Three-body nature of N(*) and Δ(*) resonances from sequential decay chains.

The Nπ^{0}π^{0} decays of positive-parity N^{*} and Δ^{*} resonances at about 2 GeV are studied at ELSA by photoproduction of two neutral pions off protons. The data reveal clear evidence for several intermediate resonances: Δ(1232), N(1520)3/2^{-}, and N(1680)5/2^{+}, with spin parities J^{P}=3/2^{+}, 3/2^{-}, and 5/2^{+}. The partial wave analysis (within the Bonn-Gatchina approach) identifies N(1440)1/2^{+} and the N(ππ)_{S wave} (abbreviated as Nσ here) as further isobars and assigns the final states to the formation of nucleon and Δ resonances and to nonresonant contributions. We observe the known Δ(1232)π decays of Δ(1910)1/2^{+}, Δ(1920)3/2^{+}, Δ(1905)5/2^{+}, Δ(1950)7/2^{+}, and of the corresponding spin-parity series in the nucleon sector, N(1880)1/2^{+}, N(1900)3/2^{+}, N(2000)5/2^{+}, and N(1990)7/2^{+}. For the nucleon resonances, these decay modes are reported here for the first time. Further new decay modes proceed via N(1440)1/2^{+}π, N(1520)3/2^{-}π, N(1680)5/2^{+}π, and Nσ. The latter decay modes are observed in the decay of N^{*} resonances and at most weakly in Δ^{*} decays. It is argued that these decay modes provide evidence for a 3-quark nature of N^{*} resonances rather than a quark-diquark structure.

[Concepts, effectiveness, and perspectives of pandemic and seasonal influenza vaccines]. / Konzepte, Wirksamkeit und Perspektiven pandemischer und nichtpandemischer Influenzaimpfungen.

For the first time in history, the conditions to influence the course of an influenza pandemic through vaccination were set during the influenza A H1N1 pandemic in 2009. The specific requirements for pandemic vaccines are to be highly immunogenic in immunologically naive individuals and to be producible quickly in large quantities. In contrast, seasonal influenza vaccines induce a booster response and a broadening of preexisting immunity. In this article the concepts of seasonal and pandemic influenza vaccines and data on their immunogenicity and clinical efficacy are reviewed and discussed. In the upcoming years, seasonal influenza vaccination will continue to be based on inactivated split-virion and subunit vaccines or the live attenuated cold-adapted vaccine. The pandemic vaccines used in 2009 proved to be more immunogenic than expected from prepandemic vaccine trials, while the adverse events observed with AS03-adjuvanted vaccines call their future use into question. However, neither seasonal nor pandemic influenza vaccines can be regarded to be an ideal solution, because they have to be frequently adapted to new virus strains and they lack effectiveness in particular risk groups. They can be regarded as interim approaches to highly immunogenic vaccines that hopefully become available in the future. The underlying principles of future vaccines are also presented in this article.

Background paper to the recommendation for the preferential use of live-attenuated influenza vaccine in children aged 2-6 years in Germany.

The German Standing Committee on Vaccination (STIKO) recommends seasonal influenza vaccination for children and adolescents with chronic medical conditions that put them at risk for severe influenza illness. In addition to trivalent inactivated influenza vaccines (TIV), a trivalent live-attenuated influenza vaccine (LAIV) was licensed for children and adolescents aged 2-17 years in the European Union in 2011. Employing the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group, we examined the evidence for efficacy and safety of LAIV relative to TIV to guide STIKO's decision on whether LAIV should be preferentially recommended for at-risk children. In our meta-analysis of data from two randomized trials directly comparing LAIV and TIV in children aged ≤ 6 years, the protective efficacy of LAIV against laboratory-confirmed influenza was 53 % [95 % confidence interval (CI): 45-61 %] higher than that of TIV. A similar study in individuals aged 6-17 years showed a 32 % (95 % CI: 3-52 %) higher efficacy of LAIV. The quality of the evidence for a superior protective efficacy of LAIV against all relevant clinical outcomes was rated 'moderate' for children aged 2-6 years and 'low' for the age group 7-17 years. Regarding safety outcomes, the available data suggest no significant differences between LAIV and TIV. Based on these results, STIKO recommends that LAIV should be used preferentially for influenza vaccination of at-risk children aged 2-6 years. In children and adolescents aged 7-17 years, either LAIV or TIV may be used without specific preference. Possible contraindications and the vaccinee's and his/her guardians' preferences should be taken into account.

