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New and Emerging Infections

Foodborne Infections

In the United States, there are 6-80 million cases and 9000 deaths per year due to foodborne infections. In addition to acute diarrheal illness, these infections can cause serious disease and sequelae. Listeria has been associated with miscarriage, meningitis and sepsis. Toxoplasmosis is definitively associated with congenital disease and severe birth defects. There are 20,000 cases of E. coli O 157:H7 each year in the United States, with 250 deaths. In 12% of cases, it causes hemolytic-uremic syndrome, and is the most common cause of acute renal failure in children. Salmonellosis, which has doubled in the past two decades secondary to centralized food production and large-scale distribution, is associated with chronic reactive arthritis. Over four-fifths of salmonella outbreaks are from known sources. Campylobacter, the leading cause of foodborne bacterial infection and the cause of 4 million cases each year in the United States, has a significant association with Guillian-Barre syndrome.

The increase in foodborne illness is due to many factors. Over the past 25 years, there has been a 50% increase in the consumption of fresh produce. More people eat meals outside the home where 80% of outbreaks occur. There has been a proliferation of fast food restaurants and salad bars, a source of many cases and outbreaks. The population as a whole is changing with many more immunocompromised and elderly people. These individuals are more likely to experience severe manifestations of these infections. There has been a change in the food industry and in its technology. There is greater geographic distribution of food products from centralized centers. The meat from one contaminated animal can be disseminated throughout the country causing

E coli O157:H7

Each hamburger can contain meat and, potentially bacteria, from hundreds of animals. The US outbreak that catapulted this organism to national prominence occurred at a fast-food chain serving hamburgers that were not thoroughly cooked. Much is now known about this infection.

E. coli O157:H7 produces a Shiga-like cytotoxin. It is named for the 157th somatic (O) antigen identified, and the 7th flagellar (H) antigen. There have been outbreaks throughout the world. It was first recognized as an enteric pathogen in 1982. Healthy cattle harbor the organism and are the major reservoir. In addition to undercooked ground beef, outbreaks have been caused by ingestion of well water, apple cider, mayonnaise, raw milk, fresh fruits and vegetables, lettuce and alfalfa sprouts and by swimming in ponds or other unchlorinated water. The organism can survive fermentation and drying. A low infectious dose is required for disease, and it can be shed from stool for weeks after symptoms resolve. Person to person transmission is common.

Shiga toxin (STX) genes are not the sole determinant of pathogenicity, eaeA is also important. EaeA is part of the Locus of Enterocyte Effacement (LEE) which makes the adhesion molecule intimin that allows enterocyte attachment. Ecoli O 157 then disrupts the brush border and causes superficial focal necrosis, hemorrhage and edema of the lamina propria, probably secondary to STX.

The incubation period is three days (1-8 days) and patients are usually better in 7 days. Over 70% have bloody diarrhea, 30-60% have vomiting and less than a third have fever. It causes a spectrum of disease from mild, non-bloody diarrhea to hemorrhagic colitis. Most significantly, in 8-12% of patients, infection is associated with hemolytic-uremic syndrome (HUS). In fact, it is the leading cause of HUS in the United States and Canada, causing over 90% of cases. The incidence is higher in children and adults over the age of 50 years.

HUS develops within one week of illness. One-half of the patients require dialysis, and one-quarter have neurological complications such as stroke, seizures, or coma. 3-5% progress to end-stage renal disease.

HUS is thought secondary to the action of the STX on vascular endothelial cells with platelet and fibrin deposition. There is also injury to red blood cells with hemolysis and occlusion of the renal vasculature, contributing to acute renal failure.

It is difficult to predict who will develop HUS. Vomiting is not usually a prominent symptom with E coli O157, but when present within the first three days of illness, it is associated with the development of HUS. Antibiotics given within the first three days of illness to children less than 13 years of age was also associated with HUS. Antibiotics may increase Shiga-toxin production, particularly if the levels are sub-inhibitory.

E coli O 157 is also associated with thrombocytopenia and microangiopathic hemolytic anemia. Other complications include colonic stricture, chronic pancreatitis and irreversible cognitive impairment. There is a 3-6% mortality, primarily in the elderly.

