Scrub Typhus in Children at Tribhuvan University Teaching Hospital in Nepal

Figures & data

Table 1 Definitions of Various Medical Conditions/Complications

Myocarditis^Citation11	(1) Congestive cardiac failure (CCF) or cardiomegaly or (2) Hemodynamic compromise that required a vasopressor (≥5 µg/kg/min of dobutamine or dopamine), use of noradrenaline/adrenaline or (3) Elevated CPK-MB (creatine phosphokinase MB) levels (>25 U/L) in the blood
Hypotension^Citation11	A systolic blood pressure below the fifth percentile for the corresponding age, sex and height
Acute Kidney Injury^Citation15	According to Kidney Disease: Improving Global Outcomes (KDIGO) definition and classification
Acute Respiratory Distress Syndrome^Citation16	According to consensus recommendations from the Pediatric Acute Lung Injury Consensus
Meningitis^Citation17	Presence of altered sensorium and signs of meningeal irritation or elevated cells and protein on cerebrospinal fluid (CSF) analysis.
Multiorgan Dysfunction (MODS)^Citation8,Citation18	Any alteration of organ function that requires medical support for maintenance involving two or more organ systems (respiratory, cardiovascular, renal, hepatic, and neurological systems)
Generalized lymphadenopathy^Citation19	When there is enlargement of more than two noncontiguous node regions
Disseminated Intravascular Coagulation (DIC)^Citation17,Citation20	Clinical manifestations of bleeding along with thrombocytopenia and elevated coagulation profile (prolong prothrombin (PT), International Normalized Ratio (INR) and activated prothrombin time (aPTT) Prolong PT as >12 seconds, prolong INR as >1.2, prolong aPTT>37 seconds
Anemia^Citation20	When hemoglobin (Hb) is less than value of that for age and gender (for 1–23 months <10.5 g/dL, 2–9 years <11.5 g/dL, 10–17 years male <12.5 g/dL, female <12 g/dL)
Hepatitis^Citation17,Citation20	When liver transaminase and or serum bilirubin are found to be elevated. Transaminitis is considered for raised serum glutamic oxaloacetic transaminase (SGOT) for 1–9 years >55 IU/L and 10–16 years >45 IU/L, raised serum glutamic pyruvic transaminase (SGPT) > 45IU/L
Hyperbilirubinemia^Citation20	Raised bilirubin is >1 mg/dL (17umol/L)
Raised serum creatinine^Citation20	Serum creatinine is raised if serum creatinine as for <1 year is >35 µmol/L, 1–9 years >62 µmol/L, 10–16 year s>88 µmol/L
Proteinuria^Citation21	Routine urine examination showing albumin ≥2+
Relapse^Citation22	The reappearance of fever and clinical manifestations of scrub typhus, in the absence of any other identifiable cause, within 30 days after completing therapy
Nonresponse to initiated drug^Citation7	When child does not achieve resolution of fever within five days of initiating drugs as mentioned in Table 2
Hemophagocytic Lymphohistiocytosis (HLH)^Citation23	Based on diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis (HLH 2004) as (1) persistent fever, (2) splenomegaly, (3) cytopenias, at least two lineages of hematopoiesis (hemoglobin <9 g/dL, neutrophils<1.0 × 10^9/L, platelets <100 × 10^9/L), (4) hypofibrinogenemia (<150 mg/dL) and/or hypertriglyceridemia (>265 mg/dL), (5) hyperferritinemia (>500 ng/mL), (6) hemophagocytosi, (7) low natural killer cell activity, and (8) high concentration of soluble receptor for interleukin 2 (sCD25). Five of the above eight criteria were sufficient for the diagnosis of HLH.

Table 2 Treatment Modality Based on EDCD Guideline on Prevention and Control of Scrub Typus of Nepal

S. No.	Treatment Modality
1	Azithromycin (10 mg/kg) single dose for children less than eight years
2	Doxycycline (2.2 mg/kg) orally twice daily was suggested for three days after resolution of fever (usually 5–10 days course) for children more than eight years old.
3	Alternative therapy advised was quinolones (oral 10 mg/kg/dose or intravenous 5 mg/kg/dose ciprofloxacin or levofloxacin) twice daily for 5–10 days and oral or intravenous chloramphenicol 25 mg/kg/dose six-hourly for 5–10 days^Citation23
4	All patients suspected to have meningitis or multiorgan involvement due to scrub typhus are started on intravenous chloramphenicol before serological report is available.

