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In areas with suboptimal resources, blood transfusion may not be feasible even when mandatory for severely anemic children with a life-threatening disease. We evaluated how much not having received a transfusion affected the survival in 171 children with an admission blood hemoglobin level of < 6 g/dL and bacterial meningitis in Luanda, Angola. Of these children, 75% (128 of 171) had received a blood transfusion during hospitalization, but 25% (43 of 171) had not. Within the first week, 33% of patients (40 of 121) with transfusion and 50% (25 of 50) without a transfusion died (P = 0.04). Early transfusion (days 1–2 of hospitalization) prolonged the time of survival from a median of 132 hours [interquartile range (IQR), 15–168] to 168 hours (IQR, 69–168; P = 0.004), and had odds of 0.49 (95% CI, 0.25–0.97; P = 0.040) for death compared with no transfusion. The effect of transfusion/no transfusion at any time during hospitalization on mortality within 30 days, and prolongation of the time of survival were similar to early transfusion but showed even clearer benefits. Our results emphasize the value of timely transfusion in facilities that care for severely anemic children with severe infections to maximize their chances of survival.

Publisher Copyright: Copyright © 2022 The Author(s). Sickle cell disease (SCD) was found in 10% of children with bacterial meningitis (BM) in Luanda, 5-fold more than in the general population. BM children with SCD versus BM children without SCD had higher inflammatory markers, more often had pneumococcal meningitis (71% vs. 39%), and either died (39% vs. 22%) or had a longer hospital stay (15 vs. 11 days).

Aim Bacterial meningitis (BM) is a common cause of hearing loss in childhood. Our aim was to investigate bacterial aetiology, hearing impairment and outcome in childhood BM with vs. without otitis media (OM) in Angola. Methods Hearing was tested by auditory brainstem response in 391 (76%) children with confirmed BM. The bacteria identified from the ear discharge were compared to those from cerebrospinal fluid (CSF). The hearing findings were compared among children with vs. without OM on days 1 and 7 of hospitalization, and at follow-ups of 1, 3 and 6 month(s). Results No correlation was found in bacteriology between the ear discharge and CSF. On day 7 in hospital, hearing impairment (>40 dB) was common, regardless of whether concomitant OM or not (in 27% vs. 30%, respectively). Any hearing deficit on day 7 was associated with a higher risk of complicated or fatal clinical course (OR 2.76, CI95% 1.43-5.29, p = 0.002). Conclusion No significant difference prevailed in hearing thresholds between children with or without OM in hospital on day 7 or at later follow-ups. Any hearing impairment during hospital stay associated with a higher risk for complicated clinical course or death.

Our objective was to explore the importance of underweight on the course of childhood bacterial meningitis (BM) at different study sites, because prior studies showed discrepant results. Using directly comparable, prospective data from three continents, weight-for-age z-scores (WAZ) were determined by WHO Anthro programs in children with BM in Finland (N = 318), LatAm (N = 580), and Angola (N = 780) and compared with data describing the admission, course, and outcome of BM. WAZ

Background: Yearly, about two million infants die during the first 28 days of life. Most of these deaths occur in sub-Saharan Africa and a third of those are caused by severe infections. The early identification of infants at risk of death is important when trying to prevent poor outcomes. Objective: The aim of this study was to identify risk factors for death among young infants with possible serious bacterial infection (pSBI) at hospital admission. Methods: This prospective, observational, single-site, descriptive study forms part of a larger study on bacterial meningitis in infants

We reviewed the characteristics of children hospitalized for bone and joint infections in Luanda, Angola. In a retrospective chart review of 45 patients with childhood osteomyelitis or septic arthritis, 51% of the patients had sickle cell disease, and these patients presented with lower hemoglobin and needed blood transfusion more frequently (p < 0.05). Out of all patients, 64% underwent surgical procedures; a pathological fracture occurred in 31% of the patients.

