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Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown.We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained.Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering.Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

Background: Rash is the most common adverse effect associated with nevirapine (NVP). We aimed to develop a model and risk score for predicting NVP-associated rash among HIV-infected patients with low CD4 cell counts. Methods: Cross-sectional study was conducted and 383 HIV-infected patients consecutively enrolled in the study. Results: Of 222 patients in the training set, 116 (52.2%) were males and median (IQR) age was 35.2 (31.1-42.0) years. Median (IQR) CD4 cell count was 104 (35-225) cells/mm3. Of these, 72 and 150 patients were in “rash” and “no rash” group, respectively. Four factors were independently associated with rash: a history of drug allergy (odds ratio (OR) 4.01, 95% confidence interval (CI), 1.75-9.20, P = 0.001), body weight 21 points defined the high risk individuals which yielded specificity and positive predictive value of 99% and 69%, respectively, with OR of 3.96 (95% CI, 1.79-8.86, p = 0.001). Conclusions: A model and risk score for predicting NVP-associated rash performed well in this study population. It might be useful for predicting the risk of rash before NVP initiation among HIV-infected patients with low CD4 cell counts.

Summary Skin rash associated with nevirapine (NVP) is common and efavirenz (EFV) is often used as a substitute. We aimed to determine the predicting factors for unsuccessful switching from NVP to EFV. A retrospective cohort study was conducted in HIV-infected patients who developed rash after taking NVP. There were 109 patients with a mean standard deviation (SD) age of 36.6 (7.4) years and 45% were males. Median (interquartile range) CD4 cell count and HIV RNA at the time of NVP initiation were 163 (50–273) cells/mm3 and 4.6 (1.7–5.4) log copies/mL, respectively. Twenty (18.3%) patients subsequently developed EFV-associated rash. By logistic regression, history of drug allergy apart from NVP (odds ratio [OR] 11.42) and CD4 cell count 3 (OR 6.14) were significant predicting factors for EFV-associated rash. Two predicting factors for unsuccessful switching from NVP to EFV were found. Patients who have these factors need to have a close follow-up if EFV is substituted.

Introduction: The aim of this paper was to assess factors that predict students’ performance in the Medical Licensing Examination of Thailand (MLET) Step1 examination. The hypothesis was that demographic factors and academic records would predict the students’ performance in the Step1 Licensing Examination. Materials and Methods: A logistic regression analysis of demographic factors (age, sex and residence) and academic records [high school grade point average (GPA), National University Entrance Examination Score and GPAs of the pre-clinical years] with the MLET Step1 outcome was accomplished using the data of 117 third-year Ramathibodi medical students. Results: Twenty-three (19.7%) students failed the MLET Step1 examination. Stepwise logistic regression analysis showed that the significant predictors of MLET Step1 success/failure were residence background and GPAs of the second and third preclinical years. For students whose sophomore and third-year GPAs increased by an average of 1 point, the odds of passing the MLET Step1 examination increased by a factor of 16.3 and 12.8 respectively. The minimum GPAs for students from urban and rural backgrounds to pass the examination were estimated from the equation (2.35 vs 2.65 from 4.00 scale). Conclusions: Students from rural backgrounds and/or low-grade point averages in their second and third preclinical years of medical school are at risk of failing the MLET Step1 examination. They should be given intensive tutorials during the second and third pre-clinical years. Key words: Basic science, National test, Prediction

