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A 5‐year longitudinal follow‐up study of serological responses to 23‐valent pneumococcal polysaccharide vaccination among patients with HIV infection who received highly active antiretroviral therapy*

Long‐term antibody responses to 23‐valent pneumococcal polysaccharide vaccine (PPV) among HIV‐infected patients receiving highly active antiretroviral therapy (HAART) are rarely investigated.

Successful prevention of syphilis transmission from a multiple organ donor with serological evidence of syphilis

SEROLOGY for syphilis is included in the standard tests of organ donors, and a positive result of the serology is usually recognized as a contraindication to organ donation. We report on a multiple organ donor with serologic eveidence of syphilis. With appropriate penbicillin prophylaxis in the postoperative period, none of the recipients had transmission of the disease in the long-term follow-up.

Impact of chronic hepatitis C infection on outcomes of patients with an advanced stage of HIV-1 infection in an area of low prevalence of co-infection

To ascertain whether hepatitis C (HCV) co-infection affects the progression of HIV infection, we initiated an eight-year prospective observational study at a university hospital in Taiwan where seroprevalences of HCV antibody and HIV antibody were low. Fifty-three (12.0%) consecutive non-haemophiliac HIV1-infected patients with HCV co-infection and 387 (88.0%) patients without HCV and hepatitis B co-infection were enrolled between June 1994 and June 2002 and observed until December 2002. Outcomes evaluated included the risk for acute hepatitis, hepatic decompensation, HIV disease progression and mortality, and changes of CD4+ count and plasma viral load (PVL) after initiation of highly active antiretroviral therapy (HAART) at the end of the study. The baseline CD4+ count, PVL and proportion of patients with AIDS-defining opportunistic illnesses (OI) at study entry were similar between patients with HCV co-infection and those without co-infection, but HCV-co-infected patients were older (39 versus 35 years, P = 0.01) and had a higher proportion of intravenous drug use (17.0% versus 0.8%, P < 0.001). After a total observation duration of 1137 patient-years (PY) (median, 791 days; range, 3–3053 days), the incidence of acute hepatitis in HCV-co-infected patients was 13.89 per 100 PY (95% confidence interval [CI], 13.31–14.49) and that in patients without co-infection was 6.39 per 100 PY (95% CI, 6.24–6.55 per 100 PY), with an adjusted odds ratio (OR) of 2.769 (95% CI, 1.652–4.640). At the end of the study, CD4+ count increased by 137 × 106 and 157 × 106/L in patients with and without HCV co-infection, respectively, (P = 0.47). The proportions of achieving undetectable PVL (<400 copies/mL) after HAART was similar (76.7% versus 74.9%, P = 0.79). The adjusted OR for development of new AIDS-defining OI was 1.826 (95% CI, 0.738–4.522) in HCV-co-infected patients as compared with HCV- uninfected patients. The adjusted hazards ratio for death of HCV-co-infected patients when compared with those without co-infection was 0.781 (95% CI, 0.426–1.432). Our findings suggested that HCV co-infection was associated with a significantly higher risk for acute hepatitis in HIV-infected patients receiving antiretroviral therapy, but it had no adverse impact on virological, immunological and clinical responses to HAART and survival when compared with patients without HCV and HBV co-infection.

Successful discontinuation of fluconazole as secondary prophylaxis for cryptococcosis in AIDS patients responding to highly active antiretroviral therapy

Seven AIDS patients with disseminated cryptococcosis who had had immune reconstitution following highly active antiretroviral therapy (HAART) had discontinued their secondary antifungal prophylaxis to prevent relapse of Cryptococcus neoformans infection. The median CD4+ count was 236 cells/µL (range, 117-404 cells/µL; mean, 247 cells/µL) and the plasma viral loads were undetectable in five patients at discontinuation of antifungal prophylaxis. No relapse of cryptococcosis was detected in these patients after a median observation duration of nine months (range, 5.5-4.1 months, mean, 14.6 months) following discontinuation. Our data and review of the literature suggest that discontinuation of fluconazole prophylaxis is safe in patients with reconstitution of immunity following initiation of HAART.

Prevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis in non-haemophiliac HIV-1-infected adults in Taiwan

We assessed the seroprevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis (TE) in 844 non-haemophiliac HIV-infected patients in Taiwan between June 1994 and April 2003. Approximately 70% (69.3%) of them had a baseline CD4+ lymphocyte count of 200 × 106/L or less, and more than 70% (73.9%) having initiated highly active antiretroviral therapy. The seroprevalence of T. gondii infection was 10.2%, which did not differ with sex, age, route of transmission, birth inside or outside of Taiwan, or CD4+ lymphocyte stratifications. After a median observation duration of 603 days (range, 1–3264 days), 10 (1.2%) patients developed 11 episodes of TE after a median interval of 30 days (range, 1–941 days) between enrolment and diagnosis of TE, with an incidence of 0.59 per 100 person-years (PY) (95% confidence interval, 0.56–0.63 per 100 PY). We concluded that the incidence of TE of HIV-infected patients in Taiwan was lower than that reported in western countries because of a lower seroprevalence of T. gondii infection and use of antimicrobial prophylaxis and antiretroviral therapy, although most of the patients were at the late stage of HIV infection.

