Clifton A. Hawkes

Hospitalizations for fungal infections after renal transplantation in the United States

Abstract: Fungal infections in renal transplant recipients have not been studied in a national population. Therefore, 33,420 renal transplant recipients in the United States Renal Data System from 1 July 1994 to 30 June 1997 were analyzed in a retrospective registry study of hospitalized fungal infections (FI). FI were most commonly associated with secondary diagnoses of esophagitis (68, 23.9%), pneumonia (57, 19.8%), meningitis (23, 7.6%), and urinary tract infection (29, 10.3%). Opportunistic organisms accounted for 95.4% of infections, led by candidiasis, aspergillosis, cryptococcosis, and zygomycosis. Most fungal infections (66%) had occurred by six months post‐transplant, but only 22% by two months. In logistic regression analysis, end‐stage renal disease due to diabetes, duration of pre‐transplant dialysis, maintenance tacrolimus and allograft rejection were associated with FI. In Cox regression analysis, recipients with FI had a relative risk of mortality of 2.88 (95% CI=2.22–3.74) compared to all other recipients. Among FI, zygomycosis and aspergillosis were independently associated with both increased patient mortality and length of hospital stay. Most fungal infections in renal transplant recipients were opportunistic, occurred later than previously reported, and were associated with greatly decreased patient survival. Recipients with diabetes, prolonged pre‐transplant dialysis, rejection, and tacrolimus immunosuppression should be considered high risk for FI.

Hospitalizations for Cytomegalovirus Disease after Renal Transplantation in the United States

PURPOSE Risk factors, sites, and mortality of hospitalized cytomegalovirus (CMV) disease in renal transplant recipients have not been studied in a national population. METHODS Therefore, 33,479 renal transplant recipients in the United States Renal Data System from 1 July 1, 1994 to June 30, 1997 were analyzed in an historical cohort study of patients with a primary discharge diagnosis of CMV disease (ICD9 Code 078.5x). RESULTS Renal transplant recipients had an incidence density of hospitalized CMV disease of 1.26/100 person years, and 79% of hospitalizations for CMV disease occurred in the first six months post transplant. The leading manifestation of hospitalized infection was pneumonia (17%). In logistic regression analysis controlling for transplant era, pre-transplant dialysis > or = 6 months, maintenance mycophenolate mofetil (MMF) therapy, and allograft rejection, but not induction antibody therapy, were significantly associated with hospitalized CMV disease. Compared with recipients with negative CMV serology (R-) who had donor kidneys with negative CMV serology (D-), D+/R- had the highest risk of hospitalization for CMV disease [adjusted odds ratio (AOR) 5.19, 95% confidence interval (CI) 3.89-6.93] followed by D+/R+ recipients, whereas D-/R+ were not at significantly increased risk. In Cox Regression analysis the relative risk of death associated with hospitalized CMV disease was 1.32 (95% CI 1.02-1.71). CONCLUSIONS Even in modern era, renal transplant recipients were at high risk for hospitalizations for CMV disease, which were associated with decreased patient survival. Current prophylactic measures have apparently not reduced the high risk of D+/R- recipients. Prolonged pre-transplant dialysis and maintenance MMF should also be considered risk factors for hospitalized CMV infection, and prospective trials of prophylactic antiviral therapy should be performed in these subgroups.

Lack of Vaccinia Viremia after Smallpox Vaccination

Although the transmission of certain viral infections (human immunodeficiency virus, hepatitis B and C viruses, and West Nile virus) through donated blood products is well described, the risk of transmitting vaccinia virus after smallpox vaccination is unknown. Blood samples from patients receiving the smallpox vaccine were obtained before vaccination; then from one-half of the study group on alternate days for each of the first 10 days after vaccination; then from all patients on days 14 and 21 after vaccination. Samples were analyzed by culture, polymerase chain reaction, and antigen detection (electrochemiluminescence) assay for the presence of vaccinia virus. Two hundred and twenty samples from 28 volunteers were processed by all 3 laboratory detection methods and all were negative for the presence of vaccinia virus (confidence interval, 0%-12.3%). Viremia with vaccinia virus after smallpox vaccination appears to be an uncommon occurrence.

