Course Of Viremia Research Articles

Virus Load Kinetics in Lassa Fever Patients Treated With Ribavirin: A Retrospective Cohort Study From Southern Nigeria

Abstract Background The standard of care for Lassa fever is the use of ribavirin with supportive therapy. There is little information on the course of viremia and its relationship with clinical outcomes in patients treated with ribavirin. Methods We conducted a retrospective analysis of virologic and clinical parameters of 152 reverse transcription polymerase chain reaction–confirmed Lassa fever cases admitted and treated with ribavirin therapy. We describe the Lassa virus RNA kinetics in blood in relation to the clinical course of the patients. Results The overall mortality was 9%. The median duration (interquartile range [IQR]) of illness before admission was 8 (5–12) days. Median (IQR) Ct values on admission (t0) were lower among patients who died (21 [20–27]) than in those who survived (34 [30–37]; P < .01). The receiver operating characteristics curve of the association between outcome and Ct value at t0 had a high classification performance, with an AUC of 0.92 (95% CI, 0.86–0.98). The median time to viral clearance (IQR) was 10 (5–15) days. The viral load decreased steadily with the duration of treatment, and all survivors achieved viral clearance within 25 days of hospitalization. Conclusions Our study demonstrates that the Ct value on admission has prognostic value and Lassa fever patients treated with ribavirin typically clear the virus within 3–4 weeks of hospitalization. This kinetics has implications for the design of clinical case management and future clinical trial protocols.

Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques

Cytomegalovirus (CMV) infection is a serious complication in immunosuppressed patients, specifically transplant recipients. Here, we describe the development and use of an assay to monitor the incidence and treatment of CMV viremia in a Cynomolgus macaque model of bone marrow transplantation (BMT) for tolerance induction. We address the correlation between the course of viremia and immune reconstitution. Twenty-one animals received a nonmyeloablative conditioning regimen. Seven received cyclosporine A for 28 days and 14 received rapamycin. A CMV polymerase chain reaction assay was developed and run twice per week to monitor viremia. Nineteen recipients were CMV seropositive before BMT. Immune reconstitution was monitored through flow cytometry and CMV viremia was tracked via quantitative polymerase chain reaction. Recipients developed CMV viremia during the first month post-BMT. Two animals developed uncontrollable CMV disease. CMV reactivation occurred earlier in cyclosporine A-treated animals compared with those receiving rapamycin. Post-BMT, T-cell counts remained significantly lower compared with pretransplant levels until CMV reactivation, at which point they increased during the viremic phase and approached pretransplant levels 3 months post-BMT. Management of CMV required treatment before viremia reached 10 000 copies/mL; otherwise clinical symptoms were observed. High doses of ganciclovir resolved the viremia, which could subsequently be controlled with valganciclovir. We developed an assay to monitor CMV in Cynomolgus macaques. CMV reactivation occurred in 100% of seropositive animals in this model. Rapamycin delayed CMV reactivation and ganciclovir treatment was effective at high doses. As in humans, CD8 T cells proliferated during CMV viremia.

EHDV-2 Infection Prevalence Varies in Culicoides sonorensis after Feeding on Infected White-Tailed Deer over the Course of Viremia.

Epizootic hemorrhagic disease viruses (EHDVs) are arboviral pathogens of white-tailed deer and other wild and domestic ruminants in North America. Transmitted by various species of Culicoides, EHDVs circulate wherever competent vectors and susceptible ruminant host populations co-exist. The impact of variation in the level and duration of EHDV viremia in white-tailed deer (Odocoileus virginianus) on Culicoides infection prevalence is not well characterized. Here we examined how infection prevalence in a confirmed North American vector of EHDV-2 (Culicoides sonorensis) varies in response to fluctuations in deer viremia. To accomplish this, five white-tailed deer were experimentally infected with EHDV-2 and colonized C. sonorensis were allowed to feed on deer at 3, 5, 7, 10, 12, 14, 18, and 24 days post infection (dpi). Viremia profiles in deer were determined by virus isolation and titration at the same time points. Blood-fed Culicoides were assayed for virus after a 10-day incubation (27 °C) period. We found that increases in deer EHDV blood titers significantly increased both the likelihood that midges would successfully acquire EHDV and the proportion of midges that reached the titer threshold for transmission competence. Unexpectedly, we identified four infected midge samples (three individuals and one pool) after feeding on one deer 18 and 24 dpi, when viremia was no longer detectable by virus isolation. The ability of ruminants with low-titer viremia to serve as a source of EHDV for blood-feeding Culicoides should be explored further to better understand its potential epidemiological significance.

