真菌感染比肺結核導致更多的愛滋病死亡—這便是我們可以著力的
Fungal infections cause more Aids deaths than tuberculosis –here’s what we can do about it
資料來源：David W. Denning /曼徹斯特大學曼徹斯特真菌感染小組首席研究員，格林威治標準時間 2022 年 2 月 9 日發佈，https://theconversation.com / 財團法人台灣紅絲帶基金會編譯
多哥洛美為 HIV 陽性患者分發藥物。羅伯特哈丁 / Alamy Stock Photo
儘管每年死於愛滋病的人數正在下降——從 2004 年的峰值 190 萬下降到 2020 年的 69 萬——但這仍然太多了。 2020 年，有 214,000 名愛滋病患者死於肺結核 (TB)，但只有約 50% 為確診病例，其餘病例不確定。在愛滋病和一般情況下，死於真菌病的人數可能多於死於結核病的人數。
隨著越來越多的人接受 HIV 感染治療，死亡人數將繼續下降。但下降的速度比應有的要慢，死亡人數下降緩慢的原因是真菌病。在開具 HIV 治療並給予工作時間之前，真菌病可能導致死亡。理想的做法是儘早發現 HIV 感染者，並在他們因免疫力下降而生病之前對其進行治療。不幸的是，這仍然是太多國家的願望：在許多地方，晚期 HIV 診斷幾乎是常態，新發現的 HIV 感染者中有 30% 到 60% 已經被診斷出患有愛滋病並且免疫系統受到嚴重損害。
目前，不同國家對抗 HIV 藥物的耐藥率在 5% 到 30% 之間。除非醫生發現這一點並轉換 HIV 療法，否則這些人的免疫力會從提高轉為下降。然後，他們罹患嚴重感染的風險增加，包括真菌病。正在引入長效可注射抗 HIV 藥物和具有較低耐藥傾向的新型抗病毒藥丸來解決這些耐藥率的問題，但這些益處需要數年時間才能產生。
以下是三種真菌感染，快速診斷可以產生真正的影響。
真菌性腦膜炎
一種特別致命的真菌感染是隱球菌性腦膜炎。這種真菌集中在鴿子糞便中，在世界各地都有發現。它會在被吸入人體時感染。通常情況下，免疫系統會破壞它，但在愛滋病患中，它會持續存在於肺部，然後在血液中傳播到大腦。這種真菌只需三到四個星期就可以殺死愛滋病患者。
然而，最好的診斷測試之一 – 花費約 4 美元（2.95 英鎊）的 10 分鐘橫向流程 -便可以在腦膜炎發作之前及早發現隱球菌感染。不幸的是，在許多國家，愛滋病毒診所和醫院尚未使用它後果很嚴重：每年有超過 120,000 人死於真菌性腦膜炎，其中 70% 是可以避免的。
真菌性肺炎
另一種毀滅性的真菌感染是肺囊蟲肺炎或 PCP，它在某些方面與 COVID 肺炎非常相似：咳嗽、呼吸困難加重、氧氣不足和 X 射線上的類似陰影。在 HIV 流行初期，大約五分之三的新診斷出患有愛滋病的人罹患 PCP，而現在它大約是七分之一。
人類肺囊蟲與人類在肺部共同進化，並通過咳嗽在人與人之間傳播。感染 HIV 的嬰兒特別容易感染 PCP，通常同時伴有細菌感染（會掩蓋 PCP）。 PCP 是一種難以在實驗室確認的診斷，非洲只有不到 15% 的國家使用最好的測試（甚至任何測試）進行診斷。 2020 年有近 100,000 名嬰兒死於愛滋病毒/愛滋病，其中許多肯定是死於 PCP，還有許多成年人，可能超過 100,000 人死亡。
模擬結核病的真菌
在美洲大部分地區、東南亞和非洲部分地區，蝙蝠和鳥糞（糞便）充滿了一種叫做組織胞漿菌的真菌。密西西比河沿岸和瓜地馬拉、千里達及托巴哥共和國、多明尼加共和國和許多其他地方的 25% 到 60% 的人口吸入了這種真菌而沒有生病。
但如果免疫失敗，真菌會重新激活（如結核病）並悄悄地傳播到骨髓（導致低血細胞計數）、肝臟、內臟和皮膚，導致在兩到三週內因播散性組織胞漿菌病而死亡。組織胞漿菌的重要性直到最近才被意識到，這要歸功於一種快速的尿液測試，該測試可以檢測到一種叫做半乳甘露聚醣的特殊糖，這種糖是真菌在體內釋放的。
一項針對瓜地馬拉 13 個 HIV 單位的 HIV 和愛滋病患者的為期三年的計劃發現，與結核病或隱球菌性腦膜炎相比，擴散性組織胞漿菌病患者更多。通過篩查這些感染，出現了幾個重要的教訓。結核病確診人數逐年下降，而結核病患者的存活率卻在上升，這意味著之前疑似結核病的一些診斷是錯誤的，很可能是組織胞漿菌病。組織胞漿菌病病例數逐年上升，生存率也有所提高。
總體而言，該診斷篩查計劃顯示，從第一年到第三年，愛滋病毒死亡人數減少了 7%。這是快速診斷真菌病對公眾健康有益的首次證明。
酵母樣真菌組織胞漿菌的孢子。科學圖片庫 / Alamy Stock Photo
