Immunorestitution diseases in patients not infected with HIV

The aim of this study was to assess the clinical spectrum of immunorestitution disease (IRD) in hospitalized patients over a 12-month period. In nine of 18 patients who presented with clinical deterioration during reduction or cessation of immunosuppressants (n = 6) or bone marrow engraftment (n = 3), IRD cases included the following infections: scabies infestation (n = 1); gastric strongyloidiasis (n = 1); hepatosplenic candidiasis (n = 1); methicillin-resistant Staphylococcus aureus abscess formation (n = 2); polyomavirus-related hemorrhagic cystitis (n = 3); and influenza A pneumonitis (n = 1). Immunopathological damage during withdrawal of immunosuppression is an incidental way to uncover an asymptomatic infectious disease. Serial monitoring of hematological and clinical profiles is essential in making a diagnosis of IRD.postprin

Clinical deterioration in community acquired infections associated with lymphocyte upsurge in immunocompetent hosts

Clinical deterioration during the course of community-acquired infections can occur as a result of an exaggerated immune response of the host towards the inciting pathogens, leading to immune-mediated tissue damage. Whether a surge in the peripheral lymphocyte count can be used as a surrogate marker indicating the onset of immunopathological tissue damage is not known. In this study, we report the clinical presentations and outcomes of a cohort of immunocompetent patients with non-tuberculous community acquired infections who experienced clinical deterioration during hospital stay (n=85). 12 (14.1%) patients had a surge in lymphocyte count preceding their clinical deteriorations, and their diagnoses included viral pneumonitis (4), viral encephalitis (3), scrub typhus (2), leptospirosis (1), brucellosis (1), and dengue haemorrhagic fever (1). The clinical manifestations during deterioration ranged from interstitial pneumonitis (6), airway obstruction (1), CNS disturbances (4), and systemic capillary leak syndrome (1), all of which were thought to represent immunopathological tissue damages. When compared with patients without lymphocyte surge, these patients were more likely to be infected with fastidious/viral pathogens (0 vs 12; p<0.05), in addition to having lower mean baseline lymphocyte counts (403±181 vs 1143±686 cells/μl; p<0.05). We postulate that the peripheral lymphocyte count may be a useful surrogate marker indicating the presence of immunopathological damage during clinical deterioration in certain infectious diseases. © 2004 Taylor & Francis.postprin

Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients

Paradoxical deterioration during antituberculosis therapy, defined as the clinical or radiological worsening of pre-existing tuberculous lesions or the development of new lesions in a patient who initially improves, remains a diagnostic dilemma. Although different clinical presentations of paradoxical response have been described, a systematic analysis of the entity in non-HIV-infected patients is lacking. Reported here are two cases of paradoxical deterioration in which sequential changes in lymphocyte counts and tuberculin skin test results are emphasized. In addition, 120 episodes of paradoxical response after antituberculosis treatment were reviewed. Of the total 122 episodes, 101 (82.8%) were associated with extrapulmonary tuberculosis. The median time from commencement of treatment to paradoxical deterioration was 60 days. The median time to onset of central nervous system manifestations (63 days) was longer than the time to onset of manifestations at other sites (56 days) (P=0.02). Development of new lesions in anatomical sites other than those observed at initial presentation was observed in 31 (25.4%) episodes. A surge in the lymphocyte count, accompanied by an exaggerated tuberculin skin reaction, was observed in our patients during the paradoxical deterioration, analogous to the findings in HIV-positive patients. Treatment of the paradoxical response included surgical intervention (60.7%) and administration of steroids (39.3%). The use of steroids appeared to be safe in this series, as 95% of the Mycobacterium tuberculosis isolates were susceptible to first-line antituberculosis therapy.postprin

Infection Control Preparedness for Human Infection With Influenza A H7N9 in Hong Kong