Background paper to the recommendation for routine rotavirus vaccination of infants in Germany.

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Ständige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO's Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children aged <5 years is high (reported 8-14 cases per 1000 children annually), and of these almost half require hositalization. In view of the available evidence and expected benefits, STIKO recommends routine rotavirus vaccination of children under the age of 6 months with the main goal of preventing RV-associated hospitalizations in Germany, especially among infants and young children.

Influenza A(H1N1)pdm09 antibodies after pandemic and trivalent seasonal influenza vaccination as well as natural infection in November 2010 in Hamburg, Germany.

The 2009 influenza pandemic has introduced the new re-assorted influenza A(H1N1)pdm09 virus which recirculated during the 2010/11 influenza season. Before that season, it was possible to acquire protective immunity either by pandemic or seasonal influenza vaccination against influenza A(H1N1)pdm09 or by natural infection. To obtain data on vaccination coverage and antibody levels in a reference population and to calculate whether or not the herd immunity threshold (HIT, calculated as 33% given an R0 of 1.5) was reached at the beginning of the 2010/11 season we performed a seroprevalence study in November 2010 in Hamburg, Germany. Antibody titres were assessed applying a haemagglutination inhibition test. Vaccination coverage was very low: 14% for pandemic and 11% for seasonal 2010/11 vaccinations. Even in those with underlying risk factors, vaccination coverage was not much higher: 17% for both vaccines. Serological analysis revealed antibody titres of ≥1:10 in 135 of 352 (38%) and of ≥1:40 in 61 of 352 study participants (17%). Specific antibodies were measurable in 26% of those without history of vaccination or natural infection, indicating a high proportion of subclinical and mild influenza disease. Nevertheless, the HIT was not reached, leaving the majority of the population susceptible to influenza A(H1N1)pdm09 and its potential complications.

[Prevention of nosocomial transmission of human immunodeficiency virus (HIV) from HIV-positive healthcare workers. Recommendations of the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V]. / Prävention der nosokomialen Übertragung von humanem Immunschwächevirus (HIV) durch HIV-positive Mitarbeiterinnen und Mitarbeiter im Gesundheitswesen. Empfehlungen der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. und der Gesellschaft für Virologie (GfV) e.V.

To the best of our knowledge, the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V. are the first in Europe to provide precise recommendations for the management of health care workers (HCWs) who are infected with human immunodeficiency virus (HIV). Requirements for HIV-infected HCWs need to be clearly defined. With a permanent viral burden of less than or equal to 50 copies/mL, HIV-positive HCWs are allowed to perform any surgery and any invasive procedure, as long as the infected HCW uses double-gloving, undergoes follow-up routinely by occupational medicine professionals, undergoes a quarterly examination of viral burden, and has a regular medical examination by a physician who has expertise in the management of HIV. Unrestricted professional activity is only possible with a strict compliance to take antiretroviral therapy and if the HIV-infected HCW strictly adheres to the recommended infection control procedures. Complete compliance with the recommendation almost certainly leads to no HIV transmission risk in patient care.

Sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies.

