An outbreak of influenza a caused by imported virus in the United States, July 1999.

We report 32 cases of culture-proven influenza A (A/Sydney) caused by virus imported into mainland US military barracks from Puerto Rico in July 1999. Despite the fact that the shelf life of the influenza vaccine is 18 months and that the outbreak strain was a component of the previous year's vaccine, no vaccine was available from manufacturers, owing to US Food and Drug Administration regulations. Formal consideration should be given to extending the date of expiration and to maintaining a supply of the influenza vaccine year-round.

Abiotrophia bacteremia in a patient with neutropenic fever and antimicrobial susceptibility testing of Abiotrophia isolates.

We report a case of bacteremia due to Abiotrophia species in a patient with neutropenic fever and cancer who was receiving levofloxacin prophylaxis, followed by empirical therapy with cefepime; the organism was resistant to both antibiotics. We provide susceptibility data on 20 additional bloodstream isolates of Abiotrophia species.

Global survey of genetic variation in CCR5, RANTES, and MIP-1alpha: impact on the epidemiology of the HIV-1 pandemic.

Expression of CC chemokine receptor 5 (CCR5), the major coreceptor for HIV-1 cell entry, and its ligands (e.g., RANTES and MIP-1alpha) is widely regarded as central to the pathogenesis of HIV-1 infection. By surveying nearly 3,000 HIV+ and HIV- individuals from worldwide populations for polymorphisms in the genes encoding RANTES, MIP-1alpha, and CCR5, we show that the evolutionary histories of human populations have had a significant impact on the distribution of variation in these genes, and that this may be responsible, in part, for the heterogeneous nature of the epidemiology of the HIV-1 pandemic. The varied distribution of RANTES haplotypes (AC, GC, and AG) associated with population-specific HIV-1 transmission- and disease-modifying effects is a striking example. Homozygosity for the AC haplotype was associated with an increased risk of acquiring HIV-1 as well as accelerated disease progression in European Americans, but not in African Americans. Yet, the prevalence of the ancestral AC haplotype is high in individuals of African origin, but substantially lower in non-Africans. In a Japanese cohort, AG-containing RANTES haplotype pairs were associated with a delay in disease progression; however, we now show that their contribution to HIV-1 pathogenesis and epidemiology in other parts of the world is negligible because the AG haplotype is infrequent in non-Far East Asians. Thus, the varied distribution of RANTES, MIP-1alpha, and CCR5 haplotype pairs and their population-specific phenotypic effects on HIV-1 susceptibility and disease progression results in a complex pattern of biological determinants of HIV-1 epidemiology. These findings have important implications for the design, assessment, and implementation of effective HIV-1 intervention and prevention strategies.

Clinical implications of identifying non-B subtypes of human immunodeficiency virus type 1 infection.

Although human immunodeficiency virus type 1 (HIV-1) infection in the United States has predominantly involved subtype B, increasing global travel is leading to wider dissemination of genetically heterogeneous subtypes. While physicians depend on HIV-1 viral load measurements to guide antiretroviral therapy, commonly used molecular assays may underestimate the viral load of patients with non-B subtypes. Nine patients with non-B subtypes of HIV-1 were identified by physicians who suspected a non-B subtype on the basis of a low or undetectable HIV-1 viral load, by the Amplicor HIV-1 Monitor test, version 1.0, in conjunction with either a declining CD4 cell count or history of travel outside the United States. Use of version 1.5 of the Amplicor HIV-1 Monitor test detected a median HIV-1 viral load that was 2.0 log(10) RNA copies/mL higher than was determined with version 1.0. Clinical management was altered in all cases after diagnosis of a non-B-subtype infection. These cases demonstrate that it is critical for physicians to suspect and diagnose non-B subtypes of HIV-1 so that an assay with reliable subtype performance can be used to guide antiretroviral therapy.

Influenza A in a basic training population: implications for directly observed therapy.

PURPOSE: To describe our evaluation of basic trainees exposed to influenza A and our experience with mass prophylaxis. METHODS: Using a structured interview, 101 individuals were evaluated for symptoms of influenza A. Nasopharyngeal wash specimens were obtained from symptomatic troops; amantadine prophylaxis was prescribed for all. Diagnosis was confirmed using a rapid influenza assay or shell vial culture. After completing prophylaxis, the group was reevaluated to determine medication compliance and perceived side effects. RESULTS: At baseline, 80 trainees reported symptoms. Three additional cases of influenza were identified, two using the rapid assay. Reported compliance with amantadine prophylaxis was 46.5%. CONCLUSIONS: Nonspecific complaints that could be consistent with viral infection were numerous in this basic trainee cohort. The rapid assay allowed us to expediently identify additional patients, who were then removed from the cohort to limit further transmission. Compliance with prophylaxis was poor; thus, directly observed therapy is recommended.

Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.

Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.

Rickets and protein malnutrition in northern Nigeria.

