Primary Infection Period Research Articles

Factors of postembryonic ontogeny: relationship with the effectiveness of tuberculosis chemoprophylaxis in children

Background. A child’s body as a functional system is formed starting from the fetal period. Therefore, analysis of even distant in time situations allows to identify factors that affect the functioning of the child’s body in the present time and, possibly, the effectiveness of chemoprophylaxis in children. Materials and methods. To study the presence of a correlation between factors of postembryonic ontogeny and the effectiveness of chemoprophylaxis of tuberculosis in children, an analysis was carried out of 300 patients aged 0 to 17 years in the early period of primary tuberculosis infection, who underwent a 3-month course of chemoprophylaxis with isoniazid. The dynamics of shin sensitivity according to the Mantoux test with 2 tuberculin units was used as a criterion for the effectiveness of chemoprophylaxis. Depending on the latter, the exa­minees were divided into two groups: a group with effective chemoprophylaxis (n = 200), in which the size of a wheal after the end of the course decreased by 4 mm or more, and a group with ineffective chemoprophylaxis, in which skin sensitivity to tuberculin increased or remained at the previous level or decreased in the size of a wheal by 3 mm or less. Results. The analysis showed that in the group with ineffective chemoprophylaxis compared to the alternative group, the following occurred significantly more often: short-term (up to 4 months) breast feeding, a history of acute bronchitis (p < 0.001) in a child, acute obstructive bronchitis. In addition, the following were characteristic of this group: the presence of tuberculosis contact (p < 0.001), tuberculosis contact with a patient with confirmed bacterial excretion (p < 0.001), age of child under 6 years (p < 0.001), the number (two and more) of concomitant pathologies (p < 0.001), a single BCG vaccination (p < 0.001), as well as the winter seasona­lity of chemoprophylaxis (p < 0.05). Conclusions. Significant correlations have been found between many factors of postembryonic ontogeny and the effectiveness of tuberculosis chemoprophylaxis in children, which allows them to be used for prognostic purposes. The closest connections with the effectiveness of chemoprophylaxis of tuberculosis in children was revealed for the presence of tuberculosis contact (ϕ = 1.08; p < 0.001), especially with a patient with confirmed bacterial excretion (ϕ = 1.72; p < 0.001), as well as the number of concomitant pathologies in a child (ϕ = 0.70; p < 0.001) and manifestations of allergy (ϕ = 0.67; p < 0.001).

Longitudinal Monitoring of Seroconversion Status in SARS-CoV-2 RT-PCR Positive Healthcare Workers

The impact of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) still continues. The duration of the immune response in individuals recovering from COVID-19 and its protection against future SARS-CoV-2 infection are not fully understood. This study aimed to longitudinally evaluate anti-SARS-CoV-2 seroconversion status in healthcare workers with positive SARS-CoV-2 Real-time reverse transcription polymerase chain reaction (rRT-PCR), test in Mersin University Hospital. A total of 68 healthcare workers with positive SARS-CoV-2 rRT-PCR test between 19 April and 27 November 2020 were included in the study. Blood samples were collected from healthcare workers for SARS-CoV-2 antibody testing in the 1st, 3rd and 5th months following PCR positivity. Healthcare workers were classified as symptomatic, asymptomatic and reinfected according to their clinical findings, and rRT-PCR cycle thresholds (Ct) were recorded. Elecsys Anti-SARS-CoV-2 (Roche Diagnostics, Germany) kit was used for antibody testing. Of the 68 healthcare workers; 46 were classified as symptomatic, 15 as asymptomatic, and seven as reinfected. Twenty-seven (39.7%) of the healthcare workers were male and 41 (60.3%) were female, and the mean age was 36.4 ± 9.04. Seroconversion was detected in 45 (66.2%) of 68 healthcare workers in the study, and only one person had sero-negative result at the end of the 5th month. While seroconversion was detected in 78.3% (n= 36/46) of symptomatic healthcare workers, it was observed in 26.7% (n= 4/15) of the asymptomatic healthcare workers. Seroconversion was detected in only one of the seven reinfected healthcare workers after primary infection. After reinfection, seroconversion was observed in five of seven reinfected healthcare workers. Antibody response was not detected in two of them after both infections. According to the rRT-PCR Ct values; the median of Ct value was found significantly lower in healthcare workers with seroconversion (23.26, IQR= 18.45-27.30), than the ones without seroconversion (36.20, IQR= 33.09-37.56) (p< 0.001). In those who had reinfection, the mean Ct value (31.77 ± 6.62) detected during the primary infection period was statistically higher than the Ct value (22.44 ± 5.54) detected during reinfection (p= 0.008). The most frequently recorded symptoms in healthcare workers were myalgia (57.3%), fatigue (51.5%), headache (51.5%) followed by sore throat (36.7%), fever (33.8%), cough (27.9%), diarrhea (23.5%) and dyspnea (16.2%). In addition, fever (52%) and fatigue (80.6%) were found to be significantly higher in seroconversion-positive healthcare workers than in those without seroconversion (p= 0.028; p= 0.005, respectively). As a result, a higher rate of antibody response was detected in healthcare workers who had symptomatic infection than those who were asymptomatic. It has been observed that patients with asymptomatic primary infection and without antibody response were more susceptible to reinfection. In addition, it was observed that the probability of immune response increased when the viral load increased (Ct value decreased) in symptomatic infections. Although these findings provide important information about the short-term seroconversion status of healthcare personnel; longer-term and larger-scale studies are needed to evaluate the long-term effectiveness of seroconversion and to better understand the effectiveness of the immune response developed after SARS-CoV-2 vaccine administrations.

