Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Incapacidade física em pessoas afetadas pela hanseníase: estudo após alta medicamentosa

Physical disability is the main problem of leprosy. Despite multidrugtherapy (MDT) success in treating leprosy, it is known that about 25%>50% of patients may have some nerve damage and develop physical disabilities, classified by WHO disability grading (DG) as 0 for normal sensation, no visible impairments, 1 for impaired sensation, no visible impairments, or 2 for visible impairments/deformity. From 2004 to 2010 Brazil registered 21,7% of the cases as DG 1, and 7% as DG 2, while in Pará State 15,3% of the patients were diagnosed with DG 1, and 5,1% with DG 2 on the diagnosis of leprosy. In order to investigate physical disabilities in MDT cured patients, we examined the sensory-motor functions of 517 people affected by leprosy reported from 2004 to 2010 in eight hyperendemic municipalities of the Brazilian Amazon Region, correlating our findings with epidemiological and socio-economic features, and comparing with data found at the National Information System for Notifiable Diseases (SINAN). Additionally, 2164 household contacts of leprosy patients were clinically evaluated for signs and symptoms of leprosy. Patients’ home visits were planned with clinical assessment, simplified neurological evaluation and determination of DG, together with an interview about their demographic and socio-economic characteristics. DG 1 was found on 16,2% and DG 2 on 12,4% of the patients evaluated. It was found a statistically significant correlation between multibacillary (MB) forms and DG 1 or 2 (p40 years-old and no BCG scar, all important risk factors for developing disability. The differences of DG found in SINAN in contrast to our study suggest worsening of the sensory-motor functions after discharge from MDT, indicating the importance of monitoring these patients for years after finishing MDT treatment. The high rate of detection in this study reflects the low level of evaluation of household contacts in Pará (58,8%), perpetuating the late diagnosis. Clinical findings suggest that there is a high rate of undiagnosed leprosy and subclinical infection in our sample, indicating a need for periodic clinical evaluation.A incapacidade física é o principal problema da hanseníase. Apesar do sucesso da poliquimioterapia (PQT) no tratamento da doença, sabe-se que cerca de 25% a 50% dos pacientes podem ter algum dano do nervo e desenvolver incapacidades físicas, classificada pela Organização Mundial de Saúde (OMS) como grau de incapacidade física (GIF) 0 para sensibilidade normal, sem deformidades visíveis, 1 para a sensibilidade diminuída, sem alterações visíveis, ou 2 para deficiências visíveis / deformidade. De 2004 a 2010 o Brasil registrou 21,7% dos casos como sendo GIF 1 e 7% como GIF 2, enquanto que no Estado do Pará, 15,3% dos pacientes foram diagnosticados com GIF 1, e 5,1% com GIF 2 no momento do diagnóstico de hanseníase. A fim de investigar as incapacidades físicas em pacientes curados, examinamos as funções sensitivo-motoras de 517 pessoas afetadas pela hanseníase, notificados 2004 a 2010 em oito municípios hiperendêmicos da Amazônia brasileira, correlacionando os achados com aspectos epidemiológicos e sócio-econômico, e comparando com os dados encontrados no Sistema Nacional de Informação de Agravos de Notificação (SINAN). Adicionalmente, 2164 contatos intradomiciliares dos pacientes visitados foram avaliados clinicamente em busca de sinais e sintomas da doença. As visitas domiciliares dos pacientes constaram de avaliação clínica, avaliação neurológica simplificada e determinação do GIF, realização de entrevista sobre suas características demográficas e sócio-econômicas. O GIF 1 foi encontrado em 16,2% e DG 2 em 12,4% dos pacientes avaliados. Foi encontrada uma correlação estatisticamente significativa entre as formas multibacilares (MB) e o GIF 1 ou 2 (p 40 anos de idade e sem cicatriz de BCG, todos os fatores de risco importantes para o desenvolvimento de deficiência. As diferenças de GIF encontradas no SINAN e no nosso estudo sugerem piora das funções sensório-motor após a alta da PQT, indicando a importância do acompanhamento destes pacientes por anos depois de terminar o tratamento MDT. A alta taxa de detecção de casos novos diagnosticados neste estudo reflete o baixo índice de avaliação de contatos no estado do Pará (58,8%), perpetuando o diagnóstico tardio. Os achados clínicos sugerem a existência de prevalência oculta e alto índice de infecção subclínica na amostra estudada, indicando necessidade de avaliação clínica periódica

Spatial analysis spotlighting early childhood leprosy transmission in a hyperendemic municipality of the Brazilian Amazon region.

