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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.
H5N1 Influenza Vaccine Approved
Source: FDA News, April 18, 2007; www.fda.gov
In April, the United States Food and Drug Administration announced the approval of the first human vaccine against H5N1 Avian Influenza virus. The inactivated vaccine is derived from a/Vietnam/1203/2004 influenza virus, is administered as a 2-part vaccine one month apart, and contains thimerosal (similar to other multidose vials of influenza vaccine). It is manufactured by sanofi pasteur Inc at their Swiftwater, PA, facility.
Clinical investigation of the vaccine in healthy adults found that 103 persons receiving two 90 microgram doses of vaccine 28 days apart had an adequate antibody response (what is thought to be sufficient levels of antibody to prevent infection). In addition, 300 adults receiving lower doses of vaccine developed a lesser antibody response that may nonetheless be sufficient to reduce the severity of disease if infected. The vaccine was generally well tolerated, and additional safety data is being examined.
The vaccine is not commercially available but has been purchased by the federal government for the U.S. Strategic National Stockpile. The idea is to make vaccine available to the public as needed within 12 hours.
Leprosy revealed with HIV treatment
Source: A ProMED-mail post, October 25, 2006; firstname.lastname@example.org
HIV/AIDS specialists in Britain and the U.S. caring for HIV+ persons from developing countries are reporting a new phenomenon - exacerbations of previously unrecognized leprosy in HIV+ persons receiving highly active antiretroviral therapy (HAART). As patients initiate HAART, and with improvement in their immune systems, their leprosy appears to "wake up." Patients have developed painful nodules around the nerves of the neck and face, with numb fingers and toes. The diagnosis of leprosy may not be immediately obvious, and the granulomatous response seen in nodules may be misleading. The clinical and histopathological presentation appears similar to a Type 1 reversal reaction, where activated CD4 cells migrate into infected lesions and produce cytokines. As such, it seems analogous to other HIV-related infections, with paradoxical worsening with immune reconstitution.
There are an estimated 300,000 new cases of leprosy diagnosed annually around the world, mostly in Brazil, India, Africa, and the Caribbean, although I have cases in my clinic from Central America, China and the Philippines. Initial concerns that HIV infection may lead to thousands of new cases of leprosy in the developing world have not been born out. Some assume this may be a function of patients dying of their HIV before developing clinically apparent leprosy, which typically incubates for up to 8 to 13 years. It is estimated that perhaps 2% of leprosy patients in places like Brazil may be co-infected with HIV. Interestingly, even in HIV+ patients with leprosy, the histology on biopsy maybe similar to that seen in non-HIV-infected persons. Even patients with advanced HIV disease appear able to mount a granulomatous response to M. leprae, in contrast to those infected with M. tuberculosis. Type 1 reversal reactions, associated with T cell activation to M. leprae have been described in 2 HIV+ patients who did not receive ART.
Clinicians caring for HIV+ patients from developing countries should be alert to the possibility of asymptomatic leprosy being unmasked by antiretroviral therapy.
Vaccine-strain smallpox masquerades as genital herpes
Source: MMWR Weekly, May 3, 2007, 556(17), 417-419.
A woman presented to a public health clinic in Alaska in October 2006 with painful herpetic-like genital lesions. She reported having a new male sex partner for 10 days, ending about 10 days earlier. Condoms were used, although on the final day of their liaison, the condom broke. Examination showed 2 shallow painful 3 to 5 mm. ulcers, one the on labia majora and one on the labia minora. She had no fever, itching, dysuria or inguinal adenopathy. A viral culture was obtained, and tests for GC and chlamydia were negative. Over the next 2 days the lesions became increasingly painful and red, and she was treated with cephalexin for possible cellulitis. The ulcers healed within 10 days.
Although the presumptive diagnosis was genital herpes, the viral culture yielded an identified viral pathogen that repeatedly tested negative for HSV. At the Alaska State Viral Laboratory, the virus was successfully passed through 2 cell lines, but consistently stained negative for HSV and CMV. An outside reference lab was also unable to make an identification. The isolate was forwarded to the CDC January 9, 2007, where pan-herpes virus PCR and a DNase-single-primer amplification restriction enzyme digestion (DNase-SISPA) tests were performed. The latter yielded distinct DNA fragments that, when amplified, matched vaccinia virus sequences. Additional PCR testing demonstrated consistency with vaccine-strain vaccinia virus. The results were relayed back to the ASVL on January 30th.
