Wikipedia

Allurar rigakafin BCG

allurar rigakafi Bacillus Calmette-Guérin (BCG) Ya kasance wani allurar rigakafi ce da aka fi amfani da ita akan tarin fuka (TB). [1] An sanya masa suna ne bayan masu kirkirarsa Albert Calmette da Camille Guérin.[2][3] A cikin ƙasashen da tarin fuka ko kuturta ya zama ruwan dare, ana ba da shawarar kashi ɗaya a cikin jarirai masu lafiya da wuri-wuri bayan haihuwa.[1] A yankunan da tarin fuka ba ta zama ruwan dare ba, yara ne kawai da ke cikin haɗari sosai ke samun rigakafi, yayin da ake zargi da tarin fuki ana gwada su da kuma kula da su.[1] Manya waɗanda ba su da tarin fuka kuma ba a riga an yi musu rigakafi ba, amma ana nuna su akai-akai, ana iya yin musu rigakafin, kuma.[1] BCG kuma yana da tasiri a kan kamuwa da cutar Buruli ulcer da sauran cututtukan da ba na ƙwayoyin cuta ba.[1] Bugu da ƙari, wani lokacin ana amfani dashi a matsayin wani ɓangare na maganin ciwon daji.[4][5]

Allurar rigakafin BCG
vaccine type (en) Fassara
Bayanai
Ƙaramin ɓangare na Allurar rigakafin tarin fuka da heterologous vaccine (en) Fassara
Suna saboda Albert Calmette (mul) Fassara da Camille Guérin (mul) Fassara
Vaccine for (en) Fassara Tarin fuka
Pregnancy category (en) Fassara US pregnancy category C (en) Fassara
Described at URL (en) Fassara nytimes.com…
Subject has role (en) Fassara immunologic adjuvant (en) Fassara

Yawan kariya daga kamuwa da tarin fuka ya bambanta sosai kuma kariya tana ɗaukar shekaru 20.[1] Daga cikin yara, yana hana kusan 20% daga kamuwa da cuta kuma daga cikin waɗanda suka kamu da cuta, yana kare rabin daga kamuwa.[6] Ana ba da allurar rigakafin ta hanyar allura a cikin fata.[1] Babu wata shaida da ta nuna cewa ƙarin allurai suna da fa'ida.[1]

Sakamakon sakamako masu tsanani ba su da yawa. Sau da yawa, ja, kumburi, da ciwo mai sauƙi suna faruwa a wurin allurar.[1] Ƙananan ulcer na iya samuwa tare da wasu scarring bayan warkewa.[1] Sakamakon sakamako sun fi yawa kuma suna iya zama masu tsanani a cikin waɗanda ke da rigakafin rigakafi.[1] Kodayake ba a lura da mummunar tasiri a kan tayin ba, babu isasshen shaida game da amincin allurar rigakafin BCG a lokacin daukar ciki sabili da haka ba a ba da shawarar allurar rigakawa don amfani a lokacin daukar hoto.[1] An samo allurar rigakafin ne daga Mycobacterium bovis, wanda aka fi samunsa a cikin shanu.[1] Duk da yake an raunana shi, har yanzu yana da rai.[1]

An fara amfani da allurar rigakafin BCG a matsayin magani a shekarar 1921.[1] Yana cikin Jerin Magunguna Masu Muhimmanci na Hukumar Lafiya ta Duniya.[7] Ya zuwa shekara ta 2004, ana ba da allurar rigakafin ga kimanin yara miliyan 100 a kowace shekara a duniya.[8] Koyaya, ba a gudanar da shi a Amurka ba.[9][10]

Amfani da kiwon lafiya

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Cutar tarin fuka

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Babban amfani da BCG shine don rigakafin tarin fuka. Ana iya ba da allurar rigakafin BCG bayan haihuwa a cikin ciki.[11] Allurar rigakafin BCG na iya haifar da gwajin Mantoux na ƙarya.[12]

Abinda ya fi rikitarwa game da BCG shine ingancin canji da aka samu a cikin gwaje-gwaje daban-daban na asibiti, wanda ya bayyana ya dogara da yanayin ƙasa. Gwaje-gwaje da aka gudanar a Burtaniya sun nuna tasirin kariya na 60 zuwa 80%, amma waɗanda aka gudanar a wasu wurare ba su nuna wani sakamako na kariya ba, kuma inganci ya bayyana ya faɗi kusa da ma'auni.[13][14]

Wani bita na tsarin 1994 ya gano cewa BCG yana rage haɗarin kamuwa da tarin fuka da kusan 50%.[13] Bambance-bambance a cikin tasiri ya dogara da yankin, saboda dalilai kamar bambance-bambancen kwayoyin halitta a cikin yawan jama'a, canje-canje a cikin muhalli, fallasawa ga wasu cututtukan ƙwayoyin cuta, da yanayin a cikin dakin gwaje-gwaje inda aka girma allurar rigakafin, gami da bambance- bambance-gidan halitta tsakanin nau'ikan da ake al'ada da zaɓin matsakaici.[15][14]

Binciken tsari da meta-analysis da aka gudanar a cikin 2014 ya nuna cewa allurar rigakafin BCG ta rage kamuwa da cuta da kashi 19-27% kuma ta rage ci gaba zuwa tarin fuka mai aiki da kashi 71. [6] Nazarin da aka haɗa a cikin wannan bita an iyakance su ga waɗanda suka yi amfani da gwajin fitar da interferon gamma.

