Scrub Typhus: A Preventable, Curable yet Deadly Disease

key Points:-

1. Scrub typhus is a bacterial disease caused by Orientia tsutsugamushi, transmitted to humans by the bite of an infected larva of trombiculid mite (chigger larva)
2. Leptotrombidium deliense is the species primarily responsible for scrub in India including Himachal Pradesh
3. Trombiculid mite has 4 stages in its life cycle Eggs, larva, Nymph, and adult. only the larval stage (chigger larva) is infective
4. Lavra of trombiculid mites feed only once in their life cycle. rest stages don’t feed on humans.
5. Chigger larvae don’t suck the blood but feed on the extracellular fluid of the host. also, they don’t cause any itching or discomfort to the host until they are detached.
6. Typhus islands are the areas where trombiculid mites love to live like- moist and grassy areas
7. Scrub typhus is easily treatable if diagnosed timely but in the absence of proper treatment, even death may occur. diagnosis is difficult as symptoms are non-specific and commonly used serological tests are negative early in the course of the disease
8. Taking a bath after coming from possible Typhus islands (like cutting grass in fields) can reduce the chances of larva biting humans, as it takes around 3-4 hours of attachment before transmitting the infection to the human body
9. Larva of trombiculid mite is very small and we can’t see it with the naked eye
10. IgM- ELISA is preferred over the Weil-felix test (low sensitivity and specificity) among commonly used tests. IFA is the gold standard and PCR can diagnose the disease in the early course of disease But cost, expertise and sophisticated setup limit the availability.
11. Doxycycline is the Drug of choice (not in pregnancy) and patients respond very quickly to it.
12. Doxycycline-resistant strains of bacteria causing scrub typhus have been found.

Scrub typhus also known as Bush typhus is a Bacterial disease that occurs following the bite of an infected Larva of a mite (Trombiculid mite). Scrub typhus is preventable and easily treatable if diagnosed timely. in the absence of timely diagnosis and treatment, it can lead to severe complications and even death.

Global Distribution of Scrub Typhus

• Most cases of scrub typhus occur in rural areas of Southeast Asia, Indonesia, China, Japan, India, and northern Australia¹

• It is endemic in Northern Japan, Southeast Asia, the western Pacific islands, Eastern Australia, china, maritime and several parts of south-central Russia, India and Shri Lanka².

• More than 1 million cases occur annually and 1 billion are at risk⁵
• The disease was first observed in Japan and was called tsutsugamushi (tsutsu- dangerous; mushi- mite or insect)⁴

Scrub Typhus in India

• Scrub typhus is Endemic to India
• Scrub Typhus has been reported from various states and UTs in India like- Himachal Pradesh, Maharashtra, Delhi, Karnataka, West Bengal, Pondicherry, Kerala, Tamil Nadu, Jammu and Kashmir, Rajasthan, Meghalaya, Manipur, Goa and Uttarakhand³
• Once thought to be a rural disease, cases have been reported from urban areas also³
• Scrub Typhus is usually seen in Rainy months from June to October in India however, can occur throughout the year.

What Causes Scrub Typhus

Before I start with difficult names let me make it simple to understand better.

Scrub typhus is caused by a bacteria which reaches the human body when an infected larva of a mite, bites humans. this larva (not visible to the naked eye) usually feeds on rats, mice, bandicoots, or other small mammals. Humans are accidental hosts.

[Bacteria present in the Larva of a mite–>larva bites human–> bacteria reach human body–> causes Scrub typhus]

• Orientia tsutsugamushi is the bacteria causing Scrub Typhus. these bacteria belong to the genus Rickettsia

• O. tsutsugamushi is an obligatory intracellular bacteria, which means it can’t survive freely in the environment. Therefore vectors are required for the transmission of disease to humans.

Transmission of Scrub Typhus

• Scrub typhus is transmitted by the bite of an infected Larva (chigger larva) of trombiculid mite [Leptrotombidium deliense– in Indian Subcontinent and Southeast Asia, Leptotrombiculum akamushi– in Japan⁶]
• Only the larva stage is parasitic. Adults or nymph stages of trombiculid mites do not bite humans and develop in soil.

• No human-to-human transmission

• L.deliense is generally found associated with established forest vegetation or secondary vegetation after clearance of forest areas. This species is generally found in abundance on grasses and herbs⁴

• In an entomologic study in Himachal Pradesh, the vector species Leptotombidium deliense was recorded.⁴

Life Cycle of Mite Causing Scrub Typhus

• Larva can’t be seen with the naked eye (200-400 micrometres⁷)
• Overall it takes around 6-12 weeks to develop into an adult mite from an egg.
  • Larva (chigger), attach to the host for feed and remain attached for 2 days to a month
  • After feeding, Larva drops on the ground/ soil. and develops into the Nymph over around a week
  • Nymph stages last for 2 weeks and then they develop into adult mites with differentiated sex.
  • Eggs are laid by adult mites into the soil and hatch into Larvae in about a week.

