梅毒的家庭測試在 COVID 之後獲得支持
隨著性傳播感染病例的增加，研究人員希望自我檢測—因大流行而普及—能夠阻止這一趨勢。
資料來源：19 May 2022 / NEWS / Nature / 財團法人台灣紅絲帶基金會編譯
一些家庭梅毒檢測還可以檢測出多種其他感染，例如 HIV 和C型肝炎。圖片: Pixel-shot/Alamy
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全球性傳播感染 (STI) 病例在有些國家中呈上升趨勢。甚至於在COVID-19 大流行時，以多種方式封鎖的生活，也沒有阻止這一趨勢。 4 月，美國疾病控制和預防中心說，大流行的第一年有 133,945 例梅毒報告病例，自 2016 年以來增加了 52%。
CDC 表示，這可能被低估了，因為在大流行開始時衛生保健診所不得不限制親自就診，而 STI 監測計畫亦發現他們的資源被轉移到了其他地方。這種情況引發了對梅毒和其他性傳播感染之家庭測試的推動。
受 COVID-19 在家檢測流行的鼓舞，自我檢測已被包括決策者和處在邊緣之人群在內的許多人所接受。 1 月，加利福尼亞州的一項法律生效，要求私人健康保險公司承擔家庭 STI 檢測的費用。支持者說，自我檢測的好處是允許個人在家中有隱私的收集樣本，不受任何可能與就診有關的污名，而且它允許來自不同背景和收入水準的人經常地檢測。
疫情再起：
在過去二十間美國梅毒的病例數在朝著減少進展並維持降低之趨勢後，感染案例又爬升回警戒水準；即使在2020年，新冠肺炎流行的頭一年，當時民眾相對地隔離，病例數仍上升。原因很複雜，包括性健康診所經費的刪減及物質的濫用，其他國家亦發現梅毒病例水準增加之現象。
資料來源：美國疾病控制和預防中心。
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但阿拉巴馬大學伯明翰分校的婦科醫生 Shweta Patel 警告說，這種轉變也可能帶來一些權衡取捨問題——其中一些與 COVID-19 的經歷相似。在家檢測時，人們不會接受到由他人檢測所帶來的諮詢，公共衛生部門亦可能會丟失有價值的統計數據。 Patel 說，使用者必須報告自己的結果，並自己執行接觸者追踪，以告知其他人他們可能需要測試，但這並不總是會發生。
儘管如此，於華盛頓特區的全國各州和地區愛滋病主任聯盟計畫的副執行主任娜塔莉·克萊默 (Natalie Cramer) 說，在大流行期間，對 COVID-19 的自我檢測被證明是有用的。她補充說道，對包括梅毒和愛滋病毒在內的性傳播感染採取類似方法已經是過去式了。「我認為我們都對自我進行測試COVID變得更加自在」，克萊默說。「它兼顧地打開了人們對它的需求和舒適度」。
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病原體解剖學
大約半個世紀以來，梅毒一直是最廣為人知的——也是最令人恐懼的——性傳播感染之一。它促進了第一種被稱為「靈丹妙藥」藥物的開發（1910 年，salvarsan，一種砷基化合物，註1），並於 30 年後青黴素問世以來，它在很大程度上被認為是可以治癒的。透過正確使用保險套，疾病傳播可以減少到趨近於零。然而，如果不及時治療，這種疾病可能會致命，導致嚴重的神經系統問題，尤其是在出生時或出生前傳播的情況下。
許多梅毒檢驗可檢測包括針對螺旋狀梅毒螺旋體在內的細菌家族之抗體。
圖片來源：Kari Lounatmaa 博士/Science Photo Library
澳大利亞墨爾本大學的微生物學家黛博拉·威廉姆森 (Deborah Williamson) 花了幾十年的時間研究梅毒，她說，檢測這種由螺旋狀細菌之梅毒螺旋體引起的疾病很容易。在診所，衛生保健工作者通常會採集血樣並進行檢測，以尋找針對包括梅毒螺旋體在內的細菌家族之抗體。如果該化驗結果為陽性，則臨床醫生會對原始樣本歸零並進一步測試，以進行診斷。
只有一小部分測試需要對開放性潰瘍或身體其他區域進行拭子採樣，實際上是在尋找細菌本身，無論是在顯微鏡下尋找它還是識別其 DNA 或蛋白質的片段。然而，無論採用何種方法，如果一個人檢測呈陽性，則治療需要醫生的處方，Patel 說。
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測試朝向DIY
當 COVID-19 大流行到來時，世界各地的臨床檢測受到了衝擊。例如，隨著 2020 年第二季度紐約市 SARS-CoV-2 感染率飆升，性傳播感染之檢測急劇下降。診所限制就診，人們亦不願在可能感染 COVID-19 的場所看醫生。 STI 傳播開始上升。華盛頓特區全國性病主管聯盟之臨床和性健康主任 Jennifer Mahn 說，儘管這些變化是必要的，但「創造了一場完美風暴」。
快速冠狀病毒檢測：疑惑者之指引
