Incidence Of Symptomatic Infection Research Articles

Vaccination Strategies based on a Mathematical Model of Epidemics Considering the Age Structure of the Population

During the COVID-19 pandemic, it is important to promote the skills needed for analyzing the disease course, including determining the relevance of vaccinations, especially among people who are unfamiliar with computer programming. This paper describes the basic epidemiological model (SIR), its extensions that allow vaccinations, and the emergence of renewed waves of disease growth. It also discusses a literature model, extended SEIRD, which includes a more detailed division of the population into susceptible, latent, symptomatic, and asymptomatic infected, recovered, and dead in eight age groups. Modifying the SEIRD model as shown on the basic SIR model, we analyzed five vaccination strategies, considering the limited vaccine supply, the number of vaccinations performed per day, and their effectiveness. The analysis was performed for a group of one million people, using the parameters of the model characteristic of the COVID-19 pandemic and Sweden's generational structure. We analyzed in terms of reducing both the number of deaths and the incidence of symptomatic infections, which represent the main burden of healthcare.

Evaluation of Lactobacillus Coryniformis K8 Consumption by Health Care Workers Exposed to COVID-19 (LactoCor2 Project): Protocol for a Randomized Controlled Trial.

Lactobacillus coryniformis K8 CECT5711 has immune-modulating properties, enhances the immune response to viral antigens leading to the production of specific antibodies, and has anti-inflammatory activity, which may help to prevent uncontrolled inflammatory processes leading to respiratory and other organ failures. The purpose of this study is to evaluate the effect of the consumption of a probiotic strain on the incidence and severity of COVID-19 in health personnel who carry out their professional work among patients with infection or suspected infection by SARS-CoV-2. This is a double-blind randomized clinical trial in which the experimental group will receive a capsule of L coryniformis K8 per day (3×109 colony former units/day), and the control group will receive a daily placebo capsule consisting of maltodextrin. A sample size of 314 volunteers was calculated. Volunteers must meet the following inclusion criteria: older than 20 years and active health personnel caring for patients with COVID-19, including all professionals such as medical doctors, nurses, and caretakers at the 2 referral hospitals that treat patients with COVID-19. The main outcome of the clinical trial will be the incidence of symptomatic infection by SARS-CoV-2 in personnel who care for patients with suspected or confirmed COVID-19. The study had to be extended to the 2 referral hospitals that treat patients with COVID-19 in the province of Granada (Andalusia, Spain); Hospital San Cecilio and Hospital Virgen de las Nieves. A total of 255 individuals met the inclusion criteria and were randomly assigned to one of the 2 groups. The results of this randomized controlled trial will provide valuable information regarding the administration of L coryniformis K8 against COVID-19, including whether there are fewer infectious processes due to this virus or, in case of occurrence, whether the disease is milder in participants taking the probiotic strain. ClinicalTrials.gov NCT04366180; http://www.clinicaltrials.gov/ct2/show/NCT04366180. RR1-10.2196/37857.

Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months

BackgroundDespite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear.MethodsWe conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months.ResultsThe study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman’s rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46).ConclusionsSix months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Modelling COVID-19 severity in the Republic of Ireland using patient co-morbidities, socioeconomic profile and geographic location, February to November 2020

Understanding patient progression from symptomatic COVID-19 infection to a severe outcome represents an important tool for improved diagnoses, surveillance, and triage. A series of models have been developed and validated to elucidate hospitalization, admission to an intensive care unit (ICU) and mortality in patients from the Republic of Ireland. This retrospective cohort study of patients with laboratory-confirmed symptomatic COVID-19 infection included data extracted from national COVID-19 surveillance forms (i.e., age, gender, underlying health conditions, occupation) and geographically-referenced potential predictors (i.e., urban/rural classification, socio-economic profile). Generalised linear models and recursive partitioning and regression trees were used to elucidate COVID-19 progression. The incidence of symptomatic infection over the study-period was 0.96% (n = 47,265), of whom 3781 (8%) required hospitalisation, 615 (1.3%) were admitted to ICU and 1326 (2.8%) died. Models demonstrated an increasingly efficacious fit for predicting hospitalization [AUC 0.816 (95% CI 0.809, 0.822)], admission to ICU [AUC 0.885 (95% CI 0.88 0.89)] and death [AUC of 0.955 (95% CI 0.951 0.959)]. Severe obesity (BMI ≥ 40) was identified as a risk factor across all prognostic models; severely obese patients were substantially more likely to receive ICU treatment [OR 19.630] or die [OR 10.802]. Rural living was associated with an increased risk of hospitalization (OR 1.200 (95% CI 1.143–1.261)]. Urban living was associated with ICU admission [OR 1.533 (95% CI 1.606–1.682)]. Models provide approaches for predicting COVID-19 prognoses, allowing for evidence-based decision-making pertaining to targeted non-pharmaceutical interventions, risk-based vaccination priorities and improved patient triage.

