The American Journal of Tropical Medicine and Hygiene - Volume 52, Issue 1, 1995

It should be clear to the readers of the American Journal of Tropical Medicine and Hygiene that a number of changes have been instituted. The size of the Journal increases with this issue to 8 1/2″ × 11″ and the cover has been updated. The larger page size will enable us to reduce the number of pages required by manuscripts and thereby reduce the page charges to individual authors. Two additional features, Short Reports and Letters to the Editor, were introduced in 1994. We believe that these changes will enhance the Journal's ability to communicate important information. Readers will also have noted that the Journal is now accepting advertising. We hope that this effort will provide some additional, much needed income to support publication costs.

In general, the health of the Journal is quite good as we begin a new year. The number of papers published has increased for the fourth consecutive year, from 180 in 1991 to 229 in 1994, and we will be making every effort to increase this number in 1995.

Material for publication should be sent to the Editor, McWilson Warren, 3088 Briarcliff Road, Suite A1, Atlanta, Georgia 30329, USA. Such material should be accompanied by a letter from the corresponding author with signatures from all submitting authors indicating that all authors listed concur with the submission and that the material has not been, and will not be, submitted elsewhere for publication as long as it is under consideration of the JOURNAL. Manuscripts and letters to the Editor should be typewritten, letter quality, in 10 point type, on one side of the paper and submitted in quadruplicate. Paper should be 8 1/2 × 11 inches, pages should be numbered, and the manuscript should be neither stapled nor folded. Double spacing should be used throughout including in the list of references, tables and figure legends.

Carrying out the obligatory ritual of reading the addresses of my predecessors I learned that the Society had met once previously in Cincinnati, in 1945, before the “and Hygiene” was added to our name. Appropriately, President Rolla Dyer's address that year was titled “Medical Research in the Postwar World”, and it contained hints of things to come. For example, Dyer mentioned that to promote the training of scientists the National Institute of Health (NIH) had established fellowships, some of which had been filled!

I am pleased that the venue of this meeting is Cincinnati, a city which at a personal level has much meaning for me. It is my mother's birthplace, and is where my parents met and married before they migrated to that then-distant land, Texas. One memorable summer my brother and I stayed with a much-loved uncle and aunt in Cincinnati who were devoted fans of the Cincinnati Reds, and they took us often to the ballpark.

To estimate the economic burden imposed by eastern encephalitis (EE), we identified a series of residents of eastern Massachusetts who had survived EE infection and enumerated any costs that could be attributed to their experience. The records of three people who suffered only a transient episode of disease were analyzed as well as those of three who suffered severe residual sequelae. Transiently affected subjects mainly required assistance for direct medical services; the average total cost per case was $21,000. Those who suffered persistent sequelae remained at home and seemed likely to live a normal span of years, but without gainful employment. Early in the course of their chronic illness, costs ranged as high as $0.4 million per year, but plateaued at about $0.1 million after three years. Hospital costs, which dominated early in the disease experience, approached $0.3 million per patient. Educational costs tended to replace hospital costs after two years as the dominant economic burden and totaled about $0.3 million per patient during the first six years. Total costs then averaged almost $0.8 million. By the time that these subjects will have reached 22 years of age, disease-related costs will have totaled about $1.5 million. Institutionalization will impose an additional lifetime cost of $1.0 million. Insecticidal interventions designed to avert outbreaks of human EE infection cost between $0.7 million and $1.4 million, depending on the extent of the treated region. The direct costs of an intervention are less than the $3 million imposed on one person suffering residual sequelae of EE.

Substantial progress has been realized in the global campaign to eradicate dracunculiasis by the end of 1995 since a previous review of the subject was published in this journal a year ago. All known endemic countries are now engaged in the eradication effort, and one or more control measures are now in place in 93% of endemic villages. Despite improved surveillance for the disease, the number of reported cases of the disease has been reduced by 41% (to about 221,000), and the number of known endemic villages has been reduced by 28% (to about 16,500) in the past year. Priorities for national eradication programs in 1994 include increasing the use of vector control and intensifying the case containment strategy in endemic villages. It is still possible to achieve the eradication target of December 1995, but greatly intensified efforts this year will be required to do so.

