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The following variables were analyzed&#58; date of diagnosis&#44; age&#44; location&#44; chest X-ray characteristics &#40;cavitary&#47;non-cavitary&#41;&#44; sputum smear &#40;bacilliferous&#47;non-bacilliferous&#41;&#44; source of case data &#40;notification of the physician responsible for diagnosis&#44; or active searches of microbiology and pathology records&#44; Aids registries&#44; penitentiary institution archives&#44; and death records&#41; and diagnostic delay since the onset of symptoms&#46; Population data were obtained from the National Institute of Statistics registry&#46; The incidence of TB in the last half of 2020 after implementation of confinement due to the COVID-19 pandemic was compared with that of the same period in 2019 by comparison of proportions&#46; Days of diagnostic delay were compared using the Mann&#8211;Whitney test&#46; Six-month trends since 2015 were analyzed using a Poisson regression analysis&#44; followed by a segmented regression analysis to detect a possible point of significant change in the trend&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The study did not require Ethics Committee approval as it is a pooled data analysis and there is no possibility of identifying patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In the second half of 2020&#44; 172 cases of TB were recorded&#44; compared with 262 in the same period of 2019&#44; corresponding to a 6-monthly incidence of 6&#46;4 vs&#46; 9&#46;7 per 100&#44;000 inhabitants &#40;risk reduction<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#46;35&#37;&#59; 95&#37; CI&#58; 20&#46;43&#8211;45&#46;84&#41;&#46; Case data were obtained from active searches in microbiology and other records in 34&#46;3&#37; &#40;59&#47;172&#41; of cases in the second half of 2020 vs&#46; 29&#46;0&#37; &#40;76&#47;262&#41; in 2019 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;29&#41;&#46; The percentage of patients with forms of TB suggestive of greater diagnostic delay &#40;patients with bacilliferous disease or cavitation on chest X-ray&#41; was similar in both periods&#58; 29&#46;1&#37; had bacilliferous disease in the second half of 2020 vs&#46; 28&#46;2&#37; in the second half of 2019 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;94&#41;&#59; whereas the percentage of patients with cavitation on chest X-ray was 14&#46;5&#37; in the second half of 2020 vs&#46; 17&#46;2&#37; in the same period of 2019 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;55&#41;&#46; The median diagnostic delay in the second half of 2020 was 60&#46;5 days &#40;IQR&#58; 23&#46;0&#8211;122&#46;0&#41; vs&#46; 65 days &#40;IQR&#58; 30&#46;5&#8211;121&#46;5&#41; in the same period of 2019 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;51&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The analysis of 6-monthly trends revealed a 32&#37; annual decrease in risk for the 2015&#8211;2020 period &#40;95&#37; CI 22&#8211;42&#37;&#41;&#44; a rate that is greater than the 20&#37; decrease observed over the 2015&#8211;2019 period as a whole &#40;95&#37; CI 7&#8211;33&#37;&#41;&#46; The segmented Poisson regression analysis shows a break point in incidence after 2020 with a RR value of 0&#46;980 &#40;95&#37; CI 0&#46;967&#8211;0&#46;993&#41; for the initial part of the regression line &#40;2015&#8211;2019&#41;&#44; compared to a steeper decline in 2020 &#40;RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;790&#59; 95&#37; CI 0&#46;635&#8211;0&#46;945&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A significant decrease was therefore observed in registered cases of TB following the introduction of preventive measures for COVID-19&#46; This could be due to 3&#44; not necessarily exclusive&#44; factors&#46; First&#44; possible under-reporting of cases&#46; Secondly&#44; possible diagnostic delay caused by re-allocation of health resources &#40;microbiology laboratories&#44; primary care&#44; and the TB programs themselves&#41;&#44; difficulties in accessing oversaturated healthcare services&#44; and&#47;or reluctance to attend hospitals or health centers for fear of exposure to