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大家好
-Hello,

我是Arnaud Trébucq
I am Arnaud Trébucq,

为法国巴黎国际防痨
working for the International Union Against Tuberculosis

和肺部疾病联合会工作
and Lung Disease based in Paris, France.

我将谈谈耐多药结核病（multiple drug resistant tuberculosis,
I will speak about the short-course treatment for multidrug-resistant tuberculosis.

简称“MDR-TB”）的短期疗法
During the 1990s,

在20世纪九十年代
the problem of resistance to rifampicin appeared

出现了利福平耐药性的难题
and the WHO, in 2006,

世界卫生组织（World Health Organization, 简称“WHO”）
published some guidelines

于2006年发行了
on how to treat the resistance to rifampicin.

利福平耐药性的治疗指南最基本的建议是
The minimal recommendations were

注射剂应持续
that the injectable agent should be continued

至少6个月 且在患者首次变为痰涂片阳性
for at least 6 months and at least 4 months

或培养阴性后至少4个月
after the patient first becomes and remains sputum smear-positive or culture-negative.

治疗应在培养转阴后持续至少18个月
And treatment should last for at least 18 months after culture conversion.

治疗指南于2008年
There were some updates to these guidelines

和2011年进行部分更新
in 2008 and 2011

但推荐的治疗方案没有变化
but there were still going for the same recommendations.

问题在于这种方案的疗效
The problem is the efficacy of this regimen.

从这个图表可以看出
You can see on this figure

根据WHO全球结核病报告
that the success rate in 2015 according to the WHO Global TB Report,

2015年的治疗成功率在50％左右
is around 50%.

同样的道理 单纯使用一线药物方案
Same thing with regimens using only first-line drugs and same thing

当您从9 000多例MDR-TB患者中
also when you take individual patients

非常认真地追踪随访个别患者时
from more than 9 000 MDR-TB patients very carefully followed,

仍然只有约50％的治愈率
you still have around 50% cured only.

后续的失败总是一个问题
You have a lot of loss of follow-up which is always a problem,

特别是造成广泛耐药肺结核(Extensive Drug Resistant TB, 简称“XDR-TB”)
especially at the origin of creating XDR-TB,

只使用一线药物而不使用二线药物时
a lot of failure when you are using only first-line drugs

很容易出现失败
and no second-line drugs.

所以
So,

我们能做些什么
what can we do?

我们必须做出改变
We have to change something.

实际上
In fact,

孟加拉国的Armand Van Deun的研究小组
the light came from Bangladesh where Armand Van Deun's team invented,

1997年起开展不同的治疗方案
after several different regimens lasting different times,

及不同的疗程
using different drugs during the intensive phase

且在强化期和继续期使用不同的药物的研究
and the continuation phase at the beginning of 1997,

并在2010年发表了一篇关于治疗方案的论文
they published a paper in 2010 with this regimen.

这个为期9个月的方案
This 9-month regimen

也被称为孟加拉方案
is also called the Bangladesh regimen

前4个月使用卡拉霉素 加替沙星
with four months kanamycin, gatifloxacin,

丙硫异烟胺 异烟肼 氯法齐明
prothionamide, isoniazid, clofazimine,

乙胺丁醇和吡嗪酰胺
ethambutol, pyrazinamide,

之后5个月使用加替沙星
followed by five months gatifloxacin,

氯法齐明 乙胺丁醇和吡嗪酰胺
clofazimine, ethambutol, pyrazinamide.

给予206个病人这个方案
And this regimen for 206 patients

治疗成功率为87.9%
gave 87.9% success rates,

远高于之前的50%
much, much better than what we had with a 50% success rate.

失败率仅5.8%
Only 5.8% failure rate,

5%的病人死亡
5% died,

0.5%失访
0.5% loss of follow-up,

以及极少数的0.5%复发
very few, and 0.5% relapsed.

在治疗MDR-TB领域
Really, that was a big change

这真的是一个巨大的改变
in the field of MDR-TB treatment.

