Scrub typhus is a kind of tropical disease-causing undifferentiated febrile illness by a bacteria named Orientia tsutsugamushi.
Scrub typhus case is reported mostly in the areas of South East Asia, Indonesia, Japan India, and Northern Australia. The infection could be transmitted from human to human at the time of traveling or living in that area.
Scrub typhus is now considered a remarkable public health hitch in Asia, where about 1 million new cases are identified annually and 1 billion people may be at risk for this disease. This disease most commonly emerges during the rainy season. However, it can exist all over the year.
The term scrub typhus is derived from a Greek word where the scrub is a type of vegetation that harbors the vector and typhus mean fever.
What is Scrub Typhus?
Scrub Typhus is a disease that spreads to humans through bites of larval mites or infected chiggers. This disease is also known as bush typhus and is one of the causes of typhus fever. Scrub typhus is caused by bacteria named Orientia tsutsugamushi with the clinical presentation of fever, headache, body ache, and sometimes rashes.
There are other causes of typhus fever which is caused by bacteria of the Rickettsia family and also by the body lice. The typhus fever caused by the Rickettsia family is murine typhus whereas the typhus by body lice is epidemic typhus.
History of Scrub Typhus
Scrub typhus was first reported in Japan in 1899 and the causative agent is Orientia tsutsugamushi. This is a tropical acute infectious vector-borne disease that is transmitted to humans by arthropods of the Trombiculidae family. Since this is a zoonotic disease the humans are the accidental host. The infectivity of scrub typhus is wide and therefore affects people of all ages even children.
The Greeks could be the ones who first discovered typhus. The history of typhus epidemics was explained in European countries a long time ago. Outbreaks were due to poor hygiene, sanitation, especially in the area where a large number of rats and mice are common.
Some example includes at the time of Napoleon Bonaparte. Retreating from Moscow in 1823, a massive outbreak in Ireland in 1830, and outbreaks in the U.S in the 19th century are its common examples. Even during World war, 3 million lives were lost due to typhus fever.
Epidemiology of Scrub Typhus
Scrub typhus is widely distributed in the area of tsutsugamushi triangle which includes a wide region of 13 million km2 starting from Japan in the east going through China, Philippines, tropical Australia in south and India, Pakistan extending to Tibet, Afghanistan, and in some southern part of Russia in Northside. Prevalence of the disease is highly seen in Southeastern and eastern parts of Asia including India, Nepal Maldives, Myanmar, Srilanka, Thailand, Pakistan, etc.
Season of Transference
In Tropical areas, Scrub Typhus transmission occurs throughout the year. But in some temperate zones, seasonal transmissions are observed. But some research has shown that it is more common in the rainy season. This is due to the increased chiggers attached to the rodents in wetter months, But some places have reported scrub typhus positive even in cooler seasons.
Vectors for Scrub Typhus
The most common vectors for scrub Typhus in southeast Asia are L. deliense and Leptotrombidium akamushi. The vector mite is commonly present in rain forest, semi-deserts, and in the Himalayan region, it is commonly found on subarctic terrains.
Wild rats that fall under the genus Rattus are the hosts of scrub typhus. Rodents found in the field and vector mites act as the reservoir of the infection that continues to grow in nature.
In humans and rodents, the infection is transmitted by chiggers that fall under trombiculid mites. These mites depend on lymph and fluids found in tissues. Once they infect the small mammals and rodents, they maintain their lifecycle become adults, and pass the infection in the form of eggs. This process is called transovarial transmission.
After transovarial transmission, the egg passes to larva or adult and this process is called transstadial transmission.
These mites’ larvae prefer to enter the body through hair follicles or pores. Large numbers of O. tsutsugamushi are present on the saliva of larvae and they enter into the host when the mites feed.
Infection to Human
Humans are accidental hosts who get the infection when they pick up infective larvae at the time of walking, sitting, or lying on the ground which is infested. Adult mites pass through four stages of the lifecycle: egg, larva, nymph, and adult. Chigger or larvae is the only stage that is capable of transmitting the disease to humans and other mammals.
Disease severity depends on the host immunity and strain of the organism.
- O. tsutsugamushi when entering inside the body causes downregulation of the host defense mechanism by decreasing the production of GP-96 on macrophages and endothelial cells. These cells play an important role in antigen presentation and dendritic cell function antibody production and cross-priming of the immune system.
- After entering the body, the organism attacks endothelial cells and causes the production of disseminated vascular and perivascular inflammatory lesions. This leads to vascular leakage and organ injury of different organs such as lungs, heart, and kidney significantly.
- This organism causes induction of cytokines like granulocyte colony-stimulating factor, interferon γ, and tumor necrosis factor-α. The Natural Killer T cells and cytotoxic T lymphocytes destroy infected cells.
- Cell-mediated immunity against Orientia is activated by T-lymphocytes resulting in the production of interferon γ by mononuclear cells in the peripheral blood.
The incubation period is generally between 6-21 days. The incubation period is the time between the exposure of the first infection and the appearance of symptoms.