Cardio-Pulmonary Sequelae in Recovered COVID-19 Patients: Considerations for Primary Care.

Background:Current literature lacks characterization of the post-recovery sequelae among COVID-19 patients. This review characterizes the course of clinical, laboratory, radiological findings during the primary infection period, and the complications post-recovery. Primary care findings are presented for long-COVID care.Methods:Adhering to PRISMA guidelines, 4 databases were searched (PubMed, Embase, CINAHL Plus, Scopus) through December 5, 2020, using the keywords “COVID-19 and/or recovered and/or cardiovascular and/or long-term and/or sequelae and/or sub-acute and/or complication.” We included published peer-reviewed case reports, case series, and cross-sectional studies providing the clinical course of COVID-19 infection, and cardiopulmonary complications of patients who recovered from COVID-19, while making healthcare considerations for primary care workers.Results:We identified 29 studies across 9 countries including 37.9% Chinese and 24.1% U.S. studies, comprising 655 patients (Mean Age = 45) with various ethnical backgrounds including Asian and European. Based on the WHO COVID-19 severity classification scale, initial disease severity was mild for 377 patients and severe for 52 patients. Treatments during primary infection included corticosteroids, oxygen support, and antivirals. The mean value (in days) for complication onset after acute recovery was 28 days. Complete blood counts and RT-PCR tests were the most common laboratory results described. In 22 of the studies, patients showed signs of clinical improvement and were prescribed medications such as anticoagulants or corticosteroids.Conclusion:Post-recovery infectious complications are common in long-COVID-19 patients ranging from mild infections to life-threatening conditions. International thoracic and cardiovascular societies need to develop guidelines for patients recovering from COVID-19 pneumonia, while focused patient care by the primary care physician is crucial to curb preventable adverse events. Recommendations for real-time and lab-quality diagnostic tests are warranted to establish point-of-care testing, detect early complications, and provide timely treatment.

Analysis of the development of tuberculosis as an epidemic process in the student environment of the Оrenburg region

The analysis of epidemic situation on tuberculosis, features of detection of disease, and also clinical and epidemiological characteristics for the first time revealed specific process in separate social group of students of the special and higher educational organizations of the Orenburg region for 2000–2018 was carried out. ­Me­thods. The indicators of incidence of tuberculosis of respiratory organs and extra-thoracic localization, indicators of morbidity with established bacterial excretion, indicators of morbidity in the presence of pulmonary tissue decay, indicators of the ratio of patients from secondary or higher educational institutions were calculated. The number of students in the region has undergone signi­ficant changes in recent decades. Since 2000, there has been a tendency for its growth with a maximum value in 2009. Subsequently, there was an annual decrease in the number of students, mainly at the expense of higher education institutions. Were identified different periods in endemic tuberculosis region's population, and the dynamics of tuberculosis morbidity students were subject to fluctuations, but generally consistent with such, the total population of the region. It was revealed that focal and infiltrative pulmonary tuberculosis remained the dominant clinical forms for nineteen years. The absence in the clinical structure of respiratory tuberculosis in students of classical forms of primary tuberculosis (tuberculosis of the intrathoracic lymph nodes, primary tuberculosis complex) confirms the completed early period of primary tuberculosis infection, that is, the previous infection of students with Mycobacterium tuberculosis. The obtained results indicate the endogenous reactivation of tuberculosis infection as a priority pathogenesis of the disease in this population group. Among the students of the region in recent years, there has been a tendency to reduce the incidence of tuberculosis. The structure of morbidity is dominated by small uncomplicated forms of tuberculosis of the respiratory system, identified during preventive examinations. Conclusion. In General, over the past de­cades in the Orenburg region there is a tense epidemic situation in the incidence of tuberculosis of students with a characteristic tendency to improve it.

