Rickettsial diseases (RD) are widely reported all over the world. Scrub typhus (ST) is a major tropical infection which is well documented all over India. Therefore, the index of suspicion of scrub typhus is high among physicians with regard to patients presenting with acute febrile illness (AFI) and acute undifferentiated febrile illness (AUFI) in India. Rickettsial diseases other than ST (non-ST RDs), which include spotted fever group (SFG) rickettsioses and typhus group (TG) rickettsioses are not uncommon in India, but the index of suspicion is not as high as ST unless there is a history of the presence of fever with rashes and/or recent arthropod bites. This review aims to look into the Indian scenario on the epidemiology of non-ST RDs, especially the SFG and TG rickettsioses based on various investigations, spectrum of clinical presentation, challenges and gaps in knowledge to suspect and diagnose these infections.

Rickettsial diseases (RDs) are major under-diagnosed causes of arthropod borne acute febrile illness (AFI) presenting with a range of symptoms from mild self-limiting fever to fatal sepsis. The spotted fever group (SFG) and typhus group (TG) are major RDs, which are commonly caused by Rickettsia conorii and Rickettsia typhi, respectively. The limited availability and role of serological tests in the acute phase of illness warrants rapid reliable molecular methods for diagnosis and epidemiological studies. Two hundred patients with AFI in whom the routine fever diagnostics were negative, were enrolled over a period of two months (April 2019 to May 2019). DNA was extracted and in-house nested PCR using primers specific for both SPG and TG pathogens was used. The positive amplified products were sequenced for species identification and phylogenetic analysis was performed using MEGA 7.0.14 software (iGEM, Temple University, Philadelphia, PA 19122, USA). The demographic details of the RD cases were documented. The prevalence of RD among AFI cases was 7% (14/200); SFG and TG were identified as the cause in 4% and 3% of AFI cases, respectively. The median age of the RD cases was 22 years (range 2–65). The median duration of fever was 3 days (range 1–12). The RD cases presented with respiratory symptoms or signs (44.44%), jaundice (22.22%), abdominal pain (22.22%), diarrhea (22.22), vesicular rash (11.11%), vomiting (11.11%), loss of appetite (11.11%), headache (11.11%), leukocytosis (88.88% with mean count 22,750/mm³), and thrombocytopenia (33.33%). The cases were treated empirically with piperacillin-tazobactam (66.66%), clindamycin (44.44%), cefotaxime (33.33%), meropenem (33.33%), metronidazole (33.33%), doxycycline (22.22%), azithromycin (22.22%), ceftriaxone (11.11%), and amoxicillin-clavulanic acid (11.11%). The mortality among the RD cases was 11.11%. The present pilot study shows that RD is not an uncommon cause of AFI in north India. The febrile episodes are usually transient, not severe and associated with heterogenous clinical presentation without documented history of tick exposure in the hospitalized patients. The transient, non-severe, febrile illness could be due to transient rickettsemia resulting from empirical antimicrobial therapy as the rickettsial organisms are expected to be more susceptible to higher doses of β-lactam antibiotics. The study emphasizes the molecular method as a useful tool to identify rickettsial etiology in AFI.

Scrub typhus (caused by Orientia tsutsugamushi) is a neglected and underdiagnosed disease due to its non-specific clinical presentation and challenging diagnostics. We document the first study of direct diagnosis of scrub typhus from the blood sample of a patient by full-length 16S ribosomal RNA gene amplicon analysis using Oxford Nanopore sequencing.

Haemophagocytic lymphohistiocytosis (HLH) is a rare complication of rickettsial infections. We report a 50-y-old man from northern India who presented with fever, respiratory distress, altered sensorium and an eschar. Despite treatment with doxycycline, his condition deteriorated with multi-organ dysfunction. PCR and sequencing from the eschar confirmed Rickettsia conorii. Bone marrow examination, elevated ferritin and triglycerides, as well as an H-score of 224 confirmed HLH. The patient was treated with corticosteroids but succumbed to refractory ventricular arrhythmias. A high index of suspicion is essential in rickettsial infections that present with multi-organ dysfunction, as early recognition of HLH enables the prompt initiation of treatment of the underlying disease and adjunctive immunosuppressive therapy. [GenBank accession nos. U59728.1 and MZ779037.]