Cosmo Del Borgo

In Vivo and In Vitro Effects of Antituberculosis Treatment on Mycobacterial Interferon-γ T Cell Response

Background In recent years, the impact of antituberculous treatment on interferon (IFN)-γ response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-γ response to M. tuberculosis-specific antigens in TB patients during antituberculous treatment by using the QuantiFERON-TB Gold (QFT-G) assay; ii) to compare the differences in T-cell response after a short or prolonged period of stimulation with mycobacterial antigens; iii) to assess the CD4+ and CD8+ T cells with effector/memory and central/memory phenotype; iv) to investigate the direct in vitro effects of antituberculous drugs on the secretion of IFN-γ. Principal Findings 38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-γ is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-γ production within the range of therapeutically achievable concentrations. Conclusions The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-γ response.

Current trends in management of hepatitis B virus reactivation in the biologic therapy era

Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk of HBV reactivation is heightened by the use monoclonal antibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and long-lasting immunosuppression. Emerging data indicate that HBV reactivation could also develop following the use of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is diagnosed, it is mandatory to suspend biologic treatment and start antiviral agents immediately. However, pre-emptive antiviral therapy prior to monoclonal antibody administration is crucial in preventing HBV reactivation and its clinical consequences. Several lines of evidence have shown that risk of HBV reactivation is greatly reduced by the identification of high-risk patients and the use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.

Severe and Persistent Depletion of Circulating Plasmacytoid Dendritic Cells in Patients with 2009 Pandemic H1N1 Infection

Background Dysregulation of host immune responses plays a critical role in the pathogenesis of severe 2009 pandemic H1N1 infection. Whether H1N1 virus could escape innate immune defense in vivo remains to be investigated. The aim of this study was to evaluate the pattern of innate immune response during human 2009 H1N1 infection. We performed the enumeration of circulating myeloid dendritic cells (mDC) and plasmacytoid DC (pDC) in blood from patients with H1N1 pneumonia shortly after the onset of symptoms and during follow-up at different intervals of time. The analysis of CD4 and CD8 count, CD38 T-cell activation marker and serum cytokine/chemokine plasma levels was also done. Methodology/Principal Findings Blood samples were collected from 13 hospitalized patients with confirmed H1N1-related pneumonia at time of admission and at weeks 1, 4, and 16 of follow-up. 13 healthy donors were enrolled as controls. In the acute phase of the disease, H1N1-infected patients exhibited a significant depletion in both circulating pDC and mDC in conjunction with a decrease of CD4 and CD8 T cell count. In addition, we found plasmatic hyperproduction of IP-10 and RANTES, whereas increase in T-cell immune activation was found at all time points. When we assessed the changes in DC count over time, we observed a progressive normalization of mDC number. On the contrary, H1N1-infected patients did not achieve a complete recovery of pDC count as values remained lower than healthy controls even after 16 weeks of follow-up. Conclusions H1N1 disease is associated with a profound depletion of DC subsets. The persistence of pDC deficit for several weeks after disease recovery could be due to H1N1 virus itself or to a preexisting impairment of innate immunity.

Antiviral treatment including entecavir plus tenofovir disoproxil fumarate for HBV reactivation following a rituximab-based regimen.

Entecavir and tenofovir disoproxil fumarate are potent and effective antiviral drugs that now represent recommended treatment options for chronic HBV infection. However, no or very limited clinical evidence is currently available on these drugs for the management of HBV reactivation in patients with haematological malignancies. Herein, we report a case of HBV reactivation in a patient with non-Hodgkins lymphoma following a rituximab-based regimen, and who was successfully treated with a combination antiviral treatment including entecavir and tenofovir disoproxil fumarate.

Postpartum fever in the presence of a fibroid: Sphingomonas paucimobilis sepsis associated with pyomyoma

BackgroundPyomyoma is a life-threatening complication of uterine leiomyoma. It may occur in post- menopausal women, during pregnancy and in the postpartum period. Fever may be the only manifestation during the early stages of the disease. We detail the first reported case of postpartum pyomyoma-related sepsis due to Sphingomonas paucimobilis, a Gram-negative bacillus that is gaining recognition as an important human pathogen.Case presentationA woman presented with an asymptomatic uterine fibroid and a two-week history of fever during the postpartum period. Suppurative uterine leiomyoma was diagnosed, and blood cultures grew Sphingomonas paucimobilis. The myoma was surgically removed from the uterus without hysterectomy. Intravenous antimicrobial therapy was given for fifteen days, and the patient was discharged from hospital in good condition.ConclusionPyomyoma should be considered in broad differential diagnosis of postpartum fever. This case highlights a unique disease manifestation of S. paucimobilis, an emerging opportunistic pathogen with increasing significance in the nosocomial setting.

