Doença mão-pé-boca no atendimento odontopediátrico

A doença mão-pé-boca é uma infecção viral, normalmente benigna que afeta comumente crianças até 10 anos, causada pelos enterovírus humano. O propósito deste estudo foi revisar os aspectos da doença que se faz presente nos dias atuais abordando a etiologia, epidemiologia, surtos, sintomatologia e comorbidades, diagnóstico, prevenção e tratamento. Foram selecionadas publicações em periódicos referenciados nas fontes de dados do Google Acadêmico, Pubmed e Periódicos Capes com as palavras chaves relacionadas ao tema desse trabalho como doença mão-pé-boca e crianças, sendo selecionados artigos produzidos até 2017. Apesar de diagnóstico clínico aparentemente simples, a doença pode ser confundida com outras enfermidades por suas características semelhantes, que podem induzir o colega odontólogo ao equívoco de diagnóstico.Descritores: Doença de Mão, Pé e Boca; Diagnóstico, Odontopediatria.ReferênciasSarkar PK, Sarker NK, Tayab A. Hand, foot and mouth disease (hfmd):an update. Bangladesh J Child Health. 2016;40(2):115-19.Sarma N. Hand, foot, and mouth disease: current scenario and Indian perspective. Indian J Dermatol Venereol Leprol. 2013;79(2):165-75.Fatahzadeh M. Oral manifestation of viral infections. Atlas Oral Maxillofac Surg Clin North Am. 2017;25(2):163-70.Nassef C, Ziemer C, Morrell DS. Hand-foot-and-mouth disease: a new look at a classic viral rash. Curr Opin Pediatr. 2015;27(4):486-91.Grinde B, Olsen I. The role of viroses in oral disease. J Oral Microbiol. 2010;2(1):1-6.Cepeda CO, Valverde AM, Recolons MMS, Salas EJ, Roig AM, López JL. A literature review and case reporto f hand, foot and mouth disease in na immunocompetent adult. BMC Res Notes. 2016;9:165.Robinson CR, Doane FW, Rhodes AJ. Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, Summer 1957- isolation of group A coxsackie virus. Can Med Assoc J. 1958;79(8):615-21.Alsop J, Flewett TH, Foster JR. Hand-foot-and-mouth disease” in Birmingham in 1959. Br Med J. 1960;2(5214):1708–11.Cristovam MAS, Osaku NO, Gabriel GFCP, Rodrigues SPSG, Pompeu CB, Pires TG. Síndrome mão-pé-boca: relato de caso. Rev Med Res. 2014;16(1):42-5.Repass GL, Palmer WC, Stancampiano FF. Hand, foot, and mouth disease: identifying and managing na acute viral syndrome. Cleve Clin J Med. 2014;81(9):537-43.Kashyap RR, Kashyap RS. Hand, foot and mouth disease- a short case report. J Clin Exp Dent. 2015;7(2):e336-38.Babu NA, Malathi L, Kasthuri M, Jimson S. Ulcerative lesions of the oral cavity - an overview. Biomed Pharmacol J. 2017;10(1):401-5.Xing W, Liao Z, Sun J, Wu J T, Chang Z, Liu F, et al. Hand, foot, and mouth disease in China, 2008–12: an epidemiological study. Lancet Infect Dis. 2014;14:308-18.Wu Y, Yeo A, Phoon MC, Tan EL, Poh CL, QuakSH et al. The largest outbreak of hand; foot and mouth disease in Singapore in 2008: the role of enterovirus 71 and coxsackievirus A strains. Int J Infect Dis. 2010;14:e1076-81.Wang J, Hu T, Sun D, Ding S, Carr M, Xin W, et al. Epidemiological characteristics of hand, foot, and mouth disease in Shandong, China, 2009-2016. Sci Rep.2017;7(1):1-9.He SZ, Chen MY, Xu XR, Yan Q, Niu JJ, Wu WH et al. Epidemics and aetiology of hand, foot and mouth disease in Xiamen, China, from 2008 to 2015. Epidemiol Infect. 2017;145:1865-74.Dantas A, Oliveira MJ, Lourenço O, Coelho PB. Doença mão-pé-boca no adulto - a propósito de um caso clínico. Rev Port Med Geral Farm. 2013;29:62-5.Chatproedprai S, Theanboonlers A, Korkong S, Thongmee C, Wananukul S, Poovorawan. Clinical and molecular characterization of hand-foot-and-mouth disease in thailand, 2008-2009. J Infect Dis. 2010;63:229-233.Zhang W, Du Z, Zhang D, Yu S, Hao Y. Quantifying the adverse effect of excessive heat on children: an elevated risk of hand, foot and mouth disease in hot days. Sci Total Environ. 2016;541:194-99.Koh WM, Bogich T, Siegel K, Jin J, Chong EY, Tan CY et al. The epidemiology of hand, foot and mouth disease in Asia: a systematic review and analysis. Pediatr Infect Dis J. 2016;35(10):e285-300.Pham HV, Hoang TNA, Duong HT, Phan LT, Phan UTN, Ho NX et al. Clinical characteristics of hand, foot and mouth disease in Daklak Province, Vietnam and associated factors of severe cases. Virus Dis.2017;28(4):430-33.Lam JM. Characterizing viral exanthems. Ped Health. 2010;4(6):623-35.World Health Organization: western Pacific Region. A guide to clinical management and public health response for hand, foot, and mouth disease (HFMD).Ganga N. Hand foot and mouth disease like illness in office practice. Indian J Pediatr. 2017; 84(3):216-18.Chang LY, Lin TY, Hung K, Huang YC, Lin KL, Hsueh C et al.Clinical features and risk factors of pulmonary oedema after en terovi rus-71-related hand, foot, and mouth disease. Lancet. 1999;354(9191):1682-86.Cabrol Y, Peah P, Mey C, Duong V, Richner B, Laurent D et al. A prospective, comparative study of severe neurological and uncomplicated hand, foot and mouth forms of paediatric enterovirus 71 infections. Int J Infect Dis. 2017;59:69-76.Alter SJ, Bennett JS, Koranyi K, Kreppel A, Simon R. Common childhood viral infections. Curr Probl Pediatr Adolesc Health Care. 2015;45:21-53.Li Y, Deng H, Li M, Wang W, Jia X, Gao N et al. Prolonged breastfeeding is associated with lower risk of severe hand, foot and mouth disease in chinese childre. Pediatr Infect Dis J. 2016;35(3):353-55.Wolf D, Otto J. Efficacy and safety of lidocaine gel in patients from 6 months up 8 years with acute painful sites in the oral cavity: a randomized, placebo-contolled, double-blind, comparative study. Int J Pediatr. 2015.2015:146717.

