Seroepidemiology of infections due to spotted fever group rickettsiae and Ehrlichia species in military personnel exposed in areas of the United States where such infections are endemic.

A prospective, seroepidemiologic study of spotted fever group rickettsiae (SFGR) and Ehrlichia infections was done among 1194 US military personnel exposed in a heavily tick-infested area of Arkansas in 1990. Seroconversion (4-fold) and seroprevalence rates were determined by indirect immunofluorescent antibody assays. Seroconversions to SFGR occurred in 30 persons (2.5%), whereas seroconversion to Ehrlichia species occurred in 15 (1.3%). The majority of seroconverters did not report symptoms (22/30 [73%] of SFGR seroconverters; 10/15 [67%] of Ehrlichia species seroconverters). History of tick attachment was associated with seroconversion to SFGR (relative risk [RR] = 4.3, P < .001) and Ehrlichia species (RR = 3.6, P < .05). Use of permethrin-impregnated uniforms significantly decreased risk of infection (P < .01); use of bed nets increased risk by 4-fold. Tickborne infections represent a significant threat to military personnel training in areas in which these infections are endemic.

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.

Immunogenicity of rabies vaccines used during an urban epizootic of rabies in Mexico.

From 1 July 1987 to 31 December 1988, 30% of 247 rabid dogs in Hermosillo, Mexico had a positive history of rabies vaccination. Serosurveys suggested that inactivated suckling mouse brain vaccine (INACT-SMBV) and inactivated tissue culture vaccine (INACT-TC) used before and during the epizootic were poor immunogens. Prospective studies showed that only about one-third of dogs vaccinated with INACT-SMBV were seropositive 5 weeks after vaccination. Lack of vaccine potency was the most likely cause of poor immunogenicity. Rabies vaccines should be evaluated periodically by measuring antibody responses in animals. In some circumstances, minimum seroconversion rates and antibody titres in vaccinated animals may be better measures of immunogenicity than relative potency.

Evaluation of specificity of indirect enzyme-linked immunosorbent assay for diagnosis of human Q fever.

Ninety-five acute- and convalescent-phase serum specimens from 48 patients suspected of having rickettsial or Legionella infections were assayed for antibodies to Coxiella burnetii, the causative agent of Q fever. To evaluate the specificity of the indirect enzyme-linked immunosorbent assay (ELISA) for human Q fever, we compared the ELISA results with those of the indirect immunofluorescence antibody (IFA) test. The ELISA data were analyzed by two different criteria for a positive test. The first criterion for positive results by ELISA was based upon diagnostic titers established in a study of 150 subjects who had no demonstrable cellular or humoral immune responses to C. burnetii phase I or phase II whole cells or phase I lipopolysaccharide. The second criterion was based upon diagnostic antibody titers in a study of 51 subjects who had been diagnosed as having clinical Q fever and had fourfold or greater rises in humoral immune responses to C. burnetii phase I and phase II whole-cell antigens. A comparison of the ELISA and IFA test results of the 95 serum specimens indicated excellent agreement between the tests (Kappa = 92.9%; P < 0.05). None of the 38 patients whose etiologies were confirmed serologically as Legionnaires' disease or rickettsial diseases other than Q fever were classified as positive for C. burnetii by the ELISA. Only one patient identified by the IFA test as having Q fever was not scored positive by the ELISA. These results suggest that the ELISA is useful for epidemiologic screening and as a diagnostic test for human Q fever.

Human ehrlichiosis in the United States, 1985 to 1990.

OBJECTIVE: To describe the epidemiology, clinical features, laboratory manifestations, response to therapy, and factors related to morbidity and mortality in a large group of patients with ehrlichiosis. DESIGN: Case-series. SETTING: Laboratory-based surveillance in the United States. PATIENTS: 237 patients whose serum had a fourfold increase or decrease in antibodies to Ehrlichia canis or E. chaffeensis. MEASUREMENTS: Epidemiologic, clinical, laboratory data, hospitalization, duration of illness, complications, and treatment response. RESULTS: From 1985 through 1990, 237 case-patients were identified in 21 states; rates exceeded 1 per 100,000 per year in only 5 counties. Incidence rates increased with age and were higher among men. Most case-patients had nonspecific illness and were not suspected of having a rickettsial infection. Many patients (60.8%) were hospitalized. Leukocyte and platelet counts typically decreased and liver function tests typically increased through day 7. Three (6.1%) of 49 outpatients treated only with tetracycline were hospitalized compared with 35 (92%) of 38 outpatients treated only with antibiotics other than tetracycline or chloramphenicol (P < 0.001). Among hospitalized patients, recovery was faster for those initially treated with tetracycline (median, 16 days) or chloramphenicol (median, 12 days) than for those initially treated with other antibiotics (median, 27 days; P = 0.03 for both comparisons). In a logistic regression analysis, severe illness or death was more probable among case-patients 60 years or older (odds ratio [OR], 4.60; 95% CI, 1.87 to 11.2) and among those who did not receive tetracycline or chloramphenicol until 8 or more days after symptom onset (OR, 4.38; CI, 1.36 to 14.0). CONCLUSIONS: The findings of this study are primarily representative of more seriously ill patients with human ehrlichiosis. Although rates are low, ehrlichiosis is found in many areas of the United States. Patients with a history of tick exposure, acute febrile illness, decreasing leukocyte counts, and decreasing platelet counts may have ehrlichiosis. Prompt treatment with tetracycline or chloramphenicol markedly decreases the morbidity.

