Epidemiology of acute undifferentiated febrile illness and acute encephalitis syndrome cases in Northern India: a prospective observational study

Acute undifferentiated febrile illness (AUFI) and acute encephalitis syndrome (AES) continue to be major public health concerns, particularly in rural areas with limited healthcare facility. We investigated the aetiological agents responsible for seasonal sporadic AUFI and AES cases in Northern India. The study included 4200 patient samples (April 2022 to March 2024), fulfilling the AUFI or AES case definition. Clinical samples were tested for IgM antibodies against dengue, chikungunya, Japanese encephalitis, scrub typhus, and leptospirosis. Further, <i>Leptospira</i> IgM ELISA positives (<i>n</i> = 79) were also tested by microscopic agglutination test (MAT) assay. In AUFI cases, scrub typhus was the predominant bacterial aetiology (24.6%, 593/2407) followed by leptospirosis (12.4%, 266/2151). Dengue (23.0%, 321/1398) was the leading cause among viral aetiologies. Similarly, among AES cases, scrub typhus (36% in cerebrospinal fluid and 34.3% in serum) remained the most common bacterial aetiology followed by leptospirosis (5.42%, 11/203). Whereas, chikungunya was the predominant viral cause (5.4%, 17/314) behind AES cases. Further, using MAT assay, 7.6% (6/79) of the AUFI samples tested positive for leptospirosis. The prevalent serogroups identified included <i>L. interrogans</i> serovars Australis, Pomona, Hebdomadis, Pyrogenes and Djasiman, and <i>L. borgpetersnii</i> serovar Tarassovi. Housewives constituted the primary risk group for leptospirosis infection, followed by individuals engaged in various farming practices. This study identifies scrub typhus as the predominant and leptospirosis as the second most common infection in sporadic cases of AUFI and AES. Therefore, continuous monitoring of changing aetiologies is crucial for the effective implementation of targeted control and preventive measures for neglected tropical diseases.