Journal Information
Vol. 87. Issue 2.
Pages 259-260 (April - June 2022)
Vol. 87. Issue 2.
Pages 259-260 (April - June 2022)
Scientific letter
Open Access
Typhoid encephalopathy as a neuropsychiatric manifestation of salmonellosis
Encefalopatía tifoidea como manifestación neuropsiquiátrica de salmonelosis
F.J. Murillo-Cerda
Corresponding author

Corresponding author at: Dr. Ignacio Morones Prieto O3000. Monterrey, Mexico. 64710. Cél. 8183963841.
, M.F. Martínez-Reséndez
Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, Mexico
Article information
Full Text
Download PDF
Full Text

A 78-year-old man, with a past history of type 2 diabetes mellitus and high blood pressure, arrived at the emergency room. He had presented with 10 diarrheic bowel movements (Bristol Stool Scale 7) 48 h earlier, nausea, and general weakness. He stated that he had no fever, had not ingested raw or contaminated food, and had no blood or mucus in his stools. In addition, 36 h earlier, he had 2 episodes of vomiting and disorientation, prompting him to seek medical attention at the emergency department. Physical examination revealed low blood pressure (90/60 mmHg), no tachycardia, dehydrated mucous membranes, and no cardiopulmonary alterations. The patient had generalized abdominal pain of 5/10 on the visual analogue scale (VAS) and no signs of peritoneal irritation. The initial neurologic examination detected somnolence and no signs of meningeal irritation. The laboratory work-up reported hemoglobin 11.6 g/dl; MCV 95.5; MCH 31; leukocytes 12,600 cell/mm3, with neutrophils 10,800 cell/mm3 and lymphocytes 700 cell/mm3; platelets 193,000 cell/mm3; creatinine 1.9 mg/dl (GFR CKD-EPI 33 ml/min/1.73 m2); urea 113.4 mg/dl; sodium 132.57 mEq/l; potassium 4.52 mEq/l; chloride 105.4 mEq/l; albumin 3.7 g/dl; normal anion GAP metabolic acidosis with pH of 7.25; HCO3 17.8 mEq/l; PCO2 42 mmHg; PO2 45 mmHg; base excess –8.4; and lactate 0.9 mmol/l. The rest of the complete blood count and biochemical profile values were within normal limits. Thyroid profile, coagulation times, ammonia level, and electrocardiogram were also ordered, and all were within normal values. The patient was admitted to the hospital, hydrated with Hartmann solution at 125 cc/h and given supportive care, with neurologic surveillance. During the first 2 days of hospitalization, he presented with fever of 38.7 °C, psychomotor agitation, and disorientation affecting the 3 spheres. The second neurologic examination, conducted 48 h after hospital admission, revealed delirium mixed with somnolence and alternating with periods of agitation, incoherent verbalization, a doubtful plantar response, and no meningism. Given his altered state, the neurologic examination was complemented 24 h later, finding: normal cranial nerve pairs, normal deep tendon reflexes, and indifferent plantar response. Due to the patient’s neurologic decline, a non-contrasted tomography scan of the brain and a lumbar puncture were carried out, the results of which were within normal parameters. An electroencephalogram was ordered, reporting: abnormal alertness and mild diffuse cortical dysfunction with triphasic waves, characteristic of encephalopathy, correlating with the clinical data. Cerebrospinal fluid culture was ordered, along with stool panel, gastrointestinal panel PCR, and stool and blood cultures. Continuing management included a decrease in fluids to 80 cc/h. After the cultures were taken, broad-spectrum antibiotic therapy was started with a carbapenem (ertapenem 1 g IV every 24 h). The results of the stool culture reported signs of inflammatory diarrhea, with more than 100 leukocytes per field and positive fecal occult blood. The cerebrospinal fluid and blood cultures were negative, Salmonella was detected through PCR testing, and the stool culture was positive for Salmonella spp. The antibiogram reported susceptibility to trimethoprim/sulfamethoxazole, ceftriaxone, and ampicillin. Antibiotic therapy was de-escalated to ceftriaxone, combined with azithromycin, and the regimen was completed with a macrolide for 10 days. Twenty-four hours after the first dose of the antibiotic treatment, the patient presented with improvement of the gastrointestinal and neurologic symptoms. On hospitalization day 5, a new neurologic examination revealed a conscious patient, oriented in the 3 spheres, with coherent speech, no agitation, no focal neurologic signs, normal deep tendon reflexes, improved sleep/wake cycle, and only 2-3 bowel movements per day (Bristol Stool scale 5). Control laboratory tests reported improved kidney function, with creatine of 1.1 mg/dl (GFR CKD-EPI 64 ml/min/1.73 m2), and a new gasometry with pH 7.35, HCO3 22 mEq/l, PCO2 41 mmHg, PO2 29 mmHg, base excess –2.8, and lactate 0.8 mmol/l. On hospitalization day 7, the patient had complete symptom resolution and was discharged with no symptoms on day 10. There are approximately 70,000 cases per year of salmonellosis in Mexico.1 The present case was one of a rare extraintestinal manifestation (neuropsychiatric) of salmonellosis (typhoid encephalopathy), considering the large number of patients with a Salmonella-induced infection in Mexico.2 As a reference of this presentation in the Americas, specifically in the United States, the neuropsychiatric manifestation of delirium is documented in less than 5% of patients with salmonellosis.3 The clinical picture of typhoid encephalopathy is characterized by a clinical spectrum of neurologic manifestations that include an altered state of alertness, delirium, confusion, convulsions, and coma, as described by Martin in 1994. Delirium is the main event and presents in 23 to 57% of patients with that diagnosis.4 The rule-out diagnosis should document an altered state of alertness, convulsions, or delirium, with no associated systemic disease, as well as microbiologic detection of Salmonella and the absence of infection in the central nervous system (CNS).5 The present case was a diagnostic challenge. Given the patient’s neurologic decline, a neuroinfection was initially ruled out. The findings of Salmonella in the gastrointestinal PCR test, the inflammatory diarrhea, and the results of the electroencephalogram led to our suspicion of the disease. In addition to being a difficult diagnosis, the fact that it was a rule-out diagnosis meant it had to made quickly, requiring a high level of suspicion. Advanced age, leukopenia, a Widal reaction ≥ 1:640, and dehydration are independent risk factors for poor prognosis.6 Our patient had several of those factors, thus treatment had to be started as quickly as possible, as was the case. Treatment is with antibiotic therapy, and high-dose glucocorticoids can be used as coadjuvant therapy in severe cases. The mortality rate is approximately 50% but adequate antibiotic management and the use of dexamethasone can reduce said rate to 13% in severe cases.7 In Mexico in 2014, Vázquez-Garcidueñas reported resistance to ampicillin, carbenicillin, and cephalothin.8 Empiric antibiotic management is indicated with third-generation cephalosporines or carbapenems. Quinolones are not indicated as empiric management due to their high resistance rate.9 Supportive care with fluids and the correct application and de-escalation of antibiotics were essential for preventing progression to a more severe form in our patient, thus avoiding the use of glucocorticoids. The antibiogram reported susceptibility to ceftriaxone, and so antibiotic therapy was de-escalated to ceftriaxone 2 g iv/every 24 h, in combination with azithromycin. The double regimen was indicated because of the delayed response to azithromycin, compared with ceftriaxone, and to ensure intravenous administration for at least 7 days.10 Due to the patient’s good response on day 7, the regimen was switched to oral azithromycin for 10 days (500 mg vo/every 24 h). The case presented herein is rare in our clinical practice, and so we consider reporting it important, to aid in the future diagnosis and opportune treatment of such cases.