Risk factors for systemic hypersensitivity reactions after booster vaccinations with human diploid cell rabies vaccine: a nationwide prospective study.

To determine the incidence of and risk factors for adverse reactions following the boosters, we conducted a nationwide prospective study of persons receiving pre-exposure booster vaccination with human diploid cell rabies vaccine (HDCV). Persons who had previously received three pre-exposure doses of HDCV and whose rabies neutralizing antibody titres were < or = 1:5 were enrolled in the study if they stated that they intended to receive a booster. Of the 98 persons enrolled in the study, 40 (41%) were in risk groups for whom boosters are not recommended. Three (3%) of 98 developed generalized urticaria or wheezing within 1 day of receiving boosters and three others (3%) developed urticaria 6 to 14 days after the booster. No differences were found between individuals with reactions (either type) and those with no adverse reaction according to age, gender, occupation, history of previous allergies, or time since or route of primary vaccination. Reactions were somewhat more common among persons who received primary vaccinations by the intramuscular route (i.m.) and booster vaccinations by the intradermal route (i.d.) (3/15, 20%) or primary vaccinations i.d. and booster vaccinations i.m. (2/10, 20%), and somewhat less common among persons who received both these vaccinations i.d. (1/52, 2%) or i.m. (0/7). The number of persons who develop allergic reactions may be minimized by administering vaccinations only when vaccination is strictly indicated. The influence of the route of primary and booster vaccinations on the development of reactions deserves further study.

Urban epizootic of rabies in Mexico: epidemiology and impact of animal bite injuries.

From 1 July 1987 to 31 December 1988, a total of 317 animals (91% of which were dogs) were confirmed to have rabies in Hermosillo, Mexico. The median age of rabid dogs was 1 year, 69% were male, and 98% were owned. The epizootic started in the southern areas of the city, rapidly involved the entire city, and persisted mainly in lower socioeconomic status areas. The area of the city and mean household size were significant predictor variables for the population density of rabid dogs around household clusters (Poisson linear regression, P < 0.001 and P = 0.03, resp). Approximately 2.5% of city residents were bitten by dogs in 1987, with the rate of reported dog bite injuries being positively correlated with mean household size and the proportion of households that owned dogs. Visits to the city health centre for evaluation of possible exposures to rabies increased by 135% after the start of the epizootic; approximately 273 per 100,000 city residents were administered a full or partial course of rabies post-exposure prophylaxis in 1987. Children were at greatest risk for exposures to rabies, accounting for 60% of all reported animal bite injuries evaluated at the health centre. Also they were more likely than older persons to have received bite injuries to the head, face, and neck (odds ratio = 21.6, 95% confidence interval = 5.4, 186.5).

PIP: Almost all cases of human rabies result from bites by rabid dogs. Controlling dog rabies is therefore crucial for humans. 317 animals, 91% of which were dogs, were confirmed to have rabies in Hermosillo, Mexico, from July 1, 1987, to December 31, 1988. The dogs were of median age 1 year, 69% were male, and 98% were owned. The epizootic started in the southern areas of the city, spread quickly through the city, and persisted largely in lower socioeconomic status areas. Approximately 2.5% of city residents were bitten by dogs in 1987, with the rate of reported dog bite injuries positively correlated with mean household size and the proportion of households which owned dogs. Visits to the city health center for evaluation of possible exposures to rabies increased by 135% after the start of the epizootic over which approximately 273 per 100,000 city residents were administered a full or partial course of rabies post-exposure prophylaxis in 1987. Comprising 60% of all reported animal bite injuries evaluated at the center, children were at greatest risk for exposures to rabies. Children were also more likely than older people to have received bite injuries to the head, face, and neck.

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.

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 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 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 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.

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.