The Population-Level Effect of Screening for Mycoplasma genitalium on Antimicrobial Resistance: A Quasi-Experimental Study.

No studies have evaluated the utility and risks of screening for Mycoplasma genitalium in men who have sex with men taking preexposure prophylaxis (PrEP). We made use of a quasi-experimental design to evaluate the effect of screening for M. genitalium in a demonstration PrEP cohort with 3-monthly follow-up. We compared the proportion of PrEP participants with M. genitalium clearance, the duration of persistence, proportion with incident symptoms, the incidence of fluoroquinolone and macrolide resistance, and the proportion of noncleared infections with resistance-associated mutations between 2 groups: those in whom the first episode of M. genitalium was treated and those in whom it was not treated. M. genitalium was detected in 70 of 179 individuals. The first episode of infection was treated in 46 individuals. Treatment was not significantly associated with the incidence of symptomatic infections or the acquisition of genotypic resistance. Treatment was associated with a higher probability of clearance of infection but at the expense of increasing the proportion of remaining infections that were resistant. In the nontreated group, the infections that did not clear were less likely to be fluoroquinolone resistant (1/6 [16.7%]) than those that did clear (4/4 [100%]; P = 0.048). In contrast, in the treated group, there was no significant difference in the proportion of fluoroquinolone resistance between the infections that persisted and cleared. If screening and treatment increase the ratio of resistant to susceptible M. genitalium in a population, then this could play a role in the spread of antimicrobial resistance.

P612 Lower incidence of COVID-19 in patients with Inflammatory Bowel Diseases treated with non-gut-selective biologic therapy: an observational multicentre study

BackgroundSince the outbreak of COVID-19, concerns have been raised as to whether IBD patients under biologic therapy might be more susceptible to the disease and its complications. This study aimed to determine the incidence and outcomes of COVID-19 in a large cohort of IBD patients on biologic therapy in Lombardy, the hardest-hit Italian region by the pandemic.MethodsThis is an observational retrospective multicentre study collecting data about COVID-19 in IBD patients on biologic therapy in regular clinical follow-up at 11 IBD referral units in Lombardy, between February 20th and May 20th, 2020. The main endpoints were to assess the cumulative incidence of COVID-19 and its outcome (hospitalization/death) among IBD patients on biologic therapy and to identify any variations among the different classes of biologic agents. Secondarily, we compared the results with the incidence of COVID-19 in the general population of Lombardy in the same period and the incidence of symptoms suggestive of COVID-19 in our study population compared with those of a second cohort of IBD patients undergoing non-biological therapies and coming from the same geographic area.ResultsOverall, 1816 IBD patients on biologic therapy were enrolled. The cumulative incidence of COVID-19 was 3.9 per 1000 (7/1816) with a hospitalization rate of 57% and a case-fatality rate (CFR) of 29%. In our Cohort, the gut-selective therapy (Vedolizumab and Etrolizumab) was the only risk factor of developing symptomatic COVID-19 (OR 8.7, 95% CI 1.7–45.0, p = 0.01). Conversely, non-gut selective anti-cytokine agents were associated with a lower incidence of infection (OR 0.13, 95%CI 0.02–0.74) and development of symptoms (OR 0.60, 95%CI 0.37–0.98). Compared to the general population of Lombardy, a lower incidence of COVID-19 was observed (3.9 vs 8.5 per 1000 with a RR 0.45, 95%CI 0.21–0.95); conversely, in terms of hospitalization rate and CFR, the clinical outcome was not statistically different. Finally, compared to a second cohort of 565 IBD patients treated with non-biologic conventional therapies, a significantly lower risk of symptomatic disease was observed in patients on biologic agents (OR 0.3, 95%CI 0.2–0.4, p<0.01).ConclusionCompared to the general population, IBD patients on biologic therapy are not exposed to a higher risk of COVID-19; compared to gut-selective agents, cytokine blockers are associated with a lower incidence of symptomatic infection, supporting the decision of maintaining the ongoing treatment.