Subclinical Epstein-Barr Virus Primary Infection and Lytic Reactivation Induce Thyrotropin Receptor Autoantibodies.

Epstein-Barr virus (EBV) is a herpes virus that mainly infects in B lymphocytes and occasionally reactivates lytically. Most individuals have been infected with EBV primarily in their childhood with no symptoms, and the virus persists latently for life. We have previously reported that EBV-infected B cells with thyrotropin receptor autoantibodies (TRAbs) on their surface [TRAb(+) EBV(+) cells] were present in the peripheral blood mononuclear cells (PBMCs) of healthy adult controls and patients with Graves' disease, and that TRAbs released in the culture medium of PBMCs containing TRAb(+) EBV(+) cells by EBV reactivation. EBV lytic reactivation induced the differentiation of host B cells into plasma cells and antibody production. Various autoantibodies have been detected during the acute phase of infectious mononucleosis (IM) that is the symptomatic primary infection of EBV. Therefore, the autoantibody production may be induced by the asymptomatic primary infection. In this study, we examined the presence of TRAb(+) cells, EBV(+) cells, and TRAb(+) EBV(+) cells in PBMCs from 29 healthy or subclinical children without Graves' disease and one cord blood that were divided into six age groups, and also measured plasma TRAb levels. The results obtained demonstrated that low levels of TRAb production occurred with EBV primary infection and lytic reactivation in children without symptoms of IM. Furthermore, the populations of TRAb(+) cells, EBV(+) cells, and TRAb(+) EBV(+) cells were small in the period of primary infection, but they potentially expand with repeated EBV lytic reactivation. This may partly explain why the onset of Graves' disease often occurs in young adults, but rarely in infancy.

Mycobacterium tuberculosis Infection and the development of laryngeal stenosis in children — is there a relationship?

The aim is to study the relationship of Mycobacterium tuberculosis infection and the development of laryngeal stenosis (croup) in children. 250 children with croup aged from 6 months to 8 years were examined.It was found that infection with Mycobacterium tuberculosis in children with laryngeal stenosis (croup) developed at the age of under 4 years. The first episode of croup coincided in 90% of cases with the early period of primary infection with Mycobacterium tuberculosis. A high proportion of close contact with adult tuberculosis patients reached 35% in patients with recurrent laryngeal stenosis (croup). The incidence of tuberculosis among children with repeated episodes of croup was 30%. Anti-TB therapy for latent tuberculosis infection or local forms of tuberculosis led to the cessation of repeated episodes of croup in 85% of cases. Infection with Mycobacterium tuberculosis and active tuberculosis infection is considered as one of the factors contributing to the recurrent course of laryngeal stenosis in children.

Aerobiology, epidemiology and management strategies in apple scab: science and its applications

