indian Ocean strains were similar to the Montreal-subgroup, whereas the French strains associated with the Johannesburg-subgroup. The Indian Ocean strains formed a homogeneous group. They shared four specific amino acids in the 3' region of the N gene and two amino acids in the H gene, which differed from other genotype D4 viruses. This suggests that the same measles lineage circulated in Mayotte and Seychelles. Sequence comparison of the French isolates with other measles strains showed that they were more closely related to strains circulating in Germany in 2005, which had their origin in Romania. This study provides the baseline for molecular epidemiology of measles virus in Mayotte and Seychelles. The knowledge of circulating measles virus will help in documenting measles elimination program. This report also highlights the fact that progress of measles elimination is blighted continually by the phenomenon of measles importation.

The benefit of molecular characterization during a measles upsurge in Denmark

Molecular characterization of measles virus was part of the epidemiological investigation of 27 measles cases reported in Denmark in 2006. RT-PCR detected measles virus RNA from various types of clinical specimens in 24 cases. Virus genotypes were determined by sequencing the nucleocapsid (N) gene. Four different genotypes, B3, D4, D5 and D9 were identified including two variants of the D4 genotype. In combination with the epidemiological data four clusters of measles cases and three sporadic cases were revealed. Our study showed that measles in Denmark resulted from imported measles virus strains. The limited duration and short chain of transmission of the identified clusters ascertain that the interruption of measles virus circulation is being sustained. However, measles transmission still has a potential to occur. To minimise the development of pools of susceptible individuals high (>/=95%) routine vaccination coverage with two doses of measles-containing vaccine needs to be attained. Molecular epidemiological studies have proved to be both a useful and a necessary component of an enhanced surveillance system required in the measles elimination phase.

Genotyping of recent measles virus strains from Russia and Vietnam by nucleotide‐specific multiplex PCR

The nucleoprotein genes of 49 measles virus (MV) strains circulating in Russia between 2000 and 2006 and in Vietnam in 2003 were analyzed by genotype-specific PCR and the results were compared with their sequences. The sequences revealed the presence of genotypes H1 and H2 in the center (Nha Trang) and the north (Hanoi) of Vietnam, respectively. The relative diversity of the H2 strains suggested an endemic circulation of these viruses in the capital. In contrast genotype H1 strains from Nha Trang were homogenous genetically, which may indicate a recent importation. The strains obtained from 12 different regions of the Russian Federation were assigned to the genotypes H1, D4, and D6. Most strains (81.4%) were correctly genotyped by a multiplex PCR method which was sensitive to genotype-specific mutations [Kremer et al. (2004): J Clin Microbiol 42: 3017-3022]. Ambiguous or negative results for some clade H and genotype D6 strains were due to point mutations in the type-specific primer binding sites. After exchanging a single nucleotide in both the clade H- and the genotype D6-specific primers, all strains were assigned correctly to their genotype. A simplified procedure for use in Vietnam was developed to distinguish directly between genotypes H1 and H2 and any non-H genotype. These results demonstrate that our multiplex PCR method can be adapted easily to new sequence variants or specific epidemiological situations, and thus be very useful for rapid genotyping of large number of samples even in laboratories which do not have sequencing facilities.

Intra- and intergenotype characterization of D6 measles virus genotype

Determination of inter- and intragenotype stability and variability is the basic tools for the molecular epidemiology and evolutionary investigation of measles virus (MV). We made a comparison between complete genome sequences of four MVs (two wt MV strains—WA.USA/17.98 and 97-45881 , and two SSPE MV strains—MVs/Zagreb.CRO/47.02/and MVs/Zagreb.CRO/08.03/), all belonging to genotype D6. Results of analyses clearly confirm that MV genome continuously changes within the viruses of the same or different genotypes by accumulation of mutations in different parts of the genome. Only a small number of these accumulated mutations induce amino acid substitutions and thus possibly introduce new biological characteristics or a new genotype over a long time period. This study clearly reveals a long untranslated region between M and F genes as the most variable region of the MV genome and detects the presence of unique residues on the level of the entire genome as a new important parameter in the investigation of molecular evolution of MVs.

