Long before Edward Jenner's cowpox-based vaccination at the end of the eighteenth century, a practice of smallpox inoculation using matter from active pustules, known as variolation, was documented in parts of India, described in some detail by European observers such as the British surgeon J. Z. Holwell in an account published in 1767 describing itinerant Bengali inoculators, and this older Indian tradition has been discussed by historians of medicine in connection with Shitala's cult, since it was practised within the same religious world that understood smallpox as the goddess's presence rather than simply a disease to be clinically eliminated. Some of the itinerant specialists who performed variolation in Bengal operated within a religious framework connected to Shitala worship, treating the controlled introduction of smallpox matter as negotiating with, rather than opposing, the goddess's presence, consistent with the broader logic of her cult that disease is managed and appeased rather than fought outright.
Historians of medicine caution against overstating how uniform this connection was, since inoculation practices and their relationship to formal Shitala worship varied by region, and colonial and later public health authorities, once vaccination became available, often worked to displace variolation and its religious framing, sometimes generating real friction with existing local practice. This history situates Shitala's cult not simply as passive accommodation to an unconquerable disease but as one thread within an older, practically engaged Indian tradition of actively intervening against smallpox, long before any biomedical understanding of immunity existed to explain why the intervention sometimes worked.