Boonmee Sathapatayavongs

Adult-onset immunodeficiency in Thailand and Taiwan

BACKGROUND Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. METHODS 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. RESULTS 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. CONCLUSIONS 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.).

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.

Use of an Immunotherapeutic Vaccine to Treat a Life-Threatening Human Arteritic Infection Caused by Pythium insidiosum

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 patients left shoulder, and 14 days later a similar dose was administered. Four weeks following the first vaccination, the patients 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.

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 Sweets 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.

Abdominal aortic aneurysms infected with salmonella: Problems of treatment

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.

Identification of a Novel 74-Kilodalton Immunodominant Antigen of Pythium insidiosum Recognized by Sera from Human Patients with Pythiosis

ABSTRACT 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.

Pythium insidiosum Thai isolates: molecular phylogenetic analysis.

Background: Pythium insidiosum is an oomycete that infects both humans and animals, leading to a life-threatening infectious disease called “pythiosis”. Animal pythiosis presents with lesions of the skin, gastrointestinal tract, lung and bone, whereas human pythiosis presents with two common clinical forms, vascular pythiosis involving arteries, and ocular pythiosis involving the eye. Pythiosis in humans has been reported exclusively from Thailand. The disease in animals has been found around the world, but its occurrence has never been reported from Thailand. Objective: To group P. insidiosum based on molecular phylogenetic analysis, investigating correlation between phylogenetic group, geographic distribution, and host specificity of this pathogen. Methods: 113 rDNA internal transcribed spacer sequences of P. insidiosum were also obtained for phylogenetic analyses. These included 32 human isolates and 59 environmental isolates from Thailand, and four additional human isolates and 18 animal isolates from around the world. Results: P. insidiosum existed in three distinct clades in accordance with geographic distribution; clade-I contained American isolates, clade-II contained Asian and Australian isolates, and clade-III contained mainly Thai isolates. The Thai isolates existed only in clade-II and clade-III. Conclusion: There were two major subpopulations of P. insidiosum in Thailand. There were no correlation between the two Thai subpopulations of P. insidiosum and geographic regions or host specificity.

Predicting factors for unsuccessful switching from nevirapine to efavirenz in HIV-infected patients who developed nevirapine-associated skin rash.

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 <100 cells/mm3 (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.

HIV-1 genotype after interruption of non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy and virological response after resumption of the same regimen

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.

A Model and Risk Score for Predicting Nevirapine-Associated Rash among HIV-infected Patients: In Settings of Low CD4 Cell Counts and Resource Limitation

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 <55 kg. (OR 2.02, 95% CI, 1.09-3.76, p = 0.026), not receiving slow dose escalation (OR 2.00, 95% CI, 1.06-3.77, p = 0.032), and no concomitant drug(s) (OR 2.48, 95% CI, 1.32-4.64, p = 0.005). Receiver-operator characteristic analysis yielded area under the curve of 71% and the goodness-offit statistics was 6.48 (p = 0.840). The variables were given scores of 14, 7, 7 and 9, respectively. A cutoff >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.