Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.

BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. CONCLUSIONS: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. CLINICAL TRIALS REGISTRATION: NCT03341767.

Adaptive, growth-oriented, and positive perceptions of mother-daughter elder caregiving relationships: a path-analytic investigation of predictors.

One hundred twenty-two pairs (n = 244) of filial caregivers (daughters) and care recipients (mothers) were interviewed separately, to investigate the factors underlying positive, growth-oriented caregiving relationships. The outcome variable examined was the type of caregiving pair (positive, negative, mixed, and neutral), as determined by "blind" raters. Based on existing research, factors examined as being significant predictors of this outcome variable were perceived roles (role changes, role relations) and individual-difference characteristics (personality dimensions, fluid intellectual ability). The results of the path model tested support the importance of individual-difference factors in understanding positive mother-daughter elder caregiving relationships.

Antibodies for the prevention and treatment of viral diseases.

This paper reviews current use and evolving role of polyclonal and monoclonal antibody products for the prevention and treatment of viral diseases. Antibodies continue to be indicated for prophylaxis either prior to an anticipated exposure especially in situations of travel, or more commonly following an exposure. The predominant indication for use of antibody products is to prevent infection. With the availability of vaccines for the prevention of chickenpox, hepatitis A, hepatitis B, measles, rabies and smallpox, the role of passive immunization is reserved for susceptible individuals and those at high risk for complications of infection. Risks of transmission of infections associated with use of human plasma-derived products have been reduced by improvements in donor screening and virus removal and inactivation procedures. An additional safety concern has been addressed by the removal of thimerosal as a preservative. Within the last 5 years, two antibodies have been licensed for a viral indication, RespiGam and Synagis both for prevention of respiratory syncytial virus infection. RespiGam is a human plasma derived antibody and Synagis is a humanized monoclonal antibody, the first such antibody to be licensed for an infectious disease indication. CytoGam for prevention of cytomegalovirus infection in kidney transplant patients has recently been granted an expanded indication to include use in lung, liver, pancreas and heart transplant patients. As the use of therapeutics becomes more sophisticated, researchers may find better ways of using antibody products.

Potency of wild-type or sabin trivalent inactivated poliovirus vaccine, by enzyme-linked immunosorbent assay using monoclonal antibiotics specific for each antigenic site.

Potency testing of inactivated poliovirus vaccine (IPV) is hampered by the absence of a standardized in vitro test, as well as the lack of a generally accepted quantitative animal test. In vitro tests must be able to measure selectively the content of the "D" antigen in the vaccine which includes virus neutralizing antibodies. We tested 12 poliovirus type 1, 12 type 2 and six type 3, D antigen-specific monoclonal mouse antibodies (mAb) for use in the enzyme-linked immunosorbent assay (ELISA). We characterized the site-specific reactivities of three mAbs, one for each poliovirus type. The reactivity of the complete mAb panel encompassed the important antigenic sites on the virus surface of each of the poliovirus serotypes. Some of the mAbs were cross-reactive between wild-type and Sabin strain IPV. At least one mAb of each poliovirus type that was D antigen-specific and reacted with both wild-type and Sabin IPV was directed against an antigenic site thought to be immunogenic in humans. These reagents may be useful for improved standardization of the ELISA for IPV.

Natural variation in a Drosophila clock gene and temperature compensation.

The threonine-glycine (Thr-Gly) encoding repeat within the clock gene period of Drosophila melanogaster is polymorphic in length. The two major variants (Thr-Gly)17 and (Thr-Gly)20 are distributed as a highly significant latitudinal cline in Europe and North Africa. Thr-Gly length variation from both wild-caught and transgenic individuals is related to the flies' ability to maintain a circadian period at different temperatures. This phenomenon provides a selective explanation for the geographical distribution of Thr-Gly lengths and gives a rare glimpse of the interplay between molecular polymorphism, behavior, population biology, and natural selection.

Resistance of previously infected chimpanzees to successive challenges with a heterologous intraclade B strain of human immunodeficiency virus type 1.

