Updates By Carol A. Kemper
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
HIV and Heart Disease: How Can We Do Better?
Grinspoon S, et al. N Engl J Med. 2005;352:48-62.
A major focus of the recent Conference Retroviruses and Opportunistic Infections (CROI) in Boston in February 2005, was the issue of cardiovascular disease and risk factors in patients with HIV infection. As we successfully extend the lives of patients with HIV well into their 50s and 60s, cardiovascular events, and metabolic complications, such as dyslipidemias, insulin resistance, and altered fat distribution are threatening to shorten them.
Before the advent of highly active antiretroviral therapy (HAART), HIV+ patients developed decreases in total cholesterol, HDL, and LDL. With the advent of HAART, total cholesterol and LDL increased to pre-infection levels, although HDL levels remain low. Protease inhibitors, with the possible exception of atazanavir, increase hepatic synthesis of triglycerides and increase plasma triglyceride levels.
Prospective data from the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study indicate that among more than 23,000 participants, first myocardial infarction occurred in 0.5% (incidence, ~3.5 persons per 1000 years). Of these, 29% were fatal, representing 6% of all deaths in the study. Duration of antiretroviral therapy, hypercholesterolemia, older age, smoking history, diabetes, male sex, and prior history of heart disease were strong predictors of MI. No one class of antiretrovirals or any agent could be singled out as causative. Importantly, the DAD study found that in the absence of other risk factors, the risk of MI from prolonged antiretroviral therapy alone was low.
Two key interventions significantly dropped the estimated risk of MI: the use of statins for hyperlipidemia and smoking cessation. In men at average risk for CAD who are beginning HAART therapy, the estimated risk of MI at 10 years was 7%. The estimated risk of an MI occurring within 10 years dropped to 3% with the use of a statin (or switching to an alternate PI or NNRTI with an estimated drop in total cholesterol of 25%). The risk dropped to 1% if the patient stopped smoking. Both measures dropped the risk to < 1%.
In men at above average risk of CAD, with evidence of lipodystrophy, who are receiving HAART, the chances of an MI occurring within 10 years was 23%. This risk could be decreased to 14% with statins, or to 9% with smoking cessation, or to 5% with the use of both measures.
Data suggest that about 40% of HIV+ men smoke cigarettes, compared with 23% of the general US adult population. (This difference is even more striking when you consider that fewer than 5% of upper class women in the United States smoke). While optimizing HIV treatment, limiting the risk of lipodystrophy, and treating hypercholesterolemia are all important measures that should be addressed, the single best thing you can do for your HIV+ patients is to convince them to stop smoking! Isn’t it time we really focused on what’s burning our patients?
Schistosomiasis in African Travelers
Schwartz E, et al. J. Travel Med. 2005;12:13-18.
Schistosomiasis may be the most under-recognized infectious disease in developing countries in both travelers and immigrants, especially because nearly half of infections are asymptomatic. In recent years, an increased number of schistosoma cases have been reported in developed countries, either because of increased travel and/or increased identification of cases. A European surveillance group catalogued over 800 cases in 2003—mostly in persons from sub-Saharan Africa. About one-fourth of these were adventure travelers.
Adventure rafting and diving tours to schistosoma endemic areas, such as Malawi and Victoria Lakes, the Dogon Country, and the Omo River, which cuts across the southwestern corner of Ethiopia before emptying into Lake Rudolf in Kenya, are increasingly popular. Schwartz and colleagues describe a series of river rafting trips down the Omo River, and examined the risk factors for schistosomiasis. Two rafting trips in particular—a group from the United States in 1993 and an Israeli group in 1997—garnered the most intensive examination because both groups had high rates of infection, compared with other similar rafting groups.
