Antibody response to human immunodeficiency virus in homosexual men. Relation of antibody specificity, titer, and isotype to clinical status, severity of immunodeficiency, and disease progression.

The titers and isotypes of antibodies to specific proteins of the human immunodeficiency virus were determined by Western blot analysis of sera from 107 homosexual men. Antibody titers were generally lower in sera from patients with the acquired immunodeficiency syndrome (AIDS) and in sera from men whose condition subsequently progressed to AIDS than in sera from men who had not progressed to AIDS. We found no evidence of isotypic prominence or restriction of the antibody response. In multivariate analysis, lower levels of CD4 helper cells were most highly associated with progression to AIDS. Lower antibody titers to the envelope protein gp110, the core protein p24, and the reverse transcriptase enzyme p51/65 were also predictive of progression to AIDS independent of their association with CD4 cell levels. These data suggest that differences in antibody levels are not simply a consequence of severe immunodeficiency but may be markers for control of infection.

Bacterial meningitis in the absence of CSF pleocytosis.

Two cases of acute bacterial meningitis occurred with an absent CSF WBC response. To determine the incidence and clinical characteristics of such patients, 50 consecutive cases of meningitis were reviewed retrospectively. In addition to the two initially noted cases, five additional cases were found. In the seven cases, there were six or fewer cells, but bacteria were detected in the CSF. A distinctive clinical and laboratory syndrome emerged. All seven patients were either old or had Hodgkin's disease or severe alcoholism. All patients had evidence of an overwhelming infection with confusion or nuchal rigidity. As compared with the remaining 45 patients with meningitis and CSF pleocytosis, no fever (less than 38 degrees C), a lower peripheral WBC count, and near-normal CSF glucose and protein concentrations were common. Organisms involved were EScherichia coli in three patients, Pneumococcus in three patients, and mixed anaerobes in patient. A fatal outcome ensued in six of seven patients. Despite the correct choice of an antibacterial agent, doses were late and suboptimal for meningitis. This syndrome is surprisingly common in host-defective cases, has an ominous prognosis, and must be treated expectantly with antimicrobial agents that enter the CSF.

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.

Community outbreak of thyrotoxicosis: epidemiology, immunogenetic characteristics, and long-term outcome.

Between January and March 1984, the first community outbreak of transient thyrotoxicosis in the United States was documented in a seven-county area of southeastern Nebraska; 36 of the total 49 patients resided in York County (2.4 cases per 1,000 population). The median age of patients was 36 years, range six to 82 years; 51 percent were women. By definition, all patients were symptomatic, visited a physician, and had a newly identified elevated serum concentration of thyroxine or triiodothyronine of unknown cause. None had a goiter or a painful thyroid gland. Low 131I uptake measurements were found in all nine patients studied. Six patients were hospitalized; none died. Investigation of all 12 household contacts of eight selected patients revealed five additional persons with thyrotoxicosis and four with asymptomatic hyperthyroxinemia. A case-control study revealed that illness was associated with a significantly higher frequency of a reported recent respiratory viral-like condition. In another case-control study, the HLA-DR3 antigen was present in more case subjects (39 percent) than control subjects (14 percent). In addition, a significantly higher proportion of patients than control subjects purchased beef from one of the three supermarkets in York Country. Concomitant with the outbreak, the supermarket implicated in the outbreak purchased an unusually large quantity of beef (7,000 pounds) from a nonregular supplier in Nebraska, which had reportedly instituted the practice of trimming gullets (a procedure that removes the muscles from bovine larynx for beef) about three months earlier. Thus, it is concluded that the Nebraska outbreak, like one in Minnesota that occurred 18 months later, probably resulted from patients having eaten ground beef that was contaminated with bovine thyroid gland. This form of thyrotoxicosis, perhaps misdiagnosed as painless thyroiditis in the past, probably represents a previously under-recognized public health problem.

Rabies.

Human rabies is extremely rare and canine rabies is largely controlled in the United States. Wild animals are now responsible for most of the rabies prevention costs and postexposure treatments in the United States, either by direct exposure of humans or by exposure of domestic animals. Although the situation is similar in most other developed countries, canine rabies remains widespread and a substantial risk to persons traveling in developing countries, where millions of people are exposed and tens of thousands die of rabies each year. People living in the United States should be advised to avoid contact with wild animals and stray or ill-appearing domestic animals. Travelers to rabies enzootic countries can substantially reduce the risk of rabies exposures by avoiding all dogs as well as wild animals; those persons whose risk of exposure cannot be reduced should be educated about rabies and should receive preexposure vaccination.

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.

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.

National surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic summary and evaluation of risk factors for fatal outcome.