2707. Non 13-Valent Pneumococcal Conjugate Vaccine Serotypes Predominate as Causes of Pneumococcal Otitis Media in Children

Background Pneumococcal acute otitis media (AOM) in children due to vaccine-related serotypes (ST) has declined after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), although some serotypes, such has 3, 19A and 19F have persisted. Among non-vaccine serotypes, 35B has been shown to contribute substantially to both OM and invasive infections. This study describes the current epidemiology of pneumococcal OM isolates obtained from the U S Pediatric Multicenter Pneumococcal Surveillance Group (USPMPSG). Methods From the USPMPSG database, we collected data from patients <18 years of age with pneumococcal OM isolates from 2014 to 2018. Analysis included demographics, immunization status, antimicrobial susceptibility data and serotype. Statistical comparisons included Fisher’s exact and Wilcoxon rank-sum tests. Results A total of 494 patients with isolates were identified within the time period from 5 children’s hospitals. Median age was 1.7 years (range 0–17.6) and 299 (60.5%) were male; 176 (35.7%) had an underlying condition. Thirty-two patients had received no dose of either PCV7 or PCV13. Thirty-five serotypes were identified (3 isolates were non-typeable), of which 6 serotypes [35B (16.8%), 3 (9.5%), 15A (7.9%), 15B (7.9%), 23B (7.9%) and 21 (6.1%)] caused more than half of the total OM infections (figure). Ninety (18.2%) isolates were of PCV13 serotypes. Twenty-five of 476 (5.3%) isolates had a penicillin MIC>2 µg/mL. These were of serotypes 11A, 15A/C, 19A/F, 35B and NT; 10/455 (2.2%) isolates had ceftriaxone MIC>1 µg/mL and were of ST 3, 15A, 19A/F and 35B. Conclusion Most pneumococcal OM were caused by non-PCV13 serotypes. Serotype 35B remained the most common serotype among pneumococcal isolates recovered from ear drainage or middle ear cultures. The low proportion of penicillin-resistant isolates along with the increasing proportion of AOM cases being due to non-pneumococcal isolates supports the consideration to switch routine antibiotic treatment for AOM to standard dose amoxicillin-clavulanate from high dose amoxicillin in PCV13 immunized children (Pediatr Infect Dis J 2018;37:1255–1257). Disclosures All authors: No reported disclosures.