Apple Scab, caused by Venturia inaequalis (Cke.) Wint. (anamorph Spilocea pomi Fr.), is considered to be one of the most important fungal diseases of apple, which occurs almost every year in severe epidemic form under favourable environmental conditions wherever apple is cultivated. The disease has two distinct phases in its life cycle i.e. the primary saprophytic stage on the fallen dead leaves and the secondary parasitic phase on the trees. The intensity of the disease varied with the environmental conditions, cultivar and orchard management practices. Yield losses during epidemic years in 1996, 2008 and 2013 in the Gangotri fruit valley of Dist. Uttarkashi went up to 84%. Among the environmental parameters, temperature, moisture and relative humidity have the highest influence on the epidemic development. The formations of pseudothecia and ascospore discharge were associated mainly with late autumn (October) infection. Urea @ 5% concentration had a significant effect on breaking of the life cycle of V. inaequalis in overwintered leaves. The pseudothecia formation takes 32–48 days more after sexual reproduction at temperature around 8–10 °C and this process completes between February and March every year. The maximum ascospores productivity was recorded at fruit development stage (pea size to walnut size) of apple with ascospore productivity of 1, 23,000/ml and thereafter declined gradually. The ascospore emission period was 64–78 days and mean numbers of cumulative degree days for 50 and 95% spore release were 456 and 960, respectively. Data accumulated over 17 years were analyzed for validation of Mills criteria to establish its relevance in rescheduling fungicide applications under monitored spray programme. On examination of the primary infection period from Gangotri valley, some differences were observed between our results and Mills table for ascospores infection. Potential ascospore dose is a useful tool for predicting the total amount of inoculums in an orchard and has been shown to effectively improve apple scab management. PAD values were 50 times higher in the poorly managed orchards than in the integrated orchards. However, integrated orchards were considered well-managed in the investigated years and showed that the epidemic risk was low and medium, while it was very high in the poorly managed orchards on the basis of PAD. Based on the long term studies carried out at different locations from 1993 to 2018, a computer based warning system was developed to forewarn the farmers for adoption of suitable management practices. The information generated are passed on to the growers by blowing a characteristic signaling, local news paper, SMS, telephonic communication, Govt. organization and through personal contacts or messages flashed 4–5 times through radio stations. In addition, growing season kisan mela, press releases and newsletters are issued via the extension workers of the University and Govt. department.

Croup syndrome and primary infection with mycobacterium tuberculosis in children

Acute respiratory viral infections (ARVI) occupy an important place in infectious pathology of children’s age. One of the frequent and severe manifestations of ARVI, accompanied by respiratory disorders, is stenosing laryngotracheitis (croup syndrome). Primary stenosing laryngotracheitis develops, as a rule, in children of the second-third year of life, rarely-older than 5 years. In 30–50% of patients, croup syndrome recur, often accompanied by signs of bronchial obstruction. The reasons for the formation of the relapses studied enough: discusses the role of concomitant allergic diseases, immune dysfunction, autonomic reactivity, etc. At the same time, the importance of such background conditions as the infection with Mycobacterium tuberculosis, the presence of local forms of tuberculosis (TB) in children in the development of croup syndrome and its recurrence in the literature is not reflected. In the course of our study, it was found that children with primary and recurrent croup are often infected with Mycobacterium tuberculosis at the age of 5 years, which allows them to be classified as at risk of tuberculosis infection; recurrent croup is significantly more often implemented in the early period of primary infection with Mycobacterium tuberculosis and the development of local forms of TB. Chemoprophylaxis and TB therapy can reduce the risk of developing recurrent croup syndrome in 82% of patients. Thus, one of the possible factors in the etiopathogenesis of the syndrome of croup can be a TB infection.

Estimation of Primary Infection Period of Apple Scab in Yamagata Prefecture, Japan

Estimation of Primary Infection Period of Apple Scab in Yamagata Prefecture, Japan

EVALUATION OF SPECIFIC ANTIGENS AT THE EARLY STAGE OF TUBERCULOUS INFECTION IN CHILDREN

More specific antigens are still being searched for in order to increase informativeness of techniques for early diagnostics of tuberculous infection. Aimed at the investigation of proteins of tuberculous mycobacteria (PPD-L, ESAT 6, 85, hybrid of ЕSAT 6 CFP 10, CFP32B, Rv2660c) the study was conducted including testing of induced IFN-γ in the children ill with tuberculosis in the early period of primary tuberculous infection and also those not infected with tuberculous mycobacteria – 130 children in the age from 6.0 ± 0.4 years old. It was found out that tuberculin remained to be valuable for evaluation of the intensity of anti-tuberculosis immunity. Antigens of ESAT 6, 85, CFP32B, Rv2660c were identified as proteins of the early stage of tuberculous infection. The presence of response when stimulating by the above antigens was typical of the favorable course of tuberculosis. Antigens of ESAT 6 and Rv2660c were valuable for assessment of latent tuberculous infections and the hybrid of ЕSAT 6 CFP 10 – for diagnostics of tuberculosis. Therefore introduction of immunological tests (in vitro) into the set of diagnostic tools allows optimizing the early diagnostics of tuberculous infection in children and forecasting the course of the disease when tuberculosis has developed.

