Management of toxoplasmic encephalitis in HIV-infected adults (with an emphasis on resource-poor settings)

 

Abstract

Background

Cerebral toxoplasmosis or toxoplasmic meningoencephalitis (hereafter referred to as TE) was one of the first opportunistic infections to be described in human immunodeficiency virus (HIV) -infected patients. Treatment of TE has been relatively successful in comparison to other opportunistic infections. Prior to the introduction of highly active antiretroviral therapy (HAART), a median survival of over a year was reported for patients who could tolerate the toxicity of TE treatment. HAART is becoming increasingly widely available in sub-Saharan Africa, where the majority of HIV-infected patients live. Many patients in Africa are diagnosed with HIV only after developing opportunistic infections such as TE. Hence, the optimal management of opportunistic infections such as TE is important if the benefits of subsequently initiating HAART are to be seen.

Objectives

The purpose of this review is to determine the most effective therapy for TE in HIV-infected adults. Different treatment regimens have been compared with regard to clinical and radiological response, mortality, morbidity, and serious adverse events.

Search methods

A comprehensive search of relevant databases and other sources was conducted to identify relevant studies.

Selection criteria

Randomised double-blinded trials were included.

Data collection and analysis

Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software.

Main results

Three trials were found to meet the inclusion criteria. Dannemann et al 1992 and Katlama et al 1996 compared pyrimethamine plus sulfadiazine (P+S) with pyrimethamine plus clindamycin (P+C). Torre 1998 compared P+S with trimethoprim-sulfamethoxazole (TMP-SMX). For the purposes of this review, clinical outcomes were analysed as complete or partial resolution vs. failure. Patients who crossed over or were lost to follow-up were analysed as failures.

Dannemann et al 1992 assessed 59 patients. Five of 26 (19%) patients randomised to P+C died in the first 6 weeks compared with 2 of the 33 (6%) patients randomised to P+S (relative risk (RR) 3.17; 95% CI 0.67-15.06). Complete or partial clinical response was obtained in 12 (46.2%) patients receiving P+C vs. 16 (48.5 %) patients receiving P+S (RR 0.95; 95% CI 0.55-1.64).

Katlama et al 1996 assessed 299 patients. Twenty-nine (19%) of the 152 patients randomised to P+C died compared with 22 (15%) of the 147 patients randomised to P+S (RR 1.27; 95% CI 0.77-2.11). We were unable to obtain data on the outcomes of patients who crossed over and therefore excluded these data from the analysis.

Dannemann et al 1992 and Katlama et al 1996 were analysed together for the outcome of death. The two treatment arms did not differ for death (RR 1.41; 95% CI 0.88-2.28).

Torre et al 1998 assessed 77 patients. There were no deaths during the study period. Twenty-eight (70%) of 40 patients randomised to TMP-SMX had a complete or partial clinical response compared with 26 (70%) of 37 patients randomised to P+S (RR 1.0; 95% CI 0.74-1.33).

Authors' conclusions

The available evidence fails to identify any one superior regimen for the treatment of TE. The choice of therapy will often be directed by available therapy. Given the current evidence, TMP-SMX appears to be an effective alternative therapy for TE in resource-poor settings where P+S are not available.

 

Plain language summary

Management of toxoplasmic encephalitis in HIV-infected adults (with an emphasis on resource-poor settings)

Cerebral toxoplasmosis, or toxoplasmic meningoencephalitis (TE), was one of the first opportunistic infections to be described in patients infected with human immunodeficiency virus (HIV). Treatment of TE has been relatively successful in comparison to other opportunistic infections. Prior to the introduction of highly active antiretroviral therapy (HAART), a median survival of over a year was reported for patients who could tolerate the toxicity of TE treatment. HAART is becoming increasingly widely available in sub-Saharan Africa, where the majority of HIV-infected patients live. Many patients in Africa are diagnosed with HIV only after developing opportunistic infections such as TE. Hence, the optimal management of opportunistic infections such as TE is important if the benefits of subsequently initiating HAART are to be seen. The purpose of this review is to determine the most effective therapy for TE in HIV-infected adults. Different treatment regimens have been compared with regard to clinical and radiological response, mortality, morbidity, and serious adverse events. Three trials were found to meet the inclusion criteria for this review. Two trials compared pyrimethamine plus sulfadiazine (P+S) with pyrimethamine plus clindamycin (P+C). One trial compared P+S with trimethoprim-sulfamethoxazole (TMP-SMX)

The available evidence fails to identify any one superior regimen for the treatment of TE. The choice of therapy will often be directed by available therapy. Given the current evidence, TMP-SMX appears to be an effective alternative therapy for TE in resource-poor settings where P+S are not available.

