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Background: To compare the morbidity and work absenteeism associated with coronavirus disease 2019 (COVID-19) and influenza among health care personnel (HCP) in 2022 to 2023., Methods: We followed 5,752 hospital-based HCP in Greece from November 14, 2022 through May 28, 2023. Symptomatic HCP was tested for SARS-CoV-2 and influenza by real-time polymerase chain reaction and/or rapid antigen detection test. The association between the duration of absenteeism and the type of disease was estimated by multivariable regression models., Results: A total of 734 COVID-19 cases and 93 influenza cases were studied. The mean duration of absence per COVID-19 case was 5.8days compared with a mean of absence of 3.6days per influenza case (P value <.001). Overall, COVID-19 accounted for 4,245days missed during the study period compared with 333days missed due to influenza. Multivariable regression estimates indicated that HCP with COVID-19 had 1.91 more days of absenteeism (95% confidence interval 1.67-2.15) compared with those with influenza, on average., Conclusions: As SARS-CoV-2 becomes endemic, COVID-19 remains the prevalent cause of morbidity and absenteeism among HCP, accounting for considerably more workdays missed compared with influenza. HCP should be up-to-date with COVID-19 booster vaccinations and annual influenza vaccination in order to protect them as well as health care systems from HCP absenteeism., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To estimate the protection that coronavirus disease 2019 (COVID-19) vaccine doses conferred to hospitalized patients with COVID-19 against adverse outcomes and longer length of stay during the Omicron BA.2 and BA.5 subvariant epidemics in Greece., Methods: The study was conducted from November 2022 to May 2023. Multivariable logistic and negative binomial regression models were applied to estimate the association between any adverse outcomes and length of stay with the number of COVID-19 vaccine doses., Results: We studied 962 patients (median age: 78 years; mean length of stay: 9.2 days), of whom 847 (88.0%) had ≥ 1 comorbidity. Of these, 39 (4.0%) were admitted to the intensive care unit, 44 (4.6%) received invasive mechanical ventilation, and 110 (11.4%) died in hospital. There were 184 (19.1%) unvaccinated patients, 125 (13.0%) with one or two vaccine doses, and 653 (67.9%) with ≥ 3 doses. In multivariable analyses, patients with ≥ 3 doses had lower odds of experiencing any adverse outcomes (adjusted odds ratio: 0.57; 95% confidence interval [CI]: 0.37-0.86) compared with unvaccinated patients. On average, patients with one or two doses and those with ≥ 3 had decreased length of hospital stay (-1.5 days [95% CIs: -2.6 to -0.4] and -2.8 days [95% CIs: -4.1 to -1.4], respectively] compared with unvaccinated patients. Other characteristics consistently associated with adverse outcomes and longer length of stay included older age, having three or more comorbidities compared with none, and being admitted to the hospital two or more weeks post-diagnosis., Conclusions: A history of ≥ 3 vaccine doses conferred significant protection against any adverse outcome and longer length of stay in hospitalized patients with COVID-19., (© 2024 The Author(s).)

Background: To evaluate the influenza-like illness (ILI) and acute respiratory infection (ARI) case definitions in the diagnosis of COVID-19 and influenza in healthcare personnel (HCP)., Methods: We followed a cohort of 5752 HCP from November 2022 to May 2023. Symptomatic HCP were tested for SARS-CoV-2 and influenza by real-time PCR and/or rapid antigen detection test. ILI was defined as the sudden onset of ≥1 systemic symptom and ≥1 respiratory symptom. ARI was defined as the sudden onset of ≥1 respiratory symptom. Patients with respiratory symptoms were grouped either as ILI or as ARI based on the presence of fever, malaise, headache and/or myalgia., Results: Overall, 466 ILI cases and 383 ARI cases occurred. HCP with ILI had an adjusted odds ratio (aOR) of 22.05 [95% confidence interval (CI): 6.23-78.04] to be diagnosed with influenza. HCP with ARI had an aOR of 2.70 (95% CI: 1.88-3.88) to be diagnosed with COVID-19. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ILI for influenza were 96.6%, 49.9%, 18.2%, and 99.2%, respectively. The sensitivity, specificity, PPV, and NPV of ARI for COVID-19 were 51.7%, 73.6%, 84.9%, and 34.8%, respectively. ILI and ARI had an overall correct classification rate of 89.6% and 74.1%, respectively., Conclusion: Our findings support the use of both ILI and ARI case definitions in the diagnosis of influenza and COVID-19 in HCP., Competing Interests: Declaration of competing interest Dr Maltezou received an honorarium from Novavax to participate in a symposium. The authors have no conflict of interest to declare., (Copyright © 2024 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Aim: We assessed the vaccination effectiveness (VE) of a COVID-19 booster vaccine dose and the association between morbidity and absenteeism with COVID-19 booster vaccine receipt among healthcare personnel (HCP) in 2022-2023 in Greece., Methods: We followed 5752 HCP from November 14, 2022 through May 28, 2023 for episodes of absenteeism. Absenteeism for non-infectious causes, pregnancy leave, or annual leave was not recorded. Full vaccination was defined as a primary vaccination series plus one booster dose within the past six months. Multivariable regression models were used to estimate the association of full COVID-19 vaccination with the outcomes of interest., Results: A total of 1029 episodes of absenteeism occurred during the study period (17.9 episodes per 100 HCP). The mean duration of absence per episode was 5.2 days, and the total duration of absence was 5237 days. COVID-19 was diagnosed in 736 (12.8 %) HCP, asymptomatic SARS-CoV-2 infection in 62 (1.1 %) HCP, and influenza in 95 (1.7 %) HCP. Overall, COVID-19, influenza, and asymptomatic SARS-CoV-2 infection accounted for 71.5 %, 9.2 %, and 6.0 % of episodes of absenteeism, respectively. Multivariable regression models indicated that fully vaccinated HCP were absent from work for shorter periods [adjusted odds ratio (aOR): 0.42; 95 % confidence interval (CI): 0.21-0.83], were less likely to develop COVID-19 [aOR: 0.37; 95 % CI: 0.17-0.81)], and were more likely to develop an asymptomatic SARS-CoV-2 infection (aOR: 5.90; 95 % CI: 1.27-27.45). The adjusted full VE against COVID-19 was 62.8 % (95 % CI: 18.6 %-83.0 %)., Conclusions: COVID-19 remains a significant cause of morbidity and absenteeism among HCP. Full COVID-19 vaccination status conferred significant protection against COVID-19 and was associated with shorter periods of absence from work., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Maltezou received an honorarium from Novavax to participate in a symposium., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, we aimed to illustrate the trajectory of humoral and cellular immunity nine months after primary vaccination with the BNT162b2 mRNA vaccine among 189 healthcare workers (HCWs). Additionally, we endeavored to identify correlations between immunity parameters and a number of common variables and comorbidities. A total of 189 healthcare workers (HCWs), vaccinated against COVID-19, were finally included in the study. All of the subjects had received two doses of the BNT162b2 vaccine; had undergone antibody tests one, four and nine months post-vaccination; and had completed a medical questionnaire. Further samples taken at nine months were tested for cellular immunity. No participants had evidence of COVID-19 infection pre- or post-vaccination. An anti-S1 receptor binding domain (RBD) antibody assay was used to assess humoral response, and cellular immunity was estimated with an INF-γ release assay (IGRA). Statistical analysis was performed using STATA. We report a statistically significant antibody drop over time. Being above the age of 40 or a smoker reduces the rise of antibodies by 37% and 28%, respectively. More than half of the participants did not demonstrate T-cell activation at nine months. Female gender and antibody levels at four months predispose detection of cellular immunity at nine months post-immunization. This study furthers the qualitative, quantitative, and temporal understanding of the immune response to the BNT162b2 mRNA vaccine and the effect of correlated factors.

