The American Journal of Tropical Medicine and Hygiene - Volume 43, Issue 5, November 1990

This list was terminated on 4 October 1990 when the December 1990 issue was sent to press. Volume 43 will consist of 90 regular articles and a supplement. Members of the Editorial Board and other colleagues as listed below have participated in the review process. In addition, they have seen other manuscripts that are still in the review process or have been rejected.

Members of the Editorial Board during this period were Ronald L. Anthony, A. S. Benenson, Donald S. Burke, Charles H. Calisher, Allen W. Cheever, David F. Clyde, Daniel H. Connor, Joel M. Dalrymple, James L. Hardy, David P. Jacobus, Rodney C. Jung, Llewellyn J. Legters, Steven Meshnick, Franklin A. Neva, Robert E. Shope, Mette Strand, Diane W. Taylor, Harold Trapido, Bryce C. Walton, Thomas H. Weller, and Thomas M. Yuill.

Malaria was transmitted to only 5 of 10 volunteers bitten by 1–2 Anopheles stephensi carrying sporozoites of the 3D7 clone of the NF54 strain of Plasmodium falciparum in their salivary glands. Parasites were detectable by culture in blood taken 7–10 days following exposure and by thick blood film 14–16.5 days after exposure. Infectivity did not correlate with the numbers of sporozoites in the salivary glands.

A panel of Brazilian and Indian sera was screened for reactivity with a variant strain of Plasmodium vivax recently isolated in Thailand. This strain has been shown to have a unique repeat region which differs from the previously described P. vivax CS proteins. A total of 21/343 human sera were found to react with a synthetic peptide representing the variant P. vivax repeat. All of the sera that reacted with the variant repeat peptide, (ANGAGNQPG)4, also reacted with variant P. vivax sporozoites. Both the anti-peptide and the antisporozoite reactivity were totally abolished by adsorption with the variant peptide. Some of the human sera contained variant antibodies that were species specific and could only be adsorbed with the specific variant peptide. These findings suggest that the variant strain of P. vivax might have a worldwide distribution. We also found that some of the variant positive sera reacted with P. brasilianum sporozoites and with the P. brasilianum/P. malariae CS repeat. The adsorption of these sera with the P. brasilianum/P. malariae repeat peptide, (NAAG)4, significantly reduced the reactivity of these sera with the P. vivax variant. In addition, polyclonal and monoclonal antibodies of mice immunized with P. brasilianum sporozoites cross-reacted with the variant P. vivax CS. These findings suggest that exposure to P. brasilianum or P. malariae may give rise to sporozoite antibodies which cross-react with the P. vivax variant CS.

The Plasmodium berghei sporozoite antigen-specific T cell repertoire was analyzed in C57BL/6 (H-2b), BALB/c (H-2d) and C3H/HeN (H-2k) mice following immunization with irradiated sporozoites. Proliferative responses were correlated with the protective status of each strain. Proliferative reactivities to sporozoite antigens were compared in cultures containing either CD4+ T cells, CD8+ T cells, or total splenic lymphocytes. CD8+ T cells had no proliferative activity to sporozoite antigens; CD4+ T cells and splenic lymphocytes responded to the priming antigen, but the responses varied according to the mouse strain tested. The proliferative activity diminished at the onset of protection, presumably due to the induction of regulatory or non-proliferative T cell subsets. Sporozoite-immune lymphocytes did not respond to P. berghei circumsporozoite synthetic peptides. The restricted utilization of T cell epitopes during anti-sporozoite responses can be interpreted as resulting in part from a limited processing of the CS protein antigen.

Quantitative in vitro drug sensitivity of 32 Leishmania isolates (16 from patients failing pentavalent antimony [SbV] therapy) was determined using a radiorespirometric microtechnique (RAM). Of 30 isolates with histories, 22 (73%) RAM tests agreed with patient history; the remaining 8 (27%) did not. There was no difference in RAM drug sensitivity:clinical correlation between 15 isolates tested blindly and 15 with known clinical history (4 did not agree with clinical history in both). Test sensitivity appeared to be limited only by the sensitivity of the Leishmania to SbV and could be detected at 2 µg/ml Sb (about 10% of serum drug level). An isolate from a patient with untreated self-healing cutaneous disease was drug resistant. Using RAM, parasite drug sensitivity can be quantified apart from patient physiologic and immunologic variables intrinsic to clinical data. Potency differed a maximum of 100% (weight% Sb:weight% Sb) among drug lots and also between Glucantime® and Pentostam®. Potency changes between drug lots were not explainable based on Sb content or test-to-test variability. This microtest offers a rapid method for evaluating the drug sensitivity of patient isolates and for determining of the activity of pentavalent antimonials and other candidate anti-leishmanials prior to the initiation of therapy.

