Impact  of  a  Point-­‐‑of-­‐‑Care  Rapid  Influenza  Test  on  Antibiotic  Prescribing  Patterns  in   Southern  Sri  Lanka   by   L.  Gayani  Tillekeratne   Duke  Global  Health  Institute     Date:_______________________   Approved:     ___________________________   Christopher  W.  Woods,  Supervisor     ___________________________   Nathan  M.  Thielman     ___________________________   Truls  Ostbye     ___________________________   Champica  K.  Bodinayake     ___________________________   Megan  E.  Reller     Thesis  submitted  in  partial  fulfillment  of   the  requirements  for  the  degree  of   Master  of  Science  in  the  Duke  Global  Health  Institute  in  the  Graduate  School  of  Duke   University     2014 ABSTRACT   Impact  of  a  Point-­‐‑of-­‐‑Care  Rapid  Influenza  Test  on  Antibiotic  Prescribing  Patterns  in   Southern  Sri  Lanka   by   L.  Gayani  Tillekeratne   Department  of  Global  Health   Duke  University     Date:_______________________   Approved:     ___________________________   Christopher  W.  Woods,  Supervisor     ___________________________   Nathan  M.  Thielman     ___________________________   Truls  Ostbye     ___________________________   Champica  K.  Bodinayake     ___________________________   Megan  E.  Reller     An  abstract  of  a  thesis  submitted  in  partial   fulfillment  of  the  requirements  for  the  degree   of  Master  of  Science  in  the  Duke  Global  Health  Institute  in  the  Graduate  School  of  Duke   University     2014 Copyright  by   L.  Gayani  Tillekeratne   2014 Abstract   Background:  Acute  febrile  respiratory  illnesses,  including  influenza,  account  for   a  large  proportion  of  ambulatory  care  visits  worldwide.  In  the  developed  world,  these   encounters  commonly  result  in  unwarranted  antibiotic  prescriptions;  data  from  more   resource-­‐‑limited  settings  are  lacking.    The  purpose  of  this  study  was  to  describe  the   epidemiology  of  influenza  among  outpatients  in  southern  Sri  Lanka  and  to  determine  if   access  to  rapid  influenza  test  results  was  associated  with  decreased  antibiotic   prescriptions.   Methods:    In  this  pretest-­‐‑  posttest  study,  consecutive  patients  presenting  from   March  2013-­‐‑  April  2014  to  the  Outpatient  Department  of  the  largest  tertiary  care  hospital   in  southern  Sri  Lanka  were  surveyed  for  influenza-­‐‑like  illness  (ILI).  Patients  meeting   World  Health  Organization  criteria  for  ILI-­‐‑-­‐‑  acute  onset  of  fever  ≥38.0°C  and  cough  in   the  prior  7  days—were  enrolled.  Consenting  patients  were  administered  a  structured   questionnaire,  physical  examination,  and  nasal/nasopharyngeal  sampling.  Rapid   influenza  A/B  testing  (Veritor  System,  Becton  Dickinson)  was  performed  on  all  patients,   but  test  results  were  only  released  to  patients  and  clinicians  during  the  second  phase  of   the  study  (December  2013-­‐‑  April  2014).     Results:    We  enrolled  397  patients  with  ILI,  with  217  (54.7%)  adults  ≥12  years  and   188  (47.4%)  females.  A  total  of  179  (45.8%)  tested  positive  for  influenza  by  rapid  testing,     iv with  April-­‐‑  July  2013  and  September-­‐‑  November  2013  being  the  periods  with  the  highest   proportion  of  ILI  due  to  influenza.  A  total  of  310  (78.1%)  patients  with  ILI  received  a   prescription  for  an  antibiotic  from  their  outpatient  provider.  The  proportion  of  patients   prescribed  antibiotics  decreased  from  81.4%  in  the  first  phase  to  66.3%  in  the  second   phase  (p=.005);  among  rapid  influenza-­‐‑positive  patients,  antibiotic  prescriptions   decreased  from  83.7%  in  the  first  phase  to  56.3%  in  the  second  phase  (p=.001).  On   multivariable  analysis,  having  a  positive  rapid  influenza  test  available  to  clinicians  was   associated  with  decreased  antibiotic  use  (OR  0.20,  95%  CI  0.05-­‐‑  0.82).   Conclusions:  Influenza  virus  accounted  for  almost  50%  of  acute  febrile   respiratory  illness  in  this  study,  but  most  patients  were  prescribed  antibiotics.  Providing   rapid  influenza  test  results  to  clinicians  was  associated  with  fewer  antibiotic   prescriptions,  but  overall  prescription  of  antibiotics  remained  high.  In  this  developing   country  setting,  a  multi-­‐‑faceted  approach  that  includes  improved  access  to  rapid   diagnostic  tests  may  help  decrease  antibiotic  use  and  combat  antimicrobial  resistance.           v Contents   Abstract  ..........................................................................................................................................  iv   List  of  Tables  .................................................................................................................................  ix   List  of  Figures  ...............................................................................................................................  