So, what is the logical explanation for this woman's genital infection? One clue: her partner was in the military, stationed at a local military base. He had just been vaccinated for vaccinia 1 day prior to beginning his 10-day liaison with the woman. He had no skin conditions or contraindications to vaccination. The woman recalled no bandages or lesions on his arms. The report indicates that manual genital contact occurred, or maybe virus was transmitted when applying the condom. She had never been vaccinated against smallpox.
Transmission of vaccine strain virus to another site on the vaccinee's body or to non-vaccinated persons was not uncommon back when people were vaccinated against smallpox. Frequent sites of secondary infection included the face, nose, eyes, lips, genitals, and anus. In the past few years, 6 cases of secondary transmission associated with military personnel to non-military persons have been reported, including 2 with genital involvement.
The accompanying editorial stressed the importance of newer molecular tools in the identification of the unknown pathogen, especially in the absence of clinical history to guide the evaluation. However, a more careful history may have prompted the correct diagnosis, especially as there was a nearby military base. And no matter how "powerful" the tools employed, it took the various laboratories involved nearly 4 months to identify the virus. Fortunately, there was no evidence of transmission to other persons, including medical personnel.
Clinicians should be aware the military personnel are still being vaccinated for smallpox with the potential for causing secondary infections in others.
Condoms prevent HPV in Sexually Naïve Women
Source: Winer RL, et al. Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med 2006,354,25;2635-2654.
The debate surrounding the relative merits of abstinence and fidelity vs. condom use (as if the two were mutually exclusive) remains a hotly contested issue, at least in the United States, where it has even spilled over into U.S. international family planning policy. In 2001, conservative groups successfully pressured Congress to pass a law requiring the FDA to define the medical accuracy of condom effectiveness in preventing STD's other than HIV. By then, condom use had clearly been shown to reduce the risk of HIV, and, at least in men, gonorrhea. But while most experts agree that condoms were likely to decrease the risk of transmission of other STDs, such as syphilis, HSV, and HPV, clear data was lacking. Indeed, controlled clinical trials to prove that condoms are effective in reducing transmission of such diseases, for example, as syphilis, are not possible, and probably unethical. However, given that sex can often be messy, it is not inherently obvious to what degree condom use may decrease the risk of HSV or HPV transmission.
Fortunately, 6 years later, the group in Seattle has weighed in with a positive result, that young women having sex for the first time whose partners use condoms 100% of the time have a 70% lower risk of HPV infection than a similar group of women whose partners infrequently used condoms.
A total of 210 female university students aged 18 to 22 years who were sexually naive or newly sexually active with a single partner were evaluated at baseline, and every 4 months for up to 2 years. Cervical and vulvovaginal specimens were tested for HPV DNA and routine Papanicolaou smears were performed, as well as testing for other STDs. The data for 82 young women who were sexually active less than 2 weeks prior to enrollment and who kept detailed daily computerized diaries of the sexual activities were analyzed. After first time intercourse with a first time partner, most HPV infections occurred within 8 months (before a second partner), and the shortest interval from the first sexual experience to an HPV event was 20 days. Thus, data for the time period of 20 days to 8 months was analyzed to best answer the FDA's question.
A total of 126 incident infections were identified in 40 women after their first intercourse, for an overall 12-month cumulative incidence of 37.2% (confidence interval, 27 to 49%). The 24-month cumulative incidence of squamous intraepithelial lesions was 15% (confidence interval 8.3 to 26.2%), including one high grade lesion and 14 low grade lesions. Three women were found to have HPV infection at baseline, before any reported sexual intercourse.
Comparing young women who partners used condoms 100% of the time vs those with <5% use, the incidence of genital HPV infection was 38 vs 89 per 100-person years, respectively (adjusted hazard ratio, 0.3). No cervical squamous intraepithelial lesions were detected in women whose partners used condoms 100% of the time, compared with 14 lesions in those whose partners used condoms less consistently. Thus regular consistent condom use resulted in a significant reduction in the transmission of HPV in young women who were sexually active for the first time. Because sex so often may involve genital contact before the application of a condom, it is not surprising that some women who reported consistent condom use nonetheless developed HPV infection, or that a small number had evidence of HPV infection even before experiencing intercourse.
It is important to note that the results may not be generalizable to older women, or women who have already been sexually active for some time, or women of lower socioeconomic class. Nonetheless, the FDA can now prominently and decisively display the benefits of condom use in the reduction of HPV transmission.