Jeffrey M. Pernica

Impact of Rotavirus Vaccination on Hospitalizations and Deaths From Childhood Gastroenteritis in Botswana.

BACKGROUND A monovalent human rotavirus vaccine (RV1) was introduced in Botswana in July 2012. We assessed the impact of RV1 vaccination on childhood gastroenteritis-related hospitalizations and deaths in 2013 and 2014. METHODS We obtained data from registers of 4 hospitals in Botswana on hospitalizations and deaths from gastroenteritis, regardless of cause, among children <5 years of age. Gastroenteritis hospitalizations and deaths during the prevaccine period (January 2009-December 2012) were compared to the postvaccine period (January 2013-December 2014). Vaccine coverage was estimated from data collected through a concurrent vaccine effectiveness study at the same hospitals. RESULTS By December 2014, coverage with ≥1 dose of RV1 was an estimated 90% among infants <1 year of age and 76% among children 12-23 months of age. In the prevaccine period, the annual median number of gastroenteritis-related hospitalizations in children <5 years of age was 1212, and of gastroenteritis-related deaths in children <2 years of age was 77. In the postvaccine period, gastroenteritis-related hospitalizations decreased by 23% (95% confidence interval [CI], 16%-29%) to 937, and gastroenteritis-related deaths decreased by 22% (95% CI, -9% to 44%) to 60. Declines were most prominent during the rotavirus season (May-October) and among infants <1 year of age, with reductions of 43% (95% CI, 34%-51%) in gastroenteritis hospitalizations and 48% (95% CI, 11%-69%) in gastroenteritis deaths. CONCLUSIONS Following introduction of RV1 into the national immunization program, significant declines in hospitalizations and deaths from gastroenteritis were observed among children in Botswana, suggestive of the beneficial public health impact of rotavirus vaccination.

Evaluation of Anatomically Designed Flocked Rectal Swabs for Molecular Detection of Enteric Pathogens in Children Admitted to Hospital with Severe Gastroenteritis in Botswana

ABSTRACT Two-hundred eighty matched bulk stool and anatomically designed flocked rectal swab samples were collected from children admitted to the hospital with acute diarrhea in Botswana. Their parents were asked about the acceptability of the swab collection method compared with bulk stool sampling. All samples underwent identical testing with a validated 15-target (9 bacterial, 3 viral, and 3 parasite) commercial multiplex PCR assay. The flocked swabs had a 12% higher yield for bacterial pathogen targets (241 versus 212; P = 0.003) compared with that of stool samples, as well as similar yields for viral targets (110 versus 113; P = 0.701) and parasite targets (59 versus 65; P = 0.345). One hundred sixty-four of the flocked swab-stool pairs were also tested with separate laboratory-developed bacterial and viral multiplex assays, and the flocked rectal swabs had a performance that was similar to that seen with commercial assay testing. Almost all parents/guardians found the swabs acceptable. Flocked rectal swabs significantly facilitate the molecular diagnosis of diarrheal disease in children.

real-time polymerase chain reaction for microbiological diagnosis of parapneumonic effusions in canadian children

Community-acquired pneumonia with parapneumonic effusion/empyema is not uncommon in children and can cause serious illness; there -fore, the timely optimization of antimicrobial therapy is essential in this situation. The aim of this study was to determine whether using real-time polymerase chain reaction of pleural fluids to identify the causative organism improves the process of microbiological diagnosis in the context of community-acquired pneumonia with parapneumonic effusion/empyema. This technique was compared with traditional culture methods for microbiological diagnosis.

Bordetella holmesii, an Emerging Cause of Septic Arthritis

ABSTRACT Bordetella holmesii is a well-described pathogen in asplenic and immunocompromised patients. Here we report the first two published cases of septic arthritis caused by B. holmesii documented in apparently immunocompetent patients and unaccompanied by bacteremia.

Clinical severity of pediatric respiratory illness with enterovirus D68 compared with rhinovirus or other enterovirus genotypes.

Background: Enterovirus D68 (EV-D68) resulted in a reported increase in the number of children needing hospital or critical care admission because of respiratory insufficiency during 2014. It remains unclear, however, whether EV-D68 infections were more severe than rhinovirus or non–EV-D68 enterovirus infections. Methods: We evaluated consecutive children presenting to a pediatric hospital between Aug. 1 and Oct. 31, 2014, with positive nasopharyngeal swabs for rhinovirus or enterovirus that were sent automatically for EV-D68 testing. We compared characteristics and outcomes of patients with EV-D68 with those with rhinovirus or non–EV-D68 enterovirus in a matched cohort study. Results: A total of 93/297 (31.3%) of rhinovirus or enterovirus samples tested positive for EV-D68, and it was possible to compare 87 matched pairs. Children with EV-D68 infection were more likely to have difficulty breathing (odds ratio [OR] 3.00, 95% confidence interval [CI] 1.47–6.14). There was no significant difference in admission to the critical care unit or death among children with EV-D68 infection compared with those with other rhinovirus or enterovirus infections (adjusted OR 1.47, 95% CI 0.61–3.52). Children with EV-D68 infection were more often admitted to hospital, but not significantly so (adjusted OR 2.29, 95% CI 0.96–5.46). Interpretation: Enterovirus D68 seems to be a more virulent pulmonary pathogen than rhinovirus or non–EV-D68 enterovirus, but we did not find a significant difference in death or need for critical care.