To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis. Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis. Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals. Treatment with diethylcar-bamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11. All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment. Antigenemia levels slowly declined over a period of several months in all but one treated individual. Forty-two months after treatment, progressively rising antigen levels are present in 10 patients. Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia. Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment.

Three generations of beagles were monitored for microfilaremia (mf) and clinical disease during repeated infection with Brugia pahangi and were selectively bred for offspring manifesting limb edema and low or amicrofilaremia. A high microfilaremic female mated to a high microfilaremic male produced 7 pups, 6 of which maintained mf >1,000/ml for >2 years after 5 monthly infections of 10 infective larvae each. An uninfected female mated to another high mf male produced 5 pups, 4 of which did not exceed 1,000 mf/ml 7 months after initiation of the repeating infection regimen; 1 of these remained amicrofilaremic after 2 additional challenges. Neither the parents nor the offspring from these matings manifested chronic limb edema. Two matings were conducted with offspring from the microfilaremic female by breeding siblings with the lowest mf and breeding siblings with the highest mf. The high mf siblings produced 4/5 offspring manifesting chronic limb edema (≥7 months duration) and either no mf (in 2 dogs) or <100 mf/ml after the repeating infection regimen. The lower mf siblings produced 5 offspring, all with > 1,000 mf/ml 6 months after the initiation of the repeating infection regimen; none manifested edema. Comparisons of IgG antibody levels, specific for extracts of adult worms, showed no consistent differences between these 2 litters of dogs that could be associated with limb edema or mf when monitored for 16 months; however, the onset of lymph node enlargement was much earlier in the group of dogs manifesting limb edema than in the other litter.

A case-control study was conducted to examine whether physical activity, sibling history of heart disease (HHD), and length of residence in an area endemic for Chagas' disease were associated with the risk of developing Chagas' cardiopathy. Two hundred forty-seven cases of Chagas' heart disease and 345 seropositive subjects with normal ECG (controls) were selected in a population survey in Goiânia, Brazil. Prevalence ratios for exposure variables were estimated for cases in relation to controls and for subgroups of seropositives with selected ECG abnormalities in relation to controls. Increasing age and male sex were consistently and significantly related to an increased risk of ECG abnormalities. HHD was significantly associated with ECG alterations in 3 of the 5 comparison subgroups (any ECG alteration, right bundle branch block, and left anterior hemiblock). No association was found between length of residence in an area endemic, physical activity, and ECG abnormalities. A sample of 529 seronegative subjects were also examined and the interaction between exposure variables and seropositivity was tested to assess whether the associations found were specific for seropositives. Males were at greater risk of any ECG alteration and left anterior hemiblock in relation to females if they were seropositive. An increasing risk of ventricular premature beats with age was clearer for seropositive than for seronegative subjects. Subjects with HHD were at an increased risk of ECG abnormalities and this was greater in those with a positive serological test (P < 0.05). The findings suggest a possible geographical clustering or a familial aggregation of cases of Chagas' heart disease.

The recurrence rate was investigated in 19 patients with non-resectable alveolar echinococcosis after discontinuation of a long-term therapy with mebendazole (average treatment 4.3 years). A control group consisted of 14 patients who underwent radical surgery and finished a course of prophylactic postoperative mebendazole treatment of 2 years. In the controls, no recurrence was observed after a post-therapy period averaging 3.5 years. In contrast, recurrence occurred in 7/19 patients (37%) with non-resectable alveolar echinococcosis an average of 1.6 years after discontinuation of the long-term mebendazole therapy. The absence of clinically detectable recurrence in the remaining 12 patients seems to be due either to spontaneous inactivation of alveolar echinococcosis preceding chemotherapy or too short post-therapy surveillance. The patients with recurrence responded favorably to reintroduction of chemotherapy. The data indicate that mebendazole therapy is parasitostatic rather than parasiticidal.

