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Most patients with type 1 diabetes mellitus have circulating antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GAD65), and tyrosine phosphatases (IA-2 and IA2- ) at the time the diagnosis is made These antibodies facilitate screening for an autoimmune cause of diabetes, particularly screening siblings of affected children, as well as adults with atypical features of type 2 diabetes (Table 27 3) Antibody levels decline with increasing duration of disease Also, low levels of anti-insulin antibodies develop in almost all patients once they are treated with insulin Family members of diabetic probands are at increased lifetime risk for developing type 1 diabetes A child whose mother has type 1 diabetes has a 3% risk of developing the disease and a 6% risk if the child's father has it The risk in siblings is related to the number of HLA haplotypes that the sibling shares with the diabetic proband If one haplotype is shared, the risk is 6% and if two haplotypes are shared, the risk increases to 12 25% The highest risk is for identical twins, where the concordance rate is 25 50% Some patients with a milder expression of type 1 diabetes mellitus initially retain enough B cell function to avoid ketosis, but as their B cell mass diminishes later in life, dependence on insulin therapy develops Islet cell antibody surveys among northern Europeans indicate that up to 15% of type 2 diabetic patients may actually have this mild form of type 1 diabetes (latent autoimmune diabetes of adulthood; LADA) Evidence for environmental factors playing a role in the development of type 1 diabetes include the observation that the disease is more common in Scandinavian countries and becomes progressively less frequent in countries nearer and nearer to the equator Also, the risk for type 1 diabetes increases when individuals who normally have a low risk emigrate to the Northern Hemisphere For example, it was recently shown that Pakistani children born and raised in Bradford, England have a higher risk for developing type 1 diabetes compared with children who lived in Pakistan all their lives Which environmental factor is responsible for the increased risk is not known There have been a number of different hypotheses including infections with certain viruses (rubella, Coxsackie B4) and consumption of cow's milk Also, in developed countries, childhood infections have become less.

Infection by Clonorchis sinensis, the Chinese liver fluke, is endemic in areas of Japan, Korea, China, Taiwan, southeast Asia, and the far eastern part of Russia Millions of people are affected and, in some communities, prevalence can reach over 80% Opisthorchiasis is principally caused by Opisthorchis felineus (regions of the former Soviet Union) or Opisthorchis viverrini (Thailand, Laos, Vietnam) Clonorchiasis and opisthorchiasis are clinically indistinguishable Parasite eggs are shed into water in human or animal feces, where they infect snails, which release cercariae, which infect fish Human

Infection by Fasciola hepatica, the sheep liver fluke, results from ingestion of encysted metacercariae on watercress or

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> 95% Chest radiographs may show varied abnormalities of the lungs or pleura, including infiltrates, nodules, cavities, and fibrosis, and the findings can be confused with those of tuberculosis With CNS disease, skull radiographs can show clusters of calcified cysts, and CT or MRI can show clusters of ring-enhancing lesions Treatment is with praziquantel (25 mg/kg orally three times daily for 2 days), which provides efficacy of at least 90% Alternative therapies are bithionol and triclabendazole As with cysticercosis, praziquantel should generally be used with corticosteroids for cerebral paragonimiasis Chronic infection may lead to permanent lung dysfunction and pleural disease requiring drainage procedures

infection follows ingestion of raw, undercooked, or pickled freshwater fish containing metacercariae These parasites excyst in the duodenum and ascend into the biliary tract, where they mature and remain for many years, shedding eggs in the bile Most patients harbor few parasites and are asymptomatic An acute illness can occur 2 3 weeks after initial infection, with fever, abdominal pain, tender hepatomegaly, urticaria, and eosinophilia The acute syndrome is difficult to diagnose, since ova may not appear in the feces until 3 4 weeks after onset of symptoms In chronic heavy infections, findings include abdominal pain, anorexia, weight loss, and tender hepatomegaly More serious findings can include recurrent bacterial cholangitis and sepsis, cholecystitis, liver abscess, and pancreatitis An increased risk of cholangiocarcinoma has been documented Early diagnosis is presumptive, based on clinical findings and epidemiology Subsequent diagnosis is made by finding characteristic eggs in stool or duodenal or biliary contents Repeated concentration tests of stool may be necessary Imaging studies show characteristic biliary tract dilatations with filling defects due to flukes Serologic tests can be helpful but are limited by suboptimal specificity The drug of choice is praziquantel A dosage of 25 mg/kg orally three times daily for 2 days provides cure rates over 95% One day of treatment may be sufficient Re-treatment may be required, especially in some areas with known decreased praziquantel efficacy The second-line drug is albendazole (400 mg orally twice daily for 7 days), which appears to be somewhat less effective

The large intestinal fluke, Fasciolopsis buski, is a common parasite of pigs and humans in eastern and southern Asia Eggs shed in stools hatch in fresh water, followed by infection of snails, and release of cercariae that encyst on aquatic plants Humans are infected by eating uncooked plants, including water chestnuts, bamboo shoots, and watercress Adult flukes mature in about 3 months and live in the small intestine attached to the mucosa, leading to local inflammation and ulceration Other intestinal flukes that cause similar syndromes include Heterophyes (North Africa and Turkey) and Metagonimus (East Asia) species; these species are transmitted by undercooked freshwater fish Infections with intestinal flukes are often asymptomatic, although in this case eosinophilia may be marked In symptomatic cases, after an incubation period of 1 2 months, manifestations include epigastric pain and diarrhea Other gastrointestinal symptoms, ileus, edema, and ascites may be seen uncommonly Diagnosis is based on identification of characteristic eggs or adult flukes in the stool In contrast to other fluke infections, illness more than 6 months after travel in an endemic area is unlikely The drug of choice is praziquantel, 25 mg/kg as a single dose Alternative therapies are triclabendazole and niclosamide (for most species)

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