了解这些结果后
Knowing these results,

我们于2008年在贝宁
we launched some studies in Benin,

喀麦隆和尼日尔开展了一些研究
Cameroon and Niger in 2008

其方案与孟加拉方案相似
with a regimen a bit similar to the one in Bangladesh,

但有一些差异
but with some differences

研究的治疗方案疗程是12个月
because it lasted 12 months

而不是9个月
instead of 9.

强化期疗程延长了
So the continuation phase was prolonged and also,

对于加替沙星 我们使用的是正常剂量
we used the normal dosage of gatifloxacin

而不是孟加拉方案中的两倍剂量
instead of a double dosage as in Bangladesh.

另外在喀麦隆
Plus in Cameroon,

我们在强化期使用了丙硫异烟胺
we used prothionamide during the continuation phase.

结果显示 尼日尔的治疗成功率为89％
The results showed 89% cured in Niger,

喀麦隆的治疗成功率为89％
89% cured in Cameroon.

这证明了孟加拉的优秀成果
Excellent results which were confirming what we had in Bangladesh.

2013年
We were interested to launch another study

我们在非洲撒哈拉以南的9个国家
using more or less exactly the same regimen than in Bangladesh

开展另一项研究
in nine countries of sub-Saharan Africa,

采用大致相同的治疗方案
and it began in 2013.

同样是9个月的疗程
It was the same 9-month regimen

但加替沙星被替换为莫西沙星
but gatifloxacin was replaced by moxifloxacin

因为莫西沙星比加替沙星更好用
because it was easier to use moxifloxacin than gatifloxacin.

另外 我们还使用了正常剂量的莫西沙星
And we also used moxifloxacin at normal dosage

而不是孟加拉方案中的两倍剂量
and not double dosage as in Bangladesh.

在贝宁 布基纳法索 布隆迪
Benin, Burkina Faso, Burundi,

喀麦隆 中非共和国 科特迪瓦
Cameroon, Central African Republic, Côte d'Ivoire,

刚果民主共和国
DR Congo,

尼日尔和卢旺达也开展了这项研究
Niger and Rwanda were involved in this study.

结果呢
The results?

治疗成功率为82%
82% success rate.

再一次证明这种治疗方案非常好
Once more, we showed that this regimen was excellent.

还有关于这种方案的更多详细内容
More details about this regimen.

在非洲
We were in Africa

结核病患者中HIV阳性率为10％
and HIV-positive patients were 10%

有200例
and we had 200 cases.

在死亡率方面是个大问题
We had a big problem with the death rate.

HIV阳性的患者 死亡率是19%
The death rate was 19% among the HIV-positives

而阴性的患者是5%
against 5% among the HIV-negatives.

显然
Obviously,

即使他们接受了抗逆转录病毒治疗
patients died much more when they were HIV-positive,

HIV阳性的结核病患者死亡病例要多得多
even if they were receiving an antiretroviral treatment.

在那些幸存者中
Among those who survived,

从细菌学的角度来看
the treatment success from a bacteriological point of view

治疗的成功率与艾滋病病毒感染状态无关
did not differ according to HIV status,

均为令人信服的89％
89%, which is reassuring.

我们根据对不同药物的初始耐药性
We looked at the success rate

来判断治疗成功率
according to the initial resistance to the different drugs.

对异烟肼敏感和耐药的患者的治疗成功率
We had for INH almost the same success rate

几乎相同
among the susceptible and the resistant,

分别为88％和81％
88% and 81%.

在二线注射类药物中
Among the second-line injectable drugs,

敏感患者治疗成功率为81％
we had 81% among the susceptible

耐药患者为71％
and we had 71% among the resistant.

对于一个小数量患者群体中来说
The difference is not significant

差别并不显著
for a number that small.

对氟喹诺酮类药物敏感的患者
Among the fluoroquinolone patients,

治疗成功率较高
there was a much better success rate,

为82％
82% among the susceptibles,

在低水平耐氟喹诺酮类药物的患者中
much lower

治疗成功率低则得多
for the low-resistance patients

高度耐氟喹诺酮类药物的患者甚至更低
and even lower for the high-level resistance.