Clinical Features of Scrub Typhus

Clinical features develop after an incubation period of 1 to 2 weeks. symptoms are usually non-specific and include:-

• Fever:– Acute onset, high-grade fever (103-104^oF) with relative bradycardia⁴. Fever may be associated with headache, arthralgia or myalgia.
• Rash:- A macular rash may (30-45 % cases³) appear around the 5^th day of illness². the rash appears first on the trunk and then on the extremities (spare palms and soles³ ) and lasts only a few days⁴. More visible on fair skin.
• Generalized swelling of lymph nodes
• Eschar:- it is a Punched-out lesion with blackened scab² at the site of larva bite, which resembles the burnt butt of a cigarette. It is painless, nonpruritic and about 1 cm in diameter. it is a pathognomic of rickettsial diseases (Though it can be seen in anthrax, bacterial ecthyma, spider bite and rat bite fever). it should be actively looked for in suspected cases.

Complications of Scrub typhus

Various complications may occus³:-

• Disseminated intravascular coagulation
• Acute Respiratory Distress syndrome
• Purpura fulminans
• Gangrene
• Myocarditis
• Even Death may occur if not treated properly

Diagnosing Scrub Typhus

History taking, clinical examination and lab investigation are used to diagnose Scrub typhus. Various lab tests used commonly are serological test:-Weil-Felix Test and IgM-ELISA for scrub typhus.

In a study conducted from July through October 2004 in the Himalayas, among several cases of acute febrile illness of unknown origin, O.tsutsugamushi (Scrub typhus causing organism) was identified as a causative agent by microimmunofluorescence and PCR⁴

Conditions similar to Scrub Typhus (Differential Diagnosis)

Other conditions like- malaria, dengue and other rickettsial disease, may present similar to Scrub typhus.

Treatment of Scrub Typhus

Doxycycline is the drug of choice. Alternative effective drugs are Macrolide (Azithromycin or Clarithromycin), Chloramphenicol and Rifampicin³

Response to Doxycycline is dramatic. Any fever persisting beyond 48 hours of doxycycline treatment should prompt consideration of an alternate diagnosis.

1. Adults:
   • Doxycycline 200 mg/day in two divided doses (i.e. 100 mg BD) in individuals above 45 kg for 7 days¹⁰
     • OR
   • Azithromycin 500 mg in a single oral dose for 5 days (if doxycycline is contraindicated)
2. Pediatric Patients:
   • For children below 45 kg: Doxycycline in the dose of 4.5 mg/kg body weight/day in two divided doses (i.e. 2.2mg/kg/dose BD)¹⁰.
   • Children weighing 45 kg or more should receive the adult dose¹¹.
     • OR
   • Azithromycin 10 mg/kg/day in a single dose (OD) for 5 days.
3. Pregnant women:
   • Azithromycin is the drug of choice in Pregnancy. The dose is 500 mg/day once a day for 5 days.
   • Doxycycline is contraindicated in pregnancy (Pregnancy Category-D drug).
4. Lactating mothers:
   • Short-term use is not necessarily contraindicated; however, the effects of prolonged exposure to doxycycline in breast milk are unknown¹¹.decision should be made on the basis of the importance of the drug to the mother and available alternate options.

Doxycycline and/or Chloramphenicol resistant strains have been seen in South-East Asia.
These strains are sensitive to Azithromycin¹⁰

Prevention from Scrub Typhus

Strategies to prevent Scrub typhus and all other Rickettsial diseases can be achieved by:-

1. Vector control measure
   • Vectors are trombiculid mites that usually complete their life cycle by infesting rodents. therefore controlling the rodents can control the vector (mite)
   • Removing the vegetation around by cutting, burning or spraying the insecticides like Lindane on it³, as trombiculid mites prefer to live in moist and grassy areas like- fields, forests, grassland, banks of rivers and even home lawns¹².
2. Avoiding bite of chiggers
   • Avoid exposure by not visiting the Typhus islands ( areas which are common habitats of vectors like- high uncut grass or weeds or bushes or rice fields or woodlands or grassy lawns or river banks or poorly maintained kitchen gardens.)
   • Wear shoes or boots and light-coloured (for tick visibility) full-sleeved clothes. shirt should be tucked into pants and pants tucked into socks or boots.
   • Insect repellants on clothes (Permethrin based) and skin (20-50% DEET based) should be applied
   • Protecting pets and periodic de-ticking should be done
   • After spending time outside- cutting grass, walking your dog, camping, gardening, hunting, for or visiting any possible typhus islands –
     • Check your body for ticks:- Under the arms, In and around the ears, Inside the belly button, Back of the knees, In and around the hair, Between the legs, Around the waist (for possible chigger attack or other tick-borne diseases)
       • Use tweezers, grasp the tick head as close to the skin and gently pull upwards with constant pressure.
       • The attachment area should be immediately cleaned with soap and water or alcohol or an iodine scrub.
       • Ticks should neither be removed nor be crushed with bare fingers¹¹.
       • Take a bath
     • Take a bath, as ticks need a minimum of 4 to 6 hours of attachment before they transmit infection¹¹
     • Tumble dry clothes in a dryer on high heat for 10 minutes to kill ticks on dry clothing after you come indoors
3. Pre-exposure prophylaxis
   • It is recommended for short-period, high-risk exposure.
   • Weekly Doxycycline, started 6 weeks before till 6 weeks after exposure³