Aim To compare the characteristics, mortality and sequelae at hospital discharge of childhood bacterial meningitis (BM) caused by the three "classical" agents Neisseria meningitidis, Haemophilus influenzae or Streptococcus pneumoniae versus BM due to other aetiology in Finland, Latin America and Angola. Methods This observational study is a secondary analysis of data from five prospective treatment trials on non-neonatal BM in Finland, Latin America and Angola in 1984-2017. Results Of the 1568 cases, 1459 (93%) were caused by the classics, 80 (5%) by other Gram-negative and 29 (2%) by other Gram-positive bacteria. Nonclassical Gram-negative disease was encountered especially in Angola (p < 0.0001). Overall, children in the nonclassical group presented later for treatment and were more often underweight and anaemic (p < 0.001). In multivariate analysis, even if the area was strongest predictor of poor outcome, nonclassical Gram-negative BM increased the odds for death twofold and the odds for death or severe sequelae 2.5-fold. Conclusion BM of a nonclassical aetiology is a particularly severe disease affecting especially Angolan children poorly armoured to fight infections. Since vaccinations are diminishing the role of classical agents, that of nonclassical agents is growing.

Background: Despite effective antibiotics and vaccines, bacterial meningitis (BM) remains one of the leading causes of morbidity and mortality in young infants worldwide. Data from Africa on the aetiology and antibiotic susceptibility are scarce. Objective: To describe the aetiology of BM in Angolan infants

Background In our previous study in Luanda, Angola, initial continuous β-lactam infusion for 24 hours combined with oral acetaminophen for 48 hours showed promising results as a new treatment for childhood bacterial meningitis. We investigated whether extending this treatment regimen to 4 days would improve the outcomes further. Methods We conducted a randomized, double-blind, parallel-group study at the same hospital in Luanda. Children aged 2 months to 15 years presenting to hospital with symptoms and signs of bacterial meningitis were randomized to receive, for the first 4 days, a continuous infusion of cefotaxime (250 mg/kg/day) with simultaneous oral acetaminophen (first dose 30 mg/kg, then 20 mg/kg every 6 hours), or cefotaxime conventionally as boluses (62.5 mg/kg, 4 times per day) with placebo orally. All children received also glycerol orally. The primary outcome was mortality by day 7. Results In all, 375 patients were included in the study between 22 January 2012 and 21 January 2017. As 2 children succumbed before treatment initiation, 187 vs 186 participants remained in the intervention and control groups, respectively. On day 7, 61 of 187 (32.6%) children in the intervention group vs 64 of 186 (34.4%) in the control group had died (risk ratio, 0.95 [95% confidence interval {CI}, .71–1.26]; absolute risk difference, 1.8% [95% CI, −7.8 to 11.4]). At discharge from hospital, the corresponding numbers were 71 of 187 (38.0%) and 75 of 186 (40.3%), respectively. Conclusions Prolonged continuous β-lactam infusion combined with oral acetaminophen did not improve the gloomy outcomes of childhood bacterial meningitis in Angola. Clinical Trials Registration NCT01540838.

Rubella is caused by an RNA virus. Infection results mostly in few or no symptoms. Viremia and viral shedding start before a rash may be seen. German physicians were probably the first to describe rubella in the early 19th century, hence the name "German measles". A British physician reported an outbreak in a boys’ school in India in 1841. He used the word rubella, "little red", a Latin diminutive from ruber (red). Rubella is often indistinguishable from other viral exanthematous diseases, but palpable posterior auricular and suboccipital lymph nodes are almost pathognomonic. Rubella infection during pregnancy may result in cataract, heart disease and deafness in an infant, forming the key triad defining “congenital rubella syndrome”, CRS. Also, mental retardation is common. After birth, rubella is a mild disease with rare complications only. There is no treatment for rubella or CRS, but vaccination programs usually with MMR-vaccine maintaining high vaccine uptake over time can virtually eliminate rubella.

Measles, known from the early ages, is caused by a paramyxovirus. A Persian colleague named Rhazes (854-925 A.D.) was likely the first to distinguish smallpox from measles, this milder disease getting the name “morbilli” (little disease) from the Latin word morbus (disease). Being one of the most contagious infections, a measles-infected individual may on average transmit the virus to 12-18 susceptible persons from 3-4 days before to soon after first clinical symptoms appear. Essentially only Man’s (and some monkey species’) disease, measles is potentially eradicable by vaccination, provided vaccine uptake exceeds 95 % for a long enough time. This remains a challenge, and we likely will continue to have measles with us for a long time.