BACKGROUND: More than 200,000 new cases of leprosy were reported by 105 countries in 2011. The disease is a public health problem in Brazil, particularly within high-burden pockets in the Amazon region where leprosy is hyperendemic among children. METHODOLOGY: We applied geographic information systems and spatial analysis to determine the spatio-temporal pattern of leprosy cases in a hyperendemic municipality of the Brazilian Amazon region (Castanhal). Moreover, we performed active surveillance to collect clinical, epidemiological and serological data of the household contacts of people affected by leprosy and school children in the general population. The occurrence of subclinical infection and overt disease among the evaluated individuals was correlated with the spatio-temporal pattern of leprosy. PRINCIPAL FINDINGS: The pattern of leprosy cases showed significant spatio-temporal heterogeneity (p<0.01). Considering 499 mapped cases, we found spatial clusters of high and low detection rates and spatial autocorrelation of individual cases at fine spatio-temporal scales. The relative risk of contracting leprosy in one specific cluster with a high detection rate is almost four times the risk in the areas of low detection rate (RR = 3.86; 95% CI = 2.26-6.59; p<0.0001). Eight new cases were detected among 302 evaluated household contacts: two living in areas of clusters of high detection rate and six in hyperendemic census tracts. Of 188 examined students, 134 (71.3%) lived in hyperendemic areas, 120 (63.8%) were dwelling less than 100 meters of at least one reported leprosy case, 125 (66.5%) showed immunological evidence (positive anti-PGL-I IgM titer) of subclinical infection, and 9 (4.8%) were diagnosed with leprosy (8 within 200 meters of a case living in the same area). CONCLUSIONS/SIGNIFICANCE: Spatial analysis provided a better understanding of the high rate of early childhood leprosy transmission in this region. These findings can be applied to guide leprosy control programs to target intervention to high risk areas

Clusters of leprosy in Castanhal.

<p>(A) The spatial distribution of individual leprosy cases overlying the respective Kernel density estimation layer, representing areas with a high and low density of cases per km². (B) LISA test (local Moran's I) characterizing areas with a statistically significant (p<0.05) positive spatial association according to the raw detection rate. The areas marked as high-high indicate a high rate in an area surrounded by high values of the weighted average rate of the neighboring areas, and low-low represents areas with a lower rate surrounded by lower values. (C) The most likely cluster of leprosy detected by the Kulldorff's spatial scan statistics (<i>p</i><0.01).</p

Characteristics of the specific regions in the urban area of Castanhal.

*<p>Annual detection rate per 100,000 people.</p><p>SEB = Spatially empirical Bayes.</p><p>LISA = Local indicator of spatial association (Local Moran's I).</p

Population density and spatial distribution of leprosy in Castanhal.

<p>(A) Population density per km² in the urban census tracts. (B) Raw number of leprosy cases per census tract. (C) Number of cases normalized by the population of each census tract per year (annual raw case detection rate per 100,000 people), classifying areas according to their level of endemicity, from low to hyperendemic, according to official parameters. (D) Spatially empirical Bayes smoothed detection rate (based on a queen spatial weight matrix) to smooth the differences between contiguous areas.</p

Space-time links among cases and proximity to students.

<p>An expanded view of a specific region identified as a cluster of leprosy (see <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002665#pntd-0002665-g002" target="_blank">Figure 2C</a>, Kulldorff's spatial scan statistics), showing the space-time links among cases and the spatial relationship with a surveyed school and seropositive students.</p

Spatial distribution of surveyed household contacts and school children.

<p>The spatial distribution of surveyed household contacts and school children according to their level of antibodies compared to the level of endemicity of the different census tracts.</p