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 Table of Contents  
Year : 2021  |  Volume : 1  |  Issue : 3  |  Page : 173-175

Neonatal scrub typhus – A sepsis mimic

1 Department of Pediatrics, Pondicherry Institute of Medical Sciences, Puducherry, India
2 Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry, India

Date of Submission06-May-2021
Date of Decision06-Jul-2021
Date of Acceptance09-Aug-2021
Date of Web Publication31-Aug-2021

Correspondence Address:
Dr. Jagruthi Reddy
Room No. 511, OPD 4th Floor, PIMS Campus, Kalapet, Kanagachetticulam, Puducherry - 605 014
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_138_21

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Background: Scrub typhus is the most prevalent rickettsial infection in India. It is caused by Orientia tsutsugamushi. Although there are few reports suggesting vertical transmission from the mother to baby, it is extremely rare. Clinical Description: We describe a 1-day-old baby who was referred to us for respiratory distress and diagnosed as meconium aspiration syndrome, the clinical features of which resolved by the 10th day. The baby developed fever on the 11th day of life and was detected to have developed pallor and hepatosplenomegaly. History revealed maternal fever preceding and continuing well beyond delivery. Management: Late-onset sepsis was initially suspected in the baby. After reviewing the maternal history, transplacental transmission of scrub typhus was considered. Immunoglobulin M enzyme-linked immunosorbent assay was positive in the mother–baby dyad, but polymerase chain reaction for scrub typhus was negative. However, both exhibited a dramatic response in resolution of fever with doxycycline in the former and clarithromycin in the latter. On follow-up, the baby was well and gaining weight. Conclusion: Proper history and early initiation of management are important for reducing the morbidity and mortality of newborns with scrub typhus.

Keywords: Polymerase chain reaction, scrub immunoglobulin M enzyme-linked immunosorbent assay, transplacental infection

How to cite this article:
Reddy J, Rajan N, Dinakaran S, Krishnan L. Neonatal scrub typhus – A sepsis mimic. Indian Pediatr Case Rep 2021;1:173-5

How to cite this URL:
Reddy J, Rajan N, Dinakaran S, Krishnan L. Neonatal scrub typhus – A sepsis mimic. Indian Pediatr Case Rep [serial online] 2021 [cited 2021 Dec 8];1:173-5. Available from: http://www.ipcares.org/text.asp?2021/1/3/173/325081

Rickettsial infections are re-emerging causes of acute febrile illnesses throughout Asia. Scrub typhus, caused by Orientia tsutsugamushi, is the most prevalent rickettsial infection in India.[1] Manifestations of scrub typhus include hepatitis, meningitis, cardiac dysfunction, and triggering of preterm labor in pregnancy. The primary mode of transmission is through the bite of the trombiculid mite larvae.

We describe a mother–baby dyad manifesting with persistent spikes of fever. Rare modes of transmission in neonates include transplacental and postnatal transmission. Vertical transmission from mother to newborn was reported for the first time in 1992.[2] An exhaustive literature search revealed only three more newborns with scrub typhus till date.[3],[4],[5] Establishing diagnosis in the neonatal period is challenging, given the low index of suspicion, nonspecific signs and symptoms, and lack of diagnostic tests with high sensitivity and specificity. If undiagnosed, there is significant morbidity and mortality.[6] In contrast, with timely diagnosis, treatment is easy, affordable, and there is often a dramatic response to antimicrobials.[1],[5]