Symptoms of Scrub Typhus
- Chilling sensation and presence of Fever
- Headache, delusion, mental impairment that could start as confusion to ends in coma
- Pain in body and muscle
- A scab-like region also called eschar can be seen in the site of insect bites. (Dark, brown, or blackish color)
- Enlargement of lymph nodes
- Skin rashes
- Fast breathing
Diagnosis of Scrub typhus
Fever and eschar support the diagnosis of scrub typhus. Several laboratory tests can be useful in diagnosing scrub typhus infection.
- Antibody Detection.
Serology is the primary test for diagnosing infection. In primary infection, a crucial rise in antibody titer can be observed at the end of 1st week. These are IgM antibodies. IgG starts to appear at the end of 2nd week.
The easiest and cheap serological method is the Weil-Felix(WF) test. This test has low sensitivity but has high specificity. The test is based on the detection of antibodies to various proteus species. These proteus species contain cross-reacting antigenic epitopes to the antigen of Rickettsia except Rickettsia akari. The positive test shows a titer of 1:320 or greater.
- Immunofluorescence antibody (IFA)
Gold Standard method for detection of scrub typhus is indirect immunofluorescence antibody (IFA). The test can confirm infection even before the seroconversion.
- Western immunoblot assay
Western immunoblotting and electrophoresis method is used for the large-scale screening of scrub typhus. This method is considered to be a very specific serodiagnostic tool for confirmation of infection and confirming cross-reactive strain.
This assay is recombinant protein-based and uses the most common and dominant protein for detecting Orienta specific antibodies.
For the culture of the organism buffy coat from the heparinized sample, necropsy tissue, a skin biopsy can be used. Different methods can be used to identify rickettsia strain like embryonated chicken yolk sacs, cell culture in Vero cells, MRC 5 cells, BHK21, L929 mouse fibroblast cell monolayer in tube culture.
- Polymerase Chain Reaction
PCR can be done from biopsy samples taken from skin rashes, lymph nodes, or EDTA blood. Real-time PCR is best for sensitive and more quantitative results.
- Loop isothermal amplification
This technique is very simple and inexpensive which amplifies DNA. It is inexpensive and simple to perform. This is a very fast method and takes only 24 hours.
- Nested PCR technique
This method is highly sensitive and gives quantified results. It can detect the infection 3rd day of fever even before the appearance of the antibody. The best samples for the nested samples are biopsies from Eschar.
- An increase in leukocytes and a decrease in platelet can be seen.
- High AST levels are seen in most cases.
- High bilirubin and low albumin can be seen.
- In highly complicated cases rise in creatinine levels can be seen.
- Liver and spleen enlargement can be seen in Ultrasonography.
- Chest X-ray may show bilateral infiltration and pleural effusion.
The following disease should be kept in consideration while treating scrub typhus. All of the below have similar symptoms therefore proper laboratory diagnosis with clinical presentation is necessary.
- Severe fever with thrombocytopenia syndrome
- Typhoid Fever
Scrub Typhus Treatment
Doxycycline is considered to be the most effective treatment for scrub typhus to date. The medicine best works when it is taken as soon as possible after the first symptoms are seen. In some cases, patients may be allergic to doxycycline ciprofloxacin is also considered to be the choice of drug.
|1.||10mg/kg single dose of Azithromycin for children less than 8 years.|
|2.||2.2 mg/kg doxycycline orally twice daily for 3 days after fever resolution. (usually 5-10 days course for children who are more than eight years.|
|3.||Quinolones as alternative therapy orally 10mg/kg dose or intravenous 5mg/kg dose ciprofloxacin or levofloxacin for about 5-10 days and oral chloramphenicol 25 mg/kg for 5-10 days six-hourly|
|4.||All patients who are suspected to have meningitis or multiorgan involvement due to scrub typhus are started on intravenous chloramphenicol before obtaining a serological report.|
Scrub Typhus Complications
If scrub typhus is not treated timely, then it may lead to some complications which are highly severe and may cause mortality. Some of them are:
- Brain and spinal cord inflammation
- Enlarged spleen
- Inflammation of the heart muscle or valves
- Internal bleeding
- Kidney damage
- Liver damage
- Low blood pressure
- Septic shock
Prevention of Scrub typhus
Till now no vaccine has been found to protect from scrub typhus. But some measures can help in the prevention of scrub typhus
- Maintain personal hygiene
- Avoid contact with chiggers
- If traveling to the areas where scrub typhus is commonly found it is better to avoid areas with lots of vegetation and brush where the possibility of finding chiggers is high.
- To get protected from chiggers Environmental Protection Agency (EPA)-registered insect repellents external icon which contains DEET can be used.
- Reapplication of insect repellant is necessary when more time is spent outdoors.
Frequently asked questions(FAQs)
Is Scrub Typhus Curable?
Ans- Scrub typhus can be easily cured with the proper administration of appropriate antibiotics.
How long does it take to recover from Scrub Typhus?
Ans- If diagnosed correctly at the appropriate time, the fever will subside within 24-36 hours of treatment started.
Is scrub typhus fatal?
Ans- Mortality from scrub typhus if untreated can range up to 30%.
Is Scrub Typhus a serious problem?
Ans- Scrub Typhus could be life-threatening if left untreated and cause organ damage and other complications.
How to confirm Scrub Typhus?
Ans- There are several tests to diagnose scrub typhus but for confirmation, an Immunofluorescence assay using rash biopsy or PCR is recommended.