Large Nosocomial Outbreak Associated with a Norwegian Scabies Index Case Undergoing TNF-α Inhibitor Treatment: Management and Control

We describe a large outbreak associated with a crusted (Norwegian) scabies case in an immunocompromised patient following treatment with TNF-α inhibitor (adalimumab) for psoriasis arthritis. The increasing use of TNF-α inhibitors should induce clinicians to consider this serious parasitic infection when evaluating skin rashes in patients receiving biologic therapies.

Bartonella henselae infection presenting with ocular and hepatosplenic manifestations in an immunocompetent child.

To the Editors: Disseminated Bartonella henselae infection is rarely described in immunocompetent subjects. Here, we report a case of an immunocompetent child who developed bartonellosis with hepatosplenic and ocular manifestations. A 10-year-old previously healthy boy was admitted to the Infectious Diseases Unit, Latina, Italy, because of a 2-week history of fever (T max 38.4°C) and recent onset of painless diminished visual acuity in the left eye. He had had no significant ocular problems in the past. There was no history of recent travel and trauma. He had no vomiting and did not complain of headache. The patient had been scratched on his left flank by a kitten 6 weeks before the onset of symptoms. On admission, his oral temperature was 38°C, heart rate 90 beats per minute, respiratory rate 22 breaths per minute and blood pressure 120/70 mm Hg. There was lymph node swelling in the left inguinal region and splenomegaly. A nearly healed lesion was present at site of scratch. The lungs and heart were normal as was the neurologic evaluation. The white blood cell count was normal and hemoglobin was 11 g/dL. Liver and kidney function tests were normal. C-reactive protein was 2.51 mg/dL (normal range 0–0.5 mg/dL), erythrocyte sedimentation rate was 42 mm/h. Cultures of blood samples and urine were sterile. Ophthalmologic evaluation showed mild conjunctival hyperemia without eye discharge and no signs of anterior uveitis. Fundus examination showed focal chorioretinitis on left eye with a circumscribed whitish retinal lesion due to a granuloma with serious retinal detachment along the inferotemporal arcade and small punctiform whitish lesions in the inferotemporal quadrant. The optic nerve appeared normal and the vitreous was clear. The right eye was normal. On the basis of fundoscopy, a diagnosis of left chorioretinitis was made. Ultrasound and magnetic resonance imaging of the abdomen demonstrated mild homogenous splenomegaly and multiple hypodense areas within the spleen and liver parenchyma. Serology was negative for Epstein-Barr virus, cytomegalovirus, hepatitis viruses, human immunodeficiency virus, syphilis, toxoplasma and Francisella. On the other hand, the serology for B. henselae (indirect immunofluorescence antibody IFA) was positive (IgG>1:256). Polymerase chain reaction for B. henselae DNA from peripheral blood sample was negative. Treatment with azythromicin (500 mg/daily) was started, and the patient was treated for 3 weeks. We observed a gradual resolution of the granuloma and flattening of the lesion that resulted in a chorioretinal scar with disappearance of the punctiform lesions. A complete resolution of clinical symptoms and hepatosplenic lesions was obtained within 3 weeks (Fig. 1). Cat-scratch disease is a benign, selflimiting zoonotic disease caused by the bacillus B. henselae. Typical cat-scratch disease presentations include fever, regional lymphadenopathy and a nontender papule in the scratch line. Other manifestations such as ocular involvement, encephalopathy, hepatosplenic infection, osteomyelitis and endocarditis are exceptional in immunocompetent subjects. We believe that this is the first report of a immunocompetent pediatric patient presenting with both chorioretinitis and hepatosplenic lesion as an initial manifestation of systemic bartonellosis.

Diagnostic and therapeutic approach in a rare case of primary bilateral adrenal tuberculosis

Here, we report a case of a febrile patient with primary bilateral adrenalitis who was successfully treated with an antituberculous regimen. Primary isolated tubercular adrenalitis is a very rare clinical entity but it should be considered in cases of fever and enlargement of the adrenal glands. Integration of radiological pattern data with epidemiological, clinical and immunological data has high accuracy and specificity, even without histological examination.

Persistent high plasma levels of sCD163 and sCD14 in adult patients with measles virus infection

Background and aims Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-α plasma levels were also evaluated. Methods sCD163, sCD14 and TNF-α were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. Results At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-α levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-α levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. Conclusions These results indicate that, despite the resolution of symptoms, an important macrophage/monocyte activation persists in measles patients, even after two months from infection.

Diplopia as isolated presentation of varicella zoster central nervous system reactivation

Here, we report a patient who developed diplopia secondary to a right cranial nerve III and IV palsy, as well as fever and headache. Cerebrospinal fluid analysis (CSF) showed high varicella-zoster virus (VZV)-DNA viral load (>300,000,000 copies/ml). VZV antibodies in CSF was ≥1:16. Diagnosis of neurological reactivation of VZV infection was made without the presence of characteristic vesicular rash. Quantitative real-time PCR for VZV and intrathecal dosage of VZV IgM and IgG should be performed in cases suspected for viral encephalitis and also in all patients with not otherwise attributable cranial nerve lesions.