What is Scrub Typhus?

Scrub typhus is a serious infectious disease caused by a type of bacteria called ‘Orientia tsutsugamushi’. This bacterium changes a lot which makes the disease hard to fight. It’s a major health problem in the Asia-Pacific area, a region also known as the “tsutsugamushi triangle”. This triangle covers over 8 million square kilometers and has more than 1 billion people. It includes countries like Pakistan, Australia, and Japan. The disease poses a big health risk in this area and can often be fatal.

A detailed review disclosed that in India, which is part of the “tsutsugamushi triangle,” scrub typhus makes up at least 25.3% of cases of people suffering from a fever with an unclear cause. Despite being a common cause of such illness, scrub typhus is often overlooked in terms of research and health care policy making.

The disease spreads to humans through the bite of young mites. This leads to widespread inflammation of blood vessels, leakage from blood vessels, and damage to organs. Anyone who travels to the areas where the disease is common and people of all ages can catch this disease. After 6 to 21 days of being infected, symptoms such as fever, headache, muscle pain, and stomach issues usually appear.

A distinctive feature of scrub typhus is an ‘eschar’, which is a crusty sore that develops at the site of the mite bite. It starts as a small raised spot and later turns into a black ulcer with tissue death in the middle. However, not everyone with scrub typhus will have an eschar, and this can vary based on the area. Doctors will often start treatment based on the suspicion of scrub typhus, and confirm with blood tests later.

What Causes Scrub Typhus?

Scrub typhus is a disease that often goes unnoticed, causing fever and discomfort. It’s particularly common in certain parts of the world. This illness can affect many body systems, mainly due to inflammation and damage to your blood vessels. It’s transmitted to humans by mite larvae or “chiggers” that carry harmful bacteria. These mites pass on the bacteria through their bites. The bacteria can remain in the mites and sometimes in small animals, allowing the disease to persist in nature.

The bacteria causing scrub typhus, called Orientia, has a very complex and repetitious genetic structure. This is due to a lot of deletions and duplications within its genome. There are also rearrangements involving transferable and connectable elements in the genome, contributing to its complex nature. Among Orientia’s structural proteins, one known as the 56-kDa type-specific antigen stands out. It’s a unique protein found on the surface of the bacteria. The study of this protein, which has variable regions, has helped identify several new subtypes of the disease in different locations. This underlines the genomic versatility of Orientia, going beyond the initially known forms of the bacteria.

The 56-kDa type-specific antigen is also known to trigger the production of neutralizing antibodies during infection. Because of the variations of Orientia bacteria present in different parts of the world, creating an effective vaccine has been challenging.

Risk Factors and Frequency for Scrub Typhus

Scrub typhus is a disease that is mostly found in Asia and is a significant cause of fever illnesses that are not related to malaria. Rates of people testing positive for the disease range from 9.3% to 27.9%, and it seems to be becoming more common. There are several theories for why this is happening. These include:

Population growth in recent years
Urban development causing changes in land use
More effective diagnostic tests leading to better case detection

In the 1990s, two drugs used to treat enteric fever and other unidentified fevers were shown to also be effective against scrub typhus. However, in the late 1990s, new drugs came into use which were found to be less effective against scrub typhus. Further factors include the increase in the population of chiggers, the carriers of the disease, in hot and humid environments. Global warming and increased levels of humidity during rainy seasons may be helping to increase rates of scrub typhus. Additionally, participation in outdoor activities that involve exposure to chiggers might also be a cause.

Currently, there are no licensed vaccines for scrub typhus, and systematic controls for its carriers have not been widely implemented. The disease can affect individuals of all ages, and there is no observed preference for gender or race.

Signs and Symptoms of Scrub Typhus

Scrub typhus is a disease caused by a bite from an infected Leptotrombidium mite, with an incubation period typically ranging from 10 to 12 days, although it can vary from 6 to 21 days. Those infected often show flu-like symptoms and develop a distinctive mark at the bite site, known as an eschar, which typically doesn’t cause pain or itching. The eschar, often appearing like a burn mark, starts as an ulcer before developing a black crust. It is usually found on the front of the body, below the belly button, and especially in women, in the breast area.