Ba a san tsawon lokacin kariya na BCG a sarari ba. A cikin waɗannan binciken da ke nuna tasirin kariya, bayanan ba su dace ba. Binciken MRC ya nuna kariya ta ragu zuwa 59% bayan shekaru 15 kuma zuwa sifili bayan shekaru 20; duk da haka, wani binciken da ke kallon 'yan asalin Amurka da aka yi wa rigakafi a cikin shekarun 1930 ya sami shaidar kariya har ma da shekaru 60 bayan rigakafi, tare da raguwa kaɗan a cikin inganci.[16]

BCG da alama tana da babban tasirin ta wajen hana tarin fuka ko Cutar tarin fuka, don haka har yanzu ana amfani dashi sosai har ma a ƙasashe inda ingancin cutar tarin fuki ba shi da mahimmanci.[17]

Bikin cika shekaru 100 na BCG ya kasance a cikin 2021. Ya kasance kawai allurar rigakafin da aka ba da lasisi game da tarin fuka, wanda shine annobar mai ci gaba. Cire tarin fuka burin Hukumar Lafiya ta Duniya (WHO), kodayake ana iya buƙatar ci gaban sabbin allurar rigakafi tare da inganci mafi girma akan tarin fuka na manya don samun ci gaba sosai.[18]

Tasiri

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An gabatar da dalilai da yawa na yiwuwar ingancin BCG a kasashe daban-daban. Babu wanda aka tabbatar, wasu an karyata, kuma babu wanda zai iya bayyana rashin inganci a cikin ƙasashe masu nauyin tarin fuka (Amurka) da ƙasashe masu ɗaukar nauyin tarin fuki (India). Dalilan ingancin canji an tattauna su a cikin takardar WHO akan BCG.[19]

  1. Bambancin kwayar halitta a cikin nau'ikan BCG: Bambancin kwaya a cikin nau-ikan BCG da aka yi amfani da su na iya bayyana ingancin da aka ruwaito a cikin gwaje-gwaje daban-daban.[20]
  2. Bambancin kwayar halitta a cikin yawan jama'a: Bambance-bambance a cikin kwayar halitta na al'ummomi daban-daban na iya bayyana bambancin inganci. An buga gwajin Birmingham BCG a shekarar 1988. Gwajin, wanda ke zaune a Birmingham, United Kingdom, ya bincika yara da aka haifa ga iyalai waɗanda suka samo asali daga yankin Indiya (inda aka nuna ingancin allurar rigakafi a baya ya zama sifili). Shari'ar ta nuna tasirin kariya na 64%, wanda yayi kama da adadi da aka samo daga wasu gwaje-gwajen Burtaniya, don haka yana jayayya da bambancin kwayar halitta.[21]
  3. tsangwama ta hanyar mycobacteria marasa ƙwayoyin cuta: Bayyanawa ga mycobacteria na muhalli (musamman Mycobacterium avium, Mycobacterium marinum da Mycobactera intracellulare) yana haifar da amsawar rigakafi mara ƙayyadadden akan mycobacteria. Gudanar da BCG ga wani wanda ya riga ya sami amsawar rigakafi mara mahimmanci akan mycobacteria ba ya ƙara amsawar da ta riga ta kasance. Saboda haka, BCG ba zai yi tasiri ba saboda mutumin ya riga ya sami matakin rigakafi kuma BCG ba ya ƙarawa ga wannan rigakafi. Wannan tasirin ana kiransa masking saboda tasirin BCG yana rufe shi da mycobacteria na muhalli. An sami shaidar asibiti don wannan tasirin a cikin jerin binciken da aka yi a layi daya a cikin yara masu zuwa makaranta a Burtaniya da Malawi.[22] A cikin wannan binciken, yaran makarantar Burtaniya suna da ƙananan rigakafin ƙwayoyin cuta ga mycobacteria wanda BCG ta kara; akasin haka, yaran makarantar Malawi suna da babban rigakafin sel ga mycoba bacteria kuma BCG ba ta kara wannan sosai ba. Ba a san ko wannan amsawar rigakafin ta halitta tana da kariya ba.[23] Wani madadin bayani ya ba da shawarar ta hanyar nazarin linzamin kwamfuta; rigakafin rigakafin mycobacteria yana dakatar da BCG daga sakewa don haka ya dakatar da shi daga samar da amsawar rigakafi. Wannan ana kiransa ra'ayi na toshewa.[24]
  4. tsangwama ta hanyar kamuwa da kwayar cuta a lokaci guda: A wani ra'ayi, kamuwa da cuta a daidai lokacin da kwayar cutar kamar helminthiasis ke canza martani na rigakafi ga BCG, yana sa ya zama ƙasa da tasiri.[25] Kamar yadda ake buƙatar amsawar Th1 don amsawar rigakafi mai tasiri ga kamuwa da tarin fuka, kamuwa da cuta tare da kwayar cuta daban-daban yana samar da amsawar Th2 a lokaci guda, wanda ke lalata tasirin BCG.[26]

Mycobacteria

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BCG yana da tasirin kariya daga wasu mycobacteria marasa tarin fuka.

  • Kwararrun: BCG yana da tasirin kariya daga kuturta a cikin kewayon 20 zuwa 80% . [1]
  • Buruli ulcer: BCG na iya karewa daga ko jinkirta farawar Buruli ulser.[1][27]
 
Micrograph da ke nuna kumburi mai yawa na ƙwayoyin wuyan hanji saboda Bacillus Calmette-Guérin da aka yi amfani da shi don magance Ciwon daji na hanji, H & E stainH&E tabo

BCG ya kasance daya daga cikin magungunan rigakafi masu nasara.[28] Allurar rigakafin BCG ta kasance "ma'auni na kulawa ga marasa lafiya tare da ciwon daji (NMIBC) " tun daga shekara ta 1977.[28][29] A shekara ta 2014 akwai fiye da takwas daban-daban da ake la'akari da kwayoyin halitta ko nau'ikan da aka yi amfani da su don maganin cutar kansa da ba ta da tsokoki.[28] [29]

  • Yawancin Allurar rigakafin cutar kansa suna amfani da BCG a matsayin ƙari don samar da motsawa na farko na tsarin rigakafin mutum.  [ana buƙatar hujja][<span title="This claim needs references to reliable sources. (December 2022)">citation needed</span>]
  • Ana amfani da BCG a cikin maganin cututtukan cututtukani. Tun daga ƙarshen shekarun 1970s, an sami shaidar cewa shigar da BCG a cikin hanji wani nau'i ne mai tasiri na rigakafi a cikin wannan cuta.[30] Duk da yake tsarin ba shi da tabbas, ya bayyana cewa an sanya maganin rigakafi na gida akan kumburi. Immunotherapy tare da BCG yana hana sake dawowa a cikin har zuwa 67% na lokuta na ciwon daji na farfajiya.  [ana buƙatar hujja][<span title="This claim needs references to reliable sources. (February 2023)">citation needed</span>]
  • An kimanta BCG a cikin karatu da yawa a matsayin magani ga ciwon daji.[31] Kamfanin biotech na Amurka Vaccinogen yana kimanta BCG a matsayin mai ba da gudummawa ga ƙwayoyin ciwon daji na autologous da aka yi amfani da su azaman Allurar rigakafi ciwon daji a mataki na II.  [ana buƙatar hujja][<span title="This claim needs references to reliable sources. (December 2022)">citation needed</span>]