Molecular mimicry between viral antigens and host proteins was often suggested to be involved in induction of autoimmune diseases. In type 1 diabetes where pancreatic beta cells are destroyed by autoimmune phenomena, a linear sequence homology between a major autoantigen, glutamate decarboxylase (GAD), and the 2C protein of coxsackie B4 was identified. In addition, a sequence homology between GAD and the mycobacterial heat shock protein 60 was described and the suggestions were made that molecular mimicry between GAD, coxsackievirus B4-2C protein, and/or heat shock protein 60 (hsp60) may be actively involved in an autoimmune reaction towards the pancreatic beta-cells. Our group was the first to isolate human monoclonal autoantibodies to GAD (MICA 1-6) from a patient with newly diagnosed type 1 diabetes. The MICA allowed a detailed characterization of the diabetes associated self-epitopes in GAD and represent a set of GAD autoantibodies present in sera from patients with type 1 diabetes. Using deletion mutants of GAD we demonstrated that the regions of GAD covering the homology sequences to coxsackievirus B4 and to the hsp60 were absolutely required for binding of the MICA to GAD. We now designed an antibody-based analysis to ask whether molecular mimicry between GAD and coxsackie B4-2C or hsp60 is relevant in type 1 diabetes. Since part of the MICA recognize conformational epitopes, they allow to test for conformational molecular mimicry in viruses that have been incriminated in the development of type 1 diabetes. Our data reveal no crossreactivity between the diabetes associated GAD epitopes defined by the MICA and hsp60, rubellavirus, cytomegalovirus, and coxsackie B1-B6 virus antigens. Neither coxsackie B4-specific antibodies in sera from normal individuals nor GAD-positive sera from patients with type 1 diabetes indicated a crossreactivity between coxsackie B4-2C and GAD. Although the regions in GAD homologous to coxsackie B4-2C and hsp60 represented parts of GAD indispensible for binding of diabetes associated autoantibodies they did not mediate a crossreactivity of autoantibodies between GAD and these two proteins. No evidence for molecular mimicry between GAD and a whole panel of foreign antigens was detected by autoantibodies in type 1 diabetes.

New measurements of the European Muon Collaboration effect in very light nuclei.

New Jefferson Lab data are presented on the nuclear dependence of the inclusive cross section from (2)H, (3)He, (4)He, (9)Be and (12)C for 0.3 < x < 0.9, Q(2) approximately 3-6 GeV(2). These data represent the first measurement of the EMC effect for (3)He at large x and a significant improvement for (4)He. The data do not support previous A-dependent or density-dependent fits to the EMC effect and suggest that the nuclear dependence of the quark distributions may depend on the local nuclear environment.

CMV monitoring using blood cells and plasma: a comparison of apples with oranges?

Quantitative cytomegalovirus (CMV) monitoring is still far from being standardized between transplant centers. In the present study, we compared assays for quantitative CMV monitoring using blood cells and plasma. Four hundred and thirty-five consecutive samples from 29 patients with active CMV infection after allogeneic T-cell-depleted hemopoietic stem cell transplantation were tested in parallel using pp65 antigenemia and quantitative CMV polymerase chain reaction (PCR) in blood cells and plasma (COBAS AMPLICOR CMV MONITOR). Although only 142 (53.1%) of 253 positive samples were concordantly identified by all three assays, the number of positive samples detected by each assay was not different and the quantitative values were correlated, provided that nucleic acid (NA) in plasma was isolated by COBAS AmpliPrep and not by the manual protocol. Six (18%) of 34 episodes with active CMV infection were not detected using CMV PCR in plasma; whereas in times of white blood cell aplasia or blast crisis of leukemia, samples with active CMV infection in plasma could not be detected using blood cells. We conclude that CMV monitoring in whole blood could be favorable compared with assays using plasma or blood cells alone. Automated NA isolation could become an attractive tool for a more sensitive and better standardized molecular diagnostics.

Male circumcision: a role in HIV prevention?

