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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.

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.

Background Bacterial meningitis (BM) is a significant cause of mortality in children; with deaths from BM in children aged \

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

Background. Synovial fluid and blood cultures often remain negative in acute bone and joint infections of childhood even when characteristic symptoms, signs, and/or radiologic proof are present. Methods. We analyzed 345 prospectively documented osteoarticular infections in children at age 3 months to 15 years. In 23% of the cases (N = 80), synovial, bone, and/or blood cultures remained negative. The characteristics of these cases were compared with patients with culture-positive bone and joint infections. Results. The 2 groups did not differ in age or gender distribution, surgical procedures performed, or outcome. In the culture-negative cases, the initial serum C-reactive protein level was lower (58 vs 87 mg/L, P < .0001) and the hospital stay was shorter (8 vs 11 days, P < .0001). Conclusions. Bone and joint infections in which cultures fail to identify the causative agent can be treated similarly as culture-positive cases.

Background 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. Methods We performed otorhinolaryngological examination, tympanometry and, at ages over 5 years, pure-tone audiometry, in 61 outpatients of the SCD clinic and 61 healthy controls in the Paediatric Hospital of Luanda. Results Bilateral hearing loss exceeding 25 dB occurred in nine (36%; median age 7.8 years) SCD children versus three (11%; P = 0.047) control children. The hearing loss in the SCD group was predominantly mild (26–40 dB), involved low- and speech-range frequencies, and was sex independent. Acute otitis media occurred in two (3%) children with SCD versus four (6%; P = 0.68) control children, chronic otitis in zero versus two (3%; P = 0.50), and middle-ear effusion in one versus one (2%; P > 0.99). We found no significant differences in the otological profiles of the study groups. Conclusions In sub-Saharan Africa, hearing screening of SCD children is a must at preschool age. The actual prevalence of otitis media and its role in the cause of hearing loss in children with SCD remain subjects for further research.

Human enteroviruses are the most common cause of viral meningitis. Viral–bacterial interaction may affect the clinical course and outcome of bacterial meningitis. In Africa, viruses might be responsible for 14–25% of all meningitis cases. However, only few studies from Africa have reported detection of viruses in the cerebrospinal fluid (CSF) or mixed viral–bacterial infections of the central nervous system (CNS). The aim of the present study was to investigate the presence of picornaviruses in the CSF of children suffering from meningitis in Luanda, Angola. The study included 142 consecutive children enrolled in a prospective study of bacterial meningitis in Luanda between 2005 and 2006, from whom a CSF sample was available. CSF samples were obtained at hospital admission, stored in a deep-freeze, and transported to Finland for testing by real-time PCR for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus influenzae meningitis recovered uneventfully. An 8-year-old girl with human enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl with human enterovirus and malaria recovered quickly. A 7-month-old girl with human enterovirus was treated for presumed tuberculous meningitis and survived with severe sequelae. Mixed infections of the CNS with picornaviruses and bacteria are rare. Detection of an enterovirus does not affect the clinical picture and outcome of bacterial meningitis. J. Med. Virol. 84: 1080–1083, 2012. © 2012 Wiley Periodicals, Inc.

The treatment of acute hematogenous bone and joint infections of children - osteomyelitis (OM), septic arthritis (SA) and OM-SA combination (OM+SA) - has simplified over the past years. The old approach included months-long antibiotic treatment, started intravenously for at least a week, followed by oral completion of the course. Recent prospective randomized trials show that most cases heal with a total course of 3 weeks (OM, OM+SA) or 2 weeks (SA) of an appropriate antibiotic, provided the clinical response is good and C-reactive protein level has normalized. If the prevalence of methicillin-resistant Staphylococcus aureus and Kingella kingae is low, clindamycin and a first-generation cephalosporin are safe, inexpensive and effective alternatives. They should be administered in large doses and four times a day. Clindamycin, vancomycin and expensive linezolid are options against methicillin-resistant Staphylococcus aureus. Extensive surgery beyond a diagnostic sample by aspiration is rarely needed in uncomplicated cases.

