Biological data and clinical symptoms as predictors of astrogliosis and neurodegeneration in patients with second-stage Trypanosoma brucei gambiense sleeping sickness.

Abstract

Abstract. Concentrations of glial fibrillary acidic protein (GFAp) and light subunit neurofilament protein (NFL) in cerebrospinal fluid (CSF) were measured in patients with second-stage Trypanosoma brucei gambiense sleeping sickness. Correlations between GFAp and NFL in CSF as markers for astrogliosis and neurodegeneration, and clinical and biological data were investigated. Abnormal levels of GFAp and NFL were significantly associated with increasing CSF cell number and protein concentration, and with the absence of lymph nodes or the absence of trypanosomes in lymph node aspirate. A significant association was found between abnormal NFL and presence of trypanosomes in CSF, abnormal limb movements, difficulties in gait and coordination, and low Karnofsky index. By multivariate analysis, it was shown that increasing CSF cell number, increasing CSF protein concentration, and the absence of lymph nodes or the absence of trypanosomes in the lymph node aspirate were the best predictors for astrogliosis and neurodegeneration among the variables tested. These results demonstrate the importance of CSF cell count and protein determination in assessment of the severity of central nervous system involvement and reinforces the importance of laboratory diagnosis to assess the stage of the disease. The clinical symptoms studied were less useful in predicting astrogliosis or neurodegeneration.

Options for Field Diagnosis of Human African Trypanosomiasis

“…Protein concentrations can also be raised in first-stage illness due to the diffusion in the CSF of IgG, which can be present in very high concentrations in the serum. Recent evidence suggests that the protein concentration threshold set by WHO (370 mg/liter) is too low and should be raised to 750 mg/liter to reflect blood-brain barrier impairment, astrocyte activation, and neurodegeneration (61,63). Despite its apparent simplicity, accurate determination of the total protein concentration in CSF is rather difficult.…”

“…Antibodies against brain-specific components such as neurofilaments and galactocerebrosides (GalC) have been detected and may be promising markers of second-stage illness (6,61,64). These autoantibodies, which might result from the CNS damage and immune activation triggered by trypanosome invasion, are associated with markers of neuroinflammation such as the CSF cell count and protein and immunoglobulin concentrations (11,61). Unfortunately, anti-GalC antibodies detectable in the serum are not correlated with neuroinflammation (11).…”

“…Exceptions to this rule occur, since fulminant illness has been described with T. b. gambiense infections and chronic disease is caused by T. b. rhodesiense in the southern end of its distribution (15,18,21). The clinical features can be indicative of HAT but are neither sufficiently sensitive (T. b. gambiense) nor specific (both species) to be used to detect all infected individuals, confirm the diagnosis, or stage the disease (12,14,26,29,46,61). Diseases such as malaria, enteric fever, tuberculous meningitis and HIV infection can mimic or even coexist with HAT.…”

Novel primer sequences for polymerase chain reaction-based detection of Trypanosoma brucei gambiense.

“…Studies on improved stage determination, therapy, drug resistance, and new drugs are being undertaken but are hampered by the low sensitivity of the parasitologic diagnostic methods. [14][15][16][17] In principle, DNA detection techniques such as the polymerase chain reaction (PCR) might partially overcome at least some of these diagnostic problems due to their alleged increased sensitivity and specificity. Indeed, PCR tests for detection of T. brucei DNA have been developed and used in several studies on sleeping sickness.…”

Fine-Needle Aspiration, an Efficient Sampling Technique for Bacteriological Diagnosis of Nonulcerative Buruli Ulcer

“…As a minimal invasive technique, fine-needle aspiration (FNA), commonly used for the cytologic diagnosis of tumors (10,11), lymphadenopathies caused by trypanosomiasis (17) and tuberculosis (8,15,27), leprous osteitis (20), or leprotic neuritis (16), would seem to offer an advantageous alternative.…”