  Clinical Description Top

A baby boy was referred to our newborn unit from a private hospital for respiratory distress that developed soon after delivery. He was born to a 33-year-old third gravida (with two previous abortions) at 39 weeks of gestation. The antecedent antenatal period had been uneventful. The mother had been screened for toxoplasma, rubella, cytomegalovirus, and herpes simplex virus, which were negative. The mother developed fever 4 days before birth. There were no localizing signs and symptoms, and the preliminary investigations were inconclusive. The mother was started on broad-spectrum antibiotics. Delivery was by an emergency cesarean section in view of meconium-stained liquor. The baby cried immediately at birth at a nearby hospital and weighed 2.79 kg. The baby was received in our tertiary care institution at 4 h of life. At admission, the baby had severe respiratory distress but was normothermic and hemodynamically stable. The baby was electively intubated for acute respiratory failure and started on synchronized intermittent mandatory ventilation with peak inspiratory pressure/positive end expiratory pressure of 20/4, respiratory rate of 40/min, and FiO2 of 80%. Two provisional diagnoses were considered; meconium aspiration syndrome (MAS) and congenital pneumonia. The baby was started on intravenous fluids and antibiotics after sending relevant investigations.

Management and outcome

The hemogram revealed normal hemoglobin (Hb) of 14 g/dL leukocytosis with a total leukocyte count (TLC) of 22,400/mm3 and normal platelet counts. Chest X-ray showed multiple patchy nonhomogenous opacities [Figure 1]. A negative sepsis screen and sterile blood culture ruled out congenital pneumonia. Hence, the diagnosis of MAS was retained. The baby was extubated on day 7 of life and started on continuous positive airway pressure. Nasogastric feeds were initiated. On day 8, status improved further, but the SpO2 could not be maintained above 94% in room air. A normal two-dimensional echocardiography ruled out persistent hypertension of the newborn, a known complication of MAS. By the 10th day, the baby was active, displayed good spontaneous movements, the oxygen requirement had resolved, and the baby was started on paladai feeds.
Figure 1: Multiple patchy opacities in both lung fields suggestive of meconium aspiration syndrome

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On the 11th day of life, the baby developed recurrent spikes of high-grade fever without any other localizing symptoms. The baby was hemodynamically stable, but it was noted that he had developed hepatosplenomegaly (liver span 7 cm and spleen palpable 3 cm below the left subcostal margin. Broad-spectrum antibiotics (vancomycin and meropenem) were started suspecting late-onset nosocomial sepsis and/or meningitis, after sending a repeat septic workup. These revealed anemia with a drop in Hb levels to 11 gm/dL, normal TLC (7200/mm3) and platelets (2.85/mm3), elevated C-reactive protein (102 mg/dL), and increased transaminase levels (Serum glutamic oxaloacetic transaminase (SGOT) 259 U/L, Serum glutamic pyruvic transaminase (SGPT) 194 U/L). Blood culture was sterile. The cerebrospinal fluid analysis (CSF) was normal with the absence of leukocytes, protein 72 mg/dL, sugar 53 mg/dL, and sterile CSF culture. The fever persisted [Figure 2].
Figure 2: Charting of Vitals showing the pattern of fever and the lyse of fever after starting clarithromycin

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In the meantime, it was discovered that the mother's fever had not abated and she had been hospitalized. Her reports had shown thrombocytopenia and leukopenia, and parenteral antibiotics had been started considering postpartum septicemia. Antifungals had been added when there was no symptomatic relief. Pleural effusion was identified on a chest radiograph. Scrub typhus was suspected, immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) was sent, and oral doxycycline was started. Diagnosis was confirmed by a positive serology report and supported by dramatic resolution of fever. In these circumstances, we considered transplacental scrub typhus infection in the baby and investigated accordingly. He was started on parenteral clarithromycin (15 mg/kg/day) empirically, while awaiting the reports. The fever disappeared within 24 hour [Figure 2] and did not recur. The baby's IgM ELISA for scrub typhus was also positive, though the scrub polymerase chain reaction (PCR) (sent on day 9 of fever) was negative. Clarithromycin was continued for 10 days. At discharge on day 32 of life, the baby was breastfeeding well and displayed adequate weight gain.

