Highlights from the ASTMH Meeting in Puerto Rico: Cancelled, but Not Forgotten
Special Coverage
The clinical sessions that had been a planned part of the American Society of Tropical Medicine and Hygiene meetings had been replete with abstracts of potential interest to our readers. When those meetings were cancelled due to hurricane damage in Puerto Rico, we attempted to retrieve and highlight clinical information that would have been presented at those annual meetings. This issue continues our reviews and highlighting of several additional clinical abstracts by the associate editors. For those who wish to obtain copies of the abstract book, it is officially designated as the Program and Abstracts of the 47th Annual Meeting of the American Society of Tropical Medicine and Hygiene (a supplement to Am J Trop Med Hyg 1998;59:no. 3 for September). Additional copies of the abstract book can be obtained from the Society (telephone: 847-480-9592). (Dr. Frank J. Bia is Professor of Medicine and Laboratory Medicine; Co-Director, Tropical Medicine and International Traveler’s Clinic, Yale University School of Medicine.)
Loiasis
Administration of diethylcarbamazine (DEC) is the current pharmacological standard of care for treatment of Loa loa infections. It is curative for approximately 60% of non-endemic patients with loiasis, yet some individuals continue to have signs and symptoms of infection despite multiple courses of DEC. In this abstract, Klion AD and Nutman TB report successful treatment of loiasis with albendazole. Three patients with refractory loiasis, defined as persistent symptoms of monthly Calabar swellings (2 patients) or malaise, myalgias, and arthralgias (1 patient) were given albendazole 200 mg by mouth, twice a day, for 21 days. Following therapy, symptoms resolved in all three patients, and, in two of them with Calabar swellings, symptoms have not recurred in seven years.
Loa loa is a filarial parasite commonly found in West and Central Africa. It is commonly known as the "eye worm" since adult worms are occasionally seen moving across the eyes of patients. It does not result in disfiguring lymphatic filariasis, yet it may cause serious complications when the organism invades the central nervous system or other vital organs. An epidemiological correlation has been observed between loiasis and the occurrence of endomyocardial fibrosis, suggesting that the hypereosinophilia induced by loiasis may lead to cardiac damage. Nephropathy and encephalopathy are far less common. Nodules in the conjunctiva, swelling of the eyelids, and proptosis have each been reported from Uganda as ocular complications of loiasis. Adult worms may be obvious when they pass under the conjunctiva of the eye or under the skin. They usually appear, but then disappear without a trace. Hypereosinophilia, especially in expatriates from nonendemic regions, is common. Clinical manifestations of loiasis include Calabar swellings that are most often observed on the wrists and ankles but can appear anywhere on the body. They are usually painless, nonpitting swellings, 5-20 cm in diameter, and last hours to days. One swelling occurs at a time, and it may recur at irregular intervals for years after the patient has left an endemic area. Other common symptoms include fatigue, generalized malaise, pruritus, and arthralgias. The death of an adult worm may cause a localized abscess, or to their calcification, making them radiographically detectable.
Albendazole has been used more broadly since its introduction—for more than just FDA-approved indications of neurocysticercosis and hydatid disease. It has had a good track record in terms of safety, and adverse events were described generally as mild, resolving without treatment. Abnormal liver function tests, abdominal pain, nausea, vomiting, headache, dizziness, meningeal signs, reversible alopecia, and fever have all been reported, but at a low incidence rate. Fewer than 1% of patients may develop leukopenia. Albendazole has been shown to be teratogenic in pregnant rats and rabbits and should be avoided in pregnant women at this time.
Although this report describes a small number of cases, each had a remarkable response with prolonged follow-up. Albendazole shows promise as an alternative agent for the treatment of loiasis. It may be an important macrofilaricidal drug addition for treatment of this disease, as well as for the treatment of strongyloidiasis. (Abstract 77.)
Strongyloidiasis
A retrospective analysis of patients attending the Tropical Disease Unit at the University of Toronto between 1990 and 1996 assessed those who received strongyloides serological evaluation by enzyme-linked immunosorbent assay (EIA). Fifty-six of 94 subjects demonstrated strongyloides on stool examinations or culture. Strongyloides serology was positive in 95% of those with documented infections. In 46 treated cases, the mean time for 50% reduction of antibody titer was six months. Within that time period, 34% of those with documented infections and 45% of those without documented infections detected developed a negative serological test. Eosinophilia was present in 70% of those with documented infection and in 81% of those who only showed a positive strongyloides seropositivity. Return to normal occurred in 66% of those with documented strongyloidiasis and in 45% of those without documented parasites. Strongyloides serology appeared to be a sensitive test in this group for predicting successful treatment, with more specificity than following eosinophilia alone.