Background Pythiosis is an emerging and life-threatening infectious disease in humans and animals that is caused by the pathogenic oomycete Pythium insidiosum. Human pythiosis is found mostly in Thailand, although disease in animals has been increasingly reported worldwide. Clinical information on human pythiosis is limited, and health care professionals are unfamiliar with the disease, leading to underdiagnosis, delayed treatment, and poor prognosis. Methods To retrospectively study the clinical and epidemiological features of human pythiosis, we analyzed clinical data from patients with pythiosis diagnosed during the period of January 1985 through June 2003 at 9 tertiary care hospitals throughout Thailand. Results A total of 102 cases of human pythiosis were documented nationwide. A substantial proportion (40%) of cases occurred in the last 4 years of the 18-year study interval. Clinical presentations fell into 4 groups: cutaneous/subcutaneous cases (5% of cases), vascular cases (59%), ocular cases (33%), and disseminated cases (3%). Almost all patients with cutaneous/subcutaneous, vascular, and disseminated pythiosis (85%) had underlying thalassemia-hemoglobinopathy syndrome. Most ocular cases (84%) were associated with no underlying disease. A majority of the patients were male (71%), were aged 20-60 years (86%), and reported an agricultural occupation (75%). Regarding treatment outcomes, all patients with disseminated infection died; 78% of patients with vascular disease required limb amputation, and 40% of these patients died; and 79% of patients with ocular pythiosis required enucleation/evisceration. Conclusions Here, we report, to our knowledge, the largest case study of human pythiosis. The disease has high rates of morbidity and mortality. Early diagnosis and effective treatment are urgently needed to improve clinical outcomes. Because P. insidiosum is distributed worldwide and can infect healthy individuals, an awareness of human pythiosis should be promoted in Thailand and in other countries.

Human pythiosis is an emerging disease in the tropical, subtropical and temperate regions of the world. It is caused by the straminipilan, fungus-like, aquatic organism Pythium insidiosum. Pythiosis occurs in localized as well as systemic or vascular forms. Most patients with arterial pythiosis usually have underlying hematologic disorders such as thalassemia and aplastic anemia/paroxysmal nocturnal hemoglobinuria (PNH) syndrome. Vascular pythiosis is characterized by ascending blood vessel infections and thrombosis of the major arteries especially those of the lower extremities. When the infection reaches a main artery, the patient usually dies within weeks. Since this pathogen is resistant to most antifungal drugs, immunotherapy was recently used to cure humans and animals with the disease. A modified P. insidiosum-antigen (PIA) formulation had already saved a young boy with life-threatening arterial pythiosis. Here, we report the therapeutic benefits of the PIA in eight patients with vascular pythiosis. Six of them had thalassemia and the other two had PNH. All of the patients had arterial occlusion of the lower limbs. P. insidiosum was isolated and identified by culture and by histopathology. All patients had evidence of active infection when immunotherapy began. After two injections of 100-200 microl of PIA (2.0mg/ml), at a 14-day interval, four patients (50%) had dramatic and complete remission. Two patients showed partial responses to PIA while the other two did not. Clinical responses correlated with the immunological reactions at the site of injection, clearance of the arteries and cytokine production. The latter included the shifting in serum levels of IL4 and IL5 to IL2 suggesting a switching from a T helper 2 (Th2) to a T helper 1 (Th1) subset. Our findings provide further evidence that immunotherapy using PIA is a safe and effective method to treat pythiosis in humans.

Objectives: A series of cases infected with rapidly growing mycobacteria was studied to determine the spectrum of disease, antimicrobial susceptibility, treatment, and outcome. Methods: The cases identified as infections with rapidly growing mycobacteria in Ramathibodi Hospital from January 1993 to December 1999 were retrospectively studied. Results: Most of the cases had no underlying disease. Only two cases were HIV-infected patients. The presenting clinical features were lymphadenitis (seven cases), skin and/or subcutaneous abscess (seven cases), localized eye infection (four cases), pulmonary infection (one case), and chronic otitis media (one case). Four of seven cases with lymphadenitis had Sweet's syndrome, and one had psoriasis as an associated skin manifestation. Anemia was present in five cases, and improved with treatment of the primary disease. The organisms were Mycobacterium chelonae/abscessus group (17 cases) and Mycobacterium fortuitum group (three cases). Susceptibility patterns of the organisms showed susceptibility to amikacin, netilmicin, and imipenem. M. fortuitum group was susceptible to more antibiotics than M. chelonae/abscessus group. The clinical responses corresponded to the antimicrobial susceptibility. Combinations of two or more drugs were used for the medical treatment. Surgical resection was performed where possible, to reduce the load of the organism, especially in cases with very resistant organisms. Conclusions: Infections with rapidly growing mycobacteria can occur in apparently normal hosts. The clinical syndrome is variable. The pathology is nonspecific. Clinical responses varied, but seemed to correlate with the in vitro susceptibility result. More studies are needed to enable us to deal with this infection effectively.

