One-third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Due to the risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding.Tolerance to the anticonvulsant effects of clonazepam occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently. Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide. In general, short-term therapy is more effective than long-term therapy with clonazepam for the treatment of epilepsy.
Microsporidiosis is an opportunistic intestinal infection that causes diarrhea and wasting in immunocompromised individuals (HIV, for example). It results from different species of microsporidia, a group of microbial (unicellular) fungi.In HIV infected individuals, microsporidiosis generally occurs when CD4+ T cell counts fall below 150. Microsporidia have emerged with significant mortality risk in immunocompromised individuals. These are small, single-celled, obligately intracellular parasites linked to water sources as well as wild, and domestic animals. They were once considered protozoans or protists, but are now known to be fungi, or a sister group to fungi. The most common causes of microsporidiosis is Enterocytozoon bieneusi and Encephalitozoon intestinalis. Cause
At least 15 microsporidian species have been recognized as human pathogens, spread across nine genera:

Anncaliia
A. algerae, A. connori, A. vesicularum
Encephalitozoon
E. cuniculi, E. hellem, E. intestinalis
Enterocytozoon
E. bieneusi
Microsporidium
M. ceylonensis, M. africanum
Nosema
N. ocularum
Pleistophora  sp. Trachipleistophora
T. hominis, T. anthropophthera
Vittaforma
V. corneae. Tubulinosema
T. acridophagusThe primary causes are Enterocytozoon bieneusi and Encephalitozoon intestinalis. Life cycle
(Coded to image at right). The infective form of microsporidia is the resistant spore and it can survive for an extended period of time in the environment. The spore extrudes its polar tubule and infects the host cell. The spore injects the infective sporoplasm into the eukaryotic host cell through the polar tubule. Inside the cell, the sporoplasm undergoes extensive multiplication either by merogony (binary fission) or schizogony (multiple fission). This development can occur either in direct contact with the host cell cytoplasm (E. bieneusi) or inside a vacuole called a parasitophorous vacuole (E. intestinalis).