Updates-By Carol A. Kemper, MD, FACP
July 15, 2000 4 minutes read
Updates-By Carol A. Kemper, MD, FACP
Clonal Divergence Predicts Outcome in HCV
Source: Farci P, et al. Science 2000; 288:339-344.
This fascinating article presents some intriguing insights into a possible mechanism leading to the differing outcomes of patients acutely infected with Hepatitis C virus (HCV). While HCV seldom results in fulminant and occasionally fatal hepatitis, most patients (~85%) are destined to develop chronic, persistent infection, although a few successfully clear the virus. There has, thus far, been no way to predict individual outcome in patients who are acutely infected.
In general, HCV elicits a strong cellular and humoral response, which is, unfortunately, insufficient in most patients to eliminate virus. The virus is then free to rapidly multiply and—similar to HIV—genetically evolve and diverge, thus creating an array of genetic variants, or quasispecies. The complex interplay between the development of these quasispecies, which may be able to evade the host immune response, and the rapidity of the host’s ability to mount an effective response is critical to the patient’s outcome.
By examining viral sequences of the envelope genes E1 and E2, both within and outside the hypervariable region (HVR1), in 12 patients with HCV and varying outcomes, Farci and colleagues observed significant differences in the genetic diversity of HCV before and after seroconversion in patients with resolving vs. fulminant hepatitis. Patients with fulminant hepatitis had the lowest genetic divergence before and after seroconversion, despite the highest viral loads. In contrast, there was a greater degree of genetic divergence, especially over the first four months of infection, in those patients who progressed to chronic infection. Farci et al postulated that this viral diversity occurs as the result of selective pressure on the HVR1 gene, with the emergence of strains more fit to replicate in the face of a marginal host response. In an interesting twist, the number of clones was not important, but rather the degree of genetic diversity or phylogenetic distance between the clones.
On the other hand, patients who clear their infection may lie somewhere in the middle, with evidence that viral clearance is associated with a reduction in viral diversity over time. Thus, as Farci et al explain, an optimally balanced response is to selectively and progressively contain viral replication—and variation—until the last clone is eliminated—but just not too quickly.
Stenotrophomonas a Dirty Organism?
Source: Daley AJ, et al. J Trauma Injury Crit Care 2000;48:536-537.
Two children presented with acute traumatic lawn mower injuries resulting in extensive lower extremity lacerations and fractures. Both cases were treated aggressively with debridement and repair of the fractures, and antimicrobials. Nonetheless, as is common with traumatic injuries from farm equipment and lawn mowers, both cases were complicated by wound infection and, in one case, osteomyelitis. In both cases, swab cultures obtained at 2 and 4 days from the surface wounds yielded Stenotrophomonas maltophilia (sensitive only to ticarcillin-clavulanate and cotrimoxazole). Although initially thought to be a wound colonizer, cultures of the deep tissues and bone repeatedly grew the same organism.
Daley and associates point out that, although it is often believed to be a wound colonizer, S. maltophilia can be a significant pathogen is certain cases. Traumatic injuries from outdoor, high-velocity mechanical equipment like corn huskers and lawn mowers are often complicated by polymicrobial infection with organisms typically found in soil and vegetation, including fungi. S. maltophilia is a motile, gram-negative bacillus that is widely distributed in the environment, including soil, vegetation, and water. It produces two distinct beta-lactamases, which result in its unique and broad resistance to most antibacterials. Its presence in these types of wounds may, therefore, be significant and should not be overlooked. These two cases also underscore the importance of obtaining good tissue and bone specimens for culture in complex wound infections.
D4T Increases the MCV, too
Source: Geene D, et al. J Infect 2000; 40:160-163.
Macrocytosis as the result of zidovudine (AZT) treatment in patients with HIV infection is so common as to be used as a surrogate marker for medication compliance. But what about HIV-infected patients with macrocytosis who are not receiving AZT?
Geene and colleagues performed a case-control study comparing 30 HIV-positive patients with macrocytosis with 60 HIV-positive patients without macrocytosis, none of whom were receiving AZT. There was no apparent difference in the two groups with regard to age, sex, CD4+ cell count, alcohol use, or underlying liver disease. In addition, none of the patients with macrocytosis had evidence of folate or B12 deficiency. However, patients with macrocytosis were significantly more likely to be receiving stavudine (d4T) than controls (93% vs 25%) (odds ratio = 40.6%, P < 0.001). Like its thymidine precursor cousin, d4T commonly results in macrocytosis in patients with HIV infection.
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