We investigated measures to prevent Toxocara egg contamination of sandpits. Replacement of contaminated sand was not effective because 1–9 new fecal deposits per sandpit were found daily, with eggs reappearing in the sand 6–9 weeks after the replacement. When the sandpit was covered with a clear vinyl sheet, the temperature of the sand to a depth of 3 cm was 42°C or more for 3 hr when the air temperature was higher than 30°C. This procedure prevented contamination by fecal deposits and also resulted in the destruction of existing eggs because the sandpit was kept dry on rainy days. The method seemed safe and inexpensive. The effectiveness of a fence around a sandpit depended on user behavior, which could not be relied upon. Therefore, a practical method for the prevention of Toxocara egg contamination of sandpits is to cover the sandpit with a clear vinyl sheet at night and on rainy days.

Electroencephalograms (EEGs) were obtained for 26 patients with snake bite to observe the cerebral impact of snake venom. All snakes were identified; 19 (73%) were Russell's vipers, one (4%) was a common cobra, five (19%) were hump-nosed vipers, and one (4%) was a dog-faced fresh water snake. The EEG was abnormal in 25 patients (96%) and these results included all the snake species identified. The EEG abnormalities observed were reduced alpha activity, increased theta/beta activity or sharp waves (grade 1), sharp waves or spikes and slow waves (grade 2), or diffuse delta activity (grade 3). Grade 1 changes occurred in 16 patients (62%), grade 11 in eight patients (31%), and grade 111 in one patient (4%). Thus, grade 2 and 3 changes, which were moderately severe to severe abnormalities, occurred in nine patients (35%). One patient had acute renal failure and two others had mild jaundice and hyponatremia. These three patients had EEG abnormalities that were similar to those observed in the remaining 22 patients. The altered EEG, suggestive of an encephalopathy, appeared within hours of the bite and persisted for several days without clinical neurologic effects. The changes were seen mainly in the temporal lobe. Similar changes occurred in both patients with and without antivenom therapy. It appeared that the EEG abnormalities are a consequence of the effects of venom from the bites of a variety of snakes.

The paper reviews a previously published case of hydatid disease in the human heart of a Brazilian person who died of tetanus. Based on present knowledge about the distinguishing characteristics of Echinococcus granulosus, E. vogeli, and E. oligarthrus, it was recognized that the infection was due to E. oligarthrus, mainly based the morphologic features of the hooklets of the protoscolex. This is the second human infection due to E. oligarthrus and the first showing wall features of cysts. Therefore, some human infections of polycystic hydatid disease observed outside the range of the bush dog, the only definitive host of E. vogeli (Panama to Northern Argentina), may be due to E. oligarthrus rather than to E. vogeli.

Finding an effective treatment for viral infections that cause encephalitis remains an important problem. A model of human alphavirus infections, Semliki Forest virus, causes lethal encephalitis in weanling mice. Mice are viremic within 24 hr of an intraperitoneal challenge with the equivalent of three 75% lethal doses of Semliki Forest virus. Virus reaches the brain by 48 hr, and mortality results in all mice in 5–7 days. Introduction of virus intracranially accelerates the course of the infection. Neither anti-Semliki Forest virus hyperimmune serum nor the potent interferon inducer poly I:CLC given intraperitoneally are protective when used therapeutically after an intracranial virus infection, but a combination of 1,000 U hyperimmune serum and 80 µg/mouse of poly I:CLC results in a 50% survival rate. This combination treatment of intracranial Semliki Forest virus infection eliminates detectable viremia and reduces virus load in the brain over the course of the infection. These data show that when combined, specific antibody and an interferon inducer can interact synergistically to protect mice from alphavirus infections of the central nervous system even when given after the virus is replicating in the target organ.

