key: cord-0836845-brmvjvgy authors: Flynn, M. F.; Kelly, M.; Dooley, J. S. title: Nasopharyngeal aspirates vs. nasal swabs for the detection of respiratory pathogens: results of a rapid review protocol date: 2020-10-23 journal: nan DOI: 10.1101/2020.10.21.20216077 sha: c016a94001f829b625e15a2fcf6e6446842e4e04 doc_id: 836845 cord_uid: brmvjvgy Background Nasal pathogen detection sensitivities are often as low as 70% despite advances in molecular diagnostics. It has been suggested that this is linked, in part, to the choice of sampling method. Methods A diagnostic test accuracy review for sensitivity, using recently developed Cochrane methods for conducting rapid reviews, and the PRISMA protocol was undertaken, with QUADAS-2 risk of bias assessments and meta-analysis of included studies. Sensitivities were calculated by a consensus standard of positivity by either method as the gold standard. Insufficient and/or inaccurate, cross sectional or anatomical site pooling methodologies were excluded. Results Of 13 included studies, 8 had high risk of bias, and 5 had high applicability concerns. There were no statistical differences in pooled sensitivities between collection methods for 8 different viruses, and neither with use of PCR, Immunofluorescence nor culture. In a single study, Influenza H1N1 favoured nasopharyngeal swabs, with aspirates having 93.3% of the sensitivity of swabs (p>0.001). Similar equivocal sensitivities were noticed in detecting bacteria. Conclusions The chain of sampling, from anatomical site to laboratory results, features different potential foci along which sensitivity may be lost. A sufficient body of evidence exists that use of a different sampling method will not yield more respiratory pathogens. The new Cochrane Rapid Reviews guidance helped rapidly answer this relevant and timely clinical question. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 23, 2020. ; https://doi.org/10.1101/2020. 10 d e c r e a s e d s e n s i t i v i t y i n c o m p a r i s o n t o o t h e r m e t h o d s d u e t o f a l s e p o s i t i v e s n o l o n g e r b e i n g i n c o r p o r a t e d 6 . P C R a v o i d s t h e d e c r e a s e d s e n s i t i v i t i e s i n p a t i e n t s o v e r 5 y e a r s o f a g e s e e n w i t h D I F , a n d i s f u r t h e r a d v a n t a g e d i n b e i n g a b l e t o q u a n t i f y v i r a l l o a d ( q P C R ) 7 8 9 . H i g h e r v i r a l l o a d s p r e s e n t i n t h e e a r l y c o u r s e o f a v i r a l i n f e c t i o n p r e d o m i n a t e i n t h e n o s e t h a n i n t h e t h r o a t , a n d s l i g h t l y p r e d o m i n a t e i n t h e n a s o p h a r y n x t h a n t h e a n t e r i o r n a s a l c a v i t y 1 0 1 1 1 2 . F o r b a c t e r i a , t h e r e i s a r e l a t e d b u t d i s t i n c t m i c r o b i o m e b e t w e e n t h e a n t e r i o r n a r e s a n d n a s o p h a r y n x 1 3 . T h e n a s o p h a r y n x i s t h e u p p e r m o s t p o r t i o n o f t h e t h r o a t l y i n g a t t h e b a c k o f t h e n a s a l c a v i t y a n d a c c e s s i b l e h o r i z o n t a l l y a l o n g t h e n a s a l f l o o r p a s t o c c a s i o n a l l y o b s t r u c t i n g t u r b i n a t e s a n d d e v i a t i o n s o f t h e s e p t u m . A n a s o p h a r y n g e a l s w a b ( N P S ) i s i n s e r t e d t o a d e p t h e q u a l t o t h e d i s t a n c e f r o m t h e n o s t r i l t o t h e e a r l o b e ( n a s o t r a g a l l e n g t h , N T L ) , o r u n t i l t h e n a s o p h a r y n x i s f e l t ( a d e p t h o f u p t o 1 4 c m ) , w i t h l e s s d e e p s w a b s > = 5 c m s a m p l i n g t h e m i d d l e m e a t u s o r a n t e r i o r n a r e s 1 4 1 5 1 6 1 7 . T h e N T L i n c h i l d r e n a n d i n f a n t s i s s h o r t e r , b u t r e m a i n s c o n s i d e r a b l y l o n g e r t h a n t h e 2 c m d e p t h o c c a s i o n a l l y c i t e d i n N P S s t u d i e s , a n d i s w e l l d e s c r i b e d i n a p p r o a c h e s t o p a e d i a t r i c i n t u b a t i o n 1 8 1 9 . L a c k o f c l a r i t y o v e r s u c h d e f i n i t i o n s a n d e n s u i n g h e t e r o g e n e i t y h a s f r u s t r a t e d m e t a a n a l y s i s o f t h i s a r e a 2 0 . A r e v i e w o f m e t h o d s f o r I n f l u e n z a d e t e c t i o n f o u n d i n c r e a s e d y i e l d w h e n p a i r i n g c o m b i n a t i o n s o f d i v e r s e m e t h o d s 2 1 . C o m b i n e d o r o p h a r y n g e a l a n d a n t e r i o r n a s a l s w a b s a r e s h o w n t o b e c o m p a r a b l e i n s e n s i t i v i t y t o a s i n g l e s a m p l e o f t h e n a s o p h a r y n x w h i l s t b e n e f i t i n g f r o m h i g h e r p a t i e n t . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted October 23, 2020. 4 s a t i s f a c t i o n 2 2 2 3 2 4 . T h e s e c o m b i n e d t h r o a t / n o s e s w a b s h a v e b e c o m e r e c o m m e n d e d p r a c t i c e f o r s e l f a d m i n i s t r a t i o n o f t h e t e s t 2 5 . P a i r e d o r o p h a r y n g e a l / N P S s c o n v e y i n c r e a s e d s e n s i t i v i t y c o m p a r e d t o N P S a l o n e 2 6 2 7 . T h e s w a b t y p e u s e d i s a n i m p o r t a n t c o n s i d e r a t i o n , w i t h g r e a t e r y i e l d o f r e s p i r a t o r y e p i t h e l i a l c e l l s a n d g r e a t e r p a t i e n t s a t i s f a c t i o n w i t h a f l o c k e d s w a b ( a k i n t o a m i n i a t u r e t o i l e t b r u s h ) t h a n a r a y o n t i p p e d s w a b ( r e s e m b l i n g a l o n g c o t t o n " e a r " b u d ) b u t p a t h o g e n d e t e c t i o n r a t e i s e q u i v o c a l 2 8 2 9 . O t h e r i m p o r t a n t p r e -l a b o r a t o r y v a r i a b l e s s u c h a s p r e -i m p r e g n a t i o n o f s w a b s w i t h t r a n s p o r t m e d i a , i m m e d i a t . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted October 23, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 23, 2020 . 6 k n o w l e d g e u s e r s i n r e s p i r a t o r y m e d i c i n e , p a e d i a t r i c s , m i c r o b i o l o g y a n d o t o l a r y n g o l o g y a s w e l l a s a f o c u s g r o u p w i t h m e m b e r s o f t h e p u b l i c t o p r o m o t e f i t n e s s f o r p u r p o s e . I n c l u s . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 23, 2020. ; 7 w e r e n o t i n c l u d e d , a n d s t u d i e s w e r e r e s t r i c t e d t o t h o s e i n E n g l i s h . P e e r r e v i e w o f s e a r c h s t r a t e g y w a s n o t u n d e r t a k e n . T h e s e a r c h w a s c o n d u c t e d o n 0 is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 23, 2020 . 8 W h e r e t h e r e w e r e a s u f f i c i e n t n u m b e r o f s t u d i e s , r e s u l t s f o r m e d a p r o p o r t i o n a l m e t a -a n a l y s i s , e l s e a n a r r a t i v e w a s u s e d . S e n s i t i v i t y a n a l y s i s a n d M c N e m a r s ' t e s t f o r p a i r e d s a m p l e s w e r e d e r i v e d u s i n g M e d c a l c a n d S c i s t a t o n l i n e s t a t i s t i c a l s o f t w a r e r e s p e c t i v e l y . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 23, 2020. T h e i n i t i a l s e a r c h i d e n t i f i e d 2 5 3 a r t i c l e s [ f i g u r e 1 ] . 1 3 w e r e a d d e d f r o m s e a r c h i n g r e f e r e n c e l i s t s o f k e y p a p e r s a n d r e v i e w s . A f t e r s c r e e n i n g t i t l e s a n d a b s t r a c t s , t h e f u l l t e x t s o f 1 8 6 p u b l i c a t i o n s w e r . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted October 23, 2020. ; a n a l y s i s o f N A a n d N P S f o r g r o u p A p a t h o g e n s , i . e t h o s e a s s o c i a t e d w i t h h o s p i t a l i s i n g i l l n e s s , i n c l u d e d R e s p i r a t o r y S y n c y t i a l V i r u s , P a r a i n f l u e n z a v i r u s , M e t a p n e u m o v i r u s a n d I n f l u e n z a A + B [ f i g u r e 4 ] . T h i s s y s t e m a t i c r e v i e w f o u n d a m o d e r a t e b o d y o f e v i d e n c e c o m p a r i n g n a s o p h a r y n g e a l s w a b s w i t h a s p i r a t e s a n d w a s h e s w i t h n o s i g n i f i c a n t d i f f e r e n c e i n s e n s i t i v i t y . T h e s e f i n d i n g s w e r e p r e d o m i n a n t l y i t i v i t i e s s e e n , a n d t h e s e n o t o n l y d i s a p p e a r e d w h e n p o o l i n g s t u d i e s , b u t c o m p a r i n g w i t h b e t t e r p o w e r e d s t u d i e s . T h i s i m p l i e s a l i m i t i n g c o m m o n d e n o m i n a t o r t o a l l . O n t h e d i a g n o s t i c c h a i n f r o m m u c o s a t o l a b b e n c h , t h e s t e p l e a s t l i k e l y t o b e c o n t r o l l e d i s t h e s p e c i f i c a n a t o m i c a l s a m p l i n g t e c h n i q u e . S i n g l e o p e r a t o r s a m p l i n g u n d e r d i r e c t v i s i o n a n d c o n t r o l l e d c o n d i t i o n s h a v e b e e n d e s c r i b e d e l s e w h e r . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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