  Discussion Top

Scrub typhus is endemic in the regions of South India and Northeast regions. Although there is definite increase in prevalence of scrub typhus in children in recent years, there is limited literature regarding infection in newborns. Usually, affected children present with fever, respiratory distress, abdominal distension, poor feeding, lethargy, seizures, and hepatosplenomegaly. These manifestations commonly mimic severe sepsis.[7] Diagnosis of scrub typhus is established by IgM ELISA and confirmed by PCR, preferably nested PCR. The Weil Felix agglutination test was has fallen into disrepute due to poor specificity and sensitivity. In this case report, the explanation for a negative real-time PCR in both mother and baby despite having reactive scrub typhus IgM antibodies may be low sensitivity (44.8%), in contrast to nested PCR(82.2%).[8] The routes of transmission of scrub typhus are transplacental, perinatal blood-borne, and postnatal infection.[2] Transplacental infection is the vertical transmission from mother to fetus, in which IgM ELISA will be positive for the baby.[1] Perinatal blood-borne infection may not have IgM positivity. Postnatal infection is when a baby acquires the infection from a tick bite that may occur ticks attach to clothes when the have been put to dry after a wash. This was ruled out in this case as the baby had been admitted in the Neonatal intensive care unit (NICU) since birth.

The case described by Wang et al. was initially considered to be aseptic meningitis.[2] Suntharasaj et al. reported positive IgM antibodies in a preterm baby of 34 weeks gestation.[3] Postnatal transmission was suspected in a 19-day-old resident of Delhi with positive IgM ELISA and scrub PCR. The mother was asymptomatic and negative for both tests, but a relative had visited from Assam and it was speculated that a tick could have got stuck on the luggage.[4] Another unusual source of postnatal transmission was suspected due to application of “vasambu,” a medicinal herb commonly used in South India for home remedies of young infants. It was assumed that chiggers may have been present in the plant.[5]

Prompt diagnosis and early initiation of management are critical in reducing mortality and morbidity of newborns with scrub typhus. Although doxycycline is the drug of choice, it is avoided in newborns because of the possible side effects, and azithromycin and clarithromycin are used instead. Since there are a few cases of azithromycin causing infantile hypertrophic pyloric stenosis,[9] we chose to treat our patient with parenteral clarithromycin.

Declaration of patient consent

The authors certify that they have obtained the appropriate consent from the parent. The legal guardian has given his consent for the images and other clinical information to be reported in the journal. The guardian understands that the name and initials will not be published, and due efforts have been made to conceal the same, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Aarthi P, Bagyalakshmi R, Mohan KR, et al. First case series of emerging rickettsial neonatal sepsis identified by polymerase chain reaction-based deoxyribonucleic acid sequencing. Indian J Med Microbiol 2013;31:343-8.  Back to cited text no. 1
[PUBMED]  [Full text]  
Wang CL, Yang KD, Cheng SN, et al. Neonatal scrub typhus: A case report. Pediatrics 1992;89:965-8.  Back to cited text no. 2
Suntharasaj T, Janjindamai W, Krisanapan S. Pregnancy with scrub typhus and vertical transmission: A case report. J Obstet Gynaecol Res 1997;23:75-8.  Back to cited text no. 3
Jajoo M, Kumar D, Manchanda S. Scrub typhus in a new born. J Clin Diagn Res 2017;11:D05-6.  Back to cited text no. 4
Paramanantham P, Sathyamoorthy DP, Sekar DP. Neonatal scrub typhus: Case report. World J Pharm Res 2018;7:836-40.  Back to cited text no. 5
Rathi N, Kulkarni A, Yewale V, et al. IAP guidelines on rickettsial diseases in children. Indian Pediatr 2017;54:223-9.  Back to cited text no. 6
McGready R, Prakash JA, Benjamin SJ, et al. Pregnancy outcome in relation to treatment of murine typhus and scrub typhus infection: A fever cohort and a case series analysis. PLoS Negl Trop Dis 2014;8:e3327.  Back to cited text no. 7
Kim DM, Byun JN. Effects of antibiotic treatment on the results of nested PCRs for scrub typhus. J Clin Microbiol 2008;46:3465-6.  Back to cited text no. 8
Smith C, Egunsola O, Choonara I, et al. Use and safety of azithromycin in neonates: A systematic review. BMJ Open 2015;5:e008194.  Back to cited text no. 9


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