沒有人知道有多少愛滋病患者會患上組織胞漿菌病，因為在世界上大多數地方都缺乏檢測。來自奈及利亞的最新數據顯示，在某些地方，組織胞漿菌病比隱球菌性腦膜炎更常見。鑑於組織胞漿菌在全球的分佈，先前已經提出了 100,000 例病例和 80,000 例死亡的估計。
結核病和 HIV 合併感染導致的死亡
結核病和 HIV 合併感染的死亡人數從 2010 年的 570,000 人下降到 10 年後的 214,000 人，這證明了病例發現的改進、更準確的檢測、預防性治療和更高的治療完成率。但是現在許多 HIV 研究人員看到更多的人被認為患有結核病，但他們的結核病檢測結果為陰性。其中一些人患有未確診的真菌病。
通常，HIV 患者的 TB 診斷更難以捉摸，肺部陰影較少且不明顯，並且沒有可檢測的痰液。一種新的具有更高敏感性的結核病尿檢將很快問世，這將使一些非常的結核病而擴播散性組織胞漿菌也極為常見的患者能夠更準確地診斷結核病。
總體而言，三種最常見可能致命的真菌感染在 HIV 患者中遠遠超過結核病病例，特別是當一些「結核病病例」根本不是結核病時。普遍缺乏對這三種感染的快速診斷導致了愛滋病所造成的死亡人數，其中有超過一半的死亡是可以避免的。
譯註：肺囊蟲肺炎(pneumocystis pneumonia，PCP)是一種潛在致命的感染，主要發生於免疫抑制的患者，包括HIV、器官移植、腫瘤(尤其是血液腫瘤)、長期用類固醇或免疫抑制劑等。肺囊蟲的生物學分類一直有相當多的爭議，目前根據基因分析，被歸類到真菌(ascomycetous fungi) 。
Fungal infections cause more Aids deaths than tuberculosis –here’s what we can do about it
Published: February 9, 2022 3.25pm GMT, https://theconversation.com/
David W. Denning/ Principal Investigator, Manchester Fungal infection Group, University of Manchester
Drug distribution for HIV positive patients, Lome, Togo. robertharding / Alamy Stock Photo
Even though annual deaths from Aids are coming down – from a peak of 1.9 million in 2004 to 690,000 in 2020 – that’s still way too many. In 2020, 214,000 people with Aids died of tuberculosis (TB), though only about 50% were confirmed cases while the rest were uncertain. More people probably die of fungal disease than of TB, both in the context of Aids and generally.
As more and more people are treated for HIV infection, deaths will continue to come down. But the fall is slower than it should be, and the reason for the tardiness of this decrease in deaths is fungal disease. Fungal disease can lead to death before treatment for HIV can be prescribed and given time to work. The ideal is to find people with HIV early and treat the virus before they become ill with declining immunity. Unfortunately, this remains an aspiration in too many countries: late HIV diagnosis is almost the norm in many places, with 30% to 60% of newly discovered HIV infections already diagnosed with Aids and hugely damaged immune systems.