Aim: We estimated vaccine effectiveness (VE) of full (booster) vaccination against severe outcomes in hospitalized COVID-19 patients during the Delta and Omicron waves., Methods: The study extended from November 15, 2021 to April 17, 2022. Full vaccination was defined as a primary vaccination plus a booster ≥ 6 months later., Results: We studied 1138 patients (mean age: 66.6 years), of whom 826 (72.6 %) had ≥ 1 comorbidity. Of the 1138 patients, 75 (6.6 %) were admitted to intensive care unit (ICU), 64 (5.6 %) received mechanical ventilation, and 172 (15.1 %) died. There were 386 (33.9 %) fully vaccinated, 172 (15.1 %) partially vaccinated, and 580 (51 %) unvaccinated patients. Unvaccinated patients were absent from work for longer periods compared to partially or fully vaccinated patients (mean absence of 20.1 days versus 12.3 and 17.3 days, respectively; p-value = 0.03). Compared to unvaccinated patients, fully vaccinated patients were less likely to be admitted to ICU [adjusted relative risk (ARR: 0.49; 95 % CI: 0.29-0.84)], mechanically ventilated (ARR: 0.43; 95 % CI: 0.23-0.80), and die (ARR: 0.57; 95 % CI: 0.42-0.78), while they were hospitalized for significantly shorter periods (ARR: 0.79; 95 % CI: 0.70-0.89). The adjusted full VE was 48.8 % (95 % CI: 42.7 %-54.9 %) against ICU admission, 55.4 % (95 % CI: 52.0 %-56.2 %) against mechanical ventilation, and 22.6 % (95 % CI: 7.4 %-34.8 %) against death. For patients with ≥ 3 comorbidities, VE was 56.2 % (95 % CI: 43.9 %-67.1 %) against ICU admission, 60.2 % (95 % CI: 53.7 %-65.4 %) against mechanical ventilation, and 43.9 % (95 % CI: 19.9 %-59.7 %) against death., Conclusions: Full (booster) COVID-19 vaccination conferred protection against severe outcomes, prolonged hospitalization, and prolonged work absenteeism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: We assessed the impact of COVID-19 vaccination status and time elapsed since the last vaccine dose on morbidity and absenteeism among healthcare personnel (HCP) in the context of a mandatory vaccination policy., Methods: We followed 7592 HCP from November 15, 2021 through April 17, 2022. Full COVID-19 vaccination was defined as a primary vaccination series plus a booster dose at least six months later., Results: There were 6496 (85.6 %) fully vaccinated, 953 (12.5 %) not fully vaccinated, and 143 (1.9 %) unvaccinated HCP. A total of 2182 absenteeism episodes occurred. Of 2088 absenteeism episodes among vaccinated HCP with known vaccination status, 1971 (94.4 %) concerned fully vaccinated and 117 (5.6 %) not fully vaccinated. Fully vaccinated HCP had 1.6 fewer days of absence compared to those not fully vaccinated (8.1 versus 9.7; p-value < 0.001). Multivariable regression analyses showed that full vaccination was associated with shorter absenteeism compared to not full vaccination (OR: 0.56; 95 % CI: 0.36-0.87; p-value = 0.01). Compared to a history of ≤ 17.1 weeks since the last dose, a history of > 17.1 weeks since the last dose was associated with longer absenteeism (OR: 1.22, 95 % CI:1.02-1.46; p-value = 0.026) and increased risk for febrile episode (OR: 1.33; 95 % CI: 1.09-1.63; p-value = 0.004), influenza-like illness (OR: 1.53, 95 % CI: 1.02-2.30; p-value = 0.038), and COVID-19 (OR: 1.72; 95 % CI: 1.24-2.39; p-value = 0.001)., Conclusions: The COVID-19 pandemic continues to impose a considerable impact on HCP. The administration of a vaccine dose in less than four months before significantly protected against COVID-19 and absenteeism duration, irrespective of COVID-19 vaccination status. Defining the optimal timing of boosters is imperative., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Our aim was to estimate vaccination and susceptibility rates against vaccine-preventable diseases among healthcare personnel (HCP) in eight hospitals., Methods: Cross-sectional survey., Results: A total of 1284 HCP participated (physicians: 31.3%, nursing personnel: 36.6%, paramedical personnel: 11.1%, administrative personnel: 13.2%, supportive personnel: 7.3%). Vaccination rates were 32.9% against measles and mumps, 38.1% against rubella, 5.7% against varicella, 9.2% against hepatitis A, 65.8% against hepatitis B, 31.8% against tetanus-diphtheria, 7.1% against pertussis, 60.2% against influenza, and 80.1% against COVID-19. Susceptibility rates were as follows: 27.8% for measles, 39.6% for mumps, 33.4% for rubella, 22.2% for varicella, 86.3% for hepatitis A, 34.2% for hepatitis B, 68.2% for tetanus-diphtheria, and 92.9% for pertussis. Older HCP had higher susceptibility rates against mumps, rubella, varicella, hepatitis A, hepatitis B, tetanus-diphtheria, and pertussis (p-values <0.001 for all). Mandatory vaccinations were supported by 81.85% of HCP., Conclusions: Although most HCPs supported mandatory vaccinations, significant vaccination gaps, and susceptibility rates were recorded. The proportion of susceptible HCP to measles, mumps, rubella, and varicella has increased in the past decade, mostly because of reduction in acquired cases of natural illness. Vaccination programs for HCP should be developed. A national registry to follow HCP's vaccination rates is urgently needed.