Hanyar gudanarwa

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Kayan aiki (4-5 cm tsawo, tare da gajerun allurar rigakafin BCG a Japan, wanda aka nuna tare da ampules na BCG da saline

Ana gudanar da gwajin fata na tarin fuka kafin a yi amfani da BCG. Gwajin fata na tarin fuka yana hana BCG saboda haɗarin kumburi mai tsanani da scarring; ba ya nuna wani rigakafi. BCG kuma an hana shi a wasu mutanen da ke da lahani na hanyar karɓar IL-12.[32]

An ba da BCG a matsayin allurar intradermal guda ɗaya a shigar da Deltoid. Idan an ba da BCG ba zato ba tsammani, to, wani abscess na gida na iya samarwa (a "BCG-oma") wanda wani lokacin zai iya haifar da ulcerate, kuma yana iya buƙatar magani tare da maganin rigakafi nan da nan, in ba tare da magani ba zai iya yada kamuwa da cuta, yana haifar da mummunar lalacewa gaɓoɓin da suka dace. Ba koyaushe ba ne ke da alaƙa da gudanarwa ba daidai ba, kuma yana ɗaya daga cikin matsalolin da suka fi dacewa da za su iya faruwa tare da allurar rigakafi. An yi nazarin likitanci da yawa game da maganin waɗannan abscesses tare da maganin rigakafi tare da sakamako daban-daban, amma yarjejeniyar ta kasance da zarar an yi burin pus kuma an bincika shi, idan babu wani bacilli na musamman, abscess zai warke da kansa a cikin makonni.[33]

Halin da aka haifar da shi wanda BCG rigakafin ya bar sau da yawa ana amfani dashi azaman tabbacin rigakafin da ya gabata. Dole ne a rarrabe wannan alamar daga na allurar rigakafin kyanda, wanda zai iya kama da shi.[32]

Lokacin da aka ba da kansa don ciwon daji, ba a yi allurar rigakafin ta hanyar fata ba, amma ana saka shi cikin hanji ta hanyar urethra ta amfani da catheter mai laushi.[34]

Sakamakon da ba daidai ba

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Magungunan BCG gabaɗaya suna haifar da ciwo da scarring a wurin allurar. Babban tasirin mummunan sakamako shine keloids - manyan, manyan alamomi masu tasowa. Ana amfani da sakawa a cikin tsoka ta deltoid akai-akai saboda yawan rikitarwa na gida ya fi ƙanƙanta lokacin da aka yi amfani da wannan shafin. Duk da haka, buttock wani madadin shafin ne na gudanarwa saboda yana samar da kyakkyawan sakamako na kayan kwalliya.[32]

Ya kamata a ba da allurar rigakafin BCG a cikin ciki. Idan aka ba da shi ta hanyar subcutaneous, yana iya haifar da kamuwa da cuta ta cikin gida kuma ya bazu zuwa yankunan lymph, yana haifar da ko dai suppurative (samar da pus) da kuma non-supurative lymphadenitis. Gudanar da ra'ayin mazan jiya yawanci ya isa ga lymphadenitis maras wadata. Idan maye ya faru, yana iya buƙatar burin allura. Don rashin warwarewa, ana iya buƙatar cirewa ta tiyata. Shaida don maganin waɗannan rikitarwa ba su da yawa.[35]

Ba a saba gani ba, ƙwayoyin nono da gluteal na iya faruwa saboda haematogenous (wanda jini ke ɗauka) da yaduwar lymphangiomatous. Cutar ƙashi ta yanki (BCG osteomyelitis ko Osteitis) da yaduwar cutar BCG sune matsalolin da ba su da yawa na allurar rigakafin BCG, amma mai yuwuwa yana barazana ga rayuwa. Magungunan rigakafin tarin fuka na iya taimakawa a cikin matsaloli masu tsanani.[36]

Idan an ba da BCG ba da gangan ga mai haƙuri mai ƙarancin rigakafi (misali, jariri mai ƙaranci mai haɗari mai haɗari), zai iya haifar da yaduwar cuta ko haɗari ga rayuwa. Rubuce-rubucen da suka faru na wannan abin da ya faru bai kai daya ba a cikin miliyan daya da aka bayar.[37] A cikin 2007, WHO ta daina ba da shawarar BCG ga jarirai masu cutar kanjamau, koda kuwa haɗarin kamuwa da tarin fuka yana da yawa, saboda haɗarin yaduwar kamuwa da cutar BCG (wanda shine kusan 400 ga 100,000 a cikin wannan haɗari mafi girma). [38][39][40]

Amfani da shi

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Shekarar mutum da kuma mitar da aka ba da BCG koyaushe ya bambanta daga ƙasa zuwa ƙasa. WHO a halin yanzu tana ba da shawarar BCG na yara ga duk ƙasashe da ke da babban kamuwa da tarin fuka da / ko babban nauyin kuturta.[1] Wannan wani ɓangare ne na tarihin da kuma ayyukan BCG na yanzu a duniya. An samar da cikakken atlas na aikin da ya gabata da na yanzu.[41]

Amurka

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  • Brazil ta gabatar da rigakafin BCG na duniya a cikin 1967-1968, kuma aikin ya ci gaba har zuwa yanzu. Bisa ga dokar Brazil, ana sake ba da BCG ga masu sana'a na bangaren kiwon lafiya da kuma mutanen da ke kusa da marasa lafiya da ke fama da tarin fuka ko kuturta.  [ana buƙatar hujja][<span title="This claim needs references to reliable sources. (December 2022)">citation needed</span>]
  • Al'ummomin 'yan asalin Kanada a halin yanzu suna karɓar allurar rigakafin BCG, kuma a lardin Quebec an ba da allurar rigakawa ga yara har zuwa tsakiyar 70s.[42][43]
  • Yawancin ƙasashe a Tsakiya da Kudancin Amurka suna da rigakafin BCG na duniya, kamar yadda Mexico ke yi.[44][45]
  • Amurka ba ta taɓa amfani da rigakafin BCG ba saboda ƙarancin tarin fuka a Amurka, ta dogara a maimakon haka akan ganowa da maganin tarin fuka.[46]

