Methods to discriminate primary from secondary dengue during acute symptomatic infection.

BACKGROUND: Dengue virus infection results in a broad spectrum of clinical outcomes, ranging from asymptomatic infection through to severe dengue. Although prior infection with another viral serotype, i.e. secondary dengue, is known to be an important factor influencing disease severity, current methods to determine primary versus secondary immune status during the acute illness do not consider the rapidly evolving immune response, and their accuracy has rarely been evaluated against an independent gold standard. METHODS: Two hundred and ninety-three confirmed dengue patients were classified as experiencing primary, secondary or indeterminate infections using plaque reduction neutralisation tests performed 6 months after resolution of the acute illness. We developed and validated regression models to differentiate primary from secondary dengue on multiple acute illness days, using Panbio Indirect IgG and in-house capture IgG and IgM ELISA measurements performed on over 1000 serial samples obtained during acute illness. RESULTS: Cut-offs derived for the various parameters demonstrated progressive change (positively or negatively) by day of illness. Using these time varying cut-offs it was possible to determine whether an infection was primary or secondary on single specimens, with acceptable performance. The model using Panbio Indirect IgG responses and including an interaction with illness day showed the best performance throughout, although with some decline in performance later in infection. Models based on in-house capture IgG levels, and the IgM/IgG ratio, also performed well, though conversely performance improved later in infection. CONCLUSIONS: For all assays, the best fitting models estimated a different cut-off value for different days of illness, confirming how rapidly the immune response changes during acute dengue. The optimal choice of assay will vary depending on circumstance. Although the Panbio Indirect IgG model performs best early on, the IgM/IgG capture ratio may be preferred later in the illness course.

Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study.

BACKGROUND: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. METHODS: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. FINDINGS: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. INTERPRETATION: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. FUNDING: EU's Seventh Framework Programme. TRANSLATIONS: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.

Central versus peripheral lesion on chest X-Ray: A case series of 31 endobronchial tuberculosis patients with negative sputum smears.

Background: Clinical characteristics of endobronchial tuberculosis (EBTB) patients whose sputum smears were negative have not been elucidated yet. Method: EBTB patients with negative sputum smears were documented retrospectively at the outpatient pulmonary clinic from late 2015 to early 2019. Results: We described the characteristics of 31 EBTB patients with negative sputum smears. The median age was 36 years (range 18-81 years). The male-to-female ratio is 1:1.58. The "peripheral" lesion group included 16 cases with opacity/consolidation, 2 cases with atelectasis, 1 case with cavitary lesion, and 1 case with pleural effusion. The "central" lesion group included four cases with normal chest X-ray and seven cases with only unilateral hilar enlargement. EBTB patients with "central" lesion were more common the presence of cough, the positive rate of bronchial lavage acid-fast bacilli smear, and the rate of misdiagnosis as pharyngitis, bronchitis, or asthma than that with "peripheral" lesion. Conclusions: EBTB with negative sputum smears was found in adult patients at any age and predominant in females. The diagnosis of EBTB with "central" lesion was more difficult than that with "peripheral" lesion. The location of the lesion could play a role in inducing cough among EBTB patients.

Exhaled Nitric Oxide as a Surrogate Marker for Obstructive Sleep Apnea Severity Grading: An In-Hospital Population Study.

PURPOSE: Our study aimed to evaluate the relationship between exhaled nitric oxide (eNO) markers and obstructive sleep apnea (OSA) severity and verify the changes in eNO profiles among mild, moderate, and severe OSA subgroups. METHODS: This study was a cross-sectional and in-hospital population-based study. We investigated 123 OSA patients (17 mild, 23 moderate and, 83 severe OSA) in the department of respiratory diseases. Studied data included anthropometry, respiratory polygraphy, biological markers, spirometry, and multi-flow eNO measurements. Data analysis implied linear correlation, non-parametric ANOVA, and pair-wise comparison. RESULTS: No significant difference could be found among 3 OSA severity subgroups for FENO at - four sampling flow rates (50-350 mL/s). The bronchial production rate of NO (J'awNO) was proportionally increased, with median values of 11.2, 33.9, and 36.2 in mild, moderate, and severe OSA, respectively (p=0.010). The alveolar concentration of NO (CANO) changed with a non-linear pattern; it was increased in moderate (6.49) vs mild (7.79) OSA but decreased in severe OSA (5.20, p = 0.015). The only correction that could be established between OSA severity and exhaled nitric oxide markers is through J'AWNO (rho=0.25, p=0.02) and CANO (rho= 0.18, p=0.04). There was no significant correlation between FENO measured at three different flow rates and the OSA severity. We also found a weak but significant correlation between FENO 100 and averaged SpO2 (rho = 0.07, p= 0.03). CONCLUSION: The present study showed that J'AWNO, which represents eNO derived from the central airway, is proportionally increased in more severe OSA, while eNO from alveolar space, indicated by CANO, was also associated with OSA severity and relatively lower in the most severe OSA patients. In contrast, stand-alone FENO metrics did not show a clear difference among the three severity subgroups.

