Luis Bernardino

Risk Factors for Death and Severe Neurological Sequelae in Childhood Bacterial Meningitis in Sub-Saharan Africa

We report a morality rate of 33% among 403 children with bacterial meningitis in Angola. A fatal outcome was associated with impaired consciousness, severe dyspnea, and seizures, and severe neurological sequelae (found in 25% of our patients) was associated with delayed presentation to the hospital, impaired consciousness, and seizures. Being underweight was of secondary importance. Treatment with ceftriaxone, rather than with penicillin plus chloramphenicol, did not improve outcome.

Acute childhood bacterial meningitis in Luanda, Angola

Incidence, morbidity and mortality of bacterial meningitis in developing countries are manifold greater than those in the industrialized world. We reviewed retrospectively children with meningitis treated in the paediatric hospital of Luanda in 2004. Among the 555 children, median age 11.0 months, the leading agents were Haemophilus influenzae type b (Hib), pneumococcus, and meningococcus in 60%, 24%, and 10%, respectively. The median length of illness before admission was 7 d. 65% had convulsed. Altered level of consciousness was observed in 61% and blood haemoglobin lower than 8 g/dl in 36% of cases. Case fatality was 35% and, of survivors, 24% were left with severe neurological sequelae. Blood transfusion appeared beneficial since fatality of children with and without transfusion was 23% versus 39% (p=0.003). While awaiting large-scale vaccinations, tools to improve the prognosis of meningitis in Angola comprise generating better awareness to reduce the delay, better fluid treatment and monitoring and active use of blood transfusions.

Chronic suppurative otitis media in children of Luanda, Angola.

Aim:  Evaluation of clinical characteristics, bacteriology and hearing in paediatric patients with and without chronic suppurative otitis media (CSOM) in Luanda, Angola.

Predictive Value of Cerebrospinal Fluid Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Concentrations in Childhood Bacterial Meningitis

Background: Increased concentrations of matrix metalloproteinases (MMP) in cerebrospinal fluid are part of the host response in bacterial meningitis (BM). We investigated whether the concentrations of MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 predict the outcome in childhood BM. Methods: Cerebrospinal fluid MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were quantified by an enzyme-linked immunosorbent assay from 264 and 335 patients, respectively; 43 children without BM served as controls. The results were compared with previously known independent predictors of death and sequelae. Results: Higher MMP-9 and TIMP-1 values distinguished the controls from the BM patients (P < 0.0001). A MMP-9 concentration >940 ng/mL proved an independent predictor of death [adjusted odds ratio: 4.03; 95% confidence interval (CI): 2.09−7.77; P < 0.0001]. If the patient additionally presented with a Glasgow Coma Score below 9, the odds increased to 13.21 (95% CI: 5.44−32.08; P < 0.0001). TIMP-1 levels correlated with the severity of sequelae (&rgr;: 0.30; P < 0.0001), but not with death. Its concentration above 390 ng/mL increased the likelihood of sequelae 3.43-fold (95% CI: 1·73−6·79; P = 0.0004), and up to 31.18-fold (95% CI: 4.05−239.8; P = 0.0009) if the patient also presented a Glasgow Coma Score < 12. Conclusions: Elevated cerebrospinal fluid MMP-9 and TIMP-1 values predict 2 important outcomes in childhood BM. Combined with a clinical evaluation, quantification of these indices augments the chances to identify the patients in greatest need of better treatment modalities.

Factors Affecting Time to Death From Start of Treatment Among Children Succumbing to Bacterial Meningitis

Background: Many risks of death in childhood bacterial meningitis are well-identified, but factors influencing survival time have received less attention. Better understanding of this issue could help explain why adjuvant medications have performed unevenly in different trials. Methods: In a post hoc analysis of prospectively collected data from a large bacterial meningitis treatment trial in Luanda, Angola, we compared time to death after initiation of antimicrobial treatment among 206 children with etiology and other patient characteristics. The risks of dying very quickly (0–4 hours), quickly (4–8 hours) or after longer periods were analyzed by logistic regression. Results: Median time to death was 18.5 hours, half the time in Streptococcus pneumoniae (11.8 hours) compared with Haemophilus influenzae (26.8 hours) meningitis. Of all deaths caused by pneumococcal or H.influenzae meningitis, 42% versus 16%, respectively, occurred within the first 8 hours. In addition, patients who succumbed within 8 hours, unlike those dying later, had a short disease history, shock, hypoglycemia and poor cerebrospinal fluid white cell response. Conclusions: Time to death in Angola is so short that hardly anything, except perhaps modern intensive care, is likely to improve outcome in a patient with meningitis, especially the pneumococcal disease.

