Quantitation of cell-associated borrelial DNA in the blood of Lyme disease patients with erythema migrans.

Bloodstream invasion is an important event in the pathogenesis of the more serious manifestations of Lyme disease. The number of spirochetes in the blood of infected patients, however, has not been determined, and, therefore, it is unknown whether the number of spirochetes can be correlated with particular clinical or laboratory features. This study was designed to measure the level of Borrelia burgdorferi in the plasma of Lyme disease patients and correlate these levels with selected clinical and laboratory findings. Nested and quantitative polymerase chain reaction (qPCR) was employed to detect cell-associated flaB gene DNA in the plasma of untreated early Lyme disease patients with erythema migrans (EM). Twenty-nine (45.3%) of 64 patients had evidence of B. burgdorferi in their plasma by at least one of the PCR methods. For the 22 qPCR-positive patients, the mean number of flaB gene copies per mL of plasma was 4,660, with a range of 414 to 56,000. The number of flaB gene copies did not significantly correlate with any of the clinical, demographic, or laboratory variables assessed. For reasons discussed, we suggest caution in extrapolating an estimate of the number of viable Borrelia in plasma from the observed number of flaB copies.

Cryptococcal infection presenting as cellulitis in a renal transplant recipient.

Opportunistic infections of skin and soft tissue represent a rare but serious complication following solid organ transplantation. We report a case of severe soft tissue infection caused by Cryptococcus neoformans in a renal transplant recipient. Physicians need to consider the possibility of opportunistic pathogens when managing infections in immunocompromised hosts, especially when symptoms persist despite seemingly appropriate empiric antimicrobial therapy. Tissue sampling for histological and microbiological evaluation is usually necessary to establish a diagnosis.

Tolerability, safety, and acceptability of zidovudine prophylaxis in health care workers.

OBJECTIVE: To evaluate the safety, tolerability, and acceptability of zidovudine used for prevention of human immunodeficiency virus (HIV) transmission to health care workers. METHODS: Prospective study between January 1989 and December 1992 at a suburban New York City medical center of health care workers who had percutaneous or permucosal exposures to blood or body fluids of HIV-infected patients. The zidovudine regimen offered was 200 mg orally every 4 hours for 42 days. RESULTS: Only 60 (53%) of 113 health care workers chose to take zidovudine, and only 21 (35%) of these health care workers completed the recommended 42-day course of therapy. Men were more likely than women to choose zidovudine therapy (P = .06), and a greater proportion of men completed the full 42 days of zidovudine therapy (P = .09). The most frequent reason for stopping treatment prematurely was clinical adverse reactions (n = 18 [30%]). Overall, clinical adverse events occurred in 44 (73%) of those taking zidovudine, with the most frequent events being nausea (n = 28 [47%]), headache (n = 21 [35%]), and fatigue (n = 18 [30%]). Selected laboratory parameters (hemoglobin level, hematocrit, alanine aminotransferase level, and white blood cell, granulocyte, and platelet counts) were compared at baseline and at week 4. Of interest, platelet counts were significantly more likely to increase by week 4 than to remain the same or decrease (P = .035). This observation may shed light on the mechanism of platelet elevation seen in zidovudine-treated patients infected with HIV. None of the laboratory changes was considered clinically significant. Of the 42 health care workers followed up for 3 months or longer (range, 3 to 32 months), none had undergone HIV antibody seroconversion. CONCLUSIONS: Zidovudine therapy is poorly accepted and tolerated by health care workers, at least in the dosage regimen used in this study. Alternative prophylactic regimens are needed.

Impact of color blindness on recognition of blood in body fluids.

BACKGROUND: Color blindness is a common hereditary X-linked disorder. OBJECTIVE: To investigate whether color blindness affects the ability to detect the presence of blood in body fluids. METHODS: Ten color-blind subjects and 20 sex- and age-matched control subjects were shown 94 photographs of stool, urine, or sputum. Frank blood was present in 57 (61%) of the photographs. Surveys were done to determine if board-certified internists had ever considered whether color blindness would affect detection of blood and whether an inquiry on color blindness was included in their standard medical interview. RESULTS: Color-blind subjects were significantly less able to identify correctly whether pictures of body fluids showed blood compared with non-color-blind controls (P =.001); the lowest rate of correct identifications occurred with pictures of stool (median of 26 [70%] of 37 for color-blind subjects vs 36.5 [99%] of 37 for controls; P<.001). The more severely color-blind subjects were significantly less accurate than those with less severe color deficiency (P =.009). Only 2 (10%) of the 21 physicians had ever considered the possibility that color blindness might affect the ability of patients to detect blood, and none routinely asked their patients about color blindness. CONCLUSIONS: Color blindness impairs recognition of blood in body fluids. Color-blind individuals and their health care providers need to be made aware of this limitation.