Aim: Evaluation of clinical characteristics, bacteriology and hearing in paediatric patients with and without chronic suppurative otitis media (CSOM) in Luanda, Angola. Methods: Interview, clinical examination, ear-discharge culture, open air pure-tone audiometry and brainstem auditory-evoked potentials of 23 outpatients with CSOM and 23 controls in a paediatric hospital. Results: Of the CSOM vs. control children, 35% vs. 26% had running water, 70% vs. 70% electricity, 64% vs. 0% HIV (p 25 dB was present in 52% of CSOM-affected ears and bilateral hearing loss in 7 (30%) CSOM children vs. zero control child (p = 0.009). Only one hearing-impaired child’s family had previously detected the handicap. Conclusion: CSOM occurred in children with high co-morbidity. Persistent otorrhoea was usually caused by Proteus spp. or Pseudomonas, and often suggestive of either HIV or hearing impairment. In the developing countries, prompt diagnosis and treatment of CSOM would enhance the children’s linguistic and academic development.

Unless acute osteomyelitis in children is diagnosed promptly and treated appropriately, it can be a devastating or even fatal disease. This review summarizes the current approach to the treatment of acute osteomyelitis in children.

Considerable uncertainty exists on the optimal duration of antimicrobials for acute hematogenous osteomyelitis (AHOM) in children. Often they are administered for 1 to 2 months, the first 1 to 2 weeks intravenously, and decompressive surgery is usually added. No prospective, randomized, sufficiently powered comparative trial has been available.Children aged 3 months to 15 years with culture-positive AHOM were randomly assigned to receive clindamycin or a first-generation cephalosporin for 20 or 30 days, including an intravenous phase for the first 2 to 4 days. Surgery was kept at minimum. Illness was monitored with preset criteria. Antimicrobial was discontinued once most signs had subsided and serum C-reactive protein decreased ≤20 mg/L. The primary end point was full recovery without need for further antimicrobial therapy because of an osteoarticular indication during the 12 months after the primary therapy.Of the 131 cases, 18% also involved the adjacent joint. Staphylococcus aureus caused 89% of cases, and all strains were methicillin susceptible. The median duration of treatment was 20 days for 67 children, and 30 days for 64 children. Most children underwent only the diagnostic percutaneous aspiration or drilling, and 24% had no surgery. Except for 1 mild sequela in both treatment groups, all patients recovered entirely.Most cases of childhood AHOM can be treated for 20 days, including a short period intravenously, with large doses of a well-absorbed antimicrobial such as clindamycin or a first-generation cephalosporin, provided the clinical response is good and C-reactive protein normalizes within 7 to 10 days. Extensive surgery is rarely needed.

Background Hearing impairment is a well-recognized sequela caused by bacterial meningitis, but the underlying pathophysiology remains largely unknown. Matrix metalloproteinase-2 (MMP-2) is known to affect neuronal cell damage and survival in different diseases of the brain. We investigated whether levels of MMP-2 in the cerebrospinal fluid (CSF) relate to the extent of hearing impairment in children with bacterial meningitis. Methods Clinical data of 179 children were obtained from a previous clinical trial examining the adjuvant treatment of bacterial meningitis in Latin America in 1996–2003. At discharge or shortly thereafter, the ability to hear was measured with brain stem evoked response audiometry or traditional pure tone audiometry. Levels of CSF MMP-2 on admission (CSF1, n = 161) and 12–24 hours later (CSF2, n = 133) were assessed by zymography. The combined results for the detected pro-form and active MMP-2 were compared with the audiological outcome of the patients. Results MMP-2 was detected in half of both the CSF1 and CSF2 samples. The median densitometric values with interquartile ranges (IQRs) were 0.04 (IQR 0.00–0.29) for CSF1 and 0.00 (IQR 0.00–0.33) for CSF2. Detectable MMP-2 associated with milder hearing impairment in CSF1 (P = 0.05), but not in CSF2 (P = 0.1). Patients who were deaf at discharge had lower levels of MMP-2 in both samples (CSF1, P = 0.05; CSF2, P = 0.04), compared with patients who were not deaf. A MMP-2 level over the 75th percentile in CSF1 predicted lower odds of any audiological sequelae (odds ratio 0.30, 95% confidence interval 0.14–0.68, P = 0.004). Conclusion The upregulation of MMP-2 in the CSF associated with a better audiological outcome in children with bacterial meningitis. The results suggest that MMP-2 might play a protective role in the development of hearing sequelae due to bacterial meningitis. Disclosures All authors: No reported disclosures.

