Updates

By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.

Quiz: Paresthesias in a soldier stationed in Hawaii

A military serviceman stationed in Hawaii, presented to base with intense pruritus, restlessness, dyspnea, and progressive paresthesias, with burning skin discomfort. His vital signs were stable, he was afebrile, and he denied any nausea, vomiting, or headache. His neurologic examination was intact, although testing with a tuning fork elicited an intense sensation of burning. He was observed overnight for possible respiratory compromise, and given gabapentin with gradual resolution of his symptoms during the next 4 weeks.

What was his diagnosis?

a. Organophosphate insecticide poisoning
b. Guillain-Barre syndrome
c. Saxitoxin toxicity (paralytic shellfish poisoning)
d. Ciguatera poisoning
e. Scombroid
f. Antipersonnel neurobiologic agents

Please see answer at the end of the article.

Flu vaccine Effective in the Elderly

Source: KL Nichols, et al. Effectiveness of Influenza vaccine in the community-dwelling elderly. N Engl J Med. 2007;357:1373-1381.

Despite concerns about the immunogenicity and durability of influenza vaccination in the elderly, as well as year-to-year variability in circulating influenza strains and vaccine efficacy, most case control and cohorted data continue to support the benefits of vaccination in the elderly. This large-scale retrospective analysis of pooled data from a large HMO in the United States evaluated the overall effectiveness of influenza vaccination in persons 65 years or older belonging to an HMO. Pool data from 18 cohorts variably dating from 1990 to 2000 were examined for the risk of hospitalization for influenza or pneumonia and death in vaccinated vs unvaccinated persons. Elderly persons residing in nursing homes or long-term care facilities were not included in this assessment.

There were a total of 713,872 person-seasons spanning the 10 consecutive flu seasons. Subgroup analyses were conducted as defined by age, gender, co-existing medical conditions, prior hospitalization, and number of recent outpatient care visits. Various confounders were also examined. Baseline characteristics of the 2 groups were similar with regard to age, although (not surprisingly) the vaccinated group had a greater prevalence of one or more pre-existing medical conditions, and number of hospitalization and outpatient visits.

During the 10 influenza seasons, there were 4599 hospitalizations for pneumonia and influenza, and 8796 deaths occurred. Raw data for hospitalization were, on average, 0.6% and 0.7% for vaccinated vs unvaccinated persons. Death rates were, on average, 1% and 1.6% per season (!). Increasing age and pre-existing medical conditions were the strongest predictor of hospitalization and death.

On average, after adjustment for important co-variates, influenza vaccination was associated with a 27% reduction in the risk of hospitalization (adjusted OR .73) and a 48% reduction in the risk of death (adjusted OR .52). This figures varied from year to year, in large part determined by whether the vaccine was a good match for circulating strains of influenza virus that season. During the 2 years where there was a poorer match, vaccine effectiveness dropped to 37% lower death rates. In seasons with a better match, vaccine effectiveness improved to 52% lower death rates. Thus, even in years with a poorer match, influenza vaccination was associated with a significant reduction in the risk of hospitalization and death, though the benefit was not quite as great as during flu seasons with a better match. Although the risks may not be immediately tangible, the data confirm that vaccination of the elderly should remain a high priority in this country.

PEP for Sex

Source: Landovitz RJ, et al. Preventing HIV infection after a potential sexual exposure. Infect Med. 2007;24:239-246.

Post-sexual exposure prophylaxis with antiretroviral treatment (ART), what is euphemistically called "PEP for sex," has now become the standard of care for persons with possible high-risk sexual exposure to HIV. However, there is still uncertainty on the part of many practitioners about "who, what, and how long."

PEP for sex can and should be administered by those on the front lines of patient care — ER and urgent care physicians and primary care practitioners — in concert with the advice of an infectious disease or HIV specialist as needed, and there is plenty of information online, including the 2005 CDC Guidelines to assist them. The following is a brief synopsis of those recommendations.

Why? In order to provide appropriate treatment recommendations and counseling, practitioners should understand the risks of HIV transmission associated with various sexual activities, which are generally quite low. The presence of certain factors, such a traumatic mucosal skin breaks, genital ulcer disease, cervical ectopy and inflammation (or certain subtypes of HIV not common in the United States) can increase that risk. In health care workers, the use of AZT monotherapy is believed to reduce the risk of transmission of HIV associated with high-risk percutaneous needles sticks by about 81%. This, and animal data, support the use of PEP for high-risk sexual exposure, although patients should be counseled that 100% efficacy is unlikely, and breakthrough infections have been documented, even when appropriate ART has been administered in a timely fashion.