P011 An experimental treatment for enteroviral sepsis

BackgroundA male infant was admitted to the neonatal unit with respiratory distress, following delivery by emergency caesarean section at 36/40 for maternal illness (viraemia). The patient’s condition deteriorated with disseminated intravascular coagulation (DIC), abnormal liver function, ascites and pleural effusions. Enteroviral sepsis was diagnosed following positive enterovirus PCR on lumbar puncture and stool sample.Summary of problemThere are no commercially available treatments for enterovirus in the UK. Following an extensive literature search, the neonatology consultant became aware of an experimental treatment with potential action against enterovirus.1 2 Pocapavir is an investigational drug candidate developed for poliovirus indications, but also has antiviral activity against nonpolio enteroviruses. The consultant was keen to exhaust every option, so reached out to the company in the US. The company (Virodefense) offered to provide the drug on a compassionate use/open label trial basis, asking that regular pharmacokinetics tests be carried out as part of the agreement to supply.Pharmacy contributionFollowing the initial contact with Virodefense, there were several challenges for the specialist pharmacist and pharmacy procurement team. Working with IDIS and Virodefense, arrangements were made for shipment of the medication to the pharmacy department. This was complicated by the urgency of the situation and the time differences involved. Pocapavir is in phase 2 clinical trial which required the MHRA to be notified to approve the importing of the drug into the country. The MHRA were quick to give a positive decision which allowed the product to be delivered direct to the hospital while IDIS handled the importing documentation. The advised dose was 25mg/kg daily, the drug came as 500 mg capsules containing 200mg of pocapavir (with 300 mg excipients).The patient (2.7 kg) required 67.5 mg daily. The pharmacy manufacturing unit packed down 170 mg capsule contents (68 mg active ingredient) into individual pots for the neonatal unit to administer. Doses were mixed with EBM and given daily for 14 days.OutcomeThe patient recovered from the acute sepsis episode. The patient was also treated with immunoglobulin and standard supportive care so it is impossible to know how much can be attributed to the pocapavir. Pharmacokinetic samples were taken as agreed. After recovering from the initial acute sepsis the patient developed hypoglycaemia between feeds. These were investigated and metabolic causes were excluded. The working diagnosis was a response to the large hit to the liver during the septic episode, although an adverse effect of pocapavir cannot be excluded. Hypoglycaemic episodes continued and the patient was still fed 3 hourly on discharge. The patient is growing and developing well, tolerating longer fasts of 6 hours without hypoglycaemia and reducing risk in the provision of parenteral nutrition for effects that could occur due to opioid toxicity. The patient has been discharged from neonatal follow up.Lessons to be learnedWhere there’s a will there’s a way! There were many barriers to overcome including regulatory, logistical and practical complications but thanks to a concerted effort from a wide variety of teams, co-ordinated by pharmacy, the patient received this treatment. Although the contribution of this experimental drug is unclear the positive outcome for a very unwell infant should be celebrated.ReferencesModlin JF. Treatment of Neonatal Enterovirus Infections. J Pediatric Infect Dis Soc 2016;5:63–64Torres-Torres S, Myers AL, Klatte M, et al. First Use of Investigational Antiviral Drug Pocapavir (V-073) for Treating Neonatal Enteroviral Sepsis. Pediatr Infect Dis J 2015;34:52–54.

P73 Paediatric population pharmacokinetic modeling for gentamicin – is the current dose recommendation justified?