Figure 1 Incidence of scrub typhus according to seasonal variation.

Table 3 Demographic Data of Children with Scrub Thypus

	Number (%)
Gender  Female  Male	45 (53.6) 39 (46.4)
Age  <3years  3–5years  6–9years  10–14years  >15 years	4 (4.8) 10 (12) 16 (19.1) 37 (44) 16 (19.1)

Table 4 Clinical Profile of Children with Scrub Typus at Presentation

Symptoms	Number (%)
Fever <7 days 7–13 days 14–29 days ≥30 days	6 (7.1) 59 (70.2) 16 (19.1) 3 (3.6)
Respiratory manifestations
Shortness of breath	42 (50)
Cough	22 (26)
Chest pain	13 (15.5)
Gastrointestinal manifestations
Abdominal pain	36 (43)
Vomiting	35 (42)
Loss of appetite	7 (8)
Loss stool	4 (5)
Central nervous system manifestations
Headache	32 (38)
Altered sensorium	17 (20.2)
Seizure	11 (13.1)
Musculoskeletal manifestations
Myalgia	11 (13)
Joint pain	2 (2.4)
Rash	1 (1.2)
Ophthalmological manifestations 13 (15.5)
Red eye (unilateral/bilateral) with/without eye pain	7
Decreased vision	4
Diplopia	2
Clinical signs Hepatomegaly	55 (65.5)
Splenomegaly	39 (46.4)
Edema (pedal/periorbital/generalized)	32 (38)
Eschar	22 (26)
Hypotension	21 (25)
Lymphadenopathy  Generalized  Cervical  Axillary  Inguinal	20 (24) 10 13 11 7
Pallor	17 (20)
Icterus	14 (17)
Ascitis	12 (14)
Raised intracranial pressure	12 (14.3)
Maculopapular rash	11 (13)
Ophthalmological manifestations	11 (13)
Conjunctivitis	9
Anterior ulcerative blepharitis (both eyes)	1
Bilateral anterior uveitis	1

Table 5 Laboratory Abnormalities in Children with Scrub Typus

Laboratory Parameters	Number n/N^a (%)
Raised SGOT	50/60 (83.3)
Raised SGPT	47/60 (78.3)
Raised bilirubin	20/36 (55.55)
Raised INR	4/16 (25)
Anemia	68/84 (81)
Leucocytosis	33/84 (39.2)
Leucopenia	3/84 (3.6)
Thrombocytopenia	44/84 (52.4)
Raised serum creatine phosphokinase MB	27/42 (64.28)
Hyponatremia	30/79 (38)
Hypoalbuminemia	14/23 (60.8)
Albuminuria	17/84 (20.2)
Raised serum creatinine	25/84 (29.76)

Notes: ^aN, total number of children investigated; n, number of children with abnormal report among total number of children investigated.

Table 6 Complications of Scrub Typus Seen in Children

Complications	Number (%)
Hepatitis	50 (59.5)
Myocarditis	34 (40.5)
CCF	23 (27.4)
Meningitis	29 (34.5)
Pneumonia	21 (25)
MODS	16 (19)
ARDS	13 (15.5)
AKI	12 (14.3)
Pleural effusion	9 (10.7)
DIC	5 (5.9)
Cranial nerve palsy (bilateral sixth cranial nerve)	2 (2.4)

Figure 2 Flowchart showing treatment, fever defervescence and other outcomes. In the remaining seven patients of total children, two children initially on oral chloramphenicol and oral azithromycin each, one each on intravenous (iv) azithromycin, iv levofloxacin, iv cefepime improved on same regimens.

Table 7 Number of Children on Different Drugs at Presentation or Initiated at the Time of Admission

S. No.	Name of Antibiotics	Number of Children
1	Oral doxycycline	34
2	Intravenous chloramphenicol	41
3	Oral chloramphenicol	2
4	Oral azithromycin	3
5	Intravenous azithromycin	1
6	Intravenous cefepime	1
7	Intravenous levofloxacin	2
	Total	84

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