To test whether the protective effects of attenuated simian immunodeficiency virus vaccines in macaques were applicable to the human immunodeficiency virus type 1 (HIV-1)-chimpanzee system, two groups of animals, previously infected with HIV-1(IIIB) or HIV-1(SF2) were each challenged with a heterologous clade B virus, HIV-1(DH12). Following challenge, the parameters measured included virus isolation (from plasma, peripheral blood mononuclear cells, and lymph node tissue); quantitative DNA PCR using primers capable of distinguishing HIV-1(IIIB), HIV-1(SF2), and HIV-1(DH12) from one another; and serologic assays to monitor changes in binding and neutralizing antibodies. In contrast to an HIV-1-naive chimpanzee that rapidly became infected following the inoculation of HIV-1(DH12), the two chimpanzees previously infected with HIV-1(IIIB) resisted repeated and escalating inoculations of HIV-1(DH12), as monitored by virus isolation and PCR. The two animals previously infected with HIV-1(SF2) became infected with HIV-1(DH12) but in contrast to the case with the HIV-1-naive chimpanzee, no cell-free viral RNA was detected in the plasma by the branched DNA procedure and levels of peripheral blood mononuclear cell-associated viral DNA were reduced 35- to 50-fold.

Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: poliovirus vaccination.

Inactivated and trivalent oral poliovirus vaccines contain either formalin-inactivated or live, attenuated poliovirus, respectively, of the three serotypes. Interference among the three attenuated poliovirus serotypes was minimized with a "balanced-formulation" vaccine, and serologic responses after IPV were optimized by adjusting the antigenic content of each inactivated poliovirus serotype. Seroconversion is dependent on both the relative content as well as the absolute quantity of virus in the vaccine. The "gold standard" method to assess humoral antibody responses following vaccination is the neutralization assay. Any detectable titer of neutralizing antibody against poliovirus is considered protective against clinical paralytic diseases. Recently, standard procedures were adopted for conducting neutralization assays. Efforts are being undertaken now to develop a combined diphtheria and tetanus toxoids and pertussis vaccine and IPV vaccine in the United States using a dual-chambered syringe that mixes the content of both vaccines at the time of injection; this approach is necessary to overcome the potential detrimental effect of thimerosal on IPV (the preservative in DTP). Other vaccines that combine DTP and/or Haemophilus influenzae type b and/or hepatitis B with IPV appear feasible but require further investigation. New combination vaccines should induce similar or superior levels of neutralizing antibody in serum for individual protection against paralytic disease and mucosal immunity that effectively decreases viral replication in the intestine and pharynx for population protection against transmission of poliovirus.

A WHO Collaborative study on assays of the antigenic content of inactivated poliovirus vaccines.

In the first phase of a two part WHO Collaborative study, fourteen laboratories from ten countries estimated the antigenic content of six trivalent inactivated poliovirus vaccine preparations using in vitro methods. All laboratories used a candidate standard method for D antigen assay (method A) and eight contributed results from established 'in-house' methods (method B). All methods assayed D antigen in an antigen capture ELISA format. Monoclonal antibodies were used as detector reagents in method A and in some laboratories for method B. The average difference in potency estimates for duplicate preparations A and C was used to assess within assay variation. Overall this was found to be 22% and 19% for methods A and B respectively. Within laboratory variation was measured as the geometric coefficient of variation for between assay repeatability. Results for methods A and B, 28% and 26% respectively were again very similar. Variation in potency estimates between laboratories was in the range 2- to 5-fold for most samples and most laboratories irrespective of the method used. However, a maximum 24-fold difference occurred when all results were taken into account. Method A gave significantly enhanced potency estimates for the type 3 component of preparation B, a vaccine shown to be immunogenic in humans in clinical trials, compared to method B. Method A also failed to assay the type 3 component of preparation F which was prepared by inactivation of the Sabin 3 strain of poliovirus. Further work is required to identify monoclonal antibodies, or combinations of monoclonal antibodies, suitable for universal application in D antigen assays of inactivated poliovirus vaccines. Further work is also required to improve control of the antigen-capture ELISA in some laboratories. The second phase of this WHO Collaborative Study evaluated the proficiency of in vivo potency assays. These results together with an evaluation of the correlation of immunogenicity and antigenic assay plus assessment of candidate reference materials will be reported separately.

