Humphreys Eliza H, Smith Nathan A, Azman Hana, McLeod Deanna, Rutherford George W
Global Health Sciences, University of California, San Francisco, 50 Beale Street, Suite 1200, San Francisco, California, USA, 94105.
Cochrane Database Syst Rev. 2010 Jun 16(6):CD008563. doi: 10.1002/14651858.CD008563.
Diarrhoea is a major cause of morbidity and mortality among infants and children worldwide, especially in low- and middle-income countries. Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a condition that similarly disproportionately affects low- and middle-income countries; of the nearly 2.1 million children under age 15 years living with HIV/AIDS, the large majority reside in sub-Saharan Africa. Infants and children with HIV infection have more frequent and more severe diarrhoea than children without HIV. Interventions including vitamin A, zinc and cotrimoxazole may contribute substantially to preventing diarrhoea in children with HIV infection or exposure to HIV.
We perform a systematic review of randomised controlled trials and nonrandomised studies that examine the effectiveness of vitamin A, zinc and cotrimoxazole on mortality and morbidity from diarrhoea in HIV-infected and -exposed infants and children.
Electronic databases including Pubmed, Central and EMBASE were searched without limits to language from 1980 to April 2010. Conference database searches were performed, experts were contacted and bibliographies were handsearched.
Randomised controlled trials (RCTs) and nonrandomised studies (NRSs) that examined the effectiveness of the three interventions were included.
Two reviewers independently assessed citations for eligibility and double-extracted included studies. Assessment of bias of individual studies was performed independently by both reviewers. Only two summary estimates were performed due to heterogeneity in study design and interventions.
Four RCTs were identified for vitamin A. One RCT was identified for zinc. One RCT and two NRSs were identified for cotrimoxazole. Vitamin A reduced mortality overall in children with HIV infection (four studies). A pooled estimate of three studies for reduction in mortality from vitamin A compared to placebo had a relative risk (DerSimonian and Laird method, random effects) of 0.50 (95% confidence interval (CI): 0.31 to 0.79) in 267 patients. Diarrheoa-specific mortality did not reach statistical significance and diarrhoeal morbidity outcomes were variable in three trials. Zinc supplementation reduced the number of physician visits for watery diarrhoea in one trial. Cotrimoxazole reduced mortality and hospitalisations compared to placebo in one RCT, although diarrhoea-specific morbidities were not significant.
AUTHORS' CONCLUSIONS: Vitamin A shows benefits in reduction of mortality in HIV-infected children. The effect of vitamin A on children with HIV exposure is not clear and needs further review. Zinc and combination vitamin A, zinc and micronutrient supplementation did not show an effect compared to vitamin A alone in children with HIV infection. Cotrimoxazole reduced mortality and some morbidity in children with HIV infection. Further research may clarify the effects of these interventions on morbidity from diarrhoea and in the population of children with HIV exposure.
腹泻是全球婴幼儿发病和死亡的主要原因,在低收入和中等收入国家尤为如此。人类免疫缺陷病毒/获得性免疫缺陷综合征(HIV/AIDS)同样在很大程度上影响着低收入和中等收入国家;在近210万15岁以下感染HIV/AIDS的儿童中,绝大多数居住在撒哈拉以南非洲。感染HIV的婴幼儿比未感染HIV的儿童腹泻更频繁、更严重。包括维生素A、锌和复方新诺明在内的干预措施可能对预防感染HIV或接触HIV的儿童腹泻有很大作用。
我们对随机对照试验和非随机研究进行系统评价,以检验维生素A、锌和复方新诺明对感染HIV和接触HIV的婴幼儿腹泻导致的死亡率和发病率的有效性。
检索了包括PubMed、CENTRAL和EMBASE在内的电子数据库,检索时间范围为1980年至2010年4月,不限语言。还进行了会议数据库检索,联系了专家并手工检索了参考文献。
纳入了检验这三种干预措施有效性的随机对照试验(RCT)和非随机研究(NRS)。
两名评价员独立评估文献的纳入资格,并对纳入研究进行双人数据提取。两名评价员独立对各个研究的偏倚进行评估。由于研究设计和干预措施存在异质性,仅进行了两项汇总估计。
确定了四项关于维生素A的RCT。确定了一项关于锌的RCT。确定了一项关于复方新诺明的RCT和两项NRS。维生素A总体上降低了HIV感染儿童的死亡率(四项研究)。三项研究对维生素A与安慰剂相比降低死亡率的汇总估计显示,267例患者的相对危险度(DerSimonian和Laird法,随机效应)为0.50(95%置信区间(CI):0.31至0.79)。腹泻特异性死亡率未达到统计学显著性,三项试验中腹泻发病率的结果各不相同。在一项试验中,补充锌减少了因水样腹泻就医的次数。在一项RCT中,与安慰剂相比,复方新诺明降低了死亡率和住院率,尽管腹泻特异性发病率不显著。
维生素A在降低HIV感染儿童死亡率方面显示出益处。维生素A对接触HIV儿童的影响尚不清楚,需要进一步审查。在感染HIV的儿童中,与单独使用维生素A相比,锌以及维生素A、锌和微量营养素联合补充未显示出效果。复方新诺明降低了HIV感染儿童的死亡率和一些发病率。进一步的研究可能会阐明这些干预措施对腹泻发病率以及接触HIV儿童群体的影响。