Bacteremia in Childhood Life-Threatening Infections in Urban Gambia: EUCLIDS in West Africa.

BACKGROUND: The limited availability of microbiology services in sub-Saharan Africa impedes accurate diagnosis of bacterial pathogens and understanding of trends in prevalence and antibiotic sensitivities. We aimed to characterize bacteremia among hospitalized children in The Gambia and to identify factors associated with bacteremia and mortality. METHODS: We prospectively studied children presenting with suspected severe infection to 2 urban hospitals in The Gambia, between January 2013 and September 2015. Demographic and anthropometric data, clinical features, management, and blood culture results were documented. Urine screens for antibiotic activity were performed in a subset of participants. RESULTS: Of 411 children enrolled (median age, 29 months; interquartile range, 11-82), 79.5% (325 of 409) reported prehospital antibiotic use. Antimicrobial activity by urinary screen for antibiotic activity was detected in 70.8% (n = 80 of 113). Sixty-six bacterial pathogens were identified in 65 (15.8%) participants and Staphylococcus aureus predominated. Gram-positive organisms were more commonly identified than Gram-negative (P < .01). Antibiotic resistance against first-line antimicrobials (ampicillin and gentamicin) was common among Gram-negative bacteria (39%; range, 25%-100%). Factors significantly associated with bacteremia included the following: gender, hydration status, musculoskeletal examination findings, admission to the Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine hospital, and meeting sepsis criteria. Those associated with increased mortality were presence of a comorbidity, clinical pallor, tachypnea, and altered consciousness. Tachycardia was associated with reduced mortality. CONCLUSIONS: The bacteremia rate in children with suspected childhood life-threatening infectious diseases in The Gambia is high. The pattern of pathogen prevalence and antimicrobial resistance has changed over time compared with previous studies illustrating the importance of robust bacterial surveillance programs in resource-limited settings.

The burden of pneumococcal meningitis in Austrian children between 2001 and 2008.

UNLABELLED: The present study was conducted to evaluate the burden of pneumococcal meningitis in Austrian children between 2001 and 2008. Clinical outcome was retrospectively analyzed both on discharge and on follow-up investigations. This study was based on a prospective multicentre surveillance study on hospitalized invasive pneumococcal infections in Austrian children with a total annual "study population" of about 399,000 children aged below 5 years per year. Between 2001 and 2008, 74 cases of pneumococcal meningitis were identified in children aged below 5 years. The mean annual incidence rate for pneumococcal meningitis was 2.3 per 100,000 children in this age group. In 57/74 children (mean age on admission 14.5 ± 13.3 months), outcome data on hospital discharge were available: 5 deaths (8.8%), 20 children (35.1%) with sequelae and 32 children (56.1%) without sequelae were observed. Sequelae on discharge included motor impairment in 8 children (14.0%), hearing impairment in 9 children (15.8%) and/or other complications in 14 children (24.6%). In 7/8 children with motor deficits, matching cerebral lesions were identified by neuroimaging: cerebral infarction in five children, cerebral vasculitis and cerebral abscess in one child each. In 40/57 children, long-term outcome (18.9 ± 20.2 months after discharge) could be assessed: 1 child (2.5%) died 9 months after hospital discharge, 11 children (27.5%) had one or two long-term sequelae and 28 children (70.0%) had no sequelae. Long-term sequelae included motor impairment in three children (7.5%), hearing impairment in nine children (22.5%) and other deficits in two children (5.0%). CONCLUSION: Our study confirms that pneumococcal meningitis causes high mortality and severe long-term sequelae. On long-term follow-up, we observed improvements of motor impairment, but not of hearing impairment.

CXCL13 chemokine in pediatric and adult neuroborreliosis.

OBJECTIVES: Diagnosis of Lyme neuroborreliosis (NB) depends on the proof of intrathecal antibody production against Borrelia burgdorferi. CXCL13 has been seen to be elevated early in NB, before antibody production has started. In this study, we determined the diagnostic role of the CXCL13 chemokine in cerebrospinal fluid (CSF) and serum for the first time in pediatric NB patients as well as in adults, compared to controls and blood donors (BD). MATERIAL AND METHODS: CXCL13 levels were measured in CSF and serum of 33 children and 42 adult patients. Serum CXCL13 was measured in 300 BD. RESULTS: CSF CXCL13 levels were significantly elevated in definite and probable acute NB in children and adults compared to seropositive and seronegative neurological controls (P < 0.001). Serum CXCL13 levels showed great fluctuations and were not significantly elevated in NB patients. CONCLUSIONS: Our study suggests that CSF CXCL13 can be used as a diagnostic marker for NB in children as well. In contrast, CXCL13 serum levels show great variance even in the healthy population and are not indicative of active NB.

