Michigan Infectious Disease Society

From Dr. Keystone’s talk at U of M, March 24, 2001, I recorded the following:

1. What is the risk of malaria in persons who do not take chemoprophylaxis in visiting certain areas of the world for > 1 month — Mexico and Central America 1:10,000; S.E. Asia 1:1,000; Africa 1:50, and Oceania 1:5;
2. 3% of persons taking mefloquine discontinue the drug; 1:200-500 have neuropsychiatric problems; seizures and psychosis occur in 1:10,000-13,000 persons on the medication.
3. Mefloquine is the only drug used as chemoprophylaxis for the pregnant woman; there are some data to suggest pregnancy increases attraction of mosquitoes;
4. There is a self diagnostic test for malaria available outside of the U.S.; the sensitivity and specificity in trials were > 90%, however, clinical experience suggests travelers don’t use the test correctly;
5. MalaroneÒ is a relatively new anti-malarial with a cure rate of ³ 98% in non-immune persons with malaria; the dose is 4 tabs/day x 3 days in adults and 1-3 tabs/day x 3 days in children; the medication may induce vomiting so an antiemetic may be needed as well.

Clinical and laboratory guidelines have been recently published for use of HIV—1 drug resistance testing as part of treatment management; AIDS 2001; 15: 309-320.

From the 3rd Surgeon Symposium on Clinical Implications of HIV Drug Resistance — Frankfurt, Germany, February, 2001

From Clifford Lane, NIH: HIV infection is characterized by the development of immunodeficiency occurring simultaneously with an increase in immune activation. Use of IL-2 may expand T-cell pool and extend half-life of CD4 cells. The clinical benefit of this strategy remains to be demonstrated.

From C. Craig of Roche Discovery, England: The level of unbound protease inhibitor (PI) is associated with antiretroviral activity, and because most PIs are highly protein bound, the level of protein in serum may have a significant effect on the efficiency of PIs in vivo. Alpha-acid glycoprotein provides the greatest contribution to PI protein binding. Use of serum in drug testing to assay antiretroviral activity of PIs may underestimate the role of serum proteins in vivo.

Treatment options for persons who have failed all 3 currently available classes of antiretroviral agents are extremely limited. A trial of amprenavir and lopinavir/r as part of lopinavir/r Easy Access Program showed moderate viral suppression and immunologic recovery for patients with documented treatment failure with all 3 classes of available agents.

Data from Wayne State/Detroit Medical Center (R. MacArthur) were presented which examined use of ritonovir-boosted indinavir in highly experienced HIV-infected patients. Using retrospective chart review of 17 patients, at 24 weeks after initiating the combination therapy, 5 patients achieved full virologic response and 6 patients had a partial response. However, 4/17 patients had confirmed or probable episodes of nephrolithiasis, with 2 of 4 discontinuing the regimen.

In terms of defining resistance, the final analysis of the HAVANA trial was presented by B. Clotet of Spain. These data, using 326 patients with first, second or third drug failure, demonstrated that, at week 24, individuals who had genotypic testing and access to expert opinion had a significant difference in viral load below detection and HIV-1 RNA reduction compared with those who did not receive genotypic testing and/or expert opinion.

Discussing transmission of resistant virus, R. Comacho of Portugal demonstrated a prevalence of 16.7% (9/54) primary resistance mutations in newly HIV-infected patients. Similarly, O. Donoso of Spain showed resistant genotypes in 14/130 (10.8%) therapy-naïve HIV-infected persons in 18 outpatient clinics in Spain.

In March, Dr. John Bennet of NIAID, Bethesda sent a query to EIN re: reports of negative EIA tests for cryptococcal antigen from serum and CSF of known cryptococcosis patients. Latex agglutination tests on the same specimens gave positive results with titers up to 1:1024. Positive controls in the EIA test kits were checked and found to be functional. Has anyone else had a similar experience?

Apparently, meningococcal group B polysaccharide is chemically very similar/identical to some sialic acid polymers in mammalian heart valves, CNS tissues and kidney. This resemblance to host antigen may help explain why B polysaccharide is poorly immunogenic compared with serogroups A, C, Y, and W-135 polysaccharides.

[Ed. note: Group B disease continues to be problematic in the U.S.; @ 30% of meningococcal disease in college students is serogroup B. Group B vaccines based on the outer membrane vesicle of the organism, which contains minimal to no group B polysaccharide, are in research trials. Unfortunately, antibody titers wane quickly and are not as efficacious as once was thought. Protein conjugation of Group B polysaccharide (similar to that already used with Hib and S. pneumoniae) may be an issue because of concern about cross-reacting antibodies to polysialic acid and epitopes on vital human organs.]

Earlier this year there was a tremendous outbreak of foot-and-mouth disease (FMD) in England and Northern Ireland. This is a very serious, easily transmissible viral disease (related to enteroviruses in humans) in cloven-hoofed ruminants [cattle, pigs, sheep, goats, deer, etc.]. The disease causes loss of meat and milk production. Humans rarely contract FMD but can unknowingly transmit FMD by coming into contact (including clothing or footwear) with FMD virus contaminated material.

To contain the outbreak, diseased and suspect animals were slaughtered and burned (Science had a very graphic picture). Travel to rural areas was significantly restricted and roads closed. Zoos and rural tourist sites were also closed.