Course of HEV viremia and anti-HEV IgM/IgG response in asymptomatic blood donors

BackgroundGlobally, an estimated 20 million Hepatitis E infections occur every year. The course of viremia and antibody response has been investigated in patients with symptomatic hepatitis E. However, the majority of HEV infections in industrialized countries take a subclinical course. ObjectivesTo investigate the course of HEV viremia and epitope specific anti-HEV IgM/IgG response in asymptomatic blood donors in order to understand the immune response and viral clearance in asymptomatic blood donors with HEV infections. MethodsIn this study 27 HEV viremic donors were identified by HEV-PCR during routine screening of blood donors and the course of anti-HEV IgM/IgG and HEV-RNA was retrospectively studied using RT-PCR and a commercial immunoblot (Mikrogen®) allowing classification of the antibody response according to HEV epitopes. ResultsAt time of donation, serological testing failed to identify viremic donors as 70.4% had no detectable antibody response. Anti-HEV IgM could be detected in 22.2% of viremic donors while anti-HEV IgG could be found in 7.4%. At least three donors experienced prolonged viremia beyond 100 days. Spontaneous HEV-RNA clearance within a median time span of 57 days was observed in all 27 donors. In all donors anti-HEV IgG specific for the immunogenic viral epitope O2C could be detected in close temporal association with viral clearance. ConclusionSerological testing is inappropriate for identifying HEV-viremic blood donors. Acute HEV infection in asymptomatic blood donors can persist for more than 100 days. HEV-RNA clearance coincided with the appearance of anti-HEV IgM/IgG confirming the importance of a B-cell mediated response in clearing acute infections. Anti-HEV IgM and IgG specific for the epitope O2C are associated with the clearance of HEV-viremia.

Virologic and Immunologic Characteristics in Mature Ducks with Acute Duck Hepatitis A Virus 1 Infection.

Duck hepatitis A virus 1 (DHAV-1) infection in mature ducks has previously been proposed as a small-animal model for human hepatitis A. However, basic research on the outcome of DHAV-1 infection in mature ducks is limited. Here, we examined the course of viremia, the characteristics of antibody responses, and the profiles of plasma cytokines in mature ducks infected with DHAV-1. During the course of infection, the viremia was detectable soon after infection and persisted for 196 days, however, the ducks presented as clinically asymptomatic. Specific and timely immunoglobulin G (IgG), IgM, and IgA1 responses were elicited. At the same time, extensive inhibition of viral replication was observed with increasing IgG concentration. With respect to pattern-recognition receptors, TLR-7 was mainly involved in triggering the innate defense against the DHAV-1 infection. In addition, plasma immune analytes were measured and were determined to have bidirectional roles in virus clearance. It was concluded that DHAV-1 spreads quickly in blood. The spontaneous clearance of DHAV-1 during asymptomatic infection in mature ducks depends on the cooperation of timely antibody responses and alert innate immune responses. Moreover, the delayed clearance may be associated with a weak interferon-γ-producing CD8+ T cell response. This study allows us to reveal the mechanism of clearance and persistence of DHAV-1 infection in mature ducks. We anticipate that it will provide a basis for future studies focused on defining the nature mechanisms involved in the clearance and persistence of human hepatitis virus.

Is Treatment with Bortezomib for Multiple Myeloma or Amyloidosis Associated with Cytomegalovirus Reactivation?