Common symptoms of scrub typhus include headaches, fever, swollen lymph nodes, nausea, vomiting, abdominal pain, and muscle pain. If not treated, the disease can worsen entering the second week, and individuals may develop more serious symptoms affecting the central nervous system and other organs. These serious symptoms can include brain inflammation, meningitis, hearing loss, eye problems, and in severe cases, seizures. Untreated scrub typhus also puts individuals at higher risk of developing a more dangerous condition known as multiple organ dysfunction syndrome (MODS), which can increase the risk of death.

Scrub typhus can also lead to various heart problems ranging from non-fatal rhythm abnormalities to signs of heart failure. It can also negatively affect the kidneys, potentially leading to acute kidney failure. The disease may cause lung issues, such as interstitial pneumonia and ARDS (a severe form of lung injury), and it can disturb the gastrointestinal system, potentially causing pancreatitis, liver problems, or diarrhea.

Testing for Scrub Typhus

It’s crucial to diagnose scrub typhus infection early in order to provide the right treatment and to prevent complications. However, in areas where the disease is prevalent, medical professionals often have limited access to quick, sensitive, and affordable diagnostic tools for this condition. As a result, doctors sometimes have to start treatment based on educated guesswork. But this approach can at times lead to diagnosing the wrong disease, which can interfere with proper patient care.

The most common way to confirm a scrub typhus infection is through blood tests. In a typical infection, there is a measurable increase in immunoglobulin M (IgM) antibodies by the end of the first week. On the other hand, higher levels of IgG antibodies usually develop about two weeks into the infection. If a person is reinfected with scrub typhus, IgG antibodies can be detected as early as the sixth day of the infection. At the same time, the amount of IgM antibodies can vary a lot in such cases.

A number of tests are available to detect scrub typhus. The oldest is the Weil-Felix test. Although it isn’t very sensitive or specific, it can help with early diagnosis. Another commonly used test is the indirect immunofluorescent antibody (IFA) test, often considered the gold standard for diagnosing scrub typhus. Yet, it requires repeated testing and cannot be used to guide the initial stage of treatment because of its limitations.

The Indirect immunoperoxidase test was developed to improve the IFA test. It doesn’t require a special kind of microscope and has shown results comparable to IFA. However, like IFA, the accuracy of this test can be influenced by different strains of bacteria.

The preferred method for diagnosing scrub typhus in the early stages is the enzyme-linked immunosorbent assays (ELISA) test. This test is often used due to the limitations of other tests and uses a specific type of antigen from a strain of bacteria, which binds with the IgM antibodies produced during the infection.

Immunochromatographic tests are quick point-of-care tests often used for scrub typhus diagnosis. Although these tests detect IgM antibodies with varying sensitivities and specificities, they are handy due to their rapid results. Polymerase chain reaction (PCR) techniques can potentially identify the disease before antibodies become detectable through blood tests, making for an early diagnosis. But PCR has a high cost, which makes it less ideal for routine diagnosis in disease-prone areas.

Culturing the bacteria causing scrub typhus is challenging due to the bacteria’s nature and requires significant technical expertise. The long and complex process renders culturing impractical for routine diagnosis. Finally, the cerebrospinal fluid (CSF) can be evaluated for patients showing signs of central nervous system involvement, though it’s more of an exception than a rule.

For patients presenting with respiratory symptoms, a chest x-ray is recommended. The x-ray images can reveal lung conditions like pleural effusions (fluid around the lungs) and pneumonia and serve as an additional diagnostic tool. In conclusion, diagnosing scrub typhus relies heavily on professional judgement and appropriate use of diagnostic tests, especially in areas where the disease is prevalent.

Treatment Options for Scrub Typhus

Scrub typhus, a bacterial infection, can be effectively treated with several types of antibiotics, which include tetracycline, azithromycin, doxycycline, and rifampicin. Each antibiotic has a different treatment duration, with doxycycline usually being used for 7 days and azithromycin for 3 days. Tetracycline and rifampicin are also known to work well for scrub typhus.