至于吡嗪酰胺
For pyrazinamide,

对吡嗪酰胺敏感的患者和耐药的患者
it was almost the same level of successs resistant

治疗成功率大致相同
or not to pyrazinamide,

分别为79％和82％
79% and 82%.

当您研究失败的危险因素时
When you study the risk factors for failures, for fluoroquinolone,

氟喹诺酮是主要的问题
that was the main problem.

那些被诊断为耐药的
We had 37% failures among those

包括低或高水平耐药的患者
who were considered resistant,

37％的患者治疗失败
low or high-level resistant.

敏感患者治疗失败率只有5％
Susceptibles, 5% only,

如此巨大的差异
so a huge difference,

是氟喹诺酮耐药性方面的大问题
a huge problem for fluoroquinolone resistance.

对于二线注射类药物
For second-line injectable,

我们没有发现治疗失败率的差异
we did not find a difference in failure rates.

对于异烟肼来说
For INH,

有更多的耐药性
there was a bit more resistance,

耐药患者中治疗失败更多
more failures among the resistants,

失败率7％
7%,

而敏感患者为1％
than among the susceptibles, 1%.

对于吡嗪酰胺
For pyrazinamide,

耐药患者的失败率为9％
we had 9% failure rate among the resistants,

敏感患者为5％
5% among the susceptibles,

差异不大
and the difference is not significant.

我们还研究了乙硫异烟胺
We also tested for ethionamide,

和乙胺丁醇的耐药性 HIV感染状态
ethambutol resistance, for HIV,

体重指数以及患病时间延长
for body mass index,

与治疗失败率的关系
for extension of the disease,

失败率差异不明显
and there was no significant difference for failure.

一些其它结果
Some other results.

死亡的危险因素是低体重指数
The risk factors for death were low body mass index,

影像学检测肺部病变范围大和年龄大
a large radiographic extent of pulmonary lesions, and older age.

上述三项都增加了
All increased the risk of death

除了感染HIV之外的死亡风险
independently of HIV status.

不良反应中
For the adverse events,

最严重的是听力损失
the most important one was hearing loss,

在治疗第4个月时的发生率为11％
11% at month 4.

延伸内容 我们的研究发现
Amplification: we documented 11 cases

559例在治疗开始时易感的患者
with acquisition of high fluoroquinolone resistance out of 559 patients

11例患者获得高度氟喹诺酮耐药性
who were susceptible at the initiation of treatment,

概率为2％
2%.

孟加拉的病例数量大得多
It is substantially larger than the single case in Bangladesh

多于500个
over more than 500 cases.

总之
In conclusion,

9个月的短期治疗方案疗效极佳
this short-course regimen of 9 months has an excellent efficacy,

已在多个大洲的一些国家得到证实
as has been proven in several countries on several continents.

现在得到了WHO的推荐
It is now recommended by the WHO.

即使对吡嗪酰胺
It works even if there is resistance to pyrazinamide,

乙胺丁醇和乙硫异烟胺耐药
to ethambutol, or to ethionamide.

这个治疗方案依然有效
It is probably better

使用双倍剂量的加替沙星
to use double dosage of gatifloxacin

和莫西沙星比单独使用可能更好
and moxifloxacin than a single one to avoid amplification

以避免增殖并克服氟喹诺酮的低水平耐药性
and to overcome low-level resistance to fluoroquinolone.

听力监视对于避免听力损失非常重要
Surveillance of hearing is very important to try to avoid hearing losses.

可能要强制要求直接面视下治疗
Directly-observed treatment is probably compulsory

因为要服用太多的药物
because there are so many drugs to swallow.

以下是一些人接受MDR-TB治疗前后的图片
Here is a picture of somebody who has been treated for MDR-TB before and after,

现在真的有希望控制MDR-TB
and there is really now hope for MDR-TB control.

谢谢
Thank you.