Is Scrub Typhus dangerous? Must Read!!

Introduction
Scrub typhus is a mite-born acute infectious disease caused by gram-negative bacteria Orientia tsutsugamushi. The disease does not spread from one human to another. Instead, it is a zoonotic disease that transmits to humans from the bite of mite larvae called “Chiggers” belonging to the Trombiculidae family. Trombiculid mites are small (0.2–0.4 mm) and have a four-stage life cycle: egg, larva (chigger), nymph, and adult. However, only the larval stage of the mite can transmit the bacterium to other human beings. The Trombiculidae mites responsible for Scrub typhus belong to a particular species called Leptotrombidium delicense. Scrub typhus affects people of all ages, including children. Scrub typhus is also known as bush typhus, tsutsugamushi disease, or chigger-borne typhus. Incidence of scrub typhus is more prominent in Far East Russia, Japan, and Northern.
Australia. Thus, those areas are also known as the “tsutsugamushi triangle.” Afghanistan, India, China, Japan, and Indonesia also show the incidence of scrub typhus.
The incubation period of scrub typhus is about 5–20 days (mean 10–12 days) after the initial chigger bite. The common areas where chigger bites are the crotch, axillae, genitalia, and neck. A chigger’s bite is painless and leads to the development of a Papule at the site of the bite. The papule dries out and blackens, forming a necrotic lesion of the skin, which is known as an “eschar.”
Upon onset, scrub typhus is associated with the following symptoms:

• Chills and Fever
• Headache
• Infection of the conjunctiva
• Respiratory distress
• Swelling of lymph nodes
• Body aches and muscle pain

After one week, spotted and maculopapular rashes appear, which blenches within a few days. Scrub typhus can lead to multiple health complications if not diagnosed and treated quickly. In severe cases, scrub typhus can lead to:

• Hypotension (low blood pressure)
• Thrombocytopenia (deficiency of platelets in the blood)
• Leucocytosis (increase in white blood cells)
• Hypoxia (difficulty breathing)
• Acute renal failure
• Hypoalbuminemia (deficit of albumin)
• Hepatic dysfunction (liver not working properly)

This article talks about the health complications associated with Scrub Typhus.