Hepatitis C virus seroprevalence in the developmentally disabled.

BACKGROUND: Hepatitis C virus (HCV) is the principal cause of nonenteric non-A, non-B hepatitis worldwide. While it has been well documented that people with developmental disabilities are at an increased risk for infections with hepatitis B virus, little is known of the prevalence of HCV infection among this population. METHODS: Serum samples obtained from 113 evaluable outpatients with developmental disabilities at one center in suburban New York City (NY) were tested for antibodies to HCV and hepatitis B core antibody. RESULTS: None of the 113 samples tested positive for HCV antibody by enzyme-linked immunosorbent assay, whereas 24 (21%) showed serologic evidence of past hepatitis B virus infection on the basis of hepatitis B core antibody positivity. Three (2.7%) were also positive for hepatitis B surface antigen. CONCLUSIONS: In contrast to hepatitis B virus, HCV infection is uncommon among outpatients with developmental disabilities in suburban New York City. Further testing for HCV is indicated to determine if these results can be generalized to individuals within institutions, or to individuals in other geographic locations.

Accuracy of IgM immunoblotting to confirm the clinical diagnosis of early Lyme disease.

BACKGROUND: A 2-test approach for the serologic diagnosis of Lyme disease has recently been proposed. A positive or equivocal result on a first-stage test (eg, an enzyme immunoassay) is followed by a Western immunoblot test. For a sample to be considered seropositive for Lyme disease, the immunoblot result must be positive. OBJECTIVES: To assess the accuracy of IgM immunoblotting for detection of early Lyme disease and to establish interpretative criteria for a commercially available immunoblot assay. METHODS: Serum samples from 44 patients with erythema migrans were tested by an IgM immunoblot assay. All patients were culture-positive for Borrelia burgdorferi. Serum samples from 2 different control groups were also tested. Interpretative criteria were developed using receiver operating characteristic curves. RESULTS: The presence of any 2 IgM bands was found to be the optimal criterion for a positive test result, and in patients with illness of less than 7 days' duration, this was significantly more sensitive than the criterion of any 2 of the 3 specific bands defined by the Centers for Disease Control and Prevention/Association of State and Territorial Public Health Laboratory Directors Lyme Disease Workgroup (P < .05). Specificity of the criterion of any 2 bands was 100% for 1 group of controls but only 96% for the more clinically relevant control group; this small difference had a large impact on the positive predictive value in populations at low risk for Lyme disease. CONCLUSIONS: Using a commercially available immunoblot test kit, the presence of any 2 IgM bands is proposed as a positive result. The predictive value of a positive IgM immunoblot result, however, is poor in patients with minimal clinical evidence for Lyme disease.

Bloodstream infections with vancomycin-resistant enterococci.

OBJECTIVES: To describe the population in whom bloodstream infections with vancomycin-resistant enterococci occur and the clinical and microbiologic features of infection. METHODS: From June 1, 1991, to January 31, 1994, 73 patients with bloodstream infections with vancomycin-resistant enterococci were identified by retrospective review of hospital charts and microbiology records. RESULTS: Fifty-two (73%) of 71 patients with evaluable data were hospitalized in an intensive care, unit, the adult oncology unit, or the acquired immunodeficiency syndrome unit. Before the development of the bloodstream infection with vancomycin-resistant enterococci, patients were hospitalized and received antibiotics for a median of 26 and 25.5 days, respectively. A hematologic malignancy, respiratory failure, or renal failure requiring dialysis was present in 59 patients (83%). Acute Physiology and Chronic Health Evaluation II scores of the patients ranged from 6 to 35 (median, 17). Forty-five (63%) of the patients died. Compared with 37 patients who had only a single positive blood culture, the 34 patients with 2 or more blood cultures positive for vancomycin-resistant enterococci more often were neutropenic or had acquired immunodeficiency syndrome (74% vs 35%; P = .002). CONCLUSIONS: Bloodstream infections with vancomycin-resistant enterococci predominantly affect severely ill patients who have received extensive antibiotic treatment during a prolonged hospitalization. Immunocompromised patients are more likely to have a persistent blood-stream infection with vancomycin-resistant enterococci.

Low-dose intermittent trimethoprim-sulfamethoxazole for prevention of Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection.

