Felicity Fitzgerald

Term and preterm labour are associated with distinct microbial community structures in placental membranes which are independent of mode of delivery.

Infection is considered a possible trigger for preterm labour, supported by evidence showing the presence of bacteria in the placenta and placental membranes from preterm births. In this study, 16S rDNA pyrosequencing was used to identify bacteria in placental membranes. Caesarean sections and vaginal deliveries at term were found to harbour common genera. Mycoplasma hominis, Aerococcus christensenii, Gardnerella vaginalis and Fusobacterium nucleatum were either only present in preterm membranes or in greater abundance than at term. These data support previous studies that used either targeted qPCR or broad-range 16S rDNA PCR and cloning but not a recent microbiome analysis of placental tissue using high-throughput sequencing.

The expanding role of co-trimoxazole in developing countries.

Co-trimoxazole is an inexpensive, broad-spectrum antimicrobial drug that is widely used in developing countries. Before antiretroviral therapy (ART) scale-up, co-trimoxazole prophylaxis reduced morbidity and mortality in adults and children with HIV by preventing bacterial infections, diarrhoea, malaria, and Pneumocystis jirovecii pneumonia, despite high levels of microbial resistance. Co-trimoxazole prophylaxis reduces early mortality by 58% (95% CI 39-71) in adults starting ART. Co-trimoxazole provides ongoing protection against malaria and non-malaria infections after immune reconstitution in ART-treated individuals in sub-Saharan Africa, leading to a change in WHO guidelines, which now recommend long-term co-trimoxazole prophylaxis for adults and children in settings with a high prevalence of malaria or severe bacterial infections. Co-trimoxazole prophylaxis is recommended for HIV-exposed infants from age 4-6 weeks; however, the risks and benefits of co-trimoxazole during infancy are unclear. Co-trimoxazole prophylaxis reduces anaemia and improves growth in children with HIV, possibly by reducing inflammation, either through direct immunomodulatory activity or through effects on the intestinal microbiota leading to reduced microbial translocation. Ongoing trials are now assessing the ability of adjunctive co-trimoxazole to reduce mortality in children after severe anaemia or severe acute malnutrition. In this Review, we discuss the mechanisms of action, benefits and risks, and clinical trials of co-trimoxazole in developing countries.

Ebola Virus Disease in Children, Sierra Leone, 2014–2015

Children died rapidly, more than half in Ebola holding units before transfer to treatment units.

Ebola response in Sierra Leone: The impact on children

Summary The West African Ebola virus disease (EVD) outbreak is the largest ever seen, with over 28,000 cases and 11,300 deaths since early 2014. The magnitude of the outbreak has tested fragile governmental health systems and non-governmental organizations (NGOs) to their limit. Here we discuss the outbreak in the Western Area of Sierra Leone, the shape of the local response and the impact the response had on caring for children suspected of having contracted EVD. Challenges encountered in providing clinical care to children whilst working in the “Red Zone” where risk of EVD is considered to be highest, wearing full personal protective equipment are detailed. Suggestions and recommendations both for further research and for operational improvement in the future are made, with particular reference as to how a response could be more child-focused.

Risk in the "Red Zone": Outcomes for Children Admitted to Ebola Holding Units in Sierra Leone Without Ebola Virus Disease

Abstract We collected data on 1054 children admitted to Ebola Holding Units in Sierra Leone and describe outcomes of 697/1054 children testing negative for Ebola virus disease (EVD) and accompanying caregivers. Case-fatality was 9%; 3/630 (0.5%) children discharged testing negative were readmitted EVD-positive. Nosocomial EVD transmission risk may be lower than feared.

Refining the paediatric Ebola case definition: a study of children in Sierra Leone with suspected Ebola virus disease

Abstract Background The case definition for suspected Ebola virus disease is broad, so many negative children are isolated for testing, risking nosocomial infection. We collected data on children admitted to Ebola holding units in Sierra Leone to refine the case definition and describe outcomes of admitted children. Methods All children aged less than 13 years admitted to 11 Ebola holding units in Sierra Leone between Aug 1, 2014, and March 31, 2015, were eligible for inclusion. Data were collected from paper-based clinical records, district-wide laboratory results, burial records, staff interviews, and follow-up telephone calls. The cohort was split into training and validation datasets. A model was developed with multivariable logistic regression and compared with laboratory results to explore the sensitivity and specificity of the alternative case definition. Findings Of 1054 children admitted, 309 (29%) tested positive for Ebola virus disease and 697 (66%) tested negative (48 [5%] missing). The model had an area under receiver operating characteristic curve of 0·80 (high performance). A case definition of Ebola virus disease contact alone, fever (in children >2 years), or fever and conjunctivitis ( 2 years) improved specificity (97%), with sensitivity of 23%. Children testing negative had a case fatality rate of 8% versus 57% in those with Ebola virus disease (p Interpretation Contact history, fever, conjunctivitis, abdominal pain, and diarrhoea are key characteristics for diagnosis of paediatric Ebola virus disease. The case definitions developed can be used flexibly—for example, for triage into risk categories to reduce risk of nosocomial infection. Funding Save the Children.