Health Complications associated with Scrub Typhus

1. Intestinal Pneumonia
   Interstitial pneumonia (IP) is a common health complication associated with scrub typhus. Apart from IP, the other chest abnormalities associated with scrub typhus include:
      • Cardiomegaly (enlarged heart)
      • Pulmonary edema (excess fluid in lungs)
      • Pleural effusion (presence of fluid between the lungs and chest)
      • Hilar lymphadenopathy (enlargement of the lymph nodes of the pulmonary hila)
      • Focal atelectasis (complete or partial collapse of the lung)
   The clinical significance or the reason behind scrub typhus causing IP is unknown. Therefore, young Ok Kim et al. carried out a study to evaluate if interstitial pneumonia can be a biomarker of the severity of scrub typhus. The study design involved 101 patients with scrub typhus.
   Clinical findings through chest radiography of the patients showed the above abnormalities.
   When compared with patients without IP, scientists found that patients with IP had higher incidences in episodes of the following:
      • Hypoxia
      • Hypotension
      • Severe Thrombocytopenia
      • Hypoalbuminemia
      • Pleural effusion
      • Focal atelectasis
      • Cardiomegaly
      • Pulmonary alveolar edema
      • Hilar lymphadenopathy
   The study concluded that IP is a common health complication associated with scrub typhus, and it also leads to other health complications that increase the severity of scrub typhus.
2. Meningoencephalitis
   Meningoencephalitis is a known complication associated with scrub typhus. Meningoencephalitis is the inflammation of the brain and its surrounding tissues due to infection. Scrub typhus is also related to other neurological complications, including:
      • Seizure
      • Cranial nerve deficits (impairment of cranial nerves)
      • Vasculitic cerebral infarct (the inflamed vessel that blocks the flow of oxygen to the brain causing loss of brain function)
      • Brain hemorrhages (ruptured blood vessel inside the brain)
      • Polyneuropathy
      • Sensorineural hearing loss (damage to the nerve connecting the ear to the brain)
   Scientists believe that the neurological complications with scrub typhus are due to its direct invasion of the CNS by the bacterium. The polymerase chain reaction of cerebrospinal fluid supports the above statement. However, some other scholars say that the neurological complications are due to the unique property of the bacterium to infect vascular endothelial cells.
   A Hospital-based observational study was carried out in Shillong, Meghalaya, on 13 patients with scrub typhus. The study results have been published by Masaraf Hussain et al. in the Journal of Neurosciences in Rural Practice, 2015. The physician diagnosed meningoencephalitis through Weil’s Felix and IgM antibody serology tests. The study results showed that doxycycline tablets showed improvement when given with or without azithromycin injection. In addition, 15.38% of the patients in this study expired due to multiorgan dysfunction. The study concluded that timely diagnosis and treatment of scrub typhus increases the chances of recovery and decreases mortality.
3. Myocarditis
   Myocarditis and other cardiac complications like cardiogenic shock and cardiac arrest are rarely reported with scrub typhus. Jung Yeon Chin et al. carried out a retrospective study to evaluate predictors of acute myocarditis in 89 patients diagnosed with severe and complicated scrub typhus and admitted to the ICU. The patients were divided into two groups. The first group of patients had myocarditis, and the second group didn’t have myocarditis. The diagnosis of myocarditis involved guidelines as per the European Society of Cardiology.
   The study found that patients with myocarditis (acute) had:
      • More elevated total bilirubin
      • High incidence of ST elevations
      • Paroxysmal Atrial Fibrillation
   The study showed Paroxysmal Atrial Fibrillation (PAF) as a predictor of myocarditis with sensitivity and specificity of 70% and 84%, respectively. The study concluded that although cardiac complications have been rarely reported, they may be more common.
   The study also concluded that patients with high bilirubin and PAF are at increased risk of acute myocarditis with scrub typhus.
4. Acute Kidney Injury/ Acute Renal Failure
   Scrub typhus infection can cause renal complications ranging from asymptomatic urinary abnormalities to dialysis-dependent renal failure. Acute Kidney Injury in scrub typhus is usually mild and non-oliguric (urine output more than 1mL/kg per hour).
   The breaking down of muscle tissue releasing protein into the blood of some patients having scrub typhus also contributes to Acute Kidney Injury.
   A prospective case-record-based study published in Clinical and Experimental Nephrology found Thrombocytopenia and intensive care requirements as significant predictors of Acute Kidney Injury in scrub typhus.
   Similarly, a retrospective study carried out in a South Indian Tertiary Care Hospital on scrub typhus patients (adults and children) resulted in the following outcomes:
      • Acute Kidney injury was predicted in scrub typhus patients who had the following health complications:
          Hypotension
          Acute Lung Injury
          Multiorgan Dysfunction Syndrome
          Increased AST levels
          Hypoalbuminemia
      • Mortality was high in patients developing Acute Kidney Injury
      • The majority of the cases of scrub typhus was in the winter season
      • Early diagnosis and treatment can prevent mortality and prevents health complications.
5. Multiorgan Dysfunction
   Epidemiologists have reported acute liver failure in patients with scrub typhus, mainly from the Indian subcontinent. The data shows that acute liver failure is common and reversible. Acute hepatic failure is defined as the development of encephalopathy and coagulopathy in patients without any pre-existing liver disease. Acute hepatic failure in scrub typhus patients generally manifests in jaundice and elevation of the transaminase enzymes. A case study published in the Cureus Journal, 2020, reported the case of a pregnant female who had acute liver failure, fever, encephalopathy, jaundice, seizure, and dead fetus during hospitalization. Despite appropriate and supportive treatment procedures, the female developed multiorgan dysfunction leading to her demise.
   An article published in the Journal of global infectious diseases, 2014, reported seven adult patients diagnosed with scrub typhus and had acute pancreatitis. The overall health complications apart from acute pancreatitis include:
      • Abdominal pain
      • Presence of eschar
      • Higher mean serum lipase and amylase
      • Hematological and Respiratory system dysfunction
      • Central nervous system dysfunction
   The study reported the demise of three patients who had multiorgan dysfunction. The study concluded that pancreatitis in scrub typhus is an infrequent complication and, when present, is associated with increased mortality.
   Other health complications associated with scrub typhus include Septic shock and acute respiratory distress syndrome (ARDS)