Turai

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Asiya

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  • China: An gabatar da shi a cikin shekarun 1930. Ya karu da yawa bayan 1949. Mafi rinjaye an yi musu allurar rigakafi a shekara ta 1979.[47]
  • Koriya ta Kudu, Singapore, Taiwan da Malaysia. A cikin waɗannan ƙasashe, an ba da BCG a lokacin haihuwa kuma a lokacin da yake da shekaru 12. A Malaysia da Singapore daga shekara ta 2001, an canza wannan manufofin zuwa sau ɗaya kawai a lokacin haihuwa. Koriya ta Kudu ta dakatar da sake yin allurar rigakafi a cikin 2008.
  • Hong Kong: Ana ba da BCG ga dukan jarirai.[48]
  • Japan: A Japan, an gabatar da BCG a cikin 1951, wanda aka ba da shi yawanci yana da shekaru 6. Daga shekara ta 2005 ana gudanar da shi tsakanin watanni biyar zuwa takwas bayan haihuwa, kuma ba daga baya ba fiye da ranar haihuwar yaro ta farko. An gudanar da BCG ba daga baya ba fiye da ranar haihuwar ta huɗu har zuwa 2005, kuma ba daga baya watanni shida daga haihuwa daga 2005 zuwa 2012 ba; an canza jadawalin a cikin 2012 saboda rahotanni na cututtukan Osteitis daga allurar rigakafi a watanni 3-4. Wasu kananan hukumomi suna ba da shawarar jadawalin rigakafi na baya.[49]
  • Thailand: A Thailand, ana ba da allurar rigakafin BCG akai-akai a lokacin haihuwa.[50]
  • Indiya da Pakistan: Indiya da Pakistan sun gabatar da rigakafin BCG a cikin 1948, ƙasashe na farko a waje da Turai don yin hakan.[51] A cikin 2015, miliyoyin jarirai an hana su allurar rigakafin BCG a Pakistan a karon farko saboda karancin duniya.
  • Mongolia: Dukkanin jarirai suna yin allurar rigakafi da BCG. A baya, an ba da allurar rigakafin a shekaru 8 da 15, kodayake wannan ba aikin gama gari ba ne.[52]
  • Philippines: An fara allurar rigakafin BCG a Philippines a cikin 1979 tare da fadada shirin rigakafi.
  • Sri Lanka: A Sri Lanka, Manufofin Kasa na Sri Lanka shine ba da allurar rigakafin BCG ga duk jarirai da aka haifa nan da nan bayan haihuwa. Ana gudanar da allurar rigakafin BCG a karkashin fadada Shirin rigakafi (EPI).[53]

Gabas ta Tsakiya

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  • Isra'ila: An ba da BCG ga dukan jarirai tsakanin 1955 da 1982.[54]
  • Iran: An aiwatar da manufofin rigakafin Iran a shekarar 1984. Allurar rigakafi tare da Bacillus Calmette-Guerin (BCG) yana daga cikin mahimman dabarun kula da tarin fuka a Iran.[2] Dangane da manufofin allurar rigakafin jarirai na Iran, an ba da BCG a matsayin kashi ɗaya ga yara masu shekaru <6, jim kadan bayan haihuwa ko a farkon hulɗa da ayyukan kiwon lafiya.[55]

Afirka

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  • Afirka ta Kudu: A Afirka ta Kudu, ana ba da allurar rigakafin BCG akai-akai a lokacin haihuwa, ga duk jarirai, ban da waɗanda ke da alamun cutar AIDS. Gidan allurar rigakafin yana cikin kafada ta dama.[56]
  • Morocco: A Morocco, an gabatar da BCG a cikin 1949. Manufar yanzu ita ce allurar rigakafin BCG a lokacin haihuwa, ga dukkan jarirai.[57]
  • Kenya: A Kenya, ana ba da allurar rigakafin BCG akai-akai a lokacin haihuwa ga dukkan jarirai.[58]

Kudancin Pacific

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  • Ostiraliya: An yi amfani da allurar rigakafin BCG tsakanin shekarun 1950 zuwa tsakiyar 1980. BCG ba wani ɓangare ne na allurar rigakafi ba tun tsakiyar 1980.[59]
  • New Zealand: An fara gabatar da BCG Immunisation ga masu shekaru 13 a shekarar 1948. An dakatar da allurar rigakafi daga 1963 zuwa 1990.[41]

Aiki

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BCG an shirya shi ne daga wani nau'in cutar tarin fuka mai rai, Mycobacterium bovis, wanda ya rasa ikon haifar da cuta a cikin mutane. An tsara shi musamman a cikin matsakaiciyar al'adu, yawanci Middlebrook 7H9.[60] Saboda kwayoyin cuta masu rai suna canzawa don yin amfani da mafi kyawun abubuwan gina jiki, sun zama marasa dacewa da jinin ɗan adam kuma ba za su iya haifar da cuta ba lokacin da aka gabatar da su cikin mai karɓar mutum. Duk da haka, suna kama da kakanninsu na daji don samar da wani matakin rigakafi daga tarin fuka na mutum. Allurar rigakafin BCG na iya zama a ko'ina daga 0 zuwa 80% tasiri wajen hana tarin fuka na tsawon shekaru 15; duk da haka, tasirin kariya ya bayyana ya bambanta bisa ga yanayin ƙasa da dakin gwaje-gwaje inda aka girma maganin rigakafin.[15]

