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Biomedical subjects

D B Fishbein

Publications and source records attributed to D B Fishbein.

At least 19 recordsLinked to original sources

Benefits and costs of using an orally absorbed vaccine to control rabies in raccoons.

In November 1989, the epizootic of rabies affecting raccoons in the mid-Atlantic states reached New Jersey. An economic evaluation was conducted in 2 counties first affected by the epizootic to estimate the costs of the epizootic and to assess the costs and benefits of orally administering a newly developed recombinant rabies vaccine to prevent further spread of the disease. Data on expenditures associated with prevention of rabies in human beings and domestic animals and laboratory testing of suspect animals were collected and analyzed for 1988 (before the epizootic) and 1990 (first full year of the epizootic). Benefit-cost ratios were calculated and used to evaluate the economic advisability of the vaccine at various vaccination program alternatives. Two indices of capital investment analysis, payback period and net present value, were used to evaluate the economic benefits of the rabies vaccine. Expenditures were estimated to be $1,952,014 in 1990 (primarily for pet animal vaccinations), compared with $768,488 in 1988. Benefit-cost ratios ranged from 2.21 for the most expensive vaccination program alternative to 6.80 for the least expensive alternative. The payback period varied from 0.69 to 2.11 years, and the net present value ranged from $2,105,453 to $4,877,452. The high costs of this epizootic necessitated the reallocation of scarce public health resources to various rabies prevention activities, particularly the vaccination of dogs. This study also demonstrated the usefulness of benefit-cost analysis in developing public health strategies. Although the mass application of this recombinant vaccine was found to be economically beneficial, other qualitative considerations must be used to supplement these findings.

Administration, Oral

Rabies surveillance in the United States during 1990.

In 1990, the United States and its territories reported 4,881 cases of rabies in animals to the Centers for Disease Control, a 1.5% increase from 1989. Of these, 553 were domestic animals, 4,327 were wild animals, and one was a human being. Pennsylvania reported the highest number (611) of rabies cases in animals in 1990. For the first time since surveillance of rabies in wild animals was begun in the 1950s, the number of cases of rabies in raccoons exceeded that in skunks. Particularly large increases of cases of rabies in wild and domestic animals were reported in New Jersey (469 cases in 1990 compared with 50 cases in 1989, an increase of 838% from 1989) and New York (242 cases in 1990 compared with 54 cases in 1989, an increase of 348%). The 1,821 cases of rabies in raccoons represented a 17.9% increase over those reported in 1989 and 24.5% over those in 1988. This increase was largely attributable to the larger number of rabid raccoons in New Jersey and New York. Other states that reported an increased number of rabies cases in animals in 1990 included Utah (77.8%), Louisiana (64.7%), North Dakota (60.3%), Arizona (28.6%), Oklahoma (27.5%), Delaware (22.2%), and Maryland (20.6%). Thirty states reported a decrease in the number of cases of rabies in animals.

Adult

Outbreak of human rabies in the Peruvian jungle.

Transmission of rabies to man by vampire bats has been known for 60 years but there have been few reports of the features of rabies transmitted in this way. These aspects of the disease were investigated during an outbreak in Peru in early 1990. Between Jan 1 and April 30, 1990, 29 (5%) of 636 residents of the two rural communities in the Amazon Jungle in Peru acquired an illness characterised by hydrophobia, fever, and headache and died shortly thereafter. A census in one of the two towns revealed that the proportion affected was significantly higher for 5-14 year olds (17%) than for other age-groups (p less than 10(-5). Interviews conducted with 23 of the patients or their families revealed that 22 (96%) had a history of bat bite, compared with 66 (22%) of 301 community members who remained healthy (p less than 10(-6). A rabies virus strain identical to those isolated from vampire bats (Desmodus rotundus) was isolated from the brain of the only person on whom necropsy could be done. Because of the extreme isolation of this and other communities affected by bat-transmitted rabies, preventive measures should be directed at decreasing the risk of nocturnal exposure to bats by bat proofing dwellings or use of mosquito nets and at prompt wound care. Rabies pre-exposure or postexposure vaccination is clearly indicated, but may not be feasible in these isolated populations.

Adolescent

Detection of the etiologic agent of human ehrlichiosis by polymerase chain reaction.

