Scrub typhus : A vector-borne zoonotic rickettsial infection
Himani Agri, Md Mir Husaain
Phd scholar, Veterinary Public Health and Epidemiology, ICAR-IVRI
Abstract: Scrub typhus, a vector-borne zoonotic rickettsial infection caused by the Orientia tsutsugamushi a mite-borne, obligate intracellular, Gram-negative bacterium , is transmitted by Leptotrombidium mites, popularly known as chiggers. Rattus genus field rats serve as reservoir hosts. The confined & most prevalent area of the Asia-Pacific region termed the ‘tsutsugamushi triangle’. The disease is mostly affects farmers and their children, although it can also harm urban residents due to exposure to gardens or visits to the countryside. In India the outbreak is mostly reported from Himachal Pradesh, Sikkim, and Darjeeling (West Bengal) in 2003–2004 and 2007. Incubates for 10 to 12 days & may develop an eschar-like lesion followed by illness is generally nonspecific to multiorgan failure. Death is due to complications such as bacterial pneumonia, encephalitis, or circulatory failure. For diagnosis of disease Weil-Felix (WF) test is performed which is based on the identification of antibodies to several Proteus species that contain cross-reacting antigenic epitopes to antigens from members of the genus Rickettsia, When the titer is 1:320 or higher, or when the titer rises fourfold from 1:50, the test is considered positive. A gold standard is an indirect immunofluorescence antibody (IFA) performed. Embryonated chicken yolk sacs, cell culture in Vero cells, MRC 5 cells, BHK21, L929 mouse fibroblast cell monolayer in tube culture is used to isolation of the organism Doxycycline and tetracycline are the approved treatments for scrub typhus.
Keywords: Tsutsugamushi triangle, multiorgan failure, epitopes, IFA
Introduction
Scrub typhus, a vector-borne zoonotic rickettsial infection caused by the Orientia tsutsugamushi, is one of the most common and clinically important rickettsial infections worldwide. Bush typhus, Japanese river disease, Tropical Typhus, Chigger-borne typhus fever, and river fever are some of the other names for scrub typhus. The disease was first discovered to be transmitted by Leptotrombidium mites, popularly known as chiggers, in Japan in 1899. Rattus genus field rats serve as reservoir hosts. During Second World War, scrub typhus killed thousands of soldiers of the Far East. Subsequently, it become endemic in the geographically confined area of the Asia-Pacific region termed the ‘tsutsugamushi triangle’ (Devasagayam et al., 2021). It is an important disease of a majority of PUO/FUO cases –pyrexia of unknown origin and fever of unknown origin.
Etiology
Orientia tsutsugamushi (from Japanese tsutsuga meaning “illness”, and mushi meaning “insect”) is a mite-borne, obligate intracellular, Gram-negative bacterium belonging to the family Rickettsiaceae under the order Rickettsiales. Bacteria can be antigenically classified into various serotypes i.e Karp, Gilliam, Kato, Shimokoshi, Kuroki, and Kawasaki. Among which Karp is highly prevalent (Yamamoto et al., 1986)
Reservoir Host
Wild rodents of subgenus Rattus, are the natural host for scrub typhus. Field rodents act as reservoir hosts and Trombiculid mites: Leptotrombidium deliensis (red mite) is a principal vector. Humans are only accidental hosts and can pick up the infection by infected chiggers.
Geographical distribution
Scrub typhus appears to be highly prevalent in the tsutsugamushi triangle, which spans a 13 million km2 area and is bordered on the east by Japan, China, the Philippines, and tropical Australia in the south, and on the west by India, Pakistan, possibly Tibet to Afghanistan, and the southern parts of the USSR in the north. The disease is mostly found in southeastern and eastern Asia; India, Pakistan, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and other islands in the region are all affected (Chakraborty, S. and Sarma, N., 2017). It mainly affects farmers and their children, although it can also harm urban residents due to exposure to gardens or visits to the countryside. There are no genetic predispositions that have been discovered. It can be found throughout India, from Kashmir to Assam, in the Shivalik mountains, the Eastern and Western Ghats, and the Vindhyachal and Satpura ranges in the middle section of the country. Scrub typhus outbreaks were reported in Himachal Pradesh, Sikkim, and Darjeeling (West Bengal) in 2003–2004 and 2007.