[Ed. note: Per two non-medical colleagues, I’m happy to report that some restrictions have been lifted and that some tourist sites recently reopened. Please check with the CDC for further updates on this tragic situation and its effect on the upcoming tourist season.]

According to Keith Sabin at CDC, billions of unsafe and unnecessary injections each year cause serious illness and millions of premature deaths. Using WHO data, Sabin claims 75% of the estimated 12 billion injections each year are unnecessary. Because of unsanitary conditions in parts of the world, these injections may be responsible for 8-16 million cases of hepatitis B virus infection, 2-5 million cases of hepatitis C virus infection, and 80,000-160,000 cases of HIV.

President Bush has proposed a fairly dramatic, 13.5% increase in NIH budget. This increase will help the Office of Research in Women’s Health, a new National Center for Minority Health and Health Disparities and AIDS research. A small amount will also be used to develop new smallpox and anthrax vaccines under an anti-bioterrorism initiative.

As evidenced by an outbreak earlier in 2001 in Seattle/King County, Washington, susceptible young adults may continue to sustain disease transmission caused by measles virus. In this recent outbreak, 42% of the reported cases were 29-39 years of age. The age cohort currently between 27 and 44 years of age may be particularly vulnerable because: 1) they were enrolled in public school before the implementation of effective school immunization laws requiring proof of immunity; 2) they may have been vaccinated before 12 months of age, thus circulating maternal antibody could have blunted the immune response to vaccine; or 3) waning immunity from receiving only one measles vaccine [Ed. Note: This latter reason is unlikely; the 1989-1991 national outbreak showed that waning measles immunity from a single vaccination is a very uncommon cause of susceptibility. It is far more likely that primary vaccine failure (~ 5% following a single dose of vaccine) occurred].

While only smallpox has been completely eradicated as a cause of human diseases, there are 10 other diseases on their way out. These diseases include those caused by polio, measles, and hepatitis B viruses, as well as maternal/neonatal tetanus. Preventive treatments are available but proper financing will be required. In order to eradicate polio by 2005, approximately $1 billion is needed to remove pockets of infection in 20-30 countries. Measles could be eliminated by 2010 at a (today’s) cost of $3 billion. To achieve elimination of hepatitis B virus infection by 2010-2015 will cost between $3 billion to $5 billion. Controlling maternal/neonatal tetanus disease by 2005 is possible with an additional sum of $130 million in aid.

Although the Lansing area received more rain in May than I remember over the past several years, Spring is finally here MIDS members! The relatively warm days and cool nights are nice for all outdoor activities.

For the first time in 3 years my daughter was not playing in a school or club volleyball tournament and I was able to go to the MIDS Business and Scientific meeting on March 24th in Ann Arbor. Our President, Don Batts, ran a very well organized Business meeting and members had an ample amount of time for discussion. The minutes from this meeting can be found elsewhere in this Newsletter. As the guest speaker, Dr. Jay Keystone, Unit Director, University of Toronto Tropical Medicine, presented “New Prophylaxis and Treatment of Malaria”. Dr. Keystone is an excellent speaker. He gave a very informative and “fun” presentation. In fact, Dr. Keystone was so good, he returned to Michigan in May as one of the featured speakers at our yearly pediatric infectious diseases meeting (see below). Following Dr. Keystone’s presentation, various scientific presentations, both orally and by poster, completed the Scientific Meeting. Thanks to Dr. Engleberg and others at the University of Michigan for hosting and organizing this year’s conference — a job well done.

Last month, Dr. Dale Bergamo (HFHS) and I organized and moderated the 4th Annual Michigan Pediatric Infectious Diseases meeting. This year’s speakers were Dr. Jonathan McCullers from St. Jude Children’s Hospital (Memphis, TN), Dr. Dwayne Newton from MDCH, Dr. Adrian Dana (formerly at Spectrum Health, Grand Rapids, now with Wyeth-Ayerst) and Dr. Keystone. Dr. Keystone gave one of those talks that I always wished that I could give: “Tropical Dermatology”. My personal thanks to all who came, both speakers and participants. A special thanks to Glory Havlin, Wyeth Lederle Vaccines, for sponsoring this worthwhile, education opportunity over the past 4 years.

Lastly, I regret I must inform you that as of August 2001, I will be moving to Augusta, Georgia. I have enjoyed my “second chance” as the MIDS Newsletter Editor and hope that my quarterly contributions of “From the Editor” and “You’ve Got Mail” made you think, smile, or merely made you more informed. On August 15th, I will be assuming the position of Professor, Department of Pediatrics and Chief, Pediatric Infectious Diseases Division, at the Children’s Hospital, Medical College of Georgia. While I will be doing a fair amount of non-ID related medical administration, I am planning, with my new colleagues, to continue to be involved in clinical research, especially research involving childhood vaccines. I will sincerely miss those of you I have gotten to know through MIDS and hope that we can renew acquaintances at the yearly IDSA meeting. I’ve come to realize that MIDS is a terrific organization, one of the best state societies in the IDSA, in large part because of you, the dedicated members. Thanks for many years of memories and allowing me to be your MIDS Newsletter Editor.

Regards,

Dennis L. Murray