Hearing loss in Angolan children with sickle‐cell disease

Hearing loss and pneumococcal infections occur in children with sickle‐cell disease (SCD). We assessed the prevalence of hearing loss and otological findings, especially otitis media, among children with SCD in Luanda, Angola.

C-reactive protein in children with malaria in Luanda, Angola: a prospective study

BACKGROUND C-reactive protein (CRP) is an acute phase reactant of which little is known in malaria, especially in central Africa. METHODS In this prospective study CRP was measured in children with suspected malaria. RESULTS Of 346 children, 234 had positive and 112 negative malaria microscopy. Their median CRP was 140 mg/L (IQR 88) vs 69 mg/L (IQR 129; p<0.001) respectively. CRP was positively correlated with parasitemia (p<0.001), and length of hospital stay (p=0.01), and negatively with thrombocyte count (p=0.01), and hemoglobin level (p=0.01). CONCLUSION C-reactive protein increases in malaria and correlates with parasitemia and some manifestations of complicated disease.

Changes in MMP-9 and TIMP-1 Concentrations in Cerebrospinal Fluid after 1 Week of Treatment of Childhood Bacterial Meningitis

ABSTRACT We explored the changes of the initially highly upgraded cerebrospinal fluid matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of MMP 1 (TIMP-1) response during recovery of childhood bacterial meningitis and their association with outcome. The sizes of these changes varied substantially, but a steeper decrease in the MMP-9 and an increase of the TIMP-1 concentrations augured a better outcome.

Ataxia and Its Association with Hearing Impairment in Childhood Bacterial Meningitis.

Introduction: Ataxia, deemed usually a minor sequela, follows childhood bacterial meningitis (BM) in up to 18% of cases. Although mostly transient and benign, it can predict permanent hearing loss and vestibular dysfunction. We explored the clinical meaning of ataxia by following its course in a large number of BM patients and examining its relation with hearing loss. Methods: The presence, degree (no, mild, moderate and severe) and course (transient, prolonged and late) of ataxia in BM were registered prospectively by predefined criteria. These data were compared with several patient, disease, and outcome variables including hearing loss (none, moderate, severe and profound) on day 7 of treatment and at a follow-up visit 1 month after discharge. Results: Ataxia was present in 243 of 361 (67%) patients on day 7, being slight in 21%, moderate in 38% and severe in 41%. Its course was transient in 41%, prolonged in 24% and late in 5%, whereas 30% of the patients did not present ataxia at any time. Ataxia associated most significantly not only with several measures of BM severity and suboptimal outcome (P < 0.0001), but also specifically, albeit not consistently, with hearing loss (P = 0.001). The degree of ataxia correlated with the extent of hearing loss (rho, 0.37; P < 0.0001). Conclusions: Ataxia is more frequent and lasts longer after BM than learned from previous studies. The presence and intensity of ataxia associate with hearing loss and its magnitude.

Predicting Outcome of Childhood Bacterial Meningitis With a Single Measurement of C-Reactive Protein

Introduction: C-reactive protein (CRP), a marker of inflammation, shows high serum levels in invasive bacterial infections. We investigated the potential of a single CRP measurement at different phases of acute childhood bacterial meningitis to predict outcomes. Methods: Using whole-blood finger-prick samples with no centrifugation, CRP was measured quantitatively on arrival and on day 3 or 4 in children participating in 2 prospective, randomized, double-blind treatment studies conducted in Latin America or Angola. The results were compared with patient outcomes. Results: Although initial CRP values from 669 children gave useful prognostic information, the 3rd or 4th day measurements taken from 275 children associated significantly with seizures, slow recovery and low scores on the Glasgow Outcome Scale, with odds ratios for CRP values above the median (62 mg/L) ranging from 2 to 6, 2 to 5, and 3 to 5 (Latin America–Angola), respectively. Hearing impairment, although not full deafness, was 3 to 7 times more likely if CRP was above the median soon after hospitalization. Conclusions: Especially in resource-poor settings, clinicians have few simple-enough tools to identify the child with meningitis who requires maximum attention. CRP is a worthy addition.