Like measles, mumps is caused by a paramyxovirus, and it is only a disease of humans. The word "mumps" may relate to an old English term meaning grimace or mumble. Mumps was first described by Hippocrates (460-377 B.C.) in his book “Epidemics”, where he noted the presence of swelling around the ears and painful swelling of the testes. Central nervous system involvement was published by R Hamilton in 1790 in Scotland. Being less contagious than measles, an infected individual may still transmit mumps to 10-12 susceptible persons from 3-4 days before onset until 2 days after the onset of symptoms. Several live virus strains were developed as vaccine strains. Jeryl Lynn and its derivative RIT-4385 are in wide use in industrialized countries, L-Zagreb in the non-industrialized world. As the interpretation of serological data is not well understood the clinical value of mumps vaccines is evaluated on the basis of impact data only.

Our objective was to quantify the differences in the outcomes from childhood bacterial meningitis (BM) and to describe the factors associated with them in different parts of the world. This study is a secondary analysis of prospectively collected data from five clinical BM trials conducted in Finland, Latin America (LatAm), and Angola between 1984 and 2017. As all data were collected uniformly, direct comparison of the series was possible. Associations between patient characteristics and death or dismal outcome—the triad of death, severe neurological sequelae, or deafness—were explored. In all, data on 2123 children with BM were analyzed. Etiology was confirmed in 95%, 83%, and 64%, in Finland, LatAm and Angola, respectively. The leading agents were Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. Dismal outcome was the end result for 54%, 31%, and 5% of children in Angola, LatAm, and Finland, respectively. Although underweight, anemia, and tardy arrival worsened prognoses in Angola and LatAm, it was the presenting condition that was central in terms of outcome. In multivariate analysis, the factors independently associated with dismal outcome were the study site (Angola vs. Finland, OR 11.91, 95% CI 5.54–25.63, p vs. Finland, OR 9.46, 95% CI 4.35–20.61, p

The diagnosis of bacterial meningitis (BM) is problematic in young infants, as clinical features may be nonspecific or even absent. Cerebrospinal fluid (CSF) analysis usually confirms the diagnosis, but the CSF parameters can be normal also in culture-proven BM. Our objective was to identify the clinical and CSF indices, that quickly and without laboratory likely lead to the diagnosis of confirmed of probable BM in young infants in Angola.We conducted a prospective, observational, single-site study from February 2016 to October 2017 in the Pediatric Hospital of Luanda. All assessed infants showed symptoms and signs compatible of BM or neonatal sepsis and were90 days of age.Of the 1088 infants, 212 (19%) showed bacteria in CSF, while 88 (8%) had probable BM. Independent clinical indicators of BM were not-clear CSF, seizures, weight2500 g and illness7 days. In infants with BM, CSF leukocytes were10 × 106/L in 46%, CSF glucose25 mg/dL in 43% and CSF protein120 mg/dL in 58%. All measured parameters were in normal range in 25% of patients. In 515 infants with normal CSF parameters, bacteria were found in 74 (14%). In these infants, illness7 days, weight2500 g and malnutrition increased the probability of BM.Our study confirms and underlines the problems in diagnosing BM in young infants. While the CSF parameters were normal in 25% of infants, the easily recognizable unclear appearance of CSF was the single strongest predictor of BM.