Objective. To assess the effectiveness of infection control preparedness for human infection with influenza A H7N9 in Hong Kong Design. A descriptive study of responses to the emergence of influenza A H7N9 Setting. A university-affiliated teaching hospital Participants. Healthcare workers (HCWs) with unprotected exposure (not wearing N95 respirator during aerosol-generating procedure) to a patient with influenza A H7N9 Methods. A bundle approach including active and enhanced surveillance, early airborne infection isolation, rapid molecular diagnostic testing, and extensive contact tracing for HCWs with unprotected exposure was implemented. Seventy HCWs with unprotected exposure to an index case were interviewed especially regarding their patient care activities Results. From April 1, 2013, through May 31, 2014, a total of 126 (0.08%) of 163,456 admitted patients were tested for the H7 gene by reverse transcription-polymerase chain reaction per protocol. Two confirmed cases were identified. Seventy (53.8%) of 130 HCWs had unprotected exposure to an index case, whereas 41 (58.6%) and 58 (82.9%) of 70 HCWs wore surgical masks and practiced hand hygiene after patient care, respectively. Sixteen (22.9%) of 70 HCWs were involved in high-risk patient contacts. More HCWs with high-risk patient contacts received oseltamivir prophylaxis (P= 0.088) and significantly more had paired sera collected for H7 antibody testing (P<0.001). Ten (14.3%) of 70 HCWs developed influenza-like illness during medical surveillance, but none had positive results by reverse transcriptionpolymerase chain reaction. Paired sera was available from 33 of 70 HCWs with unprotected exposure, and none showed seroconversion against H7N9 Conclusions. Despite the delay in airborne precautions implementation, no patient-to-HCW transmission of influenza A H7N9 was demonstrated. © 2015 by The Society for Healthcare Epidemiology of America. All rights reserved.published_or_final_versio

Effect of clinical and virological parameters on the level of neutralizing antibody against pandemic influenza A virus H1N1 2009

Background. Little is known about the antibody response in natural infection by the novel 2009 influenza A (H1N1) virus and its relationship with clinical and virological parameters. The relative lack of background neutralizing antibody against this novel virus provides a unique opportunity for understanding this issue. Methods. Case patients presenting with influenza-like illness who were positive for the pandemic H1 gene by reverse transcription polymerase chain reaction were identified. The serum antibody response was assayed by neutralizing antibody titer (NAT) against the virus in 881 convalescent donors. We retrospectively analyzed clinical parameters and viral load. Results. Ninety percent of the 881 convalescent donors had seroprotective titer of 1:40 or greater. The geometric mean titer of donors with convalescent NAT measured between day 21 and 42 was 1:101.1. Multivariate analysis by ordinal regression showed that pneumonia (odds ratio, 3.39; 95% confidence interval, 1.49-9-7.61; P=.004) and sputum production (odds ratio, 1.75; 95% CI, 1.01-3.01; P=.046) were the 2 independent factors associated with a higher level of convalescent NAT. Being afebrile on influenza presentation was associated with subsequent poor NAT (<1:40) response (P = .04). A positive correlation between the nasopharyngeal viral load on presentation and the convalescent NAT was demonstrated (Spearman correlation r, 0.238; P = .026). Conclusions. About 10% of these convalescent patients do not have a seroprotective NAT and may benefit from vaccination to prevent reinfection. The convalescent NAT correlated well with the initial viral load and was independently associated with severity of the viral illness, including pneumonia. The findings provide both the clinical and virological markers for identifying potential convalescent plasma donors with high serum NAT, which can be used to produce hyperimmune intravenous immunoglobulin in a randomized treatment trial for patients with severe pandemic H1N1 infection. © 2010 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Clinical and molecular epidemiological features of coronavirus HKU1-associated community-acquired pneumonia

Background. Recently, we described the discovery of a novel group 2 coronavirus, coronavirus HKU1 (CoV-HKU1), from a patient with pneumonia. However, the clinical and molecular epidemiological features of CoV-HKU1-associated pneumonia are unknown. Methods. Prospectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. The epidemiological, clinical, and laboratory characteristics of patients with CoV-HKU1-associated pneumonia were analyzed. The pol, spike (S), and nucleocapsid (N) genes were also sequenced. Results. NPAs from 10 (2.4%) of 418 patients with community-acquired pneumonia were found to be positive for CoV-HKU1. All 10 cases occurred in spring and winter. Nine of these patients were adults, and 4 had underlying diseases of the respiratory tract. In the 6 patients from whom serum samples were available, all had a 4-fold change in immunoglobulin (Ig) G titer and/or presence of IgM against CoV-HKU1. The 2 patients who died had significantly lower hemoglobin levels, monocyte counts, albumin levels, and oxygen saturation levels on admission and had more-extensive involvement visible on chest radiographs. Sequence analysis of the pol, S, and N genes revealed 2 genotypes of CoV-HKU1. Conclusions. CoV-HKU1 accounts for 2.4% of community-acquired pneumonia, with 2 genotypes in the study population. Without performance of diagnostic tests, the illness was clinically indistinguishable from other community-acquired pneumonia illnesses. © 2005 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

The 23-valent polysaccharide pneumococcal vaccination is not useful in BMT patients at risk of pneumococcal bacteremic sepsis

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Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection

Background: Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods: We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-withoutARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results: Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions: The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death. © 2010 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio