Scrub typhus in Punjab: an acute febrile illness with multisystem involvement

Introduction

Scrub typhus is an infectious disease caused by Orientia tsutsugamushi. While the majority of cases present with an acute febrile illness (AFI), which may resolve even without treatment, serious complications involving multiple organs can occur in some individuals. ¹ In recent years there have been several reports of outbreaks of scrub typhus from various parts of India. However, there has been no report of scrub typhus or other rickettsial diseases so far from Punjab. The aim of this paper is to describe various clinical features and complications of patients with scrub typhus diagnosed in our hospital during a 1-year period.

Materials and Methods

All patients with AFI admitted to the medical wards of Christian Medical College & Hospital, Ludhiana from 1 October 2011 to 30 September 2012, who were diagnosed with scrub typhus by serological testing, were included in the study. Clinical examination, including a careful search for an eschar, was carried out in all the cases. Other causes of fever like malaria, enteric fever, leptospirosis and dengue fever were ruled out by appropriate tests. The serological test for scrub typhus was done using Bioline SD Tsutsugamushi (Standard Diagnostics, Inc., Korea) which detects the presence of IgM, IgG or IgA antibodies to O. tsutsugamushi

Results

Sixty-two patients were diagnosed with scrub typhus during the study period of 1 year. A large majority (52/62) of these patients were seen between September and April. There were 49 male and 13 female patients with a mean age of 39.9 years (range, 16–75 years). The mean duration of fever was 8.7 days. Eschar was present in nine patients (14.5%). Thirty-one patients presented with fever and non-specific symptoms. All others had some complication, namely ARDS/ALI in 18 (29%), neurological involvement in 12 (19.4%), acute kidney injury in 16 (25.8%), hypotension in 8 (12.9%), thrombocytopenia in 23 (37.1%), hepatitis in 34 (54.8%) and MODS in 19 (30.7%).

Table 1 shows the details of 18 patients who had ALI/ARDS. All these patients had metabolic acidosis and hypoalbuminemia. Twelve of these patients were treated with hydrocortisone (100 mg 6 hourly) along with doxycycline.

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Table 1.

Pulmonary complications.

S. No.	Age (years)	Fever (days)	Blood pressure	TLC	Plts (Lacs)	LFT abnormal	Creat	ALI/ARDS	Steroids	Ventilator	Neurological signs
1	30	30	Normal	8700	1.29	No	0.4	ALI	No	No	No
2	18	15	Normal	10,500	4.8	No	0.5	ALI	No	No	No
3	48	4	Normal	8500	45000	Present	1.7	ALI	No	No	No
4	44	15	Low	7200	1.26	Present	0.8	ALI	No	No	No
5	65	7	Normal	8000	32,000	Present	3.3	ALI	Yes	No	No
6	60	15	Normal	24,000	2.32	Present	2.5	ARDS	Yes	No	No
7	46	10	Normal	7700	62000	Present	2.5	ARDS	Yes	No	No
8	27	10	Low	2000	19000	Present	0.86	ARDS	Yes	No	No
9	45	10	Normal	5100	2.31	Present	0.7	ARDS	Yes	No	Present
10	23	10	Normal	12,800	45000	Present	0.5	ARDS	Yes	NIV (1)	No
11	22	13	Normal	9000	61000	Present	4.4	ARDS	Yes	NIV (1)	No
12	19	10	Low	14,200	1.2	No	1.2	ARDS	Yes	Yes (2)	Present
13	22	8	Low	10,300	1.63	Present	1.0	ARDS	Yes	Yes (2)	Present
14*	47	10	Low	3400	22000	Present	2.9	ARDS	Yes	Yes (6)	No
15*	27	3	Low	3100	1.2	Present	3.0	ARDS	Yes	Yes (1)	No
16*	75	30	Low	31,400	1.42	Present	2.0	ARDS	Yes	Yes (16)	No
17	50	7	Low	13,200	38000	Present	3.3	ARDS	No	Yes (11)	No
18	65	5	Normal	3600	78000	Present	1.7	ARDS	No	Yes (12)	No

There were 12 patients who presented with neurological manifestations (Table 2). The cerebrospinal fluid (CSF) evaluation of these patients showed the presence of normal or slightly raised proteins with lymphocyte predominant pleocytosis.

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Table 2.

Neurological complications.