BACKGROUND Survivors of bacterial meningitis (BM) often suffer from impaired quality of life that stems from disabling sequelae. The authors aimed to estimate health-related quality of life (HRQOL) and the influence of neurologic and audiologic sequelae among pediatric BM survivors. METHODS Survivors of 2 BM treatment trials at Luanda Children's Hospital, Angola were evaluated for severity of disability via the modified Glasgow Outcome Scale, which considers neurologic and audiologic sequelae. Children who received vaccinations at the hospital during the time of the study (1-2, 2017) and survivors' siblings served as controls. The Pediatric Quality of Life Inventory tool (PedsQL) enabled identifying HRQOL disparities between the cases and controls. RESULTS In all, 68 BM survivors (median time since BM: 28 months) and 35 controls participated. Survivors scored significantly lower than controls per PedsQL parent-proxy reports, indicating lower HRQOL (physical health: 82.5 vs. 100, P = 0.001; psychosocial health: 80 vs. 90, P = 0.005; and total score: 82.61 vs. 93, P = 0.004), while no difference prevailed between cases and controls in PedsQL child self-reporting. In all Glasgow Outcome Scale classes, cases differed significantly from controls in PedsQL parent-proxy reporting terms, with total scores of 84.21 (mild/no disability), 43.54 (moderate disability) and 55.56 (severe disability), while the controls scored 91.3 (P = 0.04, P = 0.02 and P < 0.001, respectively). CONCLUSIONS Irrespective of possible disability, BM survivors' HRQOL is impaired, according to parents' perceptions. There is a need to facilitate follow-ups for all BM survivors, to enable timely rehabilitation when needed.

Background. Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) contribute to the inflammatory cascade in the cerebrospinal fluid (CSF) during bacterial meningitis. We determined levels of MPO, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase- (TIMP-) 1 in the CSF of children with bacterial meningitis and investigated how these inflammatory mediators relate to each other and to the disease outcomes. Methods. Clinical data and the diagnostic CSF samples from 245 children (median age eight months) with bacterial meningitis were obtained from a clinical trial in Latin America in 1996–2003. MMP-9 levels in the CSF were assessed by zymography, while MMP-8, MPO, and TIMP-1 concentrations were determined with immunofluorometric and enzyme-linked immunosorbent assays. Results. MPO correlated positively with MMP-8 (rho 0.496, P<0.001) and MMP-9 (rho 0.153, P=0.02) but negatively with TIMP-1 (rho -0.361, P<0.001). MMP-8 emerged as the best predictor of disease outcomes: a CSF MMP-8 concentration above the median increased the odds of death 4.9-fold (95% confidence interval 1.8–12.9). Conclusions. CSF MMP-8 presented as an attractive prognostic marker in children with bacterial meningitis.

Otitis media (OM) is a common childhood infection that may result in bacterial meningitis (BM). However, OM-associated BM remains poorly characterized. We aimed to study the occurrence, clinical presentation and outcome of this type of childhood BM in Luanda, Angola.Five hundred twelve children from our previous clinical BM trial, with the ear meticulously examined, were analyzed whether they had or not OM, and according to their age, ≤12 month old and12 month old. Prospectively collected clinical data, laboratory test results and outcome for these groups were assessed.Sixty-two children (12%) had OM-associated BM, of whom 39 had otorrhea. Ear discharge was more common in older children (median age 45 months old vs. 12 months old; P0.001). Children with OM often showed an additional infectious focus (n = 20, 32% vs. n = 82, 18%; P = 0.016), were dehydrated (n = 16, 26% vs. n = 66, 15%; P = 0.04), and showed higher odds of complicated clinical course or death (odds ratios 2.27, 95% CI: 1.004-5.15, P = 0.049) compared with children without OM. The12-month-old children with OM often arrived in poor clinical condition with coma and/or ptosis. Otorrhea was associated with HIV positivity. Infants with otorrhea frequently lived under poor socioeconomic conditions.Children with OM-associated BM were prone to many problems, such as being especially ill at presentation, undergoing a difficult clinical course and showing a higher risk of complicated or fatal outcome. HIV infection and malnutrition were common in children with otorrhea, which was also associated with low socioeconomic status.