Case Definitions of Scrub Typhus in India

Case definitions for Suspected, Probable and confirmed cases of Scrub typhus are given as below

Suspected case:-

• Acute undifferentiated febrile illness for equal or more than 5 days, with or without eschar should be suspected as a case of Rickettsial infection.
• if eschar is present, a fever of less than 5 days duration should be considered as scrub typhus.
• Other presenting features as we already discussed in clinical features may be present.

Probable case:-

• A suspected clinical case showing titres of Weil Felix test 1:80 or above for OXK antigens and an optical density (OD) > 0.5 for IgM-ELISA are considered positive for typhus

Confirmed case:-

• Rickettsial DNA is detected in eschar samples or whole blood by PCR
  • OR
• Rising antibody titers detected by Indirect Immune Fluorescence Assay (IFA) or Indirect Immunoperoxidase Assay (IPA)

Is There Any Vaccine or PEP Available for Scrub Typhus?

No.

There is no vaccine or post-exposure prophylaxis available for Scrub typhus.

Can we use Doxycycline in children younger than 8 years of age

Use of doxycycline in pediatric patients 8 years of age or below can be done only when the potential benefits are expected to outweigh the risks, as in severe or life-threatening conditions (e.g. anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies¹¹.

otherwise, Azithromycin can be used in all children.

What does a Lymph or Adult Mite of Scrub typhus feed on?

Unlike larva which feeds on a wide range of host including humans, postlarval stages- Nymph and Adult prey on small arthropods, insects and their eggs.

Can chigger Larvae on rodents or other small mammals jump to humans?

Chigger larva feeds on the host only once in their lifetime for their development into the next stages of the life cycle. therefore chiggers attached to rodents can’t infest humans and transmission of disease from rodents to humans via the same mite larva is impossible.

The larval stage feeds only once and acquires the pathogen from infected mice, rats, and other small rodents. Therefore, chiggers can:

• only acquire the pathogen and transfer it to its next generations transovarially
  • OR
• transmit it, if they were already infected.

The pathogen acquired by the larva is carried (trans-stadially) throughout the developmental stages to the adult. Pathogens acquired by the larva are carried forward and multiplied in the subsequent developmental life stages. pathogens are passed to the eggs (transovarially) and then to the larvae of the next generation (salivary glands). these pathogens are transmitted to humans when these infected chigger larvae feed on humans.

Chiggers do not suck blood!

Chiggers do not feed on blood; rather, they feed on extracellular fluid from the dermis¹⁴. they are now known to only feed once in their lifetimes. they generally do not create itching and discomfort until the larvae have withdrawn their mouthparts and departed

Reserviour of infection

Primary reservoirs are Rodents but Trombiculid Mites also act as reservoirs as they transmit infection transovarilly to the next generation.

Can Insect Repellant be Helpful in Preventing Scrub Typhus?

Yes.

Insect repellants can be helpful in preventing Scrub typhus. Insect repellants can be applied on clothes and over the skin directly.

• Those to be applied on clothes should contain Permethrin. Permethrin is applied to clothes and then allowed to dry before use. permethrin-containing insect repellants are not applied directly over the skin. Permethrin affects the nervous system in insects, causing muscle spasms, paralysis and death.

• DEET-Containing insecticides are applied over the skin directly.
  • DEET (N, N-diethyl-meta-toluamide)- containing insecticides are available from 4-100%. Please note that the percentage of DEET doesn’t tell about the strength but the duration it can provide protection. The more the percentage longer is the protection¹⁶
  • DEET doesn’t kill the mites or insects but repels them. Follow the information on the label. Can be applied to infants older than 2 months of age. Use only on exposed parts and wash with soap when not required (indoors)¹⁶

Here I am recommending some good products available on Amazon

• Buy Permethrin containing insect and mite repellent for clothes and other gear (sleeping bag, mosquito net, backpack etc while going on trek or camping in nature):-

• Buy DEET containing insect and mite repellent to be applied over skin directly:-