S. No	Age (years)	Fever (days)	TLC	CSF TLC	CSF DLC	CSF Protein	Other system involvement	Neurological features
1	23	1	3800	150	N 46 L 54	32	None	Severe headache with meningeal signs
2	17	10	21,300	10	All lymph	26	None	Altered sensorium, headache and meningeal signs
3	16	4	6600	10	All lymph	24	None	Severe headache
4	44	1	10,000	660	N 90 L 10	75	None	Altered sensorium, headache with bilateral pyramidal signs and aphasia (ADEM). MRI showed demyelination
5	56	20	8400	140	N 40 L 60	114	None	Areflexic paraparesis (NCV showed demyelinating neuropathy)
6	30	2	6800	65	All lymph	50	Hepatitis	Severe headache
7	40	10	9100	20	All lymph	32	Low platelets, hepatitis	Severe headache
8	19	10	14,200	40	N 14 L 86	60	AKI, ARDS, hypotension	Altered sensorium with seizures
9	22	8	10,300	10	All lymph	50	Hepatitis, ARDS, hypotension	Altered sensorium, headache
10	37	1	11,200	5	All lymph	40	Low platelets, hepatitis	Altered sensorium, headache and meningeal signs
11	18	8	9500	25	All lymph	32	Low platelets, hepatitis	Altered sensorium with seizures, meningeal and cerebellar signs
12	45	10	5100	35	All lymph	40	Hepatitis, ARDS	Cerebellar signs

Three out of 62 patients of the study group died. All these patients had ARDS and MODS.

Discussion

Scrub typhus is grossly under-diagnosed in India due to its non-specific clinical presentation, and limited awareness and low index of suspicion among clinicians. ¹ Studies on undifferentiated fever in hospitalised patients from India have reported high prevalence of scrub typhus, in the range of 34–47.5%. ² One-third of these patients may have serious complications like pneumonitis, ARDS, myocarditis, renal failure, hepatitis and MODS.^1,3–5

In this study the maximum number of patients (83.9%) was admitted between September and April. Clustering of cases during these months has also been observed in other studies also. ¹ This occurs because in the immediate post-monsoon period (September to the early months of the following year), there is growth of secondary shrub vegetation which is the habitat for trombiculid mites.

Chrispal et al. observed that scrub typhus has four overlapping clinical presentations, namely mild non-specific febrile illness, respiratory predominant disease, central nervous system (CNS) predominant disease and sepsis with multi-organ involvement. ⁶ A similar pattern was also observed in the present study, with 50% of patients presenting with undifferentiated fever, 29% with predominant respiratory involvement, 19.4% with CNS involvement and 30.7% with MODS.

It is difficult to differentiate the cases of scrub typhus from other febrile illnesses such as enteric fever, malaria, dengue and leptospirosis. ¹ Duration of fever more than 7 days, presence of an eschar, lymphadenopathy with thrombocytopenia, normal or raised leucocyte count, and raised liver enzymes favour the diagnosis of scrub typhus.

Multi-system involvement was present in 30.7% patients. The majority of these patients had pulmonary involvement and eight had hypotension requiring inotropic supports. Tsay et al. found that the patients with MODS had a high leucocyte count, longer duration of fever and lower albumin levels. ⁷ In a study from Thailand on 51 cases of septic shock, scrub typhus was found to be the most common cause. ⁴ Hypotension in scrub typhus has been attributed to capillary leak and myocarditis. ⁴

Eighteen patients presented with respiratory symptoms (Table 1). Twelve of these patients had radiological and clinical evidence of ARDS. Risk factors for developing ARDS, which have been reported earlier, are cough and breathlessness at the time of presentation, early pneumonitis as defined by infiltrates on chest X-ray, leucocytosis, low hematocrit, high total bilirubin and delayed use of antibiotics.^3,8 Most of the patients of ARDS/ALI, treated with steroids along with doxycycline, could be managed with high flow oxygen with venturi mask, or with non-invasive ventilation or ventilatory support for a short duration (Table 1). Two patients who had not received steroids had to be ventilated for more than 11 days.

Neurological manifestations were observed in 12 of our patients (Table 2). Severe headache and altered sensorium were the most common symptoms. CNS involvement in scrub typhus can range from aseptic meningitis to frank meningo-encephalitis. ⁹ CSF picture may resemble that of viral or tubercular meningitis.

Renal impairment was found in 16 (25.8%) patients. Renal function became normal in all patients who survived. Renal failure may be caused by pre-renal factors or by direct invasion of the kidneys by O. tsutsugamushi, leading to acute tubular necrosis. ¹⁰ Hepatic injury in scrub typhus is usually mild, and results from sinusoidal infiltration, pericholangitis and perivascular lesion in the portal area of the liver. ¹¹

The mortality rate in scrub typhus is reported to be 7–30% in different studies.^3,5 In our study, three patients out of 62 died (4.9%) and all of them had ARDS, hypotension and metabolic acidosis. Predictors of mortality reported in other studies are delay in diagnosis leading to severe complications such as ARDS, metabolic acidosis, shock and MODS. ⁶

Conclusion

Scrub typhus is an emerging cause of AFI in Punjab with a potential for serious complications and mortality. Early empirical treatment with doxycycline is life-saving. Scrub typhus should be considered in all cases of ARDS, meningitis/meningo-encephalitis, hepato-renal syndrome, fever with MODS, fever with abnormal LFT and thrombocytopenia.