Haemophilus aphrophilus bacteraemia complicated with vertebral osteomyelitis and spinal epidural abscess in a patient with liver cirrhosis

Haemophilus aphrophilus is rarely implicated as an aetiology of spinal epidural abscess. A 73-year-old woman with liver cirrhosis who developed H. aphrophilus bacteraemia complicated with vertebral osteomyelitis and spinal epidural abscess is presented. Without surgical decompression, she was successfully treated with cefotaxime for 3 weeks, followed by maintenance with ciprofloxacin for another 10 weeks. The clinical features of eight previously reported cases of vertebral osteomyelitis without epidural abscess due to H. aphrophilus are reviewed.

SP110b Controls Host Immunity and Susceptibility to Tuberculosis

Rationale: How host genetic factors affect Mycobacterium tuberculosis (Mtb) infection outcomes remains largely unknown. SP110b, an IFN‐induced nuclear protein, is the nearest human homologue to the mouse Ipr1 protein that has been shown to control host innate immunity to Mtb infection. However, the function(s) of SP110b remains unclear. Objectives: To elucidate the role of SP110b in controlling host immunity and susceptibility to tuberculosis (TB), as well as to identify the fundamental immunological and molecular mechanisms affected by SP110b. Methods: Using cell‐based approaches and mouse models of Mtb infection, we characterized the function(s) of SP110b/Ipr1. We also performed genetic characterization of patients with TB to investigate the role of SP110 in controlling host susceptibility to TB. Measurements and Main Results: SP110b modulates nuclear factor‐&kgr;B (NF‐&kgr;B) activity, resulting in downregulation of tumor necrosis factor‐&agr; (TNF‐&agr;) production and concomitant upregulation of NF‐&kgr;B‐induced antiapoptotic gene expression, thereby suppressing IFN‐&ggr;‐mediated monocyte and/or macrophage cell death. After Mtb infection, TNF‐&agr; is also downregulated in Ipr1‐expressing mice that have alleviated cell death, less severe necrotic lung lesions, more efficient Mtb growth control in the lungs, and longer survival. Moreover, genetic studies in patients suggest that SP110 plays a key role in modulating TB susceptibility in concert with NF&kgr;B1 and TNF&agr; genes. Conclusions: These results indicate that SP110b plays a crucial role in shaping the inflammatory milieu that supports host protection during infection by fine‐tuning NF‐&kgr;B activity, suggesting that SP110b may serve as a potential target for host‐directed therapy aimed at manipulating host immunity against TB.

Unexpectedly high prevalence of Treponema pallidum infection in the oral cavity of human immunodeficiency virus-infected patients with early syphilis who had engaged in unprotected sex practices

Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum, with PCR assays, from the oral cavities of 240 patients with 267 episodes of syphilis who reported engaging in unprotected sex practices. The detected treponemal DNA was subjected to genotyping. All of the syphilis cases occurred in men who have sex with men (MSM), and 242 (90.6%) occurred in human immunodeficiency virus-infected patients. The stages of syphilis included 38 cases (14.2%) of primary syphilis of the genital region, 76 (28.5%) of secondary syphilis, 21 (7.9%) of primary and secondary syphilis, 125 (46.8%) of early latent syphilis, and seven (2.6%) others. Concurrent oral ulcers were identified in 22 cases (8.2%). Treponemal DNA was identified from the swabs of 113 patients (42.2%), including 15 (68.2%) with oral ulcers. The most common genotype of T. pallidum was 14f/f. The presence of oral ulcers was associated with identification of T. pallidum in the swab specimens (15/22 (68.2%) vs. 98/245 (40.0%)) (p = 0.01). In multivariate analysis, secondary syphilis (adjusted OR 6.79; 95% CI 1.97-23.28) and rapid plasma reagin (RPR) titres of ≥1: 32 (adjusted OR 2.23; 95% CI 1.02-4.89) were independently associated with the presence of treponemal DNA in patients without oral ulcers. We conclude that detection of treponemal DNA in the oral cavity with PCR assays is not uncommon in MSM, most of whom reported having unprotected oral sex. Although the presence of oral ulcers is significantly associated with detection of treponemal DNA, treponemal DNA is more likely to be identified in patients without oral ulcers who present with secondary syphilis and RPR titres of ≥1: 32.

Fatal mycobacteremia caused by Mycobacterium tuberculosis in a patient with acute leukemia.

Fatal mycobacteremia caused by Mycobacterium tuberculosis in a patient with acute leukemia

Rapid Sputum Multiplex Detection of the M. tuberculosis Complex (MTBC) and Resistance Mutations for Eight Antibiotics by Nucleotide MALDI-TOF MS

The increasing incidence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (MTB) adds further urgency for rapid and multiplex molecular testing to identify the MTB complex and drug susceptibility directly from sputum for disease control. A nucleotide matrix-assisted-laser-desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based assay was developed to identify MTB (MTBID panel) and 45 chromosomal mutations for resistance to eight antibiotics (MTBDR panel). We conducted a 300 case trial from outpatients to evaluate this platform. An MTBID panel specifically identified MTB with as few as 10 chromosome DNA copies. The panel was 100% consistent with an acid-fast stain and culture for MTB, nontuberculous mycobacteria, and non-mycobacteria bacteria. The MTBDR panel was validated using 20 known MDR-MTB isolates. In a 64-case double-blind clinical isolates test, the sensitivity and specificity were 83% and 100%, respectively. In a 300-case raw sputum trial, the MTB identification sensitivity in smear-negative cases using MALDI-TOF MS was better than the COBAS assay (61.9% vs. 46.6%). Importantly, the failure rate of MALDI-TOF MS was better than COBAS (11.3% vs. 26.3%). To the best of our knowledge, the test described herein is the only multiplex test that predicts resistance for up to eight antibiotics with both sensitivity and flexibility.