Between 1981 and 1992, the Centers for Disease Control collected and summarized 9,223 cases of Rocky Mountain spotted fever (RMSF) reported from 46 states. Four states (North Carolina, Oklahoma, Tennessee, and South Carolina) accounted for 48% of the reports. The annual incidence per million U.S. population decreased from a high in 1981 of 5.2 to a low in 1992 of 2.0, primarily due to decreased incidence in the southeast. Case report forms were filed on 7,650 patients, of whom 4,217 had laboratory-confirmed RMSF. The age group with the highest incidence was those 5-9 years of age. Most cases (90.0%) occurred between April 1 and September 30 and included a history of tick attachment (59.6%). Reported symptoms included fever (94.0%), headache (86.2%), myalgia (82.5%), and rash (80.2%). The case-fatality ratio was 4.0%. Risk factors associated with death included older age, delay in treatment or no treatment, and treatment with chloramphenicol (compared with tetracycline); however, insufficient data existed to fully assess the confounding effect of severity of illness on antibiotic choice.

Pre-exposure rabies immunization with human diploid cell vaccine: decreased antibody responses in persons immunized in developing countries.

In November 1982, a U.S. Peace Corps volunteer in Kenya completed pre-exposure rabies prophylaxis with a standard 3 dose intradermal (ID) series of human diploid cell rabies vaccine (HDCV). In May 1983, she was bitten by a dog and died of rabies 3 months later. An initial investigation revealed that the patient, as well as 9 of 11 others immunized at the same time, had no rabies antibody titers (less than 1:5). We therefore instituted investigations into the immunogenicity of pre-exposure HDCV both in the United States and in developing countries. A serosurvey revealed unexpectedly low rabies titers in both Peace Corps volunteers and others immunized in developing countries. Antibody titers measured 2-3 weeks after ID immunization were compared in 9 groups totaling 271 persons in the United States and Kenya. There was no statistically significant difference in antibody titers in the 6 U.S. groups immunized from 1980-1984 (P greater than 0.15); however, groups immunized in the United States had significantly higher titers than a group of Kenyan nationals (P less than or equal to 0.0001), and the Kenyans had significantly higher titers than 2 Peace Corps groups immunized in Kenya (P less than or equal to 0.0001). No single hypothesis proposed (laboratory error, vaccine potency, vaccination technique, or specific immune suppression) accounted for the observed differences. Although we cannot fully explain the poor response to HDCV, it is probably due to multiple factors. We conclude that persons immunized with ID pre-exposure HDCV in developing countries should have rabies antibody titers determined to ensure their seroconversion; for persons immunized in the United States, such titers need not be routinely determined.

The early kinetics of the neutralizing antibody response after booster immunizations with human diploid cell rabies vaccine.

Persons immunized in developing countries were recently shown to have low titers after pre-exposure immunization with human diploid cell rabies vaccine (HDCV). An investigation into the response to HDCV boosters was conducted to determine if immunologic sensitization had occurred and if there was a response difference in persons immunized in and outside of the United States. Intramuscular (im) booster doses of vaccine were administered to 113 persons previously immunized outside the United States and 47 persons immunized in the United States. The post-exposure booster regimen of a single 1.0-ml im booster, as recommended by the World Health Organization for all but the most severe bites, produced a one-dilution (5-fold) rise in antibody titer in 14 (11%) of 123 persons tested 5 days after booster and in 56 (89%) of 63 persons studied 7 days after booster. Persons immunized in the United States and those immunized outside the United States had similar responses. Persons with low pre-booster titers were more likely to exhibit a 5-fold rise in antibody titer 5 days after booster (P = 0.03) than persons with higher pre-booster titers. The post-exposure booster regimen of 2 1.0-ml im doses (one each on days 0 and 3), recommended in the United States, produced a more rapid response than the single booster regimen in only some persons; a 5-fold response occurred in 6 (50%) of 12 persons 5 days after booster.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

A cluster of tick-borne infections: association with military training and asymptomatic infections due to Rickettsia rickettsii.

During the spring of 1989, 86 members of a military unit from the state of Maryland, USA, participated in two-week-long training manoeuvres in the states of Arkansas (location FC) and Virginia (location FAPH). Acute febrile illnesses due to infections with two tick-borne pathogens, Rickettsia rickettsii and Ehrlichia sp., were confirmed serologically in 2 initial cases who were admitted to the hospital. A seroepidemiological investigation among unit members found an additional 17 of 109 individuals (16%) with elevated post-exposure indirect immunofluorescent antibody (IFA) titres to R. rickettsii (16 cases) and/or E. canis (2 cases). The seropositivity rate of personnel who trained at FC was 38% (15 of 40), compared to only 13% (4 of 31) and 8% (3 of 38) of personnel who trained at FAPH or who did not train in the field, respectively (P < 0.001). Seropositivity was associated with symptoms suggestive of a tick-borne illness. Only 4 (22%) and 6 (33%) of the 18 personnel seropositive for R. rickettsii reported an erythematous or petechial type of rash or a febrile illness, respectively, within 4 weeks of exposure; 5 of 18 (28%) personnel infected with R. rickettsii reported no symptoms and only 8 of 18 (44%) received medical treatment. Mild infections with R. rickettsii, or a closely related spotted fever group agent, may have accounted for the high infection rate experienced by this group.

