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Burden of childhood tuberculosis in countries that routinely vaccinate with Bacillus Calmette-Guerin (BCG) soon after birth: a systematic review
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Introdução: A tuberculose, doença causada pela bactéria Mycobacterium tuberculosis,
é ainda hoje uma importante causa de morbilidade e mortalidade infantil em todo o
mundo, particularmente em países em desenvolvimento. Apesar de refletir transmissão
ativa na comunidade, a importância da tuberculose em idade pediátrica é
frequentemente subestimada. O subdiagnóstico, a subnotificação, a perceção de que as
crianças contribuem pouco para a transmissão da doença e a existência de poucos dados
acerca dos outcomes das crianças com tuberculose contribuíram para o reduzido
investimento em programas de saúde dirigidos a esta faixa etária. A vacina BCG
(Bacillus Calmete-Guerin) é a única vacina licenciada destinada à prevenção da
tuberculose, conferindo proteção contra as formas graves de doença em crianças. A
vacinação universal logo após o nascimento é recomendada em países com elevada
incidência.
Objectivo: O propósito desta revisão sistemática foi avaliar o impacto da tuberculose
em idade pediátrica em países que mantém a vacinação universal com a BCG nas
crianças logo após o nascimento.
Métodos: Foi realizada a pesquisa sistemática de três bases de dados distintas (PubMed,
Web of Science, SciELO), utilizando palavras chave relacionadas com a epidemiologia
da tuberculose. Procedeu-se ainda à pesquisa manual das referências bibliográficas dos
estudos incluídos para identificação de outros artigos pertinentes. Foram selecionados os
estudos considerados relevantes e publicados entre 2000 e 2020, que incluíram crianças
entre os 0 e os 14 anos. Os dados foram extraídos e apresentados em tabelas e em
gráficos em floresta. Quando apropriado foi realizada meta-análise de acordo com o
modelo de efeitos aleatórios, para cálculo de estimativas resumo. Análises de sub-grupo
foram efetuadas de acordo com a idade das crianças, região e rendimento dos países.
Resultados: Das 1806 referências bibliográficas identificadas, foram revistos os textos
completos de 220 artigos. Destes foram incluídos 35 artigos na revisão sistemática,
reportando dados de 24 países. A proporção global de desfechos desfavoráveis foi
19.52% (95% intervalo de confiança (IC) 14.44-25.84) e a taxa de letalidade global foi
de 6.06% (95% IC 4.34-8.40). Observou-se uma proporção mais elevada de mortes em
crianças entre os 0 e os 4 anos (6.56%, 95% IC 4.91-8.71). A proporção global de
tuberculose multi-resistente (MDR-TB) foi 8.14% (95% IC 4.64-13.90). A prevalência
global de infeção pelo vírus da imunodeficiência humana (VIH) nas crianças testadas foi
21.30% (IC 95% 11.89-35.17) e as crianças coinfetadas apresentaram uma maior taxa
de letalidade (15.09%, 95% CI 7.86-27.02) quando comparadas com crianças sem
infeção VIH (4.16%, 95% CI 2.00-8.44).
Conclusão: Apesar dos esforços realizados nas últimas décadas para combater a carga
global da tuberculose, o impacto desta doença nas crianças é ainda significativo, mas
frequentemente subestimado. Embora limitados por elevada heterogeneidade, os
resultados sugerem uma proporção significativa de desfechos desfavoráveis, incluindo
morte, particularmente em crianças mais novas. A coinfeção tuberculose/VIH é ainda
frequente nos países que vacinam universalmente com a BCG, associando-se a
mortalidade mais elevada. São necessários mais estudos populacionais de elevada
qualidade para preencher lacunas no conhecimento e mobilizar os recursos necessários
para abordar eficazmente este problema.
