SARS-CoV-2 Seroprevalence Among Healthcare Workers by Job Function and Work Location in a New York Inner-City Hospital.

OBJECTIVE: To describe the seroprevalence and risk for SARS-CoV-2 among healthcare workers (HCWs) by job function and work location following the pandemic's first wave in New York City (NYC). METHODS: A cross-sectional study conducted between May 18 and June 26, 2020, during which HCWs at a large inner-city teaching hospital in NYC received voluntary antibody testing. The main outcome was presence of SARS-CoV-2 antibodies indicating previous infection. Seroprevalence and adjusted odds ratios (aORs) for seropositivity by type and location of work were calculated using logistic regression analyses. RESULTS: Of 2,749 HCWs tested, 831 tested positive, yielding a crude seroprevalence of 30.2% (95% CI, 29%-32%). Seroprevalence ranged from 11.1% for pharmacy staff to 44.0% for nonclinical HCWs comprised of patient transporters and housekeeping and security staff, with 37.5% for nurses and 20.9% for administrative staff. Compared to administrative staff, aORs (95% CIs) for seropositivity were 2.54 (1.64-3.94) for nurses; 2.51 (1.42-4.43) for nonclinical HCWs; between 1.70 and 1.83 for allied HCWs such as patient care technicians, social workers, registration clerks and therapists; and 0.80 (0.50-1.29) for physicians. Compared to office locations, aORs for the emergency department and inpatient units were 2.27 (1.53-3.37) and 1.48 (1.14-1.92), respectively. CONCLUSION: One-third of hospital-based HCWs were seropositive for SARS-CoV-2 by the end of the first wave in NYC. Seroprevalence differed by job function and work location, with the highest estimated risk for nurses and the emergency department, respectively. These findings support current nationwide policy prioritizing HCWs for receipt of newly authorized COVID-19 vaccines.

Birth Prevalence of Congenital Cytomegalovirus Infection in HIV-Exposed Uninfected Children in the Era of Combination Antiretroviral Therapy.

OBJECTIVES: To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. STUDY DESIGN: The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. RESULTS: Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/µL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. CONCLUSIONS: Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

Adverse Pregnancy Outcomes Among Women Who Conceive on Antiretroviral Therapy.

Background: Adverse pregnancy outcomes for women who conceive on antiretroviral therapy (ART) may be increased, but data are conflicting. Methods: Human immunodeficiency virus-infected, nonbreastfeeding women with pre-ART CD4 counts ≥400 cells/µL who started ART during pregnancy were randomized after delivery to continue ART (CTART) or discontinue ART (DCART). Women randomized to DCART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat and as-treated approaches, we performed Fisher exact tests to compare subsequent pregnancy outcomes by randomized arm. Results: Subsequent pregnancies occurred in 277 of 1652 (17%) women (CTART: 144/827; DCART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with a median age of 27 years (interquartile range [IQR], 24-31 years) and median CD4+ T-cell count 638 cells/µL (IQR, 492-833 cells/µL). When spontaneous abortions and stillbirths were combined, there was a significant difference in events, with 33 of 140 (23.6%) in the CTART arm and 15 of 126 (11.9%) in the DCART arm (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.1-3.5]; P = .02). In the as-treated analysis, the RR was reduced and no longer statistically significant (RR, 1.4 [95% CI, .8-2.4]). Conclusions: Women randomized to continue ART who subsequently conceived were more likely to have spontaneous abortion or stillbirth, compared with women randomized to stop ART; however, the findings did not remain significant in the as-treated analysis. More data are needed on pregnancy outcomes among women conceiving on ART, particularly with newer regimens.

Predictors of Disclosure of Maternal HIV Status by Caregivers to their Children in an Inner-City Community in the United States.