We determined whether detection of antibody response against a newly detected epitope, designated Em18, among Echinococcus multilocularis antigens could be a reliable marker for differentiation of active cases of alveolar hydatid disease (AHD) from inactive cases. Fifteen Alaskan patients with either active or inactive lesions of AHD previously confirmed clinically, pathologically, and serologically by the Em2-enzyme-linked immunosorbent assay (ELISA) were used for a blind test by Western blotting. Ten and five cases were considered to be active and inactive cases, respectively. One of the 10 cases classified serologically as active was judged to be inactive based on clinical and pathologic criteria; the patient had a recognizable parasitic lesion, and following short-term treatment with albendazole, a biopsy of the liver showed a degenerated lesion that did not grow in rodents. The five cases judged to be inactive included two confirmed inactive cases with cicatrized lesions and three active cases that showed the weakest values in the Em2-ELISA. The most predominant IgG subclass responding to Em18 was IgG4. In general, there were good correlations between 1) the antibody response against Em18 and the presence of active lesions and 2) the antibody response against Em18 and the Em2-ELISA values.

With the widespread emergence of drug-resistant Plasmodium falciparum infection, febrile patients in the tropics can no longer be empirically treated with inexpensive yet effective antimalarials. The substitution of newer and more costly drugs brings with it the need for rapid, accurate, and inexpensive diagnostic procedures so that directed therapy can be used. We report a field trial comparing standard microscopic malaria diagnosis and quantitative buffy coat analysis to a new P. falciparum antigen detection system. The ParaSight™ F test (PFT) was found to be easy to learn, rapid to perform, and highly accurate. If confirmed, the use of the PFT in endemic areas may aid in the identification of patients requiring therapy for drug-resistant malaria.

We have observed specific and nonspecific reactivities to the asexual stages and gametocytes of Plasmodium falciparum and examined the effect of chloroquine and Fansidar™ (pyrimethamine/sulfadoxine) on the dynamics of gametocytemia. Schoolchildren peripheral blood films positive for P. falciparum gametocytes were identified in a malaria-endemic area of Mozambique. The children were randomly allocated into two groups to receive chloroquine or pyrimethamine/sulfadoxine, and were followed for 28 days after treatment. In patients harboring drug-sensitive parasites, asexual parasitemias were cleared by day 4, but gametocytes persisted for an additional 17 days. The prevalence of the asexual parasites was 67.6% in the chloroquine-treated group at day 0 and 61.1% at day 28, whereas in the pyrimethamine/sulfadoxine treated group, the initial parasite positive prevalence of 70.7% was reduced to 2.4% at day 28, suggesting a high prevalence of chloroquine-resistant parasites. On day 0, gametocyte prevalence was 59.5% in the chloroquine-treated group and in 68.3% in the pyrimethamine/sulfadoxine-treated group; these values were reduced to 5.6% and 2.4%, respectively, at day 28. Our results suggest strongly that there is no induction of gametocytogenesis by either course of chemotherapy.

Monoclonal antibodies (MAbs) 32F1 and 32F3 react with two independent epitopes of a protein doublet with molecular weights of 48 and 45 kilodaltons (kD) expressed on the surface of Plasmodium falciparum (Pfs48/45) macrogametes and zygotes; only 32F3 blocks transmission. These MAbs were used to develop a Pfs48/45-specific competition enzyme-linked immunosorbent assay (ELISA) using 32F1 to capture antigen and labeled 32F3 for quantification and analysis of the contribution of antibodies in human serum to transmission-blocking activity. A comparison analysis was used to determine agreement of competition ELISA titers and transmission-blocking activity as observed in the bioassay in three groups of serum samples: 37 from European travelers with previous exposure to malaria, 56 from gametocyte carriers, and 66 from schoolchildren from a malaria-endemic area in Cameroon. The index of agreement between outcomes of the ELISA and transmission-blocking assay in gametocyte carriers and in travelers was specifically defined as fair-to-moderate; in schoolchildren the agreement was not significant. The combined analysis of all sera showed a significant and fair-to-moderate agreement between the results of the competition ELISA and the transmission-blocking assay, with a relative specificity of 94% (of 105 cases negative in the transmission-blocking assay, 99 were also negative in the competition ELISA) and a relative sensitivity of 44% (of 54 cases positive in the transmission-blocking assay, 24 were also positive in the competition ELISA). This study shows that a positive C48/45-ELISA is indicative for transmission-blocking activity in the mosquito assay, while a negative result does not exclude transmission-blocking activity.

