Updates By Carol A. Kemper, MD, FACP
Updates
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
WNV Update—2006
ProMED-mailpost, June 27, 2006; www.promedmail.org
As we plunge into the late summer months, thoughts turn again to West Nile Virus. July and August are typically the hottest months for WNV. As of the end of June, 22 states in the continental United States have reported avian, animal, or mosquito WNV infections for the year. Three states (Colorado, Mississippi, and Texas) have reported 5 cases of human infection, all of whom were suffering from the more severe neuroinvasive form of the disease (not just WNV fever).
All blood donations are being pooled and screened for WNV infection. Based on these data, an estimated 1.2 to 1.3 million human infections have occurred in the United States since WNV first made its debut here in 1999. The majority of these have been asymptomatic or minimally symptomatic and clinically unrecognized. An estimated 8300 people may have developed more severe neurologic symptoms, and nearly 800 have died.
In January 2006, the CDC, in collaboration with the US Geological Service, established a website for reporting and tracking WNV and other mosquito-born diseases, called ArboNET. Detailed county-level human, avian, animal, and mosquito data are updated weekly. Now is the time to distribute literature and guidelines to patients: eg, canvas your yard and surrounding areas for pools and crevices key to the survival of mosquito larva; save and report any dead birds to the local health department; use appropriate mosquito clothing and precautions, etc. Interestingly, although dead crows may be the "canary that does not sing," other songbirds in the backyard, such as robins and sparrows, can develop high levels of WNV viremia without dying—creating a reservoir of ready infection for mosquitoes in your own backyard.
Does HCV Really Go Away?
Carreño V, et al. Detection of Hepatitis C Virus (HCV) RNA in the Liver of Healthy, Anti-HCV Antibody-Positive, Serum HCV RNA-Negative Patients with Normal Alanine Aminotransferase Levels. J Infect Dis. 2006:194:53-60.
A small number (5% to 15%) of fortunate people who become acutely infected with HCV appear to clear their infection with no residual evidence of HCV viremia and normal transaminases. Suspicions are, however, being cast on whether HCV can ever be, in fact, completely cleared from the body. Studies have shown that patients successfully treated with antiviral therapy who achieve sustained undetectable levels of plasma HCV RNA may still harbor occult intrahepatic virus. Other investigators have identified HCV RNA in the peripheral blood mononuclear cells (PBMC) of a few patients who apparently cleared their viremia and developed anti-HCV antibodies, either naturally or in response to antiviral treatment.
Carreño and colleagues in Madrid, Spain, examined liver biopsies from 12 patients with anti-HCV antibodies by recombinant immunoblot assay and negative serum HCV RNA (Amplicor HCV, version 2.0, Roche Diagnostics). Two of the patients had a remote history of blood transfusion more than 25 years earlier. The remaining patients had no history of hepatitis and no risk factor for HCV. During a mean follow-up of 29 ± 20 months, none of the patients developed clinical or laboratory evidence of HCV infection. Serum transaminases remained normal; they continued to have undetectable plasma HCV RNA, and all 12 remained HCV antibody positive.
Surprisingly, despite this lack of evidence for residual HCV infection, 10 of 12 (83%) liver biopsies were positive for genomic HCV RNA. All 10 of these specimens also demonstrated positive antigenomic HCV RNA strands, indicating occult replication. All 10 individuals had genotype 1b, raising concerns about possible cross-contamination in the lab, but nucleotide sequencing revealed distinct clones.
Genomic HCV RNA was also detected in the PBMCs of 6 of 12 patients (50%) (all of whom had positive liver biopsies); anti-genomic RNA was identified in 5 of these.
Despite a lack of clinical or other laboratory evidence of infection, histopathology in one patient revealed chronic active hepatitis and stage 1 fibrosis. Other potential causes of liver disease were ruled-out in this individual. Three patients had steatohepatitis or steatosis (2 were overweight and one was diabetic). The remaining 6 patients with positive intrahepatic HCV RNA had normal or minimal histologic changes.
Predicting Discordance in CD4 and HIV RNA
Goicoechea M, et al. Determinants of CD4+ T Cell Recovery During Suppressive Antiretroviral Therapy: Association of Immune Activation, T Cell Maturation Markers, and Cellular HIV-1 DNA. J Infect Dis. 2006:194;29-37.
