Severe sepsis due to severe falciparum malaria and leptospirosis co-infection treated with activated protein C

Co-infection with falciparum malaria and leptospirosis is uncommon. The aim of this study is to report a case of severe sepsis secondary to dual infection with falciparum malaria and leptospirosis. The literature is also reviewed on the clinical course of such co-infections, and the possible mechanisms and treatment of patients with life-threatening malaria and leptospirosis with activated protein C. The patient was a 25-year old male admitted in the Respiratory Intensive Care Unit (RICU) with fever, haemolysis, acute renal failure, hepatitis, acute lung injury (ALI) and altered sensorium. A syndromic evaluation was done and investigations revealed falciparum parasitaemia. He was treated with parenteral artesunate, ceftriaxone and doxycycline, and adjunctive therapies as for severe sepsis. Infusion of activated protein C was started 20 hours after onset of organ dysfunction, and intensive haemodialysis was instituted. Over the next four days the patient became afebrile with progressive resolution of ALI, renal failure and hepatitis. His Leptospira serology (requested as part of the evaluation) was reported positive on day 5. Dual infections are common and under-recognized in the tropics. Failure to treat potential co-infections may lead to poor outcomes. Acute lung injury in falciparum malaria has high mortality rates and therapy as for severe sepsis may improve survival. Adjunctive therapies, including activated protein C, cannot replace source eradication

Bronchiectasis in India:results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients ( 6518 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0\ub70001]) and more likely to be men (1249 [56\ub79%] of 2195). Previous tuberculosis (780 [35\ub75%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13\ub77%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1\ub717, 95% CI 1\ub703-1\ub732; p=0\ub7015), P aeruginosa infection (1\ub729, 1\ub710-1\ub750; p=0\ub7001), a history of pulmonary tuberculosis (1\ub720, 1\ub707-1\ub734; p=0\ub7002), modified Medical Research Council Dyspnoea score (1\ub732, 1\ub725-1\ub739; p<0\ub70001), daily sputum production (1\ub716, 1\ub703-1\ub730; p=0\ub7013), and radiological severity of disease (1\ub703, 1\ub701-1\ub704; p<0\ub70001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation

Diagnosing and treating hemophagocytic lymphohistiocytosis in the tropics: Systematic review from the indian subcontinent

Background. Hemophagocytic lymphohistiocytosis (HLH) is a catastrophicsyndrome of unrestrained immune activation. Evaluation and management of HLH in the tropics is challenging. Objectives. To examine the reported etiologies and management of HLH reported from the sub-continent. Methods. Systematic review of all published cases from the Indian sub-continent. Results. We found only 156 publishedcases of HLH from the sub-continent. HLH was reported fromthe immediate perinatal period to 46 years of age. Infection-associated HLH (IAHS) constituted 46.8% of all cases of HLH (44% and 51% in children and adults respectively). In adults, tropical infections triggered 51% of these cases of IAHS. Steroids were used in 47% of children and 10% of adults. Etoposide and/or cyclosporine were used in 8% children and 8% of adults only. Intravenous immunoglobulin was used in another 30% of children and 4% of the adults. HLH-relatedmortality occurred in 31.8% and 28% of children and adults respectively. Conclusions. HLH is under-reported in the sub-continentand has high mortality. Cyclosporine and etoposide are seldom administered early despite diagnosis of HLH. Larger cohorts with IAHStriggered by tropical infections are urgently needed to understand itsnatural history and implications of this differing prescription pattern on mortality

Pulmonary hypertension associated with connective tissue disease

Pulmonary hypertension (PH) is an important cause of morbidity and mortality in connective tissue diseases (CTDs). CTDs may cause PH due to several mechanisms; pulmonary arterial hypertension, associated interstitial lung disease, neuromuscular disease, and/or sleep disordered breathing leading to hypoxia, associated thromboembolic PH, and pulmonary venous hypertension due to left ventricular dysfunction. PH can be measured on echocardiography, but the gold standard for diagnosis is right heart catheterization. PH-specific therapy in addition to immunosuppression is the most common treatment used though data are scant. In this narrative review, we discuss the epidemiologic burden, clinical presentation, evaluation, and management of PH in CTDs

Phenotyping CLAD after single lung transplant: limits and prognostic assessment of the 2019 ISHLT classification system

Background: Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) is challenging, due to the native lung contribution to pulmonary function test (PFT). We aimed to assess the applicability and prognostic performance of International Society for Heart and Lung Transplantation (ISHLT) classification in SLTX. Methods: In this retrospective study of adult, first, SLTX performed 2009-2017, patients with persistent drop in FEV1≥20% were assessed by 2 independent adjudicators to determine CLAD status and phenotype. Interobserver agreement (IOA) was calculated (Cohen's Kappa) for CLAD, phenotype and presence of RAS (resttrictive allograft syndrome)-like opacities (RLO). Association of CLAD phenotypes with time to death or retransplant (ReTx), adjusted for age at SLTX, sex, CMV mismatch and native lung condition, were assessed using Cox proportional hazards models. Results: Of 172 SLTX recipients, 92 experienced a persistent drop in FEV1&gt;20%. Following adjudication, 67 were diagnosed with CLAD. We noted a moderate IOA for CLAD diagnosis (Kappa 0.69) and poor IOA for phenotype adjudication (Kappa 0.52). The final phenotype adjudication was 31 bronchiolitis obliterans syndrome (BOS) (46.3%), 13 RAS (19.4%), 2 mixed (3%), 2 Undefined (3%), and 19 remained Unclassified (28.3%). Using these adjudicated phenotypes, RAS was significantly associated with a higher risk of death/ReTx compared to other groups (HR 2.98, 95%CI [1.39-6.4]). The adjudication of RLO had the best IOA (Kappa 0.73). The presence of RLO was a strong predictor of death or ReTx (HR 2.37, 95%CI [1.2-4.5]), regardless of the final phenotype. Conclusions: PFT interpretation is challenging in SLTX. A classification essentially relying on imaging, which harbored good IOA, obtained better prognostic performance than a classification using published physiological cut-offs.</p