Doxycycline, which is often the first choice for treating rickettsial diseases (a group of diseases transmitted by ticks, fleas, and lice), works well against scrub typhus. However, there have been some instances where doxycycline was not effective, thought to be due to resistance developed by the bacteria.

Azithromycin is another good treatment option, especially when patients are suspected to be resistant to doxycycline. It has a long-lasting effect and can be administered for a shorter duration, which reduces the risk of relapse. It is effective against scrub typhus because it is good at penetrating into the specific types of white blood cells that the bacteria infect.

Rifampicin can also be used for scrub typhus, but its risk of creating resistant tuberculosis should be considered. So, it’s usually chosen after ruling out the possibility of active tuberculosis.

Some health professionals suggest preventive treatment with doxycycline for people at high risk of exposure, like agricultural workers. But this approach is controversial.

Scrub typhus can sometimes cause severe health complications, which may require intensive care and organ support. A recent study suggests using a combination of doxycycline and azithromycin for severe cases. Aggressive measures such as providing fluids intravenously and mechanical ventilation for respiratory distress may also be required. However, timely treatment with the right antibiotics can greatly aid the patient’s recovery.

Scrub typhus is a tropical fever that often goes unnoticed. It can show up as a fever with no clear cause, posing the same diagnostic problems as other similar diseases. When scrub typhus results in encephalitis (brain inflammation), it becomes hard to tell apart from other usual causes of encephalitis such as viral or bacterial infections. Due to similar symptoms, it might be mistaken for flu-related conditions. Moreover, signs of scrub typhus, like eschars (scabs or dry patches of skin), happening in 10% to 90% of cases, are easy to miss.

The diagnosis of scrub typhus is particularly challenging because it has the potential to affect almost every organ in the body. This often leads to a delay in the start of the correct treatment despite a strong suspicion based on symptoms and a good understanding of the disease. Other illnesses that should be considered when diagnosing scrub typhus include:

Malaria
Dengue
Leptospirosis
Typhoid fever

What to expect with Scrub Typhus

Research on severe scrub typhus, a kind of bacterial infection caused by mites, has found links between certain laboratory test results and a worse outcome for the patient. These tests can show an abnormally high white blood cell count (leukocytosis), lower than average blood platelets (thrombocytopenia), high liver enzymes (transaminases), abnormal chest x-rays, and high levels of creatinine in blood (sign of possible kidney damage).

Patients showing these signs, along with septic shock (a serious condition that occurs when an infection leads to dangerously low blood pressure) and unusually low body temperature, are at a higher risk of developing multiple organ dysfunction syndrome (MODS, a life-threatening condition where multiple organs begin to fail), and hence are more likely to lose the battle against the infection compared to those having just fever.

Severe lung involvement such as acute respiratory distress syndrome (ARDS) – a lung condition that causes low oxygen levels in the blood – is also tied with increased death rates. When it comes to severe scrub typhus, kidney failure can be particularly dangerous, with a creatinine level (a waste product filtered out of the blood by the kidneys) over 1.4 mg serving as an indicator likely to suggest a fatal outcome.

According to a retrospective epidemiological study by Lee and colleagues, having certain conditions on arriving at the intensive care unit (ICU), like absence of an eschar (a dry, dark scab or falling away of dead skin) and having higher scores on a severity of disease classification system (APACHE II), independently correlate with higher death rates.

In another study by Sonthayanon and others, it was found that higher amounts of scrub typhus DNA (the genetic makeup of the bacteria causing scrub typhus) at the time of admission are associated with increased mortality and longer illness duration. However, because of cost limitations in resource-limited settings, the practical value of doing DNA testing is limited.

Unfortunately, clear indicators for determining outcomes for severe scrub typhus infection have yet to be definitively established because the studies available have been limited and produced conflicting results.