但大流行也催生了家庭測試的熱潮。各國政府開始推廣在家中進行 COVID-19 測試，作為人們在旅行或社交之前檢查自己是否具有傳染性的一種方式。各種研究顯示，頻繁的自我檢測，即使是只有在病毒載量高時才能檢測到感染的快速抗原檢測，也有助於公共衛生反應。此舉還使醫生、研究人員和公眾對一般家庭檢測試劑盒的準確性和實用性更加放心。
支持者希望家庭 COVID-19 測試的普及將促進家庭 STI 測試的使用和需求。研究顯示，這些可能很受歡迎。例如，2021 年 4 月首次發表的辛巴威男男性行為者之研究顯示，參與者渴望自我檢測梅毒。
研究之合著者、位於哈拉雷的 Pangea Zimbabwe AIDS Trust 的高級項目經理 Definate Nhamo 說，家用試劑套組將大大地朝向協助這些男性獲得檢測服務。「他們可以在 20-30 分鐘內得到結果，他們不需要忍受一些醫療保健提供者的消極態度」。
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測試的準確度
2012 年，美國食品和藥物管理局批准了其首個家庭 HIV 檢測，該檢測可檢測唾液中的 HIV-1 和 HIV-2 抗體。使用者可以在幾分鐘內獲得結果，而無需將樣品送到實驗室。該測試並不像最初預期的那樣受歡迎，其價格高達 40 美元至 50 美元。然而，它激發了針對其他 STI 檢測的類似倡議：梅毒自檢在 2010 年代後期開始出現。
美國新生兒梅毒病例飆升至 20 年新高
家庭梅毒測試和他們相對應之以診所為基礎之檢驗一樣，可檢測血液樣本中針對包括梅毒螺旋體在內的細菌家族之抗體。但他們只需要一滴血，而不是一管。它們的功能就像血糖檢查和家庭妊娠試驗之間的混合體。
其他自我管理的梅毒測試要求使用者從他們的口腔、肛門和生殖器上分別取拭子，然後將樣本送到臨床實驗室進行分析。這些試劑盒直接檢測梅毒感染期間的細菌蛋白片段或細胞分泌的物質。如果使用得當，某些檢測的敏感性（真陽性率）和特異性（真陰性率）可與臨床檢測相媲美——超過 98%。然而，北卡羅來納大學教堂山分校的傳染病流行病學家 Weiming Tang 說，結果可能需要幾天時間才能收到，這使得它們在每次性接觸之前的測試不太有用。
一個缺點是試劑盒通常很貴，起價 50 美元，有些選項的價格超過 100 美元——儘管有些包含對多種 STI 的測試。在幾分鐘內提供結果的家庭測試的另一個缺點是臨床試驗發現在不同批次和使用者之間存在差異。
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自我檢測之挑戰依然存在
梅毒自我檢測的推動也帶來了與 COVID-19 大流行相呼應的公共衛生挑戰。克萊默說，任何家庭測試的準確性都取決於使用者收集樣本的能力，無論是用於 SARS-CoV-2 的鼻咽拭子還是用於梅毒的生殖器拭子。也許對某些人來說最令人擔憂的是，家庭測試缺乏基於診所的測試所帶來的諮詢和接觸者追踪，尤其是對於梅毒等性傳播感染。
快速冠狀病毒檢測：他們能做的和不能做的是什麼
克萊默說，雖然自我檢測的結果不會自動上傳到公共衛生數據庫，但這可能不會導致報告出現預期的如此大的下降。她見過的許多使用家庭測試的人無論如何都不會去診所進行測試，因此他們所關注的數據不會出現淨損失。此外，人們仍然需要與醫療保健系統接觸才能接受到治療，這也為追踪感染和追踪接觸者提供了另一個機會。一些自我檢測程序會向檢測呈陽性的人發送抗生素處方，而無需正式就診。加利福尼亞州里奇蒙 Springboard 衛生實驗室的執行長簡·赫克特 (Jen Hecht) 說，總體而言，家庭測試比沒有測試要來得好。
在大流行期間，促進在家中使用梅毒檢測試劑盒的舉措已經興起。在美國，赫克特正在試驗一項向註冊登記的人免費發送 STI 檢測套組的計劃。重要的是，該計劃還提供電話諮詢，並將使用者與當地公共衛生部門聯繫起來，以進行後續之追蹤和接觸者追踪。
「我們看到了很多積極的案例，這向我們顯示，我們正在接觸一群真正需要這種服務的人」，赫克特說。「我們希望能夠盡可能的讓人們簡便地取得」。
註1. 灑爾佛散（德語：Salvarsan），也稱作砷凡納明（英語：Arsphenamine）或606，是第一種有效治療梅毒的有機砷化合物，又用於治療昏睡病，還是第一種現代化學治療藥物，1910年代初投入應用。
Home testing for syphilis gains support in wake of COVID
資料來源：19 May 2022 / NEWS / Nature / 財團法人台灣紅絲帶基金會編譯
With cases of sexually transmitted infections growing, researchers hope self-tests — made popular by the pandemic — could stem the tide.