BackgroundBortezomib (Velcade®) is an inhibitor of the 26S proteasome used as a first line therapy for multiple myeloma, for retreatment of relapsed multiple myeloma and for treatment of AL amyloidosis. An increased incidence of reactivation of herpesviruses including varicella zoster virus (VZV) and herpes simplex virus type 1 (HSV-1) has been reported following administration of bortezomib (Oakervee et al 2005) In addition one study has described an increased incidence of cytomegalovirus (CMV) reactivation in myeloma patients post autografting treated previously with bortezomib when compared to other regimens (Marchesi et al 2014). We noted several cases of CMV viraemia with one case of likely end organ involvement (colitis) among patients given bortezomib. To determine how frequently this association occurs, we introduced a clinical protocol to monitor our patients on bortezomib for CMV infection.MethodsAll patients with myeloma or amyloidosis due their first dose of bortezomib were tested for CMV by polymerase chain reaction (PCR) on whole blood at baseline prior to treatment and then tested every 2 weeks after their initial dose or whenever they re-attended for clinic appointments, regardless of symptoms. Where possible, data on pre- treatment CMV serostatus was also recorded.We applied a protocol for pre-emptive therapy that we use for transplant patients (Atabani et al 2012). Whereas transplant patients with a viral load greater than 3000 genomes/ml (2520 IU/ml) whole blood are treated, bortezomib patients who had CMV levels in excess of 7500 copies/ml were given treatment (either oral valganciclovir or IV ganciclovir) until 2 consecutive blood samples showed undetectable levels.Results60 new bortezomib starters were tested with 43 being tested by CMV PCR at baseline i.e pre-treatment. The characteristics of these patients are shown in table 1 Table 1Patient characteristicsCharacteristicSexMale = 35 Female = 25AgeMedian 63.5 (range 33-89)Underlying diseaseAmyloidosis =39 Multiple myeloma= 21Pre-treatment CMV serostatusIgG positive = 35 IgG negative =17 Unknown= 8CMV viraemia was detected in 14/60 (23%) patients (10 myeloma and 4 amyloidosis) of whom 13 were known to be seropositive showing that the majority of the viraemias seen were reactivations/reinfections rather than primary infections. No CMV viraemia was seen in the seronegative group. Of those who had a true baseline none were positive prior to starting treatment. Of those without a true baseline, 5 had a detectable viraemia on their first blood sample. The course of the viraemia in these 14 patients is shown in figure 1. Five patients (all myeloma) reached the threshold for treatment and all responded to therapy including one patient who had 2 separate CMV reactivations. There were no cases of CMV end-organ disease.SummaryIn our cohort, 14/60 (23%) patients developed a CMV viraemia after starting bortezomib, corresponding to 13/35 (37%) who were initially CMV seropositive. Although we cannot exclude CMV reinfection from an exogenous source, we suggest that most of these were reactivations of latent CMV. Clinically, the majority of these episodes were self limiting although, because we elected to treat those patients who reached a pre-defined threshold of 7500 copies/ml, the true course of viraemia and the risk of subsequent end organ disease is unclear. Further investigation of the incidence of CMV reactivation and its clinical significance is warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Dynamics of antibody response and viraemia following natural infection of porcine circovirus 2 (PCV‐2) in a conventional pig herd

Porcine circovirus 2 (PCV-2) is a primary agent of post-weaning multi-systemic wasting syndrome (PMWS), ubiquitous in pig herds. The course of viraemia and seroconversion in naturally infected pigs were investigated in piglets from the 2nd week of their life. Piglets were divided into seropositive (Ab(+)) and seronegative (Ab(-)) groups. Subsequently, after vaccination against PCV-2 (Ingelvac(®) CIRCOFLEX™, Böehringer Ingelheim), they were further divided into non-vaccinated seronegative (NVAC/Ab(-)) and seropositive (NVAC/Ab(+)), and vaccinated seronegative (VAC/Ab(-)) and seropositive (VAC/Ab(+)). PCV-2 colostral antibodies failed to prevent development of natural PCV-2 infection in conventional piglets; however, this occurred at a higher age in comparison with seronegative pigs. Neither colostral nor post-infection antibodies prevented development of viraemia, which persisted up to the end of the study (the 19th week), but without clinical signs of PMWS. Vaccination failed to prevent development of natural PCV-2 infection, but viraemia was limited to between the 8th and 10th week. The presence of colostral anti-PCV-2 antibodies did not show any untoward effect to vaccination; on the contrary, VAC/Ab(+) animals showed the lowest titre of viraemia.