BackgroundMonitoring of gentamicin serum trough level (Cmin) is standard practice in children to prevent toxicity by accumulation1. Cmin < 2 mg/L are recommended. Peak serum concentration (Cmax) is not routinely measured although Cmax between 10 and 12 mg/L have been recommended balancing efficacy and toxicity2,3. We aimed to develop a population pharmacokinetic (PK) model for gentamicin in children to optimise current dosing regimens.MethodsAll patients receiving once daily intravenous gentamicin (5 mg/kg in children < 7 days and 7.5 mg/kg in children >7 days of age) at the University Children’s Hospital Zurich between 10/2017 and 01/2019 were eligible for this study. Children with cystic fibrosis and renal replacement procedures were excluded. Routine Cmin were measured in all patients before administration of the second or third dose. Additional gentamicin serum levels were measured 30 min (C30) and 4 h after the second dose in patients giving written informed consent. Data were analysed by non-linear mixed-effects modeling.Results165 patients (median age 34 days; IQR 15–56 days) were included in the study. A total number of 103 C30 and 166 Cmin measurements were available, respectively. C30 (mean 19.7 mg/L, SD ±6.1 mg/L) was >12 mg/L in 94/103 (91%) and Cmin >2 mg/mL in 3/166 (1.8%) measurements. The PK model successfully predicted most C30 >12 mg/L but performed poorly at the through levels.ConclusionsOur current gentamicin dosing regimen rarely leads to accumulation but most Cmax are above optimal range. The latter was successfully modelled. Although no evidence for a Cmax upper limit exists, toxicity has been associated with high drug exposure3. This calls for an adjustment of our dosing regimen using our PK model based on body height or weight in order to lower exposure. Further studies investigating the relationship between Cmax levels and clinical outcome and additional data for PK model testing are needed for validation.ReferencesRitz N, Bielicki J, Pfister M, van den Anker J. Therapeutic Drug Monitoring for Anti-infective Agents in Pediatrics: The Way Forward. Pediatr Infect Dis J. 2016;35(5):570–572.Chattopadhyay B. Newborns and gentamicin-how much and how often? J Antimicrob Chemother. 2002;49(1):13–16.Touw DJ, Westerman EM, Sprij AJ. Therapeutic drug monitoring of aminoglycosides in neonates. Clin Pharmacokinet. 2009;48(2):71–88.Disclosure(s)Nothing to disclose

A Multi-Institutional Survey of Practice Guidelines for Respiratory Syncytial Virus (RSV) Infection in Pediatric Patients Following Hematopoietic Stem Cell Transplant (HSCT)

