Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

OBJECTIVES: Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever. METHODS: Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers. RESULTS: Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1 + 2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values. CONCLUSIONS: Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease.

Increased incidence of necrotizing enterocolitis in the Netherlands after implementation of the new Dutch guideline for active treatment in extremely preterm infants: Results from three academic referral centers.

INTRODUCTION: Necrotizing enterocolitis (NEC) is a severe inflammatory disease, mostly occurring in preterm infants. The Dutch guidelines for active treatment of extremely preterm infants changed in 2006 from 26+0 to 25+0weeks of gestation, and in 2010 to 24+0 of gestation. We aimed to gain insight into the incidence, clinical outcomes and treatment strategies, in three academic referral centers in the Netherlands over the last nine years. METHODS: We performed a multicenter retrospective cohort study of all patients with NEC (Bell stage ≥2a) in three academic referral centers diagnosed between 2005 and 2013. Outcome measures consisted of incidence, changes in clinical presentation, treatment strategies and mortality. RESULTS: Between 2005 and 2013 14,161 children were admitted to the neonatal intensive care unit in the three centers. The overall percentage of children born at a gestational age of 24weeks and 25weeks increased with 1.7% after the introduction of the guidelines in 2006 and 2010. The incidence of NEC increased significantly (period 2005-2007: 2.1%; period 2008-2010 3.9%; period 2011-2013: 3.4%; P=0.001). We observed a significant decrease of peritoneal drainages (↓16%; P=0.001) and a decrease of laparotomies (↓24%; P=0.002). The mortality rate (33% in 2011-2013) remained unchanged. CONCLUSION: The incidence of NEC significantly increased in the last nine years. The increase in incidence of NEC seemed to be related to an increase in infants born at a gestational age of 24 and 25weeks. The percentage of patients needing surgery decreased, while 30-day mortality did not change. LEVEL OF EVIDENCE: Level IV.

A prospective study of the importance of enteric fever as a cause of non-malarial febrile illness in patients admitted to Chittagong Medical College Hospital, Bangladesh.

BACKGROUND: Fever is a common cause of hospital admission in Bangladesh but causative agents, other than malaria, are not routinely investigated. Enteric fever is thought to be common. METHODS: Adults and children admitted to Chittagong Medical College Hospital with a temperature of ≥38.0 °C were investigated using a blood smear for malaria, a blood culture, real-time PCR to detect Salmonella Typhi, S. Paratyphi A and other pathogens in blood and CSF and an NS1 antigen dengue ELISA. RESULTS: We enrolled 300 febrile patients with a negative malaria smear between January and June 2012: 156 children (aged ≤15 years) and 144 adults with a median (interquartile range) age of 13 (5-31) years and median (IQR) illness duration before admission of five (2-8) days. Clinical enteric fever was diagnosed in 52 patients (17.3 %), lower respiratory tract infection in 48 (16.0 %), non-specific febrile illness in 48 (16.0 %), a CNS infection in 37 patients (12.3 %), urinary sepsis in 23 patients (7.7 %), an upper respiratory tract infection in 21 patients (7.0 %), and diarrhea or dysentery in 21 patients (7.0 %). Malaria was still suspected in seven patients despite a negative microscopy test. S. Typhi was detected in blood by culture or PCR in 34 (11.3 %) of patients. Of note Rickettsia typhi and Orientia tsutsugamushi were detected by PCR in two and one patient respectively. Twenty-nine (9 %) patients died during their hospital admission (15/160 (9.4 %) of children and 14/144 (9.7 %) adults). Two of 52 (3.8 %) patients with enteric fever, 5/48 (10.4 %) patients with lower respiratory tract infections, and 12/37 (32.4 %) patients with CNS infection died. CONCLUSION: Enteric fever was confirmed in 11.3 % of patients admitted to this hospital in Bangladesh with non-malaria fever. Lower respiratory tract and CNS infections were also common. CNS infections in this location merit more detailed study due to the high mortality.