Deleterious effect of thimerosal on the potency of inactivated poliovirus vaccine.

High-potency inactivated poliovirus vaccine (eIPV) was combined with diphtheria-tetanus-pertussis (DTP) vaccine containing thimerosal as a preservative to simulate the performance of a potential tetravalent vaccine. Neither type 1 nor type 3 poliovirus antigens appeared to be affected by thimerosal after exposure for 1 h at 37 degrees C as measured by enzyme-linked immunosorbent assay (ELISA). One epitope on the type 2 antigen was damaged within 5 min of exposure; however, the overall potency was unchanged when measured using a polyclonal antibody preparation. Exposure to thimerosal at 37 degrees C decreased the potency of all three poliovirus types to well below the level caused by heat deterioration alone in 1-2 days and to 0% after 16-17 days. At 25 degrees C, the potency of type 1 poliovirus decreased by 46% in 1 day, whereas poliovirus types 2 and 3 were stable for 1 week. Storage of eIPV at 4 degrees C in the presence of thimerosal reduced the potency of type 1 poliovirus antigen to undetectable levels after 4-6 months. Type 2 and 3 antigens were less markedly affected by 8 months of exposure to thimerosal at 4 degrees C. The loss of potency of type 1 as measured by ELISA was paralleled by a reduced level of neutralizing antibodies in mice injected with these preparations. The results obtained from testing eIPV in combination with DTP and thimerosal were generally similar to those obtained using eIPV with thimerosal. It remains to be seen to what extent thimerosal will affect the immunogenicity of eIPV in humans when injected as combined eIPV-DTP vaccine.

Quantitation of D antigen content in inactivated poliovirus vaccine derived from wild-type or sabin strains.

The enzyme-linked immunosorbent assay (ELISA) is currently the in vitro method for the measurement of the D antigen content of inactivated poliovirus vaccines (IPV) of greatest interest. The sensitivity and specificity of the test is dependent on the antibodies selected for use. We evaluated monoclonal and polyclonal antibodies for specificity to D antigen and wild or attenuated (Sabin) strains used in vaccine production. When used as detection antibodies the types 1 and 2 monoclonal antibodies raised against wild-type poliovirus strains were D antigen-specific and cross-reactive with the corresponding Sabin strains. The type 3 monoclonal antibody was weakly cross-reactive with Sabin type 3 vaccine. In contrast, polyclonal antibodies were less D antigen-specific, but reacted equally well with wild-type and Sabin strain vaccines. The ELISA using monoclonal antibodies was shown to be highly reproducible. Reactivity with these monoclonal antibodies implies that a D-specific neutralizing epitope of each respective poliovirus type has been preserved in the inactivation process. Evaluation with additional neutralizing D antigen-specific monoclonal antibodies may be necessary to determine whether reactivity with one epitope of each type in an in vitro test is sufficient to predict potency of the vaccine in humans.

Antipyretic efficacy of ibuprofen vs acetaminophen.

OBJECTIVE: To compare the antipyretic efficacy of ibuprofen, placebo, and acetaminophen. DESIGN: Double-dummy, double-blind, randomized, placebo-controlled trial. SETTING: Emergency department and inpatient units of a large, metropolitan, university-based, children's hospital in Michigan. PARTICIPANTS: 37 otherwise healthy children aged 2 to 12 years with acute, intercurrent, febrile illness. INTERVENTIONS: Each child was randomly assigned to receive a single dose of acetaminophen (10 mg/kg), ibuprofen (7.5 or 10 mg/kg), or placebo. MEASUREMENTS/MAIN RESULTS: Oral temperature was measured before dosing, 30 minutes after dosing, and hourly thereafter for 8 hours after the dose. Patients were monitored for adverse effects during the study and 24 hours after administration of the assigned drug. All three active treatments produced significant antipyresis compared with placebo. Ibuprofen provided greater temperature decrement and longer duration of antipyresis than acetaminophen when the two drugs were administered in approximately equal doses. No adverse effects were observed in any treatment group. CONCLUSION: Ibuprofen is a potent antipyretic agent and is a safe alternative for the selected febrile child who may benefit from antipyretic medication but who either cannot take or does not achieve satisfactory antipyresis with acetaminophen.