We determined the prevalence of a positive tuberculin skin test (TST) and the incidence of TST conversion among new healthcare personnel (HCP) in a hospital in Thailand. During 2005-2008, TST was performed on 1438 HCP and the prevalence of positive TST was 66.3%. Age, male gender, and the presence of Bacille Calmette-Guerin (BCG) scar were associated with odds of positive TST (all P < 0.05). The incidence of TST conversion was 4.8 per 100 HCP-years. Nine (0.6%) HCP were diagnosed with active tuberculosis. The annual surveillance programme is important for the early diagnosis and prevention of tuberculosis among HCP in Thailand.

A 14-year-old Thai boy presented because of a history of headache, mandibular swelling, and facial nerve palsy. A microorganism identified as Pythium insidiosum was cultured from the mandibular abscesses. Despite treatment with amphotericin B, iodides, ketoconazole, and surgery, the infection progressed. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the neck revealed an aneurysm in the external carotid artery. The aneurysm was removed. MRA performed later showed stenosis of the internal carotid artery. Immunotherapy was recommended as a last resort. One hundred microliters of the P. insidiosum vaccine was subcutaneously injected into the patient's left shoulder, and 14 days later a similar dose was administered. Four weeks following the first vaccination, the patient's headache had disappeared, the facial swellings had dramatically diminished, the cervical lymph node had shrunk, and the proximal left internal carotid artery stenosis had significantly improved. One year after the vaccinations, the boy was considered clinically cured.

Rhinofacial entomophthoramycosis is an uncommon chronic mycotic disease caused by exposure to the organism Conidiobolus coronatus. The authors report a case series of 5 patients with rhinofacial entomophthoramycosis and review the literature. All patients had typical involvement of the rhinofacial area with formation of subcutaneous lesions causing a chronic granulomatous inflammatory response with tissue eosinophilia and Splendore-Hoeppli reaction. Diagnoses were made based on histopathologic examination in all cases and fungi were isolated and identified in one case. The clinicopathologic features and therapeutic management of rhinofacial entomophthoramycosis are described.

Seven patients with abdominal aortic aneurysms infected with salmonella organisms were surgically treated between 1985 and 1988. Salmonella culture was obtained from the wall of the aneurysm in every patient, and in five patients it was identified as Salmonella typhimurium. S. choleraesuis and salmonella group D (isolated from this patient but not speciated) were found in the other two remaining patients. Three patients underwent aneurysmal resection with axillofemoral bypass grafting, and three patients were treated by aneurysmal resection with in situ graft; two of this group had the wall and infective periaortic tissue excised. One patient died during the operation as a result of rupture of the aneurysm. Therapeutic doses of antibiotic drugs were given to all of the patients. Although two of the patients in the first group (with the axillofemoral bypass graft) died and the remaining patient had very complicated postoperative course, all the patients in the second group (with in situ graft) survived. We think that in situ graft placement after an extensive debridement of the aneurysmal wall and infected periaortic tissue together with more effective and adequate antibiotic therapy for at least 6 weeks after the operation is a satisfactory method of surgical treatment of this condition. However, graft infection is still a possibility, therefore regular follow-up is needed. (J VASC SURG 1990;12:16-9.)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have a longer half-life than nucleoside reverse transcriptase inhibitor (NRTIs). Simultaneous interruption of all drugs exposes the patients to NNRTI monotherapy. This study evaluated HIV-1 genotype after treatment interruption (TI) of NNRTI-based antiretroviral therapy (ART) and virological response after resumption of the same ART regimen. A prospective study was conducted in HIV-1-infected patients who enrolled into a CD4-guided TI study. All patients continued dual NRTIs for a further 7–10 days at NNRTI TI. HIV-1 genotypic assay was performed prior to resumption of the same ART regimen. Forty-three patients required ART resumption after TI from NNRTI-based regimens. Mean age was 42.7 years; 44% were men. Median CD4 and HIV-1 RNA at the time of ART resumption were 178 cell/mm3 and 5.78 log copies/mL, respectively. HIV-1 genotype revealed no mutations contributed to NRTI or NNRTI resistance. Of all, 56% and 100% patients achieved undetectable HIV-1 RNA at three and six months, respectively. Median CD4 were 386 and 419 cells/mm3 at the corresponding periods. In conclusion, continuation of dual NRTIs for 7–10 days after TI of NNRTI-based regimens can minimize the risk of acquired NNRTI resistance. With this strategy, the same regimen can be used for resumption and also yield good virological and immunological outcomes.