Ethical considerations

The authors declare that no experiments were conducted on animals or humans in the present research and the protocols of their work centers were followed, with respect to the publication of patient data, preserving patient anonymity at all times.

They also declare that this article contains no information that could identify the patient, thus informed consent on the part of the patient was not required.

Financial disclosure

No financial support was received in relation to this article.

M.B. Contreras Soto, J.A. Medrano Félix, J.R. Ibarra Rodríguez, et al.
The last 50 years of Salmonella in Mexico: sources of isolation and factors that influence its prevalence and diversity.
Revista Bio Ciencias, 6 (2018), pp. e540
G. Ali, S. Rashid, M.A. Kamli, et al.
Spectrum of neuropsychiatric complications in 791 cases of typhoid fever.
Trop Med Int Health, 2 (1977), pp. 314
T.A. Hoffman, C.J. Ruiz, G.W. Counts, et al.
Waterborne typhoid fever in Dade County, Florida. Clinical and therapeutic evaluation of 105 bacteremic patients.
K. Martin, M. Sharland, E.G. Davies.
Encephalopathy associated with Salmonella enteritidis Infection.
Scand J Infect Dis, 26 (1994), pp. 486
J. Arii, Y. Tanabe, M. Miyake, et al.
Clinical and pathologic characteristics of nontyphoidal salmonella encephalopathy.
Neurology, 58 (2002), pp. 1641
D.T. Leung, J. Bogetz, M. Itoh, et al.
Factors associated with encephalopathy in patients with Salmonella enterica serotype Typhi bacteremia presenting to a diarrheal hospital in Dhaka, Bangladesh.
Am J Trop Med Hyg, 86 (2012), pp. 698
S.L. Hoffman, N.H. Punjabi, S. Kumala, et al.
Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone.
N Engl J Med, 312 (1984), pp. 82
M.S. Vázquez Garcidueñas, N.L. Romero Pérez, G.A. Figueroa Aguilar, et al.
Investigation of a food-borne Salmonella Oranienburg outbreak in a Mexican prison.
J Infect Dev Ctries, 8 (2014), pp. 143
A. Karkey, G.E. Thwaites, S. Baker.
The evolution of antimicrobial resistance in Salmonella Typhi.
Curr Opin Gastroenterol, 34 (2018), pp. 25
C. Jin, M.M. Gibani, S.H. Pennington, et al.
Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of clinical and microbiological data from a controlled human infection model.
PLos NegL Trop Dis, 13 (2019), pp. 1

Please cite this article as: Murillo-Cerda FJ, Martínez-Reséndez MF. Encefalopatía tifoidea como manifestación neuropsiquiátrica de salmonelosis. Rev Gastroenterol Méx. 2022;87:259–260.

Copyright © 2021. Asociación Mexicana de Gastroenterología
Revista de Gastroenterología de México

Subscribe to our newsletter

Article options
es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.