Rabies in rodents and lagomorphs in the United States, 1971-1984: increased cases in the woodchuck (Marmota monax) in mid-Atlantic states.

A review of surveillance data on animal rabies from the Centers for Disease Control revealed 104 cases of rabies in rodents and lagomorphs for 1971 through 1984 in the United States; 80% of these were reported between 1980 and 1984. Woodchucks (Marmota monax) accounted for 64% of the cases. Most of the cases of rabies in woodchucks were associated with an epizootic of rabies in raccoons (Procyon lotor) in the mid-Atlantic states. In rabies endemic areas, humans exposed to woodchucks should receive rabies postexposure prophylaxis if the animal is not available for testing. The decision to administer postexposure prophylaxis to humans exposed to other rodents and lagomorphs should take into consideration the epidemiology of rabies in the exposing species.

Epidemiologic factors, clinical findings, and vaccination status of rabies in cats and dogs in the United States in 1988. National Study Group on Rabies.

Despite the availability of rabies vaccination through private veterinarians and government-sponsored rabies control programs, rabies was reported in an average of 338 cats and dogs per year from 1980 through 1987 in the United States. Information was collected on 90% of the 183 cats and 97% of the 119 dogs that were reported to have rabies in the continental United States in 1988. The median age of rabid cats and dogs was 1 year, and 81% were from rural areas. Compared with rabid cats, rabid dogs were more likely to have been male (66 vs 42%, odds ratio = 2.6), to have been kept as pets (84 vs 43%, odds ratio = 6.8), and to have had reported contact with wildlife before onset of illness (38 vs 14%, odds ratio = 3.8). Rabid cats accounted for a greater proportion of human rabies postexposure prophylaxis, bites to people, and exposures to other animals than did rabid dogs. Although the clinical signs of rabies varied, rabid cats were more likely than dogs to have had aggressive behavior (55 vs 31%, odds ratio = 2.8). In contrast, rabid dogs were more likely than cats to have had an illness consistent with a paralytic process. The median period between onset of illness and death was 3 days (range, less than 1 to 10) in rabid cats and dogs that were allowed to die of rabies. Vaccine failures were documented in 3 (1%) rabid animals (2 cats and 1 dog). All animals had received only a single dose of vaccine in their lifetime and were vaccinated when they were between 3 and 6 months old.

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.

Rabies surveillance in the United States during 1989.

In 1989, 4,808 cases of rabies in animals other than human beings were reported to the Centers for Disease Control, 1.8% more (4,724 to 4,808) than in 1988. Eighty-eight percent (4,224/4,808) of those affected were wild animals and 12% (584/4,808) were domestic animals. Cases were reported from 49 states, the District of Columbia, and Puerto Rico; Hawaii remained rabies-free. Skunks (1,657) continued to be the most commonly reported rabid wild animal. For the second consecutive year, more cats (212) were reported to be infected with rabies virus than any other domestic species. Compared with their 1988 reports, 5 states reported increases of greater than 100% (Alaska, 109%; New Jersey, 233%; Ohio, 133%; Oklahoma, 168%; and Washington, 125%), and 5 states reported decreases of greater than 50% (Connecticut, 63%; Mississippi, 56%; Montana, 67%; Nevada, 55%; and West Virginia, 53%) in 1989.

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.

Rabies prevention in primary care. A four-step approach.

Although most physicians in the United States have not seen a person with rabies, the primary care physician is often confronted with a patient who has been bitten by an animal capable of transmitting rabies virus. Rabies is almost always transmitted by a bite; licks and other nonbite exposures hardly ever cause the disease. The control of rabies in domestic animals has greatly reduced the risk of human disease following the bite of a dog or cat, but rabies in wild animals (especially skunks and raccoons) remains a constant threat. By obtaining epidemiologic information about animal rabies in the area where the exposure occurred, the physician can determine whether the animal in question may have been rabid. If any question remains, owned dogs and cats should be observed for ten days and any other animal should be killed and its brain examined for rabies virus. When postexposure prophylaxis is indicated, it should be administered exactly as recommended herein.

Human ehrlichiosis.

Ehrlichiosis is one of the latest tick-borne illnesses to be reported in humans. The authors describe two cases of this rickettsial disease that were apparently acquired in Missouri. They discuss diagnosis and treatment.