The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).
The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).
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撒哈拉以南非洲和南亚的中等/高死亡率地区儿童中隐孢子虫腹泻病的负担，利用来自全球企业多中心研究（GEMS）的数据。
DOI：
10.1371/journal.pntd.0004729
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发表时间：
2016-05
影响因子：
3.8
通讯作者：
Levine MM
中科院分区：
文献类型：
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作者：
Sow SO;Muhsen K;Nasrin D;Blackwelder WC;Wu Y;Farag TH;Panchalingam S;Sur D;Zaidi AK;Faruque AS;Saha D;Adegbola R;Alonso PL;Breiman RF;Bassat Q;Tamboura B;Sanogo D;Onwuchekwa U;Manna B;Ramamurthy T;Kanungo S;Ahmed S;Qureshi S;Quadri F;Hossain A;Das SK;Antonio M;Hossain MJ;Mandomando I;Nhampossa T;Acácio S;Omore R;Oundo JO;Ochieng JB;Mintz ED;O'Reilly CE;Berkeley LY;Livio S;Tennant SM;Sommerfelt H;Nataro JP;Ziv-Baran T;Robins-Browne RM;Mishcherkin V;Zhang J;Liu J;Houpt ER;Kotloff KL;Levine MM
隐孢子虫作为儿科肠道病原体在发展中国家的重要性得到了认可。分析了来自全球肠道多中心研究（GEMS）（一项为期3年、7个中心的中度至重度腹泻（MSD）病例对照研究）和GEMS-1A（为期1年的MSD和轻度腹泻[LSD]研究）的数据。对年龄<60个月的儿童中的12，110例MSD和3，174例LSD病例以及21，527例随机选择的年龄，性别和社区匹配的对照组的粪便进行隐孢子虫免疫检测。通过PCR鉴定隐孢子虫阳性标本的一个子集的种属; GP60测序鉴定出人类感染的C。小的将非洲和亚洲GEMS研究中心年龄<24个月儿童的合并隐孢子虫腹泻年发病率外推至撒哈拉以南非洲和南亚地区，以估计区域范围内的MSD和LSD负担。估计了隐孢子虫腹泻的归因死亡率和超额死亡率。隐孢子虫与24个月以下的MSD和LSD显著相关。在隐孢子虫阳性的MSD病例中，C. 77.8%（95%CI，73.0%~81.9%）的人型和C.小隐孢子虫为9.9%（95% CI为7.1%~13.6%），隐孢子虫为92%（95% CI为7.1%~13.6%）。测试的小孢子是人类基因型。隐孢子虫引起的MSD年发病率为3.48（95% CI，2.27 - 4.67）和3.18非洲和亚洲婴儿分别为每100儿童年（95%CI，1.85 - 4.52）和1.41（95% CI，0.73 - 2.08）和1.36（95% CI，0.66 - 2.05）每100儿童年。相应的隐孢子虫可归因的LSD发病率每100儿童年分别为2.52（95% CI，0.33 - 5.01）和4.88（95% CI，0.82 - 8.92），婴儿和4.04（95% CI，0.56 - 7.51）和4.71（95% CI，0.24 - 9.18）。我们估计，在撒哈拉以南非洲和印度/巴基斯坦/孟加拉国/尼泊尔/阿富汗地区，每年在24个月以下的儿童中分别有290万和470万例隐孢子虫病例，约202，000例隐孢子虫死亡（地区合并）。如果病例为隐孢子虫阴性，则隐孢子虫引起的腹泻病例中的死亡人数超过预期约59，000人。非洲/亚洲巨大的隐孢子虫病负担需要投资开发疫苗、诊断和治疗方法。隐孢子虫是一种原生动物，在发展中国家引起幼儿腹泻和营养不良，并与发达国家的腹泻病例和暴发有关。迄今为止，关于撒哈拉以南非洲和南亚隐孢子虫病负担的信息有限，那里发生了大多数隐孢子虫病死亡。我们使用全球肠道多中心研究（GEMS）的数据估计了这些地区隐孢子虫腹泻的负担和相关死亡。隐孢子虫与腹泻有关，主要发生在年龄<24个月的儿童中。感染开始于生命的最初几个月，但隐孢子虫相关腹泻疾病的临床发作在6 - 11个月大时达到高峰。据估计，在撒哈拉以南非洲和南亚的印度/巴基斯坦/孟加拉国/阿富汗/尼泊尔地区，每年24个月以下的儿童中隐孢子虫引起的腹泻病例数分别为290万和470万。在这两个地区，估计隐孢子虫每年造成约202，000人死亡，隐孢子虫引起的病例比隐孢子虫阴性病例多约59，000人死亡。我们的研究强调了隐孢子虫在非洲和亚洲造成的巨大负担，这强调了开发疫苗和治疗方法以减轻这种负担的必要性。
The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27–4.67) and 3.18 (95% CI, 1.85–4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73–2.08) and 1.36 (95% CI, 0.66–2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33–5.01) and 4.88 (95% CI, 0.82–8.92) in infants and 4.04 (95% CI, 0.56–7.51) and 4.71 (95% CI, 0.24–9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies. Cryptosporidium is a protozoan that causes diarrhea and malnutrition in young children in developing countries, and is associated with diarrhea cases and outbreaks in developed countries. To date, limited information exists on the burden of Cryptosporidium diarrheal disease in sub-Saharan Africa and South Asia, where most diarrheal disease deaths occur. We estimated the burden of Cryptosporidium-diarrhea and associated deaths in these regions using data from the Global Enteric Multicenter Study (GEMS). Cryptosporidium was associated with diarrhea mainly in children aged <24 months. Infections began in the first few months of life but clinical episodes of Cryptosporidium-associated diarrhea illness peaked at age 6–11 months. The annual number of Cryptosporidium-attributable diarrhea episodes was estimated at 2.9 and 4.7 million in children aged <24 months in sub-Saharan Africa and in the India/Pakistan/Bangladesh/Afghanistan/Nepal region of South Asia, respectively. In both regions combined, Cryptosporidium is estimated to contribute to approximately 202,000 deaths per year, and to ~59,000 more deaths in Cryptosporidium-attributable cases than if those cases had been negative for Cryptosporidium. Our study highlights the enormous burden attributable to Cryptosporidium in Africa and Asia, which underscores the need for developing vaccines and treatments to reduce this burden.