Mycobacterium tuberculosis-Associated Necrotizing Pneumonia With Adjunctive Corticosteroid Therapy.

Necrotizing pneumonia induced by Mycobacterium tuberculosis is a rare but severe condition. It is difficult to distinguish between M. tuberculosis-associated and bacterial necrotizing pneumonia. The optimal treatment for this condition is controversial. Here, we report a case of M. tuberculosis-associated necrotizing pneumonia treated with the adjunctive corticosteroid and the antituberculosis drugs.

Hilar asymmetry in endobronchial tuberculosis patients: An often-overlooked clue.

BACKGROUND: Endobronchial tuberculosis (EBTB) is a challenging diagnosis because of its varied clinical and radiological manifestations. Hilar asymmetry on chest radiograph (CXR) may be found in patient with EBTB but is often overlooked, which may lead to delayed diagnosis. CASE REPORT: We present five cases with EBTB. Clinicians failed to identify unilateral hilar abnormalities on CXR, and these patients were treated initially for pharyngitis, bronchitis, or pneumonia with no improvement. Subsequently, they visited the pulmonary clinic and bronchoscopy revealed endobronchial lesions and microbial/histopathological evidence of tuberculous infection consistent with EBTB. Anti-tuberculosis therapy resulted in complete clinical resolution in four of the five patients; one patient had persistent bronchial stenosis. CONCLUSION: Hilar asymmetry on CXR may occur with EBTB and may suggest this diagnosis in the appropriate clinical setting. Bronchoscopy has an important role in establishing the final diagnosis.

Low-voltage electricity-induced lung injury.

We report a case of bilateral pulmonary infiltrates and haemoptysis following low-voltage electricity exposure in an agricultural worker. A 58-year-old man standing in water reached for an electric watering machine and sustained an exposure to 220 V circuit for an uncertain duration. The electricity was turned off by another worker, and the patient was asymptomatic for the next 10 h until he developed haemoptysis. A chest radiograph demonstrated bilateral infiltrates, and chest computed tomography (CT) revealed ground-glass opacities with interstitial thickening. Evaluations, including electrocardiogram, serum troponin, N-terminal pro-B-type natriuretic peptide (NT-pro BNP), coagulation studies, and echocardiogram, found no abnormality. The patient was treated for suspected electricity-induced lung injury and bleeding with tranexamic acid and for rhabdomyolysis with volume resuscitation. He recovered with complete resolution of chest radiograph abnormalities by Day 7. This is the first reported case of bilateral lung oedema and/or injury after electricity exposure without cardiac arrest.

Allergic Bronchopulmonary Aspergillosis masquerading as recurrent bacterial pneumonia.

Allergic Bronchopulmonary Aspergillosis (ABPA) can be diagnosed in an asthmatic with suitable radiologic and immunological features. However ABPA is likely to be misdiagnosed with bacterial pneumonia. Here we report a case of ABPA masquerading as recurrent bacterial pneumonia. Treatment with high-dose inhaled corticosteroids was effective. To our best knowledge, this is the first reported case of ABPA in Vietnam.

Boerhaave's syndrome - tension hydropneumothorax and rapidly developing hydropneumothorax: two radiographic clues in one case.

Boerhaave's syndrome is a rare and severe condition with high mortality partly because of its atypical presentation resulting in delayed diagnosis and management. Diagnostic clues play an important role in the approach to this syndrome. Here, we report a 48 year-old male patient hospitalized with fever and left chest pain radiating into the interscapular area. Two chest radiographs undertaken 22 h apart showed a rapidly developing tension hydropneumothorax. The amylase level in the pleural fluid was high. The fluid in the chest tube turned bluish after the patient drank methylene blue. The diagnosis of Boerhaave's syndrome was suspected based on the aforementioned clinical clues and confirmed at the operation. The patient recovered completely with the use of antibiotics and surgical treatment. In this case, we describe key findings on chest radiographs that are useful in diagnosing Boerhaave's syndrome.

Hemostatic changes in Vietnamese children with mild dengue correlate with the severity of vascular leakage rather than bleeding.

The mechanisms underlying the bleeding manifestations and coagulopathy associated with dengue remain unclear, in part because of the focus of much previous work on severe disease without an appropriate comparison group. We describe detailed clinical and laboratory profiles for a large group of children with dengue of all severities, and a group with similar non-dengue febrile illnesses, all followed prospectively from early presentation through to recovery. Among the dengue-infected patients but not the controls, thrombocytopenia, increased partial thromboplastin times and reduced fibrinogen concentrations were apparent from an early stage, and these abnormalities correlated strongly with the severity and timing of vascular leakage but not bleeding. There was little evidence of procoagulant activation. The findings do not support a primary diagnosis of disseminated intravascular coagulation to explain the intrinsic coagulopathy. An alternative biologically plausible hypothesis is discussed.