Comparison of multidose ibuprofen and acetaminophen therapy in febrile children.

OBJECTIVE: To determine whether febrile children receiving 2.5-, 5-, or 10-mg/kg ibuprofen therapy via a liquid or 15-mg/kg acetaminophen therapy via an elixir every 6 hours for 24 to 48 hours show equivalent fever reduction or suffer adverse effects of the drug administered. DESIGN: Randomized, double-blind, multidose, parallel-group, variable-duration (24 to 48 hours) clinical trial. SETTING: The academically affiliated Children's Hospital in Columbus, Ohio. PARTICIPANTS: 64 febrile (defined as oral or rectal temperature of 39 degrees C to 40.5 degrees C) but otherwise healthy children aged 6 months to 11 years 7 months randomly assigned to one of the four drug regimens. INTERVENTIONS: Treatment with either ibuprofen or acetaminophen as described above. Administration of antibiotics or intravenous fluids was allowed only after at least 24 hours of treatment with the assigned drug. MEASUREMENTS/MAIN RESULTS: In 61 of the 64 evaluable patients, treatments were effective and well tolerated during the entire study. While the rates of temperature reduction and maximal reduction of fever after administration of the initial dose were equal for patients receiving 10-mg/kg ibuprofen therapy and 15-mg/kg acetaminophen therapy, and both regimens were more effective than smaller doses of ibuprofen in reducing fever, after the second dose (and continuing to the end of the study) there were no statistically significant differences in temperature response among the treatment groups. Six children were withdrawn from the study, two because of dosing errors, three because of hypothermia (temperature of less than 35.6 degrees C; all three patients were in the acetaminophen group), and one because of gastrointestinal distress (this child was in the group receiving 2.5-mg/kg ibuprofen therapy). No other significant symptoms or adverse laboratory or physical findings were noted. While further confirmatory studies are needed, ibuprofen liquid (10 mg/kg) and acetaminophen elixir (15 mg/kg) administered every 6 hours for 24 to 48 hours appeared to be most effective in reducing fever. These two regimens were equally effective and equally tolerated in febrile children. Lower ibuprofen doses (2.5 and 5 mg/kg) were less effective than acetaminophen and 10-mg/kg ibuprofen therapy after the initial dose but were at least equally effective as these two higher-dose regimens thereafter.

Variable infections with and serologic responses of rabbits to five different HIV-1 strains, including one neural tissue isolate.

The infectivity of different strains of HIV-1 in rabbits was investigated. The HIV-1RF and HIV-1MN inocula induced anti-envelope antibodies detectable by Western blot, and in the case of HIV-1RF, these antibodies were also detectable by ELISA. The peripheral blood lymphocytes (PBL) and lymph nodes from rabbits inoculated with HIV-1IIIB, HIV-1MN and HIV-1Z3, were positive for virus by culture and by polymerase chain reaction (PCR). HIV-1BRVA, originally isolated from a patient with AIDS dementia, infected the brain of the inoculated rabbit, as indicated by both virus culture and PCR. In this case PCR was positive using four different primer pairs. Throughout the study, rabbits showed no clinical signs of HIV-1 infection and no remarkable histopathology was observed in the tissues examined. The apparent differences in infectivity and tissue tropism of the five HIV-1 strains demonstrated here provide additional evidence that the rabbit may serve as a useful model for studying HIV-1 infection and pathogenesis.

Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.

Ninety-two children with juvenile rheumatoid arthritis were randomly assigned to treatment in a multicenter, double-blind, 12-week trial designed to compare the efficacy and safety of a liquid formulation of ibuprofen at a dosage of 30 to 40 mg/kg/day versus those of aspirin at a dosage of 60 to 80 mg/kg/day. No significant intergroup differences in response rates or in the amount of improvement in articular indexes of disease activity were observed. More children treated with aspirin discontinued treatment early because of adverse reactions. After this trial, 84 additional patients with juvenile rheumatoid arthritis entered a 24-week, multidose (30, 40, and 50 mg/kg/day), open trial of ibuprofen suspension. Favorable response rates for the three groups were similar, and continued improvement was observed throughout the 24-week period. A dose-response relationship was observed with respect to adverse reactions of the upper gastrointestinal tract. We conclude that ibuprofen suspension is an effective nonsteroidal antiinflammatory drug and that its tolerability in children is acceptable.