SARS-CoV-2<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">13&#44;14</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Finally&#44; there may be a real decline in TB cases associated with the reduction of respiratory-borne diseases following the introduction of confinement measures&#44; social distancing&#44; and use of masks<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a>&#46; We believe that this is the most realistic explanation in our autonomous community&#46; Although some resources allocated to the TB control program in Galicia have been diverted&#44; TB units have retained their basic structure and functions&#46; Immediate care has been maintained for patients&#44; contacts&#44; screened patients&#44; and patients with suspected TB diagnosis&#44; while active contact tracing continues&#46; There was no increase in the number of patients with advanced forms of the disease &#40;bacilliferous&#44; cavitation on X-ray&#41; or in diagnostic delays in the second half of 2020&#44; an observation that supports our hypothesis that the incidence of tuberculosis has actually decreased&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Although TB has hitherto been thought to manifest in only 50&#37; of cases in the first 2 years of infection&#44; recent evidence suggests that the incubation period is shorter in most cases<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a>&#46; This also supports the hypothesis of a real decline in TB&#44; despite the short time since the start of isolation measures in March 2020&#46; Studies conducted in other countries also describe a decrease in the incidence of TB&#44; although they do not focus so closely on the impact of COVID-19 control measures<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">17&#44;18</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The development of the pandemic over time&#44; the measures taken to control it&#44; and the longer-term monitoring of TB incidence rates will definitively confirm the existence of a real decline in the incidence of TB associated with social isolation measures&#46; Be that as it may&#44; we agree with other authors that a possible decline in TB cases is no reason to relax disease control measures&#44; but should rather serve as an incentive to reinforce vigilance<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">19&#44;20</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; social distancing and respiratory isolation measures&#44; including the widespread use of masks&#44; contribute positively to the decrease in the incidence of TB in our environment&#46;</p></span>"
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            "apendice" => "<p id="par0070" class="elsevierStylePara elsevierViewall">A&#46; Castro-Paz &#40;Complexo Hospitalario Universitario de Ourense&#41;&#59; E&#46; Cruz-Ferro &#40;Programa gallego de tuberculosis&#46; D&#46;G&#46; de Salud P&#250;blica&#41;&#59; L&#46; Ferreiro-Fern&#225;ndez &#40;Hospital Cl&#237;nico Universitario de Santiago&#41;&#59; M&#46; Otero Santiago &#40;Hospital Universitario de A Coru&#241;a&#41;&#59; A&#46; Penas Truque &#40;Hospital Lucus Augusti de Lugo&#41;&#59; M&#46;L&#46; P&#233;rez del Molino &#40;Hospital Cl&#237;nico Universitario de Santiago&#41;&#59; A&#46; Rodr&#237;guez-Canal &#40;Complexo Hospitalario Universitario de Ourense&#41;&#59; J&#46;A&#46; Taboada Rodr&#237;guez &#40;D&#46; G&#46; de Salud P&#250;blica&#41;&#59; P&#46; Vali&#241;o L&#243;pez &#40;Hospital Universitario de A Coru&#241;a&#41;&#59; E&#46; V&#225;zquez Garc&#237;a-Serrano &#40;Hospital Arquitecto Marcide de Ferrol&#41;&#59; R&#46; Zubizarreta Alberdi &#40;D&#46;G&#46; de Salud P&#250;blica&#41;&#46;</p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Galician Tuberculosis Prevention and Control Program Working Group"
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Scientific Letter
Decline of Tuberculosis Rates and COVID-19 Pandemic. Fact or Fiction?
Descenso en la incidencia de tuberculosis y pandemia COVID-19, ¿ficción o realidad?
Nuria Vázquez-Tempranoa, María Isabel Ursúa-Díazb,c, Ángel Salgado-Barreirad, Rafael Vázquez-Gallardoe,c, Victoria Túñez Bastidaf,c, Luis Anibarroa,c,g,
Corresponding author
luis.anibarro.garcia@sergas.es

Corresponding author.