The prevalence and concentration of antibodies to ring-infected erythrocyte surface antigen (RESA) were measured in blood samples collected during a cross-sectional survey conducted in Papua New Guinea. Antibodies were measured by enzyme-linked immunosorbent assay to the recombinant RESA protein in 1,398 subjects and to RESA 8 and RESA 11 synthetic peptides in a subsample of 200 adults. Overall, the seropositivity rate to recombinant RESA was 66% and the geometric mean antibody concentration was 28 µg/ml. There was a slow increase in antibody prevalence and concentration with age that continued to occur even after 40 years of age. In children less than 10 years of age, there was a significant positive correlation between both RESA antibody prevalence and concentration and concurrent infection with Plasmodium falciparum. The opposite was true in adults more than 20 years of age, with those having a high antibody concentration to RESA being less likely to be parasitemic at the time of the survey. This observation was consistent with the finding of a weak but significant negative correlation between log antibody concentration and log P. falciparum density, which was mainly found in adults. No consistent correlation was found between humoral immune response to RESA and morbidity indicators.

To determine whether protective immunity against the agent of Lyme disease may be expressed mainly within its tick vector prior to transmission, we passively immunized mice at various intervals after infected ticks had attached, and assayed such mice for evidence of spirochetal infection by xenodiagnosis one month after challenge. Groups of CD-1 mice were intraperitoneally infused with 0.5 ml of hyperimmune rabbit or mouse serum, reagents and quantities previously determined to protect against syringe-challenge with 106 low-passage JD1 spirochetes 12 hr after passive transfer. Comparison groups received normal rabbit serum or saline. All mice were protected from infection when infused no more than one day after infective ticks were allowed to attach. However, if infused three or five days post-tick attachment, 60–100% of the mice became infected. All mice became persistently infected when infused with saline or normal rabbit serum. We conclude that antibody is protective against tick-transmitted spirochetal infection only when passively administered before the spirochetes are deposited in the skin of the host. Ingested antibody may destroy spirochetes or interfere with activation and replication within the tick gut, or with dissemination to the salivary glands. Lyme disease vaccines may thus be uniquely effective because of the vulnerability of the spirochetal agent within its vector.

A thorough phenotypic characterization of yellow fever (YF) virus generated from cDNA is a necessary prerequisite for mapping virulence/attenuation determinants and exploring the potential of YF attenuated virus 17D as a carrier for heterologous protective epitopes. In this study, YF virus was produced from 17D cDNA clones after lipofectin-mediated RNA transfection of certified primary cultures of chicken embryo fibroblasts (YFiv5.2/SL). This virus was passaged once in embryonated chicken eggs according to current YF vaccine manufacture methodology to produce the experimental virus (YFiv5.2/VL). These viruses were characterized in established monkey neurovirulence safety tests and quantitative clinical and histologic scores were derived for each virus. The experimental vaccine viruses (YFiv5.2/SL and VL) compared favorably with another well-known YF vaccine strain (17DD) used as control virus for the histologic score. Although slightly higher clinical neurovirulence was observed for YFiv5.2 as compared with the 17DD virus, it should not preclude the use of YFiv5.2 for mapping YF virus virulence determinants.

