Newberry Laura, O'Hare Bernadette, Kennedy Neil, Selman Andrew, Omar Sofia, Dawson Pamela, Stevenson Kim, Nishihara Yo, Lissauer Samantha, Molyneux Elizabeth
a College of Medicine, University of Malawi , Blantyre , Malawi.
b Queen Elizabeth Central Hospital , Blantyre , Malawi.
Paediatr Int Child Health. 2017 May;37(2):121-128. doi: 10.1080/20469047.2016.1260891. Epub 2017 Feb 1.
Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in infants with vertically acquired HIV infection and the most common cause of death in HIV-infected infants.
To determine whether early administration of adjuvant corticosteroids in addition to standard treatment reduces mortality in infants with vertically acquired HIV and clinically diagnosed PJP when co-infection with cytomegalovirus and other pathogens cannot be excluded.
A double-blind placebo-controlled trial of adjuvant prednisolone treatment in HIV-exposed infants aged 2-6 months admitted to Queen Elizabeth Central Hospital, Blantyre who were diagnosed clinically with PJP was performed. All recruited infants were HIV-exposed, and the HIV status of the infant was confirmed by DNA-PCR. HIV-exposed and infected infants as well as HIV-exposed but non-infected infants were included in the study. The protocol provided for the addition of prednisolone to the treatment at 48 h if there was clinical deterioration or an independent indication for corticosteroid therapy in any patient not receiving it. Oral trimethoprim-sulfamethoxazole (TMP/SMX) therapy and full supportive treatment were provided according to established guidelines. Primary outcomes for all patients included survival to hospital discharge and 6-month post-discharge survival.
It was planned to enroll 200 patients but the trial was stopped early because of recruitment difficulties and a statistically significant result on interim analysis. Seventy-eight infants were enrolled between April 2012 and August 2014; 36 infants (46%) were randomised to receive corticosteroids plus standard treatment with TMP/SMX, and 42 infants (54%) received the standard treatment plus placebo. In an intention-to treat-analysis, the risk ratio of in-hospital mortality in the steroid group compared with the standard treatment plus placebo group was 0.53 [95% CI 0.29-0.97, p = 0.038]. The risk ratio of mortality at 6 months was 0.63 (95% CI 0.41-0.95, p = 0.029). Two children who received steroids developed bloody stools while in hospital.
In infants with a clinical diagnosis of PJP, early use of steroids in addition to conventional TMP/SMX therapy significantly reduced mortality in hospital and 6 months after discharge.
耶氏肺孢子菌肺炎（PJP）是垂直感染艾滋病毒婴儿中最常见的机会性感染，也是艾滋病毒感染婴儿最常见的死亡原因。
确定在不能排除巨细胞病毒和其他病原体合并感染的情况下，除标准治疗外早期给予辅助性皮质类固醇是否能降低垂直感染艾滋病毒且临床诊断为PJP的婴儿的死亡率。
对马拉维布兰太尔伊丽莎白女王中央医院收治的2至6个月临床诊断为PJP的艾滋病毒暴露婴儿进行了一项辅助性泼尼松龙治疗的双盲安慰剂对照试验。所有招募的婴儿均为艾滋病毒暴露婴儿，其艾滋病毒感染状况通过DNA-PCR得以确认。艾滋病毒暴露且感染的婴儿以及艾滋病毒暴露但未感染的婴儿均纳入研究。该方案规定，如果未接受治疗的任何患者出现临床恶化或有皮质类固醇治疗的独立指征，则在48小时时将泼尼松龙添加到治疗中。根据既定指南提供口服甲氧苄啶-磺胺甲恶唑（TMP/SMX）治疗和全面的支持治疗。所有患者的主要结局包括存活至出院以及出院后6个月存活。
计划招募200名患者，但由于招募困难以及中期分析得出具有统计学意义的结果，该试验提前终止。2012年4月至2014年8月期间共招募了78名婴儿；36名婴儿（46%）被随机分配接受皮质类固醇加TMP/SMX标准治疗，42名婴儿（54%）接受标准治疗加安慰剂。在意向性分析中，与标准治疗加安慰剂组相比，类固醇组的院内死亡率风险比为0.53[95%可信区间0.29 - 0.97，p = 0.038]。6个月时的死亡率风险比为0.63（95%可信区间0.41 - 0.95，p = 0.029）。两名接受类固醇治疗的儿童在住院期间出现了便血。
对于临床诊断为PJP的婴儿，除常规TMP/SMX治疗外早期使用类固醇可显著降低住院期间及出院后6个月的死亡率。