Human Immunodeficiency Virus RNA Levels in US Adults: A Comparison Based upon Race and Ethnicity

Volunteers in a natural history study of human immunodeficiency virus type 1 (HIV-1) at two military medical centers were studied to determine whether plasma HIV-1 RNA levels differ among racial and ethnic groups of US adults infected with HIV-1. Cross-sectional analyses of plasma HIV-1 RNA and CD4 cell counts were done using demographic and clinical data collected during study visits. Age, gender, CD4 cell count, seroconversion status, and use of antiretroviral therapy were studied in 545 military members (46% white, 49% black, and 6% Hispanic). No association was found between HIV-1 RNA levels and race or ethnicity among infected adults for whom access to care and socioeconomic status were not confounding factors.

CD38 expression on cryopreserved CD8+ T cells predicts HIV disease progression.

Previous studies have revealed that the expression of CD38 on CD8+ T cells is a strong predictor of disease progression in human immunodeficiency virus (HIV)-infected individuals. Those studies were performed using fresh patient samples over an extended trial period. After demonstrating the validity of assay results on cryopreserved cells, we performed a retrospective study using frozen cell samples to determine the predictive value of CD38 expression in patients with CD4 counts above 400 cells/microl. The CD38 expression as measured by antibody binding capacity and the CD38 median channel were shown to be associated with time to new opportunistic infection or death (both P < 0.001). These results suggest that CD38 expression on CD8+ T cells, whether fresh or frozen, provides a useful predictor of HIV disease progression.

An outbreak of urticaria among soldiers deploying for combat

An outbreak of urticaria among soldiers deploying for combat Dear Sir, Before deploying overseas, American military personnel receive a battery of vaccinations specific for their destination. Rabies human diploid cell vaccine (HDCV), Imovax® (Aventis Pasteur, Strasbourg, France), is administered to certain troops en route to Africa and Asia where rabies is common in feral animals and the troops do not have ready access to health care. Although adverse reactions to rabies HDCV are uncommon, 1 we report an outbreak of rabies HDCV-associated urticaria in a unit deploying for combat. A 42-year-old man developed generalized pruritus with scattered edematous red wheals over his trunk and swelling of his right upper eyelid. He had received the second immunization in the series of the rabies HDCV 14 days earlier. On examination, he was noted to have clearly defined blanching, edematous, red plaques with no evidence of petechiae, purpura, peripheral edema or lymphadenopathy. He denied fevers or arthralgias. We examined 12 additional men who over the previous few days had presented to medical personnel with similar complaints. The interval from receiving the HDCV immunization to the onset was urticaria was 5–15 days. Six patients received treatment with oral antihistamines with or without prednisone and all cases resolved without sequelae. We recently investigated an outbreak of urticaria in 13 soldiers at a processing center for overseas deployment. The 13 men all shared the common cutaneous finding of urticaria. These 13, along with 305 other soldiers in their group, had received a booster dose of the rabies HDCV or the second or third doses in the 3-dose pre-exposure series. The overall rate of urticaria was 4.3%. No other noteworthy adverse reactions were reported. The standard rabies vaccine series consists of three 1.0-ml intramuscular doses of rabies HDCV given on days 0, 7 and either 21 or 28. 2 The Advisory Committee on Immunization Practices recommends booster vaccination at 6 months or 2 years depending on the exposure risk and serologic status. Urticarial reactions to rabies HDCV occur more frequently after the booster rather than the primary immunization. 1 The reported incidence of urticaria in patients receiving the rabies HDCV ranges from 2 to 7%. 1,3 They are thought to represent a Type III hypersensitivity-mediated immune response rather than a Type 1 IgE-mediated event. 3 Skin biopsies from rabies HDCV-associated urticarial lesions often demonstrate a leukocytoclastic vasculitis with neutrophil and lymphocytic infiltrates; fibrin and C1q granular deposits may be found on direct immunofluorescence. 3 Although, histological findings support the presence of immune complex-mediated urticaria, there is no laboratory evidence (proteinuria, elevated creatinine or blood urea nitrogen) of renal or other systemic involvement. In this outbreak of HDCV-associated urticaria, none of the patients had clinical evidence of serum sickness; however, no laboratory investigations were performed. Because HDCV is rarely administered to large cohorts of individuals, an outbreak such as this one has not been reported previously.

Persistence of Vaccinia at the Site of Smallpox Vaccination

Persistence of vaccinia at vaccination sites may help determine the risk associated with secondary transmission. Culture, PCR, and antigen detection were performed on serial vaccination site swab specimens. On day 21 after vaccination, 37% of volunteers were culture positive, most of whom had received vaccine for the first time. Vaccinia is detectable at least through day 21 after vaccination.