Jan T. M. van der Meer

Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission

We retrospectively screened 1836 men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (1984-2003) for hepatitis C virus (HCV) antibodies. HCV incidence was 0.18/100 person-years (PY) in human immunodeficiency virus (HIV)-positive MSM (8/4408 PY [95% confidence interval {CI}, 0.08-0.36]) but was 0/100 PY in MSM without HIV (0/7807 PY [95% CI, 0.00-0.05]). After 2000, HCV incidence among HIV-positive men increased 10-fold to 0.87/100 PY (5/572 PY [95% CI, 0.28-2.03]). Additional hospital cases (n=34) showed that MSM in Amsterdam who acquired HCV infection after 2000 reported high rates of ulcerative sexually transmitted infections (59%) and rough sexual techniques (56%), denied injection drug use, and were infected mainly with the difficult-to-treat HCV genotypes 1 (56%) and 4 (36%). Phylogenetic analysis showed 3 monophyletic clusters of MSM-specific HCV strains. The emergence of an MSM-specific transmission network suggests that HIV-positive MSM with high-risk sexual behaviors are at risk for sexually acquired HCV. Targeted prevention and routine HCV screening among HIV-positive MSM is needed to deter the spread of HCV.

Epidemiology of Bacterial Endocarditis in the Netherlands: II. Antecedent Procedures and Use of Prophylaxis

BACKGROUND The reported frequency with which endocarditis is ascribed to an antecedent dental or medical procedure varies from 3% to 62%. METHODS We performed a nationwide prospective study of the epidemiology of bacterial endocarditis in the Netherlands. During a 2-year period, all consecutively hospitalized patients suspected of having endocarditis were visited while still hospitalized for a review of the medical record and an in-person interview that focused on antecedent procedures and administered prophylaxis. All information was checked with pharmacists and dental and medical practitioners. RESULTS Of 427 patients with late prosthetic or native valve endocarditis, 275 were eligible for antibiotic prophylaxis because of a previously known cardiac lesion (n = 197) or a prosthetic valve (n = 78). Of these 275 patients, 64 (23.3%) had undergone a procedure with an indication for prophylaxis within 180 days of onset; in 31 (11.3%) the procedures had been within 30 days of onset. Antibiotic prophylaxis had been administered to 17 (26.6%) of the 64 patients and to eight (25.8%) of the 31 patients. CONCLUSION The results indicate that medical and dental procedures cause only a small fraction of endocarditis. The majority of patients develop the disease along other routes. For an incubation period of 180 days, full compliance with prophylaxis might have prevented endocarditis in 47 (17.1%) of 275 patients with late prosthetic or native valve endocarditis involving a previously known cardiac lesion who underwent a procedure with an indication for prophylaxis. For an incubation period of 30 days, prophylaxis might have prevented endocarditis in 23 (8.4%) of these 275 patients, or 5.3% of all patients with endocarditis (n = 427).

Current features of infective endocarditis in elderly patients: Results of the international collaboration on endocarditis prospective cohort study

BACKGROUND Elderly patients are emerging as a population at high risk for infective endocarditis (IE). However, adequately sized prospective studies on the features of IE in elderly patients are lacking. METHODS In this multinational, prospective, observational cohort study within the International Collaboration on Endocarditis, 2759 consecutive patients were enrolled from June 15, 2000, to December 1, 2005; 1056 patients with IE 65 years or older were compared with 1703 patients younger than 65 years. Risk factors, predisposing conditions, origin, clinical features, course, and outcome of IE were comprehensively analyzed. RESULTS Elderly patients reported more frequently a hospitalization or an invasive procedure before IE onset. Diabetes mellitus and genitourinary and gastrointestinal cancer were the major predisposing conditions. Blood culture yield was higher among elderly patients with IE. The leading causative organism was Staphylococcus aureus, with a higher rate of methicillin resistance. Streptococcus bovis and enterococci were also significantly more prevalent. The clinical presentation of elderly patients with IE was remarkable for lower rates of embolism, immune-mediated phenomena, or septic complications. At both echocardiography and surgery, fewer vegetations and more abscesses were found, and the gain in the diagnostic yield of transesophageal echocardiography was significantly larger. Significantly fewer elderly patients underwent cardiac surgery (38.9% vs 53.5%; P < .001). Elderly patients with IE showed a higher rate of in-hospital death (24.9% vs 12.8%; P < .001), and age older than 65 years was an independent predictor of mortality. CONCLUSIONS In this large prospective study, increasing age emerges as a major determinant of the clinical characteristics of IE. Lower rates of surgical treatment and high mortality are the most prominent features of elderly patients with IE. Efforts should be made to prevent health care-associated acquisition and improve outcomes in this major subgroup of patients with IE.