RSV is a common infection in infancy and childhood. Mortality from RSV is reported to be < 0.5% in healthy children in comparison to 10-12.5% in children following HSCT (1. Chavez-Bueno S et al. Pediatr Infect Dis J 2007 26:1089-1093). There is currently no standard for management of RSV in pediatric patients with hematologic malignancies/HSCT. Many institutions have their own protocols for managing these patients. Symptomatic management is common and the use of antiviral (AV)-ribavirin, Immunomodulators like palivizumab (PVZ) and IVIG is widely debated & inconsistent in practice. Ribavirin is a guanosine analogue with AV activity. It may be administered orally (PO), intravenously (IV) or aerosolized (AR). AR is approved by Food and Drug Administration (FDA) for treatment of RSV in high-risk (HR) infants and children. In the adult HSCT setting, retrospective data has shown the benefit of AR for RSV, for both decreasing the likelihood of progression from upper respiratory infection (URTI) to lower respiratory tract infection (LRTI) and reduction in RSV-related mortality (Shah JN et al. Blood 2011; 117:2755-2763). However in the pediatric HSCT setting the benefit of AR is less clear. AR is expensive and a known teratogenic. Healthcare workers, parents, others caring for the patient stand to be exposed to Ribavirin. The delivery mechanisms to the lower airways are inefficient. AR tends to clog the endotracheal tube and cannot be used with high frequency oscillators. Ribavirin has side effects such as sudden deterioration of respiratory response. AR therapy poses many challenges and is not always feasible. PVZ is a 95% humanized and 5% murine monoclonal antibody that provides both neutralizing and fusion-inhibitory activity against RSV. It binds to the linear epitope of the Fusion glycoprotein in the A antigen site. PVZ is FDA approved for the prevention of RSV related LRTI in HR pediatric patients. In the HSCT setting, PVZ has been utilized off-label both for prophylaxis and treatment of RSV. PVZ +/- AR has been shown to be effective in decreasing morality among HR children including those requiring HSCT (1). The treatment of pediatric patients requiring HSCT has been derived from adult protocols due to a lack of randomized clinical trials in children. A recent retrospective analysis showed a reduction in mortality and progression to LRTI in 59 pediatric cancer patients with RSV when PVZ was added to the treatment regimen. (Chemaly RF et al. J Pediatr Hematol Oncol 2014; 36 (6): e376-81). To evaluate the current practice, our institution surveyed several hospitals to determine institutional standards of care for treating HSCT patients with RSV (both adults and children). Responses are shown in Table 1. Table 1 Hospital, patient population (Adult/Pediatric/Both) AR PO Ribavirin PVZ Treatment PVZ prophylaxis 1, A Y - Inpatients Y - Outpatients N N 2,B Y (Pre-engraftment, severe LRTI) Y (Post-engraftment, URTI, mild LRTI) N ? 3, A Y N N N 4, P Y – 5 (URTI) vs. 7days (LRTI) N Y (LRTI/URTI High risk) Y in <2yr 5, A N Y N NA 6, A Y (Critical) Y N NA 7, A N Y [Moderate, severe immune deficiency (SID)] N NA 8, P Y (HR + URTI/LRTI) N Y (LRTI w high risk) Y <2yr 9, A Y Y (URTI w No HR) N N 10, B Y N N N Y =Used, N=Not used,?=Unsure, NA=Not Applicable The cost of medications commonly used to treat RSV infections is shown in Figure 1. Figure 1 Figure 1. Survey Findings: PO ribavirin was commonly used to treat RSV URTI in responding hospitals. AR was used to treat severe LRTI. Engraftment status (pre vs. post) was used to classify severity of immunodeficiency and determine treatment. PVZ use for treatment is uncommon among the responding hospitals (2/10). Practice at our institution Low-risk patients with RSV (>30 days post-HSCT, minimal immunosuppression, URTI) receive only supportive care and close monitoring. Patients with RSV-LRTI or those with URTI at HR for progression (< 30 days post-HSCT, low lymphocyte counts, on immunosuppression) may be considered for AR +/- PVZ. In the last 5 years we have had 20 patients with RSV, 3 were diagnosed with RSV pre-transplant and 17 post-transplant, 1 reactivated after transplant and there was 1 death related to RSV. Conclusion Due to variance in practice and costs of therapies, further studies are needed to standardize treatment for children post-HSCT with RSV to reduce morbidity and mortality. In addition a stratification algorithm to better characterize those most likely to benefit from current treatment should be considered. Disclosures Off Label Use: Multi institutional survey regarding the use of Palivizumab and Ribavirin in the treatment of RSV..

Unusual Patterns of IgG Avidity in Some Young Children following Two Doses of the Adjuvanted Pandemic H1N1 (2009) Influenza Virus Vaccine

ABSTRACTDuring the 2009-2010 H1N1 influenza pandemic, an adjuvanted monovalent vaccine containing ∼25% of the normal antigen dose and AS03 adjuvant was widely used in Canada. This vaccine was found to be well-tolerated and immunogenic in young children (D. W. Scheifele et al., Pediatr. Infect. Dis. J. 30:402–407, 2011). We report here additional analyses to further characterize the humoral response to this vaccine. We measured standard hemagglutination inhibition (HAI) and microneutralization (MN) titers, as well as influenza virus-specific IgG avidity and subclass distribution by enzyme-linked immunosorbent assay in 73 subjects. Sera were collected before (day 0) and 3 weeks after each dose of vaccine (days 21 and 42). Most children (55/73) had undetectable HAI and MN titers at day 0 (presumed to be antigen naive) and mounted good responses at days 21 and 42. The majority of these children (43/55) had the expected pattern of an increasing IgG avidity index (AI) after each dose of vaccine (not detected [ND], 0.30, and 2.97 at days 0, 21, and 42, respectively). The avidity responses in the remaining children (12/55) were quite different, with AIs increasing abruptly after the first dose and then declining after the second dose of vaccine (ND, 8.83, and 7.15, respectively). These children also had higher concentrations of influenza virus-specific IgG1 and IgG3 antibodies at day 21. Although the antibody titers were similar, some antigen-naive children demonstrated an unusual pattern of avidity maturation after two immunizations with AS03-adjuvanted, low-dose influenza virus vaccine. These data suggest the presence of subtle differences in the quality of the antibodies produced by some subjects in response to this vaccine.