Resource concentration and herbivory in oak forests.

Larvae of the fall cankerworm (Alsophila pometaria), a polyphagous defoliator of canopy trees, hatch at the time of budbreak of scarlet oak (Quercus coccinea), about 10 days before budbreak of white oak (Quercus alba). Thus the Alsophila population was dense in a site dominated by scarlet oaks and defoliated the scattered white oaks when they came into leaf. In a site dominated by white oaks, the Alsophila population was sparse and chiefly attacked scattered scarlet oak. Thus in each stand, the rarer species of tree suffered greater herbivory, in-contrast to the more commonly reported observation that herbivore attack on a plant species increases with density.

Serum cytokine profiles in experimental human malaria. Relationship to protection and disease course after challenge.

Serum cytokine profiles were evaluated in immunized and nonimmunized human volunteers after challenge with infectious Plasmodium falciparum sporozoites. Three volunteers had been immunized with x-irradiated sporozoites and were fully protected from infection. Four nonimmune volunteers all developed symptomatic infection at which time they were treated. Sera from all volunteers were collected at approximately 20 time points during the 28-d challenge period; levels of IL-1 alpha, IL-1 beta, IL-2, IFN-gamma, tumor necrosis factor-alpha, IL-4, IL-6, granulocyte macrophage-colony-stimulating factor, and soluble CD4, CD8, and IL-2 receptor (sCD4, sCD8, and sIL-2R, respectively) were determined by ELISA. C-reactive protein (CRP) was assayed by radial immunodiffusion. Parasitemic subjects developed increases in CRP and IFN-gamma, with less marked increases in sIL-2R and sCD8; the other cytokines tested did not change. CRP increases were abrupt and occurred at the onset of fever (day 14 after challenge). IFN-gamma increases were also abrupt, preceding those of fever and CRP by one day. Increases in sIL-2R and sCD8 were more gradual. Increases in fever, CRP, IFN-gamma, and sCD8 were concordant in each volunteer. Early IL-6 increases were noted in the protected vaccinees. Thus, after challenge with virulent P. falciparum, unique systemic cytokine profiles were detectable both in immunized, nonparasitemic volunteers and in unvaccinated, parasitemic subjects. The contrasting cytokine profiles in the two groups may relate to mechanisms of protection and immunopathology in experimental human malaria.

Role of the eaeA gene in experimental enteropathogenic Escherichia coli infection.

Enteropathogenic Escherichia coli (EPEC) infections are a leading cause of infant diarrhea in developing countries. Recently eaeA, a gene necessary for the characteristic intimate attachment of EPEC to epithelial cells in tissue culture, was described. We conducted a randomized, double-blind study to determine the role of the eaeA gene in human EPEC infection. 11 adult volunteers ingested 2 x 10(10) colony-forming units of O127:H6 EPEC strain E2348/69, and an equal number received the same dose of an isogenic eaeA deletion mutant constructed from E2348/69. Volunteers were monitored for the development of diarrhea, fever, and systemic and gastrointestinal complaints. Diarrhea developed in all 11 volunteers who received E2348/69 and in 4 of 11 who received the mutant (P = 0.002). Fever was more common in recipients of the wild-type strain (P = 0.024). Stool volumes were lower in recipients of the mutant. All volunteers seroconverted to E2348/69 LPS, but the geometric mean peak titers of serum IgG and IgA in recipients of the mutant were lower than those of recipients of the wild-type strain. IgA against LPS was detected in the jejunal fluid of six of six recipients of E2348/69 and 5/6 recipients of the mutant. This study unambiguously assigns a role for eaeA as an EPEC virulence gene, but the residual diarrhea seen in recipients of the mutant indicates that other factors are involved.

Effects of anatomic site, oral stimulation, and body position on estimates of body temperature.

BACKGROUND: A prior investigation characterized the range of body temperature in healthy young adults and established the importance of diurnal variations in defining the febrile state. METHODS: Sequential rectal, oral, and tympanic membrane temperature measurements were performed on 22 healthy subjects to determine the quantitative effects of anatomic site, oral stimulation, and body position on estimates of body temperature. RESULTS: Mean rectal temperatures exceeded concurrent oral readings by 0.4 degrees C +/- 0.4 degrees C (0.8 degrees F +/- 0.7 degrees F), which, in turn, exceeded concurrent tympanic membrane readings (obtained with a digital thermometer [IVAC Corp, San Diego, Calif]) by 0.4 degrees C +/- 1.1 degrees C (0.7 degrees F +/- 2.0 degrees F). Tympanic membrane readings were significantly more variable (both intrasubject and intersubject) than rectal or oral readings, especially when cerumen was present in the external ear canal being examined (P<.05). Mastication and smoking both caused significant increases in oral temperature that persisted for greater than 20 minutes. Drinking ice water caused a significant but more transient decrease in oral temperature. Of these activities, only mastication appeared to influence tympanic membrane readings. Body position exerted a modest effect on rectal temperature readings, but did not significantly affect oral or tympanic membrane readings. CONCLUSIONS: These findings indicate that, in addition to diurnal fluctuations in body temperature, the effects of anatomic site, oral stimulation, and body position should be considered in establishing criteria for the febrile state.

