Molecular characterization of virulence and antimicrobial resistance profile of Shigella species isolated from children with moderate to severe diarrhea in northeastern Brazil.

Molecular characterization of virulence and antimicrobial resistance profiles were determined for Shigella species isolated from children with diarrhea in Fortaleza, Brazil. Fecal specimens were collected along with socioeconomic and clinical data from children with moderate to severe diarrhea requiring emergency care. Shigella spp. were isolated by standard microbiological techniques, and we developed 4 multiplex polymerase chain reaction assays to detect 16 virulence-related genes (VRGs). Antimicrobial susceptibility tests were performed using disk diffusion assays. S. flexneri and S. sonnei were the predominant serogroups. S. flexneri was associated with low monthly incomes; more severe disease; higher number of VRGs; and presence of pic, set, and sepA genes. The SepA gene was associated with more intense abdominal pain. S. flexneri was correlated with resistance to ampicillin and chloramphenicol, whereas S. sonnei was associated with resistance to azithromycin. Strains harboring higher numbers of VRGs were associated with resistance to more antimicrobials. We highlight the correlation between presence of S. flexneri and sepA, and increased virulence and suggest a link to socioeconomic change in northeastern Brazil. Additionally, antimicrobial resistance was associated with serogroup specificity in Shigella spp. and increased bacterial VRGs.

Combination of different methods for detection of Campylobacter spp. in young children with moderate to severe diarrhea.

Campylobacter spp. were detected - using culture, ELISA, PCR, and qPCR - among children (0-36months) with moderate to severe diarrhea in Northeastern Brazil. Our data showed that either the qPCR alone or PCR along with ELISA might be an alternative to culture to diagnose Campylobacter due to their enhanced sensitivity.

Off-label use and harmful potential of drugs in a NICU in Brazil: A descriptive study.

BACKGROUND: Neonates admitted to neonatal intensive care units (NICU) are exposed to a wide variety of drugs, most without any data on safety and efficacy. OBJECTIVE: To describe the drugs prescribed to different groups of neonates hospitalized in a NICU, and to analyze off-label use and harmful potential of drugs, in terms of the potential risks. METHODS: This was a six-month retrospective cohort study of drug use in a NICU, with neonates who were inpatients for a period of over 24 hours, and using prescription data from electronic medical records. Drug information found in the package leaflets, in the British National Formulary for Children 2012-2013, and in the Thomson Micromedex database were compared. Drugs and excipients considered potentially harmful were evaluated according to the literature. RESULTS: One hundred ninety-two neonates were included in the study, with a mean gestational age (GA) of 33.3 weeks (SD ± 4.3), 75.0 % were preterm, with an average of 18.8 days of hospitalization (SD ± 18.1), and a total of 3617 neonates-day. 3290 prescriptions were registered, on average 17.1 prescriptions/neonate (SD ± 17.9) and 8.8 drugs/neonate (SD ± 5.9). The number of prescriptions and drugs was higher in neonates with GA <31 weeks (p <0.05). Anti-infectives for systemic use, blood, alimentary tract and metabolism drug groups were more frequent, varying according to the GA. Neonates (99.5 %) were exposed to unlicensed drugs (UL) and off label use (OL), more frequently in GA <28 weeks (p <0.05). Most OL drugs used were indicated for newborns. 15 potentially harmful drugs were used in more than 70 % of the neonates, and most were OL; exposure to harmful excipients occurred in 91.6 % of the neonates, a percentage even higher when considering immature neonates. CONCLUSIONS: Immature neonates in a Brazilian NICU are exposed to a variety of OL, UL and potentially harmful drugs and excipients.

Efficacy of a tetravalent dengue vaccine in children in Latin America.

BACKGROUND: In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development. METHODS: In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection. RESULTS: A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. CONCLUSIONS: The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.).

A critical comparison between the World Health Organization list of essential medicines for children and the Brazilian list of essential medicines (Rename).

OBJECTIVE: To perform a critical comparison between the Brazilian national essential medicines list (Rename, 2012) with the list of essential medicines for children (LEMC, 2011) of the World Health Organization (WHO), regarding the differences among drugs and formulations listed for children. METHODS: The LEMC drugs were classified into four categories: 1) absent in Rename; 2) included in Rename but without any formulation suitable for children; 3) listed in Rename only in some formulations; 4) present in Rename in all formulations. The missing formulations were analyzed by therapeutic group. Alternatives present in Rename were searched. RESULTS: From the 261 drugs of interest on the LEMC, 30.3% are absent from Rename, 11.1% are in Rename but without any pediatric formulation, and 32.2% are present in some but not all formulations listed in LEMC. Considering all formulations items listed in the LEMC (n = 577), 349 are missing from Rename, of these 19.6% due to their strength, and 18.5% due to the the dosage form. Useful formulations specific for neonatal care, respiratory tract, central nervous system, and anti-infectives, among other groups, are missing. CONCLUSION: The lack of age-appropriate formulations of essential medicines for children in Brazil includes important therapeutic groups and indispensable drugs for severe clinical conditions. Some of these products exist in the Brazilian pharmaceutical market, but not in public facilities; others could be produced by national laboratories with commercial interest or stimulated by a specific governmental policy, as in other countries.