The aim of the study was to explore the relationship between protein nutritional status and the development of rickets in children living in northern Nigeria. The diagnosis of rickets in 16 children between the ages of 10 months and 7 years was confirmed using established, and recently developed clinical and biochemical parameters. Twenty-seven children devoid of skeletal stigmata were age- and sex-matched to the rachitic patients. A battery of clinical laboratory and anthropometric measurements designed to assess calcium homeostasis, skeletal growth, the extent of bone remodeling or resorption, and protein nutritional status were performed on all subjects. Our central finding was that although the rachitic children were moderately malnourished, their protein nutritional status was significantly better as measured by the serum prealbumin concentration (15.4 v. 12.5 mg/dl, P = 0.0012) when compared with the severely malnourished children who were devoid of any indication of rickets. This may be due, in part, to the fact that actively growing children are more likely to develop rickets than are children whose linear growth is impeded. Unexpectedly, we found that the mean concentrations of serum 1,25-dihydroxyvitamin D in both the rachitic and control group were higher than any values for the active vitamin D metabolite previously reported in the literature.

Infection in the bone marrow transplant recipient.

Bone marrow transplantation (BMT) is widely used in the treatment of myelodysplastic disorders and leukemia. Despite improvements in patient management, infection as a consequence of the immunodeficiency states that follow BMT remains a significant cause of morbidity and mortality. This article provides an overview of the major infections after BMT with an emphasis on new developments in diagnosis, treatment, and prophylaxes that have occurred in recent years.

Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor.

BACKGROUND: Cytomegalovirus (CMV) disease in immunocompromised patients correlates with a deficiency of CD8+ cytotoxic T lymphocytes specific for CMV. We evaluated the safety and immunologic effects of immunotherapy with clones of these lymphocytes in recipients of allogeneic bone marrow transplants. METHODS: Clones of CD8+ cytotoxic T cells specific for CMV proteins were isolated from the blood of bone marrow donors. Fourteen patients each received four intravenous infusions of these clones from their donors beginning 30 to 40 days after marrow transplantation. The reconstitution of cellular immunity against CMV was monitored before and during the period of infusions and for up to 12 weeks after the final infusion. The rearranged genes encoding the T-cell receptor served as markers in evaluating the persistence of the transferred T cells. RESULTS: No toxic effects related to the infusions were observed. Cytotoxic T cells specific for CMV were reconstituted in all patients. In vitro measurements showed that cytotoxic activity against CMV was significantly increased (P < 0.001) after the infusions in 11 patients who were deficient in such activity before therapy. The level of activity achieved after the infusions was similar to that measured in the donors. Analysis of rearranged T-cell-receptor genes in T cells obtained from two recipients indicated that the transferred clones persisted for at least 12 weeks. Cytotoxic-T-cell activity declined in patients deficient in CD4+ T-helper cells specific for CMV, suggesting that helper-T-cell function is needed for the persistence of transferred CD8+ T cells. Neither CMV viremia nor CMV disease developed in any of the 14 patients. CONCLUSIONS: The transfer of CMV-specific clones of CD8+ T cells derived from the bone marrow donor is a safe and effective way to reconstitute cellular immunity against CMV after allogeneic marrow transplantation.

Serum levels of the pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin in rachitic children in Nigeria.

OBJECTIVES: We measured the levels of the pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) in the serum of 12 rachitic and 27 healthy Nigerian children, and compared the performance of these relatively new markers of bone metabolism with established laboratory parameters of skeletal disease. DESIGN AND METHODS: Active rickets was diagnosed on the basis of clinical and biochemical criteria. Serum calcium and phosphorus concentration and alkaline phosphatase activity were determined using clinically accepted methods. Radioimmunoassay was performed to quantify parathyroid hormone, 1-,25-dihydroxyvitamin D, OC, and ICTP. RESULTS: The rachitic children had statistically significant serum elevations of ICTP and osteocalcin as compared with age- and sex-matched controls. Serum levels of ICTP correlated with alkaline phosphate activity. CONCLUSIONS: As a marker of abnormal bone metabolism, ICTP performs at least as well as alkaline phosphate. ICTP and OC are valuable additions to the growing repertoire of bone markers.

Feasibility of the peroral pneumocolon in evaluating the ileocecal region.

Retrograde insufflation of air into the terminal ileum via a rectal tube (peroral pneumocolon) is a simple adjunct to the conventional gastrointestinal small-bowel follow-through examination. The purpose of this study was to determine the feasibility and diagnostic value of peroral pneumocolon in 170 patients who were being evaluated by upper gastrointestinal series with conventional small-bowel follow-through. Retrograde passage of air into the terminal ileum was successful in 87% of 140 patients with normal anatomic relations and in all 30 patients with small bowel-colonic anastomoses. In most cases, retrograde air insufflation yielded additional diagnostic information, particularly in detection of ulcerations, edematous mucosa, and cobblestone patterns. The length of the small bowel segment affected by pathologic changes could be determined more accurately in over 60% of the peroral pneumocolon examinations. No procedure-related complications were observed.