ОСОБЕННОСТИ ТУБЕРКУЛЕЗА У РЕБЕНКА С СОПУТСТВУЮЩЕЙ ПАТАЛОГИЕЙ

The clinical case demonstrated the intermittent course of primary tuberculosis caused by multiple drug resistant mycobacteria in 8 year old child with concurrent disorders of CNS and locomotor apparatus and living in the social institution of the closed type. The disease was detected in 2 years after the early period of primary tuberculous infection and administered preventive treatment by two anti-tuberculosis drugs. The disease was diagnosed during examination due to aspiration pneumonia with expressed clinical manifestations. Treatment of aspiration pneumonia and multiple drug resistant pulmonary tuberculosis was successfully completed.

The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events.

Epstein-Barr virus (EBV) is a human herpesvirus that causes acute infectious mononucleosis and is associated with cancer and autoimmune disease. While many studies have been performed examining acute disease in adults following primary infection, little is known about the virological and immunological events during EBV’s lengthy 6 week incubation period owing to the challenge of collecting samples from this stage of infection. We conducted a prospective study in college students with special emphasis on frequent screening to capture blood and oral wash samples during the incubation period. Here we describe the viral dissemination and immune response in the 6 weeks prior to onset of acute infectious mononucleosis symptoms. While virus is presumed to be present in the oral cavity from time of transmission, we did not detect viral genomes in the oral wash until one week before symptom onset, at which time viral genomes were present in high copy numbers, suggesting loss of initial viral replication control. In contrast, using a sensitive nested PCR method, we detected viral genomes at low levels in blood about 3 weeks before symptoms. However, high levels of EBV in the blood were only observed close to symptom onset–coincident with or just after increased viral detection in the oral cavity. These data imply that B cells are the major reservoir of virus in the oral cavity prior to infectious mononucleosis. The early presence of viral genomes in the blood, even at low levels, correlated with a striking decrease in the number of circulating plasmacytoid dendritic cells well before symptom onset, which remained depressed throughout convalescence. On the other hand, natural killer cells expanded only after symptom onset. Likewise, CD4+ Foxp3+ regulatory T cells decreased two fold, but only after symptom onset. We observed no substantial virus specific CD8 T cell expansion during the incubation period, although polyclonal CD8 activation was detected in concert with viral genomes increasing in the blood and oral cavity, possibly due to a systemic type I interferon response. This study provides the first description of events during the incubation period of natural EBV infection in humans and definitive data upon which to formulate theories of viral control and disease pathogenesis.

Development of quantitative RT‐PCR assays for detection of three classes of HHV‐6B gene transcripts

The monitoring of active human herpesvirus 6 (HHV-6) B infection is important for distinguishing between the reactivation and latent state of the virus. The aim of this present study is to develop a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay for diagnosis of active viral infection. Primers and probes for in house quantitative RT-PCR methods were designed to detect the three kinetic classes of HHV-6B mRNAs (U90, U12, U100). Stored PBMCs samples collected from 10 patients with exanthem subitum (primary HHV-6B infection) and 15 hematopoietic stem cell transplant recipients with HHV-6B reactivation were used to evaluate reliability for testing clinical samples. Excellent linearity was obtained with high correlation efficiency between the diluted RNA (1-100 ng/reaction) and C(t) value of each gene transcript. The U90 and U12 gene transcripts were detected in all of the peripheral blood mononuclear cells (PBMCs) samples collected in acute period of primary HHV-6B infection. Only one convalescent PBMCs sample was positive for the U90 gene transcript. Additionally, the reliability of HHV-6B quantitative RT-PCRs for diagnosis of viral reactivation in hematopoietic transplant recipients was evaluated. Relative to virus culture, U90 quantitative RT-PCR demonstrated the highest assay sensitivity, specificity, positive predictive value, and negative predictive value. Thus, this method could be a rapid and lower cost alternative to virus culture, which is difficult to perform generally, for identifying active HHV-6B infection.