Kamfanoni daban-daban suna yin BCG, wani lokacin ta amfani da nau'ikan kwayoyin halitta daban-daban na kwayar cuta. Wannan na iya haifar da halaye daban-daban na samfur. OncoTICE, wanda aka yi amfani da shi don shigar da bututu don ciwon daji, Organon Laboratories ne suka kirkireshi (tun lokacin da Schering-Plough ya samu, kuma Merck &amp; Co. suka samu). Irin wannan aikace-aikacen shine samfurin Onko BCG na kamfanin Poland Biomed-Lublin, wanda ke da ƙananan M. bovis BCG Moreau na Brazil wanda ba shi da ƙarancin amsawa fiye da allurar rigakafi ciki har da sauran nau'ikan BCG.[61] Pacis BCG, wanda aka yi daga nau'in Montréal (Institut Armand-Frappier), Urocor ne ya fara tallata shi a cikin shekara ta 2002.[62] Urocor ta samo asali ne daga Dianon Systems. Evans Vaccines (wani reshe na PowderJect Pharmaceuticals). Statens Serum Institut a Denmark ta sayar da allurar rigakafin BCG da aka shirya ta amfani da kwayar cutar Danish 1331. Kamfanin AJVaccines ne ya samar da BCG Danish strain 1331 kuma daga baya ya rarraba shi tun lokacin da aka sauya mallakar kasuwancin samar da allurar rigakafin SSI zuwa AJ Vaccines Holding A / S wanda ya faru a ranar 16 ga Janairun 2017.[63][64] Japan BCG Laboratory tana tallata allurar rigakafinta, wanda ya dogara da Tokyo 172 substrain na Pasteur BCG, a cikin kasashe 50 a duk duniya.

Dangane da rahoton UNICEF da aka buga a watan Disamba na shekara ta 2015, kan tsaro na samar da allurar rigakafin BCG, bukatar duniya ta karu a shekarar 2015 daga 123 zuwa 152.2 miliyan.  Don inganta tsaro da kuma [diversity] tushen wadata mai araha da sassauci,"UNICEF ta ba da sabbin kwangilar masana'antun guda bakwai don samar da BCG. Tare da wadatar kayayyaki daga masana'antun da ke akwai, da kuma "sabon allurar rigakafin WHO" jimlar wadatar za ta kasance "ta isa ta sadu da duka buƙatun da aka hana 2015 zuwa 2016, da kuma jimlar buƙatun hasashen ta hanyar 2016-2018.[65]

Rashin wadata

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A cikin shekara ta 2011, masana'antar Sanofi Pasteur ta ambaliya, ta haifar da matsaloli tare da kumfa.[66] Ginin, wanda ke cikin Toronto, Ontario, Kanada, ya samar da samfuran rigakafin BCG da aka yi da substrain Connaught kamar allurar rigakafin tarin fuka da ImmuCYST, maganin rigakafin rigakafin cutar BCG da maganin ciwon daji.[66] A watan Afrilu na shekara ta 2012 FDA ta sami matsaloli da yawa da aka rubuta tare da rashin haihuwa a cikin shuka ciki har da mold, tsuntsaye da tsatsa na lantarki.[67] Sakamakon rufe shuka sama da shekaru biyu ya haifar da karancin cutar kansa da rigakafin tarin fuka.[68] A ranar 29 ga Oktoba 2014 Lafiya ta Kanada ta ba da izini ga Sanofi don ci gaba da samar da BCG.[69] Binciken 2018 na wadatar duniya ya kammala cewa wadatar ta isa ta cika buƙatun allurar rigakafin BCG, amma haɗarin ƙarancin ya kasance, galibi saboda dogaro da kashi 75 cikin dari na wadatar WHO a kan masu samarwa biyu kawai.[70]

Kashewa

gyara sashe

Wasu allurar rigakafin BCG ana bushe su daskare kuma suna zama foda mai kyau. Wani lokaci ana rufe foda tare da iska a cikin ampoule na gilashi. Dole ne a buɗe irin wannan ampoule na gilashi a hankali don hana iska daga busa foda. Sa'an nan kuma dole ne a narkar da foda tare da ruwan gishiri kafin a yi allura.[71]

Tarihi

gyara sashe
 
Hoton Faransanci yana inganta allurar rigakafin BCG

Tarihin BCG yana da alaƙa da na kyanda. A shekara ta 1865 Jean Antoine Villemin ya nuna cewa zomo na iya kamuwa da tarin fuka daga mutane; a shekara ta 1868 ya gano cewa zomo za su iya kamuwa le tarin fuka da shanu, kuma zomo na yiwuwar kamuwa da cutar tarin fuka Daga wasu zomo.[72] Don haka, ya kammala cewa an yadu da tarin fuka ta hanyar wasu kwayoyin da ba a san su ba (ko ""kwayar cutar"", kamar yadda ya kira shi).[73] A cikin 1882 Robert Koch ya ɗauki tarin fuka na mutum da na shanu iri ɗaya.[74][75] Amma a cikin 1895,[76] Theobald Smith ya gabatar da bambance-bambance tsakanin tarin fuka na mutum da na shanu, wanda ya ba da rahoton ga Koch.[77][78] A shekara ta 1901 Koch ya bambanta Mycobacterium bovis daga Mycobacerium tarin fuka.[79] Bayan nasarar allurar rigakafi wajen hana kyanda, wanda aka kafa a cikin karni na 18, masana kimiyya sun yi tunanin samun sakamako a cikin tarin fuka ta hanyar zana daidaituwa tsakanin tarin fuka da tarin fuka: an yi la'akari da cewa kamuwa da tarin fuki na shanu na iya karewa daga kamuwa da cutar tarin fuka na mutum. A ƙarshen karni na 19, an gudanar da gwaje-gwaje na asibiti ta amfani da M. bovisM. bovis tare da sakamako mai banƙyama, saboda an gano M. bovs yana da ƙwayoyin cuta kamar M. tarin fuka.[80]

Albert Calmette, likitan Faransa da masanin ƙwayoyin cuta, da mataimakinsa kuma daga baya abokin aiki, Camille Guérin, likitan dabbobi, suna aiki a Institut Pasteur de Lille (Lille, Faransa) a cikin 1908. Ayyukansu sun haɗa da ƙaddamar da ƙwayoyin ƙwayoyin cuta na tarin fuka da kuma gwada kafofin watsa labarai daban-daban. Sun lura da cakuda glycerin-bile-potato ya girma bacilli wanda ya zama kamar ba shi da ƙwayoyin cuta, kuma ya canza hanyar binciken su don ganin idan maimaita subculting zai samar da wani nau'i wanda aka rage shi don a yi la'akari da shi don amfani da shi azaman allurar rigakafi. An ware nau'in BCG bayan subculturing sau 239 a cikin shekaru 13 daga nau'in virulent a kan matsakaicin dankali na glycerine. Binciken ya ci gaba a duk lokacin yakin duniya na har zuwa 1919, lokacin da bacilli na yanzu ba su iya haifar da cutar tarin fuka a cikin dabbobi masu bincike ba. Calmette da Guerin sun koma Cibiyar Pasteur ta Paris a 1919. An fara amfani da allurar rigakafin BCG a cikin mutane a cikin 1921.[81]