Disclosure of HIV status to children is a challenge parents living with HIV face. To evaluate predictors of maternal HIV disclosure in a low-income clinic in the U.S. that serves an African American, Hispanic and immigrant population with high HIV prevalence, 172 caregivers with 608 children completed a standardized survey. Caregivers were 93 % female, 84 % biological mothers, and 34 % foreign born. Sixty-two (36 %) caregivers had at least one disclosed child, 42 of whom also had other nondisclosed children. Of all children, 581 (96 %) were uninfected and 181 (30 %) were disclosed. Caregiver's U.S. birth (OR: 2.32, 95 % CI 1.20-4.52), child's age (OR: 1.2/year, 95 % CI 1.16-1.24), and increased HIV-stigma perception by caregiver (1.06/point increase, 95 % CI 1.04-1.09) predicted disclosure. Children were more often disclosed if their caregiver was born in the U.S. or reported higher HIV-related stigma. These findings suggest that complex family context may complicate disclosure, particularly among immigrants.

Sexually Transmitted Infections in Youth With Controlled and Uncontrolled Human Immunodeficiency Virus Infection.

BACKGROUND: Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), disproportionately affect adolescents and young adults (AYAs) ages 13-24 years. Sexually transmitted infections likewise are a risk factor for HIV acquisition and transmission; however, there is a lack of data on STI acquisition in HIV-infected AYAs. METHODS: We determined the incidence of STIs in HIV-infected AYAs 12.5 <25 years of age in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 observational cohort study. Univariate and multivariable logistic regression models were used to evaluate the association of HIV control (mean viral load <500 copies/mL and CD4+ T cells >500 cells/mm3 in the year preceding STI diagnosis) and other risk factors with STI occurrence. RESULTS: Of 1201 enrolled subjects, 1042 participants met age criteria and were included (49% male, 61% black, 88% perinatally infected; mean age 18.3 years). One hundred twenty participants had at least 1 STI on study, of whom 93 had their first lifetime STI (incidence rate = 2.8/100 person-years). For individual STI categories, 155 incident category-specific events were reported; human papillomavirus (HPV) and chlamydial infections were the most common. In the multivariable model, having an STI was associated with older age (adjusted odds ratio [aOR] = 1.13; 95% confidence interval [CI], 1.05-1.22), female sex (aOR = 2.65; 95% CI, 1.67-4.21), nonperinatal HIV acquisition (aOR = 2.33; 95% CI, 1.29-4.22), and uncontrolled HIV infection (aOR = 2.05; 95% CI, 1.29-3.25). CONCLUSIONS: Sexually transmitted infection acquisition in HIV-infected AYAs is associated with older age, female sex, nonperinatal HIV acquisition, and poorly controlled HIV infection. Substantial rates of STIs among HIV-infected AYAs support enhanced preventive interventions, including safe-sex practices and HPV vaccination, and antiretroviral adherence strategies.

Genetically determined ancestry is more informative than self-reported race in HIV-infected and -exposed children.

The Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants.In this study, we compared genetically determined ancestry (GDA) and self-reported race/ethnicity (SRR) in the PHACS cohort. GDA was estimated using a highly discriminative panel of 41 single nucleotide polymorphisms and compared to SRR. Because SRR was similar between the PHIV and PHEU, and between the AMP and SMARTT cohorts, data for all unique 1958 participants were combined.According to SRR, 63% of study participants identified as Black/African-American, 27% White, and 34% Hispanic. Using the highest percentage of ancestry/ethnicity to identify GDA, 9.5% of subjects were placed in the incorrect superpopulation based on SRR. When ≥50% or ≥75% GDA of a given superpopulation was required, 12% and 25%, respectively, of subjects were placed in the incorrect superpopulation based on SRR, and the percent of subjects classified as multiracial increased. Of 126 participants with unidentified SRR, 71% were genetically identified as Eurasian.GDA provides a more robust assessment of race/ethnicity when compared to self-report, and study participants with unidentified SRR could be assigned GDA using genetic markers. In addition, identification of continental ancestry removes the taxonomic identification of race as a variable when identifying risk for clinical outcomes.

