P - ISSN : 2349-6592    |    E - ISSN : 2455-7099
Year : 2019 | Volume : 6 | Issue : 3 | Page : 58 - 61
Source of Funding:None Conflict of Interest:None
A 6 year old girl presented with a history of fever for 3 weeks, headache and multifocal seizures for 4 days with altered sensorium. Clinical assessment was consistent with hypotensive shock and encephalopathy. Her IgM and IgG Typhidot test was positive. Laboratory evaluation revealed deranged renal and liver functions with coagulopathy, anemia and thrombocytopenia. She did not respond to broad spectrum intravenous antibiotics, vaso-active infusions, corticosteroids and had refractory status epilepticus. She progressed rapidly to refractory septic shock and multiple organ dysfunction with AKI and ARDS. She succumbed to her illness despite antibiotics and other adjunctive therapies. This case highlights a rare and catastrophic presentation of typhoid fever.
Typhoid fever, Typhidot, Multi Organ Dysfunction Syndrome, Septic shock.
Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is one of the common causes of community acquired bacterial sepsis worldwide, especially in the Indian subcontinent. There were approximately 11.9 million typhoid fever cases annually worldwide as per latest global estimates. Typhoid fever also accounted for close to 1, 29,000 deaths in low and middle income countries.1 The estimated incidence of typhoid fever in India is 370 per 100,000 person years. The incidence is higher in children with the commonest age group affected being between 2-4 years with comparatively higher rates of complications and hospitalization.2Typhoid is transmitted by fecal–oral route with a 7-14 day incubation period. Fever is the commonest symptom with associated infl uenza like symptoms (malaise, anorexia, headache, dry cough, sore throat) and predominant abdominal symptoms (nausea, vomiting, diarrhea, constipation, diffuse abdominal pain).3 Complications occur in 10-15% patients usually beyond 2nd week of illness. The commonly reported complications of typhoid fever are gastrointestinal bleeding and perforation, typhoid encephalopathy and other end organ involvement(cholecystitis, hepatitis, pneumonia, acute kidney injury, myocarditis).4,5 The case fatality ratio for complicated typhoid fever is usually <1%. Typhoid fever manifesting as septic shock and multi-organ dysfunction syndrome has been reported infrequently and mortality estimates for the same are not clearly known.6-8 We present one such case of typhoid fever with multi-organ dysfunction which could not be salvaged despite best efforts.
A 6 year old Indian girl presented with history of fever for 20 days, multifocal convulsions and headache since 5 days and altered sensorium for 1 day. She was evaluated at a medical centre where CSF analysis was performed which was normal and her blood and CSF cultures were reported sterile.She received intravenous antibiotic (Ceftriaxone), antimalarial (Chloroquine)and anti-epileptics (Phenytoin) for 4 days at the referring hospital and was referred to our institute for further management. She was developmentally normal and there was no signifi cant past history.There was no contributory family history. On examination at admission she was febrile and had tachycardia (HR-130/min) with a capillary refi ll time of 3 sec with BP 84/54(58) mm Hg (< 5th centile for age). Her central and peripheral pulses were well felt with warm peripheries. She had tachypnea (RR- 26/min) with sub-costal and inter-costal retractions along with a oxygen saturations of 90% at room air. Neurological evaluation revealed a low GCS 7/15 (E2M1V4) with intermittent decorticate posturing. Her pupillary reaction was bilaterally equal and brisk. Respiratory examination revealed bilaterally equal vesicular breath sounds. She had a soft hepatomegaly with a liver span of 11cm along with moderately enlarged soft spleen. She was commenced on 100% high fl ow oxygen with non-re-breathing mask. Rapid vascular access was secured and fl uid resuscitation was initiated in view of clinical features consistent with warm septic shock. Elective endotracheal intubation was performed with modifi ed RSI technique in view of persistently low GCS, increased work of breathing and signs of decreased peripheral perfusion. She was commenced on broad spectrum intravenous antibiotics (Inj. Meropenem, Vancomycin, Metronidazole), anti-malarial (Inj. Artesunate). She required vasoactive infusions in view of hypotension and fl uid unresponsive shock. Noradrenaline at a dose of 0.5 mcg/kg /min, Adrenaline at a maximal dose of 0.5 mcg/kg/min, Vasopressin at a dose of 0.06 IU/ kg/min were commenced and titrated to response. High dose corticosteroid (Inj. Methylprednisolone) was also added in view of catecholamine refractory shock. Echo-cardiographic assistance was utilized to optimize and enhance intravascular volume with fl uid therapy and inotropic dose adjustments to achieve targeted hemodynamic parameters. Osmotherapy for raised intracranial pressure was initiated with 3% hypertonic saline intravenously and loading followed by maintenance doses of antiepileptic drugs were administered for status epilepticus as per protocol. Midazolam infusion was commenced and escalated under continuous EEG monitoring in view of progression to refractory status epilepticus. General anesthesia with Inj. Propofol was utilized in view of seizures refractory to Midazolam infusion.
