Updates
by Carol A. Kemper, MD, FACP
An Oral Agent for Smallpox?
Source: Aldern KA, et al. Mol Pharmacol. 2003;63:678-681.
Cidofovir (CDV), which was licensed in the United States in 1996 for the treatment of cytomegalovirus retinitis, has been used successfully in a number of other viral infections, including those due to drug-resistant herpes simplex, varicella-zoster, and adenovirus. Furthermore, as reported previously in Infectious Disease Alert,* CDV may be the only licensed agent available with efficacy against smallpox virus. When administered parenterally, it protected against lethal poxvirus challenge in a murine model. Finding an orally bioavailable drug with similar efficacy is a priority.
Aldern and colleagues have been investigating 2 orally active derivatives of CDV and cyclic CDV, called HDP-CDV and HDP-cCDV. Compared with the parent compounds, the derivatives demonstrate greater than 100-fold increased activity against cells infected with orthopoxvirus, cowpox, and vaccinia virus.
The basis for this tremendous increase in antiviral activity may be due to an unusual characteristic of the 2 derivatives, which appear to be rapidly taken up by human cells, possibly by associating with the cellular membrane phospholipids. When MRC-5 human fibroblasts were exposed in vitro to HDP-CDV compared with CDV, their intracellular half-lives were 10 vs 2.7 days. In addition, intracellular concentrations of the cellular metabolites of these agents were more than 100 times greater with HDP-CDV than with CDV. Intracellular uptake of CDV and cCDV, which appears to occur as the result of fluid endocytosis, was considerably slower.
*Kemper CA. Infectious Disease Alert. 2003;22(12):96.
Neonatal Legionella from Home Water Birth
Source: Nagai T, et al. J Clin Microbiol. 2003;41:2227-2229.
Water births have become increasingly popular in Europe and the United States but still are uncommon in Japan, where an apparently healthy baby girl died unexpectedly 8 days after delivery in a home water bath system. The mother had no problems during her pregnancy, and the 42-week gestation infant was healthy at birth. On the fourth day, she developed fever and jaundice requiring admission to hospital for 1 day, which quickly resolved. On the eighth day, she developed sudden apnea and could not be resuscitated. Autopsy revealed numerous scattered pulmonary nodules (< 5 mm in diameter). Many Gram-negative, Gimenez-positive red bacteria were found within pulmonary macrophages. Legionellosis was suspected, but cultures could no longer be obtained. However, molecular analysis demonstrated a 100% match with the mip gene of L pneumophila serogroup 1, 2, and 6, and immunofluorescence staining detected Legionella serogroup 6. Further investigation of the home found numerous legionella organisms in the home water spa system.
Nosocomial legionella from contaminated hot water systems in hospitals has been well described, and a single case of nosocomial legionella was reported in a water birth baby in Italy in 1999. This is the first case of community-acquired neonatal legionella as the result of a contaminated home water system.
The 24-hour ever-ready home water spa is apparently quite popular in Japan, where more than 1.5 million units have been sold. The system fits in an ordinary bathtub, circulates and filters the water, which is heated to 40°C, and then applies various chemical disinfectants. The water does not have to be changed for up to 1 month. While probably adequate for most bacteria, such a system is a perfect milieu for all kinds of organisms, including legionella, pseudomonas, free-living amoeba, and atypical bacteria. In fact, several members of a Japanese family developed cutaneous Mycobacterium avium complex infection from a similar contaminated home water spa.
Nagai and colleagues point out that, although these systems are probably suitable for normal hosts, they represent a potential hazard to immunocompromised persons and neonates. Patients should be counseled that home water births in a similar spa or hot tub should not be attempted.
Waiting in the Wings?
Source: Wolf R, Wolf D. J Am Acad Dermatol. 2003;48:S73-S74.
Speaking of cutaneous mac infection resulting from a home spa, Wolf and Wolf report a case of cutaneous atypical mycobacteria infection from a butterfly tattoo. Although tattooing is a well-recognized risk for transmission of several key infectious agents, especially hepatitis C infection, this is first reported case of transmission of a nontuberculous bacteria from a tattoo. Skin biopsy specimens revealed acid-fast bacilli, with positive Ziehl Neelsen staining. PCR tests were positive for a nontuberculous mycobacteria, but the organism was not further identified.
Diagnostic Testing for SARS
Sources: ProMEDmail, June 4, 2003, and June 19, 2003; the WHO WER and Epidemiological Bulletin, http://www.who.int/csr/don; CDC. MMWR. Morb Mortal Wkly Rep. 2003;52:500-501.
As of June 2, The Weekly Epidemiological Record is reporting a cumulative total of 8384 probable cases of SARS and 770 deaths from 29 countries. The 27 new deaths were reported from China and Hong Kong. Although several laboratories are working hard to develop commercially available diagnostic tests for SARS corona virus (SARS Co-V), the process has been slower than hoped, mostly because of several unusual and unexpected features of the SARS Co-V infection. Indirect immunoflourescence assays for IgM and IgG antibodies directed against SARS Co-V have been developed, and PCR testing can be done on clinical specimens, including nasal swabs, sputum, serum, and stool, but the diagnostic sensitivity of these tests is not adequate, especially in the early phases of infection. Whereas a greater amount of viral shedding typically occurs during the initial phase of most viral illnesses, SARS appears to be different. It turns out that viral shedding is fairly low during the initial phase of SARS but then peaks in respiratory and stool specimens about 10 days after the onset of symptoms. Serologic response to infection does not begin to appear until the fifth or sixth day of symptomatic illness, and current antibody tests may not be able to detect antibodies until at least day 10.
In the United States, the MMWR reports that 363 SARS cases were reported from 41 states and Puerto Rico; 297 (82%) of these were classified as suspect and 66 (18%) as probable. Serologic testing for SARS Co-V antibody has been performed in 32 (48%) of the probable cases, 7 of which were positive. Among these, 4 had positive serology within 12 days of symptom onset, 3 others had negative serologies at days 4, 6, and 14, respectively, but serologic tests performed on the next available specimen were positive at days 28, 25, and 41, respectively. A sputum specimen collected at 14 days of illness was PCR positive in 1 patient, but serum antibody was not detected until later.
Although greatly complicating the diagnostic evaluation, this pattern of viral shedding in SARS infection may be fortunate in one respect—there is thus far no evidence that transmission has occurred from asymptomatic persons or during the incubation period (which appears to be about 4-6 days).
The WHO continues to advocate the use of the SARS case definition for management and isolation of suspect cases, at least until such time as better testing is available. The CDC is presently classifying a case as non-SARS only if a negative serology is obtained more than 21 days after symptom onset. Authorities were initially clearing patients if a cause other than SARS, such as influenzae B, co
uld be identified. However, one patient with respiratory symptoms and pneumonia, who had contact with another probable case, was demonstrated to have Mycoplasma pneumonia and cleared from isolation. Weeks later, blood tests showed evidence of seroconversion to SARS—in addition to Mycoplasma! As several physicians have pointed out, patients with respiratory illness may have 2 concurrent infections, as has been demonstrated in about 10-15% of pneumonias.
Based on the current situation, officials are anticipating that SARS is here to stay, although the incidence of infection may eventually prove to be more seasonal. In the United States, we may be moving toward a need for better containment policies and the designation of specific facilities for medical care of possible cases.
Dr. Kemper is Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center Section Editor, Updates Section Editor, HIV
Cidofovir (CDV), which was licensed in the United States in 1996 for the treatment of cytomegalovirus retinitis, has been used successfully in a number of other viral infections, including those due to drug-resistant herpes simplex, varicella-zoster, and adenovirus.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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