African trypanosomiasis, or "sleeping sickness," is caused by Trypanosoma brucei subspecies that are transmitted by tsetse flies. It causes serious human illness that is fatal unless treated. An estimated 300,000—500,000 Africans carry the infection, and over 60 million people are at risk. It is extremely rare in the U.S. The parasite is entirely extracellular, and early infection is characterized by the presence of replicating parasites in the bloodstream or lymph without central nervous system (CNS) involvement (stage 1). Manifestations of early stage disease include fever, lymphadenopathy, splenomegaly, and occasional myocarditis that result from systemic dissemination of the parasites. Stage 2 is characterized by CNS involvement. There are two types of African trypanosomiasis, the East African and West African, caused by T. brucei rhodesiense and T. brucei gambiense, respectively. T. brucei rhodesiense produces a progressive, rapidly fatal disease marked by early CNS involvement and frequent terminal cardiac failure; T. brucei gambi-ense causes illness that is characterized by later CNS involvement and a prolonged course that progresses to the classical symptoms of sleeping sickness over months to years. Neurological symptoms include confusion, poor coordination, sensory deficits, an array of psychiatric signs, and eventual progression to coma and death.

Standard therapy for early-stage disease is pentamidine for T. brucei gambiense and suramin for T. brucei rhodesiense. These agents are not effective against late-stage disease, and standard treatment of the CNS phase is melarsoprol. All three compounds must be given parenterally over long periods. Eflornithine offers the only alternative for the treatment of late-stage disease; it has marked efficacy against early and late stages of human T. brucei gambiense infection. It has significantly fewer side effects than melarsoprol but is expensive, difficult to administer, and ineffective as monotherapy for infections of T. brucei rhodesiense.

American trypanosomiasis, or Chagas' disease, is caused by Trypanosoma cruzi. It affects ~20 million people from Mexico to South America, where the chronic form of the disease is a major cause of cardiomyopathy, megaesophagus, megacolon, and death. Bloodsucking triatomid bugs most commonly transmit this infection to young children; transplacental transmission also may occur in endemic areas.

Reactivation also may occur in patients who are immunosuppressed after organ transplantation or because of other conditions (e.g., AIDS, leukemia, and other neoplasias). Occurrences of T. cruzi infection in transplant patients or through blood transfusions have been reported in the U.S. Acute infection is evidenced by a raised tender skin nodule (chagoma) at the site of inoculation; other signs may range from fever, adenitis, skin rash, and hepatosplenomegaly to, rarely, acute myocarditis and death. Invading metacyclic trypomastigotes penetrate host cells, especially macrophages, where they proliferate as amastigotes and then differentiate into trypomastigotes that enter the bloodstream. After recovery from the acute infection, individuals usually remain asymptomatic for years despite sporadic parasitemia. An increasing fraction of adults develops overt cardiac and GI chronic disease as they age. Progressive destruction of myocardial cells and neurons of the myenteric plexus results from the tropism of T. cruzi for muscle cells. Two nitro-heterocyclic drugs, nifurtimox and benznidazole, are used to treat this infection. Both agents suppress parasitemia and can cure the acute phase of Chagas' disease in 60—80% of cases. Current recommendations are that patients with either acute- or recent chronic-phase disease should be treated. For patients with late chronic-phase disease (>10 years), parasitological cure is less likely, and there is no consensus on management. Both drugs are toxic and must be taken for long periods. Isolates vary with respect to their susceptibility to nifurtimox and benznidazole. In the absence of new drugs, alternative measures such as improved vector control and housing accommodations have reduced the transmission of Chagas' disease substantially.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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