Clinical and epidemiological analyses of human pythiosis in Thailand.

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.

Cryptococcosis in human immunodeficiency virus-negative patients.

OBJECTIVE: To describe the clinical characteristics, treatment, and outcomes of cryptococcosis in HIV-negative patients. METHODS: HIV-negative adult patients with positive culture for Cryptococcus neoformans who attended Ramathibodi Hospital between 1987 and 2003 were retrospectively reviewed. RESULTS: During the 17 year review period, 40 HIV-negative patients with cryptococcosis were identified. Of these, 37 patients had medical records available for study. The mean age was 49+/-18 (range 16-83) years and 73% were female. Twenty-four patients (65%) had associated underlying conditions. The most common associated conditions included immunosuppressive drug treatment (41%), presence of systemic lupus erythematosus (16%), malignancies (16%), and diabetes mellitus (14%). C. neoformans was mainly recovered from cerebrospinal fluid (32%), blood (28%), and sputum/bronchoalveolar lavage/lung tissue (28%). Twenty-three patients (62%) had disseminated cryptococcosis. Six of 14 patients with cryptococcal meningitis were asymptomatic. About half of the patients were treated with amphotericin B and subsequent fluconazole. Five patients (14%) were initially misdiagnosed and treated for tuberculosis or bacterial infection. The overall mortality rate was 27%. CONCLUSIONS: Cryptococcosis is not rare in HIV-negative patients. The mortality rate is high. Early recognition of cryptococcosis and use of appropriate antifungal therapy in these patients may improve clinical outcomes.

Cryptococcuria as a manifestation of disseminated cryptococcosis and isolated urinary tract infection.

Fungal infection of the genitourinary system is a relatively uncommon presentation. Cryptococcuria has rarely been recognized in clinical practice. Patients with positive urine culture for Cryptococcus neoformans from 1992 to 2003 were retrospectively reviewed. Sixteen patients were identified. Nine (56%) patients were male, with a mean age of 44 +/- 21 (range, 16-88) years. Fifteen (94%) patients had underlying conditions such as HIV infection, diabetes mellitus, hypertension, and/or systemic lupus erythematosus. Thirteen (81%) patients had cryptococcuria as a manifestation of disseminated cryptococcosis, and the rest had only isolated cryptococcuria. Urinary analysis revealed proteinuria (75%), pyuria (31%), and budding yeast (13%). Nine (56%) patients received antifungal therapy. Other patients were misdiagnosed or died before treatment. The mortality rate was 64%. In conclusion, cryptococcuria is not extremely rare and can present as a manifestation of disseminated cryptococcosis or isolated urinary tract infection.

Infections with rapidly growing mycobacteria: report of 20 cases.

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.

Rapidly growing mycobacterial infections: spectrum of diseases, antimicrobial susceptibility, pathology and treatment outcomes.

OBJECTIVES: A series of cases infected with rapidly growing mycobacteria were studied to reveal the spectrum of disease, antimicrobial susceptibility, pathology, and treatment outcomes. METHOD: The cases identified as rapidly growing mycobacterial infections in Ramathibodi Hospital from January 1993 to June 1999 were retrospectively studied. RESULTS: 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. CONCLUSIONS: 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.

Chronic diarrhoea caused by Cryptococcus neoformans in a non-human immunodeficiency virus-infected patient.

A 43-y-old woman with underlying cervix carcinoma stage IIIB, status postirradiation, and diabetes mellitus with tripathy suffered from chronic diarrhoea for more than 6 months. Stool examination showed few white blood cells and red blood cells. Rectal swab cultures disclosed Cryptococcus neoformans in 2 samples obtained 2 weeks apart. The diarrhoea responded to treatment with oral fluconazole for 4 weeks. Repeated rectal swabs revealed no yeast growth. During follow-up for 4 y, she had no problems with diarrhoea. Chronic diarrhoea caused by C. neoformans is rare and clinical suspicion is needed.

Concomitant tuberculous and cryptococcal thyroid abscess in a human immunodeficiency virus-infected patient.

Suppurative thyroiditis is a rare condition caused mostly by Staphylococcus aureus and streptococci. Both tuberculous and cryptococcal thyroid abscess are even rarer. The incidence of extrapulmonary forms of tuberculosis and cryptococcosis has increased in areas with a high prevalence of human immunodeficiency virus (HIV) infection. A case is reported of dual infection by M. tuberculosis and Cryptococcus neoformans presenting as a thyroid abscess in a 32-y-old woman with symptomatic HIV infection. Atypical presentations of both tuberculosis and cryptococcosis should be considered in areas with a high incidence of these diseases.

Correlation between susceptibility of Mycobacterium tuberculosis by microtiter plate alamar blue assay and clinical outcomes.

A rapid, inexpensive, and reliable antimycobacterial susceptibility assay is needed to effectively deal with the increasing prevalence of resistant strains of M. tuberculosis in Thailand. The microtiter plate Alamar blue assay (MABA) appears to be promising but requires additional data regarding correlation with clinical outcome. The correlation between the susceptibility by MABA and clinical outcomes was studied. There were 123 specimens obtained from extra-pulmonary sites of 108 patients at Ramathibodi Hospital in 1999. The authors found that susceptibility of M. tuberculosis isolates by the MABA correlated with the clinical outcome; patients with isolates sensitive to isoniazid, rifampicin, and ethambutol had a better clinical outcome than patients with isolates resistant to at least one of these drugs (p=0.004). Studies to determine this correlation in pulmonary tuberculosis are still needed.

Development and evaluation of an in-house enzyme-linked immunosorbent assay for early diagnosis and monitoring of human pythiosis.

Human pythiosis is an emerging, fatal, infectious disease caused by Pythium insidiosum and occurs in both tropical and subtropical countries. Thalassemic patients, farmers, and aquatic-habitat residents are predisposed to this disease. Delayed treatment due to the long time required for isolation and identification of the causative organism, as well as the difficulty in obtaining internal organ specimens, results in high morbidity and mortality. To facilitate rapid diagnosis, an in-house enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G antibodies against P. insidiosum was developed and evaluated for the diagnosis and monitoring of human pythiosis. Sixteen sera were collected from seven culture-proven human pythiosis cases. A total of 142 sera from thalassemic patients, from patients with other infectious diseases, and from healthy blood donors served as controls. All sera were tested in duplicate. By choosing a suitable cutoff point to maximize sensitivity and specificity, sera from pythiosis cases were all determined to be positive, whereas sera from control groups were all determined to be negative. ELISA signals from serial samples of sera taken from treated patients showed gradually declining levels of antibodies to P. insidiosum. The ELISA test was highly sensitive (100%) and specific (100%) and was useful for early diagnosis and for monitoring the treatment for pythiosis.