Polymerase chain reaction (PCR) primers derived from a variable region of the 16S rRNA gene sequence were used to amplify DNA specifically from Ehrlichia chaffeensis (the recently proposed name for the etiologic agent of human ehrlichiosis). The 389-bp product defined by the specific primers was not detected when DNA samples from any of the other recognized species of Ehrlichia were used as amplification templates. When the PCR was applied to five suitable blood specimens obtained from patients subsequently shown to be serologically positive for E. chaffeensis, all five were positive. The same technique was applied to a total of six control blood specimens, three from febrile patients who had no serologic evidence of infection with Ehrlichia or Rickettsia species and three from patients diagnosed with Rocky Mountain spotted fever, and all six were negative. A chemiluminescent, group-specific oligonucleotide probe was shown to hybridize only with the PCR products obtained upon amplification of the five blood specimens from patients serologically diagnosed as having human ehrlichiosis. The results indicate that PCR, coupled with a nonisotopic method of confirming the identity of the PCR product, is a highly specific and efficient method of detecting the agent of human ehrlichiosis in blood. The results also suggest that E. chaffeensis is the sole etiologic agent of human ehrlichiosis in the United States. The technique was also applied to four ticks that were positive by direct immunofluorescence for Ehrlichia species, and one tick was PCR positive, indicating that E. chaffeensis DNA can be detected in ticks harboring this organism, although the sensitivity may be low.

Animals

A case of human ehrlichiosis acquired in Mali: clinical and laboratory findings.

We report on the clinical, epidemiologic, and laboratory characteristics of the first case of human ehrlichiosis acquired outside the United States caused by an Ehrlichia sp. other than E. sennetsu. The patient, a 24-year-old woman, presumably acquired the infection in Mali in northern Africa; the diagnosis was made when she returned to North America. The patient reported a fever and diarrhea a week before she left Mali; the diarrhea resolved, but the fever and chills continued. She also reported intermittent tingling in both hands and feet and muscle discomfort. Her temperature was 37.8 degrees C and her pulse rate was 100 per minute. She had two erythematous maculopapules (0.5 x 0.7 mm) on her thigh and ankle that resembled infected insect bites. Her hemoglobin level was 148 g/l with normal indices, and her white blood cell count was 10, 500/mm3 with many atypical lymphocytes and platelets. This report is intended to increase physicians' awareness of ehrlichiosis in foreign travelers and other patients, and suggests the need for further research to determine the prevalence and distribution of this disease.

Adult

A field evaluation in Mexico of four baits for oral rabies vaccination of dogs.

We evaluated four baits for the delivery of oral rabies vaccines to dogs. In a controlled study in a town in rural Mexico, 177 randomly selected dogs were assigned to receive one of four experimental baits (two of which were developed by the Denver Wildlife Research Center [DWRC]): one of two cylindrical polyurethane sponges with a corn meal coating (one fried in corn oil [DWRC-corn], the other in fish oil [DWRC-fish]), a fish-flavored polymer bait, or a wax bait. Each dog was also offered a commercial dog biscuit. We recorded whether or not the bait was completely consumed, and used the following measures to estimate the amount of oropharyngeal contact with each bait: total chewing time, presence of pieces of bait on the ground following administration, the total area of ground surrounding the location of ingestion that was covered with green dye contained in each bait, and condition of ampules that contained the dye. The dog biscuits were completely consumed significantly more often than the baits (155 of 176 [88%] for the biscuits versus 89 of 176 [50.5%] for the four baits; P less than 10(-6)), but were chewed for a significantly shorter time than the baits (mean time 34 sec for the biscuit versus 60-82 sec for the four baits: P less than 0.001). The ideal bait would probably combine the attractiveness of the commercial biscuit and the ability of the sponge baits to promote contact with the mucous membranes.

Administration, Oral

Prevention of canine rabies in rural Mexico: an epidemiologic study of vaccination campaigns.