Some at-home syphilis tests also detect multiple other infections, such as HIV and hepatitis C. Credit: Pixel-shot/Alamy
Global cases of sexually transmitted infections (STIs) have been on the rise in some countries. Even the COVID-19 pandemic — which locked down life in many ways — hasn’t halted the trend. In April, the US Centers for Disease Control and Prevention reported that the first year of the pandemic saw 133,945 cases of syphilis, a 52% increase since 2016 (see ‘Resurgence’).
And this is probably an underestimate, the CDC says, given that health-care clinics had to limit in-person visits at the start of the pandemic, and STI surveillance programmes found their resources shifted elsewhere. The situation sparked a push for at-home tests for syphilis and other STIs.
Encouraged by the popularity of at-home tests for COVID-19, self-testing has been embraced by many, including policymakers and people in marginalized populations. In January, a California law went into effect that requires private health insurers to cover the cost of at-home STI testing. Supporters say that self-testing has the benefit of allowing individuals to collect samples in the privacy of their homes, free from any stigma that might be associated with attending clinics, and that it allows people from all backgrounds and income levels to test frequently.
Source: US Centers for Disease Control and Prevention.
But the shift could also have trade-offs — some of them similar to those experienced for COVID-19, cautions Shweta Patel, a gynaecologist at the University of Alabama at Birmingham. With at-home tests, people do not receive the counselling that comes with in-person testing, and public-health departments might lose valuable statistics. Users must report their own results, and perform their own contact tracing to inform others that they might be in need of testing, Patel says, and this doesn’t always happen.
Still, during the pandemic, self-testing for COVID-19 proved to be useful, says Natalie Cramer, deputy executive director of programmes at the National Alliance of State and Territorial AIDS Directors in Washington DC. She adds that it’s past time for a similar approach to be taken for STIs including syphilis and HIV. “I think we’ve all become more comfortable self-testing with COVID,” Cramer says. “It’s opened up both a need and a comfort level that folks have around it.”
Anatomy of a pathogen
For around half a millennium, syphilis has been one of the most widely recognized — and feared — STIs. It spurred the development of the first drug dubbed a magic bullet (salvarsan, an arsenic-based compound, in 1910) and, since the advent of penicillin three decades later, has largely been considered curable. With proper condom use, disease transmission can be reduced to near zero. Left untreated, however, the disease can prove deadly, causing severe neurological issues, especially if transmitted at or before birth.
Many syphilis tests detect antibodies against the bacterial family that includes the corkscrew-shaped Treponema pallidum.Credit: Dr Kari Lounatmaa/Science Photo Library
Detecting the disease, which is caused by the corkscrew-shaped bacterium Treponema pallidum, is easy enough, says Deborah Williamson, a microbiologist at the University of Melbourne in Australia, who has spent several decades studying syphilis. At a clinic, a health-care worker usually takes a blood sample and runs an assay to look for antibodies against the bacterial family that includes T. pallidum. If this assay is positive, the clinician runs further tests on the original sample to zero in on a diagnosis.
Only a small subset of tests, which require swabs of open sores or other regions of the body, actually look for the bacterium itself, whether searching for it under a microscope or identifying bits of its DNA or protein. Regardless of the method, however, if a person tests positive, treatment requires a physician’s prescription, Patel says.