Background In resource-poor settings, otorrhea causes a significant burden of disease in children. Etiologic studies and structured data on otorrhea and chronic otitis media among African children remain scarce. Methods Here, we reviewed 678 bacteriologically analyzed otorrhea samples from Luanda Children's Hospital from children ≤15 years of age between 2008 and 2015. We then compared these with data from other studies among African children through a literature review of 20 articles published over 2 decades. Results Overall, 32 different bacteria were identified among 542 isolates from 654 children in Luanda. Gram-negative bacteria constituted the majority of all isolates (85%), whereby Pseudomonas spp. was the most common (n = 158; 29%), followed by Proteus spp. (n = 134; 25%). Among Staphylococcus aureus (n = 54; 10%), 69% of tested isolates were Methicillin-resistant S. aureus, and among Enterobacteriaceae, 14% were expanded-spectrum β-lactamase isolates. Resistance to quinolones was rare. Furthermore, in a review of the literature, we found a high occurrence of otorrhea and chronic suppurative otitis media in children as well as possible gaps in existing knowledge. Conclusions In Angola, Gram-negative rods emerged as common causative agents of otorrhea in children followed by S. aureus. The magnitude of chronic otorrhea in Africa represents a cause for public health concern.

Background: Bacterial meningitis (BM) is a common cause of hearing loss in childhood. Our aim was to investigate bacterial etiology, hearing impairment, and outcome in childhood BM with vs. without otitis media (OM) in the resource-poor settings of Angola. Methods: Hearing was tested through brainstem-evoked response audiometry (ABR) in 391 (76%) of 512 children with confirmed BM. The bacteria identified from the ear discharge were compared to those from CSF and the relevance of findings was examined in terms of hearing among children with or without OM on day 1 and 7 of hospitalization, and at follow-ups of 1, 3 and 6 month(s).Results: No correlation was found in bacteriology between the ear discharge and CSF, and the most common ear pathogens more likely reflected chronic than acute middle ear infections. On day 7 in hospital, hearing impairment (>40 dB) was common, regardless of whether concomitant OM or not (in 27% vs. 30%, respectively), whereas on day 7, profound hearing loss (>80 dB) was diagnosed slightly more in children without OM 16% vs. 10% accordingly. Any hearing deficit on day 7 was associated with a higher risk of complicated or fatal clinical course (OR 2.76, CI95% 1.43-5.29, P = .002).Conclusion: No significant difference prevailed in hearing thresholds between children with or without OM in hospital on day 7 or at later follow-ups. Any hearing impairment on day 7 associated with a higher risk for complicated clinical course or death. Trial registration: ISRCTN62824827. Registered 22 June 2005, http://www.isrctn.com/ ISRCTN62824827.

ObjectivesTo describe the prevalence and severity of anaemia and to examine its associations with outcome in children with bacterial meningitis (BM).DesignSecondary analysis of descriptive data from five randomised BM treatment trials.SettingHospitals in Finland, Latin America and Angola.ParticipantsConsecutive children from 2 months to 15 years of age admitted with BM and who had haemoglobin (Hb) measured on admission.Outcome measuresPrevalence and degree of anaemia using the WHO criteria, and their associations with recovery with sequelae or death.ResultsThe median Hb was 11.8 g/dL in Finland (N=341), 9.2 g/dL in Latin America (N=597) and 7.6 g/dL in Angola (N=1085). Of the children, 79% had anaemia, which was severe in 29%, moderate in 58% and mild in 13% of cases. Besides study area, having anaemia was independently associated with age 3 days, weight-for-age z-score ConclusionAnaemia, mostly moderate, was common in children with BM, especially in Angola, in underweight children, among those with treatment delay, and in pneumococcal meningitis. Poor outcome was associated with anaemia in all three continents.Trial registration numberThe registration numbers of Angolan trials were ISRCTN62824827 and NCT01540838.

Aim Vitamin D deficiency impairs the immunological system and has been associated with worse outcomes of infectious diseases, but its role in bacterial meningitis remains unknown. We investigated whether serum 25-hydroxyvitamin D concentrations related to disease outcomes and to cerebrospinal fluid (CSF) cathelicidin concentrations in childhood bacterial meningitis. Methods Results All consecutively enrolled patients in a clinical trial on childhood bacterial meningitis in Latin America in 1996-2003 were considered, and 142 children, with a median age of seven months who had a confirmed bacterial aetiology and frozen serum available for further analyses, were included in this study. Serum 25-hydroxyvitamin D concentrations were determined with a chemiluminescence immunoassay analyser, while CSF cathelicidin was measured by enzyme-linked immunosorbent assay. The median serum 25-hydroxyvitamin D concentration was 96 (range 19-251) nmol/L. No relationship was found with patient survival, but children with any neurological sequelae had lower serum 25-hydroxyvitamin D levels than children without sequelae. Serum 25-hydroxyvitamin D was unrelated to cathelicidin concentrations in CSF. Conclusion Although serum 25-hydroxyvitamin D in children with bacterial meningitis was not associated with survival or CSF cathelicidin concentrations, its relationship with more detailed disease outcomes warrants further study.