Forty-one schoolchildren with positive stools for Schistosoma mansoni eggs and 39 age- and sex-matched children with negative stools were given 3 doses, 5 µg each, of a plasma derived hepatitis B vaccine. Their sera were examined 3 and 9 months after the third dose for hepatitis B surface antibody (anti-HBs). At 9 months after vaccination, both the number of responders and the mean of antibody titers were significantly higher in the control group than in the group infected with S. mansoni (97% vs. 56% and 334.8 ± 192.9 vs. 67.7 ± 74.4 mIU/ml). There was a negative correlation between anti-HBs titers and the long diameter of the spleen as well as between the titers and the long diameter of the spleen and the liver span in the mid-clavicular line (right lobe) taken together. There was also a positive correlation between anti-HBs titers and the diameters of the portal vein. There was no correlation between anti-HBs titers and any of the followin 3 parameters: liver span in the mid-clavicular line (right lobe) alone, liver span in the middle line (left lobe) alone, and the degree of thickness of the periportal fibrosis. There was also no correlation between anti-HBs titers and egg counts in the stools. An interpretation of these findings was made in the light of the role of phagocytic activity of the liver and spleen as well as of porta-caval shunts in the immune mechanism.

Scrub and murine typhus have been identified as causes of illness among the 238,000 displaced Khmer people residing in temporary settlements on the Thai side of the Thai-Cambodian border. Still, the true extent of the problem and the relative frequency of infection with scrub typhus as compared to murine typhus are unknown. We evaluated consecutive patients with unexplained pyrexia (documented fever, no exclusionary diagnosis, and constitutional symptoms) in 1 temporary settlement over 1 month. Laboratory studies included culture of blood and assay of paired sera for rickettsial IgM and IgG antibody, for dengue IgM and IgG antibody, and for leptospiral IgM and IgG antibody. Among 37 patients (27 adults and 10 children), 28 (75%) had a rickettsiosis (26 cases of murine typhus and 2 cases of scrub typhus). No case of enteric fever, dengue, or leptospirosis was diagnosed. The illnesses of 9 patients were not identified. Signs and symptoms did not distinguish confirmed rickettsial infections from undiagnosed illnesses. The 1 month attack rate of rickettsial infection was 29/100,000 for children and 185/100,000 for adults. Murine typhus was a major cause of febrile illness in this settlement.

Protestant missionaries (n = 360) serving in sub-Saharan Africa between 1967–1984 were studied to determine the risk of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection. Personnel were serologically screened for antibody to both the hepatitis A virus (anti-HAV) and the surface antigen to the hepatitis B virus (anti-HBs) prior to departure, periodically during service abroad, and upon completion of their African tour. Rates of seroconversion were used as measures of the incidence of infection. Prior to service, 16% of the staff had anti-HAV and 3% had anti-HBs; post-service rates were 42% and 26%, respectively. Over 90% of the staff with > 20 years of service were seropositive for anti-HAV. For both viruses, the infection rate was highest during the first 1–2 years of service, when 28% of those susceptible to HAV and 11% of those susceptible to HBV became infected. Over the next decade, the median annual attack rate was 5.4% for HAV and 4.2% for HBV. Differences in the missionary HBV infection rate among the various African nations served tended to reflect differences in the magnitude of chronic HBV carriage among indigenous population groups. We conclude that missionaries to sub-Saharan Africa are at enhanced risk of both HAV and HBV infection, and that all should receive passive immunization with immune globulin and active immunization with hepatitis B vaccine.

The effects of environmental temperature on Ockelbo virus infection, dissemination, and transmission were studied in Culex torrentium and in the Uppsala and the El Gabal strains of Cx. pipiens. Temperatures tested included 10°C, 17°C, 24°C, and a cyclic (10–24°C, mean = 17°C) regimen designed to mimic typical hourly temperatures in an area endemic for Ockelbo disease in Sweden during the transmission season. The vector competence of both the Uppsala and the El Gabal strains of Cx. pipiens was directly related to environmental temperature. Mosquitoes held at 10°C had a reduced ability to transmit virus as compared to those held at 17°C, 24°C, or in the cyclic temperature regimen. A rapid increase in dissemination rates was observed in mosquitoes exposed to a shift in temperature from 10°C to 24°C. After 4 days at 24°C, these mosquitoes had vector competence similar to those held at 24°C for the entire incubation time. In contrast, virus dissemination in Cx. torrentium was rapid at all temperatures tested and appeared unaffected by environmental temperature; infection and dissemination rates were consistently higher in Cx. torrentium than in either the Uppsala or the El Gabal strains of Cx. pipiens. It seems the transmission of Ockelbo virus by Cx. pipiens might be interrupted by a prolonged period of cold weather, while transmission by Cx. torrentium would continue.

