We would like to thank Furuya-Kanamori et al.¹ for commenting on our paper ‘Single Visit Rabies Pre-Exposure Prophylaxis: A Literature Review’,² in which we conducted a 20-year literature review (until 31 December 2022) on single visit rabies Pre-Exposure Prophylaxis (PrEP).

Our colleagues were concerned by our analytical approach, therefore they re-analysed the data by performing a prevalence meta-analysis.¹ They state having updated the literature review to identify any relevant articles published in the last 2 years, but as their article was submitted in October 2023, they only added a maximum of nine supplementary months and found no further studies comparing to our research.

We do not agree with the method proposed by our colleagues. Indeed, we consciously chose not to perform a meta-analysis, as an inference was not sought due to the numerous methodological biases that would have distorted the result. Before performing a meta-analysis, it is essential to conduct a rigorous assessment of the homogeneity of the included studies. In our case, we found that the heterogenicity of the studies was too great: different rabies vaccines and concentrations used, heterogeneity in the administration routes for both PrEP and postexposure prophylaxis (PEP), heterogeneity in the tests used to determine the rabies virus neutralizing antibodies titers, etc. Consequently, we decided against performing a meta-analysis and opted for a descriptive approach, and therefore did not propose a confidence interval whose interpretation made little sense. Furthermore, because the number of studies and subjects included is already limited, we think it was impossible to analyse different subgroups and, therefore, we disagree that these results allow us to say that the route of administration and schedule of PEP have an impact on effectiveness. Firstly, regardless of the statistical method used, no statistically significant difference between PEP administration routes and schedules was found. Secondly, the two anecdotic subjects reported by Soentjens et al.,³ which failed to seroconvert on Day 7 after intradermal (ID) PEP, ultimately seroconverted without additional boosters at 3 and 6 months, respectively. As a reminder, there is also no proof that the current PEP schedules without rabies immunoglobulins recommended by the World Health Organization,⁴ which are virtually 100% protective, necessarily reach 100% seroconversion rate at Day 7. While we fully agree with our colleagues that for a completely vaccine-preventable and practically 100% lethal disease such as rabies a PEP schedule with a failure rate of 1% or higher would be unacceptable,¹ we would like to point out that in the current context of at-risk populations having difficulties in accessing rabies PrEP and/or timely PEP,⁵ we should take into account limitations of both our studies^1,2 and thoroughly investigate the ID dose-sparing schedules before cautioning against their use. While public health bodies and health practitioners from high-income countries might feel reticent to adopt off-label dose-sparing regimens and choose to use the more reassuring two-visit intramuscular schedules,⁵ low-resource settings, where most rabies cases occur, might not always have the luxury of this choice.

Funding

None.

Author Contributions

Diana Isabela Costescu Strachinaru (Conceptualization, Resources, Writing—Original Draft, Writing—Review and Editing), Alain Levêque (Conceptualization, Resources, Writing—Review and Editing, Supervision, Validation), and Benjamin Damanet (Conceptualization, Resources, Writing—Original Draft, Writing—Review and Editing, Supervision, Validation).

Conflict of interest: The authors have declared no conflicts of interest.

Data availability

No new data were generated or analysed in support of this research.

Peer-Reviewed Journals A-Z