PIP: Speculation has existed for decades on the association between the lack of male circumcision and the sexual transmission of disease. It has been suggested that the surface epithelium of the glans develops a protective keratin layer following circumcision which functions like a natural condom against contracting disease. Circumcised males may therefore be less susceptible to contracting sexually transmitted diseases (STD), including HIV. The identification of simian immunodeficiency virus-infected mononuclear cells in the dermis and epidermis of the penile foreskin of macaques also suggests that male circumcision may reduce the infectivity of men with HIV. The authors review the evidence in support of the association between the lack of circumcision and STDs, and the possible biological explanations. They also discuss the implications for public health interventions and suggest areas and methods for further research. Twenty-three published study reports linking circumcision status to HIV infection are identified and include retrospective studies including partner studies, cross-sectional serosurveys, a longitudinal study, and ecological correlations. Five studies linked the lack of circumcision to STDs other than HIV infection. In interpreting the data, the authors consider susceptibility versus infectivity, assessment of behaviors and adjustment for confounding, selection bias, misclassification of exposure, measure of association, and publication bias. It is ultimately concluded that more studies are needed to quantify the relative risk associated with the lack of male circumcision. Observational designs could be employed to that end along with laboratory and primate research.^ieng

Validating population surveys for the measurement of HIV/STD prevention indicators.

OBJECTIVE: To validate the World Health Organization/Global Programme on AIDS (GPA) protocol for measuring HIV/sexually transmitted disease prevention indicators pertaining to knowledge and sexual practices of the general population. METHODS: Data were collected in Uganda during 1993. Three different interview strategies were complemented with qualitative methods, including observations at visits and key-informant interviews. Two interview strategies consisted of structured questionnaires which were applied to 460 randomly selected people aged 15-49 years and 60 intentionally selected women who were known prostitutes. The third strategy involved in-depth interviewing and was applied to a random subset of all respondents (n = 75). RESULTS: The three interview strategies generated similar results for demographic characteristics. The strategies using structured questionnaires gave similar results with regards to the number of reported sex partners and the prevalence of condom use, but differed from in-depth interviews on these aspects. The high numbers of casual sex partners of female prostitutes was confirmed by in-depth interviews but not via the questionnaires. CONCLUSION: The GPA questionnaire may not be optimal to capture people at high risk and to assess sexual behaviour, especially of people at high risk. Nevertheless, the questionnaire provides the most realistic option, since in-depth interviews are expensive and not as objective in assessing trends over time. Evaluation studies of HIV interventions in the general population should therefore be complemented with small qualitative studies to detect and iron out biases in interpreting results.

Epidemiological methods to study the interaction between HIV infection and other sexually transmitted diseases.

Numerous studies performed over the past 5 years have indicated an association between HIV infection and other sexually transmitted diseases (STDs), particularly those involving genital ulceration. Such an association may be causal, indicating that STDs increase susceptibility to, or infectivity of, HIV infection or may result, in whole or in part, from the mutual dependence of HIV and STDs on patterns of sexual activity, or from an effect of HIV infection on the clinical course of STDs. In this paper we discuss the issues arising in the design and analysis of studies conducted to investigate this association. A numerical illustration is used to demonstrate non-causal associations that may arise in observational studies due to confounding and misclassification. Published cross-sectional and longitudinal studies are reviewed, and recommendations made for future studies. Special emphasis is given to the use of randomized intervention trials to overcome many of the biases associated with observational studies, and to provide information on the efficacy of intensive STD treatment programmes in reducing the transmission of HIV.

Prevention indicators for evaluating the progress of national AIDS programmes.