Reply to Fierer et al

To the Editor—We are thankful for the comments made by Fierer et al, which enrich the current discussion on the natural course of acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)–infected individuals [1]. However, we do feel that the authors may have over-interpreted our data when stating that we demonstrated a “sharp decrease in the fibrosis progresssion rate (FPR) to a clinically unimportant level soon after the primary HCV infection period has waned.” This statement is not correct. We showed that the calculated FPR using a linear model most likely overestimates fibrosis progression in the setting of acute HCV infection, for which only short follow-up times are available. We are happy to see that Fierer et al agree with this interpretation and no longer calculate FPRs when reporting the outcome of liver biopsies of acute HCV infections. Indeed, concordant to the current consensus statement on acute HCV infections in HIV-infected individuals, we recommended that every HIV-infected patient should be advised to consider early treatment of acute HCV infection if spontaneous clearance does not occur [2]. We fully agree that further follow-up in patients withholding treatment is warranted to detect advancing liver fibrosis early and avoid the development of significant fibrosis and/or cirrhosis and ultimately end-stage liver disease [3].

Early-Onset Liver Fibrosis Due to Primary Hepatitis C Virus Infection Is Higher Over Time in HIV-Infected Men

To the Editor—We were pleased to read the recent report by Vogel et al [1] of their study undertaken in response to our findings of rapid onset fibrosis during primary hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)–infected men [2]. Their study, plus the recent publication of the liver biopsy results of Bottieau et al [3], seems to cement that this unexpected outcome is a true consequence of primary HCV infection in HIV-infected men. We disagree, however, that their results using transient elastography demonstrate a sharp decrease in the fibrosis progression rate (FPR) to a clinically unimportant level soon after the primary HCV infection period has waned.

Managing summer apple scab epidemics using leaf scab incidence threshold values for fungicide sprays

In several apple production areas, most fungicide sprays applied to orchards target apple scab management. Recently, action thresholds were established to aid in decision making as to whether fungicide sprays are required to manage summer scab. To facilitate grower adoption of these thresholds, a sequential sampling for classification procedure (SSCP) was developed. The SSCP with an action threshold of 0.5% foliar scab was evaluated from 2005 to 2008 in seven commercial orchards as a tool to time fungicide sprays. At each site, at the end of the primary infection period, the orchard was divided into two sections: in one, summer scab was managed using the grower’s standard practices and in the other, summer scab was managed based on scan incidence. Starting in mid-June, each orchard section managed based on scab incidence was classified using the SSCP as below or above the action threshold or as in the “no decision” zone. When an orchard section was classified as above the action threshold, a fixed-interval spray program was initiated and generally continued until harvest. When an orchard section was classified as below the action threshold, initiation of the fungicide spray program was postponed until the threshold was reached. When an orchard was in the “no decision” zone, sampling was repeated one or two weeks later depending on the frequency of rain events. Similar incidences of foliar scab of 0.27% and 0.22% and of fruit scab of 1.11% and 1.27% were observed in orchard sections managed based on scab incidence and standard grower’s practices, respectively. However, fruit scab at harvest was above the economic threshold of 2.0% at three and six occasions in the sections managed using foliar scab incidence and using the growers’ standard practices, respectively. For the four years of the study, an average of 6.4 and 9.1 fungicide sprays were used to control summer scab in the orchard sections managed based on scab incidence and in those managed according to the growers’ standard practices, respectively. Considering that the same fungicide was used in all orchards, we concluded that the reduced number of fungicide sprays (30%) resulted from the elimination of sprays when scab incidence was below the action threshold of 0.5% leaves scabbed.

O1-S11.01 Time evolution of the fraction of new HIV infections due to primary infection among high risk groups in southern India

BackgroundHIV infectivity is considerably higher during primary infection (PI: first few months after infection). PI is believed to be an important biological driver of HIV transmission at the population level,...

Evaluation of a Dynamic Model for Primary Infections Caused by Plasmopara viticola on Grapevine in Quebec

Downy mildew is major grape disease in several areas of the world. Recently, a dynamic model for primary infections of grapes by Plasmopara viticola, forecasting time of primary lesions emergence, was developed in Italy. The model simulates the development of predicted oospore cohorts during the primary infection period. The efficacy of this disease-cycle-based model was evaluated in eastern Canada by comparing the time of lesion emergence predicted by the model with field observations in 20 and 23 vineyards in 2008 and 2009, respectively. For each vineyard, one to 20 simulation runs were performed depending on the number of oospore cohorts expected to form, for a total of 545 simulations. The model evaluation was based on the true positive proportion (lesion emergence was predicted and observed) and the true negative proportion (lesion emergence was not predicted and not observed) which were 0.996, and 0.907, respectively. A total of 313 simulations resulted in no infection among which 284 corresponded to no lesion emergence. In only one situation, lesions were observed and not predicted by the model. On the contrary, in 29 simulations run, lesion emergence was predicted but not observed in the field. Further validation of this model is required, but the results of this study are encouraging and this model may be used to improve timing of fungicide sprays against P. viticola. Accepted for publication 17 November 2010. Published 26 January 2011.

