BACKGROUND Child mortality from sickle cell disease in sub-Saharan Africa is presumed to be high but is not well quantified. This uncertainty contributes to the neglect of sickle cell disease and delays the prioritisation of interventions. In this study, we estimated the mortality of children in Nigeria with sickle cell disease, and the proportion of national under-5 mortality attributable to sickle cell disease. METHODS We did a model-estimated, population-level analysis of data from Nigeria's 2018 Demographic and Health Survey (DHS) to estimate the prevalence and geographical distribution of HbSS and HbSC genotypes assuming Hardy-Weinberg equilibrium near birth. Interviews for the survey were done between Aug 14 and Dec 29, 2018, and the embedded sickle cell disease survey was done in a randomly selected third of the overall survey's households. We developed an approach for estimating child mortality from sickle cell disease by combining information on tested children and their untested siblings. Tested children were aged 6-59 months at the time of the survey. Untested siblings born 0-14 years before the survey were also included in analyses. Testing as part of the DHS was done without regard to disease status. We analysed mortality differences using the inheritance-derived genotypic distribution of untested siblings older than the tested cohort, enabling us to estimate excess mortality from sickle cell disease for the older-sibling cohort (ie, those born between 2003 and 2013). FINDINGS We analysed test results for 11 186 children aged 6-59 months from 7411 households in Nigeria. The estimated average birth prevalence of HbSS was 1·21% (95% CI 1·09-1·37) and was 0·24% (0·19-0·31) for HbSC. We obtained data for estimating child mortality from 10 195 tested children (who could be matched to the individual mother survey) and 17 205 of their untested siblings. 15 227 of the siblings were in the older-sibling cohort. The group of children with sickle cell disease born between 2003 and 2013 with at least one younger sibling in the survey had about 370 excess under-5 deaths per 1000 livebirths (95% CI 150-580; p=0·0008) than children with HbAA. The estimated national average under-5 mortality for children with sickle cell disease born between 2003 and 2013 was 490 per 1000 livebirths (95% CI 270-700), 4·0 times higher (95% CI 2·1-6·0) than children with HbAA. About 4·2% (95% CI 1·7-6·9) of national under-5 mortality was attributable to excess mortality from sickle cell disease. INTERPRETATION The burden of child mortality from sickle cell disease in Nigeria continues to be disproportionately higher than the burden of mortality of children without sickle cell disease. Most of these deaths could be prevented if adequate resources were allocated and available focused interventions were implemented. The methods developed in this study could be used to estimate the burden of sickle cell disease elsewhere in Africa and south Asia. FUNDING Sickle Pan African Research Consortium, and the Bill & Melinda Gates Foundation.

中文翻译：

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尼日利亚镰状细胞病儿童死亡率：对 2018 年人口与健康调查数据进行的模型估计、人口水平分析。


背景 据推测，撒哈拉以南非洲地区镰状细胞病儿童死亡率很高，但尚未得到很好的量化。这种不确定性导致了对镰状细胞病的忽视，并延迟了干预措施的优先顺序。在这项研究中，我们估算了尼日利亚镰状细胞病儿童的死亡率，以及全国 5 岁以下儿童因镰状细胞病死亡的比例。方法 我们对尼日利亚 2018 年人口和健康调查 (DHS) 的数据进行了模型估计、人群水平分析，以估计 HbSS 和 HbSC 基因型的患病率和地理分布（假设出生时哈迪-温伯格平衡）。该调查的访谈是在2018年8月14日至12月29日之间进行的，嵌入式镰状细胞病调查是在整个调查的家庭中随机选择的三分之一进行的。我们通过结合接受测试的儿童及其未经测试的兄弟姐妹的信息，开发了一种估算镰状细胞病儿童死亡率的方法。调查时，接受测试的儿童年龄为 6 至 59 个月。调查前 0-14 岁出生的未经测试的兄弟姐妹也被纳入分析。作为国土安全部一部分的检测是在不考虑疾病状况的情况下进行的。我们使用比测试队列年长的未测试兄弟姐妹的遗传衍生基因型分布来分析死亡率差异，使我们能够估计年长兄弟姐妹队列（即 2003 年至 2013 年出生的兄弟姐妹）因镰状细胞病造成的超额死亡率。结果 我们分析了尼日利亚 7411 个家庭的 11186 名 6-59 个月大儿童的测试结果。 HbSS 的估计平均出生患病率为 1·21% (95% CI 1·09-1·37)，HbSC 的估计平均出生患病率为 0·24% (0·19-0·31)。 我们从 10 195 名接受测试的儿童（可以与个别母亲调查相匹配）和 17 205 名未经测试的兄弟姐妹中获得了估计儿童死亡率的数据。 15 227 名兄弟姐妹属于年长兄弟姐妹队列。调查中，2003 年至 2013 年间出生且至少有一名弟弟妹妹的镰状细胞病儿童群体中，每 1000 名活产婴儿中，5 岁以下儿童死亡人数比患有镰状细胞病的儿童多出约 370 例（95% CI 150-580；p=0·0008）。血红蛋白AA。据估计，2003 年至 2013 年间出生的镰状细胞病儿童全国 5 岁以下儿童平均死亡率为每 1000 名活产儿 490 人 (95% CI 270-700)，高出 4·0 倍 (95% CI 2·1-6·0)高于患有 HbAA 的儿童。全国 5 岁以下儿童死亡率中约 4·2% (95% CI 1·7-6·9) 可归因于镰状细胞病造成的过高死亡率。解释 尼日利亚镰状细胞病儿童死亡负担仍然不成比例地高于未患镰状细胞病儿童的死亡负担。如果分配足够的资源并实施现有的重点干预措施，大多数死亡都是可以避免的。本研究开发的方法可用于估计非洲和南亚其他地区镰状细胞病的负担。资助 Sickle 泛非研究联盟和比尔及梅琳达·盖茨基金会。