Tropical and Geographic Medicine

Special Feature

By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

The following is a summary of selected abstracts of papers presented at the 54th Annual Meeting of the American Society of Tropical Medicine and Hygiene which took place from December 11-December 15, 2005 in Washington, DC.

Refugees

Thirty-three of the more than 3000 "lost boys of Sudan" (mean age, 25 years) in the United States were evaluated. All but 6 reported chronic abdominal pain. Ten (48%) of 21 had Schistosoma mansoni and one had S. haematobium infection, while 5 (20%) of 25 were HBsAg carriers and 3 (12%) of 25 had chronic hepatitis due to HBV. Three were found to have Entamoeba histolytica infection. Cases of filariasis and strongyloidiasis were identified, as were several cases of Helicobacter pylori infection. Most were lactose intolerant.

Since 1999, the CDC has recommended that all refugees from Southeast Asia and Africa receive a single oral dose of 600 mg albendazole prior to embarkation for the United States. Strongyloides was highly prevalent in Southeast Asians while Schistosoma was frequently found in Africans. Since the introduction of this policy of empiric presumptive therapy, the prevalence of individuals in whom there was detection of at least one stool helminth decreased from 21.5% to 8.4%. There were significant reductions in the frequency with infestation due to Trichuris, Ascaris, hookworm, or Strongyloides. Thus, empiric single-dose albendazole is effective in reducing the prevalence of intestinal parasitic infection in refugees, but does not eliminate the problem.

Nematode Infections

Onchocerciasis

Several studies demonstrated the benefit of annual mass drug administration, with ivermectin for control of onchocerciasis.

Lymphatic Filariasis

Antibiotic therapy directed at Wolbachia, the Gram-negative bacillary endosymbiont critical to reproduction of Wucheria bancrofti, is associated with reduced microfilaremia. The plasma concentration of vascular endothelial growth factor (VEGF), which is important in the growth and differentiation of vascular and lymphatic endothelial cells and which is also associated with increased vessel permeability, are increased in patients with lymphatic filariasis. In a placebo-controlled, randomized trial in Ghana, a 6-week course of doxycycline following single initial doses of ivermectin and albendazole (the control group received an ivermectin placebo plus albendazole) was associated with significant reductions in microfilaremia and Wolbachia bacterial loads per microfilaria. Also reduced were mean supratesticular lymphatic vessel dilatation and the frequency of detection of the filarial dance sign, an indicator of macrofilaricidal activity. Mean plasma VEGF-C concentration was reduced, as was that of its soluble receptor, sVEGFR-3. Thus, doxycycline therapy aimed at eliminating Wolbachia reverses some of the pathophysiological factors operative in lymphatic filariasis.

In a randomized trial, single-dose treatment with diethylcarbamazine alone appeared to be as effective as its combination with albendazole in the treatment of bancroftian filariasis in Papua New Guinea.

In several villages in Papua New Guinea, 2 annual administrations of albendazole and diethyl carbamazine were associated with a decrease in the prevalence of microfilaremia from 20.5% to 3.5% and a significant decrease in the prevalence of mosquito infection. Annual mass drug administration was also associated with significant decrease in the incidence of acute adenolymphangitis in Papua New Guinea.

Visceral Larva Migrans

A 16-year-old girl ate an earthworm on a dare. One month later she developed cough, multiple pulmonary nodules due to eosinophilic organizing pneumonitis, and an eosinophil count of 32,000/mm3. Testing of serum found an antibody titer of > 1:4096 to Toxocara. The earthworm apparently served as a carrier of larvae of Toxocara from soil to patient. This case has been published (Cianferoni A, et al. Pediatrics. 2006;117:e336-e339).

Trematode Infections

Schistosomiasis

All 120 patients with a diagnosis of schistosomiasis in Israel from 1994-2003 had traveled to sub-Saharan Africa. Of the total, 65% swam in Lake Malawi and 23% had rafted on the Omo River in Ethiopia. Approximately one-third had Schistosoma haematobium infection, one-third were infected with S. mansoni, and the species was not determined in the remainder. Two-thirds of the 72 patients with detailed information had symptoms of acute schistosomiasis, with 52% having fever, 36% cough and shortness of breath, and 19% having urticaria. Thus, most cases present during early stage infection when ova may not be detectable in stool and when antiparasitic treatment with praziquantel has reduced efficacy.

Cestode Infections

Cysticercosis

In a study of 7 communities in northern Peru, identification of human cysticercosis hotspots within 50 meters of the residence of Taenia solium tapeworm carriers was made.

Investigators at the NIH have used methotrexate as a replacement of or supplement to corticosteroids as adjunctive anti-inflammatory therapy in neurocysticercosis patients with subarachnoid cysts, cysticercal meningitis, multiple ventricular cysts, inflammatory parenchymal cysticercosis, and refractory calcific cysticercosis associated with perilesional edema. All patients were reported to have dramatic improvement without serious side effects.

Protozoan Infections

Leishmaniasis

Of 57 patients with mucocutaneous leishmaniasis due to L. braziliensis in Bolivia who completed 6 months of follow-up after treatment with miltefosine, 54 (85%) had improved while the remainder were unchanged.