Background In Sub-Saharan Africa, both malaria (M), and bacterial meningitis (BM) cause fever and central nervous system (CNS) disturbance. We studied their prevalence, characteristics, outcome, and risk factors for poor outcome to better understand the clinical impact of suspected CNS infection in children. Methods We conducted a prospective study in the Children’s Hospital (HPDB) in the capital of Angola which attends 300 new patients daily. Spinal tap (ST) was performed for children presenting with altered consciousness, convulsions, prostration, or meningism. The analysis included children aged 3 month to 15 years with confirmed discharge diagnosis in 2016–2017. Results Of 941 children, the diagnosis was M in 56% (525), BM in 12% (116), epilepsy/convulsions in 9% (88), and other infections in 6% (60). Of all children, 16% (150/941) died, 6% (45/733) had severe, 14% (93/655) any neurological sequelae, and 27% (243/897) either died or had neurological sequelae. In children with M, the corresponding figures were 7% (35/525), 1.5% (7/476), 4% (19/443), and 11% (54/514). In children with BM, the figures were 41% (47/116), 15% (8/54), 33% (11/33), and 55% (58/105), respectively. Comparing with M, children with BM were younger (median age (IQR) 28 (61) vs. 60 (68) months, P < 0.0001), had an underlying illness (23/97 vs. 19/374, P < 0.0001), like sickle-cell disease (18/96 vs. 9/372, P < 0.0001), longer duration of illness (4 (4) vs. 3 (3) days, P < 0.0001, dyspnea (70/119 vs. 210/463, P = 0.009), were dehydrated (36/113 vs. 67/441, P < 0.0001), or malnourished (38/115 vs. 75/447, P = 0.0001). Multivariate analysis revealed as independent risk factors for death or neurological sequelae age 3 days (2.48, 1.68–3.64, P < 0.0001), malnutrition (1.92, 1.20–3.05, P = 0.006), and dehydration (1.92, 1.16–3.14, P = 0.01). When BM vs. M was included in the analysis, BM appeared as the most important risk factor (OR 8.06, 4.44–14.65, P < 0.0001) and age lost its significance. Conclusion In suspected CNS infection, M was the final diagnosis of most children. However, BM caused more deaths and neurological sequelae. Amendable factors, such as delay in treatment, dehydration, and malnutrition, appeared as risk factors for poor outcome. Disclosures T. Pelkonen, sanofi pasteur: Investigator, Sanofi Paster funded this study. Paediatric Research Foundation, Helsinki, Finland: Grant Investigator, Grant recipient. Päivikki and Sakari Sohlberg Foundation, Helsinki, Finland: Grant Investigator, Grant recipient

In our multicenter treatment study on pediatric nonneonatal osteoarticular infections we had 62 septic hip arthritides. All had confirmed joint effusion, were culture-positive, and Staphylococcus aureus was isolated in 71% of the cases. Sixty-one of the 62 had a diagnostic joint aspiration. Following protocol, arthrotomy was to be performed only if the response to antimicrobial treatment was slow. The course of illness was monitored by preset criteria. Analysis of 95% of the patients who attended the last checkup >/=1 year posthospitalization showed that invasive surgery had been avoided in 81% of the patients. All patients recovered completely. Routine arthrotomy in nonneonatal hip arthritis warrants reconsideration.