SARS-CoV-2 in Myelodysplastic Syndromes: A Snapshot From Early Italian Experience.

SARS-CoV-2 in Myelodysplastic Syndromes: A Snapshot From Early Italian Experience.

P1699EFFECT OF UREMIA IN THE POSTOPERATIVE OF PREEMPTIVE LIVING-DONOR KIDNEY TRANSPLANT PATIENTS

Abstract Background and Aims Getting a preemptive kidney transplant has many benefits but no studies have assessed the potential deleterious effect of uremia on peritransplant complications. Uremic toxins interact negatively with biologic functions and may contribute to infections and bleeding or thormbosis. Method we evaluated 255 living-donor kidney transplant recipients (117 preemptive and 138 non-preemptive) from January 2006 to December 2015. Patients iniciated immunosuppression treatment 3 days prior to transplant. Exclusion criteria included: history of solid organ transplant, chronic immunosuppression treatment at the time of transplant (including prednisone), peritransplant rituximab/eculizumab treatment and HIV infection. An analysis of baseline characteristics and the incidence of symptomatic infection, bleeding or thrombosis during first week was performed in both groups. To analyze bleeding, the need of transfusion, drop of hematocrit in 72h and need of bladder washout was assessed. Results baseline characteristics are descrived in table 1. Non preemptive patients were older (50 vs 46 years) and had a higher prevalence of Diabetes Mellitus and dialypemia (22 vs 11% and 43 vs 30% respectively), without differences in the immunosupression scheme. The median eGFR in preemptive group at transplant was 12 ml/min. A more anemic profile was detected in the preemptive group with median hemoglobin of 116 vs 127 g/L in the non-preemptive group with no-differences in albumin levels. There were a total of 38 symptomatic infections (22 in the preemptive and 16 in the non-preemptive group), without statistical differences in the incidence between the groups (OR 1,75 CI 0,879-3,5, P =0,107). Hematocrit drop was greater in the non-preemptive group (8 vs 6 points in the first 72h p = 0.004) but thrombosis was more common in the preemptive group (5 vs 1, OR 6,116 CI 0,704-53,1, p = 0.062). Conclusion Uremia in preemptive living kidney transplant recipients does not seem to have influence on the incidence of infections in the first week after transplantation. The bleeding profile in the non-preemptive group in contrast to the prothrombotic profile in preemptive recipients needs further investigation in future studies that assess parameters of platelet and coagulation function as well as endothelial activation.

The incidence of symptomatic infection with influenza virus in the Netherlands 2011/2012 through 2016/2017, estimated using Bayesian evidence synthesis.

Due to differences in the circulation of influenza viruses, distribution and antigenic drift of A subtypes and B lineages, and susceptibility to infection in the population, the incidence of symptomatic influenza infection can vary widely between seasons and age-groups. Our goal was to estimate the symptomatic infection incidence in the Netherlands for the six seasons 2011/2012 through 2016/2017, using Bayesian evidence synthesis methodology to combine season-specific sentinel surveillance data on influenza-like illness (ILI), virus detections in sampled ILI cases and data on healthcare-seeking behaviour. Estimated age-aggregated incidence was 6.5 per 1000 persons (95% uncertainty interval (UI): 4.7-9.0) for season 2011/2012, 36.7 (95% UI: 31.2-42.8) for 2012/2013, 9.1 (95% UI: 6.3-12.9) for 2013/2014, 41.1 (95% UI: 35.0-47.7) for 2014/2015, 39.4 (95% UI: 33.4-46.1) for 2015/2016 and 27.8 (95% UI: 22.7-33.7) for season 2016/2017. Incidence varied substantially between age-groups (highest for the age-group <5 years: 23 to 47/1000, but relatively low for 65+ years: 2 to 34/1000 over the six seasons). Integration of all relevant data sources within an evidence synthesis framework has allowed the estimation - with appropriately quantified uncertainty - of the incidence of symptomatic influenza virus infection. These estimates provide valuable insight into the variation in influenza epidemics across seasons, by virus subtype and lineage, and between age-groups.