It is increasingly recognized that non-O157 E coli can cause a similar syndrome. There is a lower incidence of bloody diarrhea and less HUS associated with this strain. However, if it carries the eaeA gene, the incidence of protracted or bloody diarrhea and HUS markedly increases. E. coli O157:H7 may have a more complete repertoire of virulence traits, and is therefore more often associated with bloody diarrhea, HUS and death.

Diagnosis begins with stool culture. Fecal leukocytes are often positive, but a negative result does not rule out the diagnosis. If stool is obtained early in disease, the diagnosis can be made by Sorbitol-MacConkey agar. E coli O157 are colorless colonies on this media because they don't ferment sorbitol, unlike most other E. coli. These colonies can then be assayed for O157 antigen. Any history of bloody diarrhea or visible blood in the stool sample can detect over 90% of cases by screening only 22% of stool samples. Non-O 157 do ferment sorbitol, and are very difficult to diagnose.

Prevention is by completely cooking ground beef, avoiding non-chlorinated water and being aware of the risks associated with fresh produce. There is no specific treatment needed for the acute illness, and management of sequelae, eg, HUS, is supportive.

Salmonella Serotype Typhimurium DT 104 (DT104)

Salmonella infections have increased significantly over the past two decades. Particularly worrisome is the presence of DT104. This strain has been recognized in Europe for the past ten years. It is resistant to at least five antibiotics - ampicillin, chloramphenicol, streptomycin, sulfonamides and tetracycline. 14% in the United Kingdom are also ciprofloxacin resistant and 24% also trimethoprim resistant. The incidence of DT104 is increasing in the United States. Salmonella causes 800,000 to 4 million cases per year in the US, and at least 500 deaths. About 25% are due to S. typhimurium. Of the strains evaluated by the Centers for Disease Control, one third had five drug resistance, most were DT104. In California and Connecticut, over half of the strains are

Fluoroquinolone-Resistant Campylobacter

Campylobacter is the most common bacterial enteric infection. Transmission from infected poultry is the major source. In Europe, when fluoroquinolone use was begun in poultry, resistant campylobacter strains began to appear in people. By controlling the use of this antibiotic, the incidence of resistance began to decline again.

In the United States, fluoroquinolones were approved for use in poultry in 1995. A recent study looked at the campylobacter strains identified between 1992 and 1998 in Minnesota. There were about 950 cases of campylobacter infection identified per year, or 20.7 cases per 100,000 population. Almost 5,000 isolates were evaluated. In 1996-1998, 91% of all isolates were submitted. 95% were C. jejuni. The resistance to nalidixic acid rose from 1.3% in 1992 to 10.2% in 1998. In 1996, 142 of 1,576 isolates were fluoroquinolone resistant. Strains resistant to ciprofloxacin which is commonly prescribed for traveler's diarrhea, were usually resistant to all other fluoroquinolones tested. The findings of the study also revealed that infection was associated with foreign

Tick-Borne Infections

Ticks have long been associated with the transmission of infectious diseases. The tickborne infections that have become most prominent in the past decade are lyme disease, ehrlichiosis and babesiosis. All of these infections can be transmitted by the same deer ticks, and the white-footed mouse is the reservoir for all three organisms.

Lyme Disease

There has been a 25-fold increase in recognized cases of lyme disease since 1982. Almost 12,500 cases are reported to the CDC each year.

Lyme disease is caused by Borrelia burgdorferi. The tick that most commonly transmits lyme disease in the United States is Ixodes scapularis (dammini). Most lyme disease is transmitted by ticks in the nymphal stage. Numbers of nymphs peak in late spring and early summer. In endemic areas, 15-30% of tick nymphs are infected with B. burgdorferi. Activities that increase risk are property maintenance, outdoor occupations or outdoor recreation. There is no person to person transmission, but congenital infection can Occur.

It takes 24-36 hours before the nymph transmits the spirochete to the human host. After prolonged feeding, the spirochetes are inoculated and disseminate to skin, lymphatics and bloodstream.

After an incubation period of 7-14 days, asymptomatic infection takes place or a rash appears. The classic rash is erythema chronicum migrans (ECM) and is present in up to 90% of patients. Early disseminated lyme disease has many manifestations. There may be a single ECM lesion or multiple lesions. Non-specific symptoms occur such as fatigue, myalgias, arthralgias, headache,

Prevention of lyme disease includes use of insect repellents such as DEET to clothing and skin, and permethrin applied to clothing. Since it takes 24-36 hours to transmit the infection, careful daily checks for ticks can prevent disease.