PIP: Major interventions to reduce HIV transmission involve increasing knowledge about preventing HIV transmission for sustained behavioral changes; and enhancing the control of sexually transmitted diseases (STD), which increase the probability of HIV transmission. Activities have also been developed to prevent the transmission of HIV by blood, donor selection, and more rational use of transfusions. Behavioral changes among injecting drug users have also been promoted. Recommendations are made for the evaluation of AIDS programs, focusing on prevention of sexual transmission of HIV, and outlining the approach developed by the Global Program on AIDS (GPA; Geneva, Switzerland) for use by national programs. Based on the feasibility, accuracy, reliability and validity of the quantitative assessment of programs, 10 indicators of progress and outcomes of prevention activities have been developed by GPA. These include indicators of population knowledge regarding preventive practices, reported sexual behavior and use of condoms in the general population, STD service evaluation, and indicators of program impact. The latter are measured through the reported STD incidence in the general male population, and syphilis and HIV prevalence in women. The four methods are proposed for measuring the 10 core prevention indicators (PI). Five PIs are measured during a population survey: reported knowledge of preventive practices (PI-1), condom availability at peripheral level (PI-3), reported frequency of nonregular sexual partners (PI-4), reported condom use during nonregular sexual encounters (PI-5), and reported STD incidence among men (PI-9). Condom availability at central level (PI-2) is assessed through key-informant interviews with major distributors. Structured health facility surveys allow assessment of the appropriateness of STD case management (PI-6 and PI-7). A serosurvey among antenatal clinic attenders aged 15-24 years allows the measurement of HIV and syphilis seroprevalence in that population (PI-8 and PI-10). GPA recommends that such surveys be repeated after a period of 1 to several years.^ieng

DNA vector constructs that prime hepatitis B surface antigen-specific cytotoxic T lymphocyte and antibody responses in mice after intramuscular injection.

We tested the efficiency of induction of immune responses to the small hepatitis B surface antigen (HBsAg) in mice by intramuscular DNA immunization using different vector constructs that allow high levels of HBsAg expression in mouse cells. The HBsAg-specific responses of class I-restricted cytotoxic T lymphocytes (CTL) and of B cells (serum antibody titers) were measured. Following the intramuscular inoculation of 'naked' DNA, five different vector constructs of 4-8 kb, that contained or did not contain an intron and/or the neo gene, in which HBsAg expression was driven by promoter sequences derived from the immediate early region of HCMV, the SV40 enhancer/promoter region, or a retroviral 3' LTR efficiently primed responses of class I-restricted CD8+ CTL precursors. In contrast, the constructs in which HBsAg expression was driven by HCMV-derived promoter sequences stimulated significantly higher levels of HBsAg-specific serum antibody titers after intramuscular DNA injection than the SV40 or MPSV vector constructs. Large (15 kb) episomal vector constructs did not stimulate CTL or antibody responses. The data demonstrate that: (i) intramuscular DNA immunization represents an efficient technique for priming CTL and antibody responses to HBsAg; (ii) many vectors can be constructed that express an immunogenic product after intramuscular inoculation of 'naked' DNA; (iii) the efficiency of the tested vector constructs to prime after DNA immunization, either a CTL response, or an antibody response, differs.

Indolocarbazoles exhibit strong antiviral activity against human cytomegalovirus and are potent inhibitors of the pUL97 protein kinase.

We have analyzed a panel of protein kinase inhibitors (PKIs) and found that some indolocarbazoles (Gö6976, K252a, K252c) proved to be highly effective inhibitors of GCV-sensitive and -resistant human cytomegalovirus (HCMV) strains, but did not show any effect against herpes simplex virus. Antiviral activity was determined by focus reduction assays (IC(50) ranging from 0.009 to 0.4 microM). Other inhibitors of serine/threonine kinases (Gö6850, H-7, roscovitine) were found to be ineffective. Virus yield at 5 days after infection was reduced by three orders of magnitude with nanomolar concentrations of the indolocarbazoles. These compounds were fully effective when added up to 24 h post infection and showed reduced activity up to 72 h post infection. Cytotoxicity assays in proliferating and non-proliferating cells demonstrated that the effective antiviral concentration of these compounds was significantly lower than either antiproliferative (IC(50)/CC(50) ranging from 6.5 to 390) or cytotoxic (IC(50)/CC(50) ranging from 72. 5 to 1000) doses. The effects of PKIs on the virus-encoded protein kinase pUL97 were studied using recombinant vaccinia viruses. Indolocarbazoles strongly inhibited both pUL97 autophosphorylation (IC(50) ranging from 0.0012 to 0.013 microM) and pUL97-dependent ganciclovir phosphorylation (IC(50) ranging from 0.05 to 0.26 microM). Other inhibitors of serine/threonine kinases showed only weak (Gö6850) or no (H-7, roscovitine) effect on these pUL97 functions, while oxoflavone tyrosine kinase inhibitors had no effect at all.

