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View of Scrub Typhus:Clinicalprofile, Laboratory Findings and Outcome in Hospitalized Children, from a Tertiary Care Hospital in Eastern India

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Scrub Typhus:Clinicalprofile, Laboratory Findings and Outcome in Hospitalized Children, from a Tertiary Care Hospital in Eastern India

J Bikrant Kumar Prusty1, Swayamprabha Sahoo2, Swarup Kumar Bisoi1*, JatindraNath Mohanty2

1Department of Pediatrics, IMS and SUM Hospital, SOA deemed to be University, Bhubaneswar, Orissa, India.

2Medical Research Laboratory, IMS and SUM Hospital, SOA deemed to be University, Bhubaneswar, Orissa, India.

Corresponding Author

Swarup Kumar Bisoi, Associate Professor, Department of Pediatrics, IMS and SUM Hospital, SOA deemed to be University, Bhubaneswar, Orissa, India.

Mail Id- [email protected] Abstract

Scrub typhus is a common cause of acute undifferentiated fever in children. Early detection and prompt treatment help reduce morbidity and mortality. Methods: This study included all children who visited our pediatric outpatient clinic between January 2017 and February 2020, who were clinically suspected of having typhoid peeling and who were treated with positive serum IgM by ELISA. A total of 166 cases were registered during the study period. Of these, 110 are male and 56 female. The average age of beneficiaries was seven years and the youngest was only five months old. Most of these patients were from rural areas (86%). About two-thirds (77%) of the study group had open defecation. The maximum number of cases (65; 78.3%) was reported during the rainy season (between September and January). Persistent fever (100%), gastrointestinal symptoms (76%) such as vomiting, diarrhea and abdominal pain, lymphadenopathy (96%) and hepatosplenomegaly (61%) are common signs and symptoms of typhus. Only six patients suffered from serious illness. Diagnosis is based on positive serum IgM for typhoid peeling. All IgM patients were positive. Of these 166 patients, ulcers were seen in 100 (60%) patients. Weil Felix's test was positive in 30 of the 66 cases tested. Twelve children were coinfected with 4 cases of malaria and four cases of dengue fever. Conclusion: Typhus is one of the most common causes of acute undifferentiated fever in children. High index of clinical suspicion and scabies monitoring facilitate early diagnosis of typhoid peeling.

Keywords: Acute undifferentiated fever, Eschar, Orientiatsutsugamushi, Rickettsial infections, Scrub typhus, WeilFelix test

Introduction

Typhus, also known as Tsutsugamushi disease, is a new zoonotic bacterial infection in the region known as the Tsutsugamushi Triangle in South and Southeast Asia, Asia Pacific, and Northern Australia (1,2,3,4). It is estimated that one billion people are at risk of developing typhus, and

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about one million cases occur each year (5). Typhoid scrubs are also the most frequently reported rickets infection in the Indian subcontinent at present (6). The clinical manifestations of cases reported by India show variability when compared to cases from other endemic Asian countries (7).

The pathogen, orientiatsutsugamushi, is transmitted to humans through the bite of the larva (chigger) of the thrombiculid mite, the most common of which is Leptotrombidiumdeliense.

Orientiatsutsugamushi are obligate intracellular gram-negative bacteria that infect a wide variety of cells, including endothelial cells and phagocytic cells, causing acute vasculitis. Serious complications, including acute respiratory distress syndrome (ARDS), hepatitis, kidney failure, meningoencephalitis, and myocarditis shock, can occur in a wide variety of patients. Due to different clinical manifestations, a high index of suspicion is required for early diagnosis and timely treatment. .

Diagnostic tests such as the Weil-Felix test are very insensitive and non-specific. Current options for serological diagnosis are the IgM ELISA test, DNA PCR, and immunofluorescent analysis (IFA), which are considered the gold standard. A positive correlation between Weil-Felix test results and detection of IgM antibodies using indirect immunofluorescence (IFA) analysis has been found in various studies (8,9).

Study methodology

This prospective observational study was conducted in the pediatric ward, at IMS & SUM Hospital, on inpatients aged 1 month to 14 years. Those enrolled with undifferentiated acute febrile illness> 5 days with no apparent cause with one or more characteristics such as lymphadenopathy, organomegaly, headache, edema, rash, and scabies will be included in this study. Detailed history, socio-demographic data and clinical findings are documented. Other common clinical conditions that resemble typhoid peeling are ruled out by performing a rapid diagnostic test and smearing of malaria, dengue serology, leptospires, and uptake tests. Complete blood count, liver function tests, serum electrolytes, and kidney function tests will be performed on the suspected child. CSF examination, chest X-ray, abdominal ultrasound and echocardiography in certain cases depending on clinical manifestations.

Weil Felix's test, IgM ELISA, is recommended for all suspected cases. In certain cases, DNA PCR is performed. The WF test for protein agglutination (Proteus vulgaris, strain OX-K) was carried out on each sample by diluting the serum from 1:20 to 1280. A titer of 1:80 or more is considered a positive result. Detection of IgM antibodies in ELISA for O.tsutsugamushi in your serum sample and an optical density (OD) of more than 0.5 is considered a positive typhus result.