Experimental co-infections of calves with bluetongue virus serotypes 1 and 8

The contemporary circulation of multiple bluetongue virus (BTV) serotypes or strains within the same territory can imply the co-infection of the ruminant and/or the vector populations. As a consequence, the clinical and pathological outcomes of co-infections as well as the biological properties of the viral progeny could be influenced and exhibit relevant variation. In this study, two independent co-infection experiments were carried out in calves using European strains of BTV serotypes 1 and 8 (BTV-1 and BTV-8, respectively), with the objective of studying the clinical and virological outcomes in comparison with BTV-1 and BTV-8 single infections. Synchronous co-infections using the same titre for the two viral strains were performed and the clinical signs were quantified using a standardized clinical form. Serotype-specific real-time RT-PCRs and viral isolation were used to monitor the course of viraemia. Neutralizing antibody titres were measured during the experiments, and necropsy with viral detection in the affected organs was performed. In the co-infected calves, a high BTV-8 viraemia was detected, while BTV-1 viraemia was irregular and sporadic. During BTV-1 single infection the development of viraemia and high titres of anti-BTV-1 neutralizing antibodies proved that the inoculum was infectious and the detection protocols were efficient. Several hypotheses could explain the predominant detection of BTV-8 in the co-infected calves, such as the occurrence of a privileged BTV-8 segment 2 reassortment, as recently described during in vitro BTV-1/BTV-8 co-infections; interference between the two viral strains; or a higher BTV-8 tropism for the bovine species.

A Steady State of CD4+ T Cell Memory Maturation and Activation Is Established during Primary Subtype C HIV-1 Infection

The functional integrity of CD4(+) T cells is crucial for well-orchestrated immunity and control of HIV-1 infection, but their selective depletion during infection creates a paradox for understanding a protective response. We used multiparameter flow cytometry to measure activation, memory maturation, and multiple functions of total and Ag-specific CD4(+) T cells in 14 HIV-1- and CMV- coinfected individuals at 3 and 12 mo post HIV-1 infection. Primary HIV-1 infection was characterized by elevated levels of CD38, HLA-DR, and Ki67 in total memory and Gag-specific CD4(+) and CD8(+) T cells. In both HIV-infected and 15 uninfected controls, the frequency of activated cells was uniformly distributed among early differentiated (ED; CD45RO(+)CD27(+)), late differentiated (CD45RO(+)CD27(-)), and fully differentiated effector (CD45RO(-)CD27(-)) memory CD4(+) T cells. In HIV-1-infected individuals, activated CD4(+) T cells significantly correlated with viremia at 3 mo postinfection (r = 0.79, p = 0.0007) and also harbored more gag provirus DNA copies than nonactivated cells (p = 0.04). Moreover, Gag-specific ED CD4(+) T cells inversely associated with plasma viral load (r = -0.87, p < 0.0001). Overall, we show that low copy numbers of gag provirus and plasma RNA copies associated with low CD4 activation as well as accumulation of ED HIV-specific CD4(+) memory. Significant positive correlations between 3 and 12 mo activation and memory events highlighted that a steady state of CD4(+) T cell activation and memory maturation was established during primary infection and that these cells were unlikely to be involved in influencing the course of viremia in the first 12 mo of HIV-1 infection.

Human Immunodeficiency Virus-Specific Gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point

It is unknown whether patterns of human immunodeficiency virus (HIV)-specific T-cell responses during acute infection may influence the viral set point and the course of disease. We wished to establish whether the magnitude and breadth of HIV type 1 (HIV-1)-specific T-cell responses at 3 months postinfection were correlated with the viral-load set point at 12 months and hypothesized that the magnitude and breadth of HIV-specific T-cell responses during primary infection would predict the set point. Gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay responses across the complete proteome were measured in 47 subtype C HIV-1-infected participants at a median of 12 weeks postinfection. When corrected for amino acid length and individuals responding to each region, the order of recognition was as follows: Nef > Gag > Pol > Rev > Vpr > Env > Vpu > Vif > Tat. Nef responses were significantly (P < 0.05) dominant, targeted six epitopic regions, and were unrelated to the course of viremia. There was no significant difference in the magnitude and breadth of responses for each protein region with disease progression, although there was a trend of increased breadth (mean, four to seven pools) in rapid progressors. Correlation of the magnitude and breadth of IFN-gamma responses with the viral set point at 12 months revealed almost zero association for each protein region. Taken together, these data demonstrate that the magnitude and breadth of IFN-gamma ELISPOT assay responses at 3 months postinfection are unrelated to the course of disease in the first year of infection and are not associated with, and have low predictive power for, the viral set point at 12 months.