Сравнительная эффективность стандартной антибиотикотерапии и терапии препаратом Канефрон Н бессимптомной бактериурии у беременных

A retrospective analysis was performed on 60 pregnant women who received either a standard antibiotic regimen (n=32) or the herbal preparation Canephron N (n=28). The primary outcomes were the incidence of symptomatic infections (cystitis or pyelonephritis), premature birth and low birth weight delivery, and incidence of persistent/recurrent bacteriuria. In the group of antibiotic therapy, one patient developed cystitis and three had pyelonephritis; in the Canephron N group, cystitis occurred in one patient, no pyelonephritis cases were observed. Among the whole study cohort (n=60), the incidence of symptomatic infections and pyelonephritis was 8.3 and 5.0%, respectively. The incidence of symptomatic infections (cystitis, pyelonephritis) did not differ statistically significantly between the study groups (p=0.2157). There were three and one premature births in the group of antibiotic therapy and the Canephron N group, respectively (p=0,373), and two low birth weight deliveries in each group (p=0.891). Recurrent bacteriuria was registered in 17 patients from the group of antibiotic therapy and in three in the Canephron N group (p=0.0006). The management of asymptomatic bacteriuria in pregnancy using Canephron N is not inferior to standard antibiotic therapy regarding the incidence of symptomatic infection, premature birth, and low birth weight delivery. Persistent/recurrent bacteriuria was more common in women receiving the antibiotic therapy.

Infecção natural pelo vírus da diarreia viral bovina (BVDV) em bovinos de corte no Estado do Pará

Background: Bovine viral diarrhea virus (BVDV) is a pathogen that causes great economic losses in dairy and beef herds.The main disturbances caused by this virus are related to abortion, fetal malformation and mummification, and the birth ofweak calves. In addition, this disease may result in persistently infected animals, as well as individual immune tolerance tothe virus. However, the symptoms are nonspecific and variable, and dependent on the age of affected animal. The objectiveof the present study was to report three cases with clinical signs of BVDV infection, with subsequent confirmation of thediagnosis by reverse transcription - polymerase chain reaction technique (RT-PCR).Cases: In a beef production farm located at the state of Para, Brazil, three animals presented severe diarrhea; the feces wereliquefied and greenish-yellow in color; crusted lesions were visible and scattered over various parts of the animals’ bodies,including the muzzle, nostrils, periauricular region, and hooves; the tongue mucosa was undergoing an intense desquamationprocess. One of the affected animals, a 6-month-old calf, was euthanized following the recommendations of the “Brazilianguide to good practices for animal euthanasia” of the Ethics, Bioethics and Animal Welfare Committee / Federal Council ofVeterinary Medicine. After euthanasia, this calf was necropsied and some of its organs, including the tongue and skin, weresent to the Biological Institute of Sao Paulo State for histopathology examination (HE) and identification and isolation of thevirus. Positive samples for the presence of BVDV were diagnosed by RT-PCR, confirming the suspicion and explaining thesigns observed in that animal and reported in other dead animals of the farm. Because RT-PCR was performed in ulcerativelesions present in the tongue, negative reactions were detected for bovine herpesvirus (BoHV) and positive reactions forBVDV. The cutaneous tissue was marked with lymphocytic infiltration, observed in both epidermis and dermis, which refersto crusted lesions distributed in several regions of the animal’s body. In the lungs, we observed rare areas of emphysema andmarked lymphocytic interstitial pneumonia with hemorrhagic spots, correlated with symptoms of respiratory disease. Also,marked renal damage and spleen lesions were identified, indicating glomerulonephritis and lymphocytic splenitis.Discussion: This study evidenced the occurrence of BVDV in two calves and one adult animal, which is in agreementwith the described higher incidence of symptomatic infection in young animals. Clinical signs of severe greenish-yellowdiarrhea and crusted lesions distributed throughout several regions of the animals’ bodies, including the muzzle, nostrils,periauricular region, and hooves were described, with intense tongue epithelium desquamation, which is a particular andcharacteristic symptom of Mucosal Disease - the classical form of the physiopathogeny caused by bovine viral diarrheavirus. The clinical findings of severe diarrhea are possibly related to the histopathological results, which showed hyaliniza-tion of the intestinal mucosa and rare mononuclear cells in the liver nodules. Pulmonary histopathological findings of rareareas of lymphocytic interstitial pneumonia, severe emphysema, and hemorrhagic foci refer to respiratory diseases. Basedon the clinical signs and laboratory findings, we conclude that the affected animals showed classic symptoms of bovineviral diarrhea. This diagnosis highlights the presence of the disease in cattle raised in the state of Para, Brazil.

