Our two cases presented with atypical fever accompanied by neurological symptoms. The first case was misdiagnosed as viral encephalopathy and the second case was misdiagnosed as tuberculous meningitis. Both patients were initially treated inadequately until serology and blood culture results were positive for S. typhi.
The incidence of typhoid encephalopathy varies. In endemic typhoid countries, encephalopathy may happen in more than 15% of cases.(6) If left untreated, typhoid may cause serious complications and high mortality rates.(7) Severe typhoid complications are more likely to occur in males, aged more than 5-year-old up to young adults(8), which is in accordance with our 1st case. Signs and symptoms of typhoid infection are similar to other causes of fever, such as Dengue virus and Rickettsia, therefore it may baffle physicians. (3) After five days, the patient may present with confusion, apathetic effect, seizures, delirium, stupor, or coma, and is associated with a high risk of mortality.(3) The classical fever description in typhoid, the step ladder type of fever, is rarely found (9); therefore, in a highly endemic area, three or more days of non-focal fever along with the ill appearance and abdominal complaints should prompt consideration of enteric fever.(3) There were no typical signs from routine blood examination as leukocyte count is relatively normal and thrombocytopenia may be found in typhoid and viral etiologies.(3, 9, 10) CSF analysis in typhoid patient is often normal or similar to viral meningitis (11) as in both our cases. This may lead to misdiagnosis.
Isolation of S. typhi is the gold standard in diagnosing typhoid.(3) Culture from CSF specimen has a low sensitivity, only positive in 2% (12, 13). Blood culture, which was not a standard practice, in our hospital, was performed as both patients were enrolled in 2 different studies and resulting in the detection of S. typhi. Meanwhile, CSF culture was negative. This finding emphasizes the need to also do blood culture, when possible, in addition to CSF culture, in patients with suspected CNS infection accompanied by fever, especially in typhoid endemic countries.
In our 2nd case, Ceftriaxone was given after a positive result in the rapid IgM Salmonella test. IgM Salmonella is commonly used in clinical settings, including the IDL Tubex and Typhidot assays (3). However, diagnostic accuracy for those tests was moderate. The average sensitivity for Tubex and Typhidot was 78% and 84%, while specificity for those tests was 87% and 79%, respectively (14). Despite all the limitations, rapid IgM is currently the fastest diagnostic test for typhoid that are affordable and can be done in almost all healthcare facilities. Therefore, it is important to do the test in fever patients in high endemic typhoid countries.
Lack of appropriate antibiotics is one of the causes of the higher case fatality rate in developing countries. Appropriate antibiotics and supportive care reduce the mortality of enteric fever from 10–15% to less than 1%(3). Therefore, having proper knowledge and alertness to the possibility of typhoid fever with appropriate diagnosis steps is important.
Misdiagnosis of typhoid encephalopathy is rarely reported. Therefore, these case reports may increase physicians’ awareness of typhoid infection in patients presenting with neurological symptoms. These reports also gave a description to physicians about patients’ progress during hospitalization until several months after they were discharge. However, these case reports cannot represent the burden of typhoid encephalopathy in the population, which needs further research. Long term outcome of typhoid encephalopathy must be investigated further especially in neurodevelopment area.
To conclude, in a typhoid endemic area, typhoid encephalopathy should always be considered as one of the causes of CNS infection. Blood culture in patients presented with neurological complaints accompanied by a fever of unknown cause and abdominal symptoms may help diagnose typhoid. Research on the etiological proportion of CNS infection is severely needed.