BACKGROUND Large cerebrospinal fluid (CSF) bacterial load in bacterial meningitis (BM) relates to poor outcome. However, the antimicrobial peptide cathelicidin seems important to host defense. We studied how cathelicidin concentrations and bacterial load in CSF relate in childhood BM and to what extent they may predict the disease outcome. METHODS The patient data originated from a large prospective clinical trial in Latin America in 1996-2003 in which the CSF samples were collected on admission (CSF1) and 12-24 hours later (CSF2). The cathelicidin concentrations were measured by enzyme-linked immunosorbent assay and the CSF bacterial load by real-time polymerase chain reaction. This analysis comprised 76 children with meningitis caused by Haemophilus influenzae type b (n = 44), Streptococcus pneumoniae (n = 28) or Neisseria meningitidis (n = 4). RESULTS The cathelicidin concentration correlated with the bacterial genome count in both samples (CSF1: ρ = 0.531, P < 0.001; CSF2: ρ = 0.553, P < 0.001). A high CSF1 ratio of cathelicidin to the bacterial genome count was associated with fewer audiologic sequelae (odds ratio: 0.11, 95% confidence interval: 0.02-0.61, P = 0.01) and more favorable neurologic outcomes (odds ratio: 3.95, 95% confidence interval: 1.22-12.8, P = 0.02), but not with better survival. CONCLUSIONS In conclusion, CSF cathelicidin and the bacterial load were closely related in childhood BM. A high initial cathelicidin-to-bacterial genome count ratio predicted better outcomes in survivors.

Background: Globally, diarrhea kills almost 1500 children daily. In diagnostics, molecular methods are replacing traditional assays. We aimed to investigate enteropathogens in children with and without diarrhea in Luanda, the capital of Angola. Methods: One hundred and ninety-four stool samples from 98 children with acute diarrhea and 96 children without diarrhea were investigated for 17 enteropathogens with multiplex real-time polymerase chain reaction. Results: The median age of children was 10.5 months. Enteropathogens, bacteria, viruses and parasites were detected in 91%, 78%, 50% and 25%, respectively. A positive finding was significantly (P = 0.003) more common in diarrhea when testing for all pathogens combined, for bacteria alone and for viruses alone. More than one pathogen was found more frequently in diarrhea than in non-diarrhea stool samples, in 87% and in 59% (P

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.

Magnetic resonance imaging studies are compatible with osteomyelitis of the distal right femur in a 6-year-old child with a 5-day history of increasing leg pain and fever. Blood culture at the time of admission has grown methicillin-resistant Staphylococcus aureus susceptible to clindamycin. There is no associated deep vein thrombosis. A follow-up blood culture obtained after 24 hours of vancomycin therapy is negative at 48 hours, and the child is much improved clinically at that time.

1. INTRODUCTIONThe European Society for Paediatric Infectious Diseases (ESPID) Bone and Joint Infection Guidelines (ESPID Guidelines) are intended for use by health providers who take care of children with bone and joint infection (BJI). Although BJI can include a diverse range of presentations, the

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 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 (ρ: 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.

