Malaria prevention reduces in-hospital mortality among severely ill tuberculosis patients: a three-step intervention in Bissau, Guinea-Bissau.

BACKGROUND: Malaria and Tuberculosis (TB) are important causes of morbidity and mortality in Africa. Malaria prevention reduces mortality among HIV patients, pregnant women and children, but its role in TB patients is not clear. In the TB National Reference Center in Guinea-Bissau, admitted patients are in severe clinical conditions and mortality during the rainy season is high. We performed a three-step malaria prevention program to reduce mortality in TB patients during the rainy season. METHODS: Since 2005 Permethrin treated bed nets were given to every patient. Since 2006 environmental prevention with permethrin derivates was performed both indoor and outdoor during the rainy season. In 2007 cotrimoxazole prophylaxis was added during the rainy season. Care was without charge; health education on malaria prevention was performed weekly. Primary outcomes were death, discharge, drop-out. RESULTS: 427, 346, 549 patients were admitted in 2005, 2006, 2007, respectively. Mortality dropped from 26.46% in 2005 to 18.76% in 2007 (p-value 0.003), due to the significant reduction in rainy season mortality (death/discharge ratio: 0.79, 0.55 and 0.26 in 2005, 2006 and 2007 respectively; p-value 0.001) while dry season mortality remained constant (0.39, 0.37 and 0.32; p-value 0.647). Costs of malaria prevention were limited: 2€/person. No drop-outs were observed. Health education attendance was 96-99%. CONCLUSIONS: Malaria prevention in African tertiary care hospitals seems feasible with limited costs. Vector control, personal protection and cotrimoxazole prophylaxis seem to reduce mortality in severely ill TB patients. Prospective randomized trials are needed to confirm our findings in similar settings.

Pulmonary hypertension in sickle cell disease children under 10 years of age.

Despite the finding of elevated Tricuspid Regurgitant Velocity (TRV) in children below 5 years of age, the prevalence and evolution of Pulmonary Hypertension (PH) in young children with sickle cell disease (SCD) are unclear. In order to identify predictive factors of precocious PH development, SCD children > or =3 years old, at steady state, underwent annual echocardiography and Tissue Doppler Imaging (TDI). Patients receiving chronic transfusion were excluded. Thirty-seven of seventy-five patients were > or =3 years, with measurable TRV. In our young population (mean age 6.2 years) of mainly African, HbS/HbS patients, 8/37 (21.6%) had TRV > or =2.5 m/s, 8% being only 3 years old. Significant correlation was found between precocious TRV elevation and high platelet and reticulocyte counts and frequent acute chest syndromes (ACS). In multivariate analysis, ACS was the only variable predicting TRV > or =2.5 m/s. TDI of the 37 patients showed signs of diastolic dysfunction of the left ventricle. At follow-up all eight patients with high TRV displayed further increase and seven more developed TRV > or =2.5 m/s. PH seems to begin in children earlier than expected. Factors involved in its early onset might be different from the ones causing its development in older children or adults. African children might benefit from early screening and re-assessment once a year.

Coagulation activation in children with sickle cell disease is associated with cerebral small vessel vasculopathy.

BACKGROUND: Thrombotic complications in Sickle Cell Disease (SCD) arise since infancy, but the role of the coagulation system in children has been poorly explored. To determine its role in the development of clinical complications in childhood we measured coagulation and endothelial parameters in children with SCD at steady state. METHODS: Markers of thrombin generation, fibrin dissolution and endothelial activation were evaluated in 38 children with SS-Sß°, 6 with SC disease and 50 age and blood group matched controls. Coagulation variables were correlated with markers of hemolysis and inflammation, with the presence of cerebral and lung vasculopathy and with the frequency of clinical complications. RESULTS: SS-Sß° patients presented higher levels of factor VIII, von Willebrand factor antigen (VWF:Ag) and collagen binding activity, tissue plasminogen activator antigen (t-PA:Ag), D-dimer, p-selectin, prothrombin fragment1+2 (F1+2) and lower ADAMTS-13:activity/VWF:Ag (p<0.05) compared to controls and SC patients. In SS-Sß° patients coagulation variables correlated positively with markers of inflammation, hemolysis, and negatively with HbF (p<0.05). Patients with cerebral silent infarcts showed significant decrease in t-PA:Ag and ADAMTS-13 Antigen and a tendency toward higher D-dimer, F1+2, TAT compared to patients without them. D-dimer was associated with a six fold increased risk of cerebral silent infarcts. No correlation was found between coagulation activation and large vessel vasculopathy or other clinical events except for decreased t-PA:Ag in patients with tricuspid Rigurgitant Velocity >2.5m/sec. CONCLUSIONS: SS-Sß° disease is associated with extensive activation of the coagulation system at steady state since young age. ADAMTS-13 and t-PA:Ag are involved in the development of cerebral silent infarcts.

Tricuspid regurgitant velocity elevation in a three-year old child with sickle cell anemia and recurrent acute chest syndromes reversed not by hydroxyurea but by bone marrow transplantation.

Elevated Tricuspid Regurgitant Velocity (TRV) has been related to higher mortality in adults and to hemolysis, lower oxygen saturation during 6-minute walk test and acute chest syndrome (ACS) in children with sickle cell disease (SCD). Hydroxyurea (HU) has reduced TRV value in children and adults. We describe a three year old HbSS child with recurrent ACS, hypoperfusion of the left lung, mild hemolysis and persistent TRV elevation. TRV did not normalize after HU, despite improvement in clinical conditions and in baseline laboratory parameters related to hemolysis and blood viscosity, but normalized after bone marrow transplantation (BMT). Our experience suggests that in young patients, TRV reduction can be a positive concomitant effect of BMT.