Studies were conducted to determine the effect of environmental temperature on the ability of Aedes aegypti and Ae. taeniorhynchus to transmit Ockelbo (OCK) virus. Temperatures tested were 10°C, 17°C, 24°C, and a cyclic (10–24°C, mean = 17°C) regimen designed to mimic continuously temperatures to which a mosquito might be exposed in July and August in central Sweden. Both species were highly susceptible to oral infection, with no consistent association between incubation temperature and infection rates. However, dissemination of OCK virus to the hemocoel in infected mosquitoes was directly related both to the dose of virus ingested and to the extrinsic incubation temperature. After ≥ 14 days extrinsic incubation, once a disseminated infection was achieved, transmission by bite to a susceptible chick did not appear to be affected by either the initial dose ingested, the holding temperatures of 17°C, 24°C, nor the cyclic regimen. When re-fed, 93% (68/73) and 82% (67/82) of the disseminated Ae. taeniorhynchus and Ae. aegypti, respectively, transmitted virus. In contrast, when mosquitoes were held at 10°C, fewer disseminated Ae. taeniorhynchus (0/5) and Ae. aegypti (2/6) transmitted virus. There were no significant differences in infection, dissemination, or transmission rates for Ae. taeniorhynchus held at the cyclic temperature regimen vs. those held at a constant 17°C. Environmental temperature affected the vectorial capacity of Ae. aegypti and Ae. taeniorhynchus for OCK virus, with transmission occurring earlier and at a higher rate in mosquitoes held at higher temperatures.

To determine whether the quantity of food available to mosquitoes in their aquatic environment limits the effectiveness of microbial pathogens as biological control agents, experimentally well-nourished and malnourished larval Aedes aegypti (Linn.) were exposed to graded inocula of the entomopathogenic fungus, Metarhizium anisopliae. First instar larvae were provided access either to 3 or to 5 mg of food, and lots from each food regimen were inoculated with 20, 40, 60, or 80 µg of fungal spores/ml water. Application of the fungus to well-nourished larvae reduced the proportion developing to the adult stage, and increased the size of those adults that developed; their survival was not affected. In the case of malnourished larvae, such applications appeared not to effect the proportion of larvae that matured, and, paradoxically, increased the size and longevity of these resulting adults. By destroying a portion of the larvae, the pathogen apparently reduced competition among malnourished larvae, thereby enhancing their survival, as well as the size of the resulting adults. Thus, biocontrol agents may fail when used as larvicides against such nutrient-deprived mosquitoes as frequently occur in nature.

The spatial pattern in Senegal of Crimean-Congo hemorrhagic fever (CCHF) virus IgG antibody prevalence in human and sheep was determined as was the relative abundance of potential tick vectors. A systematic, country-wide serological survey of sheep demonstrated that 10.4% of sheep exhibited IgG to CCHF virus. Sexes were infected equally. Antibody prevalence increased with age from 2.1% during the first year to 18.2% among sheep ≥3 years of age. IgG prevalence was highest in the northern, arid Sahelian zone, averaging 75.7% seropositivity, and decreased to zero in the southern, moister Sudano-Guinean and Guinean zones. Human IgG prevalence ranged from 21% to <1% among the 8 sites that were sampled throughout the country, being greatest in the arid north and least in the south. Hyalomma ssp. ticks predominated in those biotopes where antibody prevalence was highest. The abundance of Hyalomma ticks may be the proximal determinant of endemic transmission.

I hate to tell people that I am a parasitologist because I always get the same responses. Most often the person I'm talking to changes the subject, since he probably has no idea of the functions of a parasitologist. The second most common response is, “It must be really fascinating to study ESP.” Sometimes, the person has had a stool examination at one time, and thinks that parasitologists spend all their time looking at feces. These people usually ask me what made me decide to choose such an “interesting” career. I used to have trouble answering this question. Well, not anymore. Now I simply tell them to read Ben Kean's book.

I count myself among the 5,000 or so Cornell Medical School students who have heard Kean lecture on parasitology. Some teachers of parasitology give dense, detailed lectures about life cycles, epidemiology, symptomatology, and control. Not Ben Kean. He tells stories.