Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
  Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login  
  Home Print this page Email this page Small font sizeDefault font sizeIncrease font size Users Online: 161       

   Table of Contents      
CORRESPONDENCE
Year : 2020  |  Volume : 152  |  Issue : 1  |  Page : 144-145

Authors' response


1 Translational Global Health Policy Research Cell, New Delhi, India
2 Multidisciplinary Research Unit/Model Rural Health Research Unit, New Delhi, India
3 ICMR-National Institute of Medical Statistics, New Delhi, India
4 Division of Reproductive Biology, Maternal Health & Child Health, New Delhi, India
5 Division of Non-Communicable Diseases, Indian Council of Medical Research, New Delhi, India
6 Division of Clinical Medicine, ICMR-National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India
7 Informatics, Systems & Research Management Cell, Indian Council of Medical Research, New Delhi, India
8 Division of Epidemiology & Communicable Diseases, Indian Council of Medical Research, New Delhi, India
9 Department of Health Research, Ministry of Health & Family Welfare; Indian Council of Medical Research, New Delhi, India
10 ICMR-National AIDS Research Institute, Pune, Maharashtra, India

Date of Web Publication04-Aug-2020

Correspondence Address:
Samiran Panda
ICMR-National AIDS Research Institute, Pune, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


Read associated with this article

DOI: 10.4103/0971-5916.291398

Rights and Permissions

How to cite this article:
Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, Singh H, Praharaj I, Gangakhedkar RR, Bhargava B, Panda S. Authors' response. Indian J Med Res 2020;152:144-5

How to cite this URL:
Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, Singh H, Praharaj I, Gangakhedkar RR, Bhargava B, Panda S. Authors' response. Indian J Med Res [serial online] 2020 [cited 2021 Apr 14];152:144-5. Available from: https://www.ijmr.org.in/text.asp?2020/152/1/144/291398

We thank the authors of the letter for their critical reading of our case-control investigation[1]. During this investigation, we matched the cases and controls by time and location using the date of testing and laboratory where they were tested following the development of symptoms of respiratory tract infection, to limit the variability between cases and controls. The overall purpose of our investigation was to identify factors associated with SARS-CoV-2 infection (protective or risk posing). However, we realize that examining the safety and efficacy of pre-exposure prophylaxis, based on hydroxychloroquine (HCQ), would require clinical trials as indicated in the discussion section of our article[1].

Chloroquine (CQ) and HCQ are known to have extensive tissue spread, resulting in a large volume of distribution in the human body. Single-dose kinetics studies in the context of malaria chemoprophylaxis show that adequate plasma levels of chloroquine may be achieved only after four weeks. During this period, the individual taking CQ prophylaxis may not achieve the desired plasma concentration of the drug needed for protection[2]. These findings prompted the recommendation that CQ prophylaxis in malaria-naïve travellers be initiated at least two weeks prior to entry into malaria-endemic areas. Interestingly, our study also provided a similar hint of protection against SARS-CoV-2 infection obtained through HCQ chemoprophylaxis, where a dose-response relationship appeared unfolding after the intake of four or more maintenance doses following the initial loading dose.

Importantly, although CQ and HCQ are efficiently concentrated in lung tissue over time, reaching at least 11.8 times the concentration in plasma, in vivo concentrations needed to counter SARS-CoV-2 infection, may be achieved in a dose-dependent manner[3],[4]. For a drug like HCQ where lysosomal sequestration is known and can lead to variable concentrations in various body tissues compared to plasma levels[5], information regarding HCQ levels, specifically in lung tissues, is important as far as the activity against SARS-CoV-2 and other respiratory viruses is concerned. With the current evidence, it is unclear if parameters such as area under the curve (AUC) can be reliably used to predict levels in respiratory tissues and drug efficacy[6].

As our study was specifically conducted to identify the associations between various exposure variables and SARS-CoV-2 infection in symptomatic healthcare workers (HCWs), it would be inappropriate to extrapolate the findings to home-based contacts of confirmed cases of COVID-19. Notwithstanding the findings of our study, we would still like to underscore the necessity of pondering over protective behavioural factors and appropriate use of personal protective equipment along with plausible chemoprophylaxis-based biologic intervention while examining the occurrence of SARS-CoV-2 infection in HCWs.

 
   References Top

1.
Chatterjee P, Anand T, Singh Kh, Rasaily R, Singh R, Das S, et al. Healthcare workers and SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19. Indian J Med Res 2020; 151 : 459-67.  Back to cited text no. 1
    
2.
Frisk-Holmberg M, Bergqvist Y, Termond E, Domeij-Nyberg B. The single dose kinetics of chloroquine and its major metabolite desethylchloroquine in healthy subjects. Eur J Clin Pharmacol 1984; 26 : 521-30.  Back to cited text no. 2
    
3.
Adelusi SA, Salako LA. Kinetics of the distribution and elimination of chloroquine in the rat. Gen Pharmacol 1982; 13 : 433-7.  Back to cited text no. 3
    
4.
Smit C, Peeters MYM, van den Anker JN, Knibbe CA. Chloroquine for SARS-CoV-2: Implications of Its unique pharmacokinetic and safety properties. Clin Pharmacokinet 2020; 59 : 659-69.  Back to cited text no. 4
    
5.
Collins KP, Jackson KM, Gustafson DL. Hydroxychloroquine: A physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther 2018; 365 : 447-59.  Back to cited text no. 5
    
6.
Arnold SL, Buckner F. Hydroxychloroquine for treatment of SARS-CoV-2 Infection? Improving our confidence in a model-based approach to dose selection. Clin Transl Sci 2020; 13 : 642-5.  Back to cited text no. 6
    




 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    References

 Article Access Statistics
    Viewed586    
    Printed52    
    Emailed0    
    PDF Downloaded105    
    Comments [Add]    

Recommend this journal