Emerging viral diseases and infectious disease risks.

New pathogens and antimicrobial-resistant forms of older pathogens continue to emerge, some with the potential for rapid, global spread and high morbidity and mortality. Pathogens can emerge either through introduction into a new population or when the interaction with the vector changes; emergence is also influenced by microbiological adaptation and change, global travel patterns, domestic and wild animal contact and other variants in human ecology and behaviour. Quick, decisive action to detect and control novel pathogens, and thereby contain outbreaks and prevent further transmission, is frequently hampered by incomplete or inadequate data about a new or re-emerging pathogen. Three examples of pathogens that are current causes for human health concern are avian influenza, West Nile virus (WNV) and the severe acute respiratory syndrome (SARS) coronavirus. Pathogens directly or indirectly transmitted by aerosolized droplets, such as avian influenza and SARS, pose considerable containment challenges. Rapid screening tests for other newly described pathogens such as WNV require time for development and may be <100% reliable. The importance of vigilance in the detection and control of newly recognized infectious threats cannot be overstressed. The presence of infectious agents in the blood supply could again have a significant impact on the safe use of both blood and blood-derived products in the care of patients with haemophilia, as did the human immunodeficiency virus in the 1980s. Emerging pathogens will continue to be a reality requiring the collaborative efforts of public health and individual healthcare providers worldwide to contain outbreaks and prevent transmission.

Tuberculosis control in health care.

This article describes the basic framework for developing a tuberculosis (TB) control program. We suggest how to assess the risk of TB in a healthcare delivery setting, how to prioritize control measures based on their effectiveness, and how to meet current regulatory requirements. In addition, we discuss some problematic issues, examples of how other hospitals have confronted these issues, and where to obtain additional information on nosocomial TB.

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

Frequency of hyponatremia and nonosmolar vasopressin release in the acquired immunodeficiency syndrome.

The frequency and pathophysiology of hyponatremia were studied in the acquired immunodeficiency syndrome. Of 71 hospitalized patients surveyed retrospectively, hyponatremia was observed in 37 (52%). Of 48 patients studied prospectively, 27 (56%) were hyponatremic. In 16 hyponatremic patients, volume status; serum and urine osmolalities; renal, adrenal, and thyroid function; and plasma vasopressin levels were assessed. Urine osmolalities were inappropriately elevated (mean, 377 mmol/kg of water) relative to serum osmolalities (mean, 268 mmol/kg of water). Four patients had moderate renal insufficiency. Plasma vasopressin levels were elevated in 15 patients, with the highest levels seen in patients who died (median, 7.08 pmol/L). Hyponatremia of multiple etiologies occurred in a majority of inpatients with the acquired immunodeficiency syndrome, often following the administration of hypotonic fluids, and was associated with a 30% (8/27) short-term mortality.

Successful prophylaxis of Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole in AIDS patients with previous allergic reactions.

Thirty-four homosexual patients with AIDS were treated for Pneumocystis carinii pneumonia between April 1984 and November 1985. All 31 survivors were treated with oral trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis immediately upon completion of intravenous therapy, despite the prior occurrence of hypersensitivity reactions to intravenous TMP-SMX in 21 of these patients. Only four patients had subsequent reactions to oral TMP-SMX requiring the drug's discontinuation. None of the patients remaining on prophylaxis developed recurrent Pneumocystis pneumonia. Oral TMP-SMX appears effective at preventing recurrent Pneumocystis pneumonia in patients with AIDS. Hypersensitivity reactions during therapy with TMP-SMX may not be a contraindication to continuation of therapy and subsequent oral prophylaxis.

Cytomegalovirus infection of the alimentary tract: a clinicopathological correlation.

Alimentary tract cytomegalovirus (CMV) infections of 24 patients were reviewed, including 19 with the acquired immune deficiency syndrome. CMV inclusion bodies (CMV-IB) were calibrated per mm2 of tissue. CMV-IB counts were correlated with biopsy site, inflammatory response, and clinical parameters. Colonic biopsies showed the highest counts. Biopsies of the right colon had about three times as many CMV-IBs as those of the left. Upper alimentary tract biopsies had low counts. Mesenchymal cells were most affected (97%); 35% were identified as endothelial and 6% as smooth muscle. Only 3% of CMV-IBs were in epithelial cells. Grades of inflammation, 1-5, correlated directly with CMV-IB counts up to grade 4. In grade 5 inflammation tissue destruction was so severe that CMV-IBs were difficult to recognize. Ulcers were demonstrated in more than half of all patients, either histologically or endoscopically. The inflammatory response was nonspecific, except for patchy infiltrates and the absence of lymphoid follicles, crypt abscesses, or granulomas. Gastrointestinal infections, such as shigellosis, candidiasis, mycobacteriosis, and cryptosporidiosis coexisted in 17 patients. No correlation was found between CMV-IB counts and severity of symptoms or length of survival. Alimentary tract CMV infections was the first manifestation of the acquired immune deficiency syndrome in 11 patients. Survival ranged from 2 wk to 19 months.

