Confronting the opioid crisis: Practical pain management and strategies: AOA 2018 critical issues symposium

The United States is in the midst of an opioid crisis. Clinicians have been part of the problem because of overprescribing of narcotics for perioperative pain management. Clinicians need to understand the pathophysiology and science of addiction to improve perioperative management of pain for their patients. Multiple modalities for pain management exist that decrease the use of narcotics. Physical strategies, cognitive strategies, and multimodal medication can all provide improved pain relief and decrease the use of narcotics. National medical societies are developing clinical practice guidelines for pain management that incorporate multimodal strategies and multimodal medication. Changes to policy that improve provider education, access to naloxone, and treatment for addiction can decrease narcotic misuse and the risk of addiction

Lethal Factor Toxemia and Anti-Protective Antigen Antibody Activity in Naturally Acquired Cutaneous Anthrax

Cutaneous anthrax outbreaks occurred in Bangladesh from August to October 2009. As part of the epidemiological response and to confirm anthrax diagnoses, serum samples were collected from suspected case patients with observed cutaneous lesions. Anthrax lethal factor (LF), anti-protective antigen (anti-PA) immunoglobulin G (IgG), and anthrax lethal toxin neutralization activity (TNA) levels were determined in acute and convalescent serum of 26 case patients with suspected cutaneous anthrax from the first and largest of these outbreaks. LF (0.005–1.264 ng/mL) was detected in acute serum from 18 of 26 individuals. Anti-PA IgG and TNA were detected in sera from the same 18 individuals and ranged from 10.0 to 679.5 μg/mL and 27 to 593 units, respectively. Seroconversion to serum anti-PA and TNA was found only in case patients with measurable toxemia. This is the first report of quantitative analysis of serum LF in cutaneous anthrax and the first to associate acute stage toxemia with subsequent antitoxin antibody responses

Shigella in Africa: New Insights From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: We evaluated the burden of Shigella spp from children aged 0-59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018. METHODS: Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis. RESULTS: The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold <35); shigellosis was higher in The Gambia (30.8%) than in Mali (9.3%) and Kenya (18.7%). Bloody diarrhea attributed to Shigella was more common in 24- to 59-month-old children (50.1%) than 0- to 11-month-old infants (39.5%). The Shigella flexneri serogroup predominated among cases (67.6% of isolates), followed by Shigella sonnei (18.2%), Shigella boydii (11.8%), and Shigella dysenteriae (2.3%). The most frequent S. flexneri serotypes were 2a (40.6%), 1b (18.8%), 6 (17.5%), 3a (9.0%), and 4a (5.1%). Drug-specific resistance among 353 (98.3%) Shigella cases with AMR data was as follows: trimethoprim-sulfamethoxazole (94.9%), ampicillin (48.4%), nalidixic acid (1.7%), ceftriaxone (0.3%), azithromycin (0.3%), and ciprofloxacin (0.0%). CONCLUSIONS: A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin

Prevalence of Salmonella in Stool During the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa. METHODS: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0-59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015-2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007-2010) and the GEMS-1A study (2011). Salmonella spp. was detected by quantitative real-time PCR (qPCR) and culture-based methods. Identification of serovars was determined by microbiological methods. RESULTS: By qPCR, the prevalence of Salmonella spp. among MSD cases was 4.0%, 1.6%, and 1.9% and among controls was 4.6%, 2.4%, and 1.6% in The Gambia, Mali, and Kenya, respectively, during VIDA. We observed year-to-year variation in serovar distribution and variation between sites. In Kenya, Salmonella enterica serovar Typhimurium decreased (78.1% to 23.1%; P < .001) among cases and controls from 2007 to 2018, whereas serogroup O:8 increased (8.7% to 38.5%; P = .04). In The Gambia, serogroup O:7 decreased from 2007 to 2018 (36.3% to 0%; P = .001) but S. enterica serovar Enteritidis increased during VIDA (2015 to 2018; 5.9% to 50%; P = .002). Only 4 Salmonella spp. were isolated in Mali during all 3 studies. Multidrug resistance was 33.9% in Kenya and 0.8% in The Gambia across all 3 studies. Ceftriaxone resistance was only observed in Kenya (2.3%); NTS isolates were susceptible to ciprofloxacin at all sites. CONCLUSIONS: Understanding variability in serovar distribution will be important for the future deployment of vaccines against salmonellosis in Africa

Prevalence, Clinical Severity, and Seasonality of Adenovirus 40/41, Astrovirus, Sapovirus, and Rotavirus Among Young Children With Moderate-to-Severe Diarrhea: Results From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: While rotavirus causes severe diarrheal disease in children aged <5 years, data on other viral causes in sub-Saharan Africa are limited. METHODS: In the Vaccine Impact on Diarrhea in Africa study (2015-2018), we analyzed stool from children aged 0-59 months with moderate-to-severe diarrhea (MSD) and without diarrhea (controls) in Kenya, Mali, and The Gambia using quantitative polymerase chain reaction. We derived the attributable fraction (AFe) based on the association between MSD and the pathogen, accounting for other pathogens, site, and age. A pathogen was attributable if the AFe was ≥0.5.The severity of attributable MSD was defined by a modified Vesikari score (mVS). Monthly cases were plotted against temperature and rainfall to assess seasonality. RESULTS: Among 4840 MSD cases, proportions attributed to rotavirus, adenovirus 40/41, astrovirus, and sapovirus were 12.6%, 2.7%, 2.9%, and 1.9%, respectively. Attributable rotavirus, adenovirus 40/41, and astrovirus MSD cases occurred at all sites, with mVS of 11, 10, and 7, respectively. MSD cases attributable to sapovirus occurred in Kenya, with mVS of 9. Astrovirus and adenovirus 40/41 peaked during the rainy season in The Gambia, while rotavirus peaked during the dry season in Mali and The Gambia. CONCLUSIONS: In sub-Saharan Africa, rotavirus was the most common cause of MSD; adenovirus 40/41, astrovirus, and sapovirus contributed to a lesser extent among children aged <5 years. Rotavirus- and adenovirus 40/41-attributable MSD were most severe. Seasonality varied by pathogen and location. Efforts to increase the coverage of rotavirus vaccines and to improve prevention and treatment for childhood diarrhea should continue