Lamivudine Treatment in Hbeag-Negative Chronic Hepatitis B Patients with Low Level Viraemia

Our aim was to determine the short-term natural course of viraemia and the response to lamivudine treatment in HBeAg-negative chronic hepatitis B patients with a persistently low hepatitis B virus (HBV)-DNA level. A total of 55 patients were included. Group 1 consisted of 37 patients with low-level viraemia and high serum alanine aminotransferase (ALT) levels and further randomized to two groups: group 1a (n=19) patients received 1 year of lamivudine therapy and group 1b (n=18) patients were untreated controls. Group 2 consisted of 18 inactive carriers who were followed as controls of untreated low viraemic chronic hepatitis B patients. HBV DNA was longitudinally determined by real-time polymerase chain reaction assay. A female predominance in group 2 was observed while males were predominant in group 1. Mean age and baseline HBV-DNA levels did not differ between group 1 and 2 patients while group 1 patients had a higher histological score (P<0.01). Of group 1a patients, 44% had complete ALT normalization at end of treatment, whereas 21% untreated group 1b patients had normal ALT at the end of the follow-up. No change in histological activity was observed in group 1a patients at the end of treatment. HBV-DNA levels did not significantly change from baseline to end-of-treatment/observation period in patient groups. The viraemia course was not different across the groups. Low viraemic HBeAg-negative patients with high ALT present with minimal/mild histological activity. Inactive carriers cannot be differentiated from low viraemic patients with high ALT based on HBV DNA determination. Although lamivudine treatment can be effective in some cases, observation rather than a prompt treatment attempt seems to be more logical because of mild histological changes and low response rate to treatment in these patients.

Parvovirus B19 viraemia in Dutch blood donors

Blood, donated by asymptomatic donors, may contain and transmit parvovirus B19. To investigate the dynamics of parvovirus viraemia in asymptomatic blood donors, we studied the amounts of parvovirus DNA in pools of donor plasma, the prevalence of parvovirus antibodies among blood donors in relation to age, and the seasonal and year-to-year variation of the incidence of parvovirus infection in The Netherlands. The incidence of parvovirus infection follows a seasonal cycle and a cycle of several years. Among Dutch blood donors the incidence was estimated to be 0.56% per year. Forty seven out of 100 pools of 5000 plasma donations tested positive for parvovirus DNA. We inferred that the course of viraemia in asymptomatic donors shows a short peak (> 10(9) copies parvovirus DNA/ml), followed by viraemia below 10(6) copies/ml for about 2 weeks.

Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease.

To define the early events that determine the outcome of acute hepatitis C virus (HCV) infection, we compared the course of viremia with the peripheral and intrahepatic T cell response and intrahepatic cytokine profile in six acutely infected chimpanzees. Three different outcomes were observed after peak viral titers were reached: sustained viral clearance, transient viral clearance followed by chronic infection, and chronic infection that persisted at initial peak titers. The results indicate that HCV spread outpaces the T cell response and that HCV rapidly induces but is not controlled by IFN-alphabeta; that viral clearance follows the entry and accumulation of HCV-specific IFN-gamma-producing T cells in the liver; and that it may not require the destruction of infected cells.

Human Immunodeficiency Virus: The Initial Physician-Patient Encounter

Human Immunodeficiency Virus: The Initial Physician-Patient Encounter

Viral dynamics in primary HIV-1 infection

To study the natural course of viremia during primary HIV infection (PHI). Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. HIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/mL. This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.

Intravenous administration of recombinant adenoviruses causes thrombocytopenia, anemia and erythroblastosis in rabbits.

Recombinant adenoviruses are highly efficient gene transfer vehicles but their administration to mammals is accompanied by a strong inflammatory response. The present study reports additional side effects observed during adenoviral gene transfer studies in rabbits. Hematological and serological parameters, the course of viremia and the organ distribution were analyzed after in vivo administration of E1-deleted adenoviruses in rabbits. The systemic administration of a therapeutic dose of 5 x 10(11) infectious particles/kg (infusion time 20 min) led to an average reduction of 80-90% in the platelet count within 48 h. Full recovery took 10-14 days. Virus administration induced a strong but transient erythroblastosis (peaking 24 h after administration) which settled 48 h later. Normochromic anemia occurred over the next 10 days with hemoglobin levels dropping by about 40% to reach the lowest level 10 days after administration and taking two months for full recovery. Dose-dependent thrombocytopenia was also found in mice, but neither erythroblastosis nor anemia was observed (in equivalent doses). The hematological findings did not improve after local injection via the portal vein. Local and systemic administration led to a comparable course of viremia. Only minor differences were found in the biodistribution of viruses between local and systemic administration. Large amounts of viral DNA and transgene expression were found in the lungs, the kidneys and the ovaries, even after local administration via the portal vein. Local intravenous injection via the portal vein does not prevent systemic spread of viral vectors and the occurrence of vector-related side effects. The hematological changes observed in rabbits suggest the need for careful monitoring of hematological and rheological parameters in clinical trials.