Goicoechea and colleagues examined immunologic factors affecting CD4 T cell recovery in HIV+ patients who had achieved successful virologic control with a non-nucleoside containing antiretroviral (ART) regimen. These patients were part of a clinical trial enrolling patients with baseline CD4 ≥ 100 cells/mm3 and with viral loads ≥ 5000 particles/mL, 162 of HIV plasma RNA at weeks 24 and 48. The other 88 were missing data or failed to achieve virologic suppression. The 162 patients were divided into 2 groups: those with concordance virologic responses to ART, with a ≥ 100 CD4 cells/mm3 increase from baseline at 48 weeks, and those with discordant responses with CD4 cell increases at 48 weeks. Those with concordant responses gained an average of 111 CD4 cells/mm3, and those with discordant responses gained an average of 22 cells/mm3 over the 48-week study.
Measures of cellular and plasma HIV DNA levels and T cell immunophenotypes were compared between the 2 groups. Increased CD4 and CD8 T cell activation at baseline was a significant independ ent predictor of CD4 T cell recovery. The odds of developing an increasing number of CD4 cells fell by 20% for every 5% increase in activated CD4 cells. In particular, the presence of high memory (CDRA-CD62L-) CD8+ cells at baseline was a significant predictor of poor CD4 cell count recovery.
A greater portion of naïve CD4 T cells at baseline was associated with a concordant increase in CD4 counts and virologic suppression. Such patients also had significantly better recovery of naïve CD4 cells and CD8 cells than did discordant subjects at week 12, as well as weeks 24 and 48. This suggests that naïve CD4 cells not only play a role in the early recovery CD4 phase, eg, the first 3 months after initiation of ART, when extrathymic cells are being redistributed into the circulation. But these concordant subjects continue to display increased regeneration capacity, presumably from thymic expansion for up to 48 weeks. Neither cell-associated HIV DNA levels at baseline or at week 48 were predictive of outcome. Interestingly, progressive age was associated with poorer CD4 count recovery, perhaps reflecting the duration of progressive HIV disease and naive CD4 cell depletion. Identification of patients with immunophenotypic markers of immune system activation and naive CD4 cell depletion may provide a rationale for earlier initiation of ART.
Raw Food Pet Treats: Good for Them, Bad for You?
ProMED-mailpost, June 29, 2006; www.promedmail.org
Earlier outbreaks of human salmonellosis related to feeding your pet pig ears or a nice undercooked hamburger patty off the grill have been discussed in this column. This account is the third published report of human salmonellosis associated with pet treats in North America. Investigations have confirmed that raw beef and salmon-containing pet treats were responsible for 9 cases of human salmonellosis in Western Canada and Washington state in 2004-2005. Six of the 9 patients from British Columbia, Washington State, and Alberta recalled feeding pet treats to their dogs prior to onset of illness, and another 2 owned dogs. This is likely just the tip of what really occurred, since studies suggest that for every clinically identified case of salmonella infection, 38 unrecognized cases occur in the community.
Stool cultures yielded S. thompson, which was indistinguishable by pulse field gel electrophoresis from strains found in dog and salmon pet treats. Samples of salmon and beef pet treats manufactured at the Washington plant and those collected at the BC plant by Canadian authorities yielded a variety of organisms, predominately S. thompson. Up to 80,000 colony-forming units of salmonella per gram of salmon treats were discovered. Other Salmonella serotypes, including Montevideo, Newport, Give, Meleagridis, Cerros, Muenster, Agona, and Anatum were also found in treats from both the British Columbia and Washington plants. The treats are made from dehydrated, then rehydrated, raw beef and salmon. No irradiation or heat treatment intended to destroy bacteria was employed. No warning labels on the packages advised pet owners to wash their hands after handling. This article serves as a reminder that hand washing is important when handling any kind of raw foods or meats, even if it comes nicely packaged.
As we plunge into the late summer months, thoughts turn again to West Nile Virus. July and August are typically the hottest months for WNV. As of the end of June, 22 states in the continental United States have reported avian, animal, or mosquito WNV infections for the year.Subscribe Now for Access
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