Transmission cycles
Infectious trombiculid mites (“chiggers,” L. deliense, and others) spread the infection to humans and rodents, and it feeds on lymph and tissue fluid rather than blood. Adults measure 1 to 2 mm in length, are crimson, and can survive for up to 15 months. Females lay about 400 eggs on the soil in wet areas, such as under leaves, throughout a 3- to 5-month period. Larval mites hatch and must wait 10 to 12 days for a host to feed on. The larva is the only stage (chigger) that can transmit the disease to humans and other vertebrates. The engorged larval mite, drops from the host to the ground after 1 to 10 days of feeding. Once infected in nature by feeding on the body fluid of tiny mammals, such as rodents, they keep the virus throughout their lives and, as adults, pass the infection on to their eggs through a mechanism known as transovarial transmission..
Pathogenesis and clinical manifestation
- tsutsugamushi incubates for 10 to 12 days after being transmitted to the host. At the site of the larval bite, the patient may develop an eschar-like lesion. Which might reach a diameter of 8 to 12 mm. The illness is generally nonspecific, ranging from preclinical to multiorgan failure. The onset of the disease is characterized by a fever of unknown origin, headache, myalgia, cough, and gastrointestinal symptoms. However, in severe cases O. tsutsugamushi infects endothelial cells, causing widespread vasculitis and perivascular inflammatory lesions that cause considerable vascular leakage and end-organ harm in organs such as the lungs, heart, and kidney. Spleen enlargement, neurological problems, psychosis, and prostration are some of the other symptoms. The severity of the symptom depends upon the host immunity and virulence of the rickettsial pathogen. Eschar formation is one of the prevalent pathognomic lesions of scrub typhus. About 7%-80% of cases with scrub typhus show eschar formation. Mortality rates range from 6% to 35% and depend upon the. Death might happen from the disease itself or complications such as bacterial pneumonia, encephalitis, or circulatory failure.
Diagnosis
Clinical symptoms and the patient’s history of mite bites can be used to make a diagnosis. The Weil-Felix (WF) test is the cheapest and most widely available serological test. The WF test is based on the identification of antibodies to several Proteus species that contain cross-reacting antigenic epitopes to antigens from members of the genus Rickettsia, except for Rickettsia akari, and has high specificity but low sensitivity. When the titer is 1:320 or higher, or when the titer rises fourfold from 1:50, the test is considered positive. This test is now being replaced by a complement-fixation test. The antibody titer is observed at different levels of infection, with a significant level of antibody titer at the end of the first week of infection due to IgM antibodies, whereas the antibody titer of IgG appears to be substantial at the end of the second week of infection. In the early stages of pathogen dispersion, serological tests combined with polymerase chain reaction can add value to the diagnosis. A gold standard is an indirect immunofluorescence antibody (IFA). This approach detects scrub typhus-specific antibodies linked to smears of scrub typhus antigen. Before seroconversion, this might be used to confirm infection. Indirect immunoperoxidase (IIP) is a light-microscope-based variation of the classic immunofluorescence assay (IFA), and the results are comparable to IFA. Other serological tests such as ELISA and western blotting are also used in epidemiological studies. The organism can be produced in tissue culture or mice from the blood of scrub typhus patients, but the results aren’t accessible in time to help with clinical management. Buffy coat of heparinized blood, defibrinated whole blood, triturated clot, plasma, necropsy tissue, skin biopsy, and arthropod samples are among the samples that can be collected for isolation. Embryonated chicken yolk sacs, cell culture in Vero cells, MRC 5 cells, BHK21, L929 mouse fibroblast cell monolayer in tube culture, shell-vial assay, and other procedures were used to identify the rickettsial strains. HEL or MRC5 cells resist contact inhibition, whereas Vero or L929 cells allow for better and faster Rickettsiae separation.
Treatment
Doxycycline (2.2 mg/kg/dose twice PO or IV, maximum 200 mg/day for 7–15 days) and tetracycline (25–50 mg/kg/day split every 6 h PO, maximum 2 g/day per mouth, duration 7–15 days) are the approved treatments for scrub typhus. A single dose of 200 mg can be administered for prophylaxis. Natural resistance reports, on the other hand, make selecting an antibiotic problematic. Chloramphenicol (50–100 mg/kg/day split every 6 h IV, maximum 3 g/24 h, or 500 mg qid orally for 7–15 days for adults) is another option. If chloramphenicol is prescribed, serum values of 10-30 g/mL should be preserved. To avoid relapse, therapy should be continued for at least 5 days and until the patient is afebrile for at least 3–4 days. Chloramphenicol should be avoided during pregnancy, and hepatic impairment should be treated with lower doses. Intensive care may be required for hemodynamic management of severely affected individuals
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