Clinical features of Pneumocystis pneumonia in the acquired immune deficiency syndrome.

The courses of 19 patients with Pneumocystis carinii pneumonia complicating the acquired immune deficiency syndrome (AIDS) were reviewed. Compared with previous reviews of Pneumocystis pneumonia in patients without AIDS, Pneumocystis pneumonia in patients with AIDS often has a more prolonged clinical prodrome, with pulmonary symptoms occurring for an average of 3 wk prior to presentation, and often has a slower response to therapy, with radiographic and blood gas improvement occurring an average of 13 and 6 days, respectively, after initiation of therapy. No patient diagnosed during life died as a result of Pneumocystis infection; however, 5 required repeat courses of therapy, and 7 required repeat lung biopsies during the course of treatment. Serious side effects of trimethoprim-sulfamethoxazole therapy included fever, rash, and leukopenia, and occurred in 12 patients. Aggressive diagnostic and therapeutic measures combined with prolonged therapy are required for a satisfactory outcome in patients with AIDS and Pneumocystis pneumonia.

'Culture-negative' prosthetic valve endocarditis. Hazards of postoperative steroid therapy for unexplained fever.

Two patients had prolonged unexplained fever along with multiple negative blood cultures after cardiac valve replacement surgery. Following the administration of corticosteroids for presumed postpericardiotomy syndrome, both patients improved symptomatically and defervesced, only to have positive blood cultures for Staphylococcus epidermidis shortly thereafter. The theoretical and practical risks of the empiric use of anti-inflammatory agents for unexplained post-operative fever are reviewed. "Culture-negative" prosthetic valvular infection due to prior antibiotic prophylaxis or therapy must be strongly considered in the evaluation of such unexplained fever.

Opportunistic infection complicating acquired immune deficiency syndrome. Clinical features of 25 cases.

Twenty-five cases of acquired immune deficiency syndrome (AIDS) complicated by opportunistic infections were diagnosed at Lenox Hill Hospital during an 18 month period and followed for at least 1 year or until the patients' deaths. Twenty-three patients were homosexual men, including 1 i.v. drug user, and 2 were heterosexual i.v. drug users, including the sole woman. Seventy infections were diagnosed. The commonest etiologic agents included Candida albicans, Pneumocystis carinii, cytomegalovirus, and Mycobacterium avium-intracellulare. Less frequent pathogens included Cryptococcus neoformans, Toxoplasma gondii, Cryptosporidium, JC virus, Mycobacterium xenopi, and Mycobacterium tuberculosis. Seven men also had Kaposi's sarcoma. Prodromal symptoms lasted up to 8 months before the diagnosis of AIDS. Immunologic and serologic evaluation demonstrated lymphopenia, polyclonal hypergammaglobulinemia, cutaneous anergy, reversal of the T-cell helper/suppressor ratio, and serologic evidence of previous exposure to CMV, EBV, and HBV. Pneumocystis pneumonia was diagnosed during life in 17 patients, by transbronchial biopsy and bronchoscopic washings, and all 17 cases were successfully treated. However, pneumocystis was more refractory to treatment than previously described and required an average of 29 days of antimicrobial therapy. Disseminated infections with atypical mycobacteria and cytomegalovirus were the leading causes of death. Bone marrow aspirates and biopsies often revealed a cellular abnormality (82%) but only occasionally yielded an infectious diagnosis (32%). However, bone marrow examinations were the major means of detecting atypical mycobacteriosis. Colonoscopic biopsies were most useful for establishing the presence of cytomegalovirus colitis. Transbronchial biopsies and bronchial washings gave a high yield of opportunistic pathogens including 34 infectious diagnoses confirmed by 31 procedures. Multiple site biopsies and close communication between the clinician and the pathologist were needed for early diagnosis of opportunistic infections. Twenty-two patients (88%) died, and the few survivors remain debilitated.

Renal disease in patients with AIDS: a clinicopathologic study.