We compared three vaccination strategies in three rural communities in Mexico to determine the factors associated with the success of vaccination programs in areas where canine rabies is poorly controlled. In town A, intensive publicity and community participation were used; owners were instructed to bring their dogs to temporary centralized clinics for vaccination. In town B, only brief precampaign publicity was used, followed by vaccination at a centralized site. Minimal publicity was also used in town C, but the vaccination campaign was conducted house to house. A total of 5,426 residents and 1,597 dogs were counted in the three towns (mean human:dog ratio 3.4:1). In Town A, 70.1% (472 of 673) of the dogs were vaccinated; the campaign required 40 person-minutes per dog. Significantly greater proportions were vaccinated in town B (262 of 318 [82.4%]; P less than 0.001) and town C (483 of 561 [86.1%]; P less than 0.00001); each of these latter campaigns required 10 person-minutes per dog. The following factors were positively associated (by multivariate analyses) with vaccination of individual dogs: non-intensive publicity, house-to-house vaccination, dogs owned by a single member of the household, and dogs acquired greater than 15 days after birth. Intensive publicity did not increase the overall success of the vaccination program; the efficiency of centralized versus and house-to-house vaccination was comparable.

Administration, Oral

A cluster of Coxiella burnetii infections associated with exposure to vaccinated goats and their unpasteurized dairy products.

An outbreak of Q fever occurred among patients and staff of a psychiatric institution in southern France. Some of the patients and staff left the institution daily to work on a farm where goats were raised for raw milk and cheese production. The goats had all been vaccinated annually with a commercial vaccine containing phase II Coxiella burnetii antigen. A serologic survey revealed that 40 (66%) of the 61 patients and staff had elevated titers to C. burnetii. Seropositive persons were more likely to report an acute illness (P = 0.001), fever (P = 0.04), weakness (P = 0.04), arthralgia (P = 0.04), and headaches (P = 0.06) in the preceding year than were seronegative persons. Seropositivity rates were significantly higher among persons who worked on the farm and consumed unpasteurized milk products (69% [22 of 32]; P = 0.007), those who only had worked on the farm (75% [9 of 12]; P = 0.009), and those who only had consumed unpasteurized milk products (75% [9 of 12]; P = 0.009), compared with those who had not worked with the goats or consumed unpasteurized milk products (0 of 5). Despite vaccination against Q fever, no antibodies to C. burnetii were detectable in 17 (59%) of 29 goats. All 12 seropositive goats had antibodies to both phase I and phase II antigens, indicating that they were naturally infected, and two of three goats examined were shedding C. burnetii in their milk. Vaccination of this herd did not prevent the outbreak and might have increased shedding of C. burnetii in the dairy products.

Adult

Ten-year follow-up of HIV-infected homosexual men with lymphadenopathy syndrome: evidence for continuing risk of developing AIDS.

Seventy-five homosexual men with lymphadenopathy syndrome (LAS), subsequently shown to be seropositive for the human immunodeficiency virus (HIV), were enrolled in a prospective study in Atlanta in 1982 and 1983. Subjects have been followed up at 3- to 6-month intervals with clinical and immunologic evaluations, including analysis of T-cell subsets. As of February 28, 1991, AIDS had developed in 36 (48%) of the 75 men. The AIDS cases continued to occur through the 10th year after onset of LAS; the 10-year cumulative incidence of AIDS was 56.6% (Kaplan-Meier survival analysis). Six-year incidence rates following the first observation of a T-helper cell count greater than or equal to 500/mm3, 400-499/mm3, 300-399/mm3, 200-299/mm3, and less than 200/mm3 were 29, 35, 50, 58, and 88%, respectively. Among individual symptoms and signs, only thrush conferred a poorer prognosis (odds ratio = 5.80; 95% confidence interval, 2.93, 11.39, p less than 0.001, Mantel-Byar analysis). The risk of AIDS persists 10 years after the onset of LAS. The AIDS incidence is related directly to T-helper cell depletion; with the exception of thrush, the presence or absence of symptoms and signs appears to be of lesser prognostic significance.

AIDS-Related Complex

Unexplained rabies in three immigrants in the United States. A virologic investigation.