 

摘要

背景

感染人類免疫缺乏病毒的成人患有弓漿蟲腦炎的處理(特別在資源不足的環境)

大腦弓漿蟲病或是弓漿蟲腦膜腦炎(以下簡稱TE)是人類免疫缺乏病毒(HIV)感染患者首先被發現的伺機性感染的其中之一。相對於其他伺機性感染，弓漿蟲腦炎的治療是比較成功的。在使用高效能抗反轉錄病毒治療法(HAART)的時代之前，曾有報告指出對可以忍受TE治療的病人，平均存活超過一年。在撒哈拉沙漠以南的非洲地區，大部分的HIV感染患者住在這個地區，愈來愈多患者可以負擔接受HAART。在非洲，很多病人被診斷出有HIV感染是在已經發展出伺機性感染像是弓漿蟲腦炎之後才診斷出來。因此，一開始伺機性感染像是TE的理想的處置是很重要的，否則我們將看不見隨後啟始HAART的效益。

目標

這篇回顧的目標是為了決定對於在HIV感染的成人上，對於他們感染了TE最有效的治療方法。比較不同的治療法在臨床上、放射學上的反應以及死亡率、罹病率以及嚴重併發症等方面的差異。

搜尋策略

經由廣泛搜尋相關資料庫及其他醫學資源以找出相關之研究報告。

選擇標準

包含了隨機雙盲試驗。

資料收集與分析

資料使用了標準化形式的萃取並使用了Rev Man 4.2.7的軟體的分析。

主要結論

三個試驗符合了納入的條件。Dannemann等人在1992年 和Katlama等人在1996年比較了pyrimethamine plus sulfadiazine (P+S)和pyrimethamine plus clindamycin (P+C)。Torre在1998年比較了P+S和trimethoprimsulfamethoxazole (TMPSMX)。為了這篇回顧的目標，我們分析比較完全或部分臨床緩解比上完全或部分臨床失敗的結果。途中換組或者失去追蹤的病人被分析為失敗。Dannemann等人在1992年評估了59位病患。隨機分配到P+C組的26個病人有五個(19%)在前六週死亡而隨機分配到P+S組的33個病人有2個(6%)在前六週死亡(relative risk (RR) 3.17; 95% CI 0.67 – 15.06)。接受P+C的病人有12個(46.2%)獲得完全或部分臨床反應比上接受P+S的病人有16個(48.5 %)獲得完全或部分臨床反應(RR 0.95; 95% CI 0.55 – 1.64)。Katlama等人在1996年評估了299位病人。隨機分配到P+C組的152個病人有29個(19%)病人死亡而隨機分配到P+S組的147個病人有22個(15%)病人死亡(RR 1.27; 95% CI 0.77 – 2.11)。我們無法獲得途中換組病人的結果並從分析中排除這些資料。Dannemann等人在1992年和Katlama等人在1996年的資料被一起合併分析去評估死亡的結果。這兩種治療對於死亡並沒有差異(RR 1.41; 95% CI 0.88 – 2.28)。Torre等人在1998年評估了77位病人。研究期間無並人死亡。隨機分配到TMPSMX 組的40個病人有28個(70%)有完全或部分臨床反應而隨機分配到P+S組的37個病人有26個(70%)病人有完全或部分臨床反應(RR 1.0; 95% CI 0.74 – 1.33)。

作者結論

目前現有的證據無法確認哪一種處方對弓漿蟲腦炎是較好的治療方法。治療的選擇時常是根據可獲得的治療來做決定。目前的證據顯示，在無法提供P+S治療的資源缺乏地區，TMPSMX是一個對於弓漿蟲腦炎有效的替代治療法。

翻譯人

本摘要由臺北榮民總醫院林晉皓翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

大腦弓漿蟲病或是弓漿蟲腦膜腦炎(TE),是HIV感染患者最早被發現的伺機性感染之一。相對於其他伺機性感染，TE的治療是比較成功的。在使用HAART的時代之前，曾有報告指出對可以忍受TE治療的病人，平均存活超過一年。在撒哈拉沙漠以南的非洲地區，大部分的感染人類免疫缺乏病毒的病人住在這個地區，高效能抗反轉錄病毒治療法變的廣泛的可獲得。在非洲，很多病人被診斷出有HIV感染是在已經發展出伺機性感染像是弓漿蟲腦炎之後才診斷出來。因此，一開始伺機性感染像是TE的理想的處置是很重要的，否則我們將看不見隨後啟始HAART的效益。這篇回顧的目標是為了決定對於在HIV感染的成人上，對於他們感染了TE最有效的治療方法。比較不同的治療法在臨床上、放射學上的反應以及死亡率、罹病率以及嚴重併發症等方面的差異。三個試驗符合了這篇回顧的包含條件。兩個試驗比較了pyrimethamine plus sulfadiazine (P+S)和pyrimethamine plus clindamycin (P+C)。一個試驗比較了P+S和trimethoprimsulfamethoxazole (TMPSMX)。可獲得的證據無法確認哪一種TE的治療方法較好。治療的選擇時常是根據可獲得的治療來做選擇。目前的證據顯示，TMPSMX是一個有效的對於TE的替代治療法，尤其是在P+S不可獲得的資源缺乏地區。