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.
Watching my sniffling boy-friend boil six garlic cloves into tea the other day, he explained his Sicilian grandmother would do the same for them as kids when they had colds. Apparently, the Chief Medical Officer for the Moldovan Army agrees. With increasing numbers of H1N1 influenza cases occurring in Eastern Europe, the Moldovan Army will be providing every soldier two extra garlic cloves and a small onion with the usual daily rations in an effort to boost their immune systems.
Garlic has been used for centuries for its "antimicrobial" effects, along with several other foodstuffs and herbs, including allspice, pepper, oregano, thyme, lemon balm, onions, and green and black tea. Studies suggest that garlic extract may inhibit the growth of various bacteria, such as E. coli and pseudomonas. The garlic enzyme alliinase has been shown to have a wide range of antifungal activity, appears to act synergistically with azoles against Candida spp. in vitro, and has been used to target fungi using antibody-alliinase conjugates. In food preparation and storage, biofilms of oregano oil or garlic oil have been tested to help provide an aesthetically pleasing and palatable "antimicrobial barrier." Besides possible antimicrobial effects, some individuals believe that garlic functions as both an antioxidant and has potential beneficial cardiovascular effects by lowering blood pressure.
TB Screening Before Anti-TNF-alpha Therapy
Screening for latent TB in-fection (LTBI) seems to have only gotten that much more complicated and, increasingly, infectious disease experts are being asked to interpret the newer tests results, especially in persons with inflammatory disorders or underlying immune suppression. In addition to the different gamma-interferon-based (GIB) assays available on the market, newer versions of outdated tests have been introduced. While GIB assays are more sensitive and specific for LTBI than TST, especially in previously BCG-vaccinated persons, only a minority of healthy individuals with LTBI remain at risk for reactivation TB. What is really needed is a diagnostic test that can tell you who those people are.
On the other hand, GIB results have reportedly waned in some patients with prior TB exposure, suggesting that some patients at risk for reactivation TB may be missed with currently available screening tools. Immunosuppression, such as the use of corticosteroids, not only increases the risk of falsely-negative TST, but increases the risk of indeterminate GIB assay results.
A retrospective analysis examined 50 patients with psoriasis who were screened for LTBI using TST, T-SPOT.TB, and chest radiographs in advance of treatment with an anti-TNF-alpha agent.1 Risk factors for LTBI, including prior TB exposure, abnormal chest radiograph suggestive of prior granulomatous disease, or residence in a country endemic for TB were compared to TST and T-SPOT.TB results. Ninety percent of the patients reported prior BCG vaccination; 20% had come from a country endemic for TB, 22% had had prior exposure to someone with TB, and 8% had abnormal chest radiographs.
The agreement between the TST and T-SPOT.TB tests, using kappa-quantified statistics, was poor (K =.3). Test results were discordant in 14 persons (28%) (both tests were negative in 28 persons and positive in 8). Twelve persons had a positiv TST (defined as > 5 mm), a negative T-SPOT.TB test, and a normal chest radiograph, while two persons had a negative TST, a positive T-SPOT.TB test, and an abnormal chest radiograph. The T-SPOT.TB test strongly correlated with risk factors for LTBI compared with the TST.
Ten of 12 patients with a positive TST/negative T-SPOT.TB and a normal chest radiograph received no treatment for LTBI. This group received anti-TNF therapy with a mean follow-up of 76 weeks, with no evidence of reactivation TB. In contrast, one of 10 patients with a +T-SPOT.TB test developed miliary TB while receiving treatment for LTBI and anti-TNF-alpha therapy. Remarkably, 68% of the patients had received prior immunosuppressive therapy, which, while not further specified, raised the possibility of selection of patients at lower risk for developing reactivation TB.