Aim: Healthcare personnel (HCP) are prioritized for coronavirus disease 2019 (COVID-19) vaccination to protect them and non-disruptive provision of healthcare services. We assessed the impact of the Pfizer-BioNTech vaccine on morbidity and absenteeism among HCP., Methods: We studied 7445 HCP in five tertiary-care hospitals in Greece from November 15, 2020 through April 18, 2021., Results: A total of 910 episodes of absenteeism and 9695 days of absence were recorded during the entire study period. Starting from January 4, 2021, 4823/7445 HCP (64.8%) were fully or partially vaccinated. Overall, 535 episodes of absenteeism occurred from January 4, 2021 through April 18, 2021, including 309 (57.76%) episodes among 2622 unvaccinated HCP and 226 (42.24%) episodes among 4823 vaccinated HCP (11.8 versus 4.7 episodes of absenteeism per 100 HCP, respectively; p-value < 0.001). The mean duration of absenteeism was 11.9 days among unvaccinated HCP compared with 6.9 days among vaccinated HCP (p-value < 0.001). Unvaccinated HCP more frequently developed acute respiratory infection, influenza-like illness, and COVID-19 (p-values < 0.001 for all comparisons). Vaccine effectiveness for fully vaccinated HCP was estimated at 94.16% [confidence interval (CI): 88.50%-98.05%) against COVID-19, 83.62% (CI: 73.36%-90.38%) against SARS-CoV-2 infection (asymptomatic or COVID-19), and 66.42% (CI: 56.86%-74.15%) against absenteeism., Conclusion: The COVID-19 pandemic had a considerable impact on healthcare workforce. The Pfizer-BioNTech vaccine significantly reduced morbidity, COVID-19, absenteeism and duration of absenteeism among HCP during a period of high SARS-CoV-2 circulation in the community. It is expected that HCP vaccination will protect them and healthcare services and contain healthcare costs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: To investigate intention rates to get vaccinated against COVID-19 among healthcare personnel (HCP) in Greece., Methods: Cross-sectional survey., Results: The response rate was 14.5%. Of 1521 HCP with a known profession, 607 (39.9%) were nursing personnel, 480 (31.6%) physicians, 171 (11.2%) paramedical personnel, 72 (4.7%) supportive personnel, and 191 (12.6%) administrative personnel. Overall, 803 of 1571 HCP (51.1%) stated their intention to get vaccinated while 768 (48.9%) stated their intention to decline vaccination. Most HCP (71.3%) who reported intent to get vaccinated noted contributing to the control of the pandemic and protecting their families and themselves as their reasons, while the most common reason for reporting intent to decline vaccination was inadequate information about the vaccines (74.9%), followed by concerns about vaccine safety (36.2%). Logistic regression analysis revealed that the probability of intending to get vaccinated increased with male gender, being a physician, history of complete vaccination against hepatitis B, history of vaccination against pandemic A (H1N1) in 2009-2010, belief that COVID-19 vaccination should be mandatory for HCP, and increased confidence in vaccines in general during the COVID-19 pandemic. The following factors were associated with a lower intention to get vaccinated: no vaccination against influenza the past season, no intention to get vaccinated against influenza in 2020-2021, and no intention to recommend COVID-19 vaccination to high-risk patients., Conclusion: There is an urgent need to built safety perception towards COVID-19 vaccines and raise vaccine uptake rates by HCP, and thus to protect the healthcare workforce and the healthcare services., (Copyright © 2021 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Background: As of late February 2020, Greece has been experiencing the coronavirus disease 2019 (COVID-19) epidemic. Healthcare personnel (HCP) were disproportionately affected, accounting for ~10% of notified cases. Exclusion from work for 7 days was recommended for HCP with high-risk occupational exposure. Our aim was to evaluate the 7-day exclusion from work policy for HCP with high-risk exposure., Methods: HCP with a history of occupational exposure to COVID-19 were notified to the Hellenic National Public Health Organization, regardless of their exposure risk category. Exposed HCP were followed for 14 days after last exposure., Results: We prospectively studied 3398 occupationally exposed HCP; nursing personnel accounted for most