The important role of chemoprophylaxis for the prevention of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus type 1 (HIV)-infected patients is undisputed. The most cost-effective regimen, however, is unknown. We reviewed our experience at two hospitals in the New York City area in which low-dose, intermittent therapy with the combination of trimethoprim and sulfamethoxazole was used to prevent PCP in HIV-infected patients. During a total of 202 months of primary prophylaxis in 32 patients and 319 months of secondary prophylaxis in 35 patients, PCP was diagnosed only once. More than 80% of patients were receiving zidovudine concomitantly. Adverse reactions to trimethoprim-sulfamethoxazole occurred in 31% and 52% of those receiving primary or secondary prophylaxis, respectively. When those patients who were considered ineligible to receive trimethoprim-sulfamethoxazole prophylaxis (principally based on a prior adverse drug reaction) are also factored in, then approximately 50% of HIV-infected patients are candidates for long-term trimethoprim-sulfamethoxazole prophylaxis. The projected cost savings of this prophylaxis regimen, compared with those currently recommended by the US Public Health Service, are enormous.

A first-tier rapid assay for the serodiagnosis of Borrelia burgdorferi infection.

BACKGROUND: The present recommendation for the serologic diagnosis of Lyme disease is a 2-tier process in which a serum sample with a positive or equivocal result by an enzyme-linked immunosorbent assay (ELISA) or immunofluorescent assay is then followed by supplemental testing by Western blot. Our laboratory has developed recombinant chimeric proteins composed of key Borrelia epitopes. These novel antigens are consistent and are easily standardized. METHODS: We adapted these recombinant proteins into a new immunochromatographic format that can be used as a highly sensitive and specific first-tier assay that can be used to replace the ELISA or immunofluorescent assay. RESULTS: This rapid test was equally sensitive (P>.05) and more specific (P<.05) than a frequently used commercial whole cell ELISA. The overall clinical accuracy achieved on agreement studies among 3 Lyme research laboratories on clinically defined serum panels was shown to be statistically equivalent to the commercial ELISA. The assay can detect anti-Borrelia burgdorferi antibodies in either serum or whole blood. CONCLUSION: This sensitive and specific rapid assay, which is suited for the physician's office, streamlines the 2-tier system by allowing the physician to determine if a Western blot is necessary at the time of the initial office visit.

Acquired immunodeficiency syndrome (AIDS) in an economically disadvantaged population.

Forty patients with acquired immunodeficiency syndrome (AIDS), 70% of whom were intravenous drug abusers (IVDAs), were seen over a 20-month period (July 1, 1981, through Feb 28, 1983). Most of the patients came from two inner-city sections of New York City and from nearby correctional facilities. Eighty-five percent of the patients were black or Hispanic; only 15% were white. Unique features of AIDS in this mostly heterosexual population were the high incidence of opportunistic infections (90% of the patients), the low incidence of Kaposi's sarcoma (10%), and the high mortality rate (34% died during initial hospitalization, 74% after one year of follow-up). Tuberculosis occurred in 10% of cases, preceding other opportunistic infections by four to 24 months. We found that AIDS was a common disease among inpatient IVDAs, and in one of the participating hospitals, its incidence was similar to that of infective endocarditis. Acquired immunodeficiency syndrome should be considered as the underlying illness in all IVDAs with oral thrush, shortness of breath, pneumonia, or extra-pulmonary tuberculosis.

Utility of dapsone for prophylaxis of Pneumocystis carinii pneumonia in trimethoprim-sulfamethoxazole-intolerant, HIV-infected individuals.

OBJECTIVE: To determine the safety and efficacy of 100 mg dapsone three times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients. DESIGN: Retrospective chart review of patients followed-up to 22 May 1992. SETTING: Infectious diseases outpatient clinic of a tertiary care center in suburban New York City. PATIENTS: Twenty-three HIV-infected patients requiring PCP prophylaxis with documented intolerance to TMP-SMX. MAIN OUTCOME MEASURES: Patients were followed clinically and with laboratory testing at approximately monthly intervals. RESULTS: Dapsone was discontinued in nine (39%) patients because of adverse reactions. All reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 14 patients developed histologically proven PCP over 126 patient-months of follow-up. CONCLUSION: Approximately 40% of TMP-SMX-intolerant HIV-infected individuals are also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 100 mg dapsone three times weekly. More experience with other dose regimens and alternative agents is needed.

Salmonella meningitis and infection with HIV.