Similar data were observed using the first-generation Quantiferon TB Gold test compared with TST in a group of 302 patients with inflammatory diseases (ie., rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis) who were candidates for anti-TNF-alpha therapy.2 Sixty percent of the patients were female, with an average age of 50 years. In those with available histories, 152 of 200 reported prior BCG vaccination (76%), 9% reported prior exposure to TB, 8% were from countries endemic for TB, 4% had abnormal chest radiographs consistent with previous granulomatous infection, and 3% had received prior TB treatment. In all, 69 (29%) of the patients had one or more risk factor for LTBI. Using Danish guidelines, 45/241 (19%) patients had a positive TST (> 6 mm, or > 12 mm for those with prior BCG vaccination), while using U.S. Guidelines, 66 (28%) had a positive TST. In comparison, the Quantiferon was positive in 7%, negative in 88%, and indeterminate in 5%. Higher CD4 counts in patients correlated with a higher level of interferon-gamma production and greater likelihood of indeterminate quantiferon test results. In addition, corticosteroid therapy increased the number of indeterminate tests results, while decreasing the sensitivity of the TST.
Using kappa-quantified statistics results, the agreement between the two tests was only K = .2. The Quantiferon TB Gold was significantly associated with risk factors for TB (RR 4.7, p = .002), especially prior residence in a TB endemic area (RR 7.8, p > .0001). Interestingly, 18 of 45 had +TST negative Quantiferon TB Gold test. Of those 18 with a positive Quantiferon results, only nine (50%) had a positive TST. Thus, the authors postulate that by using the TST alone significantly more patients would have received unnecessary treatment for LTBI, especially based on U.S. guidelines, but 50% of those at risk for reactivation LTBI would have been missed. Based on the lower sensitivity of the TST in this group compared with the Quantiferon TB Gold, and despite the discordant results, the authors advocate that both tests should be taken in consideration when screening for LTBI in patients with inflammatory diseases.
- Laffitte E., et al. Tuberculosis screening in patients with psoriasis before antitumor necrosis factor therapy: Comparison of an interferon-gamma release assay vs tuberculin skin test. Brit J Dermatol. 2009;1-4.
- Soborg B, et al. Comparison of screening procedures for Mycobacterium tuberculosis infection among patients with inflammatory diseases. J Rheumatol. 2009;36:1-9.
Chronic HEV in HIV
Source: Dalton HR, et al. Persistent carriage of Hepatitis E Virus in Patients with HIV infection. N Engl J Med. 2009;361:1025-1027.
Hepatitis E virus, similar to Hepatitis A virus, is transmitted by fecal-oral contact, and is believed to cause a self-limited acute viral hepatic infection. Recently, chronic HEV infection with progression to chronic liver disease has been described in solid organ recipients with immunosuppression and in a patient with lymphoma taking rituximab.
Dalton et al describes a 48-year-old HIV-positive man with a history of heavy alcohol use and a CD4 count less than 200 cells/mm3, despite virologic suppression. For nearly two years, he had modest elevation in transaminases. Using PCR, HEV RNA was found in serum and feces — and looking back at samples from 18 months earlier, HEV was isolated from earlier specimens. ELIZA tests were positive for IgM and IgG during the previous 18 months (but were negative using an alternate assay). Genotyping confirmed HEV as genotype 3, the most prevalent genotype in developing countries. Liver biopsy confirmed active inflammation and cirrhosis.
This report indicates that patients with more advanced HIV may develop chronic HEV infection and progressive liver disease. How frequently this occurs is not known. HEV seroprevalence data from various countries vary from 5.9% in healthy Indonesian adults, to 11.4% in healthy Iranian blood donors, to 17.7% in Brazilian women attending an STD clinic for HIV screening. In Malaysia, anti-HEV antibodies were found in 14.4% of HIV-seropositive patients, although RNA studies were not performed. However, no evidence of HEV infection was found in 50 HIV-positive individuals with CD4 counts < 200 mm3 or in 43 HIV-positive individuals with cryptogenic cirrhosis in Spain. A single report from France described a case of acute HEV infection in an HIV-infected patient with a CD4 count of 246 cells/mm3. Initial studies demonstrated HEV RNA in serum, but subsequent studies demonstrated resolution of infection.
HEV screening should be considered in patients with HIV infection, especially those with persistent unexplained elevations in hepatic transaminases. Serum HEV RNA may be useful in monitoring resolution of active HEV replication in HIV+ persons.