Resurgence of scrub typhus fever

Early detection is crucial in treating the disease spread by mites found in scrub land

Scrup typhus fever is again in news. Once restricted to rural areas, it has now spread to cities, with a few cases being reported in Delhi and over 1,000 cases being reported from places across Himachal Pradesh since June this year.

Scrub typhus has been known to mankind for centuries. The first documented reports of scrub typhus from India date back to 1946 and were from Assam-Burma border. The disease occurs in an area called “Tsutsugamushi Triangle”, with Japan in the east, Afghanistan and Middle-East region in the west and the pacific islands area, north Australia, Indonesia, south-east Asia, China, Korea in between. It is caused by a bacterium called Orientia tsutsugamushi. It belongs to a group which is smaller than bacteria but larger than viruses. The occurrence of the disease is a result of an interaction between bacteria, environment and humans.

The word “typhus” has been derived from the Greek word “typos” which means fever with stupor. The earliest medical accounts of typhus were written by Girolamo Cardano, an Italian physician, in 1536; in 1578, Johannes Coyttarus, dean of the faculty of the University of Poiters in France,  suggested that typhoid and typhus were different diseases. Scrub typhus is transmitted to humans by interaction with animal (a zoonotic disease). Japanese folklore knew it to be associated with the jungle mite or chigger, which was for this reason named “dangerous bug” (tsutsugamushi). In 1810 the Japanese Hakuju Hashimoto described a tsutsuga (disease) along the tributaries of the Shinano river. A similar disease, thought to be carried by mites, or mushi in Japanese, had also been known at least since the 16th century in southern China. During World War II, the incidence of scrub typhus rose dramatically among military troops, reaching 900 per 1,000 personnel in some areas. The larval forms of mites (trombiculid mites) act as reservoir for the bacteria (vector). These larvae feed on wild rats which reside in zones of scrub growth. These zones are often made up of secondary “scrub” growth, which grows after clearance of primary forest; hence the term “scrub typhus”. However, mites can survive on seashore, in rice fields and in semi desert areas also. These mites probably act as the major reservoir of the organisms and are capable of transmitting the disease from one generation to the next, and 90 to 100 per cent offsprings of infected female mites are capable of transmitting the bacteria and causing disease.

Chigger bite

Because of unique characteristics of mites and chiggers, and as chiggers can only stay within few metres of the the place where they hatch, there is formation of highly focal “islands of infection” in affected areas. There are four stages of life cycle of mites: egg, larva (chigger), nymph and adult. It is only in the chigger phase that the mite requires a blood meal to convert itself to adult mite, and hence it is the only stage of mite capable of transmitting disease to humans. These larvae feed on rodents, particularly wild rats. Humans get infected accidentally, on straying into a zone of infected mites. Once the chiggers have grasped a passing host, they prefer to feed where the skin is thin, tender or wrinkled and clothing is tight, and while feeding large numbers of bacteria (O. tsutsugamushi) found in the salivary glands of the chigger are injected into humans.  After feeding, the engorged chigger will drop off its host to transform into a mature adult.

Early diagnosis must

The bacteria enter the blood of humans and render the white blood cells (first line of defense against infection) useless by entering these cells and multiplying in these cells. At this stage, the disease will manifest and the initial presentation of scrub typhus has no specific signs and symptoms. It will present as fever with chills and rigors with severe headache and muscle pains.  Some of patients will develop a rash on the body and formation of knots around neck, in groin or arm pits, which can be painful. There is formation of a painless sore, and subsequently a black painless crust (resembling the skin burn of a cigarette butt; see photograph) where the chigger bites, in many patients; the sore is called “eschar”. The presence of eschar virtually confirms the diagnosis of scrub typhus. The disease, if suspected and treated at this early stage, is easily treated, however, if untreated at early stage the bacteria will invade various organs (kidneys, liver, lungs, brain and heart etc.) via blood stream, leading to inflammatory changes in these organs, causing failure of functions of various organs. The consequent  complications will manifest in the form of appearance of jaundice, decreased urine production, fall in blood pressure, increased respiratory rate and changes in consciousness levels during late phase of disease—during second week of illness.

The disease at this late stage will require admission in hospital, in an intensive care unit in many cases. The disease is easily treated with simple antibiotics at the early stage with minimal morbidity but it can be dangerous in later stages, and various studies have reported mortality due to scrub typhus ranging from 7 per cent to 30 per cent. It is a very difficult disease to diagnose as O. tsutsugamushi cannot be cultured in a laboratory. Moreover, highly sophisticated laboratories are needed for diagnosis of scrub typhus. These tests are useful, but it is not required in most of situations to subject patient to these expensive tests in routine clinical practice, especially when disease can be treated on clinical suspicion with simple and inexpensive antibiotics. Sometimes, it is not wise to wait for results of clinical tests for diagnosis of scrub typhus as it can lead to delay in starting treatment and can lead to onset of complications.

Treatable with low-cost antibiotics

Detection of IgM antibodies by ELISA in blood of patient is quite sensitive with reasonably high specificity for diagnosis of scrub typhus; this test can be performed in most of laboratories of our country. Thus, it is very important to recognise this disease at an early stage in order to prevent morbidity and mortality. Scrub typhus is treated with doxycycline 100 mg twice a day for seven to 10 days or azithromycin 500 mgs once daily for three days. For children below eight years and pregnant women, azithromycin is the preferred drug.

Literature on the disease mentions presence of scrub typhus in few pockets of India in the east and north, but sporadic cases were reported from Maharashtra, Punjab and Jammu area, mainly in military population. But in the past two decades, it is being increasingly reported from all parts of India. At present, this disease has been reported from Jammu and Kashmir, Himachal Pradesh, Uttarakhand, Punjab, Haryana, Delhi, Sikkim, West Bengal, Assam, Manipur, Andhra Pradesh, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu and Puducherry. The disease was known to occur in rural areas of India in the first half of the last century which was followed by a period of disappearance for three to four decades. But in the past two decades, large number of cases are being reported from all parts of India.  Now, the plains of north India (Haryana) and metropolitan cities like Delhi and Hyderabad are also affected by the disease.

Beware of rodents

In an entomological study conducted in some areas of Delhi, rodents traps were laid in parks and kitchen gardens and 15 per cent rodents collected were found to be infested with the mite species responsible for transmission of rickettsia (O.tsutsugamushi), responsible for causing scrub typhus. A study published in Indian Journal of Medical Research in 2012, found that during 2005-09, blood tests on 87 patients of fever of unknown cause from Delhi were tested  and about one-third (29) of them tested positive for rickettsial diseases, and scrub typhus was most common. In the second half of August 2013, four cases of scrub typhus have been reported from Lady Hardinge Medical College, New Delhi. All four of them had classic eschar on body and the disease was confirmed in three of them by the presence of IgM antibodies in ELISA test.

Reasons for return

Researchers all over the world are facing this sudden explosion of cases of scrub typhus and few of factors have been attributed for this. Tetracycline and chloromycetin were the main antibiotics which were in use for various types of fevers till the last decade of 20th century. These two antibiotics not only treated diseases like typhoid effectively but were effective in treating scrub typhus also. So it is possible that many cases of scrub typhus were also being treated unknowingly. There was introduction of newer antibiotics (like cephalosporins and betalactam) towards the end of last century; these are effective in treating various fevers with lesser side-effects but are not effective in treating scrub typhus. Thus, resurgence of scrub typhus has coincided with decreased use of tetracycline and chloromycetin.

Another possible reason for the return of the disease could be rapid deforestation in the past few years, thus increasing chances of growth of scrub grass required for laying eggs of mite and transmission of scrub typhus. Urbanisation and human behaviour of camping in jungles for recreation has also brought humans in contact with the “zones” of scrub typhus. In this era of rapid transport, there are chances of transportation of disease-infested rodents from one place to other. Thus, the present resurgence of scrub typhus can be partially attributed to human behaviour also.

Prevention

The disease can be prevented in infested areas  by simple measures like avoiding sitting directly over grass and cover it with mat before sitting and rub the body with soap, especially armpits and groin after visiting such areas; and most important of all, report to the doctor in case of fever and for doctors it is important to suspect and treat on suspicion as scrub typhus can be fatal if it remains undiagnosed or is diagnosed late.

All about scrub typhus

• Scrub typhus is prevalent in various parts of India
• These are one of the most difficult infections to diagnose in their early course and high index of suspicion is the key to it’s early diagnosis
• Fever, rash, headache, muscle pains, knots in neck, groin or in armpits and eschar are the main clinical symptoms
• Epidemiological features and history of exposure to vector are crucial for diagnosis
• Failure of early diagnosis is associated with significant mortality and morbidity and also leads to expensive tests
• It is easily treatable with simple and inexpensive antibiotics with dramatic results and needs to be started on clinical suspicion as in majority of cases blood tests may not be required
• Doxycycline is the drug of choice for treatment

Sanjay K Mahajan is Assistant Professor in the Department of Medicine at IG Medical College in Shimla, Himachal Pradesh. He has been working on different aspects scrub typhus for last ten years. He has published research papers in international and national journal of repute