Antibiotic-Prescribing Practices for Management of Childhood Diarrhea in 3 Sub-Saharan African Countries: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: Despite antibiotic prescription being recommended for dysentery and suspected cholera only, diarrhea still triggers unwarranted antibiotic prescription. We evaluated antibiotic-prescribing practices and their predictors among children aged 2-59 months in the Vaccine Impact on Diarrhea in Africa (VIDA) Study performed in The Gambia, Mali, and Kenya. METHODS: VIDA was a prospective case-control study (May 2015-July 2018) among children presenting for care with moderate-to-severe diarrhea (MSD). We defined inappropriate antibiotic use as prescription or use of antibiotics when not indicated by World Health Organization (WHO) guidelines. We used logistic regression to assess factors associated with antibiotic prescription for MSD cases who had no indication for an antibiotic, at each site. RESULTS: VIDA enrolled 4840 cases. Among 1757 (36.3%) who had no apparent indication for antibiotic treatment, 1358 (77.3%) were prescribed antibiotics. In The Gambia, children who presented with a cough (adjusted odds ratio [aOR]: 2.05; 95% confidence interval [95% CI]: 1.21-3.48) were more likely to be prescribed an antibiotic. In Mali, those who presented with dry mouth (aOR: 3.16; 95% CI: 1.02-9.73) were more likely to be prescribed antibiotics. In Kenya, those who presented with a cough (aOR: 2.18; 95% CI: 1.01-4.70), decreased skin turgor (aOR: 2.06; 95% CI: 1.02-4.16), and were very thirsty (aOR: 4.15; 95% CI: 1.78-9.68) were more likely to be prescribed antibiotics. CONCLUSIONS: Antibiotic prescription was associated with signs and symptoms inconsistent with WHO guidelines, suggesting the need for antibiotic stewardship and clinician awareness of diarrhea case-management recommendations in these settings

Epidemiology of Enteroaggregative, Enteropathogenic, and Shiga Toxin-Producing Escherichia coli Among Children Aged <5 Years in 3 Countries in Africa, 2015-2018: Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: To address knowledge gaps regarding diarrheagenic Escherichia coli (DEC) in Africa, we assessed the clinical and epidemiological features of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), and Shiga toxin-producing E. coli (STEC) positive children with moderate-to-severe diarrhea (MSD) in Mali, The Gambia, and Kenya. METHODS: Between May 2015 and July 2018, children aged 0-59 months with medically attended MSD and matched controls without diarrhea were enrolled. Stools were tested conventionally using culture and multiplex polymerase chain reaction (PCR), and by quantitative PCR (qPCR). We assessed DEC detection by site, age, clinical characteristics, and enteric coinfection. RESULTS: Among 4840 children with MSD and 6213 matched controls enrolled, 4836 cases and 1 control per case were tested using qPCR. Of the DEC detected with TAC, 61.1% were EAEC, 25.3% atypical EPEC (aEPEC), 22.4% typical EPEC (tEPEC), and 7.2% STEC. Detection was higher in controls than in MSD cases for EAEC (63.9% vs 58.3%, P < .01), aEPEC (27.3% vs 23.3%, P < .01), and STEC (9.3% vs 5.1%, P < .01). EAEC and tEPEC were more frequent in children aged <23 months, aEPEC was similar across age strata, and STEC increased with age. No association between nutritional status at follow-up and DEC pathotypes was found. DEC coinfection with Shigella/enteroinvasive E. coli was more common among cases (P < .01). CONCLUSIONS: No significant association was detected between EAEC, tEPEC, aEPEC, or STEC and MSD using either conventional assay or TAC. Genomic analysis may provide a better definition of the virulence factors associated with diarrheal disease

Population Enumeration and Household Utilization Survey Methods in the Enterics for Global Health (EFGH): Shigella Surveillance Study

Background: Accurate estimation of diarrhea incidence from facility-based surveillance requires estimating the population at risk and accounting for case patients who do not seek care. The Enterics for Global Health (EFGH) Shigella surveillance study will characterize population denominators and healthcare-seeking behavior proportions to calculate incidence rates of Shigella diarrhea in children aged 6–35 months across 7 sites in Africa, Asia, and Latin America. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will use a hybrid surveillance design, supplementing facility-based surveillance with population-based surveys to estimate population size and the proportion of children with diarrhea brought for care at EFGH health facilities. Continuous data collection over a 24 month period captures seasonality and ensures representative sampling of the population at risk during the period of facility-based enrollments. Study catchment areas are broken into randomized clusters, each sized to be feasibly enumerated by individual field teams. Conclusions: The methods presented herein aim to minimize the challenges associated with hybrid surveillance, such as poor parity between survey area coverage and facility coverage, population fluctuations, seasonal variability, and adjustments to care-seeking behavior

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article