Genetic diversity of the merozoite surface antigen-2 gene of the human malaria parasite Plasmodium falciparum has been analyzed in a Senegalese village where malaria is holoendemic. A cross-sectional survey of 65 residents was performed in 1992 during the high transmission season. Plasmodium falciparum was detected both by microscopy (77% positive samples) and DNA amplification using a single (29% or 38% positive samples, depending on the primers used) or nested polymerase chain reaction (PCR) (78% positive samples). The overlap between the positive nested PCR and microscopic examination was not complete. The PCR fragments were analyzed for size polymorphism on agarose gels, and were subsequently assigned to the major allelic families 3D7 or FC27 by hybridization with family-specific probes. Both allelic families were found, with a slightly higher prevalence for FC27. Chimeric alleles that failed to hybridize under stringent conditions to the reference probes were also observed. Some were typed using a novel PCR approach, using hybrid pairs of primers, consisting of a family-specific sense oligonucleotide combined with an antisense oligonucleotide specific for the other family. Combining typing techniques, 82% of the positive PCR results yielded more than one band. Both the overall number of fragments and the number of allelic types per carrier were markedly reduced around the age of 15 years. The number of DNA fragments decreased abruptly from an average of four per carrier before the age of 15 years to an average of two in individuals more than 15 years of age. Similarly, the number of individuals carrying more than one allelic type decreased with age, with a cutoff at the age of 15 years. This parallels the observed decrease in prevalence and parasite density in this village. There was, however, no age-dependent carriage of any particular allele, with the various alleles being detected in all age groups. The results, therefore, indicate that acquiring anti-parasite immunity not only results in decreasing parasite load, but also in decreasing the complexity of the infections.

The microsporidia Enterocytozoon bieneusi is reported in 10–30% of those infected with the human immunodeficiency virus. The parasite appears to be a cause of gastralgia, malabsorption, and diarrhea. A Western blot technique using another microsporidian species, Glugea atherinae, has demonstrated an antigenic similarity between this parasite and E. bieneusi. Preliminary results show the variability of the antigenic profiles obtained from the sera of immunodeficient patients infected with E. bieneusi and also of the cross-reactivity to Glugea sp. antigens of some sera from patients with cryptosporidiosis. The origin of this cross-reactivity is undetermined. The possibility of coinfection with undetected microsporidia is not excluded. These results raise questions concerning the interpretation of serologic data and of the potential immunodiagnostic value of microsporidian antigens.

Ivermectin treatment of onchocerciasis patients can be accompanied by adverse reactions. Not much is known concerning the pathogenesis of these reactions. Previous studies have demonstrated that the occurrence and extent of adverse reactions are related to infection intensity. However, some severely infected patients experience relatively few adverse effects. The aim of the present study was to investigate whether this seeming discrepancy could be due to diminished ivermectin absorption. Ivermectin concentrations one and two days after treatment were measured by high-performance liquid chromatography in sera of 71 skin snip-positive onchocerciasis patients (21 without reactions, 25 with mild reactions, 14 with moderate reactions, and 11 with severe reactions). The overall mean ± SD ivermectin concentrations one and two days after a single oral dose (150 µg/kg) were 16.4 ± 6.4 and 6.6 ± 3.1 ng/ml, respectively. The overall mean ± SD half-life was estimated to be 19.9 ± 8.6 hr. The data presented did not show a relationship between ivermectin concentrations and the grade of adverse reactions.

Information is lacking on the prevalence of hepatitis C virus (HCV) infection in most African countries. An algorithm based on a combination of enzyme immunoassays (EIAs) with different formats (a commercial test, an HCV antibody [Ab] III test, and an HCV core Ab EIA) was used to estimate the prevalence of HCV infection in different population groups from southern Cameroon. An overall high prevalence was observed, with a significant increasing trend for both sexes with respect to age. A high proportion (67.4%) of HCV-positive sera were viremic as demonstrated by the reverse transcription-polymerase chain reaction. We conclude that the prevalence of HCV is high in southern Cameroon and increases linearly with age.