xi   Acknowledgements  ....................................................................................................................  xii   1. Background  ................................................................................................................................  1   1.1  Global  burden  and  seasonality  of  influenza  .................................................................  1   1.2  Epidemiology  of  influenza  in  Sri  Lanka  ........................................................................  3   1.3  Influenza,  antibiotic  use,  and  the  impact  of  rapid  diagnostic  testing  .......................  5   2. Objectives  ..................................................................................................................................  8   3. Setting  .........................................................................................................................................  9   3.1  Background  on  Sri  Lanka  and  its  healthcare  infrastructure  ......................................  9   3.2  Duke-­‐‑Ruhuna  Collaboration  .........................................................................................  10   4. Methods  ....................................................................................................................................  12   4.1  Study  setting  ....................................................................................................................  12   4.2  Study  procedures  ............................................................................................................  12   4.3  Sample  processing  ..........................................................................................................  13   4.4  Study  design  ....................................................................................................................  15   4.5  Analysis  plan  ...................................................................................................................  16   4.6  Ethical  considerations  ....................................................................................................  17   5. Results  ......................................................................................................................................  18   5.1.  Description  of  study  population  .................................................................................  22     vi 5.1.1  Sociodemographic  characteristics  ...........................................................................  22   5.1.2  Exposures  and  risk  factors  .......................................................................................  26   5.1.3  Prior  care  .....................................................................................................................  27   5.1.4  Clinical  presentation  .................................................................................................  28   5.1.5  Rapid  influenza  test  results  ......................................................................................  30   5.1.6  Clinical  management  ................................................................................................  34   5.1.7  Impact  on  finances  and  productivity  ......................................................................  34   5.2  Comparison  of  first  and  second  phases  ......................................................................  35   5.2.1  Sociodemographic  characteristics,  exposures,  and  impact  on  finances  and   productivity  .........................................................................................................................  35   5.2.2  Clinical  characteristics  and  physical  exam  findings  .............................................  36   5.2.3  Rapid  influenza  test  results  and  clinical  management  ........................................  37   5.3  Bivariable  analysis  of  features  associated  with  influenza  ........................................  38   5.3.1  Sociodemographic  characteristics,  exposures,  and  clinical  symptoms  .............  38   5.3.2  Clinical  management  ................................................................................................  39   5.4  Bivariable  analysis  of  features  associated  with  antibiotic  prescriptions  ................  43   5.4.1  Sociodemographic  characteristics,  exposures,  and  clinical  symptoms  .............  43   5.4.2  Clinical  management  ................................................................................................  43   5.5  Multivariable  analysis  of  features  associated  with  influenza  ..................................  48   5.6  Multivariable  analysis  of  features  associated  with  receipt  of  an  antibiotic   prescription  ............................................................................................................................  