Maternal interleukin-6 (-174) C/C polymorphism is associated with chorioamnionitis and cystic periventricular leucomalacia of the preterm infant.

OBJECTIVE: To evaluate the association between maternal interleukin (IL)-6 G(-174)C polymorphism and cystic periventricular leukomalacia (cPVL) of the preterm newborn. STUDY DESIGN: After searching a local database, we recruited 132 preterm infants with diagnosis of cPVL, 44 Caucasian mothers were also recruited to participate in this candidate gene-association study at a single teritary care center. Data related to maternal IL-6 G(-174)C polymorphisms were compared with 41 controls, and furthermore compared with data from umbilical cord blood samples from a consecutive birth cohort of 395 healthy newborns, and published data from Caucasian populations including 1104 adults, respectively. In addition, subgroup analysis was performed in cases with either history of preterm premature rupture of the membranes (PPROM) or clinical chorioamnionitis (CCA). IL-6 genotyping was performed using an allele-specific polymerase chain reaction technique. RESULT: Frequencies of the IL-6 G(-174)C polymorphisms did not differ between cases (GG, 29.5%; GC, 54.5% and CC, 15.9%) and controls (GG, 34.2; GC, 51.2 and CC, 14.6%). Subgroup analysis of 31 cases with history of PPROM (GG, 25.8; GC, 54.8 and CC 19.4%) and controls did not reveal significant differences, but a significantly higher frequency of the CC genotype was found in 23 cases with a history of CCA (34.8%) compared with controls by either univariate (P=0.032; odds ratio 3.11, 95% confidence interval (CI) 1.11 to 8.68) or multivariate analysis (P=0.049, odds ratio 2.54, 95% CI 1.01 to 6.45). These data were confirmed by a comparing the CC genotype frequency to 395 term controls (CC 14.7%, P=0.005) and to the mean CC genotype frequency of 1104 Caucasian adults (CC 15.6%, P<0.0001). CONCLUSION: Frequencies of the IL-6 G(-174)C polymorphisms did not differ between groups. Subgroup analysis revealed an association of the CC genotype with CCA and cPVL in the preterm newborn.

4G4G genotype of the plasminogen activator inhibitor-1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia.

BACKGROUND: Meningococcal disease may present as sepsis, meningitis or a combination of both. Impaired fibrinolysis and massive elevation of the plasminogen activator inhibitor-1 (PAI-1) is a characteristic feature of meningococcal sepsis. We and others have reported an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1 gene in children with meningococcal sepsis. OBJECTIVE: Multicenter study to investigate the association of the 4G/5G PAI-1 polymorphism and disseminated intravascular coagulation (DIC) in children with meningococcal disease in a Central European population. PATIENTS/METHODS: Blood samples and clinical information of 326 previously healthy children with meningococcal infection were collected from 95 pediatric hospitals in Germany, Switzerland, Italy, and Austria from 2000 to 2002. RESULTS: DIC, defined as platelet counts below 100 G L(-1), increased D-dimer levels and prolonged prothrombin time, was significantly associated with the 4G4G genotype [31 of 63 (49%) vs. 55 of 175 (31%), P = 0.014], resulting in a hazard ratio (HR) of 1.5 (95% confidence interval 1.1-2.1) to develop DIC. Carriers of the 4G4G genotype showed significantly lower platelet counts (183 G L(-1) vs. 227 G L(-1), P = 0.009) on admission. Fibrinogen and C-reactive protein levels were not associated with the PAI-1 4G/5G polymorphism, nor were white blood cell counts. CONCLUSIONS: Our data show a correlation between the 4G4G genotype of the PAI-1 gene and development of DIC in meningococcal infection.

[Congenital hypopituitarism and giant cell hepatitis in a three month old girl]. / Konnataler Panhypopituitarismus und Riesenzellhepatitis bei einem 3 Monate alten Säugling.

CASE REPORT: A three month old girl, with recurrent hypoglycemia and neonatal cholestasis, is reported. A metabolic disease could be excluded. The liver biopsy revealed giant cell hepatitis and intrahepatic bile duct hypoplasia. ACTH, Cortisol and hGH measured during hypoglycemia were low. Magnetic tomography (MR) of the brain showed an "empty sella". After beginning a replacement therapy with hydrocortisone, growth hormone and thyroxine there was no further episode of hypoglycemia. Transaminases and bilirubin levels normalized. The girl is in good condition, growth and development are normal. DISCUSSION: Hypoglycemia is often the first sign in childrens with neonatal hypopituitarism. The association of liver disease and hypopituitarism has been documented in a few reports. The pathophysiological mechanism leading to the liver dysfunction is not well understood. The prognosis of neonatal hypopituitarism as well as the concomitant liver disease is good under sufficient replacement therapy.