All diagnosed patients were treated and delayed therapeutic response was recorded.

Complications and treatment during illness and hospitalization are documented. The results were analyzed with Windows SPSS software (version 12).

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Result

A total of 166 children were diagnosed to have scrub typhus during the study period. Among these 83 children,110(66%) were boys, and 56(34%) were girls. The age of these children ranged from 5 months to 12 years of age with an average age of presentation of seven years. Children aged between 7 to 12 years accounted for nearly 60 % of the total cases. Majority of these patients were from nearby districts of Tamil Nadu and lived in rural areas (86%). Roughly, two- thirds (77%) of the study group practised open defecation (Table 1). A maximum number of cases (130;78.3%) were reported during monsoon season (between September and January) Fever was a consistent finding in all scrub cases with 95% having either mild or moderate fever.

Only just over one-third (52;31%) of children reported fever for less than a week at hospitalization. Majority of pediatric scrub cases had fever for more than a week (56%), and a small group (13%) had fever lasting for more than two weeks. Over one-quarter of these febrile patients had chills or rigour.Maculopapular rashes were noticed among 28(17%) of patients.

Other clinical features reported were headache and myalgia (12% each), cough and runny nose (25%). The gastrointestinal system was significantly affected in patients with scrub typhus which was evident in 76% of patients who had symptoms such as vomiting, diarrhoea and abdominal pain 86(52%),8(5%) and 19% (32) respectively. Symptoms suggestive of severe illness were observed in a small number of cases. Tachypnea was noticed in 12 cases, and 8 of them had retractions also. Tachycardia was documented in 12(14%) cases. Nevertheless, only one patient had shock and oliguria. Presentation of oedema varied with facial puffiness in 8, and ascites and/or pleural effusion noted in 4 out of 12 (7%) cases of oedema.

On clinical assessment, 96% of children had lymphadenitis with the majority of them (n=118;

71%) presenting with generalized lymph node involvement. Additionally, enlarged regional lymph nodes were noticed among a quarter of the admitted children. Eschar, which is considered as a pathognomonic feature of scrub typhus was seen in 100 cases (60%). Common sites of eschar were axilla and groin. Another common finding in scrub typhus was hepatosplenomegaly.

Hepatomegaly was noticed in (n=54; 32%) children and hepatosplenomegaly in (N=102; 61%) children. Isolated splenomegaly was found only in (N=10; 7%) cases (Table 2). Laboratory analysis showed the involvement of all three cell lines in scrub typhus cases. Anaemia, Abnormal total leukocyte counts, and thrombocytopenia were noted in 116, 52 and 90 patients respectively. Nearly all the patients 112(68%) had mild to moderate anaemia. Severe anaemia was seen only in 4 cases. Total leukocyte counts were normal in the majority of patients.

Leukocytosis and leukopenia were observed in 36(22%) and 16(10%) children respectively.

Although thrombocytopenia was a prominent laboratory parameter among pediatric scrub cases which was noted in 96(54%) cases, nearly 50% of them had only mild to moderate thrombocytopenia. Only 6 cases had severe thrombocytopenia. Only a small number of patients showed raised SGOT and SGPT (5/24), elevated creatinine (1/7) and hyponatremia (1/32). The diagnosis was based on positive serum IgM for scrub typhus. All the patients were IgM positive.

Out of these 166 patients, eschar was seen in 100(60%) patients. Weil Felix test was positive in a

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total of 30 cases among 66 tested cases. The positive titre of 1: 80, 1:160 and 1:320 was seen in 5, 2 and 8 children respectively.

Table 1: Clinical profile and demographics findings Demographic data Total cases

(n=166) %

< 6 months 4 2

7-12 months 10 6

Age 1-6 years 56 34

7-12 years 96 58

Sex Male 110 66

Female 56 34

Rural 144 87

Area Urban 22 13

Yes 128 77

Open defecation

No 38 2

3

Figure 1: Infection sites of the child

DISCUSSION

Typhus, also known as tsutsugamushi fever, is one of the most common causes of acute undifferentiated fever in all age groups, especially in children. Recently, several outbreaks have been reported from all parts of India, especially during the monsoon season (June to December) in southern India and winter (September to January) in northern India (1,12,11,13-15).Most of the cases who presented with persistent and nonspecific fever.Undifferentiated signs and