Severe scrub typhus can present as multiple organ dysfunction syndrome (MODS), showing in forms like ARDS, inflammation of the heart muscle (myocarditis), liver failure, acute kidney failure, inflammation of the brain (encephalitis), shock from blood vessel inflammation (vasculitis), and these can occur in various combinations. Any delay in treatment increases the mortality index (the rate of patient deaths) significantly, which can sometimes go up as high as 30%.

Possible Complications When Diagnosed with Scrub Typhus

People affected by scrub typhus often experience complications that span across several body systems. These complications are usually reflective of the seriousness of the disease and its impact on the individual’s body.

Pulmonary or lung-related issues include conditions like ARDS (severe lung disease) and pneumonitis (lung inflammation). Doctors often observe abnormal results in chest X-rays, with issues like water in the lungs (pleural effusion) and various heart conditions like heart failure. Scrub typhus can cause fluid to build up in the lungs, especially in older individuals or people with heart issues or low albumin levels (a type of protein in the blood).

Cardiac or heart-related complications are not well-defined with scrub typhus, but many patients are known to have reversible enlarged heart. A review of heart activity through an electrocardiogram (ECG) can show a wide range of changes, from a fast heart beat to a slow heart rate. Other heart complications include atrial flutter (irregular heartbeat), heart block, and sometimes even premature beats from the ventricles (lower chambers of the heart). Notably, ECG changes might come from imbalances in the body’s electrolytes (mineral levels) or acid levels, not directly from the scrub typhus infection itself. Still, a rare condition called myocarditis (heart inflammation) can present severe symptoms ranging from fever and muscle aches to shortness of breath and even sudden death.

Neurological complications from scrub typhus primarily occurs due to inflammation of the blood vessels in the brain. Patients can present with stiff neck, headache, confusion, and sometimes show results similar to tuberculosis meningitis. Further, the more severe form, meningoencephalitis, can potentially lead to death by causing confusion and seizures, but with appropriate treatment, these complications usually improve.

Gastrointestinal complications often present within a week from fever onset, with symptoms ranging from diarrhea and stomach pain to liver dysfunction and spleen enlargement. Understandably, the presence of these symptoms often leads to a mistaken diagnosis of an acute abdomen condition requiring surgery.

Renal or kidney-related complications are rare but can lead to acute kidney injury and is a significant factor indicating the potential for mortality. The development of kidney injury can be due to a number of factors and makes treatment with antibiotics and supportive care crucial.

Additional complications of scrub typhus can lead to severe problems like abnormal blood clotting or overactive immune response. Eye complications like papilledema (swelling of the optic nerve) and various pregnancy complications like preterm deliveries, miscarriages, and small-for-gestational-age babies are also possible. Sadly, severe cases have even led to neonatal deaths.

Common Complications:

Lung-related issues like ARDS and pneumonitis
Cardiac complications like enlarged heart and irregular heartbeats
Neurological issues leading to inflammation of the brain’s blood vessels
Gastrointestinal symptoms like diarrhea and liver dysfunction
Rare kidney-related complications causing acute kidney injury
Additional complications including abnormal blood clotting and eye issues
Pregnancy complications leading to preterm deliveries and small-for-gestational-age babies

Preventing Scrub Typhus

The signs of scrub typhus, a type of bacteria-caused infection, can often appear similar to symptoms of other diseases. This can make it tricky to diagnose. It’s prominent in certain parts of the world, so it’s important for people to tell their doctors if they’ve recently traveled to those areas, especially if they start feeling unwell.

People should see a doctor if they are in these areas and start to have a fever with a skin lesion called an eschar (a dry, dark scab). It’s important to get treatment for scrub typhus as soon as possible because it can be cured without causing further health problems if caught early.

Those traveling to areas where scrub typhus is common should be aware of how to avoid mite bites because mites are how the disease is spread. One possible way to prevent the disease is by taking an antibiotic called doxycycline at a dose of 200mg every week, but this is not agreed upon by all health specialists.

Currently, there is no vaccine available to prevent getting scrub typhus.