Effects of interferon-alpha in patients with AIDS-associated Kaposi's sarcoma are related to blood interferon levels and dose.

Definition of improved therapeutic regimens of interferon-alpha (IFN-alpha) for the treatment of Kaposi's sarcoma (KS) would be useful since currently recommended doses are sometimes associated with unacceptable toxicity. IFN concentrations were measured in serum samples from men with AIDS-associated KS who were enrolled in a trial of IFN-alpha alone (16 patients) or a trial of IFN-alpha combined with zidovudine (25 patients). Analyses were done to examine the relationship between the dose of IFN-alpha, blood level of IFN, and the patient's clinical response to treatment. There was no correlation between dose of zidovudine given and response. As expected, there was a high correlation between dose of IFN-alpha and blood level in both studies (p less than 0.001). Furthermore, we found relationships between clinical response and both dose of IFN-alpha and blood level achieved. In the two studies combined, among men with greater than 200 CD4+ cells/mm3 of blood at baseline on average daily doses of greater than or equal to 10 million international units (MIU) of IFN-alpha, 13/19 (68%) responded compared to 6/17 (35%) on less than MIU (p = 0.05). Similarly, of men with IFN blood levels greater than or equal to 100 IU/mL 12/16 (75%) responded compared to 7/20 (35%) of those with blood levels less than 100 IU/mL (p = 0.02). The dose and blood levels of IFN achieved and maintained may be important factors in determining responses of KS. Additional clinical trials of IFN-alpha treatment of KS at doses about 10 MIU/day appear warranted.

Possible beneficial effects of neutralizing antibodies and antibody-dependent, cell-mediated cytotoxicity in human immunodeficiency virus infection.

We studied the relationship between early human immunodeficiency virus type 1 (HIV-1) specific immune responses and pathogenesis of infection in participants enrolled in the multicenter AIDS cohort study (MACS). Sera collected at 6-month intervals for 2 years (visit 1-5) from 39 persons who seroconverted by enzyme-linked immunosorbent assay (ELISA) 6 months (visit 2) after enrollment were examined for isotype-specific Western blot reactivity, neutralizing antibodies (NA) against two divergent strains of HIV-1 (HIV-1IIIB and HIV-1RF), and for antibodies capable of participating in antibody-dependent, cell-mediated cytotoxicity (ADCC). These results were compared with changes in CD4+ cell number and episodes of lymphadenopathy. Twenty-five subjects had antibodies of at least one isotype reactive to at least one HIV-1 protein by Western blot at visit 1, before they became ELISA positive. NA reactive with HIV-1IIIB were detected before those reactive with HIV-1RF. NA were first observed in 11 sera at visit 2, in 22 sera at visit 3, and in 3 sera at visit 4; sera from three patients remained nonneutralizing through visit 5. In most cases, NA were detected after a decline in CD4+ cell numbers. The data are consistent with the interpretation that NA develop after about 16 to 18 months of declining CD4+ cell numbers, following which the rate of decline in CD4+ cell numbers slows. In contrast, HIV-1 envelope antigen-specific ADCC responses were first observed in 11 subjects at visit 1 when all 39 were NA and ELISA negative, in 12 subjects at visit 2, in 13 subjects at visit 3, and 1 subject at visit 4. Early ADCC responses were associated with high mean % CD4+ cell numbers and absence of lymphadenopathy throughout the 2-year observation period. Not all subjects who developed ADCC developed NA. In some subjects, ADCC and NA were detectable for the first time at the same visit, for others ADCC was detectable prior to NA, and for a few NA was detectable prior to ADCC. These findings suggest that ADCC and neutralization are mediated by different antibody populations, that they may partially inhibit the progress of HIV-1 infection, and that the late appearance of NA may relate to the failure of immunity to effect recovery from this infection.

