UPDATES

By Carol A. Kemper, MD, FACP, is Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, HIV, Associate Editor, Infectious Disease Alert, and Section Editor,Updates.

Improved Blood Donor Screening for WNV

Source:MMWR Morb Mortal Wkly Rep. 2004;53:281-284.

Most persons (around 80%) with WNV infection are asymptomatic, despite ongoing viremia for a median of 6.5 days. This group of asymptomatic but viremic individuals represents a risk to the safety of the US blood supply. In addition, some persons may develop symptoms only after their blood donation. Thus, screening based on reported symptoms is not sufficient.

As previously reported in this column, by March 2003, the CDC had received reports of 61 possible cases of WNV transfusion-associated infection (Infectious Disease Alert. 2003;23:12). As a result, in June 2003, the United States begun screening all blood donations using investigational nucleic acid-amplification tests (NATs). Two differing screening algorithms were used, including either testing small "mini-pools" of 6 or 16 individual donations, depending on the test kit used, or screening individual donations in certain areas during limited periods of seasonal WNV activity. Screening of individual donations was performed on any reactive mini-pools.

From June through December, a total of 6 million units of blood were screened using these techniques, resulting in the identification of 818 viremic blood donations. Data available on the donors for 811 of these units found that 654 people (81%) remained asymptomatic, 137 (17%) developed WNV fever, and 6 people (1%) subsequently developed WNV encephalitis or meningitis. Of the potential viremic donors, 85% were residents of 9 states: Colorado, Kansas, Nebraska, New Mexico, North Dakota, Oklahoma, South Dakota, Texas, and Wyoming.

Despite the success of this screening program, 6 cases of WNV transfusion-associated infection occurred, presumably because of an inability to detect low-level viremia in some donations. In each of the 6 cases, the recipients received components from multiple donations, although only one infected unit was later identified in each case. Four recipients developed WNV encephalitis, one developed WNV fever with a maculopapular rash, and one developed an illness not compatible with WNV although IgM antibody studies were positive. All cases were diagnosed based on positive WNV IgM Ab and later confirmed by PCR.

While additional infected units could have escaped detection but not resulted in clinically apparent disease, these data suggest that the current NAT kit tests fail to detect ~0.7% of infected donations. The estimated viral load from recalled plasma samples from 4 of the 6 donors was 0.11 plaque-forming units (pfu) per mL. Three of the recalled units tested negative for IgM Ab. Interestingly, for reasons that are not clear, the estimated level of viremia for 2003 appears significantly lower than that detected in 2002: estimated viral loads were 0.8-75 pfu/mL in 2002 vs 0.06-0.5 pfu/mL in 2003. The lowest level of viremia that can cause clinical illness is not known.

Azithromycin Failure as Prophylaxis or Treatment of Syphilis

Source: Eurosurveillance Weekly. April 1, 2004.

San francisco—along with several other major cities in Europe, North America, and Australia—has been experiencing a minor epidemic of syphilis, especially in men who have sex with men (MSM). It is not unusual for HIV physicians in my neighborhood to have seen 5-10 new cases of syphilis within the past year, and I have personally seen 2 cases of penile chancre during the past few months (2 more than I’ve seen in as many years)—in which the diagnosis had either been missed or was in question.

In this report, the San Francisco Public Health Department presents the results of their investigation of treatment failure in syphilis patients receiving single-dose azithromycin therapy. It was hoped that the tolerability and feasibility of single-dose azithromycin for the treatment of high-risk STD contacts might facilitate the management of these cases, especially because azithromycin has excellent coverage against a number of other STD agents including chlamydia and chancroid. A single 1.0 gram dose of azithromycin has been used as prophylaxis for patients at high risk with other STDs and for contacts of patients diagnosed with syphilis; a single 2.0 gram dose has been used in the treatment of primary syphilis.