Patients infected with HIV demonstrate increased susceptibility to serious infections with non-typhoidal salmonellae. However, no cases of salmonella meningitis have been reported in this population. We now report three cases of salmonella meningitis which occurred in a population of 1800 patients with AIDS or AIDS-related complex at our hospitals. The incidence of meningitis complicating salmonella infection in our HIV-infected population appears to be much higher than that reported in non-AIDS patients (7.5 versus 0.15%). All had cerebrospinal fluid parameters consistent with bacterial meningitis, and two of three revealed organisms on cerebrospinal fluid Gram stain. Two presented with a fulminant illness and died despite therapy; the third developed a brain abscess associated with a relapse of meningitis. Salmonella meningitis should be considered as a cause of acute neurological deterioration in patients at risk for HIV-related disease. Relapses may occur, and mortality is high.

Reduced frequency of percutaneous injuries in surgeons: 1993 versus 1988.

OBJECTIVE: To compare the frequency of occupational injuries reported by surgeons in 1993 with similar data obtained in 1988. DESIGN AND SETTING: Two point-prevalence studies of percutaneous injuries of surgeons practicing in tertiary and non-tertiary-care hospitals in the New York metropolitan area. PARTICIPANTS: A total of 202 surgeons and surgical residents surveyed in 1988 and 347 surveyed in 1993 (67 and 65% of the eligible groups, respectively), including 85 surgeons in 1993 (71% of the eligible group) who had participated in the 1988 survey. OUTCOME MEASURES: Yearly frequency of percutaneous injuries, and injury frequency per 1000 operative hours. RESULTS: There was a significant decrease in the frequency of reported percutaneous injuries over the 5-year period. For all surgeons, the mean number of yearly injuries decreased from 5.5 +/- 14.4 SD to 2.1 +/- 6.0 SD (P < or = 0.001). Paired analysis of the subgroup of 85 surgeons who participated in both surveys showed a nearly identical decrease (P = 0.001). Significant decreases were observed in general surgeons, specialists and residents. CONCLUSIONS: During the 5 years studied, surgeons practicing in the greater New York metropolitan area reported a significant reduction in the frequency of occupationally associated percutaneous injuries. The reduced risk of percutaneous injuries should substantially lower the rate of acquired infections from blood-borne pathogens.

Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques.

Recently, a number of refinements in diagnostic modalities for detection of Borrelia burgdorferi infection have been developed. These include large-volume blood cultures, quantitative polymerase chain reaction (PCR) techniques, and 2-stage serologic testing. In the present study, we compared 6 diagnostic modalities in 47 adult patients who had a clinical diagnosis of erythema migrans. Quantitative PCR on skin biopsy-derived material was the most sensitive diagnostic method (80.9%), followed by 2-stage serologic testing of convalescent-phase samples (66.0%), conventional nested PCR (63.8%), skin culture (51.1%), blood culture (44.7%), and serologic testing of acute-phase samples (40.4%). Results of all assays were negative for 3 patients (6.4%). We conclude that the clinical diagnosis of erythema migrans is highly accurate in an area where B. burgdorferi is endemic if it is made by experienced health care personnel, but some patients with this diagnosis may not have B. burgdorferi infection. No single diagnostic modality is suitable for detection of B. burgdorferi in every patient with erythema migrans.

Nocardiosis in patients with human immunodeficiency virus infection. Report of 2 cases and review of the literature.

Nocardia infection is a rarely reported opportunistic infection in HIV-infected patients. Nocardiosis typically occurs in HIV-infected patients with advanced immunodeficiency (89% of cases), often as the initial serious opportunistic infection (42% of cases). In most HIV-infected patients, nocardia infection is disseminated at the time of diagnosis and is characterized by an indolent course that may be difficult to differentiate from other systemic infections. Invasive procedures to obtain tissue of fluid for culture are frequently necessary to make the diagnosis, although a Gram or modified acid-fast stain of sputum or other infected material may suggest the etiologic agent. Although trimethoprim-sulfamethoxazole is the most commonly used initial therapy, it was discontinued in 50% of cases because of adverse reactions. Even though the optimal treatment has not been defined, nocardiosis in HIV-infected patients can be treated successfully with or without sulfa-containing antimicrobial regimens, along with surgical drainage when necessary. Recurrence is noted after short duration of treatment, and consideration should be given to lifelong maintenance therapy.

Erythema migrans and early Lyme disease.