Brief Report: APOL1 Renal Risk Variants Are Associated With Chronic Kidney Disease in Children and Youth With Perinatal HIV Infection.

APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a nested case-control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.5-fold increased odds of CKD in those carrying high-risk APOL1 genotypes using a recessive model [95% confidence interval (CI): 1.2 to 10.0]. We report an unadjusted incidence of 1.2 CKD cases/100 person-years (95% CI: 0.5 to 2.5) in PHIV youth carrying APOL1 high-risk genotypes, with important implications for sub-Saharan Africa.

Nephrotic-range proteinuria in an eight-year-old traveler with severe dengue: Case report and review of the literature.

We report a case of an eight-year-old male, native of the Dominican Republic, who visited the U.S. and was admitted to a pediatric intensive care unit with severe dengue. He needed aggressive fluid management for dengue shock syndrome and developed proteinuria on the sixth day of his illness, shortly after his nadir thrombocytopenia. His proteinuria peaked on the eight day, and reduced to trace levels by the tenth day of his illness, coinciding with normalization of his platelet count. His highest random urine protein/creatinine ratio was in the nephrotic range, at 3.9 g/g. Dengue fever can cause a wide spectrum of acute kidney injury (AKI), ranging in incidence from 0.9 to 36%. Review of the literature shows that nephrotic-range proteinuria is an uncommon complication of AKI caused by dengue, reported thus far only in Southeast Asia. Immune-mediated mechanisms may explain the observed association between dengue-induced thrombocytopenia and severe proteinuria, in this case, and previously reported cases. Dengue virus infection is the commonest mosquito-borne disease in the world with substantial morbidity and mortality. Well-designed prospective studies are needed to further characterize the extent and mechanisms of AKI in populations living in countries with ongoing transmission, as well as in those with travel-associated disease.

Prevalence and Persistence of Varicella Antibodies in Previously Immunized Children and Youth With Perinatal HIV-1 Infection.

BACKGROUND: Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥ 15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status. METHODS: The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites. In a cross-sectional analysis, we tested participants' most recent stored sera for varicella antibody using whole-cell and glycoprotein enzyme-linked immunosorbent assay. Seropositivity predictors were identified using multivariable logistic regression models and C statistics. RESULTS: Samples were available for 432 children with PHIV and 221 PHEU children; 82% of children with PHIV and 97% of PHEU children were seropositive (P < .001). Seropositivity after 1 vaccine dose among children with PHIV and PHEU children was 100% at <3 years (both), 73% and 100% at 3-<7 years (P < .05), and 77% and 97% at ≥ 7 years (P < .01), respectively. Seropositivity among recipients of 2 vaccine doses was >94% at all intervals. Independent predictors of seropositivity among children with PHIV were receipt of 2 vaccine doses, receipt of 1 dose while on ≥ 3 months of cART, compared with none (adjusted odds ratio [aOR]: 14.0 and 2.8, respectively; P < .001 for overall dose effect), and in those vaccinated ≥ 3 years previously, duration of cART (aOR: 1.29 per year increase, P = .02). CONCLUSIONS: Humoral immune responses to varicella vaccine are best achieved when children with PHIV receive their first dose ≥ 3 months after cART initiation and maintained by completion of the 2-dose series and long-term cART use.

Changing Trends in Complications and Mortality Rates Among US Youth and Young Adults With HIV Infection in the Era of Combination Antiretroviral Therapy.

BACKGROUND: Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. METHODS: We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. RESULTS: Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. CONCLUSIONS: Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed.

Immunity to Measles, Mumps, and Rubella in US Children With Perinatal HIV Infection or Perinatal HIV Exposure Without Infection.