In the US group, of 17/18 rafters available for assessment, 10 (59%) were seropositive for S. mansoni. Among the 10 infected, fever (60%), cough (40%) and abnormal liver tests (30%) were common findings. Eggs were demonstrated in stools in only 5/10 (50%) seropositive individuals, and egg counts were low. In the Israeli group, 18/20 (90%) rafters available for testing were seropositive for S. mansoni. Among the 18 infected, eosinophilia (83%), fever (44%), and abnormal liver function tests (17%) were common, but cough was less common (11%). Symptoms generally occurred within 3-6 weeks of exposure.
In contrast, Schwartz et al examined a total of 84 US rafters from 12 other similar expeditions in 1994-1995, and found that none were infected. Assessment of a small convenience sample from a group of 133 Israeli rafters from 13 similar expeditions in 1995-1998 found only 1 seropositive individual (10%). Most of these rafting trips were done on either the first or second upstream leg of the Omo River (~300 Km each), and lasted about 8-15 days. Schwartz et al determined that the 2 rafting tours with high rates of infection had required re-routing because of bad road conditions, and took rafters an additional ~200 km downstream. The Omo River in this area is wider, slower moving, and more populated. In addition, large numbers of infected snails have been found in one of the Omo tributaries in this area. The US rafting company has since stopped tours to the Omo, and the Israeli river rafting company has stopped using this route.
Since 43% of infected persons in this series were asymptomatic but are at risk for late sequelae of infection, Schwartz et al advocate serologic screening of all travelers exposed to fresh water in these endemic areas. Egg counts and peripheral eosinophilia are insensitive and inadequate markers for infection. Fortunately, because the parasite load is low in many of these infected individuals, significant end-organ dysfunction is uncommon.
Rabies in Transplant Recipients: Where Did it Go Wrong?
ProMED-mail post, February 17, 18, 20, 221, 2005; www.promedmail.org
Three of 6 patients receiving transplanted organs from a single donor in Germany have developed rabies and are critically ill. The donor was a young woman, admitted to hospital in December 2004, who died suddenly from a cardiac arrest with brain death. Rabies in the donor was not suspected, although has now been confirmed. A similar event occurred in the United States in 2004, when 4 people died of rabies after transplantation from an infected donor in Arkansas. The donor had died of a cerebral hemorrhage, and had no apparent signs of rabies.
The 3 German patients who are critically ill received a lung, combined kidney/pancreas, and kidney. Three other patients received a liver and corneas from the same donor, and appear to be doing well. Remarkably, once the information became known to the transplant team, the liver transplant recipient was re-admitted on February 15, immediately received active/passive rabies immunization, and was started on a combination of ribavirin and pegylated interferon. He continues to do well, and has developed unexpectedly high levels of rabies antibody, raising suspicions that he may have had pre-existing low level immunity for obscure reasons.
How and when the donor contracted rabies is unclear, but this case has prompted much discussion about screening of potential transplant donors. It was known that she had traveled to India in October 2004. Rabies is a real risk in India and Nepal (India reports ~20,000 deaths annually from rabies!). German newspapers have learned that she developed poorly characterized symptoms of headache and possible bizarre behavior, and had been evaluated at 3 different medical centers before her admission to hospital. Whether this information was available to transplant physicians is not clear, but certainly the circumstances of her death sound unusual. She did undergo all required medical screening procedures before her organs were harvested (which do not include rabies).
Interestingly, a 51-year-old Bavarian man died of rabies in German hospital in May 2004, after also returning from a trip to India. Although he had symptoms consistent with rabies encephalitis, all laboratory evaluations were negative. In the absence of brain tissue, laboratory studies are often negative.
It could be argued that in the German donor above, her recent travel history, coupled with her unusual behavior, may have prompted further investigation, but laboratory tests may still have been unrevealing. Some experts have suggested that individuals who have recently traveled to third world countries, such as India, within the prior 3-6 months, be excluded from donation—this would likely have little impact on the donor pool.
A major focus of the recent Conference Retrovirus and Opportunistic Infections (CROI) in Boston in February 2005, was the issue of cardiovascular disease and risk factors in patients with HIV infection.Subscribe Now for Access
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