Seroprevalence of Helicobacter pylori in Seventh-Day Adventists and other groups in Maryland. Lack of association with diet.

To evaluate the possible role of diet in the transmission of Helicobacter pylori, we compared H pylori seroprevalence among Seventh-Day Adventists (who are vegetarian and abstain from alcohol, caffeine, and meat; n = 94) and two non-Seventh-Day Adventist control groups (n = 168). With the use of an enzyme-linked immunosorbent assay H pylori antigen prepared in a French pressure cell, we found no difference in seroprevalence among these groups; however, seropositivity strongly correlated with age and black race.

Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative.

OBJECTIVE: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1MN, HIV-1RF, HIV-1EV91, and HIV-1Can0A. DESIGN: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center. METHODS: Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. RESULTS: Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1MN, HIV-1RF, or HIV-1(4489-5) laboratory-adapted HIV isolates. 3H-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls). CONCLUSIONS: C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-infected patients.

Effects of IFN-beta on human cerebral blood flow distribution.

The effect of interferon-beta1b (IFN-beta) on human cerebral blood flow distribution was examined in five multiple sclerosis patients using functional brain single-photon emission tomography (SPECT). Of nine regions of interest studied, only the basal ganglia exhibited a significant change (increase) in relative photon emission intensity (i.e., relative blood flow) when comparing SPECT scans obtained 6 h after s.c. IFN-beta injection with scans obtained at the same time of day (noon) 30 h after IFN-beta injection (IFN-beta-free day). The increase in relative blood flow to the basal ganglia following IFN-beta injection correlated positively with changes in mean arterial pressure (MAP). Additional studies will be required to determine the relevance of these observations for IFN-beta-induced central nervous system side effects.

Comparison of immunogenicity and efficacy of rhesus rotavirus reassortant vaccines in breastfed and nonbreastfed children. US Rotavirus Vaccine Efficacy Group.

OBJECTIVE: To evaluate whether breastfeeding affected the immunogenicity and/or efficacy of candidate rhesus-human rotavirus reassortant vaccines. METHODS: A total of 989 healthy infants between 4 and 26 weeks of age were enrolled into a 23-center, prospective, randomized, double-masked, controlled study of the safety, immunogenicity, and efficacy of three doses (4 x 10(4) plaque-forming units) of monovalent rhesus-human viral protein 7, or G, serotype 1 reassortant vaccine, (RRV-S1) or tetravalent vaccine (RRV-TV) consisting of rhesus-human reassortant G serotypes 1, 2, and 4, and the parent RRV G serotype 3. Vaccine efficacy was compared in the breastfed and nonbreastfed children as well as seroconversion rates and postvaccination geometric mean titers (GMTs) of neutralizing antibodies to human serotypes 1, 2, 3, and 4, RRV, and immunoglobulin A to RRV. GMTs in the two feeding groups were compared with and without adjustment for age at initiation of vaccination, prevaccination antibody titers, and the age and prevaccination titer interaction. RESULTS: The seroconversion rates to both vaccines by one or more assays were similar for the breastfed and the nonbreastfed groups (RRV-S1, 84% and 85%, respectively; RRV-TV, 94% and 93%, respectively). There were no significant differences in postvaccination GMTs to either vaccine, measured by any serologic assay, in the two feeding groups. The efficacy of the RRV-S1 vaccine was not significantly lower among the breastfed children than the nonbreastfed children (28% and 39%, respectively). RRV-TV, which is the vaccine being further evaluated for licensure, was equally protective in breastfed and nonbreastfed infants (50% and 51%, respectively). Logistic regression analysis, taking into account differences in age at vaccination and day 1 titer, revealed no evidence of differential vaccine efficacy in the two feeding groups for either vaccine. CONCLUSIONS: These results indicate that the RRV-TV vaccine, given as three doses of 4 x 10(4) plaque-forming units, induces similar seroresponses and protection in breastfed and nonbreastfed US children.