Uma comparação crítica entre a Lista de Medicamentos Essenciais para Crianças da Organização Mundial de Saúde e a Relação Nacional de Medicamentos Essenciais (Rename) / A critical comparison between the World Health Organization list of essential medicines for children and the Brazilian list of essential medicines (Rename)

OBJECTIVE: To perform a critical comparison between the Brazilian national essential medicines list (Rename, 2012) with the list of essential medicines for children (LEMC, 2011) of the World Health Organization (WHO), regarding the differences among drugs and formulations listed for children. METHODS: The LEMC drugs were classified into four categories: 1) absent in Rename; 2) included in Rename but without any formulation suitable for children; 3) listed in Rename only in some formulations; 4) present in Rename in all formulations. The missing formulations were analyzed by therapeutic group. Alternatives present in Rename were searched. RESULTS: From the 261 drugs of interest on the LEMC, 30.3% are absent from Rename, 11.1% are in Rename but without any pediatric formulation, and 32.2% are present in some but not all formulations listed in LEMC. Considering all formulations items listed in the LEMC (n = 577), 349 are missing from Rename, of these 19.6% due to their strength, and 18.5% due to the the dosage form. Useful formulations specific for neonatal care, respiratory tract, central nervous system, and anti-infectives, among other groups, are missing. CONCLUSIONS: The lack of age-appropriate formulations of essential medicines for children in Brazil includes important therapeutic groups and indispensable drugs for severe clinical conditions. Some of these products exist in the Brazilian pharmaceutical market, but not in public facilities; others could be produced by national laboratories with commercial interest or stimulated by a specific governmental policy, as in other countries.

OBJETIVO: Realizar uma comparação crítica entre a Relação Nacional de Medicamentos Essenciais (Rename, 2012) e a Lista de Medicamentos Essenciais para Crianças (LMEC, 2011) da Organização Mundial de Saúde (OMS), com relação às diferenças entre os medicamentos e as formulações listadas para crianças. MÉTODOS: Os medicamentos da LMEC foram classificados em quatro grupos: 1) não constam na Rename; 2) constam na Rename, porém sem qualquer formulação adequada para crianças; 3) listados na Rename apenas com algumas formulações; 4) constam na Rename em todas as formulações. As formulações que faltam foram analisadas por grupos terapêuticos. As alternativas presentes na Rename foram pesquisadas. RESULTADOS: Dos 261 medicamentos de interesse listados na LMEC, 30,3% não estão presentes na Rename, 11,1% estão na Rename, mas sem qualquer formulação pediátrica, e 32,3% estão presentes em algumas, mas não todas as formulações listadas na LMEC. Considerando todos os itens de formulações listados na LMEC (n = 577), 349 não constam na Rename, desses, 19,6% devido à intensidade de dosagem, e 18,5% devido à forma farmacêutica. Faltam formulações úteis específicas para cuidado neonatal, trato respiratório e sistema nervoso central, anti-infecciosos, entre outros grupos. CONCLUSÃO: A ausência de formulações adequadas à idade de medicamentos essenciais para crianças no Brasil inclui importantes grupos terapêuticos e medicamentos indispensáveis para quadros clínicos graves. Alguns desses produtos são encontrados no mercado farmacêutico brasileiro, porém não existem em unidades públicas; outros poderiam ser produzidos por laboratórios nacionais com interesse comercial ou estimulados por uma política governamental específica, como é feito em outros países.

Campylobacter jejuni infection and virulence-associated genes in children with moderate to severe diarrhoea admitted to emergency rooms in northeastern Brazil.