, the Galician Tuberculosis Prevention and Control Working Group
a Unidad de tuberculosis, Servicio de Medicina Interna, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
b Programa gallego de tuberculosis, Dirección General de Salud Pública, Consellería de Sanidade, Xunta de Galicia, Santiago de Compostela, Spain
c Grupo de Trabajo del Programa de Prevención y Control de la Tuberculosis de Galicia, Spain
d Unidad de Metodología y Estadística, Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain
e Unidad de tuberculosis, Servicio de Neumología, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
f Unidad de tuberculosis, Servicio de Medicina Preventiva, Hospital Clínico Universitario de Santiago de Compostela, A Coruña, Spain
g Grupo de investigación en Inmunología, Instituto de investigación Sanitaria Galicia Sur, Vigo, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The outbreak of the COVID-19 pandemic has led to a far-reaching re-allocation of economic&#44; social&#44; and health resources that has affected the control&#44; diagnosis&#44; and prognosis of other diseases<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#8211;3</span></a>&#46; Tuberculosis &#40;TB&#41; control and prevention programs have also suffered from resources being diverted to efforts to control the pandemic<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">4&#44;5</span></a>&#46; The World Health Organization believes that 21&#37; of people with tuberculosis remained undiagnosed in 2020&#44; resulting in 500&#44;000 more mortalities than the organization&#39;s own targets set out in its &#8216;End TB&#8217; strategy<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">However&#44; social distancing and respiratory isolation measures implemented since the outbreak of the pandemic have had a beneficial effect on the incidence of other infectious diseases transmitted via the respiratory route that have a short incubation period&#44; such as influenza&#44; respiratory syncytial virus&#44; and others<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">8&#8211;11</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The impact of anti-COVID-19 measures on TB&#44; a disease with a longer incubation period that is also transmitted by the respiratory route&#44; is not sufficiently understood&#46; In this study&#44; we present data on the incidence of TB relative to the COVID-19 pandemic in Galicia&#44; Spain&#44; where there is a recognized and consolidated TB prevention and control program that includes active contact tracing<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">All cases of TB included in the Galician TB Registry between 2015 and 2020 were pooled for review on 7 May 2021&#46; The following variables were analyzed&#58; date of diagnosis&#44; age&#44; location&#44; chest X-ray characteristics &#40;cavitary&#47;non-cavitary&#41;&#44; sputum smear &#40;bacilliferous&#47;non-bacilliferous&#41;&#44; source of case data &#40;notification of the physician responsible for diagnosis&#44; or active searches of microbiology and pathology records&#44; Aids registries&#44; penitentiary institution archives&#44; and death records&#41; and diagnostic delay since the onset of symptoms&#46; Population data were obtained from the National Institute of Statistics registry&#46; The incidence of TB in the last half of 2020 after implementation of confinement due to the COVID-19 pandemic was compared with that of the same period in 2019 by comparison of proportions&#46; Days of diagnostic delay were compared using the Mann&#8211;Whitney test&#46; Six-month trends since 2015 were analyzed using a Poisson regression analysis&#44; followed by a segmented regression analysis to detect a possible point of significant change in the trend&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The study did not require Ethics Committee approval as it is a pooled data analysis and there is no possibility of identifying patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In the second half of 2020&#44; 172 cases of TB were recorded&#44; compared with 262 in the same period of 2019&#44; corresponding to a 6-monthly incidence of 6&#46;4 vs&#46; 9&#46;7 per 100&#44;000 inhabitants &#40;risk reduction<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#46;35&#37;&#59; 95&#37; CI&#58; 20&#46;43&#8211;45&#46;84&#41;&#46; Case data were obtained from active searches in microbiology and other records in 34&#46;3&#37; &#40;59&#47;172&#41; of cases in the second half of 2020 vs&#46; 29&#46;0&#37; &#40;76&#47;262&#41; in 2019 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;29&#41;&#46; The percentage of patients with forms of TB suggestive of greater diagnostic delay &#40;patients with bacilliferous disease or cavitation on chest X-ray&#41; was similar in both periods&#58; 29&#46;1&#37; had bacilliferous disease in the second half of 2020 vs&#46; 28&#46;2&#37; in the second half of 2019 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;94&#41;&#59; whereas the percentage of patients with cavitation on chest X-ray was 14&#46;5&#37; in the second half of 2020 vs&#46; 17&#46;2&#37; in the same period of 2019 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;55&#41;&#46; The median diagnostic delay in the second half of 2020 was 60&#46;5 days &#40;IQR&#58; 23&#46;0&#8211;122&#46;0&#41; vs&#46; 65 days &#40;IQR&#58; 30&#46;5&#8211;121&#46;5&#41; in the same period of 2019 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;51&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The analysis of 6-monthly trends revealed a 32&#37; annual decrease in risk for the 2015&#8211;2020 period &#40;95&#37; CI 22&#8211;42&#37;&#41;&#44; a rate that is greater than the 20&#37; decrease observed over the 2015&#8211;2019 period as a whole &#40;95&#37; CI 7&#8211;33&#37;&#41;&#46; The segmented Poisson regression analysis shows a break point in incidence after 2020 with a RR value of 0&#46;980 &#40;95&#37; CI 0&#46;967&#8211;0&#46;993&#41; for the initial part of the regression line &#40;2015&#8211;2019&#41;&#44; compared to a steeper decline in 2020 &#40;RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;790&#59; 95&#37; CI 0&#46;635&#8211;0&#46;945&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A significant decrease was therefore observed in registered cases of TB following the introduction of preventive measures for COVID-19&#46; This could be due to 3&#44; not necessarily exclusive&#44; factors&#46; First&#44; possible under-reporting of cases&#46; Secondly&#44; possible diagnostic delay caused by re-allocation of health resources &#40;microbiology laboratories&#44; primary care&#44; and the TB programs themselves&#41;&#44; difficulties in accessing oversaturated healthcare services&#44; and&#47;or reluctance to attend hospitals or health centers for fear of exposure to SARS-CoV-2<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">13&#44;14</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Finally&#44; there may be a real decline in TB cases associated with the reduction of respiratory-borne diseases following the introduction of confinement measures&#44; social distancing&#44; and use of masks<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a>&#46; We believe that this is the most realistic explanation in our autonomous community&#46; Although some resources allocated to the TB control program in Galicia have been diverted&#44; TB units have retained their basic structure and functions&#46; Immediate care has been maintained for patients&#44; contacts&#44; screened patients&#44; and patients with suspected TB diagnosis&#44; while active contact tracing continues&#46; There was no increase in the number of patients with advanced forms of the disease &#40;bacilliferous&#44; cavitation on X-ray&#41; or in diagnostic delays in the second half of 2020&#44; an observation that supports our hypothesis that the incidence of tuberculosis has actually decreased&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Although TB has hitherto been thought to manifest in only 50&#37; of cases in the first 2 years of infection&#44; recent evidence suggests that the incubation period is shorter in most cases<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a>&#46; This also supports the hypothesis of a real decline in TB&#44; despite the short time since the start of isolation measures in March 2020&#46; Studies conducted in other countries also describe a decrease in the incidence of TB&#44; although they do not focus so closely on the impact of COVID-19 control measures<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">17&#44;18</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The development of the pandemic over time&#44; the measures taken to control it&#44; and the longer-term monitoring of TB incidence rates will definitively confirm the existence of a real decline in the incidence of TB associated with social isolation measures&#46; Be that as it may&#44; we agree with other authors that a possible decline in TB cases is no reason to relax disease control measures&#44; but should rather serve as an incentive to reinforce vigilance<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">19&#44;20</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; social distancing and respiratory isolation measures&#44; including the widespread use of masks&#44; contribute positively to the decrease in the incidence of TB in our environment&#46;</p></span>"
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            "apendice" => "<p id="par0070" class="elsevierStylePara elsevierViewall">A&#46; Castro-Paz &#40;Complexo Hospitalario Universitario de Ourense&#41;&#59; E&#46; Cruz-Ferro &#40;Programa gallego de tuberculosis&#46; D&#46;G&#46; de Salud P&#250;blica&#41;&#59; L&#46; Ferreiro-Fern&#225;ndez &#40;Hospital Cl&#237;nico Universitario de Santiago&#41;&#59; M&#46; Otero Santiago &#40;Hospital Universitario de A Coru&#241;a&#41;&#59; A&#46; Penas Truque &#40;Hospital Lucus Augusti de Lugo&#41;&#59; M&#46;L&#46; P&#233;rez del Molino &#40;Hospital Cl&#237;nico Universitario de Santiago&#41;&#59; A&#46; Rodr&#237;guez-Canal &#40;Complexo Hospitalario Universitario de Ourense&#41;&#59; J&#46;A&#46; Taboada Rodr&#237;guez &#40;D&#46; G&#46; de Salud P&#250;blica&#41;&#59; P&#46; Vali&#241;o L&#243;pez &#40;Hospital Universitario de A Coru&#241;a&#41;&#59; E&#46; V&#225;zquez Garc&#237;a-Serrano &#40;Hospital Arquitecto Marcide de Ferrol&#41;&#59; R&#46; Zubizarreta Alberdi &#40;D&#46;G&#46; de Salud P&#250;blica&#41;&#46;</p>"
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ISSN: 03002896
Original language: English
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