Introduction: Tuberculosis, caused by the bacteria Mycobacterium tuberculosis, is still an important cause of morbidity and mortality in children worldwide, particularly in developing countries. Despite reflecting ongoing transmission in the community, the importance of childhood tuberculosis has often been overlooked. Underdiagnosis, underreporting, the perception that children contribute little to disease transmission and limited data on the outcomes of childhood tuberculosis have led to a lack of investment in health programmes directed at this age group. Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine against tuberculosis and confers protection against severe forms of tuberculosis in children. Universal vaccination of infants soon after birth is recommended in countries with a high burden of disease. Objective: This systematic review aimed to evaluate the burden of childhood tuberculosis in countries that still routinely vaccinate children with BCG vaccine soon after birth. Methods: Systematic research was performed in three different databases (PubMed, Web of Science, SciELO), using keywords related to the epidemiology of tuberculosis. Hand searches of the reference lists of included studies were also conducted. Relevant studies, published from 2000 to 2020 and reporting data on children between 0 and 14 years old, were selected. Data were extracted and presented in tables and forest plots. When appropriate, random-effects meta-analysis was used to obtain summary estimates. Sub-group analyses were carried out based on the age of children, region and country income. Results: Of the 1806 references identified, 220 underwent a full-text review. Thirty-five eligible studies were included in this systematic review, reporting data from 24 countries. The overall proportion of unfavourable results was 19.52% (95% confidence interval (CI) 14.44-25.84) and pooled case fatality ratio was 6.06% (95% CI 4.34-8.40). A higher proportion of deaths was observed among children between 0 and 4 years old (6.56%, 95% CI 4.91-8.71). The overall proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.14% (95% CI 4.64-13.90). Pooled prevalence of human immunodeficiency virus (HIV) infection among tested children was 21.30% (CI 95% 11.89-35.17) and co-infected children presented a higher case fatality ratio (15.09%, 95% CI 7.86-27.02) when compared to HIV negative children (4.16%, 95% CI 2.00- 8.44). Conclusion: Despite efforts made in the last few decades to tackle the global burden of tuberculosis, the impact on children is still significant but often underestimated. Although limited by high heterogeneity, our findings suggest a significant pooled proportion of unfavourable results, including death, particularly in younger children. Tuberculosis/HIV co-infection remains common in countries that routinely vaccinate with BCG and is associated with higher mortality. More high-quality population-based studies are necessary to fill existing gaps in knowledge and mobilise the resources needed to effectively address this problem.
Introduction: Tuberculosis, caused by the bacteria Mycobacterium tuberculosis, is still an important cause of morbidity and mortality in children worldwide, particularly in developing countries. Despite reflecting ongoing transmission in the community, the importance of childhood tuberculosis has often been overlooked. Underdiagnosis, underreporting, the perception that children contribute little to disease transmission and limited data on the outcomes of childhood tuberculosis have led to a lack of investment in health programmes directed at this age group. Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine against tuberculosis and confers protection against severe forms of tuberculosis in children. Universal vaccination of infants soon after birth is recommended in countries with a high burden of disease. Objective: This systematic review aimed to evaluate the burden of childhood tuberculosis in countries that still routinely vaccinate children with BCG vaccine soon after birth. Methods: Systematic research was performed in three different databases (PubMed, Web of Science, SciELO), using keywords related to the epidemiology of tuberculosis. Hand searches of the reference lists of included studies were also conducted. Relevant studies, published from 2000 to 2020 and reporting data on children between 0 and 14 years old, were selected. Data were extracted and presented in tables and forest plots. When appropriate, random-effects meta-analysis was used to obtain summary estimates. Sub-group analyses were carried out based on the age of children, region and country income. Results: Of the 1806 references identified, 220 underwent a full-text review. Thirty-five eligible studies were included in this systematic review, reporting data from 24 countries. The overall proportion of unfavourable results was 19.52% (95% confidence interval (CI) 14.44-25.84) and pooled case fatality ratio was 6.06% (95% CI 4.34-8.40). A higher proportion of deaths was observed among children between 0 and 4 years old (6.56%, 95% CI 4.91-8.71). The overall proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.14% (95% CI 4.64-13.90). Pooled prevalence of human immunodeficiency virus (HIV) infection among tested children was 21.30% (CI 95% 11.89-35.17) and co-infected children presented a higher case fatality ratio (15.09%, 95% CI 7.86-27.02) when compared to HIV negative children (4.16%, 95% CI 2.00- 8.44). Conclusion: Despite efforts made in the last few decades to tackle the global burden of tuberculosis, the impact on children is still significant but often underestimated. Although limited by high heterogeneity, our findings suggest a significant pooled proportion of unfavourable results, including death, particularly in younger children. Tuberculosis/HIV co-infection remains common in countries that routinely vaccinate with BCG and is associated with higher mortality. More high-quality population-based studies are necessary to fill existing gaps in knowledge and mobilise the resources needed to effectively address this problem.
Descrição
Palavras-chave
Doenças tropicais Tuberculose Crianças BCG Epidemiologia