Vaccines for preventing malaria (pre-erythrocytic)

 

Abstract

Background

Vaccines against all stages of the malaria parasite are in development, mainly for Plasmodium falciparum, which causes the most serious form of malaria. Pre-erythrocytic vaccines act to prevent or delay a malaria attack by attacking the sporozoite and liver stages before the parasite reaches the bloodstream.

Objectives

To assess the efficacy and safety of pre-erythrocytic malaria vaccines against any type of human malaria.

Search methods

In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field.

Selection criteria

Randomized controlled trials comparing pre-erythrocytic vaccines with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection.

Data collection and analysis

Both authors independently assessed trial quality and extracted data. Results of meta-analyses were expressed as risk ratios with 95% confidence intervals (CI) using an intention-to-treat analysis.

Main results

Nine safety and efficacy trials, and two safety trials, with over 3000 participants were included. In semi-immune children, RTS,S vaccine reduced clinical episodes of malaria by 26% (95% CI 13% to 37%) and severe malaria by 58% (95% CI 15% to 79%) for up to 18 months. Prevalence of parasitaemia was also reduced by 26% (95% CI 11% to 38%) at six months after immunization. RTS,S also reduced clinical malaria episodes by 63% (95% CI 18% to 83%) in semi-immune adult men in the second year of follow up after a booster dose. No severe adverse events were judged to be related to RTS,S vaccine, although the frequencies of injection site pain, swelling, arm motion limitation, headache, and malaise were increased in the vaccine groups. There was no evidence for effect of the CS-NANP vaccines (307 participants, 3 trials), CS102 peptide vaccine (14 participants, 1 trial), or the ME-TRAP vaccine (372 participants, 1 trial).

Authors' conclusions

RTS,S vaccine was effective in preventing a significant number of clinical malaria episodes, including good protection against severe malaria in children for 18 months. No severe adverse events were attributable to the vaccine. Progression of this vaccine towards licensing is justified while efforts to increase its efficacy continue. The other vaccines do not look promising and further research is a priority.

 

Plain language summary

Vaccines for preventing malaria in the pre-erythrocytic phase

Malaria is a parasitic disease spread by mosquitoes. It affects millions of people worldwide and causes significant illness and mortality. The symptoms of uncomplicated malaria include fever, headache, muscle pain, and vomiting; and children commonly present also with rapid breathing, cough, and convulsions. Severe malaria leads to unconsciousness and death. Uncomplicated malaria can almost always be cured with appropriate drugs, given soon after symptoms appear, but in small children in particular, progression and death can come within 48 hours. The hope − bolstered by several decades of increasingly promising research − remains that one or more vaccines to prevent malaria will augment the existing malaria control tools. The expectation is that successful vaccines will decrease malaria incidence, but because of the complexity of the organism and other factors, protection will not be complete. The malaria parasite develops through several phases in the human body that evoke different immunologic responses, and vaccines for all phases are under development. This review looks at vaccines targeted at the 'pre-erythrocytic' phase of the parasite's life, the phase before the parasites first enter the bloodstream from the liver. Trials of four types of vaccine against P. falciparum, the most important human malaria species, were available for this review. One of these (the RTS,S vaccine) significantly reduced the number of episodes of clinical malaria and severe malaria in children, while the other three vaccines were not effective under the conditions of the trials. No severe adverse events observed following the RTS,S vaccination were judged to be related to vaccination, though minor adverse events like headache, swelling, and malaise were.