Background Non-nucleoside reverse transcriptase inhibitor (NNRTI) with stavudine and lamivudine is widely used as the first-line antiretroviral therapy (ART) in resource-limited settings. Lipodystrophy is common and options for switching ART regimen are limited; this situation can lead to patients' poor adherence and antiretroviral resistance. Treatment interruption (TI) in patients with high CD4 cell counts, lipodystrophy, and limited options may be an alternative in resource-limited settings. This study aimed to determine time to resume ART after TI and predictors for early resumption of ART in a resource-limited setting. Methods A prospective study was conducted in January 2005 to December 2006 and enrolled HIV-infected patients with HIV-1 RNA 350 cells/mm3, and willing to interrupt ART. CD4 cell count, HIV-1 RNA, lipid profile, and lipodystrophy were assessed at baseline and every 3 months. ART was resumed when CD4 declined to 3 or developed HIV-related symptoms. Patients were grouped based on ART regimens [NNRTI or protease inhibitor (PI)] prior to TI. Results There were 99 patients, 85 in NNRTI group and 14 in PI group. Mean age was 40.6 years; 46% were males. Median duration of ART was 47 months. Median nadir CD4 and baseline CD4 were 151 and 535 cells/mm3, respectively. Median CD4 change at 3 months after TI were -259 (NNRTI) and -105 (PI) cells/mm3 (p = 0.038). At 13-month median follow-up, there was no AIDS-defining illness; 38% (NNRTI) and 29% (PI) of patients developed HIV-related symptoms. ART was resumed in 51% (NNRTI) and 36% (PI) of patients (p = 0.022). By Kaplan-Meier analysis, median time to resume ART was 5.5 (NNRTI) and 14.2 (PI) months (log rank test, p = 0.026). By Cox's regression analysis, NNRTI-based ART (HR 4.9; 95%CI, 1.5–16.3), nadir CD4 3 (HR 2.7; 95%CI 1.4–5.3) and baseline CD4 3 (HR 1.6; 95%CI, 1.2–3.1) were predictors for early ART resumption. Conclusion TI of NNRTI-based ART leads to rapid CD4 decline and high probability of early ART resumption and should be avoided. It is necessary to scale-up the options for HIV-infected patients with lipodystrophy in resource-limited settings.