Implications of a 2005 Measles Outbreak in Indiana for Sustained Elimination of Measles in the United States

Measles was declared eliminated from the United States in 2000 but remains endemic worldwide. In 2005, a 17-year-old unvaccinated girl who was incubating measles returned from Romania, creating the largest documented outbreak of measles in the United States since 1996. We conducted a case-series investigation, molecular typing of viral isolates, surveys of rates of vaccination coverage, interviews regarding attitudes toward vaccination, and cost surveys. Approximately 500 persons attended a gathering with the index patient one day after her return home. Approximately 50 lacked evidence of measles immunity, of whom 16 (32 percent) acquired measles at the gathering. During the six weeks after the gathering, a total of 34 cases of measles were confirmed. Of the patients with confirmed measles, 94 percent were unvaccinated, 88 percent were less than 20 years of age, and 9 percent were hospitalized. Of the 28 patients who were 5 to 19 years of age, 71 percent were home-schooled. Vaccine failure occurred in two persons. The virus strain was genotype D4, which is endemic in Romania. Although containment measures began after 20 persons were already infectious, measles remained confined mostly to children whose parents had refused to have them vaccinated, primarily out of concern for adverse events from the vaccine. Seventy-one percent of patients were from four households. Levels of measles-vaccination coverage in Indiana were 92 percent for preschoolers and 98 percent for sixth graders. Estimated costs of containing the disease were at least 167,685 dollars, including 113,647 dollars at a hospital with an infected employee. This outbreak was caused by the importation of measles into a population of children whose parents had refused to have them vaccinated because of safety concerns about the vaccine. High vaccination levels in the surrounding community and low rates of vaccine failure averted an epidemic. Maintenance of high rates of vaccination coverage, including improved strategies of communication with persons who refuse vaccination, is necessary to prevent future outbreaks and sustain the elimination of measles in the United States.

Characterization of full‐length hepatitis C virus genotype 4 sequences

Over 85% of the world's nearly 170 million hepatitis C virus (HCV)-infected subjects exist in regions of Africa, Southeast Asia and Middle Eastern countries where genotypes 4-6 are very common. In particular, HCV genotype 4 is highly prevalent in Egypt with more than 19% of the population infected and chronic HCV representing one of the top five leading causes of death, due in part to ineffective interferon alpha treatment against this genotype. Despite this, very little work has been carried out to characterize the sequence diversity of genotype 4, which will be critical to the development of effective vaccines and antiviral therapies against this genotype. As a result of the paucity of sequence data available for HCV genotype 4, for which only one full genome sequence is currently available, we were interested in characterizing additional genotype 4 sequences and to provide reagents for amplification of this genotype. Here we describe seven unique HCV genotype 4a full genomes, in addition to a single genotype 4d genome, and characterize their sequence diversity in relation to other more closely characterized HCV genotypes.

Prevalent HBV genotypes and subtypes in a South Indian population

Background Genotypes or genetic subtypes describe genetically related strains and have been described for viruses belonging to several different families. The eight major genotypes of hepatitis B virus (HBV) have distinct geographic distribution. Recent studies suggest possible pathogenic and therapeutic differences among HBV genotypes. Objectives To evaluate the HBV genotypes of 85 samples by RFLP analysis and sequence the desired region to look for variations and identify the subtypes of the surface region. Study design We studied 85 patients with HBV in order to identify the most prevalent genotype and subtype. Patients with HBV-related liver disease attending the Department of Gastroenterology at Owaisi Hospital and Research Centre were studied. Results and conclusions Genotype D1 was most prevalent. Genotyping was carried out by RFLP analysis and confirmed by sequencing. Nucleotide sequences showed significant homology (96–97%) with the other genotypes that have been reported. Subtype ayw was the most prevalent subtype within the surface region. Construction of a phylogenetic tree incorporating these isolates and other published HBV sequences showed that the isolates are derived from the same evolutionary tree. The study adds to our understanding of the genetic diversity of HBV and the geographical distribution of its subtypes, and will be useful for reconstructing the evolutionary history of HBV.

