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.

Schistosomiasis as IRES in HIV

Source: Psevdos G Jr. Schistosoma mansoni colitis in an AIDS patient. The AIDS Reader. December 16, 2009.

An increasing number of HIV-positive immigrants and refugees, many from Africa, are cared for in the United States. The standard battery of HIV-related blood studies does not include screening studies for strongyloides and schistosomiasis. HIV co-infection with these two parasites is common in certain countries. At least 20% of HIV+ patients with bloody diarrhea in Zimbabwe had schistosomiasis. In a 10-year post-mortem survey in Puerto Rico, histologic evidence of S. mansoni was found in 10% of AIDS patients who died.

This author describes a patient with newly diagnosed AIDS, who had just started antiretroviral therapy four weeks earlier, who developed non-bloody diarrhea, fever, and peripheral eosinophilia (13%). Stool studies for bacteria, C. difficile, and ova and parasites were negative, and he failed to respond to an empiric course of metronidazole. Colonoscopy showed diffuse hyperemia, and biopsy showed an intense granulomatous response to schistosoma ova. Within days of starting praziquantel, his diarrhea resolved. A second similar case, described elsewhere, also presented with diarrhea within weeks of initiation of HAART therapy. Colonoscopy revealed patchy colitis with a granulomatous response to schistosoma ova. Schistosoma infection may result in acute symptomatic enteritis in patients with HIV as a manifestation of immune reactivation.

Tick-borne B. henselae

Source: Angelakis E, et al. Scalp eschar and neck lymphadenopathy caused by Bartonella henselae after tick bite. Clin Infect Dis. 2010;50:549-551.

Tick-borne lymphadenopathy (also referred to as TIBOLA) is usually a mild illness characterized by the presence of an eschar, usually on the scalp, with surrounding erythema and painful cervical lymphadenopathy. In Spain, the disease has also been referred to as Debonel, or Dermacen-tor-borne necrosis-erythema-lymphadenopathy. The disease tends to occur in the cooler months of the year (in late fall or early spring) on the Eurasian continent, where the dermacentor ticks are prevalent in wooded areas and fields. The median time of incubation is 4 to 7 days. Most bites occur on the scalp, and are associated with an eschar, or tache noire, and painful, regional lymphadenopathy in the head and neck area. Fever occurs in some cases, but skin rash is uncommon. Persistent local alopecia at the site of the tick bite may occur, and some infections appear to respond to doxycycline.

Molecular-based studies suggest that about one-fourth of these infections are due to Rickettsia slovaca, a rickettsial species first isolated in Czechoslovakia from its tick vector, Dermacentor marginatus. Further research has identified a second rickettsial species, R. raoultii, in a small number of cases. Another case of TIBOLA has been described with co-infection due to R. slovaca and Coxiella burnetii.

For a number of these cases, researchers have not been able to identify a causative agent. On a hunt to investigate other possible bacteriologic causes of TIBOLA, the authors performed extensive serological, microbiological, and molecular studies on blood and tissue specimens from 28 patients (ages 3 to 68 years) with the syndrome. Specimens were routinely tested for Rickettsial and Bartonella spp, C. burnetii, B. burgdorferi, and Francisella spp. About half (53%) of the cases were infected with R. slovaca and another 10.7% with R. raoultii; three (10.7%) cases had serological evidence of B. henselae. Tissue specimens from the site of the eschar were positive for R. henselae DNA in two of these patients, both of whom had animal contact. Tissue biopsy in the third patient, performed about 1.5 months following the infection was negative using real-time PCR, but the Dermacentor tick provided by the patient tested positive for B. henselae DNA.

Although this is not conclusive evidence that Dermacentor is a competent vector for B. henselae, it seems likely that tick-transmitted B. henselae may result in TIBOLA.

Update on ACIP Adult Immunization Guidelines

Sources: ACIP. Recommended Adult Immunization Schedule: United States, 2010. Ann Intern Med. 2010;152:36-39; Hopkins RH, Jr, and Vyas KS. Adult Immunization Guidelines: Challenges and Opportunities. Ann Intern Med. 2010;152:59-60.

The revised acip adult vaccination Schedule, published January 5, 2010, includes the following changes (documented in full at www.cdc.gov/vaccines/recs/ACIP/default.htm):

HPV

• A second HPV vaccine is now approved for use in young adults within the United States. In contrast to the earlier HPV quadrivalent vaccine, which provided protection against four strains of HPV, including two strains associated with genital warts, the newer bivalent vaccine includes only two HPV strains associated with 70% of cases of genital dysplasia and cervical cancer.