Introduction: The teaching of evidence-based medicine (EBM) has now been incorporated as an integral part of medical curriculum at the Faculty of Medicine, Ramathibodi Hospital but there is little research into the effectiveness of the course. The purpose of this report is to evaluate the EBM skills of medical students and competency of the faculty member. Materials and Methods: The EBM course was created by the EBM Working Group at the Faculty of Medicine, Ramathibodi Hospital for 3rd- to 6th-year medical students. The principles of EBM, clinical epidemiology and biostatistics were gradually instilled during the 4 years of medical school. Information technology infrastructure was also provided to facilitate critical appraisal skills. At the end of the Community Medicine clerkship, students anonymously evaluated aspects of the course regarding their EBM skills and faculty member competency with Likert scale questions. Results: Medical students generally gave high evaluations to all aspects of the EBM course taught in the Community Medicine Department. For each of the evaluation questions, the means were higher for faculty member competency. Conclusions: The teaching of EBM course at the Faculty of Medicine, Ramathibodi Hospital is useful for medical students to enhance their critical thinking skills, and they seem to value the sessions positively. Key words: Community Medicine, Critical thinking skill, Evaluation, Medical curriculum

The oomycetous, fungus-like, aquatic organism Pythium insidiosum is the etiologic agent of pythiosis, a life-threatening infectious disease of humans and animals that has been increasingly reported from tropical, subtropical, and temperate countries. Human pythiosis is endemic in Thailand, and most patients present with arteritis, leading to limb amputation and/or death, or cornea ulcer, leading to enucleation. Diagnosis of pythiosis is time-consuming and difficult. Radical surgery is the main treatment for pythiosis because conventional antifungal drugs are ineffective. The aims of this study were to evaluate the use of Western blotting for diagnosis of human pythiosis, to identify specific immunodominant antigens of P. insidiosum , and to increase understanding of humoral immune responses against the pathogen. We performed Western blot analysis on 16 P. insidiosum isolates using 12 pythiosis serum samples. These specimens were derived from human patients with pythiosis who had different forms of infection and lived in different geographic areas throughout Thailand. We have identified a 74-kDa immunodominant antigen in all P. insidiosum isolates tested. The 74-kDa antigen was also recognized by sera from all patients with pythiosis but not by control sera from healthy individuals, patients with thalassemia, and patients with various infectious diseases, indicating that Western blot analysis could facilitate diagnosis of pythiosis. Therefore, the 74-kDa antigen is a potential target for developing rapid serodiagnostic tests as well as a therapeutic vaccine for pythiosis. These advances could lead to early diagnosis and effective treatment, crucial factors for better prognosis for patients with pythiosis.

Sweet's syndrome has been reported to be associated with many underlying conditions, such as non-tuberculous mycobacterial infections (NTMI). In the literature, only twelve patents with Sweet's syndrome in association with NTMI have been reported (most of the patients were from Thailand). Here, the authors report six more patients who developed Sweet's syndrome as a reaction to NTMI. Four patients had Mycobacterium chelonae/abscessus group infection; one patient had been infected with Mycobacterium avium complex first and became infected with M. chelonae/abscessus group 17 months later; and, the other one had Mycobacterium fortuitum infection. In each patient, the skin lesions of Sweet's syndrome relapsed many times while they still had NTMI, and these lesions usually responded well to short courses of systemic steroids without any deterioration of NTMI.