Amincewar jama'a ya yi jinkiri, kuma Bala'in Lübeck, musamman, ya yi yawa don cutar da shi. Tsakanin 1929 da 1933 a Lübeck, an yi wa jarirai 251 allurar rigakafi a cikin kwanaki 10 na farko na rayuwa; 173 sun kamu da tarin fuka kuma 72 sun mutu. Daga baya aka gano cewa BCG da ke gudanarwa a can an gurɓata shi da wani nau'i mai guba wanda ake adanawa a cikin wannan incubator, wanda ya haifar da matakin shari'a a kan masana'antun allurar rigakafin.[82]

Dokta R. G. Ferguson, yana aiki a Fort Qu'Appelle Sanatorium a Saskatchewan, yana daga cikin masu gabatarwa wajen bunkasa aikin rigakafin tarin fuka. A Kanada, an yi amfani da yara sama da 600 daga makarantun zama a matsayin mahalarta ba tare da son rai ba a gwajin allurar rigakafin BCG tsakanin 1933 da 1945.[83] A cikin 1928, Kwamitin Lafiya na Kungiyar Al'ummai (wanda ya riga ya zama Hukumar Lafiya ta Duniya (WHO)) ya karɓi BCG. Saboda adawa, duk da haka, an yi amfani da shi sosai bayan yakin duniya na biyu. Daga 1945 zuwa 1948, kungiyoyin agaji (Kamfen na Tuberculosis na Duniya ko Kasuwanci na hadin gwiwa) sun yi allurar rigakafi ga jarirai sama da miliyan takwas a gabashin Turai kuma sun hana hasashen karuwar tarin fuka bayan babban yaƙi.[84]

BCG yana da inganci sosai a kan cutar tarin fuka a cikin rukunin yara, amma ingancinsa a kan cutar fuka-fuki na huhu ya bayyana ya bambanta. Wasu ƙasashe sun cire BCG daga allurar rigakafi ta yau da kullun. Kasashe biyu da ba su taɓa amfani da shi ba akai-akai sune Amurka da Netherlands (a cikin ƙasashe biyu, ana jin cewa samun gwajin Mantoux mai aminci sabili da haka samun damar gano cututtukan da ke aiki daidai ya fi fa'ida ga al'umma fiye da yin allurar rigakafi game da yanayin da yanzu yake da wuya a can).[85][86]

Sauran sunayen sun hada da "Vaccin Bilié de Calmette et Guérin vaccine" da "Bacille de Calmetde et Guérine vaccine".[87]

Bincike

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Akwai shaidar gwaji don tasirin da ba takamaiman ba na allurar rigakafin BCG akan yawan mace-mace a cikin ƙasashe masu ƙarancin kuɗi, ko kuma don rage sauran matsalolin kiwon lafiya ciki har da sepsis da cututtukan numfashi lokacin da aka ba su da wuri, tare da fa'ida mafi girma a baya an yi amfani da shi.[88][89]

A cikin Rhesus macaques, BCG yana nuna ingantaccen kariya lokacin da aka ba shi ta hanyar intravenous.[90][91] Dole ne a kimanta wasu haɗari kafin a iya fassara shi ga mutane.[92]

Cibiyar Jenner ta Jami'ar Oxford tana gudanar da bincike wanda ke kwatanta ingancin allurar rigakafin BCG da aka sha a cikin manya da suka riga sun yi allurar rigata.[93]

Ciwon sukari na nau'i na 1

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Ya zuwa shekara ta 2017, allurar rigakafin BCG tana cikin matakan farko na nazarin cutar sukari ta 1 (T1D).[94][95]

COVID-19

gyara sashe

Amfani da allurar rigakafin BCG na iya samar da kariya daga COVID-19.[96][97] Koyaya, abubuwan lura da annoba a wannan bangaren ba su da tabbas.[98] WHO ba ta ba da shawarar amfani da shi don rigakafi har zuwa 12 ga .[99]

Ya zuwa watan Janairun , gwaje-gwaje ashirin na BCG suna cikin matakai daban-daban na asibiti.[100] Ya zuwa Oktoba , sakamakon ya kasance mai rikitarwa sosai. Wani gwaji na watanni 15 wanda ya shafi mutanen da aka yi wa allurar rigakafi sau uku a cikin shekaru biyu kafin annobar ya nuna sakamako mai kyau wajen hana kamuwa da cuta a cikin mutanen BCG-naive da ke da nau'in ciwon sukari na 1.[101] A gefe guda, gwajin watanni 5 ya nuna cewa sake yin allurar rigakafi tare da BCG ba ya taimakawa hana kamuwa da cuta a cikin ma'aikatan kiwon lafiya. Dukkanin wadannan gwaje-gwaje sun kasance gwaje-gaje masu sarrafawa guda biyu.[102]