Danaparoid sodium (Orgaran) in four children with heparin-induced thrombocytopenia type II.

UNLABELLED: We report on four children with heparin-induced thrombocytopenia type II. In three patients, therapy with unfractionated heparin was associated with development of cardiac thrombi or with thrombosis progression up to the inferior vena cava or with aggravation of peripheral arterial occlusion. In the fourth child, the disease was recognized early on, and no complication occurred. Heparin-induced thrombocytopenia type II was confirmed by heparin-induced platelet activation assay and/or heparin/platelet factor 4-ELISA. Concomitant elevated antiphospholipid antibodies were seen in all patients. Danaparoid sodium applied at a dosage of between 1.2 and 7.1 U/kg/h stopped the disease progression in each patient. Three children had a clinical recovery with partial recanalization, but for the child with peripheral arterial occlusion disease, amputation of some of the toes became necessary. CONCLUSION: Our data indicate that heparin-induced thrombocytopenia type II is a potential life-threatening disease in children and danaparoid sodium is beneficial in this age group.

Stroke following appendectomy under general anesthesia in a patient with basilar impression.

We report a boy who developed a vertebral stroke immediately after an appendectomy. Basilar impression was diagnosed eight years after this event when skull roentgenograms revealed basilar impression with high standing tip of the odontoid. We speculate that muscle relaxation and cervical hyperextension during intubation in the presence of basilar impression resulted in vertebral artery dissection and stroke. We suggest that patients with vertebral stroke and no obvious risk factors should be evaluated for the presence of malformations of the craniovertebral junction to be able to take precautions against excessive neck movement during intubation.

[Congenital malaria due to Plasmodium falciparum and Plasmodium malariae]. / Konnatale Malaria durch Plasmodium falciparum und Plasmodium malariae.

Increasing tourism and growing numbers of immigrants from malaria-endemic countries are leading to a higher importation rate of rare tropical disorders in European countries. We describe, to the best of our knowledge, the first case of connatal malaria in Austria. The patient is the first child of a 24 year old mother who was born in Ghana and immigrated to Austria one and a half years before delivery. She did not stay in an endemic region during this period and did not show fever or any other signs of malaria. The boy was healthy for the first six weeks of his life. In the 8th week of life he was admitted to our hospital due to persistent fever of unknown origin. On physical examination he showed only mild splenomegaly. Routine laboratory testing revealed mild hemolytic anemia with a hemoglobin value of 8.3 g/l. In the blood smear Plasmodium falciparum and Plasmodium malariae were detected. Oral therapy with quinine hydrochloride was successful and blood smears became negative for Plasmodia within 6 days. This case shows that congenital malaria can occur in children of clinically healthy women who were born in malaria-endemic areas even one and a half year after they have immigrated to non-endemic regions.

[Acute erythromelalgia with hypertension in a 5-year old boy]. / Akute Erythromelalgie mit Hypertonie bei einem 5jährigen Knaben.

BACKGROUND: Burning pain of red and warm hands and/or feet are the classical symptoms of erythromelalgia. CASE REPORT: We describe the symptoms of acute idiopathic erythromelalgia and arterial hypertension in a five-year-old boy. Five days after a gastroenteritis the patient developed burning hands and feet in combination with arterial hypertension. Typically continuous cooling of all affected limbs was necessary to relieve the pain. Drug therapy with sodium nitroprusside only relieved the pain and dropped the blood pressure temporarily. Five weeks after onset of the disease all symptoms disappeared and the patient is still free of complaints (follow up period: 2 years). In the view of the presented case we discuss the differential diagnoses as well as therapeutical options.

Factor V Leiden and prothrombin gene G 20210 A variant in children with ischemic stroke.

OBJECTIVE: To investigate if the factor V Leiden mutation (F-V-LM) and/or the prothrombin gene G 20210 A variant (P-G20210A-V) are risk factors for acute stroke in Austrian children. PATIENTS: 33 children with acute ischemic stroke documented by computer tomography and/or magnetic resonance imaging of the brain were enrolled in an open multicenter survey. RESULTS: 6/33 children had F-V-LM (5 heterozygous, 1 homozygous). This represents 18% (95% CI: 6.7-39.9%) of our pediatric stroke population and thus exceeds the expected prevalence in the Austrian population of 4,6% (Fischer's exact test, p = 0.01). F-V-LM was not found in 11 children with neonatal stroke but in 6/22 children with stroke after the neonatal period. 5/6 children with F-V-LM had an underlying disorder that is a risk factor for stroke in children. The P-G20210A-V was detected in 1/26 (3.85%; 95% CI: 0.1-21.4%) patients. Comparison of the prevalence of P-G20210A-V in our study with that in the general population of Austria of 1% revealed no statistical significance (Fischer's exact test, p = 0.38). CONCLUSION: Our data suggest that the F-V-LM is a risk factor for acute stroke in Austrian children beyond the neonatal period. The P-G20210A-V apparently does not represent a risk factor for stroke in Austrian children.