Enteric adenovirus infection and childhood diarrhea: an epidemiologic study in three clinical settings.

During a 2-year prospective study of gastroenteritis in children less than 2 years of age, the role of enteric adenovirus as a cause of infantile diarrhea was examined in three clinical settings in a case-control fashion. Using a monoclonal antibody-based enzyme-linked immunosorbent assay with specificity for adenovirus serotypes 40 and 41, enteric adenovirus was identified in 10 of 246 episodes of diarrhea in outpatients (4.1%), 13 of 211 children admitted to the hospital with diarrhea (6.2%), and 5 of 81 children in whom nosocomial diarrhea developed (6.2%), making this agent the third most commonly identified etiologic agent of diarrheal disease. Asymptomatic infections were uncommon (5 of 372 control subjects, or 1.3%) and were seen most frequently in the nosocomial setting. Cases occurred in every calendar month except March and April of each year. A syndrome of watery diarrhea of longer duration compared with other patients with diarrhea (mean 5.4 vs 3.8 days, P = .01), associated with vomiting and dehydration, was present in most cases. Compared with patients with rotavirus, patients were as likely to experience fever and dehydration and more likely to vomit. Household contact with gastroenteritis, often with a child 2 to 5 years of age, was a predisposing factor. It was concluded that enteric adenovirus is an important cause of infantile diarrhea in Baltimore children. Although far less common than rotavirus, this agent was associated with diarrheal illnesses that were at least as severe as those seen with rotavirus.

Palatability, reactogenicity and immunogenicity of engineered live oral cholera vaccine CVD 103-HgR in Chilean infants and toddlers.

BACKGROUND: Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults, school age children and preschool children in a single 5 x 10(9) colony-forming unit dose. Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to investigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age. METHODS: The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102). One-half of the subjects were randomly allocated to receive vaccine and the other one-half to receive placebo, in double blind fashion. After 2 weeks of double blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing. The buffered vaccine "cocktail" had a volume of 100 ml; subjects who ingested > or =70 ml were considered fully vaccinated. FINDINGS: Only 37% of subjects overall (25% of 3- to 5-month-olds) ingested > or =70 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo. Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%). Of subjects who ingested two doses, 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose. INTERPRETATION: Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested. The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immunizing infants must be sought.

Acute diarrhea in Baltimore children attending an outpatient clinic.

Acute diarrheal illnesses in Baltimore children younger than 2 years of age attending an outpatient clinic were studied during a 12-month period. One in five acute care visits made to the clinic by children younger than 2 years was for diarrhea, and 5% of diarrhea cases required hospitalization. With the use of comprehensive methodology, a potential etiologic agent was identified in the stool of 105 (43%) of the 246 episodes of diarrhea in cases and in 43 (28%) of the 155 controls. Viral pathogens were found in 26% of episodes, and bacterial pathogens were found in 14%. Only rotavirus, enteric adenovirus and Salmonella were significantly associated with diarrhea. Cases were more likely to have measures of socioeconomic deprivation, such as household crowding, low maternal educational level and low birth weight, when compared to controls. Racial differences in morbidity from diarrheal illnesses were observed but could be attributed to these specific sociodemographic factors. Despite the low mortality caused by infantile gastroenteritis in the United States, it remains an important public health problem. However, even with intensive investigation the etiologies remain largely unknown.

Large scale, postlicensure, selective vaccination of Chilean infants with PRP-T conjugate vaccine: practicality and effectiveness in preventing invasive Haemophilus influenzae type b infections.

BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccines have demonstrated an impressive impact in diminishing Hib disease in industrialized countries. However, their high cost prompts nonindustrialized countries to corroborate their effectiveness under local conditions before considering their programmatic implementation. Such a postlicensure evaluation of vaccine effectiveness was undertaken in Chile. METHODS: After its licensure in Chile polyribosylribitol phosphate-tetanus toxoid protein conjugate vaccine (PRP-T), combined with diphtheria-tetanus-pertussis vaccine, was introduced into the Expanded Program on Immunization schedules in 36 health centers throughout metropolitan Santiago for 12 months, whereas 35 similar health centers administered only diphtheria-tetanus toxoid-pertussis vaccine. Bacteriologic surveillance data for invasive Hib cases collected over the ensuing 30 months were analyzed. RESULTS: In an intent-to-vaccinate (effectiveness) analysis, PRP-T provided 90.2% protection (95% confidence interval, 74.5 to 100%) against invasive Hib disease (40 vs. 4 cases, P < 0.001). Vaccine effectiveness was 91.3% against meningitis (22 vs. 2 cases) and 80% against pneumonia and empyema (10 vs. 2 cases, P = 0.039). Vaccine efficacy among infants who received all three doses of PRP-T was 91.7% (95% confidence interval, 64.8 to 100%). CONCLUSIONS: Programmatic use of Hib conjugate vaccine administered in combination with diphtheria-tetanus-pertussis vaccine constitutes a highly effective and practical intervention in Chile, a newly industrializing country.

Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218.

We conducted a phase II, randomized, double-blind, placebo-controlled, safety and immunogenicity study of a serially passaged, plaque-purified live chikungunya (CHIK) vaccine in 73 healthy adult volunteers. Fifty-nine volunteers were immunized one time subcutaneously with the CHIK vaccine and 14 were immunized with placebo (tissue culture fluid). Vaccinees were clinically evaluated intensively for one month, and had repeated blood draws for serological assays (50% plaque-reduction neutralization test) for one year. Except for transient arthralgia in five CHIK vaccinees, the number and severity of local and systemic reactions and abnormal laboratory tests after immunization were similar in CHIK vaccinees and placebo recipients. Fifty-seven (98%) of 58 evaluable CHIK vaccinees developed CHIK neutralizing antibody by day 28, and 85% of vaccinees remained seropositive at one year after immunization. No placebo recipients seroconverted. This promising live vaccine was safe, produced well-tolerated side effects, and was highly immunogenic.

Plasmids in Salmonella typhi in Lima, Peru, 1987-1988: epidemiology and lack of association with severity of illness or clinical complications.

A prospective study was conducted to better characterize the epidemiology of plasmid-bearing strains of Salmonella typhi in an endemic area of Lima, Peru, and to determine if plasmids were associated with specific manifestations of typhoid fever. Of 228 S. typhi isolated from patients at Cayetano Heredia University Hospital in Lima during 1987-1988, 76 (33%) contained plasmids. Ten different plasmid profiles were identified, with ten distinct plasmids present within these profiles. There was significant temporal clustering of isolates having common plasmid profiles. Two plasmids (both from the same isolate) carried antibiotic resistance genes. Two cryptic plasmids with approximate sizes of 55 and 65 kilobases (kb) appeared to be closely related, based on restriction endonuclease digestions and Southern blot analysis. An ampicillin resistance plasmid from a 1989 patient isolate differed by only a single restriction fragment from the cryptic 65-kb plasmid. No association was found between any plasmid or plasmid profile and severity or clinical manifestations of disease.

Serologic response to Helicobacter pylori among children and teenagers in northern Chile.

The serologic response to Helicobacter pylori was determined in 388 children and teenagers living in Iquique, Chile by using an IgG enzyme-linked immunosorbent assay. Serum antibody levels, as measured by optical density, correlated strongly with age. Increases in the mean antibody level were seen primarily after age five, with rates of seropositivity increasing to > or = 70% among teenagers. The reasons for this age-related pattern of acquisition of infection remain to be determined.

Phase 1 studies of Walter Reed Army Institute of Research candidate attenuated dengue vaccines: selection of safe and immunogenic monovalent vaccines.

We describe the results of initial safety testing of 10 live-attenuated dengue virus (DENV) vaccine candidates modified by serial passage in primary dog kidney (PDK) cells at the Walter Reed Army Institute of Research. The Phase 1 studies, conducted in 65 volunteers, were designed to select an attenuated vaccine candidate for each DENV serotype. No recipient of the DENV candidate vaccines sustained serious injury or required treatment. Three vaccine candidates were associated with transient idiosyncratic reactions in one volunteer each, resulting in their withdrawal from further clinical development. Increasing PDK cell passage of DENV-1, DENV-2, and DENV-3 candidate vaccines increased attenuation for volunteers, yet also decreased infectivity and immunogenicity. This effect was less clear for DENV-4 candidate vaccines following 15 and 20 PDK cell passages. Only one passage level each of the tested DENV-2, -3, and -4 vaccine candidates was judged acceptably reactogenic and suitable for expanded clinical study. Subsequent studies with more recipients will further establish safety and immunogenicity of the four selected vaccine candidates: DENV-1 45AZ5 PDK 20, DENV-2 S16803 PDK 50, DENV-3 CH53489 PDK 20, and DENV-4 341750 PDK 20.

Antibodies that react with the capsular polysaccharide of Vibrio vulnificus are detectable in infected patients, and in persons without known exposure to the organism.