OBJECTIVE. Several studies have evaluated dexamethasone for prevention of hearing loss in childhood bacterial meningitis, but results have varied. We compared dexamethasone and/or glycerol recipients with placebo recipients, and measured hearing at 3 threshold levels.METHODS. Children aged 2 months to 16 years with meningitis were treated with ceftriaxone but were double-blindly randomly assigned to receive adjuvant dexamethasone intravenously, glycerol orally, both agents, or neither agent. We used the Glasgow coma scale to grade the presenting status. The end points were the better ear's ability to detect sounds of >40 dB, ≥60 dB, and ≥80 dB, with these thresholds indicating any, moderate-to-severe, or severe impairment, respectively. All tests were interpreted by an external audiologist. Influence of covariates in the treatment groups was examined by binary logistic regression.RESULTS: Of the 383 children, mostly with meningitis caused by Haemophilus influenzae type b or Streptococcus pneumoniae, 101 received dexamethasone, 95 received dexamethasone and glycerol, 92 received glycerol, and 95 received placebo. Only the presenting condition and young age predicted impairment independently through all threshold levels. Each lowering point in the Glasgow scale increased the risk by 15% to 21% (odds ratio: 1.20, 1.21, and 1.15 [95% confidence interval: 1.06–1.35, 1.07–1.37, and 1.01–1.31]; P = .005, .003, and .039) for any, moderate-to-severe, or severe impairment, respectively. Each increasing month of age decreased the risk by 2% to 6% (P = .0001, .0007, and .041, respectively). Neither dexamethasone nor glycerol prevented hearing loss at these levels regardless of the causative agent or timing of antimicrobial agent.CONCLUSIONS: With bacterial meningitis, the child's presenting status and young age are the most important predictors of hearing impairment. Little relief is obtained from current adjuvant medications.

Purpose of review Intravenous dexamethasone (DXM) is used as adjuvant medication in bacterial meningitis of childhood, although no single study has proven its efficacy against death, severe neurological sequelae, or hearing impairment. Meta-analyses do not facilitate interpretation, because they combine profoundly dissimilar populations and neglect the child's presenting condition. Important new information was revealed by a large double-blind, prospective study from Latin America in which the effects of oral glycerol (GLY) were compared with those of DXM. Recent findings Of 654 children, mainly with Haemophilus influenzae type b or pneumococcal meningitis, 166 received DXM, 159 DXM and GLY, 166 GLY, and 163 placebo. Neither of the adjuvants prevented hearing impairment, regardless of agent or timing of antibiotic. Instead of the causative agent, the presenting status was the only characteristic that associated with all three outcomes. GLY, but not DXM, prevented neurological sequelae, especially in Haemophilus influenzae type b meningitis. The likely mechanism of GLY is the increase in plasma osmolality. Cerebrospinal fluid genome counts differ enormously and predict death in pneumococcal but not Haemophilus influenzae type b meningitis. Summary Being the first adjuvant in childhood meningitis with documented clinically meaningful benefits, GLY seriously challenges the position of DXM as adjuvant medication. Severe neurological sequelae are relieved by GLY, whereas no current medication prevents hearing impairment.

Background. The standard treatment for septic arthritis in children is antimicrobials for several weeks (initially administered intravenously) and arthrotomy (at least for the hip and shoulder joints). No sufficiently powered study has examined the true need for these treatments. Methods. In a randomized, multicenter prospective trial in Finland, children aged 3 months to 15 years who had culture-positive septic arthritis were randomized to receive clindamycin or a first-generation cephalosporin for 10 days or 30 days (intravenously for the first 2‐4 days). The number of surgical procedures was kept to a minimum. Illness was monitored with preset criteria. Antimicrobial therapy was discontinued when the clinical response was good and the C-reactive protein level decreased to 20 mg/L. The primary end point was full recovery without need for further administration of antimicrobial therapy because of an osteoarticular indication during the 12 months after therapy. Results. Of the total 130 cases, 88% were caused by Staphylococcus aureus, Haemophilus influenzae, or Streptococcus pyogenes; 63 patients were in the short-term treatment group, and 67 were in the long-term treatment group. The median durations of antimicrobial treatment were 10 days and 30 days, respectively. Surgical procedures that were more extensive than percutaneous joint aspiration were performed for 12% of patients, with no preponderance to hip or shoulder arthritis. Two late-onset infections occurred in 1 child in the long-term treatment group; however, all patients recovered without sequelae. Conclusions. Large doses of well-absorbed antimicrobials for !2 weeks (initially administered intravenously) and only 1 joint aspiration are sufficient for treatment of most cases of childhood septic arthritis, regardless of the infecting pathogen or anatomical site, if the clinical response is good and the C-reactive protein level normalizes shortly after initiation of treatment.

