Scrub Typhus: A neglected, but important, tropical disease in Lucknow and eastern Uttar Pradesh

Dr Raghav Gattani, CNS Medical Correspondent
CNS image library 9/2013/Myanmar
[Scrub typhus is a neglected, but important, tropical disease (NTD), which puts one-third of the world’s population at risk. Read this important article] Working in a tertiary care centre in Lucknow, we observed an increasing number of cases diagnosed with Scrub Typhus, from February, 2015 to August, 2015, a lesser known potentially fatal infection.

Scrub typhus is an acute, febrile illness first described in Japan in 1899. This infection is caused by the obligate intracellular Gram-negative bacterium Orientia tsutsugamushi. During the Second World War, scrub typhus caused major epidemics resulting in significant morbidity and mortality in the border regions of India and Burma. Although reports of the disease were rare for several decades, a clear re-emergence has been documented from several states in India, including Himachal Pradesh, Tamil Nadu, Kerala, Maharashtra, Bihar, Karnataka, Jammu and Kashmir, Uttaranchal, Rajasthan, West Bengal, and Meghalaya.

Although the disease is endemic in our country, it is grossly under diagnosed owing to the non-specific clinical presentation, lack of access to the specific diagnostic facilities in most areas, and low index of suspicion by the clinicians.

Scrub typhus is a potentially fatal infection that affects about one million people every year. There have been outbreaks in areas located in the sub- Himalayan belt, from Jammu to Nagaland.  There were reports of scrub typhus outbreaks in Himachal Pradesh, Sikkim, Darjeeling (West Bengal) during 2003-2004 and 2007. Outbreaks of scrub typhus are reported in southern India in cooler months of the year. All our cases were natives of Uttar Pradesh. More than half of the patients were from eastern Uttar Pradesh. None of them had a history of travel, prior to their illness, to any other state where scrub typhus is prevalent. This shows the existence of the disease in the state and its significant presence in Lucknow, the capital of Uttar Pradesh.

The disease is transmitted to humans by the bite of the larval stage of the trombiculid mite (chigger) of the Leptotrombidium genus, which typically feeds on wild rats. Humans are accidental hosts in this zoonotic disease. O. tsutsugamushi is injected into the human host from the chigger’s digestive system and subsequently adheres to and invades human’s phagocytes and endothelial cells. Once inside these cells, as with other rickettsial illnesses, an acute vasculopathy ensues, which can affect a broad range of organs, leading to various potentially life-threatening complications.

Acute fever is the most common presenting symptom, often associated with breathlessness, cough, nausea, vomiting, myalgia, and headache. An eschar at the site of inoculation can be found, if searched for thoroughly, in a highly variable percentage of people (10–92%). The infection can range from a self-limiting disease to a fatal illness in 35–50% of cases, with multiorgan dysfunction, if not promptly diagnosed and appropriately treated. Severe complications, including acute respiratory distress syndrome (ARDS), hepatitis, renal failure, meningoencephalitis, and myocarditis with shock, may occur in varying proportions of patients. The vast variability and non-specific presentation of this infection have often made it difficult to diagnose clinically. Immunochromatographic assay was performed on serum samples using the One Step Scrub Typhus Antibody Test (SD BIOLINE TSUTSUGAMUSHI kit, Republic of Korea) as per manufacturer’s instructions, with a reported sensitivity of 99%, specificity of 96% and a serological agreement of 97.5%. Detection of IgM antibodies to Orientia tsutsugamushi was considered to be positive test.

Our patients presented to the hospital with a mean duration of illness of 9 days, with symptoms of fever, nausea/vomiting, shortness of breath, cough, headache, decreased urine output and altered mental status. About half of our patients had evidence of MODS and the overall mortality was 7.4%. The mortality over the period in various studies has shown a declining trend. This may primarily be due to increased awareness and early recognition and treatment of the cases by physicians.

Multi-organ failure was seen in a very high proportion (40%) of our patients. Renal dysfunction was the most common complication (62.9%) though none of them required Renal Replacement Therapy.

This incidence of renal impairment is much higher than the 23.2% incidence reported by Attur et al, 18% incidence reported by Varghese et al and almost similar to the 66.4% incidence reported by Mahajan et al. Our incidence of meningoencephalitis (29.6%) was found to be higher than the 9.5% and 14% reported in other studies from India,  although it was almost similar (23.3%) to that reported by Varghese et al. Pulmonary dysfunction was present in 44% of patients and only 16.6% of them required invasive ventilator support. NIPPV (Non-invasive positive pressure ventilation) was used in 62.9% of our patients. Most of the previous studies from India have shown an incidence of ARDS of 8–10%, except the one by Varghese et al which showed the incidence of pulmonary dysfunction to be 33.7%.

The occupation and scrub vegetations surrounding the house of the patients are known to have a strong association with acquisition of the infection. Most of our patients were from rural areas, indicating an increased risk of infection in those who encounter scrub vegetation in their daily life. A necrotic eschar at the inoculating site of the mite is pathognomonic of scrub typhus, however, it is rarely seen in south East Asia and Indian subcontinent. Eschar was not seen in any of our patients. The variation in prevalence of an eschar may represent the different geographic distribution of the various strains of the organism, or inadequate search for the eschar. Though lymphadenopathy is common in scrub typhus it was seen in only one patient.

In conclusion, scrub typhus is a serious acute febrile illness associated with significant mortality. Respiratory dysfunction, shock, and acute renal failure are serious life-threatening complications of this disease. Scrub typhus is present in regions that are co-endemic for diseases that may present with similar clinical syndromes, such as malaria, dengue, typhoid, and leptospirosis. The mortality from this infection does appear to have been decreasing over the last several years. However, increasing awareness of this infection among clinicians and reliable methods for more rapid diagnosis will be the key to further reducing the mortality caused by this deadly disease.

The government of India along with governments of other countries have committed earlier this week to achieve the Sustainable Development Goals (SDGs) at 2015 UN General Assembly, one of which (SDG 3.3) promises: "By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases." We need to accelerate progress on neglected tropical diseases (NTDs) if we are to achieve the SDGs by 2030 or earlier.

(About the author: Dr Raghav Gattani, MBBS, Junior Consultant at Avadh Hospital and Heart Center is also the honorary Medical Correspondent for CNS - Citizen News Service)
30 September 2015