BACKGROUND Hearing loss from childhood bacterial meningitis is believed to develop early and have little tendency for recovery. We performed serial hearing evaluations in a large number of children with bacterial meningitis in Luanda, Angola to clarify if, and how often, the result changed. METHODS Children with confirmed bacterial meningitis and hearing evaluations on admission, day 7 of treatment and the follow-up visit formed the study group. Hearing was tested by auditory brainstem response audiometry using stimuli of 40 dB, 60 dB and 80 dB. Threshold changes are described between the composite levels of 40/60 dB and 80/>80 dB. RESULTS In all, 235 ears were tested. While the ≤ 60 dB and ≥ 80 dB levels were maintained through all 3 examinations in 54% and 5% of ears, respectively, changes occurred in 41%. Deterioration from the ≤ 60 dB level to ≥ 80 dB was found in 10% of the ears transiently and in 7% permanently. Improvement from the ≥ 80 dB level to ≤ 60 dB occurred in 22% of the ears. Half of the ears with ≥ 80 dB impairment at the follow-up visit arrived with this finding; the others lost hearing later. Maintaining the ≤ 60 dB level throughout was associated with milder disease (P = 0.003), fewer convulsions (P < 0.0001) and older age (P = 0.009). CONCLUSIONS Almost half of the ears showed threshold changes after admission during recovery from bacterial meningitis, most frequently improvement of initially severely impaired hearing, but some normal ears or with moderate impairment became severely impaired.

Preceding trauma may play a role in the etiology and pathogenesis of hematogenous bone and joint infections. Among 345 children with an acute hematogenous bone and/or joint infection, 20% reported trauma during a 2-week period leading to infection. Blunt impact, bruises, or excoriations were commonly reported. The rate was similar to that in the general pediatric population obtained from the literature. In the study group, patients with and without trauma were similar in age, serum C-reactive protein and erythrocyte sedimentation rate, length of hospitalization, and late sequelae. Preceding minor trauma did not prove to be significant as an etiological or as a prognostic factor.

In Angola during 2003–2012, we detected Haemophilus influenzae in 18% of 2,634 and 26% of 2,996 bacteriologically positive pleural or cerebrospinal fluid samples, respectively, from children. After vaccination launch in 2006, H. influenzae empyema declined by 83% and meningitis by 86%. Severe H. influenzae pneumonia and meningitis are preventable by vaccination.

The role of human rhinoviruses (HRV) and human enteroviruses (HEV) in common colds, as well as their seasonality, remains largely unknown in tropical environments. The study aimed to define the frequency and clinical features of HRV and HEV in children with respiratory symptoms in tropical Africa during autumn and winter.Clinical data and PCR assays of nasopharyngeal swabs (NPS) were collected from 67 (66%) children with and 35 (34%) children without chronic illnesses who were attending different outpatient clinics at a paediatric tertiary-care hospital in Luanda, Angola.Thirty-six (35%) children had HIV infection, and 27 (26%) were malnourished. Thirty-seven (36%) out of 102 NPS specimens were virus-positive: 34 (33%) for HRV and 10 (10%) for HEV. Seven (7%) had co-infection. The highest HRV-positivity rate (47%) occurred in July (P = 0·02), a mid-winter month with high relative humidity but no precipitation. Virus positivity was associated with younger age (median 36 vs 52 months, P = 0·02) but not with specific symptoms or findings.HRVs play a major role in young children's respiratory infections in urban tropical Angola during autumn and winter. A better understanding is required of the seasonality and clinical outcomes of these viruses in children living in resource-poor tropical countries.

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.

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

Aim Bacteraemia is common in childhood acute bone and joint infections and demands urgent treatment. Blood C-reactive protein (CRP), erythrocyte sedimentation rate and white blood cell count (WBC) are well known and established markers in these infections. Instead, no information is available on serum alkaline phosphatase whose concentration is known to increase in septic conditions. Methods In our large prospective treatment trial comprising of 265 children with acute culture-positive bone or joint infection, all these laboratory indices were monitored on admission to hospital. The predictive value to detect bacteraemia was assessed for each of these four indices. Results In all, 59% of the patients showed bacteraemia. CRP was significantly (P < 0.05) higher among bacteraemic patients, whereas erythrocyte sedimentation rate, white blood cell count and alkaline phosphatase were not. The area under receiver operator characteristic curve for CRP was 0.588 (CI95% 0.524–0.649) and the significance level P (Area = 0.5) was