Timing and duration of therapy? Following transmission, there is a window period of about 3 to 5 days before HIV infection is established. Therefore, PEP must be administered < 72 hours after exposure (the sooner, the better) and continued for 28 days. Breakthrough infections have been documented when treatment was initiated later than 72 hours, or the duration of treatment was 3 or 10 days (in animal models).

Who? PEP should be administered to any person with insertive or receptive anal, vaginal, or oral contact, regardless of whether ejaculation occurred (eg, the condom slipped or broke). Mucous membrane or non-intact skin contact with any potentially infected body fluids (eg, ejaculate, genital secretions) is also an indication for PEP. The case must be known HIV-negative, unknown HIV status, or have a preliminarily positive rapid HIV test pending confirmation; a positive rapid test is not a basis for refusing PEP. The contact should be known HIV positive, or someone considered at reasonably high risk of being positive based on sexual behavior, drug use, or local epidemiology. Administering PEP for random sexual encounters where the risk of HIV transmission is believed to be reasonably low should be avoided. However, it is reasonable to err on the conservative side of this equation, especially when dealing with a patient who is distraught or adamant about receiving PEP. In other words, PEP should never be refused to someone who truly believes it is necessary, even if you do not. There is adequate time for reassurance and further consideration of the risks in the days following.

Which agents? Two nucleoside analogs are considered standard PEP prophylaxis (eg, combivir, or various combinations of stavudine, lamivudine or emtricitabine, and tenofovir). A third drug should be added if there is a > 15% prevalence of nucleoside resistance in your area, or the contact person is believed to be receiving ART and may have HIV resistance. In such circumstances, individualization of therapy may be necessary, and an HIV or ID specialist can be consulted. Third agents include protease inhibitors (kaletra, atazanavir, fosamprenavir, crixivan, nelfinavir), a non-nucleoside reverse transcriptase inhibitor (Sustiva, but not nelfinavir), or tenofovir.

What tests to order? At baseline, routine HIV antibody testing should be performed, along with hepatitis B and C, RPR, and other STD tests. Follow-up HIV testing should be done no sooner than 4 weeks, and is probably best done at 2 to 3 month post-exposure. Plasma HIV testing using PCR is not recommended, as the frequency of false-positives is too high. Follow-up testing for hepatitis B and C and RPR is recommended. Routine labs (cell counts, liver panel, serum creatinine) may be done at baseline, at 2 weeks, and at 4 to 6 weeks, but some argue that it is reasonable to defer such testing unless the person experiences symptoms or toxicity.

Answer to Quiz

The key was in the history: The soldier had eaten healthy portions of fish for both lunch and dinner. Although ciguatera toxin is present in Hawaii, especially in Amberjack or Kahala, in an ironic twist, the man had purchased frozen fish from a local grocer. The fish was packaged in Fiji, and identified as a Cephalopholis miniata, or coral cod, and contained high amounts of ciguatera toxin, especially the head.

Ciguatera toxin exposure is a risk for military personnel stationed anywhere where ciguatera toxin is present in the environment, including Hawaii, the South Pacific, the Gulf Coast, the Caribbean, and the parts of Asia. In these areas, military personnel should be cautioned about the potential risks of eating certain fish (especially reef fishes, such as amberjack in Hawaii and the South Pacific, and barracuda in Florida and the Gulf), limiting portion size to less than 50 grams, and avoiding eating the head, viscera and roe.

There is no antitoxin or known treatment for the symptoms, which can last weeks. Studies suggest that some of the symptoms may be improved with gabapentin, but mannitol is no longer recommended. For reasons which are not clear, nuts, nut oils, sesame oil, and alcohol may make the symptoms worse, and should be avoided for 3 months after exposure.

Military health care providers should be able to distinguish ciguatera toxicity from other illnesses, toxins, and biologic and chemical agents. Ciguatera toxicity is commonly associated with acute-onset nausea, vomiting, abdominal pain, and progressive paresthesias, and can occasionally result in bradycardia and hypotension, but not muscular paralysis. In contrast, saxitoxin (paralytic shell fish poisoning) or tetrodotoxin, which is produced by dinoflagellates, and becomes concentrated in shellfish, is one of the more potent toxins. Similar to ciguatera toxicity, patients present with abdominal pain, nausea and vomiting, and paresthesias, or burning sensation of lips, face, tongue, and fingertips, progressing to the extremities, but then develop muscle weakness, progressing to respiratory failure. Botulinum toxin would present with similar symptoms of nausea, vomiting, with descending muscular weakness, beginning with the smaller muscles of the eye, throat (diplopia, dysphagia, dysarthria), with bradycardia and hypotension in more severe cases. On the other hand, Clostridium perfringens toxin, a common cause of food poisoning, results in acute upper gastrointestinal symptoms and abdominal crampy discomfort but quickly resolves within 1 to 2 days.