BACKGROUND: Children with perinatal human immunodeficiency virus (HIV) infection (PHIV) may not be protected against measles, mumps, and rubella (MMR) because of impaired initial vaccine response or waning immunity. Our objectives were to estimate seroimmunity in PHIV-infected and perinatally HIV-exposed but uninfected (HEU) children and identify predictors of immunity in the PHIV cohort. METHODS: PHIV and HEU children were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) at ages 7-15 years from 2007 to 2009. At annual visits, demographic, laboratory, immunization, and clinical data were abstracted and serologic specimens collected. Most recent serologic specimen was used to determine measles seroprotection by plaque reduction neutralization assay and rubella seroprotection and mumps seropositivity by enzyme immunoassay. Sustained combination antiretroviral therapy (cART) was defined as taking cART for at least 3 months. RESULTS: Among 428 PHIV and 221 HEU PHACS participants, the prevalence was significantly lower in PHIV children for measles seroprotection (57% [95% confidence interval {CI}, 52%-62%] vs 99% [95% CI, 96%-100%]), rubella seroprotection (65% [95% CI, 60%-70%] vs 98% [95% CI, 95%-100%]), and mumps seropositivity (59% [95% CI, 55%-64%] vs 97% [95% CI, 94%-99%]). On multivariable analysis, greater number of vaccine doses while receiving sustained cART and higher nadir CD4 percentage between last vaccine dose and serologic testing independently improved the cumulative prediction of measles seroprotection in PHIV. Predictors of rubella seroprotection and mumps seropositivity were similar. CONCLUSIONS: High proportions of PHIV-infected children, but not HEU children, lack serologic evidence of immunity to MMR, despite documented immunization and current cART. Effective cART before immunization is a strong predictor of current seroimmunity.

Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection.

BACKGROUND: Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications. METHODS: Data collected from HIV-infected youth followed for ≥ 48 months were analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. RESULTS: Of the 1,874 at-risk children enrolled in the study, 428 (23 %) developed RLE, which persisted in 229 of these (54 %). CD4 percentages of <25 % [hazard ratio (HR) 0.63, p < 0.002) and an HIV viral load of >100,000 copies/ml (HR 0.31, p < 0.01) were associated with reduced rates of resolution, while in most cases exposure to highly active antiretroviral therapy (HAART)/nephrotoxic HAART prior to or subsequent to RLE were not. Persistence of RLE was 88 % sensitive for identifying new RD. Negative predictive values for RD were >95 % for both the at-risk cohort and those with RLE. CONCLUSIONS: Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD.

Chronic kidney disease associated with perinatal HIV infection in children and adolescents.

BACKGROUND: This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection. METHODS: Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria. RESULTS: Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD. CONCLUSIONS: A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.

Language impairment in children perinatally infected with HIV compared to children who were HIV-exposed and uninfected.

OBJECTIVE: To investigate the risk for language impairment (LI) in children perinatally infected or exposed to HIV. METHODS: We evaluated the prevalence of LI in 7- to 16-year-old children with perinatal HIV infection (HIV+) compared with HIV-exposed and uninfected children, using a comprehensive standardized language test (Clinical Evaluation of Language Functioning-Fourth Edition [CELF-4]). LI was classified as primary LI (Pri-LI) (monolingual English exposure and no cognitive or hearing impairment), concurrent LI (Con-LI) (cognitive or hearing impairment), or no LI. Associations of demographic, caregiver, HIV disease, and antiretroviral treatment factors with LI category were evaluated using univariate and multivariable logistic regression models. RESULTS: Of the 468 children with language assessments, 184 (39%) had LI. No difference was observed by HIV infection status for overall LI or for Pri-LI or Con-LI; mean (SD) CELF-4 scores were 88.5 (18.4) for HIV+ versus 87.5 (17.9) for HIV-exposed and uninfected children. After adjustment, black children had higher odds of Pri-LI versus no LI (adjusted odds ratio [aOR] = 2.43, p = .03). Children who were black, Hispanic, had a caregiver with low education or low intelligence quotient, or a nonbiological parent as caregiver had higher odds of Con-LI versus no LI. Among HIV+ children, viral load >400 copies/mL (aOR = 3.04, p < .001), Centers for Disease Control and Prevention Class C (aOR = 2.19, p = .02), and antiretroviral treatment initiation <6 months of age (aOR = 2.12, p = .02) were associated with higher odds of Con-LI versus no LI. CONCLUSIONS: Children perinatally exposed to HIV are at high risk for LI, but such risk was not increased for youth with HIV. Risk factors differed for Pri-LI and Con-LI.