Manazarta

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  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 World Health Organization (February 2018). "BCG vaccines: WHO position paper – February 2018". Weekly Epidemiological Record. 93 (8): 73–96. PMID 29474026. |hdl-access= requires |hdl= (help)
  2. ↑ Hawgood BJ (August 2007). "Albert Calmette (1863-1933) and Camille Guérin (1872-1961): the C and G of BCG vaccine". Journal of Medical Biography. 15 (3): 139–146. doi:10.1258/j.jmb.2007.06-15. PMID 17641786. S2CID 41880560.
  3. ↑ Luca S, Mihaescu T (March 2013). "History of BCG Vaccine". Maedica. 8 (1): 53–58. PMC 3749764. PMID 24023600.
  4. ↑ Fuge O, Vasdev N, Allchorne P, Green JS (May 2015). "Immunotherapy for bladder cancer". Research and Reports in Urology. 7: 65–79. doi:10.2147/RRU.S63447. PMC 4427258. PMID 26000263.
  5. ↑ Houghton BB, Chalasani V, Hayne D, Grimison P, Brown CS, Patel MI, Davis ID, Stockler MR (May 2013). "Intravesical chemotherapy plus bacille Calmette-Guérin in non-muscle invasive bladder cancer: a systematic review with meta-analysis". BJU International. 111 (6): 977–983. doi:10.1111/j.1464-410X.2012.11390.x. PMID 23253618. S2CID 24961108.
  6. ↑ 6.0 6.1 Roy A, Eisenhut M, Harris RJ, Rodrigues LC, Sridhar S, Habermann S, Snell L, Mangtani P, Adetifa I, Lalvani A, Abubakar I (August 2014). "Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis". BMJ. 349: g4643. doi:10.1136/bmj.g4643. PMC 4122754. PMID 25097193.
  7. ↑ Empty citation (help)
  8. ↑ "BCG Vaccine: WHO position paper" (PDF). Weekly Epidemiological Record. 4 (79): 25–40. 23 January 2004. Archived (PDF) from the original on 21 September 2015.
  9. ↑ "The Role of BCG Vaccine in the Prevention and Control of Tuberculosis in the United States A Joint Statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices". www.cdc.gov. Archived from the original on 23 July 2024. Retrieved 23 July 2024. In the United States, the use of BCG vaccination is rarely indicated. BCG vaccination is not recommended for inclusion in immunization or TB control programs, and it is not recommended for most HCWs. Physicians considering the use of BCG vaccine for their patients are encouraged to consult the TB control programs in their area.
  10. ↑ Vaudry, Wendy (March 2003). ""To BCG or not to BCG, that is the question!". The challenge of BCG vaccination: Why can't we get it right?". Paediatrics & Child Health. 8 (3): 141–144. doi:10.1093/pch/8.3.141. PMC 2792660. PMID 20020010.
  11. ↑ "FREEZE - DRIED GLUTAMATE BCG VACCINE (JAPAN) FOR INTRADERMAL USE" (PDF) (in English). World Health Organization. Archived (PDF) from the original on 19 October 2021. Retrieved 18 November 2021.CS1 maint: unrecognized language (link)
  12. ↑ "Tuberculin Skin Testing Fact Sheet". 12 July 2023. Archived from the original on 9 January 2017. Retrieved 9 June 2023.
  13. ↑ 13.0 13.1 Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F (March 1994). "Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature". JAMA. 271 (9): 698–702. doi:10.1001/jama.1994.03510330076038. PMID 8309034.
  14. ↑ 14.0 14.1 Fine PE (November 1995). "Variation in protection by BCG: implications of and for heterologous immunity". Lancet. 346 (8986): 1339–1345. doi:10.1016/S0140-6736(95)92348-9. PMID 7475776. S2CID 44737409.
  15. ↑ 15.0 15.1 Venkataswamy MM, Goldberg MF, Baena A, Chan J, Jacobs WR, Porcelli SA (February 2012). "In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG". Vaccine. 30 (6): 1038–1049. doi:10.1016/j.vaccine.2011.12.044. PMC 3269512. PMID 22189700.
  16. ↑ Aronson NE, Santosham M, Comstock GW, Howard RS, Moulton LH, Rhoades ER, Harrison LH (May 2004). "Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study". JAMA. 291 (17): 2086–2091. doi:10.1001/jama.291.17.2086. PMID 15126436.
  17. ↑ Rodrigues LC, Diwan VK, Wheeler JG (December 1993). "Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis". International Journal of Epidemiology. 22 (6): 1154–1158. doi:10.1093/ije/22.6.1154. PMID 8144299.
  18. ↑ "Tuberculosis kills as many people each year as COVID-19. It's time we found a better vaccine". The Conversation. 14 January 2021. Archived from the original on 24 June 2021. Retrieved 18 June 2021.
  19. ↑ Fine PE, Carneiro IA, Milstein JB, Clements CJ (1999). "Chapter 8: Reasons for variable efficacy" (PDF). Issues relating to the use of BCG in immunization programmes: a discussion document (Report). Geneva, Switzerland: World Health Organization. hdl:10665/66120. WHO/V&B/99.23. Archived (PDF) from the original on 20 February 2011. Retrieved 17 February 2014.
  20. ↑ Brosch R, Gordon SV, Garnier T, Eiglmeier K, Frigui W, Valenti P, Dos Santos S, Duthoy S, Lacroix C, Garcia-Pelayo C, Inwald JK, Golby P, Garcia JN, Hewinson RG, Behr MA, Quail MA, Churcher C, Barrell BG, Parkhill J, Cole ST (March 2007). "Genome plasticity of BCG and impact on vaccine efficacy". Proceedings of the National Academy of Sciences of the United States of America. 104 (13): 5596–5601. Bibcode:2007PNAS..104.5596B. doi:10.1073/pnas.0700869104. PMC 1838518. PMID 17372194.
  21. ↑ Packe GE, Innes JA (March 1988). "Protective effect of BCG vaccination in infant Asians: a case-control study". Archives of Disease in Childhood. 63 (3): 277–281. doi:10.1136/adc.63.3.277. PMC 1778792. PMID 3258499.
  22. ↑ Black GF, Weir RE, Floyd S, Bliss L, Warndorff DK, Crampin AC, Ngwira B, Sichali L, Nazareth B, Blackwell JM, Branson K, Chaguluka SD, Donovan L, Jarman E, King E, Fine PE, Dockrell HM (April 2002). "BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies". Lancet. 359 (9315): 1393–1401. doi:10.1016/S0140-6736(02)08353-8. PMID 11978337. S2CID 24334622.