Recently, two vaccines have been developed. Both use recombinant Borrelia burgdorferi lipidated outer-surface protein A (rOSPA). The mechanism of action is unique. The tick attaches to the host, and has OspA in its gut. As it continues to feed, OspC increases, and OspA begins to decline. The infected host is primarily exposed to OspC and has antibodies to OspC, but low levels of antibody to OspA. However, the vaccine causes the host to have OspA antibodies, which enter the tick and destroy the spirochete prior to infection. These vaccines may not be as useful in Europe where there are different strains, and different OspA proteins. However, in the United States to date, there is a single dominant OspA.

The efficacy has been shown to be 49% after a two shot regimen, and 76% if a third injection is given at 12 months. Data indicate a third shot at 2 or 6 months may prove equally efficacious. Antibody titers seem to decline quickly, even with three injections, with a two-thirds reduction in geometric mean titer within 8 months. The need for booster shots is not yet known. The third dose should be administered by March so vaccination is complete prior to the peak tick season.

Because the incidence of disease does not justify indiscriminate vaccination, the vaccine was approved with the suggestion that administration be limited to those at high risk. The cost to the pharmacist of a single dose is $61.25. Persons 15-70 years of age with activities that result in frequent or prolonged exposure to tick habitats should be vaccinated. It is not yet licensed for children nor in pregnancy. There is no data on its safety in compromised hosts. Patients with uncomplicated prior lyme at continued risk should be vaccinated, but patients with treatment-resistant lyme arthritis should not receive the vaccine.

Most lyme disease is in the northeastern US, the mid-atlantic states and the upper midwest. A single course of early antibiotic therapy cures over 90% of people infected with lyme. In addition, the vaccine makes the ELISA positive, so western blot testing must be done on any vaccinated individual in which the diagnosis of lyme disease is being considered. Also, the vaccine does not

Ehrlichiosis

Human Monocytic Ehrlichiosis (HME)

This is a gram-negative bacteria that is found intracellularly within phagosomes in monocytic cells. The organism was described at Fort Chaffee and is named Ehrlichia chaffeensis, It is transmitted by the lone star tick (Amblyomma americanum) or the American dog tick (Dermacentor variabilis). White tailed deer are reservoirs, and can be infected. It is endemic in the same areas as Rocky Mountain Spotted Fever, and is more prevalent in some locales. There is a history of a tick bite in over half the patients within the preceding three weeks. After the tick bite,

Babesiosis

This is caused by a protozoa that parasitizes red blood cells. The most common strain in the US is B. microti, a rodent babesia. In Europe, B. divergens and B. bovis, from cattle, are more common. The illness is more severe in Europe, and is usually in asplenic individuals (86%) with over 50% mortality rate from fulminant hemolytic disease. In the United States, babesia is transmitted by Ixodes scapularis, from rodents to man. 60% of the mice on Nantucket are infected. The nymph is the primary vector and feeds for hours to days. Sporozoites are injected from the tick salivary gland to the hosts bloodstream. It enters erythrocytes, forms trophozoites and merozoites and then destroys the erythrocyte and infects new red blood cells. The schizogony is asynchronous, unlike that seen in malaria. There is therefore no classic patterns of fever.

Most patients are asymptomatic. After a 1-3 week incubation, there might be malaise, fatigue, anorexia, chills, fever, headache, myalgias, arthalgias, nausea, vomiting, abdominal pain, depression, dark urine, photophobia, conjunctival injection, sore throat, cough. Patients over 50 years, asplenic patients, patients coinfected with B. burgdorferi or E. equi are more likely to be

Viral Pandemics - Influenza A, I-ISN1

In May of 1997, a three-year-old child in Hong Kong died from acute respiratory distress syndrome. The child may have had exposure to sick chickens. Influenza A H5N1 was identified, a virus previously only known in birds. This virus seemed to have crossed the avian-human species barrier without prior adaptation in another mammalian species. In the prior pandemics of 1957 and 1968, pigs acted as a type of"mixing vessel" for avian and human influenza viruses. The fear, without this mixing, was that this strain would be so different from prior strains that the population at large would have no immunity and would potentially cause a pandemic equal to or worse than the Swine Flu Pandemic of 1918. After the initial case, 17 more cases were