Infant acceptance of a bitter-tasting liquid medication: a randomized controlled trial comparing the Rx Medibottle with an oral syringe.

The calibrated oral syringe is considered the standard system for administering liquid formulations of medications to infants. Medication acceptance using the syringe may not always be favorable, particularly with unpleasant-tasting liquids. The Rx Medibottle (The Medicine Bottle Co, Hinsdale, Illinois), an alternate drug-delivery device, is an infant-feeding bottle that contains a central sleeve within its body into which a syringe is inserted. Depressing the syringe's plunger in quick, short squirts synchronized with an infant's sucking allows drug ingestion, preventing dilution of the drug in the formula within the bottle's nipple. The Rx Medibottle costs $14.95 retail. Kraus et al demonstrated that it was more efficacious, with a higher level of infant acceptance compared with the syringe, when used to administer a 1-time dose of a pleasant-tasting liquid (acetaminophen, Tempra Syrup; Mead Johnson Nutritionals, Evansville, Indiana). Our study tests the efficacy of this bottle in administering a single dose of generic prednisolone liquid, a bitter-tasting drug, with an oral syringe serving as the control method of delivery.

A blinded survey of the seroprevalence of HIV-1 infection in an inner-city adolescent and young adult population attending a community hospital in the United States.

The seroprevalence of HIV-1 infection in youth aged 12-24 years attending a Bronx community hospital was studied by blinded testing of unused sera. A crude prevalence of 0.98% (95% CI 0.08-1.88%) was observed, higher than rates in United States national HIV surveys, underscoring the need for enhanced screening and preventive services.

Effect of ciprofloxacin on lethal and sublethal challenge with endotoxin and on early cytokine responses in a murine in vivo model.

The influence of ciprofloxacin on immune responses has been suggested by results of in vitro and in vivo studies. This effect was studied using a murine model that measured mortality and early cytokine responses after challenge with endotoxin. C57/BL6 mice weighing between 18 and 21 g were given a single intraperitoneal dose of lipopolysaccharide (LPS), ranging from 200 to 1000 microg. Mice were pre-treated with an intraperitoneal injection of 5% dextrose in sterile water containing 0.0-6.0 mg of ciprofloxacin 1 h before LPS challenge. Cytokine responses were assessed by measuring concentrations in serum separated from blood obtained by cardiac puncture of anaesthetized mice at 0, 1, 3, 6 and 24 h following LPS administration. Mice were observed for 72 h following administration of LPS and serum cytokines were measured using ELISA. More than 4.5 mg of ciprofloxacin (675-900 mg/m(2) or 225-300 mg/kg) given 1 h before LPS challenge consistently protected mice from a lethal dose of LPS (14/14 versus 0/7, P < 0.00001). Ciprofloxacin significantly attenuated the production of tumour necrosis factor-alpha and interleukin-12 response after LPS challenge. In addition, ciprofloxacin significantly increased serum interleukin-10 concentrations but had little or no effect on interleukin-6 or interleukin-1beta serum concentrations. Similar effects were evident with sublethal doses of LPS and were most pronounced at the lowest dose of LPS studied. These observations indicate that ciprofloxacin can prevent endotoxin-mediated death and alter early host cytokine responses. This effect may influence the course of infection in a manner that is independent of the drug's antimicrobial activity.