Campylobacter is an important cause of foodborne gastroenteritis. We determined the occurrence of Campylobacter jejuni and Campylobacter coli, using culture-based methods and PCRs targeting virulence-associated genes (VAGs) among children aged ≤14 years who were treated for diarrhoea at emergency rooms in northeastern Brazil. Genomic DNA was extracted directly from stool samples collected from 366 children. A questionnaire was also applied to qualify the clinical conditions presented by each child at the time of admission. C. jejuni and C. coli were detected in 16.4 % (60/366) and 1.4 % (5/366) of the diarrhoeal samples, respectively, by PCR, a much higher proportion than that detected by conventional methods. C. jejuni VAGs were detected in the following proportions of hipO-positive samples: ciaB, 95 % (57/60); dnaJ, 86.7 % (52/60); racR, 98.3 % (59/60); flaA, 80 % (48/60); pldA, 45 % (27/60); cdtABC, 95 % (57/60); and pVir 0 % (0/60). Particular symptoms, such as blood in faeces, vomiting, fever, and/or abdominal pain, were not associated with detection of C. jejuni nor were they associated with any particular VAG or combination of VAGs (P>0.05). C. jejuni and its VAGs were detected in a substantial proportion of the children admitted. Further efforts shall be directed towards elucidating whether these genetic factors or their expressed proteins play a role in Campylobacter pathogenesis.

Infectious diseases in paediatric pathology: experience from a developing country.

Infectious and parasitic diseases have always challenged man. Although many of them are typically seen in some areas of the world and can be adequately managed by just improving socioeconomic status and sanitary conditions, they are still quite prevalent and may sometimes be seen outside their original geographical areas. Human migration due to different reasons, tourism, blood transfusion and solid organ transplantation has created new concerns for health professionals all over the world. If not for diagnostic purposes, at least these tropical and infectious diseases should be largely known because their epidemiology, pathogenesis, host/parasite interaction, inflammatory and reparative responses are quite interesting and teach us about human biology. Curiosity is inherent to pathology practice and so we are compelled to look for things other than tumours or degenerative diseases. This review focuses on infectious and parasitic diseases found in a developing country and brings up-to-date information on diseases caused by viruses (dengue, yellow fever), bacteria (typhoid fever, leprosy), parasites (Chagas' disease, cutaneous and visceral leishmaniasis, amoebiasis, Capillaria hepatica, schistosomiasis, cysticercosis) and caused by fungi (paracoccidioidomycosis, cryptococcosis, histoplasmosis) that may be useful for pathologists when facing somewhat strange cases from developing countries.

Streptococcus pneumoniae isolado de nasofaringe em crianças sadias e com pneumonia de fortaleza: sorogrupos e resistência aos antibióticos / Nasopharyngeal streptococcus pneumoniae isolate from health and pneumonia children in Fortaleza, Brazil: serogroups and antibiotic resistance

As pneumonias por pneumococos são importante causa de morbi-mortalidade de crianças em nosso meio. As crescentes taxas de resistência à penicilina e outras drogas são hoje motivo de preocupação no mundo todo. Para comparar as taxas de colonização, a resistência às drogas e os sorogrupos de pneumococos isolados de nasofaringe de crianças com e sem pneumonia, 911 crianças menores de cinco anos, 482 com pneumonia e 429 sadias foram recrutadas aleatoriamente em creches e postos de vacinação de Fortaleza. De 500 (54,9 por cento) amostras de pneumococo isoladas de nasofaringe, a colonização nos controles usuários de creches atingiu 71,8 por cento, contra 50,4 por cento nas crianças com pneumonia. A triagem pelo disco de oxacilina revelou sensibilidade reduzida à penicilina em 64"/o das amostras; foram determinadas as concentrações inibitórias mínimas (CIW de oito antibióticos em 441 amostras (88,2 por cento). Os níveis de CIM mostraram 44,9 por cento de resistência intermediária e 3,6 por cento de resistência plena à penicilina. As taxa de resistência plena dos pneumococos aos demais antibióticos foram: cotrimoxazol, 41,7 por cento, eritromicina 23,1 por cento, clindamicina 18,5 por cento, cloranfenicol 6,6 por cento, rifampicina 2,7 por cento, ceftriaxona I, I por cento e vancomicina O por cento. Os sorogrupos mais prevalentes em 269 amostras testadas foram 6, 19, 23, 14, 15, 9, 16, 11 e 18. Os sorogrupos 6, 14, 19 e 23 constituíram 78 por cento da amostra, sendo mais freqüentes nas pneumonias (83,7 por cento) do que nos controles (72,9 por cento) e apresentaram maiores taxas de resistência à penicilina (86,2 por cento contra 50,83 por cento). Em conclusão, observamos que a resistência dos pneumococos à penicilina e ao cotrimoxazol em crianças portadoras foi elevada, associada à permanência em creches, ao consumo prévio de antibióticos e aos sorogrupos 6, 14, 19 e 23, mas não associada ao estado clínico