Longitudinal Outcomes in the 2014 Acute Flaccid Paralysis Cluster in Canada: A Nationwide Study

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.

Hospital-based surveillance for rotavirus gastroenteritis using molecular testing and immunoassay during the 2011 season in Botswana.

We describe rotavirus testing and clinical characteristics for children admitted with acute gastroenteritis during Botswanas 2011 rotavirus season. The rotavirus season extended from June to October with rotavirus-specific case fatality being 2.8%. Using molecular testing as reference, the immunochromatographic test had a sensitivity of 76.5% and specificity of 68.0%. Rotavirus vaccine may significantly reduce childhood morbidity and mortality in Botswana.

Risk factors predisposing to pedestrian road traffic injury in children living in Lima, Peru: a case–control study

Objective To describe the epidemiology of pedestrian road traffic injury in Lima and to identify associated child-level, family-level, and school travel-related variables. Design Case–control study. Setting The Instituto Nacional de Salud del Niño, the largest paediatric hospital in the city. Participants Cases were children who presented because of pedestrian road traffic injury. Controls presented with other diagnoses and were matched on age, sex and severity of injury. Results Low socioeconomic status, low paternal education, traffic exposure during the trip to school, lack of supervision during outside play, and duration of outside play were all statistically significantly associated with case–control status. In multivariate logistic regression, a model combining the lack of supervision during outside play and the number of the streets crossed walking to school best predicted case–control status (p<0.001). Conclusions These results emphasise that an assessment of childrens play behaviours and school locations should be considered and integrated into any plan for an intervention designed to reduce pedestrian road traffic injury. A child-centred approach will ensure that children derive maximum benefit from sorely needed public health interventions.

Identification and management of Shigella infection in children with diarrhoea: a systematic review and meta-analysis

Summary Background Shigella infections are a leading cause of diarrhoeal death among children in low-income and middle-income countries. WHO guidelines reserve antibiotics for treating children with dysentery. Reliance on dysentery for identification and management of Shigella infection might miss an opportunity to reduce Shigella-associated morbidity and mortality. We aimed to systematically review and evaluate Shigella-associated and dysentery-associated mortality, the diagnostic value of dysentery for the identification of Shigella infection, and the efficacy of antibiotics for children with Shigella or dysentery, or both. Methods We did three systematic reviews (for mortality, diagnostic value, and antibiotic treatment of Shigella and dysentery), and meta-analyses where appropriate, of studies in resource-limited settings. We searched MEDLINE, Embase, and LILACS database for studies published before Jan 1, 2017, in English, French, and Spanish. We included studies of human beings with diarrhoea and accepted all study-specific definitions of dysentery. For the mortality and diagnostic value searches, we excluded studies that did not include an effect estimate or data necessary to calculate this estimate. The search for treatment included only randomised controlled trials that were done after Jan 1, 1980, and assessed antibiotics in children (aged <18 years) with dysentery or laboratory-confirmed Shigella. We extracted or calculated odds ratios (ORs) and 95% CIs for relative mortality and did random-effects meta-analysis to arrive at pooled ORs. We calculated 95% CIs assuming a binomial distribution and did random-effects meta-regression of log-transformed sensitivity and specificity estimates for diagnostic value. We assessed the heterogeneity of papers included in these meta-analyses using the I2 statistic and evaluated publication bias using funnel plots. This review is registered with PROSPERO (CRD42017063896). Findings 3649 papers were identified and 60 studies were included for analyses: 13 for mortality, 27 for diagnostic value, and 20 for treatment. Shigella infection was associated with mortality (pooled OR 2·8, 95% CI 1·6–4·8; p=0·000) whereas dysentery was not associated with mortality (1·3, 0·7–2·3; p=0·37). Between 1977 and 2016, dysentery identified 1·9–85·9% of confirmed Shigella infections, with sensitivity decreasing over time (p=0·04). Ten (50%) of 20 included antibiotic trials were among children with dysentery, none were placebo-controlled, and two (10%) evaluated antibiotics no longer recommended for acute infectious diarrhoea. Ciprofloxacin showed superior microbiological, but not clinical, effectiveness compared with pivmecillinam, and no superior microbiological and clinical effectiveness compared with gatifloxacin. Substantial heterogeneity was reported for meta-analyses of the Shigella-associated mortality studies (I2=78·3%) and dysentery-associated mortality studies (I2=73·2%). Too few mortality studies were identified to meaningfully test for publication bias. No evidence of publication bias was found in this analysis of studies of diagnostic value. Interpretation Current WHO guidelines appear to manage dysentery effectively, but might miss opportunities to reduce mortality among children infected with Shigella who present without bloody stool. Further studies should quantify potential decreases in mortality and morbidity associated with antibiotic therapy for children with non-dysenteric Shigella infection. Funding Bill & Melinda Gates Foundation and the Center for AIDS Research International Core.

A comparison of flocked swabs and traditional swabs, using multiplex real-time PCR for detection of common gastroenteritis pathogens in Botswana

We compared the performance of flocked and matched traditional rectal swabs collected from 236 children admitted with gastroenteritis in Botswana. All samples were tested using real time multiplex-PCR assays for nine enteric pathogens. There was a 20% higher detection of Shigella from flocked swabs, but most other pathogens had similar detection rates.