Alarming incidence of hepatitis C virus re-infection after treatment of sexually acquired acute hepatitis C virus infection in HIV-infected MSM

Background:Recent data indicate that seroprevalence of sexually transmitted hepatitis C virus (HCV) infection among MSM is stabilizing in Amsterdam. However, little is known about the incidence of HCV re-infection in MSM who have cleared their HCV infection. We, therefore, studied the incidence of re-infection in HIV-infected MSM who were HCV RNA-negative following HCV treatment of acute primary infection. Methods:Our study population comprised HIV-infected MSM at two large HIV outpatient clinics in Amsterdam, who were previously diagnosed with a sexually transmitted acute HCV infection and tested HCV RNA-negative at the end of treatment. We defined HCV re-infection as detectable HCV RNA in individuals with an undetectable HCV RNA at the end of treatment accompanied by a switch in HCV genotype or clade. Person–time methods were used to calculate the incidence of re-infection. Results:Fifty-six persons who became HCV RNA-negative during primary acute HCV treatment were included. Five of the 56 cases relapsed and were not analysed. Eleven persons were re-infected. The incidence of HCV re-infection in this group was 15.2 per 100 person-years (95% confidence interval 8.0–26.5). The cumulative incidence was 33% within 2 years. Discussion:An alarmingly high incidence of HCV re-infection was found in this group. This high re-infection rate indicates that current prevention measures should be discussed, frequent HCV RNA testing should be continued after successful treatment and, in case of possible relapse, clade typing should be performed to exclude re-infection.

Herpes zoster, immunological deterioration and disease progression in HIV-1 infection.

ObjectiveTo study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. Design and methodsA total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model. ResultsThe incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1-seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositivesthe incidence was 31.2 per 1000 PY at CD4+ cells ≥; 500 × 106/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (Cl), 0.78–2.94] at CD4+ cells 200–499 × 106/l and 97.5 per 1000 PY (RR, 3.13; 95%Cl, 1.54–6.32) at CD4+ cells < 200 × 106/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T-cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% Cl, 1.1–2.4) and for death 1.7 (95% Cl, 1.1–2.5), but these were not independent from CD4+ cell counts. ConclusionIn HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression.

Summary of the international consensus symposium on advances in the diagnosis, treatment and prophylaxis of cytomegalovirus infection

CMV infection and CMV disease can be difficult to differentiate and the diagnosis is usually based on a compatible clinical picture and the results of a diagnostic test for CMV. The only exception to this rule is in HIV-infected patients where fundoscopy is sufficient to diagnose CMV retinitis. Of the current diagnostic tests, qualitative and quantitative PCR, branched DNA and Hybrid Capture, are the most promising. The pp65 antigenemia assay has the disadvantage of being more labor-intensive than the DNA based tests. Preliminary data show that a positive qualitative PCR in a HIV-infected patient has a predictive value for the development of CMV retinitis. However, of the patients positive by qualitative PCR, those with high viral loads in quantitative PCR were at the greatest risk of CMV disease. This might make it possible to identify with great certainty the patients who will go on to develop CMV retinitis, thereby decreasing the number of patients eligible for preemptive or prophylactic therapy and increasing the cost-benefit of this therapeutic measure. Quantitative test might also be useful in monitoring response to therapy, but randomized trials comparing the test are needed. Prophylactic antiviral agents should not be used in seronegative transplant recipients receiving organs from seronegative donors. In high-risk transplant recipients, ganciclovir should be used. CMV vaccines are useful for the protection of babies from CMV seronegative mothers against congenital CMV disease. It also may be useful in seronegative transplant recipients receiving a seropositive donor organ, although the benefit of chemo prophylaxis may surpass that of vaccine. HIV-infected patients with CMV retinitis who relapse under either ganciclovir or foscarnet benefit from subsequent combination therapy, rather than switching to the other drug. However, the cost is high in terms of quality of life. Intravitreal therapy for CMV retinitis is very efficacious, suggesting that drug delivery is a problem in systemic therapy. However, intravitreal therapy does not protect against the development of CMV retinitis in the contralateral eye or from CMV disease elsewhere. Therefore, systemic therapy should be added. CMV disease of the CNS should be diagnosed early and treated agressively, possible with combination therapy. A diagnosis of CMV disease should be based on a compatible clinical picture and the demonstration of CMV in CSF by DNA or antigen assays which are more sensitive than culture.

