Scrub Typhus - A potentially life threatening fever ?

 What is scrub typhus ?

    Orientia tsutsugamushi, an obligate intracellular gram-negative bacterium, is the source of the acute febrile illness known as scrub typhus. Although scrub typhus caused by other Orientia species has been reported in Africa, France, the Middle East, and South America, it is believed to be endemic to the tsutsugamushi triangle, which includes Asia, northern Australia, and islands in the Indian and Pacific Oceans. According to a recent systematic review from hospital-based studies in India, scrub typhus was the root cause of 25% of acute undifferentiated febrile illnesses. 

     O. tsutsugamushi transmitted by the bites of infected chiggars( trombiculid mite) has been linked in recent studies to acute encephalitis syndrome (AES) outbreaks in India, particularly in the northern states of Uttar Pradesh, Bihar, West Bengal, and Assam. Outbreaks of AES pose a major public health problem in India, predominantly affecting children. 

Spectrum of Clinical Features-

      All patients who exhibit an acute onset of fever and altered mental status are included in the broad definition of Acute Encephalitis Syndrome used for syndromic surveillance. Typical clinical features include fever with chills & rigor ,headache,bodyaches,muscle cramps,altered sensorium ,lymphadenopathy and rash .

 The pathognomonic classical scrub typhus rash has been described as a dark scab like region at the site of the chiggar bite, popularly known as 'Eschar'.

      The clinical manifestation may be brought on by encephalitis, meningitis, or encephalopathy without CNS invasion, such as in cases of severe systemic infection, metabolic disturbance, or other neurologic complications following the infection. 

Diagnostic Challenges-

        Early diagnosis is essential for starting prompt, targeted treatment, which can lower scrub typhus complications and fatality rates. Due to the symptoms' similarity to those of other tropical infections that are endemic to the region and can also cause AES, such as dengue, chikungunya, malaria, and leptospirosis, clinical diagnosis can be difficult. 

       There are drawbacks to the current microbiological diagnostics for scrub typhus, which are typically based on IgM detection in serum samples or nucleic acid by PCR. IgM can persist for a long time after the onset of acute illness, and it can react with IgM from other cocirculating pathogens. IgM first appears in serum 5–6 days after the onset of illness .Therefore, it is challenging to determine O. tsutsugamushi as the cause in AES patients who also have microbiological evidence of another potential pathogen.

        Patients with suspected neurologic scrub typhus do not undergo routine IgM detection in cerebrospinal fluid (CSF).The immunofluorescence assay has long been regarded as the gold standard in serologic testing, but its use is constrained by its high cost and difficult interpretation. Serologic tests' limitations in terms of cross-reacting and persistent antibodies may be addressed by PCR, but a positive result is only likely to occur during the bacteremia stage of infection .

        Additionally, blood or eschar material are suggested samples for O. tsutsugamushi PCR, whereas it is unknown how sensitive PCR is to CSF.

          More than 50% of patients had anaemia, leukocytosis, thrombocytopenia, transaminitis, hypoalbuminemia, and uremia. Most patients' CSF tests showed lymphocytic pleocytosis and increased protein concentration.

Treatment-

       Doxycycline 100mg twice daily x 10 days has been the drug of choice for most of the patients without having obvious comorbid conditions. Supportive therapy in terms of Paracetamol, Intravenous Fluids etc are often required. Comorbid conditions like Diabetes Mellitus, Pre-existing Nephropathy can lead to AKI like manifestations in selected group of patients. Hence a constant vigilant monitoring of serum creatinine, electrolytes along with CRP/Procalcitonin  may be of importance to optimise the therapeutic outcome.