The cell tropism of human immunodeficiency virus type 1 determines the kinetics of plasma viremia in SCID mice reconstituted with human peripheral blood leukocytes.

Most individuals infected with human immunodeficiency virus type 1 (HIV-1) initially harbor macrophage-tropic, non-syncytium-inducing (M-tropic, NSI) viruses that may evolve into T-cell-tropic, syncytium-inducing viruses (T-tropic, SI) after several years. The reasons for the more efficient transmission of M-tropic, NSI viruses and the slow evolution ofT-tropic, SI viruses remain unclear, although they may be linked to expression of appropriate chemokine coreceptors for virus entry. We have examined plasma viral RNA levels and the extent of CD4+ T-cell depletion in SCID mice reconstituted with human peripheral blood leukocytes following infection with M-tropic, dual-tropic, or T-tropic HIV-1 isolates. The cell tropism was found to determine the course of viremia, with M-tropic viruses producing sustained high viral RNA levels and sparing some CD4+ T cells, dual-tropic viruses producing a transient and lower viral RNA spike and extremely rapid depletion of CD4+ T cells, and T-tropic viruses causing similarly lower viral RNA levels and rapid-intermediate rates of CD4+ T-cell depletion. A single amino acid change in the V3 region of gp120 was sufficient to cause one isolate to switch from M-tropic to dual-tropic and acquire the ability to rapidly deplete all CD4+ T cells.

The course of viremia and antibody seroconversion following human immunodeficiency virus exposure: Busch MD, Satten GA. Am J Med 102:117, 1997

The course of viremia and antibody seroconversion following human immunodeficiency virus exposure: Busch MD, Satten GA. Am J Med 102:117, 1997

Time course of viremia and antibody seroconversion following human immunodeficiency virus exposure

Rational application of diagnostic assays in the management of healthcare workers (HCWs) following occupational exposure is needed to rule out pre-existing human immunodeficiency virus (HIV) infection, detect HIV infection or seroconversion as early as possible in the small proportion individuals who become infected, and to rule out infection in the high proportion of individuals who remain uninfected following occupational exposure to HIV. An understanding of the time course of viremia and seroconversion following HIV exposure is essential in developing recommendations for management of occupational exposure among HCWs. Several data sources that address the timing and dynamics of HIV viremia and seroconversion following primary infection are reviewed. The implications of each data source for management of occupational exposure among HCWs is assessed. Although the majority of infected HCWs seroconvert within 2 months of exposure, the possibility of delayed seroconversion is well established, with approximately 5% of infected HCWs estimated to seroconvert >6 months after exposure. In contrast, the period of viremia (detectable by p24 antigen or RNA assays) preceding antibody seroconversion is consistently brief (1-3 weeks). Animal inoculation studies indicate that a variable period of localized viral replication in lymphoid tissue draining inoculation sites exists prior to systemic viremia and subsequent seroconversion.

Susceptibility of human retinal pigment epithelial cells to different viruses

• BackgroundDifferent viruses have been reported to be involved in retinal diseases in animalsystems. In humans, herpes simplex virus and cytomegalovirus have been found to cause retinal disease. Most of the studied viruses are neurotropic. In this study, the in vitro susceptibility of human retinal pigment epithelial cells (RPEC) to representative members of different groups of human pathogenic viruses was investigated.• MethodsEarly cultures of RPE C — after two or three passages — were infected with the following viruses: herpes simplex virus (HSV) type 1, human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus types 1 and 7, measles virus, parainfluenza virus and coxsackie virus B3.• ResultsCultures of RPE C could be infected with neurotropic viruses like HSV or measles virus as well as with typical respiratory viruses like parainfluenza or adenoviruses. Coxsackievirus, an enterovirus, replicated as well as human CMV whereas EBV and HHV-6, two lymphotropic viruses, failed to infect RPE.• ConclusionThese findings suggest that a variety of viruses, including those causing rather common illnesses, might be capable of inducing retinal lesions under certain circumstances due to haematogenous spread during the course of viraemia.