exposures (n = 1705; 50.2%). Of the 3398 exposed HCP, 1599 (47.1%) were classified as low-risk, 765 (22.5%) as moderate-risk, and 1031 (30.4%) as high-risk exposures. Sixty-six (1.9%) HCP developed COVID-19 at a mean of 3.65 (range: 0-17) days postexposure. Of the 66 HCP with COVID-19, 46, 7, and 13 had a history of high-, moderate- or low-risk exposure (4.5%, 0.9%, and 0.8% of all high-, moderate-, and low-risk exposures, respectively). Hospitalization and absenteeism were more prevalent among HCP with high-risk exposure. A logistic regression analysis showed that the following variables were significantly associated with an increased risk for the onset of COVID-19: male, administrative personnel, underlying disease, and high-risk exposure., Conclusions: HCP with high-risk occupational exposure to COVID-19 had increased probability of serious morbidity, healthcare seeking, hospitalization, and absenteeism. Our findings justify the 7-day exclusion from work policy for HCP with high-risk exposure., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Aim: Data about susceptibility rates in young adults are scarce. We estimated the complete vaccination rates, timeliness of vaccinations and susceptibility rates among male military recruits in Greece., Methods: A standardized form was used to collect data. Immunity against measles, rubella, varicella, hepatitis A and hepatitis B was serologically estimated., Results: We studied 385 recruits with a mean age of 23.5 years (range: 18.3-29.9 years). Complete vaccination rates were 94.3% for measles, 100% for rubella, 15% for varicella, 73.9% for hepatitis A and 96.5% for hepatitis B. Only 10.8% of participants were fully vaccinated against all five diseases. Timely vaccination was 47.2% for measles, 89.3% for rubella and 48.1% for hepatitis B. Recruits >23 years had a 1.5-fold increased probability for incomplete vaccinations compared to younger recruits. Laboratory-confirmed immunity rates were 80% against measles, 85.7% against rubella, 85.2% against varicella, 69.4% against hepatitis A and 77.1% against hepatitis B. It is estimated that approximately 388,696 persons aged 18-30 years are susceptible to measles, 277,640 persons to rubella, 287,736 persons to varicella, 595,664 persons to hepatitis A and 444,224 persons to hepatitis B in Greece., Conclusion: Our study showed that young adults have significant immunity gaps against measles, rubella, varicella, hepatitis A and hepatitis B. Complete vaccination rates were suboptimal against hepatitis A and varicella. Strategies to access young adults and increase immunity rates through catch-up vaccination services should be investigated. A third dose of MMR vaccine should be considered for young adolescents in Greece., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Bundles of preventive measures may improve patient outcomes. The aim of this study is to investigate if a surgical site infections (SSIs) preventive bundle in orthopedic surgery patients can result in reduction of such infections, hospitalization length and cost., Methods: The present is a retrospective cohort study. A total of 1299 patients was admitted to hospital for an elective orthopedic procedure during 2012-2015. The patients were subjected to either an integrated three-stage SSIs preventive protocol or standard preventive measures. The two groups were compared for incidence of SSIs, median hospitalization length and median cost., Results: The incidence of SSIs was lower in the new-protocol group, when compared to the old protocol one (p=0.102). Median (md) hospitalization length was significantly lower in the new protocol group (md = 2) compared to "old-protocol" group (md= 5) [U = 280520, p<0.001]. Regarding arthroscopies, the median cost in the new protocol patients (md= 1500) was significantly lower compared to "old-protocol" patients (md= 1585) [(U= 112660), p < 0.001]. Knee arthroplasties' median costs did not differ (both mds= 4400, U = 2002, p > 0.05). For hip arthroplasties, the new protocol's patient median cost (md= 3000) was significantly lower than that of "old-protocol" (md = 4000) [U = 19680, p < 0.001]., Conclusions: The use of a bundle of measures for the prevention of SSIs in a hospital's orthopedic operations proved effective, since it resulted in substantial decrease of SSIs, statistically significant decreased hospitalization length, as well as cost.

