A patient with typhoid fever presenting with neuropsychiatric complications is a common occurrence in the tropics; however, such atypical manifestations can present a diagnostic challenge, even to an experienced clinician. Various authors have highlighted protean neuropsychiatric presentations of typhoid fever, such as an acute confusional state, myelitis cerebellitis, parkinsonism, acute psychosis, meningo-encephalitis and generalized anxiety disorder1-5. Because of these varying neuropsychiatric presentations, typhoid fever is often misdiagnosed as a primary psychiatric disorder and patients are mismanaged in psychiatric centers. Reports of typhoid fever with presenting depressive features are rare6.
The Family Health Centre, Okeilewo, is a Comprehensive Health Centre of Abeokuta-south local government area in south-western Nigeria. It receives referrals from three primary health centres and 12 rural health posts. Approximately 20 000 patients visit the hospital annually for consultations. A 12 year old female with typhoid fever presenting as delirium with depressive features was received and managed at this centre.
On 29 May 2009, a 12 year-old female developed a moderate grade continuous fever without chills or rigors with generalized body weakness, insomnia and vague abdominal pain. On the second day of her illness these features persisted and she became anorexic. She was given artesunate and an antipyretic purchased by her parents at a drug store but there was no improvement. On the third day, she began talking irrationally, expressing inappropriate guilt and feelings of worthlessness.
She had no prior psychiatric history, nor had there been any family stresses. Apart from occasional febrile illnesses (treated as malaria) her medical history was unremarkable. She lived with her parents and attended a day secondary school.
On days 4 and 5 of her illness she was taken to a church where prayers were made for her 'deliverance'. On the sixth day she was taken to a community psychiatric center where plans were commenced for her management as a patient with a primary psychiatric disorder. However a social worker in her treatment team had recently been involved in the treatment of two cases of probable typhoid psychosis in adults. The social worker suggested that the patient should be evaluated by a clinician initially, and she was referred to our hospital.
The patient was admitted to our hospital on 5 June 2009 for medical evaluation and management. On admission she was found to be an unkempt, poorly nourished adolescent female who was conscious, disoriented in time and who occasionally obeyed verbal commands. She was found to have a depressed mood, poor concentration, and episodes of irrational speech with expressions of inappropriate guilt and worthlessness accompanied by related psychomotor disturbance (intermittently kneeling and begging for forgiveness). She was febrile (37.9°C) and moderately dehydrated. There were no focal neurologic deficits, her pulse rate was 92/min and BP 100/80 mmHg. Chest and abdominal examinations were unremarkable.
After physical examination a differential diagnosis was made of malaria and typhoid fever with depressive features, or sepsis syndrome. Investigations revealed a PCV of 30% with normal total and differential leucocyte counts. Rapid diagnostic testing for Plasmodium falciparum showed mild parasitaemia. A Widal test revealed Salmonella typhi O and H titres of 1:360 and 1:160, respectively; and 1:160 for O titres of Salmonella paratyphi A and B. H titres of S. paratyphi A, B and C, and O titre of S. paratyphi C were all below 1:80.
While investigations were being conducted she was treated empirically with IM chlorpromazine 25 mg 8 hourly for 24 hours; IV 5% dextrose/saline 500 mL 8 hourly for 24 hours; IV metronidazole 500 mg 8 hourly; IV ciprofloxacin 200 mg 12 hourly; oral paracetamol 500 mg 8 hourly; and oral amodiaquine 400 mg daily for 3 days.
By the 3rd day of admission, her psychomotor disturbances had reduced but she remained febrile and her altered mental state persisted. On the 4th day, when investigation results were available, metronidazole and ciprofloxacin were withdrawn and she commenced IM chloramphenicol 500mg 6 hourly.
On the 5th day of antibiotic therapy she became afebrile and her mental state, appetite and sleep pattern improved. She was discharged on the 6th day of admission on oral chloramphenicol 500 mg 6 hourly for 10 days. At discharge she had normal sensorium with a Folstein's mini-mental score of 30/30. On follow up at 2 weeks and 1 month after discharge she was without medication and her clinical state was unremarkable.
Typhoid fever presenting with depressive elements is rare; however, our patient's signs and symptoms at presentation were sufficient to make the diagnosis of typhoid fever and delirium associated with depressed mood using DSM IV7. In a review of 136 typhoid patients, of which 26 developed psychiatric morbidity, only one had a depressive episode6. A case of typhoid fever presenting as bipolar disorder has also been reported8. The low incidence of reports of depression among the neuropsychiatric presentations of typhoid fever may be due to features of depression being missed by non-psychiatric clinicians during medical evaluation6. Clinicians should therefore exclude features of depression when evaluating patients with a neuropsychiatric presentation of typhoid.
Two Nigerian studies found that psychiatric morbidities in typhoid fever were common among children and young adults4,6; however, the reason/s for this were not clear. The current patient developed features of depression at the height of her fever. While she remained febrile her psychiatric morbidities endured. This suggests that fever caused by salmonella endotoxemia may be implicated in the development of depression in patients with typhoid fever. However there is controversy about the role of fever in the pathogenesis of neuropsychiatric complications associated with typhoid fever. In some series a relationship was found to exist, while others it was not1,3-4,6.
The pathogenesis of neuropsychiatric manifestations of typhoid fever is unclear. Several factors have been suggested, including neuro-endotoxin interactions, altered immune response, fluid and electrolyte imbalance, and nutritional disturbances1,3-6. The presence of pyrexia, dehydration and high titres of S. typhi antigens in our patient are consistent with reports suggesting such factors play a role4,9.