Testing goes DIY
When the COVID-19 pandemic arrived, clinic-based testing around the world took a hit. For instance, as rates of SARS-CoV-2 infection soared in New York City in the second quarter of 2020, STI testing sharply declined. Clinics restricted visits, and people hesitated to see physicians in spaces where they might contract COVID-19. STI transmission began to rise. Although necessary, these changes “created a perfect storm”, says Jennifer Mahn, director of clinical and sexual health at the National Coalition of STD Directors in Washington DC.
Rapid coronavirus tests: a guide for the perplexed
But the pandemic also spawned a boom in at-home testing. Governments began promoting at-home COVID-19 testing as a way for people to check whether they might be contagious before travelling or socializing. A variety of studies showed that frequent self-testing, even with rapid antigen tests that could detect infections only when viral load was high, could aid the public-health response. The move also made physicians, researchers and the public more comfortable about the accuracy and utility of home-testing kits in general.
Proponents hope that the popularity of at-home COVID-19 testing will boost the use of and demand for at-home STI tests. Research shows that these could be popular. For instance, a study of men who have sex with men in Zimbabwe, first published in April 2021, showed that the participants were eager to self-test for syphilis.
At-home kits would go a long way towards helping these men access testing services, says study co-author Definate Nhamo, senior programmes manager at Pangaea Zimbabwe AIDS Trust in Harare. “They can get a result within 20–30 minutes and they do not need to endure some of the health-care providers’ negative attitudes.”
Test accuracy
In 2012, the US Food and Drug Administration approved its first at-home test for HIV, which detects antibodies against HIV-1 and HIV-2 in saliva. Users could get results in minutes, without having to send samples to a laboratory. The test was not as popular as first expected, and its price was high at US$40–$50. However, it inspired similar initiatives for other STIs: syphilis self-tests began appearing in the late 2010s.
Syphilis cases in US newborns spike to 20-year high
Like their clinic-based counterparts, at-home syphilis tests detect antibodies against the family of bacteria that includes T. pallidum in a blood sample. But they require only a drop of blood, rather than a tubeful. They function like a hybrid between a blood-glucose check and a home pregnancy test.
Other self-administered syphilis tests ask users to take separate swabs of their mouth, anus and genitals, and send the samples to a clinical lab for analysis. These kits directly test for pieces of bacterial protein from T. pallidum, or for substances secreted by cells during syphilis infection. When used correctly, some tests can have sensitivities (true positive rates) and specificities (true negative rates) comparable to those of clinic-based tests — above 98%. Results, however, can take several days to receive, which makes them less useful for testing before every sexual encounter, says Weiming Tang, an infectious-disease epidemiologist at the University of North Carolina at Chapel Hill.
One drawback is that kits are often pricey, starting at $50, with some options costing over $100 — although some include tests for multiple STIs. Another drawback for the at-home tests that provide results within minutes is that clinical trials have found variabilities across different lots and users.
Self-test challenges remain
The push for syphilis self-testing is also creating public-health challenges that echo those from the COVID-19 pandemic. The accuracy of any at-home test depends on how well the user can collect the sample, Cramer says, whether it’s a nasopharyngeal swab for SARS-CoV-2 or a genital swab for syphilis. Perhaps most concerning to some is that home tests lack the counselling and contact tracing that come with clinic-based tests, especially for STIs such as syphilis4.
Fast coronavirus tests: what they can and can’t do
Cramer says that although the results of self-testing aren’t automatically uploaded to public-health databases, that might not cause such a big drop in reporting as expected. Many people whom she has seen use at-home tests wouldn’t go to a clinic for testing anyway, so there would be no net loss in data where they are concerned. Furthermore, people still need to engage with the health-care system to receive treatment, which provides another opportunity to track infections and trace contacts. Some self-testing programmes send antibiotic prescriptions to people who test positive, without the need for a formal clinic visit. Overall, society is better off with at-home tests than without them, says Jen Hecht, executive director at Springboard HealthLab in Richmond, California.
Initiatives to promote the use of at-home syphilis test kits have picked up steam during the pandemic. In the United States, Hecht is trialling a programme to send free STI kits to people who sign up. Importantly, the programme also provides phone counselling and connects users with local public-health departments for follow-up and contact tracing.
“We’re seeing quite a number of positive cases, which is indicating to us that we’re reaching a group of people who really needed this kind of service,” Hecht says. “We want to be able to make it as easy as possible for folks to access.”
Nature 605, 598-599 (2022)
doi: https://doi.org/10.1038/d41586-022-01363-1
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