Modelling the impact of extended vaccination strategies on the epidemiology of pertussis

SUMMARYThe aim of this study was to investigate the optimal pertussis booster vaccination strategy for The Netherlands. A realistic age-structured deterministic model was designed. Assuming a steady-state situation and correcting for underreporting, the model was calibrated using notification data from the period 1996–2000. Several sensitivity analyses were performed to explore the impact of different assumptions for parameters surrounded by uncertainty (e.g. duration of protection after natural infection, underreporting factors, and transmission probabilities). The optimal age of an additional booster dose is in the range of 10–15 years, and implementation of this booster dose will reduce both symptomatic and asymptomatic infections, although the incidence of symptomatic infections in older age groups will increase. The impact of the different assumptions used in the model was in general limited. We conclude that over a wide range of assumptions, an additional booster dose can reduce the incidence of pertussis in the population.

PIN99 Modelling the Impact of Extended Vaccination Strategies on the Epidemiology of Pertussis

The aim of this study was to investigate the optimal pertussis booster vaccination strategy for The Netherlands. A realistic age-structured deterministic model was designed. Assuming a steady-state situation and correcting for underreporting, the model was calibrated using notification data from the period 1996–2000. Several sensitivity analyses were performed to explore the impact of different assumptions for parameters surrounded by uncertainty (e.g. duration of protection after natural infection, underreporting factors, and transmission probabilities). The optimal age of an additional booster dose is in the range of 10–15 years, and implementation of this booster dose will reduce both symptomatic and asymptomatic infections, although the incidence of symptomatic infections in older age groups will increase. The impact of the different assumptions used in the model was in general limited. We conclude that over a wide range of assumptions, an additional booster dose can reduce the incidence of pertussis in the population.

The severity of pandemic H1N1 influenza in the United States, April -- July 2009.

BackgroundAccurate measures of the severity of pandemic influenza A/H1N1 (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely. Methods and FindingsWe used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data: medically attended cases in Milwaukee or self-reported influenza-like illness in New York, were used to estimate ratios of symptomatic cases:hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic cases that died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated sCFR of 0.048% (95% credible interval, CI 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-9x lower. sCFR and sCIR appear to be highest in persons 18 and older, and lowest in children 5-17. sCHR appears to be lowest in persons 5-17; our data were too sparse to allow us to determine the group in which it was the highest. ConclusionsThese estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with greatest impact in young children and non-elderly adults. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the proportion infected or symptomatic were lower.

The severity of pandemic H1N1 influenza in the United States, from April to July 2009: a Bayesian analysis.

Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data--medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York--were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-9 x lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.

Cytomegalovirus infection in pregnancy

Primary and recurrent infections of human cytomegalovirus (HCMV) can occur during pregnancy. Both can result in congenital infection, the leading infectious cause of mental retardation, sensorineural deafness and visual impairment. The intrauterine transmission of HCMV and an adverse outcome are mainly related to a primary maternal infection. However, there is currently increasing evidence that the incidence of symptomatic infections in infants born to immune mothers is higher than previously thought. The option of a prenatal diagnosis therefore has a crucial role in the management of pregnancies complicated by active HCMV infection. In spite of the potentially devastating consequences of congenital HCMV infection, little information is available concerning antiviral therapy as prophylactic treatment for women at high risk of the transmission of HCMV during pregnancy. Passive immunization for the prevention of vertical transmission of the virus appears promising. Until a HCMV vaccine is available, education is needed regarding the risk involved and the strategies to be adopted for the prevention of HCMV infection during pregnancy.

Impact of targeted oral ganciclovir prophylaxis for transplant recipients of livers from cytomegalovirus‐seropositive donors

Symptomatic cytomegalovirus (CMV) infection can cause significant morbidity and occasional mortality after liver transplantation. In a previous audit, we showed that donor CMV seropositivity (D+) was a risk factor for symptomatic infection, and we estimated the likely clinical and financial impact of 14 weeks of oral ganciclovir prophylaxis given to recipients of CMV-seropositive organs. In August 2001, we adopted this policy of targeted oral ganciclovir prophylaxis for recipients of CMV-seropositive livers. The additional costs of adopting targeted prophylaxis policy for 1 year, patient and doctor compliance with the new strategy, and its clinical impact were analysed. Targeted prophylaxis reduced the incidence of symptomatic CMV infection from 9.5% (in the earlier cohort that did not receive prophylaxis) to 5.8% (P = NS). Symptomatic infection was not observed in CMV-seropositive recipients of CMV-seropositive donor livers (P = 0.06 for comparison of the 2 cohorts), but the incidence of symptomatic infection in the CMV-seronegative recipients of CMV-seropositive organs did not change. However, symptomatic infection appeared to be less severe and was delayed by ganciclovir prophylaxis (median time from transplantation to symptom onset 96 vs. 39 days without prophylaxis). Death attributable to CMV infection was not observed in the cohort that received prophylaxis. The additional cost associated with implementation of the prophylaxis strategy was 108,068 pounds sterlings. Targeted CMV prophylaxis with oral ganciclovir reduces the incidence and severity of symptomatic infection and appears to be a cost-effective means of improving outcome following liver transplantation.