• Vaccination of young men at risk for HPV is now also recommended.

MMR

• Two doses of MMR vaccine, administered four weeks apart, are now additionally recommended for certain groups, including health care workers, students in post-secondary educational institutions, international travelers, and adults with exposure to measles or mumps.

• All other adults born after 1957 do not require a booster dose of MMR if they have documentation of an initial primary dose.

• Heath care facilities should consider pre-emptively providing MMR for non-immune employees born before 1957.

Hepatitis A Vaccine:

• HAV is now recommended for all parents and caregivers of international adoptees.

Meningococcal Vaccine:

• A one-time booster dose of meningococcal conjugate vaccine is recommended after five years for anyone with ongoing risk factors for meningococcus, except those in campus housing.

Haemophilus Influenzae
Type B (Hib) Vaccine;

• A footnote in the guidelines suggests that Hib is not "contraindicated" in adults with leukemia, sickle cell disease, HIV, or splenectomy, for those clinicians wondering what to do for patients at increased risk for encapsulated organisms.

The accompanying editorial discusses the likelihood of an increased focus on adult immunization as a quality measure. Newer electronic medical records will have embedded prompts for routine adult vaccination. Providers should anticipate that audits of electronic medical records may more readily provide feedback to clinicians regarding rates of adult vaccination, and remuneration may eventually be tied to this in some areas. I recommend posting the updated ACIP document (and the ACIP document from 2009) somewhere near your desk for quick reference, as some of the recommendations for adult vaccination are not always as straightforward as the authorities make them out to be, and questions are likely to arise.

Strategies for Pandemic Flu

Source: Perlroth D, et al. Health outcomes and costs of community mitigation strategies for an influenza pandemic in the United States. Clin Infect Dis. 2010;50:165-174.

Numerous strategies for managing outbreaks of Influenza within the community were variously employed during the 2009 Influenza A/H1N1 pandemic, with little coordination on a broader scale and no real good sense of which strategy — or strategies — was most important or most necessary. These included antiviral therapy and prophylaxis, recommendations for social distancing (whereby you voluntarily limit your non-household, non-work social contact by approximately 50%) for either children or adults, network modeling for controlling behaviors, school closures, and household quarantine. But which strategy is most cost-effective?

A community-based simulation model was developed based on influenza disease severity and mortality, transmissibility (Ro, meaning the average number of secondary cases caused by one case patient in a susceptible population), and cost of the interventions and medical care. The baseline model estimated a 1% influenza mortality rate, an Ro of 2.1, a 60% compliance rate with the interventions, and no circulating resistance to antiviral therapy.

The "do nothing" approach was compared to various interventions, used singly or in combination. Using the above estimates, the single, most cost-effective intervention was the use of antiviral therapy and prophylaxis. Social distancing for both adults and children was the least costly intervention, and did result in modest improvement in health outcomes. In contrast, school closure alone was the most expensive intervention.

Based on the above model, the most cost-effective approach proved to be a multilayered one, using a combination of antiviral therapy, school closure, and social distancing, resulting in a reduction in cases from 35% to 10% of the population, with a price tag of approximately $1,250 per community member. This combined approach resulted in a quality-adjusted life expectancy of 20.2 years per community member, for a cost of $2,700 per case averted, and an overall gain of $31,300 per quality-adjusted life year (QALY).

However, as soon as antiretroviral drugs are no longer available — or effective — this same multilayer strategy reduces the percentage of cases in the community to only 22%, and is no longer as cost-effective. And if the influenza mortality rate falls below 1%, then the success of the model depends on the infectivity rate and compliance with interventions. For low-severity epidemics with a case-fatality rate < 0.5 and Ro < 1.6, the most cost-effective strategy shifts away from more costly interventions, such as school closure. Interestingly, while the case-fatality rate for the Influenza A/H1N1 epidemic is not clear, the higher estimates from Mexico suggest a CFR of 0.4%, with an Ro of 1.4-1.6. Based on these figures, the most cost-effective policy choice would be the combined use of antiviral therapy and voluntary social distancing; in this scenario, school closure would up the cost by almost $300,000 per QALY.