Background The persistence of antibodies against measles, mumps, and rubella induced by the measles-mumps-rubella (MMR) vaccine and the kinetics of antibody decline after the second MMR vaccine dose were studied in the same cohort for 20 years. Methods Measles, mumps, and rubella antibodies were measured by enzyme immunoassay in 20-year follow-up serum samples (n= 183) of twice-vaccinated individuals, and measles antibodies were also measured in oral fluids (n = 177). Antibody decay was determined in a group (n = 58) with subsequent samples collected 1, 8, and 15 years after the second MMR dose. Results In total, 95%, 74%, and 100% of 183 vaccinees were still seropositive for measles, mumps, and rubella, respectively, and 85% of 177 vaccinees had measurable measles antibodies in their oral fluids. The antibody levels declined significantly after the second dose, but subsequently the rate of decline was slower. Conclusions A high rate of seropositivity was found 20 years after the first MMR dose, particularly for rubella and measles. Our results show that MMR vaccine-induced antibodies wane significantly after the second dose. According to epidemiological data, the protection induced by MMR vaccination in Finland seems to persist at least until early adulthood. However, the situation requires constant vigilance.

In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.

Mumps epidemics in Canada and the United States prompted us to review evidence for the effectiveness of 5 different vaccine strains. Early trials with the Jeryl Lynn vaccine strain demonstrated an efficacy of approximately 95%, but in epidemic conditions, the effectiveness has been as low as 62%; this is still considerably better than the effectiveness of another safe strain, Rubini (which has an effectiveness of close to 0% in epidemic conditions). The Urabe vaccine strain has an effectiveness of 54%-87% but is prone to cause aseptic meningitis. Little epidemiological information is available for other vaccines. The Leningrad-Zagreb vaccine strain, which is widely used in developing countries and costs a fraction of what vaccines cost in the developed world, seems to have encouraging results; in 1 study, the effectiveness of this vaccine exceeded 95%. Aseptic meningitis has also been reported in association with this vaccine, but the benign nature of the associated meningitis was shown recently in Croatia. Also, the Leningrad-3 strain seems to be effective but causes less-benign meningitis. No mumps vaccine equals the best vaccines in quality, but the virtually complete safety of some strains may not offset their low effectiveness. Epidemiological data are pivotal in mumps, because serological testing is subject to many interpretation problems.

Objective Childhood bacterial meningitis (BM) damages hearing, but the potential of different agents to cause impairment in developing countries is poorly understood. We compared the extent of hearing impairment in BM caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae or Neisseria meningitidis among children aged 2 months to 13 years in Luanda, Angola. Methods Hearing of 685 ears of 351 (78%) survivors among 723 enrolled patients was tested by brainstem-evoked response audiometry on day 7 of hospitalization. The causative agent was sought by cerebrospinal fluid culture, PCR or the latex-agglutination test. Results Altogether, 45 (12%) of the survivors were deaf (threshold >80 dB), and 20 (6%) had a threshold of 80 dB. The incidence of any kind of hearing loss, with ≥60 dB, was 34% with Hib, 30% with S. pneumoniae , 19% with N. meningitidis and 33% with other bacteria. Examining all ears combined and using the ≥60 dB threshold, the agents showed dissimilar harm ( P = 0.005), Hib being the most frequent and N. meningitidis the most infrequent cause. Compared to other agents, S. pneumoniae more often caused deafness ( P = 0.025) and hearing impairment at ≥60 dB ( P = 0.017) in infants, whereas this level of hearing loss in older survivors was most commonly caused by Hib ( P = 0.031). Conclusions BM among children in Angola is often followed by hearing impairment, but the risk depends on the agent. S. pneumoniae is a major problem among infants, whereas Hib is mainly a risk beyond 12 months. N. meningitidis impairs hearing less frequently.