Recently, the use of ciprofloxacin in the treatment of typhoid fever has been abused. This patient showed no clinical response after 72 hours of IV ciprofloxacin and metronidazole. However, her dramatic recovery within 48 hours of commencing IM chloramphenicol suggests that, despite many reported cases of cloramphenicol-resistant S. typhi locally in the last decade10, chloramphenicol might still be useful in the treatment of typhoid fever as S. typhi and S. paratyphi become resistant to quinolones and other newer antibiotics. Chloramphenicol has also been found effective for treating typhoid fever in India and Indonesia - world regions where quinolone-resistant typhoid fever has emerged11,12.
Our patient's delirium may have been due to malaria. However, she completed artemisinin monotherapy (artesunate) prior to presentation, and on admission received a complete dose of amodiaquine with no change in her clinical or mental state. Studies have shown that in malaria endemic areas, as many as 80% of children in the community may be parasitaemic13.
Other relevant biochemical investigations were not available from our laboratory. Blood culture, for example, was not performed to confirm S. typhi infection, and controversies exist regarding the role of a single Widal test in the diagnosis of typhoid fever14,15. However, studies in Nigeria have suggested that a high index of suspicion combined with a single Widal test (using a cut off of at least 1:160 for O and H antigens of salmonella infection) has high sensitivity and specificity, and is sufficient for the initiation of typhoid fever treatment16-18. This is practiced in our centre. It was not possible to demonstrate a rising titre during the patient's illness and recovery due to treatment costs.
Self-medication and the common belief that psychiatric problems are caused by demons resulted in a delay in presentation for our patient. However, one wise decision by a social worker in a community psychiatric center meant that she eventually received appropriate care.
I thank the reviewers for their useful suggestions and the editorial team for their assistance during the preparation of this report. Also, I acknowledge the contribution of the laboratory scientists that participated in the management of this patient.
1. Osuntokun BO, Bademosi O, Ogremi K, Wright SG. Neuropsychiatric manifestation of typhoid in 959 patients. Archives of Neurology 1972; 27: 7-13.
2. Khosla SN. Changing pattern of typhoid (a reappraisal). Asian Medical Journal 1982; 25: 185-198.
3. Samia GA, Rashid S, Kamli MA, Shah PA, Allagaband GQ. Spectrum of neuropsychiatric complications in781 cases of typhoid fever. Tropical Medicine and International Health 1997; 2(4): 314 -318.
4. Stanley PC, Nwaneri DU, Stanley CN. The pattern of typhoid psychosis in childhood at the university of Port Harcourt teaching hospital Port Harcourt January 2000 to December 2003. Research Journal of Medical Sciences 2008; 2(1): 1-4.
5. Nair RK, Mehta SR, Kumaravelu S. Typhoid fever presenting as acute psychosis. Medical Journal Armed Forces India 2003; 59: 252-253.
6. Aghanawa HS, Morakinyo O. Correlates of psychiatric morbidity in typhoid fever in a Nigerian general hospital setting. General Hospital Psychiatry 2001; 23(3): 158-162.
7. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edn. Washington, DC: American Psychiatric Association, 1994.
8. Santangelo CG, Goldstein D, Green S. A case of bipolar disorder and typhoid fever. International Journal of Psychiatry in Medicine 2004; 34(3): 267-269.
9. Vidyasagar S, Nalloor S, Shashikiran U, Prabhu MM. Unusual neurological complications of typhoid fever. Calicut Medical Journal 2004; 2(2): e3. Available: http://www.calicutmedicaljournal.org/2004/2/2/e3 (Accessed 20 April 2010).
10. Akinyemi KO, Smith SI, Oyefolu AO, Fasure KA, Coker AO. Trends of multiple drug resistance in Salmonella Enterica Serovar Typhi in Lagos, Nigeria. East and Central African Journal of Surgery 2006; 12(1): 83-88.
11. Pohan HT. Clinical and laboratory manifestations of typhoid fever at Persahabatan Hospital, Jakarta. Acta Medica Indonesiana 2004; 36(2): 78-83.
12. Chowta MN, Chowta NK. Study of Clinical profile and antibiotic response in typhoid fever. Indian Journal of Medical Microbiology 2005; 23(2): 125-127.
13. Bodker R, Msangeni HA, Kisinza W, Lindsay SW. Relationship between the intensity of exposure to malaria parasites and infection in the Usambara Mountains, Tanzania. American Journal of Tropical Medicine and Hygiene 2006; 74: 716-723.
14. Tupasi ET, Lucas-Aquino R, Mendoza MT, Tuazon CU, Lolekha S. Clinical application of the Widal test. Philippines Journal of Microbiology and Infectious Disease 1991; 20(1): 3-26.
15. Olopoenia LA, King Al. Widal agglutination test - 100 years later: still plagued by controversy. Postgraduate Medical Journal 2000; 76: 80-84.
16. Mohammed JO, Chikwem F, Gashau J. Determination by Widal agglutination of the baseline titre for the diagnosis of typhoid fever in two Nigerian States. Scandinavian Journal of Immunology 1992; 36(Suppl.11): 153-156.
17. Ibekwe AC, Okonko I O, Onunkwo AU, Donbraye E, Babalola ET, Onoja BA. Baseline Salmonella agglutinin titres in apparently healthy freshmen in Awka, South Eastern Nigeria. Scientific Research and Essay 2008; 3(9): 425-430.
18. Taiwo SS, Fadiora SO, Oparinde DP, Olowe OA. Widal agglutination titres in the diagnosis of typhoid fever. West African Journal of Medicine 2007; 26(2): 97-101.