In a double-blind, placebo-controlled trial, 23 patients in Brazil with mucosal leishmaniasis were given stilbamidine for 30 days with randomization to also receive either pentoxifylline 400 mg tid or placebo for 30 days. All pentoxifylline recipients, but only 42% (P = 0.037) of placebo recipients, were cured. The mean time to lesion healing was significantly shorter in the pentoxifylline arm (84 days vs 146 days). No relapses were observed in either arm after one year.

Malaria

Three hundred ninety eight-children in Papua New Guinea with severe malaria by the WHO definition (asexual parasitemia plus recent seizures or coma or respiratory distress or hemoglobin < 5 g/dL) were evaluated. Of those with mixed plasmodial infection, 15.7% had severe malaria, as did 11% with P. falciparum infection, 14.5% with P. vivax, and 6.4% with P. malariae. Seizures occurred in 22% of P. falciparum and 26% of P. vivax infections, while 2% and 3%, respectively, experienced coma. Respiratory distress occurred more frequently in those with P. vivax (58%) than in P. falciparum infection (40%). This report flies in the face of the common perception that P. vivax infection is almost invariably mild-to-moderate in severity and seldom life-threatening.

Of 102 evaluable nonimmune travelers with P. falciparum infection treated with artemether/lumefantrine, 95% had parasitological cure at 28 days. The mean time to parasitological clearance was 42 hours and that to fever resolution was 39 hours. Treatment was well tolerated.

Almost 500 patients in Mali with uncomplicated P. falciparum infection were randomized to treatment with either artesunate/mefloquine or artemether/lumefantrine. Although fever resolved more rapidly with the former regimen, there was no difference, after correction for reinfection (which occurred less frequently in the artesunate/mefloquine arm), in the 28 day cure rates (96% vs 97%). Vomiting occurred more frequently in those given artesunate/mefloquine (5.1%) than in recipients of artemether/lumefantrine (1.7%; P = 0.042).

Concern has been raised regarding the potential for the use of trimethoprim/sulfamethoxazole (TMP/SMX) as prophylaxis in AIDS patients in Africa to lead to resistance of P. falciparum to antimalarial agents targeting folic acid synthesis. In a prospective trial in an area of Kenya with a high preexisting level of malarial antifolate resistance, both HIV infected and non-HIV infected individuals were randomized to receive either TMP/SMX or a multivitamin daily for a mean of 5.4 months. While the number of multiple resistance mutations increased in both treatment arms, they did so with similar frequency. It was concluded that, at least in an area with a high frequency of preexisting antifolate resistance in P. falciparum, widespread use of TMP/SMX "is unlikely to contribute substantially to further increase in antifolate resistance."

One hundred adults in Thailand with uncomplicated P. falciparum infection were randomized to receive one of 4 regimens, 2 of which utilized azithromycin and artesunate and 2 azithromycin and quinine. The artesunate combinations arms had a significantly faster time to parasitological cure (33 hours vs 72 hours).

The frequent identification of P. vivax resistant to chloroquine and/or tolerant to primaquine has been increasing in Southeast Asia and the Southwest Pacific. Twenty-eight Vietnamese adults (mean weight, 49 kg) were treated with artesunate 200 mg bid for 2 days followed by primaquine 22.5 mg bid for 7 days. Blood stage parasites were eliminated within 24 hours in all patients, and no asexual parasites were detected during the 28 day follow-up period.

The failure rate of chloroquine treatment of P. vivax infection in Papua, Indonesia, is currently reported to exceed 70%. An open trial found that treatment with either artekin or amodiaquine had high degrees of efficacy.

HIV infection did not affect the response to therapy of uncomplicated malaria in Uganda.

Bacterial Infections

Salmonella Paratyphi

Of 64 individuals in the United States with Salmonella paratyphi A infections, almost all of those interviewed reported recent international travel, most to Southeast Asia. Twelve (75%) of 16 isolates tested were resistant to nalidixic acid, with most of the latter associated with travel to Southeast Asia. Treatment of infections due to nalidixic acid-resistant Salmonella with fluoroquinolones, such as ciprofloxacin, is known to have impaired efficacy, even though many of the isolates remain susceptible by current in vitro breakpoints.

Viral Infections

Nipah

Of 22 individuals in Bangladesh who had survived Nipah virus infection in 2003-2005, 17 (77%) had encephalitis and the remainder only a febrile syndrome. All but one reported disabling fatigue after recovery from the acute illness, with a mean duration of 2 months. One-third of those with prior encephalitis had persisting neurological dysfunction, but none had overt seizures.

Dengue

A prospective evaluation of almost 3000 factory workers in Bandung, Indonesia, over 4 years identified 1431 febrile illnesses, of which 176 were due to dengue and 4 of the latter had 2 separate episodes of dengue. One individual with preexisting neutralizing antibody to DEN-1 developed DEN-3 infection followed by infection by an unknown serotype. Two subjects had preexisting antibody to DEN-2; one developed sequential infections with DEN-3 and DEN-1, while the other had subsequent DEN-4 and DEN-3 infections. One individual with preexisting antibody to DEN-2, 3, and 4 had subsequent infections due to DEN-4 (which manifested as dengue hemorrhagic fever) and DEN-3.

The lack of protection across serotypes is well known, but evidence of repeat infection with an organism of the same serotype, as seen in one individual, indicates lack of complete protection even within a serotype. In addition, despite these repeated infections, only one resulted in dengue hemorrhagic fever, a disease manifestation believed to be the result of immune enhancement in an individual with reinfection with a new serotype of the virus.