Antibiotic resistance, a major negative consequence of antibiotic overuse, is an important problem worldwide. Various means have been used to control antibiotic usage including the use of an antibiotic order form (AOF), restricted antibiotic formularies and provision of educational information. The present study was designed to evaluate the use of antimicrobials in a 1,000-bed university hospital. Antimicrobial agents, likely to be abused namely ceftazidime, cefepime, cefoperazone/sulbactam, imipenem/cilastatin, meropenem, ciprofloxacin, netilmicin, vancomycin, azithromycin and clarithromycin, were selected for evaluation. A simple AOF with educational information was used as a mean to follow up the treatment. The investigator collected data from the filled AOF and the patient's charts of the Department of Internal Medicine from June to November 2000; all relevant data were assessed. The appropriateness of antibiotic use, assessed according to the criteria specified in the AOF, showed that 74% of these antibiotics were prescribed appropriately; this may prove the effectiveness of the system used in the present study. However, 348 of the 430 prescriptions (80.9%) were prescribed empirically at the initial stage for treatment of nosocomial infections in patients with serious conditions like pneumonia, sepsis and febrile neutropenia. Drugs that were frequently used empirically were ceftazidime (37.9%), imipenem/cilastatin or meropenem (19.3%), and cefoperazone/sulbactam (12.1%) respectively. Ceftazidime and imipenem/cilastatin or meropenem were also frequently used inappropriately among 111 prescriptions that were classified as an inappropriate prescribing. The most common misuses were prescriptions of the drug that did not follow the specified indications (70 prescriptions), no dosage adjustment in patients with renal impairment (39 prescriptions), improper dose (12 prescriptions) and improper dosing interval (9 prescriptions). The results suggested overuse of certain antibiotics remain to be an unsolved problem. Better monitoring and strict controlled use of the problematic antibiotics, ie ceftazidime, imipenem/cilastatin or meropenem and vancomycin are essential to promote rational drug use as well as to reduce the frequency of drug resistance.

A series of cases infected with rapidly growing mycobacteria were studied to reveal the spectrum of disease, antimicrobial susceptibility, pathology, and treatment outcomes.The cases identified as rapidly growing mycobacterial infections in Ramathibodi Hospital from January 1993 to June 1999 were retrospectively studied.There were 20 patients and most of the cases had no underlying disease. Only two cases were HIV-infected patients. The presenting clinical features were lymphadenitis (7), skin and subcutaneous abscess (7), eye infection (4), pulmonary infection (1), and chronic otitis media (1). Four of the seven cases with lymphadenitis had Sweet's syndrome. The organisms were Mycobacterium chelonae/abscessus group (17 cases) and Mycobacteriumfortuitum group (3 cases). The organisms were susceptible to amikacin, netilmicin and imipenem. The M. fortuitum group was susceptible to more antibiotics than the M. chelonaelabscessus group. Pathology of the infected tissue varied from non-specific findings to suppurative or caseous granuloma. The clinical responses corresponded to the antimicrobial susceptibility. Most of the patients had a good clinical outcome. A combination of two or more drugs was used for the medical treatment. Surgical resection was performed where possible to reduce the load of the organism, especially in cases with very resistant organisms.Rapidly growing mycobacterial infections can occur in apparently normal hosts. Clinical syndrome is variable. The pathology is non-specific and culture is needed for definite diagnosis. Clinical responses varied but seemed to correlate with the in vitro susceptibility result. More studies are needed before one can deal with these infections more effectively.

To facilitate the laboratory diagnosis of human cases of pythiosis insidiosi, an immunological test was evaluated. A soluble antigen was prepared from a human isolate of Pythium insidiosum, an aquatic, thermotolerant oomycete that causes infections in cattle, dogs, horses, and humans. Sera from seven proven cases of disseminated human pythiosis insidiosi were tested in an immunodiffusion test along with appropriate control sera from patients with a variety of actinomycotic, bacterial, and mycotic diseases as well as sera from uninfected individuals. Titers ranged from 1:1 to 1:32 in the seven serum samples from the disseminated cases of pythiosis insidiosi of varying severity. The heterologous sera gave negative reactions. The rapidity and specificity of the immunodiffusion test makes it a useful diagnostic tool for the serodiagnosis of P. insidiosum infections.

Central nervous system manifestations occur in 10 to 20% of patients with disseminated histoplasmosis. Additionally, histoplasmosis may be the cause of cases of chronic meningitis in patients with no other evidence for dissemination. Histoplasmosis may also cause cerebral or spinal cord mass lesions resembling neoplasms or abscesses, and encephalitis. Diagnosis of chronic meningitis or mass lesions caused by H. capsulatum may be difficult and involves careful analysis of serologic tests for antibodies, cultures and tests for HPA in body fluids. Amphotericin B remains the treatment of choice, but relapses occur in half of cases despite total courses of at least 35 mg/kg. Accordingly, careful long-term follow-up is required to identify patients with relapsing infection. Newer antifungal agents which cross the blood brain barrier are needed. A trial of amphotericin B treatment without surgical excision can be justified in patients with cerebral or spinal cord histoplasmomas, in view of the apparent success of such treatment in a few cases. Progression of clinical abnormalities or persistence of the lesion following completion of treatment would support the need for surgical excision.