High Incidence of Asymptomatic Syphilis in Hiv-infected Msm Justifies Routine Screening

Background: Recently, the incidence of syphilis has risen, mainly among men having sex with men (MSM), many of whom are coinfected with HIV. Current guidelines recommend at least yearly syphilis testing in this group. In this study, we assessed the yield of routine syphilis screening in outpatient HIV-patients. Methods: From March through June 2003, syphilis serology was routinely performed in HIV-infected patients visiting our outpatient clinic. Serology was repeated six months later. Positive test results of the first episode were compared to historical test results (retrospective analysis). Test results of the second episode were compared to test results from the first episode (prospective analysis). Case records of all patients with a new infection were reviewed for symptomatic disease or testing because of syphilis contacts, versus asymptomatic disease. Results: In the retrospective analysis, 1,105 patients were included. In 68 patients, 81 syphilis infections were identified, of which 33% asymptomatic. 77/81 infections were acquired between 2000 and 2003, resulting in a total incidence of 2.7/100 person years (PY) of follow-up, and 0.9/100 PY for asymptomatic disease. In MSM, the incidence rate was 4.6/100 and 1.5/100 PY respectively. In the prospective analysis, 1,010 patients were included. Seventeen patients, all MSM, had a new or recurrent syphilis infection, of whom 4 asymptomatic, accounting for a total event rate of 3.5/100 PY. In MSM, the event rate was 6.2/100 PY, with an incidence of asymptomatic disease of 1.4/100 PY. Conclusion: Routine screening for syphilis identifies significant numbers of asymptomatic syphilis infection in HIV-infected MSM.

Complications of varicella zoster virus reactivation in HIV-infected homosexual men.

ObjectTo study the complication rate of varicella zoster virus (VZV) reactivation and the relationship between complications, presentation and localization of zoster and immune function in HIV disease. Design and methodsA total of 142 episodes of VZV reactivation in 113 out of 544 HIV-1-infected participants in the Amsterdam Cohort Study of homosexual men were studied. Persistent hyperkeratotic or necrotic skin lesions, post-herpetic neuralgia, other neurological events, ocular events and pneumonitis occurring within 6 months of the onset of the last episode of VZV reactivation were defined as complications, provided that other possible diagnoses were excluded and the event had been previously described in the literature as related to VZV reactivation. ResultsTwenty-four complications occurred in 15(11%) of these 142 episodes. Complications occurred exclusively in the 40 episodes with either multidermatomal or disseminated presentation, or a trigeminal localization, or both. In the group of episodes of unidermatomal zoster at a non-trigeminal localization no complications occurred. Twenty-one episodes of herpes zoster were localized in the trigeminal area. Localization was not significantly associated with the level of immune function. Compared to unidermatomal presentation (n = 120), multidermatomal (n = 15) and disseminated presentation (n = 7) occurred at lower median CD4+ cell counts (330, 240 and 50×106/l, respectively; P= 0.003) and significantly lower levels of CD3 monoclonal antibodies or phytohaemagglutinin-inducecl T-cell reactivity in vitro. Complications were related to CD4+ cell counts, but in the cases of disseminated, multidermatomal or trigeminal zoster a CD4+ cell measurement provided no additional information on the risk of complications. ConclusionIn HIV-infected individuals the extent of the clinical presentation and the occurrence of complications of VZV reactivation are related to the degree of immunodeficiency. In episodes of VZV reactivation with either multidermatomal or disseminated presentation or a trigeminal localization, or both the complication rate was high. CD4+ cell counts provided no additional information on the complication risk. Oral acyclovir appears to be sufficient as therapy for unidermatomal zoster at a non-trigeminal localization.

Treatment of acute hepatitis C virus infection in HIV-infected MSM: the effect of treatment duration

We evaluated hepatitis C virus (HCV) treatment and the effect of treatment duration (24 versus 48 weeks) on treatment outcome among 50 HIV-infected men who have sex with men with acute HCV infection in Amsterdam. Overall sustained virological response (SVR) rate was 76%. Treatment duration was not significantly associated with SVR (adjusted odds ratio = 2.32; 95% confidence interval 0.39–13.97), suggesting that 24-week treatment may be sufficient for acute HCV infection in HIV-coinfected patients.

Propionibacterium endocarditis: A case series from the International Collaboration on Endocarditis Merged Database and Prospective Cohort Study

Propionibacterium species are occasionally associated with serious systemic infections such as infective endocarditis. In this study, we examined the clinical features, complications and outcome of 15 patients with Propionibacterium endocarditis using the International Collaboration on Endocarditis Merged Database (ICE-MD) and Prospective Cohort Study (ICE-PCS), and compared the results to 28 cases previously reported in the literature. In the ICE database, 11 of 15 patients were male with a mean age of 52 y. Prosthetic valve endocarditis occurred in 13 of 15 cases and 3 patients had a history of congenital heart disease. Clinical findings included valvular vegetations (9 patients), cardiac abscesses (3 patients), congestive heart failure (2 patients), and central nervous system emboli (2 patients). Most patients were treated with β-lactam antibiotics alone or in combination for 4 to 6 weeks. 10 of the 15 patients underwent valve replacement surgery and 2 patients died. Similar findings were noted on review of the literature. The results of this paper suggest that risk factors for Propionibacterium endocarditis include male gender, presence of prosthetic valves and congenital heart disease. The clinical course is characterized by complications such as valvular dehiscence, cardiac abscesses and congestive heart failure. Treatment may require a combination of medical and surgical therapy.