Unfortunately, between September 2002 and July 2003, 8 HIV-infected MSMs failed single-dose azithromycin therapy, either for acute primary syphilis or for high-risk contact. Despite receipt of azithromycin 2.0 gram single-dose therapy for primary syphilis, one patient with a penile ulcer had positive darkfield microscopy at 5 days, a second patient with a penile ulcer had positive darkfield at 5 weeks, and a third with an oral chancre was positive at 18 days. Five additional patients with high-risk contact received a single dose of azithromycin 1.0 gram; all either seroconverted their serology or developed early syphilis after treatment. All 8 patients were subsequently successfully treated with either penicillin or doxycycline.

While animal studies show good activity of azilides against Treponema pallidum, other data suggest that resistance to erythromycin may be developing in certain strains. Whether this finding explains the treatment failures identified in San Francisco is unknown but is being investigated. In the absence of other good clinical data demonstrating the success of azilide therapy, azithromycin should not be considered a dependable second- or third-line agent for either the treatment of active syphilis or the prophylaxis of high-risk sexual contact.

United Kingdom Cracks Down on Potential Blood Donors

Source: Eurosurveillance Weekly. 2004;8.

As reported in this column in August 2002, public health experts in the United Kingdom were debating the merits of enhanced screening criteria for blood donations based on a "theoretical" risk of transmission of bovine spongiform encephalopathy (BSE) through blood transfusion. Successful experimental transmission of BSE has been demonstrated from sheep, fed cattle brain naturally infected with BSE, to other sheep, even in advance of symptoms of disease in the donor. However, there had been no firmer data to suggest transmission of BSE in humans. Britain, therefore, elected to recall any tissue or blood components from patients diagnosed with vCJD since 1997 and has been using only leukopoor blood because of concerns that white blood cells may carry infection since August 1999. By the end of 2002, 115 people in Britain had died of BSE (variant Creutzfeldt-Jakob disease [vCJD]); 4 of those had received blood transfusions, but this was not believed to be the source of their infection. Twenty-two people had received donations from persons who later died of BSE; none had demonstrated disease.

Based on the first possible case of transfusion-associated vCJD in a blood recipient, the UK Blood Service has decided to block the blood donation of anyone who has ever received donated blood since January 1, 1980 (effective April 5, 2004). The patient in question received a transfusion in 1996 and was diagnosed with vCJD last year; the source patient was well at the time of donation but developed symptoms of vCJD in 1999 and died the following year.

The United Kingdom will also start importing fresh frozen plasma from the United States for use in patients born after January 1, 1996. The UK officials believe this is a highly precautionary move; although ~2.5 million persons in the United Kingdom receive blood products each year, only one case of possible transfusion-associated disease has been reported. On the other hand, cases of definite or probable vCJD in the United Kingdom have continued to increase and now number 146; one case has occurred in Ireland. n

Human and Feline Sporotrichosis in Rio

Source:Barros M, et al.Clin Infect Dis. 2004;38:529-535.

For the past few years, rio de Janeiro has been experiencing the largest epidemic of feline and human sporotrichosis ever reported. From 1998 to 2001, 178 culture-proven cases of sporotrichosis occurred in persons living in various municipalities of Rio—beginning with 9 cases in 1998 and peaking at 91 cases in 2001. Human cases occurred coincident with an outbreak of feline sporotrichosis in the same areas. Further investigation demonstrated that 156 affected persons (91%) had close household or professional contact with cats with sporotrichosis, and 111 (65%) reported a cat scratch or bite before developing their infection. Five percent of those affected were veterinarians, although adult women were the most commonly affected group, possibly because they are in closer contact with pets or provided more care for the animals.

About 55% of the human cases presented with lymphocutaneous disease, 25% presented with localized cutaneous disease, 16% presented with extensive cutaneous involvement, and 3% with mucosal or conjunctival involvement. In addition, 30% of patients presented with arthralgias, 4% developed erythema nodosum, and 1% developed erythema multiforme. All of the patients received itraconazole as first-line therapy, except for 13 (7%) patients who had spontaneous remission. Spontaneous remission has been rarely reported in the past, but may have occurred more frequently in this group given the nature of the inoculation and the lack of significant underlying disease in most of the patients.