An enzyme-linked immunosorbent assay was developed to detect urinary antigen excreted by patients with Legionnaires' disease. Of 47 patients tested, antigen was detected in 39. Of these 39 specimens, 35 gave clearly positive results by visual analysis; four others required spectrophotometric verification of positive results. Antigen was not detected in any of 178 urine specimens from patients with other pulmonary, bacteremic or urinary tract infections after a quick and simple confirmatory test. The assay required more time to perform than a previously described radioimmunoassay but was of equivalent sensitivity and specificity and did not require expensive equipment or contact with radioactive reagents. We conclude that enzyme-linked immunosorbent assay is a rapid, sensitive and specific means for rapidly diagnosing Legionnaires' disease that can be performed in clinical laboratories unwilling or unable to use radioisotopes.

Clinical and laboratory features have been reviewed in 66 episodes of disseminated histoplasmosis that occurred during two large urban outbreaks in Indianapolis. Immunosuppression, age greater than 54 years, and presence of other serious underlying illnesses predisposed to the disseminated form of the disease; only 21% of patients lacked one of these risk factors. Central nervous system findings, splenomegaly, hepatomegaly, and lymphopenia suggested disseminated disease but were present in only about one-third of patients. Miliary or diffuse pulmonary infiltrates also suggested dissemination and were noted in about one-third of patients, while mediastinal lymphadenopathy was present in only 17%. Histoplasmal serologic tests, positive in 90% of patients, provided useful diagnostic clues. The diagnosis could be confirmed by culture in 88% of patients, and special stains were positive in about two-thirds. Although 10% of patients recovered without treatment, 11 patients (17%) died because of failure to suspect the diagnosis and initiate therapy promptly. Amphotericin B was effective in all patients receiving at least 500 mg, but relapse occurred if the total dose was less than 30 mg/kg. Ketoconazole appeared effective in non-immunosuppressed patients but not in those with underlying immunosuppression; however, a controlled trial comparing ketoconazole and amphotericin B is required to establish the role of this new fungistatic oral agent.

Pythium infection (pythiosis) in humans has not previously been described, even in areas endemic for animal pythiosis. We report five patients with a unique presentation of fungal arteritis. The medium- to large-sized arteries were involved, and in some cases this involvement led to gangrene of the limbs, aneurysm formation, and ultimately fatal arterial leakage. All five patients were farmers. All patients, with the possible exception of one who had hemoglobin typing performed after receiving a blood transfusion, had thalassemia hemoglobinopathy syndrome. Fungal isolation was difficult. Amphotericin B treatment seemed to be ineffective. Radical surgical removal of infected tissues and oral administration of a saturated solution of potassium iodide are proposed therapy. In the tropics, where Pythium is ubiquitous, one should actively look for this fungal infection in patients with unexplained arterial occlusion, especially in the case of patients with thalassemia hemoglobinopathy syndrome.

An outbreak of histoplasmosis in Indianapolis involving 488 clinically recognized cases including 60 patients with disseminated or fatal infection permitted statistical analysis of risk factors. Being male, white, under 5 years of age, having chronic obstructive lung disease, and living near the presumed source of the outbreak were not risk factors for fatal or disseminated histoplasmosis. Age greater than 54 years and immunosuppression were the only risk factors for disseminated or fatal infection. Dissemination should be excluded in patients with histoplasmosis who are immunosuppressed or older than 54 years. Specific antifungal treatment is more likely to be required in those two groups rather than in patients without risk factors.