An epidemic of acute hemorrhagic conjunctivitis in American Samoa caused by coxsackievirus A24 variant.

Between May 25 and July 5, 1986, an epidemic of acute hemorrhagic conjunctivitis affected an estimated 47% of the population on American Samoa. Coxsackievirus A24 variant was isolated from 18 of 22 patients. This is the first documented outbreak of acute hemorrhagic conjunctivitis due to coxsackievirus A24 variant outside of Southeast Asia and the Indian subcontinent. When this outbreak was compared with an outbreak on the island in 1981-1982 caused by enterovirus 70, conjunctival hemorrhage or injection and the severity of hemorrhage were less prevalent among cases in 1986, while upper respiratory and systemic symptoms were more common. Residents of traditional housing had significantly higher attack rates (48%) than residents of government housing (23%). Serum specimens collected from the residents of Samoa in 1985, before the outbreak, unexpectedly revealed the presence of neutralizing antibodies against coxsackievirus A24 variant. The presence of these antibodies correlated with protection against coxsackievirus A24 variant infection in this outbreak.

Combined zidovudine and interferon-alpha therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS)

STUDY OBJECTIVE: To evaluate the toxicity and potential clinical efficacy of combined therapy with zidovudine and interferon-alpha for patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). DESIGN: Nonrandomized, open trial study. SETTING: Outpatient clinic of a government referral-based research hospital. PATIENTS: Volunteer sample of 39 patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. INTERVENTIONS: Patients received zidovudine, 250, 100, or 50 mg orally every 4 hours; 6 weeks after interferon-alpha was begun at a dose of 5 million U/d, and the dose was increased every 2 weeks until a maximum tolerated dose was determined. Patients then received the maximum tolerated dose of the combination for a minimum of 12 weeks before formal efficacy evaluations. MEASUREMENTS AND MAIN RESULTS: In the dose-escalation phase, the ability to tolerate interferon-alpha was clearly related to the zidovudine dose. Of the 13 patients receiving 250 mg of zidovudine, only 1 patient was able to tolerate at least 10 million U/d of interferon-alpha. Of the 12 patients receiving 100 mg of zidovudine, 8 tolerated 10 million U/d, 5 tolerated 15 million U/d, and none tolerated higher doses. Of the 12 patients receiving 50 mg of zidovudine, 8 tolerated 10 million U/d, 7 tolerated 15 million U/d, and 6 tolerated 20 million U/d or more. Dose-limiting toxicities included neutropenia (57%), fatigue (16%), thrombocytopenia (14%), and hepatic dysfunction (10%). Of the 22 patients who received a stable dose of both drugs for 12 weeks, 11 patients had a complete or partial tumor response and 8 showed an anti-HIV effect. Peak serum levels of interferon-alpha (32 to 250 U/mL) and zidovudine (0.40 to 3.85 microM) were in the ranges previously shown to be synergistic against HIV. CONCLUSIONS: Combination therapy with zidovudine and interferon-alpha can be administered to patients with HIV infection and Kaposi sarcoma in doses that effect antiviral and antitumor responses; it appears to have a potential role in managing such patients.

An outbreak of ehrlichiosis in members of an Army Reserve unit exposed to ticks.

An outbreak of unexplained illness occurred in members of an army reserve unit after field training in an area of New Jersey endemic for Lyme disease. Nine (12%) of the 74 who attended the exercise had serological evidence of Ehrlichia infection, defined as a single rise in titer of antibody to Ehrlichia canis greater than or equal to 1:160 four weeks after training. Two reservists with early serum samples had documented seroconversion, defined by a four-fold or greater increase in titer of antibody to E. canis, with a peak titer of greater than or equal to 1:160. Reservists with serological evidence of Ehrlichia infection were more than three times as likely to report arthralgia, myalgia, headache, appetite loss, nausea, eye pain, and abdominal pain than the other reservists. No reservist with serological evidence of Ehrlichia infection was hospitalized and most had minimal or no symptoms. This outbreak of ehrlichiosis suggests that the usual symptoms of Ehrlichia infection are milder than previously reported and that ehrlichiosis must be considered in symptomatic persons with recent tick exposure.