Background: The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013., Methods: There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI. Samples were tested for the presence of glutamate dehydrogenase antigen (GDH) and toxins A/B of C. difficile; samples positive for GDH and negative for toxins were further tested by culture and PCR for the presence of toxin genes. An analysis was performed to identify potential risk factors for CDI among patients with diarrhea., Results: 5,536 and 6,523 patients were screened during the first and second study periods, respectively. The respective point-prevalence of CDI in all patients was 5.6 and 3.9 per 10,000 patient bed-days whereas the proportion of CDI among patients with diarrhea was 17% and 14.3%. Logistic regression analysis revealed that solid tumor malignancy [odds ratio (OR) 2.69, 95% confidence interval (CI): 1.18-6.15, p = 0.019] and antimicrobial administration (OR 3.61, 95% CI: 1.03-12.76, p = 0.045) were independent risk factors for CDI development. Charlson's Comorbidity Index (CCI) >6 was also found as a risk factor of marginal statistical significance (OR 2.24, 95% CI: 0.98-5.10). Median time to CDI from hospital admission was shorter with the presence of solid tumor malignancy (3 vs 5 days; p = 0.002) and of CCI >6 (4 vs 6 days, p = 0.009)., Conclusions: The point-prevalence of CDI in Greek hospitals was consistent among cases of diarrhea over a 6-month period. Major risk factors were antimicrobial use, solid tumor malignancy and a CCI score >6.

In January 1996, during an outbreak of meningococcal disease at a Hellenic Air Force recruit center in southern Greece, we collected paired serum specimens from 55 randomly selected recruits and tested for antibodies against influenza virus types A and B. Of 55 specimens, 15 (27%) were found to be positive for recent influenza B infection, confirming previous reports that respiratory tract infection due to influenza is probably a predisposing factor for meningococcal disease.

Leishmania are parasites that survive within macrophages by mechanism(s) not entirely known. Depression of cellular immunity and diminished production of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha are potential ways by which the parasite survives within macrophages. We examined the mechanism(s) by which lipophosphoglycan (LPG), a major glycolipid of Leishmania, perturbs cytokine gene expression. LPG treatment of THP-1 monocytes suppressed endotoxin induction of IL-1 beta steady-state mRNA by greater than 90%, while having no effect on the expression of a control gene. The addition of LPG 2 h before or 2 h after endotoxin challenge significantly suppressed steady-state IL-1 beta mRNA by 90% and 70%, respectively. LPG also inhibited tumor necrosis factor alpha and Staphylococcus induction of IL-1 beta gene expression. The inhibitory effect of LPG is agonist-specific because LPG did not suppress the induction of IL-1 beta mRNA by phorbol 12-myristate 13-acetate. A unique DNA sequence located within the -310 to -57 nucleotide region of the IL-1 beta promoter was found to mediate LPG's inhibitory activity. The requirement for the -310 to -57 promoter gene sequence for LPG's effect is demonstrated by the abrogation of LPG's inhibitory activity by truncation or deletion of the -310 to -57 promoter gene sequence. Furthermore, the minimal IL-1 beta promoter (positions -310 to +15) mediated LPG's inhibitory activity with dose and kinetic profiles that were similar to LPG's suppression of steady-state IL-1 beta mRNA. These findings delineated a promoter gene sequence that responds to LPG to act as a "gene silencer", a function, to our knowledge, not previously described. LPG's inhibitory activity for several mediators of inflammation and the persistence of significant inhibitory activity 2 h after endotoxin challenge suggest that LPG has therapeutic potential and may be exploited for therapy of sepsis, acute respiratory distress syndrome, and autoimmune diseases.

The genus Leishmania, an obligate intramacrophage parasite, causes a wide spectrum of clinical diseases. It is worldwide in distribution and causes 20 million new cases annually with an at risk population of approximately 1.5 billion persons. The most severe forms are associated with high morbidity, mortality and relapses with conventional therapy. The therapeutic issues and responses to standard and alternative therapies are reviewed. Recent developments in molecular biology and immunology methods employed in the study of leishmaniasis have defined an intricate interaction of the parasite with host immune system. Perturbation of the host immune responses may be part of the survival mechanisms of Leishmania. In murine model, the finding of T helper cells that differ by their panel of cytokines has allowed a more precise definition of immunopathogenesis of leishmaniasis. Preliminary data from leishmaniasis patients lend support to this concept of altered immunomodulation. Furthermore, the data from leishmaniasis patients lend support to this concept of altered enhancement of therapeutic response by interferon-gamma has provided a new approach for treatment of patients using recombinant cytokines and for the study of the disease. Current research for early diagnosis, alternative therapies and need for vaccines are reviewed in the context of the immunopathology of leishmaniasis.