Laboratory evaluation was done for ascertaining etiology and assessing end organ damage. Complete blood picture revealed anemia (Hb-6.8gm/dl) and thrombocytopenia (platelets-77000/mm3) and normal TLC. She received group and cross matched packed cell transfusion on the day of admission. Blood gas analysis showed increased anion gap metabolic acidosis (pH-7.19, HCO3- 12mmol/l), alongwith elevated serum lactate levels (19.6mg /dl). She had markedly elevated CRP levels at admission (95.7mg/l). Her peripheral smear examination showed burr cells and spherocytes, whereas smear for malarial parasites was negative. She had deranged renal functions (BUN-94.9mg/dl, serum creatinine - 3.7 mg/dl) at admission while maintaining normal urine output. She also had deranged liver function tests (SGOT 131U/L, SGPT-62U/L) and coagulation profi le (PT- 17.9sec, aPTT->100 sec, INR-1.41). She was commenced on supplemental doses of Inj. Vitamin K and closely monitored for bleeding manifestations. She also had other metabolic abnormalities in the form of Hypo-natremia (129meq/L) and hypocalcemia (Ionic Ca++ 2.7mg/dl) which were corrected. Her rapid test (Typhidot) for IgM and IgG antibodies to Salmonella typhi was reported positive. She tested negative for Dengue serology, Rapid malarial antigen, IgM antibody to Leptospira. Her complete urine examination was normal. Ultrasound examination of the abdomen showed hepato-splenomegaly, minimal ascitis with no intra-abdominal focus of infection. Her surveillance cultures (blood, urine and tracheal aspirate cultures) were reported to be sterile.
She went on to develop progressively worsening multi organ dysfunction with laboratory evidence of severe thrombocytopenia (23000/mm3), deranged RFT (Serum creatinine-71.7 mg/dl, BUN-3.2mg/ dl). Peritoneal dialysis was commenced in view of progression to oliguric AKI and resource constraints. She also developed features of ARDS with new onset patchy bilateral infi ltrates on chest radiograph and worsening oxygenation (oxygenation index-10.34) despite alveolar recruitment and high mean airway pressures.
She was provided necessary organ system support at appropriate levels during the course of MODS. However, she deteriorated rapidly onto irreversible multi-organ dysfunction syndrome and succumbed to her illness by day 2 of admission.
Majority of children with typhoid fever recover completely with appropriate treatment with no major complications. The important determinants of complications in typhoid fever are duration of illness before initiation of appropriate antibiotic therapy, age of the patient, immunization status, virulence of the strain and the host nutritional and immune status. There are many reported cases of complications in typhoid fever due to target organ involvement, commonest of which are gastrointestinal and central nervous system.5 However typhoid fever causing multi-organ dysfunction syndrome is rare occurrence.
Hazouard E et al. have reported a similar case of a 20 year old woman presenting with shock and coma who responded to antibiotics.9 Huang GC et al. have reported two adult cases of typhoid fever complicated by multi-organ dysfunction.6 Typhoid fever complicated by meningitis, myocarditis, hepatitis and AKI has been reported in a 12 year old girl.7 A case of typhoid fever manifesting with hepatitis, AKI, serosal effusions and thrombocytopenia in a 8 year old boy has been reported from India.8 Septic shock along with ARDS has been reported in a 16 year old adolescent male with Typhoid fever which successfully responded to antibiotics and steroids.10 Our index case presented with nervous system manifestations in the form of seizures and encephalopathy progressing rapidly to refractory septic shock with multi-organ dysfunction. Typhoid fever with hemodynamic compromise and multiorgan involvement carries a high case fatality ratio, as exemplifi ed by this case.3 Although blood culture is the defi nitive test for diagnosis, its sensitivity decreases from 80% in the fi rst week to as low as 40% with increasing duration of illness.3 This along with prior antibiotic use could explain the inability to isolate the organism in our case. The Typhidot test is a qualitative Enzyme-Linked Immunosorbent Assay (ELISA) that detects specifi c IgM and IgG antibodies against a 50-kDa Salmonella serovar Typhi outer membrane protein. A recent Cochrane review has estimated the average sensitivity and specifi city of this test to be 84% and 79% respectively.11 Thus a point of care test like Typhidot could be a good alternative for diagnosis in such an emergency setting. The protean complications seen in this case and failure to respond to standard fi rst and second line antibiotics raises the possibility of a multidrug resistant strain. Recent studies from India have reported strains resistant to Ceftriaxone and Azithromycin. Also these studies have shown re-emergence of susceptibility to traditional antibiotics like amoxicillin, Co-trimoxazole and chloramphenicol.12, 13 These interesting trends call for further studies and tailoring antimicrobial therapy as per local susceptibility patterns.
Typhoid fever should be considered in the differential diagnosis of any acute febrile illness in endemic areas. It can have varied presentations with involvement of multiple extra-intestinal organ systems. Rapid diagnostic test like Typhidot may be valuable for an emergent diagnosis. A protracted disease course with complications and failure to respond to fi rst line antibiotics portend a poor outcome. Early referral to advanced centers should be considered for such complicated cases of typhoid fever.
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