BACKGROUND: Extensive investigation of three patients who died of rabies in the United States failed to reveal any source of exposure to the disease. The three patients had immigrated to the United States from areas in Laos, the Philippines, and Mexico where rabies is endemic. METHODS: We studied rabies viruses isolated from the three patients, other patients with a known source of exposure, and animals in the United States, Thailand (as a proxy for Laos), the Philippines, and Mexico. The viruses were characterized by indirect immunofluorescence and neutralization tests according to their reactions to panels of monoclonal antibodies. Transcribed complementary DNA from these isolates was amplified by the polymerase chain reaction; the DNA product was then analyzed by differential digestion with restriction enzymes. RESULTS: The viral isolate from each of the three patients was a rabies variant with distinctive antigenic or genetic characteristics. For each of the three isolates, identical variants were found in specimens from rabid animals obtained from or near the country in which the patient lived before immigrating to the United States. None of these variants were found among the isolates collected from rabid animals in the United States. CONCLUSIONS: Rabies infection in these three patients did not originate in the United States but resulted from exposures in Laos, the Philippines, and Mexico. Since the three patients had lived in the United States for 4 years, 6 years, and 11 months, our findings suggest that the onset of the clinical manifestations of rabies occurred after long incubation periods.

Adolescent

Epidemiology of rickettsial diseases.

Rickettsial diseases have a diversity of epidemiologic characteristics reflective of the variety of ecologic situations in which the obligate intracellular bacteria are transmitted to humans. For the spotted fever group (SFG) rickettsiae, Rickettsia typhi, R. tsutsugamushi, Coxiella burnetii, and the human ehrlichial agent, humans are a dead-end host who plays no role in the maintenance of the organism in nature. All rickettsioses exist as zoonoses. Moreover, all rickettsiae are found in infected arthopods, which generally serve as the natural hosts and can transmit the infection to the next generation of ticks, mites, chiggers, or fleas. From our anthropocentric viewpoint, Q fever aerosol infection from parturient animals and Brill-Zinsser disease ignited epidemics of louse-borne epidemic typhus are exceptions. However, silent cycles of C. burnetii in ticks and R. prowazekii in the flying squirrel flea may have maintained these agents in transovarial or enzootic cycles for eons before humans and their domestic animals arrived on the scene. Thus, the epidemiology of rickettsial diseases must be recognized as an unfortunate aberration of the rickettsial economy. Several excellent reviews of rickettsial ecology contain a wealth of useful information.

Animals

Pre-exposure rabies prophylaxis for travellers: are the benefits worth the cost?

Pre-exposure rabies prophylaxis is recommended by the Immunization Practices Advisory Committee of the US Public Health Services (PHS) as a safe and effective method for reducing the risk of rabies in international travellers. The United States Peace Corps provides pre-exposure prophylaxis with human diploid cell rabies vaccine (HDCV) to over 2000 new volunteers each year going to rabies-endemic countries. During the year November 1987 through October 1988, 175 rabies exposures (and no deaths) were documented in Peace Corps Volunteers serving in 31 rabies-endemic countries, for an overall postexposure treatment rate of 43.6/1000 volunteers per year. Although PHS treatment protocols were strictly followed, the postexposure prophylaxis rate for these Peace Corps Volunteers was 550 times higher than that for the US general population, and 55 times higher than the average rate for 30 developing countries. The use of pre-exposure prophylaxis in travellers was not cost-effective and will not become so until the price of a dose of vaccine declines substantially to $7.00 for the Peace Corps, and even lower for groups with less rabies exposure. However, despite the high vaccine cost, pre-exposure prophylaxis continues to be recommended in the Peace Corps for important non-economic reasons which may also be applicable to other groups of travellers.

Cost-Benefit Analysis

One-year study of the 2-1-1 intramuscular postexposure rabies vaccine regimen in 100 severely exposed Thai patients using rabies immune globulin and Vero cell rabies vaccine.

The 2-1-1 rabies postexposure treatment schedule is an abbreviated regimen in which a tissue culture rabies vaccine is administered intramuscularly at two sites on day 0, and at one site on days 7 and 21. Compared to the standard five-dose intramuscular regimen, the 2-1-1 schedule reduces the number of clinic visits from five to three and the amount of vaccine used by 20%. One hundred Thai patients, who were severely exposed to rabies, were treated with rabies immune globulin and the 2-1-1 regimen using purified Vero cell rabies vaccine. They were followed for 1 year. Rabies antibody titres were measured in 10% of this group. All patients survived and adverse reactions were mild. A satisfactory antibody response (a titre greater than 0.5 IU ml-1) occurred in all ten patients studied at day 14, but persisted for 90 days in 80% and for 360 days in only 50%. The authors therefore do not recommend use of the 2-1-1 schedule in severely exposed patients who also need to receive rabies immune globulin.