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symptoms of acute fever. However, serious complications such as acute encephalitis syndrome, multi-organ organ dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), hemophagocyticlymphohistiocytosis and aortic valve endocarditis are not uncommon. Although scab has only been identified as a pathognomonic feature in a few cases that has questioned the clinical diagnosis.(16,17,9,18,19,20,21) The main risk factor for increased morbidity and mortality is delayed diagnosis. the current study 58% of children go to school and are therefore exposed to the presence of infected seabirds in the bush. However, an unexpected finding was the incidence of flaking typhus in infants aged less than one year who were predominantly indoors, which was most likely related to changes in habitat during the rainy season.15 The increased incidence of flaking typhus in males in this study. in previous research, it may be the result of social behavior that allows boys to trust each other while playing. The absolute increase in the rural population is understandable given the habitat of these seabirds. Seventy-seven percent of the study population reported open defecation, which is closely related to the likelihood of exposure to thrombiculide mites. Studies, can provide different data after use Indoor toilet. This study shows an increased incidence of typhoid fever during the monsoon season in Tamil Nadu (September to January). Bhat K et al. However, like other studies conducted in north and northeast India, it reports a peak number of typhoid friction cases after the monsoon (between September and November) which coincides with the rainy season, suitable for vegetation growth and thrombiculid mites. The ability of marine fish to migrate to a safer place (home) during the rainy season may explain the higher incidence of typhoid in infants in this study (8,11,13). Mild to moderate fever is the most persistent clinical disease. This fever symptom is consistent with most previous studies and available literature. The low incidence of prolonged fever for two weeks was associated with the presence of antibiotics in the range 6.25.

Maculopapular rash was observed in 17% of cases, contrary to previous studies. The reported rash in this study may be related to the dark skin of the study population, which may have made the rash less noticeable. Gastrointestinal systems such as vomiting (n = 43; 52%), diarrhea (n = 4; 5%) and abdominal pain (n = 19%; 16) reported this according to previous studies.

Documented by Narayanasamy et al. The gastrointestinal tract was the system most frequently affected (51%), and vomiting (68%) and abdominal pain (42%) were the most common symptoms. and the groin area. Previous research has shown that scabs vary between 30% and 67%. (23,26) In addition, escalators are observed in various places such as the hairline, navel, gluteal grooves, neck and buttocks. Escher's higher incidence in this study provides direct evidence of a precise clinical examination and a targeted search for Escher in hidden areas in cases where there is a high clinical suspicion of typhus. Lymphadenopathy is a common finding in children with flaking typhus. Regional lymphadenitis at the Escher site was a characteristic finding in previous studies (14). Although sores were reported in 60% of cases in this study, only (24; 29%) children developed local lymphadenitis. The majority (59/83) of cases with or without Escherichia coli had generalized lymphadenopathy and many had bilateral epitrochlear lymphadenopathy. None of the previous studies reported these clinical findings. In clinical settings, high suspicion of typhoid peeling and lack of scleral examination of the

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epitroclearlymph nodes may be possible clues. Therefore, the importance of these findings must be taken into account through more comprehensive studies and related investigations. This study is documented in comparison with previous studies with dominant hepatomegaly6 Hepatosplenomegaly (n = 51; 61%) was a significant finding and only hepatomegaly was found in (n = 27; 32%) cases. All isolated cases of splenomegaly were associated with co-infection.

The associated co-infections were two cases of smear positive malaria and four cases of dengue fever. The high incidence of hepatosplenomegaly and generalized lymphadenopathy is one direction of involvement of the reticuloendothelial system in typhus. Localized lymphadenitis may not have significant involvement of the reticuloendothelial system. The importance of these findings requires further investigation. The specific pathology of edge smears with two positive malaria smears in the non-migratory population suggests the need for urgent public health interventions. The insignificance of anemia as a significant risk factor in this study contradicts Thomas et al. The conclusions after a study of 262 children should be viewed against the background of a small number of working patients (6). The blood count of this study contradicts the typical findings of dietary anemia, where thrombocytosis occurs. Forty-seven percent of the study population reported thrombocytopenia. Compared to previous studies, this study showed a significantly higher incidence of moderate thrombocytopenia (27, 28). Six cases of severe thrombocytopenia were co-infected. Although liver enzymes were elevated in some cases, none of them showed clinical or biochemical signs of jaundice. Renal function is performed only in patients with oliguria or edema. The echo is normal in patients with tachycardia and edema.

There is no evidence of myocarditis. Scraping typhus was diagnosed based on a positive IgM ELISA. Weil-Felix is intended for children who rarely have scabs. Of the 33 cases without Escher, Weil Felix was only positive in (15; 44%) cases. This low percentage of positives demonstrates the usefulness of Weil Felix as a diagnostic tool for typhoid peeling. Clinical suspicion, together with the presence of Escherichia coli, anemia, thrombocytopenia, and positive serum IgM, diagnoses typhoid peeling in most cases. According to individual protocols, children under eight years of age were treated with azithromycin (10 mg / kg / day x 5 days) and children over eight years with doxycycline (5 mg / kg / day x 5 days). This led to complete clinical healing without recurrence during follow-up.

CONCLUSION

Scrub typhus is a common cause of acute undifferentiated fever in children and should be viewed as a differential diagnosis in infants as well. A high index of clinical suspicion with clinical expertise as well as IgM positivity in serum covered almost all cases of typhoid peeling.

Therefore, Weil-Felix may not always consider poor resource management. Hepatosplenomegaly with generalized lymphadenopathy, especially with epitrochlear lymph nodes, occurring in cases under favorable climatic conditions, should cause doctors to suspect typhoid peeling.

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