Erythema migrans (EM) must be distinguished from other entities including streptococcal and staphylococcal cellulitis, hypersensitivity reactions to arthropod bites, plant dermatitis, tinea, and granuloma annulare. Although EM lesions may be pruritic or painful, these complaints are generally mild. Central clearing may be absent in > 50% of patients. Multiple lesions, formerly present in 50% of U.S. patients, now occur in approximately 20%. EM develops days to 1 month after a tick bite (median 7-10 days), and lesion diameter increases with duration. Most patients have associated complaints, with fatigue (54%), myalgia (44%), arthralgia (44%), headache (42%), and fever and/or chills (39%) being the most common. Respiratory and gastrointestinal complaints are infrequent. Symptoms may begin prior to the onset of, concomitant with, or after resolution of the rash. The incidence of viral-like illness due to Lyme disease without EM is unknown. Antibodies to Borrelia burgdorferi are absent in up to 50% of patients at presentation, with initial seropositivity most likely in those with EM of longer duration. The vast majority of patients will become seropositive within the first month of illness, even with treatment. Although there is evidence that B. burgdorferi can spread to the blood and central nervous system soon after onset of infection, oral therapy is highly effective in preventing objective extracutaneous complications of Lyme disease. The most appropriate choice, route of administration, and duration of therapy require further study. Because of variations in the etiologic agent between North America and Europe, comparisons of disease manifestations, treatment, and prognosis of Lyme disease must be made cautiously.

Peritonitis in cirrhotic patients with LeVeen shunts.

Six cirrhotic patients are described in whom peritonitis developed from 10 days to 15 months after the insertion of a LeVeen shunt. The presenting clinical features of fever, increasing ascites and deterioration in mental status resembled these previously reported for cirrhotic patients but with spontaneous peritonitis without shunts. Important differences were observed, however, in microbiology, incidence of bacteremia and therapy. Staphylococcus aureus, a rare cause of spontaneous peritonitis, was found in one half of our cases, suggesting that perioperative contamination during shunt placement was an important etiologic factor. All six had concomitant bacteremia which may be attributable to the direct peritoneal-venous connection. Appropriate systemic antimicrobial therapy without shunt removal failed to eradicate the infection irrespective of the patency of the shunt or absence of inflammation at the sites of insertion. Recommended treatment for suspected peritonitis in patients with shunts is systemic antimicrobial therapy with an agent active against staphylococci plus an aminoglycoside, followed by removal of the shunt if the diagnosis is confirmed.

Strongyloides stercoralis hyperinfection in a patient with the acquired immune deficiency syndrome.

Severe infections with Strongyloides stercoralis occur in immunocompromised patients. Strongyloides hyperinfection syndrome complicated by gram-negative bacteremia and meningitis in a bisexual man with the acquired immune deficiency syndrome (AIDS) is described. Increased awareness of this infection, which may also be sexually transmitted, is recommended when caring for patients with AIDS who are homosexual, or have resided in areas endemic for strongyloidiasis. Multiple stool examinations should be performed routinely for such patients. Examination of sputum for the parasite is recommended if pneumonia is present. Prompt diagnosis and therapy are essential for prevention of fatal dissemination.

PIP: Severe infections with Strongyloides stercoralis occur in immunocompromised patients. Strongyloides hyperinfection syndrome complicated by gram-negative bacteremia and meningitis in a bisexual man with acquired immune deficiency syndrome (AIDS) is described. Increased awareness of this infection, which may also be sexually transmitted, is recommended when caring for patients with AIDS who are homosexual, or have resided in areas endemic for strongyloidiasis. Multiple stool examinations should be performed routinely for such patients. Examination of sputum for the parasite is recommended if pneumonia is present. Prompt diagnosis and therapy is essential for prevention of fatal dissemination.

Persistence of multiply antibiotic-resistant Campylobacter jejuni in a patient with the acquired immune deficiency syndrome.

Chronic diarrhea due to Campylobacter jejuni has been described in patients with hypogammaglobulinemia. A patient with the acquired immune deficiency syndrome (AIDS) and normal total serum immunoglobulins had persistent diarrhea and C. jejuni on stool culture for seven and a half months despite repeated antibiotic therapy. Antibiotic sensitivity studies revealed the C. jejuni to be multiply antibiotic-resistant. Evaluation of the mechanism of resistance showed the organism harbored a conjugative plasmid capable of transferring resistance to tetracycline, but not to other antibiotics. It is concluded that C. jejuni infection may rarely result in chronic diarrhea in patients with AIDS. The combination of an immune deficiency state including abnormal B cell function previously described in AIDS and multiple antibiotic resistance may have contributed to the persistence of the organism in this case.