Adolescent

Rabies control in the Republic of the Philippines: benefits and costs of elimination.

We compared the benefits and costs of eliminating animal and human rabies in the Philippines. If rabies had been eliminated in 1988, economic benefits would total P52.8 (US$2.5) million in 1989. These benefits would largely arise from the abolition of expenses associated with rabies prevention: P29.7 (US$1.4) million for animal vaccination, P21.6 (US$1.0) million for human postexposure prophylaxis, and P0.3 (US$0.02) million for animal rabies examinations. Benefits also included P1.2 (US$0.06) million in additional earnings of humans whose death due to rabies would be prevented. Nationwide elimination was estimated to cost between P88.1 (US$4.2) million and P317.2 (US$15.0) million, assuming a canine-to-human ratio of 1:10, vaccine coverage of 60%, and a cost per vaccination of no less than P25 (US$1.19) and no more than P90 (US$4.27). These costs would be recouped 4.1-11.0 years after the initiation of a one-year elimination campaign. A sensitivity analysis showed that an elimination programme would be economically beneficial in all but the most extreme cases.

Animals

Serologic diagnosis of human ehrlichiosis using two Ehrlichia canis isolates.

Ehrlichia canis or a closely related rickettsial organism has been implicated serologically and morphologically as the causative agent of human ehrlichiosis in the United States. Although E. canis has been serially propagated in primary canine monocytes, only a limited quantity of antigen is obtained by this method. A continuous canine macrophage cell line, DH82, supports the growth of a new isolate of E. canis established from the whole blood of a carrier dog in Oklahoma. Serologic comparison of the Oklahoma isolate in the continuous canine cell line with a Florida isolate in commercial antigen slides revealed 100% specificity and 87.5% sensitivity.

Animals

An outbreak of cat-associated Q fever in the United States.

Q fever is usually acquired by contact with aerosols generated during parturition of domestic ungulates (e.g., sheep, cows, goats). In the maritime provinces of Canada, parturient cats have also been implicated in its transmission. A 66-year-old woman from eastern Maine developed high fever, rigors, headache, myalgias, pulmonary infiltrates, and elevated hepatocellular enzymes, and the diagnosis of acute Q fever was confirmed serologically. She and 14 other family members had attended a family reunion in Maine 2 weeks earlier, when they were exposed to a parturient cat. All 11 adults and older children attending the reunion developed symptoms consistent with acute Q fever. Serum samples were obtained from 10 who attended the reunion and 8 who did not attend. Titers greater than or equal to 1:64 to Coxiella burnetii were present in all who attended the reunion but in none of those who did not. Cat-associated Q fever should be considered when sporadic cases of the disease occur in the United States.

Adolescent

Isolation and characterization of an Ehrlichia sp. from a patient diagnosed with human ehrlichiosis.

A new disease was recognized in the United States in 1986. The etiologic agent, although not previously isolated from a human, appeared to be serologically related to Ehrlichia canis, a canine leukotropic rickettsia. We obtained blood specimens from 27 febrile patients with a history of tick exposure. Leukocytes from 24 patients not treated with tetracycline were placed onto a monolayer of DH82 cells. We performed indirect immunofluorescence on sera from all 27 febrile patients as well as sera from 12 patients with previously diagnosed ehrlichiosis. Intractoplasmic inclusions were first observed in culture 35 days after the addition of infected blood from one patient. Partial sequencing of the rRNAs from the human isolate and E. canis indicated that they are 98.7% related. Positive indirect immunofluorescence reactions to the human isolate were obtained for all 12 previously diagnosed patients and for 33% of the 27 febrile patients. Two patients were seropositive for the human isolate but not for E. canis. No sera were positive for E. canis and negative for the human isolate. We report the isolation of a previously unrecognized Ehrlichia sp. that appears to be the etiologic agent of human ehrlichiosis. Serologic data (range of antibody titers, 256 to 32,768) in combination with rRNA sequencing indicated that the newly isolated Ehrlichia sp. is similar, but not identical, to E. canis.

Adult