  23. ↑ Palmer CE, Long MW (October 1966). "Effects of infection with atypical mycobacteria on BCG vaccination and tuberculosis". The American Review of Respiratory Disease. 94 (4): 553–568. doi:10.1164/arrd.1966.94.4.553 (inactive 27 June 2024). PMID 5924215. Archived from the original on 25 July 2024. Retrieved 14 June 2024.CS1 maint: DOI inactive as of ga Yuni, 2024 (link)
  24. ↑ Brandt L, Feino Cunha J, Weinreich Olsen A, Chilima B, Hirsch P, Appelberg R, Andersen P (February 2002). "Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis". Infection and Immunity. 70 (2): 672–678. doi:10.1128/IAI.70.2.672-678.2002. PMC 127715. PMID 11796598.
  25. ↑ Natukunda A, Zirimenya L, Nassuuna J, Nkurunungi G, Cose S, Elliott AM, Webb EL (September 2022). "The effect of helminth infection on vaccine responses in humans and animal models: A systematic review and meta-analysis". Parasite Immunology. 44 (9): e12939. doi:10.1111/pim.12939. PMC 9542036 Check |pmc= value (help). PMID 35712983 Check |pmid= value (help).
  26. ↑ Rook GA, Dheda K, Zumla A (March 2005). "Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?" (PDF). Vaccine. 23 (17–18): 2115–2120. doi:10.1016/j.vaccine.2005.01.069. PMID 15755581. Archived (PDF) from the original on 22 September 2017.
  27. ↑ Tanghe A, Content J, Van Vooren JP, Portaels F, Huygen K (September 2001). "Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer". Infection and Immunity. 69 (9): 5403–5411. doi:10.1128/IAI.69.9.5403-5411.2001. PMC 98650. PMID 11500410.
  28. ↑ 28.0 28.1 28.2 Rentsch CA, Birkhäuser FD, Biot C, Gsponer JR, Bisiaux A, Wetterauer C, Lagranderie M, Marchal G, Orgeur M, Bouchier C, Bachmann A, Ingersoll MA, Brosch R, Albert ML, Thalmann GN (October 2014). "Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy". European Urology. 66 (4): 677–688. doi:10.1016/j.eururo.2014.02.061. PMID 24674149.
  29. ↑ 29.0 29.1 Brandau S, Suttmann H (July 2007). "Thirty years of BCG immunotherapy for non-muscle invasive bladder cancer: a success story with room for improvement". Biomedicine & Pharmacotherapy. 61 (6): 299–305. doi:10.1016/j.biopha.2007.05.004. PMID 17604943.
  30. ↑ Lamm DL, Blumenstein BA, Crawford ED, Montie JE, Scardino P, Grossman HB, Stanisic TH, Smith JA, Sullivan J, Sarosdy MF (October 1991). "A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder". The New England Journal of Medicine. 325 (17): 1205–1209. doi:10.1056/NEJM199110243251703. PMID 1922207.
  31. ↑ Mosolits S, Nilsson B, Mellstedt H (June 2005). "Towards therapeutic vaccines for colorectal carcinoma: a review of clinical trials". Expert Review of Vaccines. 4 (3): 329–350. doi:10.1586/14760584.4.3.329. PMID 16026248. S2CID 35749038.
  32. ↑ 32.0 32.1 32.2 Sable SB, Posey JE, Scriba TJ (December 2019). "Tuberculosis Vaccine Development: Progress in Clinical Evaluation". Clinical Microbiology Reviews. 33 (1). doi:10.1128/CMR.00100-19. PMC 6822991. PMID 31666281.
  33. ↑ "BestBets: Is medical therapy effective in the treatment of BCG abscesses?". bestbets.org. Archived from the original on 25 July 2024. Retrieved 15 August 2022.
  34. ↑ "Intravesical Therapy for Bladder Cancer". www.cancer.org (in Turanci). Archived from the original on 30 March 2020. Retrieved 15 August 2022.
  35. ↑ Cuello-García CA, Pérez-Gaxiola G, Jiménez Gutiérrez C (January 2013). "Treating BCG-induced disease in children". The Cochrane Database of Systematic Reviews. 2013 (1): CD008300. doi:10.1002/14651858.CD008300.pub2. PMC 6532703. PMID 23440826.
  36. ↑ Govindarajan KK, Chai FY (April 2011). "BCG Adenitis-Need for Increased Awareness". The Malaysian Journal of Medical Sciences. 18 (2): 66–69. PMC 3216207. PMID 22135589.
  37. ↑ Centers for Disease Control and Prevention (April 1996). "The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices" (PDF). MMWR. Recommendations and Reports. 45 (RR-4): 1–18. PMID 8602127. Archived (PDF) from the original on 6 January 2020. Retrieved 6 January 2020.
  38. ↑ World Health Organization (May 2007). "Revised BCG vaccination guidelines for infants at risk for HIV infection". Weekly Epidemiological Record. 82 (21): 193–196. PMID 17526121. |hdl-access= requires |hdl= (help)
  39. ↑ Trunz BB, Fine P, Dye C (April 2006). "Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness". Lancet. 367 (9517): 1173–1180. doi:10.1016/S0140-6736(06)68507-3. PMID 16616560. S2CID 40371125.
  40. ↑ Mak TK, Hesseling AC, Hussey GD, Cotton MF (September 2008). "Making BCG vaccination programmes safer in the HIV era". Lancet. 372 (9641): 786–787. doi:10.1016/S0140-6736(08)61318-5. PMID 18774406. S2CID 6702107.
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  42. ↑ "Bacille Calmette–Guerin (BCG) Information for Health Professionals". toronto.ca. January 2020. Archived from the original on 6 May 2020. Retrieved 8 April 2020.
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  44. ↑ "Ficha metodológica". Archived from the original on 2 April 2015. Retrieved 12 March 2015.
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  46. ↑ "Fact Sheets | Infection Control & Prevention | Fact Sheet - BCG Vaccine | TB | CDC". www.cdc.gov (in Turanci). 16 August 2022. Archived from the original on 20 July 2013. Retrieved 22 June 2024.
  47. ↑ Chen ZR, Wei XH, Zhu ZY (June 1982). "BCG in China". Chinese Medical Journal. 95 (6): 437–442. PMID 6813052.
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  102. ↑ Upton CM, van Wijk RC, Mockeliunas L, Simonsson US, McHarry K, van den Hoogen G, Muller C, von Delft A, van der Westhuizen HM, van Crevel R, Walzl G, Baptista PM, Peter J, Diacon AH (June 2022). "Safety and efficacy of BCG re-vaccination in relation to COVID-19 morbidity in healthcare workers: A double-blind, randomised, controlled, phase 3 trial". eClinicalMedicine. 48: 101414. doi:10.1016/j.eclinm.2022.101414. PMC 9098089 Check |pmc= value (help). PMID 35582122 Check |pmid= value (help).
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