Full‐Length Sequence Analysis of Subacute Sclerosing Panencephalitis (SSPE) Virus, a Mutant of Measles Virus, Isolated from Brain Tissues of a Patient Shortly after Onset of SSPE

Subacute sclerosing panencephalitis (SSPE) virus, a measles virus (MeV) mutant, was isolated from brain tissues of a patient shortly after the clinical onset, and the entire viral genome was sequenced. The virus, named SSPE-Kobe-1, formed syncytia on B95a and Vero/SLAM cells without producing cell-free infectious virus particles, which is characteristic of SSPE virus. Phylogenetic analysis classified SSPE-Kobe-1 into genotype D3. When compared with an MeV field isolate of the same genotype (Ich-B strain), SSPE-Kobe-1 exhibited mutation rates of 0.8-1.6% at the nucleotide level in each of the proteincoding regions of the viral genome. It is noteworthy that the mutation rate of the M gene (1.2%) of SSPE-Kobe-1 was considerably lower than for other SSPE virus strains reported so far, but that the majority of the mutations (75%) were the uridine-to-cytidine biased hypermutation characteristic of the SSPE virus M gene. At the amino acid level, the viral proteins, such as N, P, C, V, M, F, H and L proteins, had point-mutations on 3, 7, 1, 4, 3, 9, 8 and 14 residues, respectively, compared with the Ich-B strain. In addition, the F and H proteins had mutated C-termini due to single-point mutations near or at the stop codons. Two of the three mutations in the M protein were Leu-to-Pro mutations, which are likely to affect the conformation and, therefore, the function of the protein. Because of the relatively small number of mutations, SSPE-Kobe-1 would be a useful tool to study genetic evolution of SSPE virus.

Two outbreaks of measles in Germany 2005

Measles re-emerged in some counties in Germany in 2005, despite increasing vaccination coverage rates in children at school entry in recent years, which had led to decreasing incidence (with the lowest incidence ever recorded, 0.2 cases per 100,000 inhabitants in 2004). Regional outbreaks have been detected by the mandatory reporting system in the states of Hesse and Bavaria. Although both outbreaks led to similar incidences in the affected areas (14 and 12 cases respectively per 100,000 inhabitants) they differed in age distribution, transmission patterns and measles virus genotype. In Hesse, 223 cases were submitted, from which 160 belonged to 41 clusters mainly defined by ,000). Results of measles virus diagnosis showed genotype D4 and identical nucleotide sequences for all analysed cases from Hesse. In Bavaria, 279 cases were submitted, most of which had occurred in schools and preschool facilities. Age-specific attack rate was highest in children aged between 5-9 years (129 per 100,000). Laboratory diagnosed viruses were identified as genotype D6 and were identical at the nucleotide level. In both outbreaks the vast majority of cases (95% in Hesse and 98% in Bavaria) were in unvaccinated children, but vaccination coverage differed in the affected areas and was slightly lower in Bavaria than in Hesse. Local accumulation of unvaccinated children and their concentration in schools and kindergarten preceded the outbreak in Bavaria. Despite high average vaccination coverage levels, local variations may lead to regionally limited outbreaks.

Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy

Recent studies have suggested an increased risk of acute hepatitis C (HCV) infection in homosexual HIV-infected men and that early treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution in HIV-infected patients. A retrospective analysis of 12 HIV-infected patients who were consecutively diagnosed as developing acute HCV infection, defined by both seroconversion of anti-HCV antibodies and detection of serum HCV RNA in those with previous negative results. Ten of these patients received early antiviral treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin. The only risk factor in these patients was unprotected sexual intercourse with men. Acute HCV infection was asymptomatic in 10 patients, and the HCV genotype was 4d in 10 patients. The 10 genotype 4d viruses formed a monophylogenetic group and clustered separately from other local sequences of HCV genotype 4d, suggesting a common source of infection. None of the 10 patients who were treated early with antiviral therapy had a sustained virological response, as defined by undetectable HCV RNA 6 months after therapy. There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men; the cluster of HCV genotype 4d suggested a common source of infection and a failure in prevention counselling. Early treatment with standard interferon-alfa failed to prevent chronic evolution of HCV infection in this particular group of HIV-infected patients who had acquired this peculiar cluster of genotype 4 strains.