Human T cell lymphotropic virus type 1 (HTLV-1) is endemic in South America and the Caribbean basin. To clarify the genetic and phylogenetic relationship between an HTLV-1 strain isolated from a Brazilian woman with adult T cell leukemia and viral isolates from elsewhere in South America and from other geographic regions, selected regions of the gag, pol, env, and pX genes were amplified and directly sequenced. The overall sequence similarities between the Brazil-R-1 strain and the Japanese prototype ATK strain were 98.7% based on 1,295 nucleotides and 99.1% based on 429 amino acids. Phylogenetic analysis indicated that strain Brazil-R-1 clustered with other Brazilian and South American HTLV-1 isolates and was more closely related to Caribbean isolates from Martinique and Guadeloupe than to virus strains from other geographic regions. These data suggest a common source of HTLV-1 infection in the Caribbean basin and South America.

To determine whether military personnel deployed outside the United States are at increased risk of Helicobacter pylori infection, 1,000 male U.S. Navy and Marine Corps personnel (mean age 22 years) were evaluated. Study subjects included 200 recruits, 500 shipboard personnel deployed for six months to South America, West Africa, and the Mediterranean, and 300 ground troops deployed for five months to Saudi Arabia. Among all 1,000 subjects, 247 (25%) were seropositive for H. pylori IgG antibody by an enzyme-linked immunosorbent assay; 24% of new recruits and 25% of troops who had been on active duty for a mean of four years. The prevalence of H. pylori antibody was higher among subjects who were older, nonwhite, foreign-born, and seropositive for antibody to hepatitis A virus. Among the 601 initially seronegative subjects evaluated before and after a 5–6-month deployment outside the United States, five seroconverted, for a rate of infection of 1.9% per person-year of exposure. As found in other populations in developed countries, these data indicate that among U.S. military personnel a large proportion of H. pylori infections occur before adulthood and infection is related to demographic factors. These preliminary findings also suggest that deployed U.S. military personnel may be at increased risk of H. pylori infection compared with adult populations in developed countries either from exposure in developing countries or from crowding.

Missionaries of Science is a collection of seven essays that recount the interactions between U.S. scientists of the Rockefeller Foundation and the scientists, politicians, and people of several Latin American countries in the first half of the twentieth century. The collection is unique in that it concentrates on the perceptions and viewpoints of the recipients of the philanthropy rather than the donors.

Five of these essays were presented at a conference entitled “Science, Philanthropy and Latin America: Cross-Cultural Encounters in the Twentieth Century” held at the Rockefeller Archive Center in Tarrytown, New York in 1991. Two additional chapters were included because they share the perspective of the conference.

Marcos Cueto is a researcher and medical historian at the Instituto de Estudios Peruanos in Lima, Peru. He and six colleagues reviewed the holdings of the Rockefeller Archive Center as well as the institutional archives of the concerned countries.

The 44th Annual Meeting of the American Society of Tropical Medicine and Hygiene will be held November 5–9, 1995 in San Antonio, Texas. Meeting and hotel reservation forms and local information will be mailed separately to all ASTMH members later this spring.

Call for Abstracts. Members of the ASTMH are invited to contribute new information in one of the many areas of interest to our Society and to do this as a poster (discussion) presentation at the Annual Meeting or via the traditional route of a 10-minute oral presentation with five additional minutes allowed for discussion. For both types of presentation, abstracts must be submitted on diskette with an accompanying hard copy. An ASTMH abstract submission program has been specifically created for use with either MS/DOS or Macintosh systems. The program is menu-driven and has been designed to be user-friendly. If you plan to submit an abstract for the 1995 Meeting, you should obtain the submission program NOW!

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Gorgas Memorial Institute Fellowship Program. This fellowship program is supported by the Gorgas Memorial Institute to facilitate the development of linkages between scientists from Panama, nations of Central America and the Caribbean Islands, and the United States through the award of short-term travel grants for young investigators from these regions. The program is intended to allow young scientists the opportunity to acquire new techniques or develop new approaches for the study and control of tropical diseases, and to initiate collaborative studies. Applicants should have Ph.D. or M.D. level training in a relevant field and be no more than 40 years of age, although exceptional cases may be considered. Applicants must be a citizen or permanent resident of one of the countries in the above-mentioned regions.