Unpublished data from our own hospital in Rhode Island support the use of serum antibodies against Strongyloides stercoralis to follow patients treated for strongyloidiasis. One family practice physician, who has become popular with the Cambodian community in Rhode Island, has followed approximately 40 asymptomatic patients who had eosinophilia and positive strongyloides antibody titers and treated them with thiabendazole. Nearly all tended toward lower antibody titers, although not all were done by the same lab using the same methods. Reference labs had changed hands and altered methodologies, but his findings support the data reported in this abstract from another "real-life" clinical care setting. (Abstract 78.) (Dr. Maria D. Mileno is Director, Travel Medicine, The Miriam Hospital; Assistant Professor, Brown University, Providence, RI.)
Leptospirosis
Following a 1996 hurricane, the incidence of leptospirosis rose in Puerto Rico and Nicaragua (TMA Update 1998;8:2). Now, following Hurricane Mitch, leptospirosis is being increasingly identified in Central America. In addition to prompting cancellation of the 1998 ASTMH meeting, a hurricane can also increase flooding and stimulate increased contact between humans and spirochete-contaminated fresh water.
Had the 1998 ASTMH meeting taken place, DA Person from the Tripler Army Medical Center in Hawaii would have presented a report of nine children from Kosrae State, Federated States of Micronesia, who were diagnosed with severe leptospirosis. Infection is usually acquired through contact of mucus membranes or broken skin with contaminated fresh water, soil, vegetation, or infected animals. Each of these nine children had a history of exposure to a potential source of leptospirosis, and the majority were boys. Pancreatitis and acute renal failure, with anuria lasting 3-6 days, were common; pulmonary findings and a large pleural effusion were noted in one child. In the more recently treated patients, a "pulse" dose of corticosteroids was associated with reversal of renal failure and avoidance of dialysis. (There have been other anecdotal reports of the usefulness of steroids in leptospirosis, but controlled studies are lacking.) Leptospirosis is a common zoonosis. The diagnosis should be considered in individuals with febrile illnesses after potential spirochete exposure. Severe disease with liver and kidney involvement is still treatable. Antibiotic and, perhaps, corticosteroid therapy should be initiated for potentially affected individuals. For a review of the leptospirosis symposium presented at the 1997 ASTMH meetings, see TMA Update 1998;8:1-3. (Abstract 404.)
Praziquantel Chemotherapy
For years, praziquantel has been a mainstay of therapy for schistosomiasis. In 1995, reduced schistosomiasis cure rates were noted in Senegal, and decreased effectiveness of praziquantel was confirmed in the laboratory (Am J Trop Med Hyg 1995;53:61-62). Then, in 1996, a report from the Nile delta region of Egypt noted tolerance of some schistosome strains to repeated treatments with praziquantel (Am J Trop Med Hyg 1996;55:214-218).
Morshedy and colleagues from Alexandria University were slated to discuss an area of reduced praziquantel susceptibility in the Nile delta that is hyperendemic for schistosomiasis. In the studied village, 58% of people were infected. Eight weeks following treatment with praziquantel (40 mg/kg), only 53% of previously infected individuals showed parasitologic cure; in children, only about one-third were cured with treatment. Morshedy et al question whether this village is a site of a tolerant or resistant schistosome strain.
Further studies of praziquantel susceptibility in different areas will help confirm if, indeed, this agent is losing effectiveness. In the meantime, further anti-schistosomal drug development efforts must continue. Practitioners of travel medicine might consider follow-up parasitological testing after praziquantel therapy to confirm cure, especially in travelers who have been to Senegal or Egypt. (Abstract 81.)
Malaria
The combination of atovaquone and proguanil (Malarone) has been demonstrated to be effective in the prophylaxis and treatment of malaria. (See TMA Update 1998;8:35-36.) Is it safe in subjects who are glucose-6-phosphate dehydrogenase (G6PD) deficient?
Researchers evaluated the use of atovaquone-proguanil in 31 G6PD deficient individuals with uncomplicated falciparum malaria who were enrolled in clinical trials at several sites, and they compared the safety and efficacy of treatment between these patients and "normal" subjects. Similar adverse effects occurred in the two groups, and no G6PD deficient subject was withdrawn due to side effects. Measures of hemolysis were not different when compared in the two groups. Each G6PD deficient patient achieved clinical and parasitologic cure with a three-day course of treatment.
Atovaquone-proguanil appears to be safe in G6PD deficient subjects. It also provides effective cure of falciparum malaria. As resistance to antimalarials increases around the world, this combination therapy holds great potential for increasing usefulness. (Abstract 75.) (Dr. Philip R. Fischer is Associate Professor of Pediatrics, Department of Pediatric & Adolescent Medicine, Mayo Clinic, Rochester, MN.)
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