In serious infections with Vibrio vulnificus, IgG antibodies to the capsular polysaccharide of the infecting strain were demonstrable in patient serum. It was not possible to show that persons with probable increased exposure to V. vulnificus (shellfish industry workers) had increased levels of antibodies to any one of three capsular types tested when compared with persons who would be expected to have had minimal exposure to the organism (Seventh Day Adventists). Antibodies that reacted with the capsular polysaccharides were demonstrable in persons without a history of V. vulnificus infection, suggesting that cross-reacting antibodies are present in the general population.

Factors underlying variation in spontaneous and clastogen-induced sister chromatid exchanges and chromosome breakage frequencies.

The latent "factors" influencing spontaneous and clastogen-induced genetic damage, measured by rates of sister chromatid exchange (SCE) and chromosome breakage (CB), were investigated in a small sample of 20 unrelated, healthy individuals. The covariation of spontaneous and clastogen-induced (bleomycin [BLM], streptonigrin [SN], mitomycin-C [MMC], 4-nitroquinoline-1-oxide [4NQO]) SCEs and CBs was analyzed by maximum-likelihood factor analysis. A single-factor model resulted in large standardized regression coefficients of measured variables on the factor for spontaneous and BLM- and SN-induced SCE frequencies, and a modest regression coefficient for MMC-induced SCEs. A two-factor model, after varimax rotation, yielded one factor strongly associated with spontaneous and BLM- and SN-induced SCE frequencies, and a second factor associated with spontaneous and BLM- and SN-induced CBs. A bootstrap analysis of this data set indicated the statistical significance of one regression coefficient (i.e., P less than or equal to 0.05) and borderline significance (0.07 less than or equal to P less than or equal to 0.11) of three other regression coefficients on the first factor, to be interpreted as an effector of SCE frequencies. However, for the second factor, none of the bootstrapped regression coefficients was significant (P greater than 0.22). Due to the modest sample utilized in this study, the validity of this model should be further explored using additional, larger data sets.

Extension of the volunteer challenge model to study South American cholera in a population of volunteers predominantly with blood group antigen O.

The volunteer challenge model was used to study the virulence of strains of Vibrio cholerae O1 El Tor recently isolated from cases of cholera in South America. Fifteen of the 24 volunteers (62%) were of blood group O, the group most prevalent in South America and the group at increased risk of more severe cholera. Two El T or Inaba strains and 2 El Tor Ogawa strains were given to volunteers at a dose of 1-2 x 10(6) colony-forming units. All 4 strains caused diarrhoea in 67-83% of volunteers. Volunteers with blood group antigen O had an increased attack rate for diarrhoea (P = 0.015) and a marginally increased mean diarrhoeal stool volume (P = 0.08) after challenge. One-third of the volunteers with blood group O, and none of the volunteers with other blood groups, developed severe diarrhoea (> 5 L) (P = 0.01). This study established a model of South American cholera that can be used to predict field efficacy of candidate vaccines among populations with a high prevalence of blood group antigen O.

Effect of antipyretic therapy on the duration of illness in experimental influenza A, Shigella sonnei, and Rickettsia rickettsii infections.

STUDY OBJECTIVES: To determine whether antipyretic therapy prolongs the course of experimental influenza A, Shigella sonnei, and Rickettsia rickettsii infections. DESIGN: Retrospective observational study. SETTING: University Center for Vaccine Development. SUBJECTS: Fifty-four volunteers with experimentally induced influenza A, 45 with S. sonnei, and 21 with R. rickettsii infections participated. INTERVENTIONS: Subjects from the six influenza A studies were challenged intranasally. If they met certain criteria, they were offered aspirin or acetaminophen for symptomatic relief. Subjects from the three Shigella studies were challenged with the bacteria and then given trimethoprimsulfamethoxazole. Acetaminophen also could be administered. In the one R. rickettsii trial, subjects were inoculated intradermally and treated with tetracycline. Again, acetaminophen was administered for symptomatic relief. MEASUREMENTS AND MAIN RESULTS: Data, excerpted from subjects' study records, were evaluated using Wilcoxon tests, Spearman's correlation coefficients, and multiple regression analysis. Two-tailed hypotheses with a p value of 0.05 were used for all of the analyses. There was a striking correlation between antipyretic therapy and duration of illness in subjects infected with influenza A and S. sonnei, but not R. rickettsii. CONCLUSIONS: Multivariate analysis suggested that antipyretic therapy prolonged illness in subjects infected with influenza A, but its use was the result of prolonged illness in those infected with S. sonnei. The precise nature of these relationships requires a prospective, randomized, placebo-controlled trial.