Preconceptional immunity to cytomegalovirus and the risk of symptomatic congenital infection

Congenital cytomegalovirus infections remain the leading viral cause of congenital malformations in the developed world. Women with preconceptional immunity to human cytomegalovirus (HCMV) rarely if ever deliver infants with symptomatic infection. In contrast the incidence of symptomatic infection in babies born following primary maternal infection is approximately 10%. The present study was conducted to determine: (1) the percentage of seropositivity for HCMV among pregnant women due to preconceptional infection; and (2) to estimate the percentage of IgM antibodies against HCMV in fetal blood due to congenital or perinatal infection in relation to the clinical picture of the newborn. (excerpt)

Fosfomycin: A Review

FOSFOMYCIN WAS NOT mentioned as a therapeutic option for the treatment of urinary tract infections (UTIs) in the latest editions of two major textbooks of infectious diseases [1,2], despite the fact that it has been available in the United States for 4 years. It has been a commonly prescribed antibiotic in Japan and many parts of Europe for 2 decades. Fosfomycin was listed as a potentially useful antibiotic for the treatment of uncomplicated cystitis in an earlier review [3]. Currently, it has the approval of the U.S. Food and Drug Administration for the treatment of adult women with uncomplicated UTIs that are caused by Escherichia coli and Enterococcus faecalis. These introductory facts prompted this review of fosfomycin. We believe this discussion will be useful to practicing clinicians, especially those in the fields of internal medicine, gynecology, urology, and infectious diseases. Fosfomycin trometamol was first described in 1969 [4]. It is a phosphonic acid derivative, which acts primarily by interfering with bacterial peptidoglycan synthesis, thereby disrupting cell wall synthesis [5]. It has a broad spectrum of activity against aerobic bacteria, including those that cause UTIs [6]. There seems to be little cross-resistance between fosfomycin and other antibiotics commonly used to treat UTIs; thus, its efficacy is not affected by development of resistance to other antibiotics. It can be administered orally with a convenient dosing schedule, including single-dose therapy for uncomplicated cystitis.

Solid organ transplantation: Results and implications of acyclovir use in liver transplants

CMV infection is a major cause of morbidity and mortality following liver transplantation (LT). A prospective study of 218 LT recipients showed that 55% of patients developed CMV infection during the 1st year post-transplantation. Symptomatic CMV infection developed in 25% of all patients, being a major cause of death (21% of all deaths). Of 62 episodes of documented organ invasion, liver was the major site (38 episodes), followed by lung (20), gastrointestinal (4), and retina (4). The main patient group at risk (according to CMV serology of the recipient [(R)/donor(D)]) was the R-/D+: 77% of patients developed CMV infection, all of them with symptoms. The lowest group at risk was the R-/D-: 13% of patients developed CMV infection, half of whom developed symptoms. Time-dependent multivariate statistical analysis of risk factors indicated that the R-/D+ group was the main risk factor for CMV infection (P < .02) and symptomatic infection (P < .0001). To decrease the incidence and severity of CMV infection following LT, a randomized study is ongoing to evaluate the efficacy of ganciclovir (5 mg/kg/IV/q 12 hours for the first 14 days post-LT) followed by acyclovir (800 mg/po/qid for 14 weeks) GCV + ACV (group I), versus acyclovir (same dose for 16 weeks, starting immediately post-LT) ACV (group II). These treatment groups are compared to matched historical controls (C). Preliminary analysis of 83 LT recipients indicates that in group I the median date for the first evidence of CMV infection is delayed (82 days) as compared to group II and C (41 and 33 days, respectively) (P = .004).(ABSTRACT TRUNCATED AT 250 WORDS)