49   6. Discussion  ................................................................................................................................  51   6.1  ILI  and  influenza  patterns  in  southern  Sri  Lanka  ......................................................  51     vii 6.2  Clinical  presentation  of  influenza  ................................................................................  55   6.3  ILI  and  antibiotic  use  ......................................................................................................  56   7. Ongoing work  ..........................................................................................................................  66   8. Conclusions  .............................................................................................................................  67   Appendix A  ...................................................................................................................................  68   References  ...................................................................................................................................  70       viii List  of  Tables   Table  1:  Sociodemographic  characteristics  of  outpatients  enrolled  with  ILI  in  southern   Sri  Lanka  from  March  2013-­‐‑  April  2014,  listed  for  the  entire  study  population  as  well  as   for  each  phase  of  the  study.  .......................................................................................................  25   Table  2:  Exposures  and  risk  factors  for  outpatients  with  ILI  in  southern  Sri  Lanka,  March   2013-­‐‑  April  2014,  listed  for  the  entire  study  population  as  well  as  for  each  phase  of  the   study.  .............................................................................................................................................  27   Table  3:  Clinical  symptoms,  exam  findings,  and  clinical  diagnoses  and  treatment   received  among  outpatients  with  ILI  in  southern  Sri  Lanka,  March  2013  to  April  2014  ..  29   Table  4:  Impact  of  illness  on  finances  and  productivity  among  outpatients  with  ILI  in   southern  Sri  Lanka  from  March  2013-­‐‑  April  2014,  listed  for  the  total  study  population  as   well  as  for  each  phase  of  the  study.  ..........................................................................................  35   Table  5:  Bivariable  analysis  of  sociodemographic  characteristics,  exposures,  and  clinical   characteristics  associated  with  rapid  influenza  positivity  among  outpatients  with  ILI  in   southern  Sri  Lanka,  March  2013-­‐‑  April  2014.  ..........................................................................  40   Table  6:  Bivariable  analysis  of  cost  and  productivity  variables  associated  with  rapid   influenza  positivity  among  outpatients  with  ILI  in  southern  Sri  Lanka,  March  2013-­‐‑   April  2014.  ....................................................................................................................................  42   Table  7:  Bivariable  analysis  of  clinical  diagnoses  and  treatments  associated  with  rapid   influenza  positivity  in  outpatients  with  ILI  in  southern  Sri  Lanka,  March  2013-­‐‑  April   2014  ................................................................................................................................................  42   Table  8:  Bivariable  analysis  of  sociodemographic  characteristics  and  clinical  features   associated  with  antibiotic  prescriptions  for  outpatients  with  ILI  in  southern  Sri  Lanka,   March  2013-­‐‑  April  2014.  .............................................................................................................  45   Table  9:  Bivariable  analysis  of  cost  and  productivity  variables  associated  with  antibiotic   prescriptions  for  outpatients  with  ILI  in  southern  Sri  Lanka,  March  2013-­‐‑  April  2014.  ...  47   Table  10:  Bivariable  analysis  of  clinical  diagnoses  and  treatments  associated  with   antibiotic  prescriptions  for  outpatients  with  ILI  in  southern  Sri  Lanka,  March  2013-­‐‑  April   2014.  ...............................................................................................................................................  47     ix Table  11:  Multivariable  analysis  of  sociodemographic  characteristics,  exposures,  clinical   symptoms,  and  exam  findings  associated  with  rapid  influenza  positivity  among   outpatients  with  ILI  in  southern  Sri  Lanka,  March  2013-­‐‑  April  2014.  .................................  49   Table  12:  Multivariable  analysis  of  sociodemographic  characteristics,  exposures,  clinical   symptoms,  and  exam  findings  associated  with  antibiotic  prescriptions  among   outpatients  with  ILI  in  southern  Sri  Lanka,  March  2013-­‐‑  April  2014.  .................................  50         x