Currently, resistance to anti-HIV drugs ranges from 5% to 30% in different countries. Unless doctors identify this and switch therapy for HIV, these people revert from improving to declining immunity. They then have an increased risk of severe infection, including fungal disease. Long-acting injectable anti-HIV drugs and new antiviral pills with a lower propensity for resistance are being introduced to address these resistant rates, but it will take years for the benefits to accrue.
Here are three fungal infections where rapid diagnosis could make a real difference.
Fungal meningitis
One particularly lethal fungal infection is cryptococcal meningitis. The fungus is concentrated in pigeon droppings and found across the world. It infects people when breathed in. Normally, the immune system destroys it, but in Aids, it persists in the lung and then travels in the bloodstream to the brain. It takes only three to four weeks for this fungus to kill someone with Aids.
Yet one of the best diagnostic tests – a ten-minute lateral flow costing about US$4 (£2.95) – can detect cryptococcal infection early, before meningitis sets in. Unfortunately, in many countries, HIV clinics and hospitals don’t yet use it and the consequences are grim: over 120,000 people die from fungal meningitis every year and 70% of those are avoidable.
Fungal pneumonia
Another devastating fungal infection is Pneumocystis pneumonia, or PCP, which is quite similar in some ways to COVID pneumonia: cough, increasing breathlessness, shortage of oxygen and similar shadows on the X-ray. In the early days of the HIV epidemic, about three in five people newly diagnosed with Aids had PCP, though now it is more like one in seven.
Pneumocystis co-evolved with humans in the lungs and is passed from person to person with coughing. Babies with HIV are especially vulnerable to PCP, often with bacterial infection alongside (obscuring PCP). PCP is a tricky diagnosis to confirm in the laboratory and less than 15% of countries in Africa use the best test (or even any test) for diagnosis. Nearly 100,000 babies died of HIV/Aids in 2020, many assuredly from PCP, along with many adults, probably over 100,000 deaths.
Fungus mimicking TB
Bat and bird guano (poop) is full of a fungus called Histoplasma in most of the Americas, south-east Asia and parts of Africa. Between 25% and 60% of the population along the Mississippi River and other spots like Guatemala, Trinidad and Tobago, Dominican Republic and many others have breathed in this fungus without becoming ill.
But if immunity fails, the fungus can re-activate (like TB) and travel silently to the bone marrow (causing low blood counts), liver, guts and skin, leading to death in two to three weeks from disseminated histoplasmosis. The importance of Histoplasma has only recently been realised thanks to a rapid urine test that detects a special sugar called galactomannan that the fungus releases in the body.
A three-year programme for HIV and Aids patients in 13 HIV units in Guatemala found more people with disseminated histoplasmosis than either TB or cryptococcal meningitis. By screening for these infections, several salient lessons emerged. The number of confirmed TB patients went down year on year, and the survival of TB patients went up, implying that some of the previously suspected TB diagnoses were wrong and probably histoplasmosis. The number of cases of histoplasmosis went up year on year, and survival also increased.
Overall, this diagnostic screening programme showed a decrease in HIV deaths of 7% from year one to year three. This was the first demonstration of the public health benefit of rapid fungal disease diagnosis.
Spores of the yeast-like fungus, Histoplasma. Science Photo Library / Alamy Stock Photo
No one knows how many people with Aids develop histoplasmosis because testing is so scarce in most of the world. Recent data from Nigeria shows that, in some localities, histoplasmosis is more common than cryptococcal meningitis. A prior estimate of 100,000 cases and 80,000 deaths has been proposed, given the global distribution of Histoplasma.
Deaths from TB and HIV co-infection
The fall in deaths from TB and HIV co-infection from 570,000 in 2010 to 214,000 ten years later is a testament to improved case finding, more accurate tests, preventative therapy and better treatment completion rates. But now many HIV researchers are seeing more people dying who were thought to have TB, but their tests for TB are negative. Some of these people have an undiagnosed fungal disease.
Often, the diagnosis of TB in HIV patients is elusive, with fewer and non-distinct lung shadows and no phlegm to test. A new urine test for TB with greater sensitivity will soon be available, which should allow more accurate TB diagnosis in the very patients in whom disseminated histoplasmosis is also most common.
Overall, the three most common potentially fatal fungal infections far outnumber TB cases in HIV patients, especially when some “TB cases” are not TB at all. The general lack of rapid diagnosis of these three infections contributes to the death toll from Aids, and well over half of these deaths are avoidable.