 

摘要

背景

用於預防瘧疾(紅血球感染之前)之疫苗

對抗所有階段之瘧疾寄生蟲疫苗皆正在研發之中，主要係針對惡性瘧原蟲(Plasmodium falciparum)，其會造成最嚴重形式之瘧疾。紅血球感染之前之疫苗係藉著在瘧疾寄生蟲到達血液之前及肝臟時期攻擊其孢子以預防或延遲瘧疾之發作。

目標

評估紅血球感染之前對抗任何類型人類瘧疾之瘧疾疫苗的功效及安全性。

搜尋策略

2006年3月, 我們搜尋 Cochrane Infectious Diseases Group Specialized Register, CENTRAL (Cochrane Library 2006, Issue 1)、 MEDLINE, EMBASE, LILACS,以及 Science Citation Index. We also searched研討會手冊以及文章的參考資料清單，並與本領域相關機構及研究人員聯繫。

選擇標準

針對接受人工挑戰或是天然接觸瘧疾感染之任何年齡試驗者，比較紅血球感染之前之疫苗與安慰劑、控制組疫苗、或慣常抗瘧疾控制措施的隨機對照試驗。

資料收集與分析

由2位作者獨立評估試驗品質並摘錄數據。整合分析之結果係使用治療意向分析法而以相對風險及95%信賴區間(confidence interval；CI)表示。

主要結論

共收錄包括超過3000名參與者之9項安全及功效試驗以及2項安全性試驗。在半免疫之兒童之中，於18個月內，RTS, S疫苗可減少26%之瘧疾臨床發生(95% CI 13% to 37%)並減少58%之嚴重瘧疾(95% CI 15% to 79%)。在免疫接種6個月後，寄生蟲血症之發生率亦降低26% (95% CI 11% to 38%)。在半免疫之成人之中，於加強免疫後第二年之追蹤中，RTS, S亦可減少63%之臨床瘧疾發生(95% CI 18% to 83%)。未有任何嚴重之不良作用被認為與RTS, S疫苗有關，但在疫苗組中仍有較高頻率之注射位置疼痛、腫脹、手臂運動限制、頭痛、及不適。並無證據指明CSNANP疫苗(307名參與者，3項試驗)、CS102?疫苗(14名參與者，1項試驗)、或METRAP疫苗(372名參與者，1項試驗)之效應。

作者結論

RTS, S疫苗可有效預防顯著數目之臨床瘧疾發生，包括對兒童之嚴重瘧疾提供18個月的良好保護。該疫苗並未造成任何嚴重之副作用。此種疫苗應可繼續進行其認證程序，並同時繼續努力提升其功效。其他疫苗似乎尚無有望之結果，進一步之研究應優先考慮。

翻譯人

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

總結

用於在紅血球感染之前預防瘧疾之疫苗。瘧疾是一種由蚊子傳播之寄生蟲性疾病。其影響全世界數以百萬計的人，並造成重大之疾病及死亡。非重症瘧疾之症狀包括發燒、頭痛、肌肉痛、及嘔吐；而兒童亦常具有呼吸急促、咳嗽、及痙攣之症狀。嚴重之瘧疾會造成昏迷及死亡。如在一發生症狀時立即給予適當之藥物，非重症瘧疾幾乎都可被治癒，但是特別就幼兒而言，其可在48小時內惡化及死亡。數十年來日益有望之研究所支持之希望仍是期待一或多種瘧疾疫苗可擴大既有之瘧疾控制工具。其雖期望成功之疫苗可降低瘧疾發生率，但是因為該微生物及其他因子之複雜性，仍無法取得完整之保護。瘧疾寄生蟲在人體內會經過數個發育期，各期皆引發不同之免疫反應，而針對所有發育期之疫苗皆仍在研發之中。本回顧係探究靶向瘧疾寄生蟲生命之「紅血球感染之前」的疫苗，亦即該等寄生蟲首次由肝臟進入血液前之階段。本回顧取得對抗惡性瘧原蟲(P. falciparum)之四種類型疫苗，其為最重要之人類瘧疾寄生蟲種類。其中1種疫苗(RTS, S疫苗)可顯著降低兒童之臨床瘧疾及嚴重瘧疾發生數目，而另外3種疫苗在該等試驗之條件下並無效用。在進行RTS, S疫苗接種後所觀察到之嚴重不良作用中，並無任何一種被判定為與該疫苗接種相關，但其會造成如頭痛、腫脹、及不適之輕微不良作用。