Intracerebral hemorrhage during fibrinolytic therapy in children: a review of the literature of the last thirty years.

In a retrospective study all available publications concerning children with thromboembolic disease and fibrinolytic therapy between January 1, 1964, and June 30, 1995, were reviewed with regard to the occurrence of intracerebral hemorrhages (ICH). ICH was found in 14/929 patients analyzed. According to the age when thrombolytic therapy was performed, ICH was described in 2/468 children after the neonatal period, in 1/83 term infants; and in 11/86 preterm infants; 10/40 preterm infants who were treated in the first week of life developed ICH. ICH during thrombolytic therapy in children is reported with the use of streptokinase, urokinase (UK), UK-activated plasmin, UK and plasminogen, and recombinant tissue plasminogen activator (rt-PA). The risk of developing an ICH from thrombolytic therapy seems to be low in children after the neonatal period and in term infants. Because of the high incidence of "spontaneous" ICH in preterm infants, it cannot be established whether the more frequently described ICH in these patients is a complication of thrombolytic therapy. In the absence of randomized trials this analysis may be helpful for decision making in children with thromboembolic disorders. However, the data have to be regarded with caution because of the summation of cases with different thromboembolic disorders, treatment with different substances in different dosages, and the retrospective study design that could lead to an underrepresentation of this complication.

Catheter-directed thrombolysis with recombinant tissue plasminogen activator for acute pulmonary embolism after fontan operation.

We report the case of a 3-year-old girl who presented with near-lethal pulmonary thrombembolism 3 weeks after an uneventful Fontan operation. Complete occlusion of the left lower lobe pulmonary artery had occurred together with a cerebral infarction. Recombinant tissue plasminogen activator (rt-Pa) was used for thrombolysis because of its short half-life and its clot-selective properties. To further minimize the systemic effects of rt-PA, local catheter-directed lysis was performed. A prolonged course of low-dose rt-PA therapy achieved complete lysis without side effects.

Inherited defects of the protein C anticoagulant system in childhood thrombo-embolism.

Childhood thrombo-embolism is mostly the result of inherited thrombophilia or vascular insults combined with risk factors such as peripartal asphyxia, fetopathia diabetica, exsiccosis, septicaemia, central lines, congenital heart disease, cancer, trauma, surgery or elevated antiphospholipid antibodies. Inherited thrombophilia includes mainly defects of the protein C pathway, resistance to activated protein C, protein C or protein S deficiency. Resistance to activated protein C, in the majority of cases caused by the point mutation Arg 506 Gln of the factor V gene, has emerged as the most important hereditary cause of thrombo-embolism in adults and children. However, since an acquired risk of thrombo-embolic complications frequently masks the inherited deficiency in affected children, children with thrombo-embolism should have adequate laboratory evaluation for inherited coagulation disorders, especially the protein C pathway. Until more data on childhood thrombo-embolism are available, treatment recommendations will continue to be extrapolated from guidelines for adults.

Activation of the clotting system during extracorporeal membrane oxygenation in term newborn infants.

OBJECTIVES: To determine the degree of clotting activation that occurs with the usual anticoagulation regimen with systemic heparinization. METHODS: To allow a standardized comparison of the patients, this study focused on the first 48 hours of extracorporeal membrane oxygenation (ECMO) in term newborn infants. The ECMO perfusion circuit consisted of a roller pump, silicone membrane lungs, and silicone rubber tubing. Coagulation was controlled routinely by measuring prothrombin time, fibrinogen, antithrombin III, and reptilase time. Platelet counts, activated clotting time, and heparin concentration were controlled regularly. The following specific activation markers of the clotting system were measured: prothrombin activation fragment 1 + 2(F1+2), thrombin-antithrombin III complexes, and D-dimer. Measurements were done before the start of ECMO, after 5 minutes, and at hours 1, 2, 3, 4, 6, 12, 24 and 48. RESULTS: All seven term infants had excessively high levels of clotting activation markers within the first 2 hours of ECMO: F1+2, 11.6(+/- O.9) nmol/L (mean +/- SEM); thrombin-antithrombin, 920(+/- 2.2) microg/L; D-dimer, 15.522(+/- 3.689) ng/L. During the next 46 hours of ECMO, F1+2 and thrombin-antithrombin III complexes decreased from those high values, whereas D-dimer did not. The increase of activation markers was accompanied by low fibrinogen, low platelet counts. and prolongation of reptilase time. CONCLUSIONS: These findings fit the pattern of consumptive coagulopathy during neonatal ECMO, especially in the first 24 hours.