Ebola virus disease in children in Sierra Leone: a retrospective cohort study

Abstract Background The outbreak of Ebola virus disease in West Africa has claimed more than 11 200 lives with more than 28 000 cases. Infected children under the age of 5 years have a high mortality rate but little is known about disease progression and possible predictors of outcome. Circumstantial factors such as transfer distances from Ebola holding units to Ebola treatment centres and admission with a caregiver might affect outcome. We aimed to identify clinical, epidemiological, and management risk factors for mortality in children with Ebola virus disease. Methods Children under the age of 12 years admitted to 11 Ebola holding units in the Western Area of Sierra Leone from Aug 1, 2014, to April 1, 2015, were eligible for inclusion. Retrospective data were collected from site admission books, case investigation forms, and clinical records, and cross-referenced with district-wide laboratory results, burial records, child protection records, staff interviews, and telephone calls to guardians. Univariate and multivariate analyses were used to identify features independently associated with mortality. Findings 309 children with Ebola virus disease (aged 2 days to 12 years) were admitted (median age 6 years, IQR 3–10). Outcomes were available for 282 children (91%). 161 children (57%) died with 89 deaths (55%) occurring at Ebola holding units and 72 (45%) at Ebola treatment centres. Marked derangement of white cell count, C-reactive protein, and renal and liver function were seen with extensive hypoglycaemia. Up to 60% of children were admitted without a caregiver. Factors that potentially affected mortality such as age, clinical features, delayed attendance, transfer distance, caregiver accompaniment, and medications received are being examined. Multiple imputation is being performed to account for missing data. Interpretation This is the most comprehensive paediatric cohort of Ebola virus disease to date, and the only cohort to incorporate data from both Ebola holding units and Ebola treatment centres. Data sharing between sites is crucial to identify potentially modifiable risk factors and guide future operational responses. Funding This study was funded by Save the Children and supported by the Medical Research Council and the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.

Case Series of Severe Neurologic Sequelae of Ebola Virus Disease during Epidemic, Sierra Leone

We describe a case series of 35 Ebola virus disease (EVD) survivors during the epidemic in West Africa who had neurologic and accompanying psychiatric sequelae. Survivors meeting neurologic criteria were invited from a cohort of 361 EVD survivors to attend a preliminary clinic. Those whose severe neurologic features were documented in the preliminary clinic were referred for specialist neurologic evaluation, ophthalmologic examination, and psychiatric assessment. Of 35 survivors with neurologic sequelae, 13 had migraine headache, 2 stroke, 2 peripheral sensory neuropathy, and 2 peripheral nerve lesions. Of brain computed tomography scans of 17 patients, 3 showed cerebral and/or cerebellar atrophy and 2 confirmed strokes. Sixteen patients required mental health followup; psychiatric disorders were diagnosed in 5. The 10 patients who experienced greatest disability had co-existing physical and mental health conditions. EVD survivors may have ongoing central and peripheral nervous system disorders, including previously unrecognized migraine headaches and stroke.

Development of a pediatric ebola predictive score, Sierra Leone

We compared children who were positive for Ebola virus disease (EVD) with those who were negative to derive a pediatric EVD predictor (PEP) score. We collected data on all children <13 years of age admitted to 11 Ebola holding units in Sierra Leone during August 2014–March 2015 and performed multivariable logistic regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the strongest positive predictors for EVD. The PEP score had an area under receiver operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and 44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could correctly classify 79%–90% of children and could be used to facilitate triage into risk categories, depending on the sensitivity or specificity required.

Review of UK malaria treatment guidelines 2016 (Public Health England Advisory Committee on Malaria Prevention)

This guideline covers the diagnosis and management of malaria, and was published in the Journal of Infection in June 2016.1 It was written by the Public Health England Advisory Committee on Malaria Prevention (PHE ACMP) based on review of available evidence and expert consultation (using a modified Grading of Recommendations Assessment, Development and Evaluation criteria for assessment of evidence and strength of recommendation), to be in line with WHO guidelines on management of malaria.2 It relates to malaria in both adults and children in the UK although here we focus on the diagnosis and management of children returning to the UK with suspected malaria. Malaria is the most common imported tropical pathogen in the UK, and children comprise about 10% of the 1300–1800 UK cases per annum. Plasmodium falciparum is by far the most common (around 75% of cases) and is associated with more severe disease. This guideline replaces the previous PHE ACMP UK malaria treatment guideline (2007),3 and suggested guidance/recommendations from Maitland et al 4 which advocated more aggressive fluid resuscitation in severe malaria than now suggested. ### When to suspect malaria? Malaria should be considered in any unwell or feverish child who has visited an endemic country regardless of whether prophylaxis was taken. P. falciparum usually presents within 1 month of exposure (minimum 6 days), although later presentations can occur. Other species may present over a year post-travel. ### Clinical features Malaria in children can be notoriously non-specific, even without fever. Although fever, malaise and lethargy are the most common symptoms, children can present with gastrointestinal symptoms (including diarrhoea), jaundice, breathing difficulties or sore throat. Examination may reveal hepatomegaly and/or splenomegaly and lethargy. ### Diagnosis Thick and thin blood films remain the gold standard for detection and speciation of malarial parasites, but rapid diagnostic tests (RDT) are almost as accurate for P. falciparum and P. vivax. …