HUMAN AFRICAN TRYPANOSOMIASIS (T.b. GAMBIENSE): A STUDY OF 16 FATAL CASES OF SLEEPING SICKNESS WITH SOME OBSERVATIONS ON ACUTE REACTIVE ARSENICAL ENCEPHALOPATHY

Abstract

The principal clinical and pathological findings in 16 fatal cases of human African trypanosomiasis caused by T.b. Gambiense are described. The changes in the brain took the form of a non-specific lymphoplasmacytic meningo-encephalitis of varying intensity. Other features included morular cells, diffuse microglial hyperplasia, and large reactive astrocytes in the white matter. Carditis was identified in 10 cases. Acute reactive arsenical encephalopathy appeared to be the principal cause of death in 10 patients. Convulsions figured prominently in this type of encephalopathy in seven patients and were sufficiently severe to produce hypoxic brain damage. In three cases of acute reactive arsenical encephalopathy the structural changes in the brain were those of acute haemorrhagic leucoencephalopathy.

Detection of light subunit neurofilament and glial fibrillary acidic protein in cerebrospinal fluid of Trypanosoma brucei gambiense-infected patients.

“…Therefore, the results should be interpreted with caution. The increase of CSF GFAP found in some of the patients with second-stage HAT is consistent with the astrogliosis observed in HAT and experimental models of HAT, 2,4,6,[20][21][22]24,25 but in the present study, no conclusions regarding the use of CSF GFAP as a second-stage disease marker can be made. Increased CSF GFAP occurs only when astrogliosis is very pronounced, such as in Alzheimer's disease, vascular dementia, and multiple sclerosis.…”

“…30,32 In HAT patients, pathologic levels of GFAP in the CSF might indicate an advanced stage and/or a bad prognosis. Astrogliosis has been described as one of the pathologic findings in the brain of 16 fatal HAT cases, 4 of which an acute reactive arsenical encephalopathy appeared to be the principal cause of death in 10 cases. Treatment-related reactive encephalopathy occurs in up to 6% of the patients treated with melarsoprol and is fatal in most of these patients.…”

“…The meningoencephalitis observed in African trypanosomiasis is characterized by parasite invasion of the meninges and choroid plexus, infiltration of the leptomeninges and perivascular areas by IgM producing plasma cells, Mott cells, and T helper/inducer cells, diffuse microglial hyperplasia, astrogliosis in the white matter, and demyelination of neurons. [2][3][4][5][6] A correct stage determination is indispensable since it is directly related to the choice of an optimal treatment with minimal risk for the patient. This is currently carried out by examining the cerebrospinal fluid (CSF) for cell number, protein concentration, and presence of trypanosomes.…”

6-Arylpyrazine-2-carboxamides: A New Core for Trypanosoma brucei Inhibitors

“…Gastrointestinal (nausea, vomiting, diarrhoea) and skin reactions (pruritus) are common; severe complications like exfoliative dermatitis occur in < 1% of cases (53). Cardiac failure is common during treatment and can be a frequent cause of death (152), but it is still unclear whether this is due to an adverse drug reaction or the well-known cardiac involvement of HAT itself (153)(154)(155). Other adverse reactions that have been reported occasionally are peripheral motor (palsy) or sensorial (paresthesia) neuropathy, renal dysfunction (proteinuria and hypertension) and hepatotoxicity (elevated liver enzymes, bilirubinaemia) (142).…”

“…HAT is a focal disease. The previous estimate that 60 million people in the tropical belt of Africa are at risk for HAT is a "best guess" based on estimates of the total population of the tsetse-infested areas of the continent (135,152).…”