T-Cell Vaccination Reduces Simian Immunodeficiency Virus Levels in Semen

Recent findings suggest that most sexual transmission of human immunodeficiency virus type 1 (HIV-1) occurs during the acute phase of infection when viral replication is most intense. Here, we show that vaccine-elicited cellular immune responses can significantly reduce simian immunodeficiency virus levels in the semen during the period of primary infection in monkeys. A vaccine that decreases the quantity of HIV-1 in the semen of males during primary infection might decrease HIV-1 transmission in human populations and therefore affect the spread of AIDS.

Diagnostic algorithm for HBV safe transfusion.

Nucleic acid testing (NAT) has been introduced in blood donation screening in the late 1990s and was progressively extended with the availability of commercial assays initially for HCV, to HIV-1 and more recently to HBV1, 2. The main objective of HCV and HIV-1 RNA screening was the detection of window period infections (WP) for viruses that replicate very quickly with a viral load doubling time of 14 and 20 hours, respectively3. As a result, substantial increase in concentration of viral genomes is achieved in a short period of time ( 10E4IU/mL. Under such circumstances, the dilution factor introduced by pooling 24–96 plasma samples from individual donations did not substantially affect the identification of HCV and HIV-1 WP infections. However, plasma pooling being introduced for the economic purpose of decreasing the cost of NAT, several cases of HIV-1 transmission by lack of assay sensitivity related to sample pooling were reported4–6. Despite these few failures, the impact of NAT for HCV and HIV-1 reduced the residual risk of transfusion-transmission of these viruses below 1 per million donations in most developed countries where it was introduced2, 7. The issue of decreased sensitivity due to sample pooling became considerably more critical when HBV DNA screening was added to HCV and HIV-1 in triplex assays able to simultaneously detect all three viral genomes. Contrary to the relatively simple situation of HCV and HIV-1 where nearly 100% of samples containing viral RNA after the WP were seropositive for virus specific antibodies, discrepancies between serological HBV screening with HBsAg and DNA were found with considerable frequency8. Depending on the studies and the HBV genotype, 2–15% of HBV infected samples contained HBsAg without detectable DNA9 or DNA without detectable HBsAg10. As a result, 65–95% of potentially infectious HBV-containing donations were reactive to both types of assays. In addition, during the window period, the viral replication doubling time is considerably longer than for HCV and HIV-1 (estimated between 2 to 3 days) and it takes several weeks before viral load reaches concentrations ranging between 10E3 to 10E5 IU/mL and HBsAg becomes detectable3, 11. In this situation, the effect of pool size becomes more critical for WP identification. In addition, preliminary data collected in the past 10 years as well as more recent data obtained in areas where HBV DNA was screened in blood donor populations revealed substantial numbers of what is now known as 'occult' HBV infection (OBI) or carriage. This condition is defined as viral DNA without detectable HBsAg observed after the initial period of primary infection and most of the time accompanied by the presence of anti-HBc12. OBIs identified in apparently healthy blood donors have been further studied and characterised serologically, molecularly and to some extent clinically8, 13–15. OBIs are found mostly in older men, the viral load is generally below 1,000 IU/mL, in most cases <100 IU/mL, accompanied by anti-HBc and normal ALT level. Approximately half of these cases also carry anti-HBs indicating viral persistence in otherwise resolved infections. In very few cases, OBI may be negative for both anti-HBc and anti-HBs corresponding to 'primary' occult HBV infection16, which is defined as acute HBsAg negative infection. The very low viral load observed in most OBIs has two important consequences: 1. sample pooling considerably reduces the yield of cases and affects blood safety improvement; 2. It complicates the screening algorithm as well as the confirmation process. The present review will focus on the issue of confirmation of blood donation samples positive for HBV DNA but negative for HBsAg.