Conclusion
Scrub typhus is a dangerous disease. Without timely and proper diagnosis and treatment, it can lead to multiple health complications, as mentioned above, and ultimately death due to multiple organ failures. Published literature in journals reports that approximately 6% of death cases if left untreated. The death rate varies between complications with multiorgan failure resulting in maximum death (24%) followed by brain infections (14%). However, people diagnosed early and undergoing doxycycline antibiotics recover quickly from scrub typhus. Apart from this, patients need to take necessary actions to prevent bites from mites (chiggers). Finally, always follow the advice of your physician and report them if you have any unwanted health complications.

References

1. Scrub Typhus. Accessed at
   https://www.medindia.net/patients/patientinfo/scrub-typhus.htm#what-is-scrub-typhus
2. Scrub typhus. Accessed at
   https://www.nhp.gov.in/disease/scrub-typhus#:~:text=Scrub%20typhus%20is%20an%20acute,by%20arthropod%20vector%20trombiculid%20mite.
3. Scrub Typhus. Accessed at
   https://www.cdc.gov/typhus/scrub/index.html
4. Chakraborty, S., & Sarma, N. (2017). Scrub Typhus: An Emerging Threat. Indian Journal of dermatology, 62(5), 478–485. https://doi.org/10.4103/ijd.IJD_388_17
5. Chin, J. Y., Kang, K. W., Moon, K. M., Kim, J., & Choi, Y. J. (2018). Predictors of acute myocarditis in complicated scrub typhus: an endemic province in the Republic of Korea. The Korean Journal of internal medicine, 33(2), 323–330. https://doi.org/10.3904/kjim.2016.303
6. Jayaprakash V, Vamsikrishna M, Indhumathi E, Jayakumar M. Scrub typhus-associated acute kidney injury: A study from a South Indian Tertiary Care Hospital. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2022 Mar 3];30:883-90. Available from: https://www.sjkdt.org/text.asp?2019/30/4/883/265464
7. Jamil, M. D., Hussain, M., Lyngdoh, M., Sharma, S., Barman, B., & Bhattacharya, P. K. (2015). Scrub typhus meningoencephalitis, a diagnostic challenge for clinicians: A hospital-based study from North-East India. Journal of neurosciences in rural practice, 6(4), 488–493. https://doi.org/10.4103/0976-3147.169769
8. Song, S. W., Kim, K. T., Ku, Y. M., Park, S. H., Kim, Y. S., Lee, D. G., Yoon, S. A., & Kim, Y. O. (2004). Clinical role of interstitial pneumonia in patients with scrub typhus: a possible marker of disease severity. Journal of Korean medical science, 19(5), 668–673. https://doi.org/10.3346/jkms.2004.19.5.668
9. Attur RP, Kuppasamy S, Bairy M, Nagaraju SP, Pammidi NR, Kamath V, Kamath A, Rao L, Bairy I. Acute kidney injury in scrub typhus. Clin Exp Nephrol. 2013 Oct;17(5):725-729. doi: 10.1007/s10157-012-0753-9. Epub 2013 Jan 5. PMID: 23292176.
10. Gaba, S., Sharma, S., Gaba, N., & Gupta, M. (2020). Scrub Typhus Leading to Acute Liver Failure in a Pregnant Patient. Cureus, 12(9), e10191. https://doi.org/10.7759/cureus.10191
11. Ahmed, A. S., Kundavaram, A. P., Sathyendra, S., & Abraham, O. C. (2014). Acute pancreatitis due to scrub typhus. Journal of global infectious diseases, 6(1), 31–34. https://doi.org/10.4103/0974-777X.127949
12. Bonell A, Lubell Y, Newton PN, Crump JA, Paris DH. Estimating the burden of scrub typhus: A systematic review. PLoS Negl Trop Dis. 2017 Sep 25;11(9):e0005838. doi: 10.1371/journal.pntd.0005838. PMID: 28945755; PMCID: PMC5634655.