To determine the nature and frequency of renal disorders in AIDS we reviewed the records of thirty-two patients hospitalized over a twenty-two month period. Group I, including all patients with AIDS who demonstrated proteinuria and/or renal insufficiency, numbered thirteen patients, in ten of whom renal tissue was available. Renal abnormalities included proteinuria in twelve patients, which exceeded two grams per day in seven. The glomerular histologic lesions included focal glomerulosclerosis, diffuse mesangial hypercellularity, diffuse proliferative glomerulonephritis, and membranoproliferative glomerulonephritis. The nonglomerular histologic lesions included acute tubular necrosis, nephrocalcinosis, focal interstitial nephritis, and one case each of intrarenal cryptococcal infection and renal cell carcinoma. Nine of these thirteen patients developed renal insufficiency, and four of them required dialysis. Their mortality by the end of the study period was eleven of thirteen patients (85 percent), significantly worse in the short term than AIDS patients without renal problems. The patients in Group I were compared to the nineteen AIDS patients without renal abnormalities in Group II. The Group I patients had a higher incidence of oral and esophageal candidiasis, other fungal infections, and infections with Mycobacterium avium-intracellulare. They also had a higher incidence of exposure to aminoglycoside antibiotics and amphotericin B, and experienced more clinical shock than their Group II counterparts. It is concluded that patients with AIDS may demonstrate renal abnormalities on the basis of immune, hemodynamic, infectious, and neoplastic derangements.

A prospective study of the ophthalmologic findings in the acquired immune deficiency syndrome.

A prospective evaluation of ophthalmologic findings in 26 patients (25 men and one woman) with the acquired immune deficiency syndrome disclosed that 19 patients had significant ocular abnormalities. These included isolated retinal hemorrhages, cotton-wool spots, cytomegalovirus retinitis, acute retinal necrosis, cranial nerve palsies, and orbital Kaposi's sarcoma. Hemorrhages and cotton-wool spots appeared and disappeared spontaneously. Cytomegalovirus retinitis and acute retinal necrosis were progressive and destructive. The fundus findings did not correlate with the patient's general clinical status.

Central-nervous-system toxoplasmosis in homosexual men and parenteral drug abusers.

Central-nervous-system toxoplasmosis developed in 7 of 269 patients with the acquired immunodeficiency syndrome reported to the New York City Health Department through July 1982. Focal neurologic abnormalities, mass lesions on computed-tomographic brain scans, lymphocytic cerebrospinal fluid pleocytosis, and detectable IgG antibody to Toxoplasma gondii were common; but IgG titers of 1:1024 or more, IgM antibody to T. gondii, and positive open brain biopsies were uncommon. Serologic findings suggested that the disease resulted from recrudescent rather than primary infection. Four of five patients improved when treated with sulfonamides and pyrimethamine, but 2 had relapses. An aggressive diagnostic approach and sometimes even empiric therapy are warranted when central-nervous-system toxoplasmosis is suspected in a seropositive patient with the acquired immunodeficiency syndrome.

The lymphoid lesions associated with the acquired immunodeficiency syndrome.

In the present epidemic of opportunistic infections affecting homosexual men, systemic, persistent, unexplained lymphadenopathies have frequently accompanied and often preceded other manifestations of the acquired immunodeficiency syndrome (AIDS). Studies of the lymphadenopathies associated with AIDS have not yet been published, and the lymph node lesions have been generally considered to represent reactive lymphoid hyperplasia. The present study concerns the lymph node biopsies of 36 homosexual males with systemic, persistent lymphadenopathy. The lesions were essentially uniform and consisted of focal hemorrhages, extreme hyperplasia of germinal centers, extensive cellular destruction, accumulation of neutrophils, phagocytosis of nuclear debris, proliferation of blood vessels, immunoblasts, and peculiar aggregates of clear cells. These lesions diagnosed as acute lymphadenitis accompanied diseases indicative of AIDS in six cases and preceded them by months in three cases. In two cases, the lymphadenitis was associated with Kaposi's sarcoma of lymph node and in two cases with non-Hodgkin's lymphomas. It is suggested that the systemic, persistent lymphadenitis of homosexual males is induced by a microorganism, probably a virus. The lymphotropic activity of such an agent may include the destruction of a certain class of lymphocytes leading to the induction of the acquired immunodeficiency syndrome. Under special, unknown circumstances, the uncontrolled lymph node hyperplasia may progress to the development of lymphoma.

Lymphadenopathies in homosexual men. Relationships with the acquired immune deficiency syndrome.

Generalized, persistent lymphadenopathies were observed in homosexual men and considered a possible prodrome of acquired immune deficiency syndrome (AIDS). To evaluate these lymphadenopathies, 25 lymph node biopsy specimens from homosexual men with lymphadenopathy (18), lymphadenopathy associated with AIDS (five), and lymphadenopathy associated with non-Hodgkin's lymphoma (two) were reviewed and correlated with the clinical symptoms. In the absence of opportunistic infections, the lymph node lesions were essentially uniform and represented acute inflammatory processes resembling those commonly seen in viral lymphadenitides. This suggests that a lymphotropic agent, probably a virus, causes AIDS as a result of its destructive effects on certain populations of lymphoid cells.