Phosphorylation of aciclovir, ganciclovir, penciclovir and S2242 by the cytomegalovirus UL97 protein: a quantitative analysis using recombinant vaccinia viruses.

We used recombinant vaccinia viruses (rVV) containing the UL97 open reading frame (ORF) of the human cytomegalovirus (HCMV) to investigate the UL97-dependent phosphorylation of different nucleoside analogs. The rVV T1 expressed the wild-type UL97 protein whereas rVV A5 contained a 12 bp deletion in the UL97 which had been known to be responsible for resistance of HCMV to ganciclovir (GCV). The rVV T1opal was generated which contained a stop codon at position 1089 of the UL97 ORF and which expressed a truncated UL97 protein. We quantitatively analyzed the capability of these rVVs to phosphorylate GCV, penciclovir (PCV), aciclovir (ACV) and 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl] purine (S2242) as well as the natural nucleosides deoxycytidine and deoxythymidine. Moreover, we compared their phosphorylating capability with that of herpes simplex virus type 1 strains. In thymidine kinase (TK)-deficient 143B cells infected with rVV T1, the three compounds GCV, ACV and PCV were phosphorylated with different efficiency whereas in cells infected with the rVV A5 a markedly reduced but not completely abolished phosphorylation of these compounds was observed. In rVV T1opal-infected cells no specific phosphorylation of the compounds was detectable at all. Neither S2242 nor the natural substrates of TKs were phosphorylated by any of the vaccinia recombinants. The rVVs proved to be a suitable tool for analysis of UL97-dependent phosphorylation of nucleoside analogs and also allowed to quantitatively study the influence of UL97 mutations on drug phosphorylation.

Provisional country estimates of prevalent adult human immunodeficiency virus infections as of end 1994: a description of the methods.

BACKGROUND: A country-by-country review of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) data was undertaken by the World Health Organization. This paper describes the methods used to make estimates of HIV prevalence. RESULTS: It is estimated that, globally, approximately 16.9 million adults were living with HIV infections at the end of 1994. The majority (66%) of the infections were in sub-Saharan Africa (over 11000000), followed by South and South East Asia (over 3000000). Estimated prevalence rates for HIV infection ranged from less than 1 per 100000 sexually active adult population to 18 per 100 (18%), with a median prevalence of 14 per 10000. In 50 countries the estimated HIV prevalence rate was less than 5 per 10000 sexually active adults. In 15 countries (all in sub-Saharan Africa) the prevalence rate was above 5%. The lowest estimated prevalence rates were seen in Central and East Asia and the highest in Central and Southern Africa. CONCLUSIONS: Estimates of prevalent HIV infections are intended to give an indication of the magnitude of the HIV pandemic but, due to the difficulties in accurately assessing the levels of HIV infections in national populations, should be considered provisional.

PIP: During 1995, the World Health Organization (WHO) reviewed country-level data on adult HIV/AIDS cases and, in consultation with local and regional experts, revised its estimates of HIV prevalence as of the end of 1994. Data sources included cases reported to WHO by Member States, routine HIV surveillance, published studies, and blood banks. Globally, an estimated 16.9 million adults were infected with HIV at the end of 1994. About 66% of HIV infections were in sub-Saharan Africa and 18% in South and South East Asia. HIV prevalence ranged from less than 1/100,000 sexually active adults to 18/100, with a median of 14/10,000. 43% of adult HIV infections were in the least developed countries and another 50% in developing and middle-income countries. Although these statistics should be considered provisional, they provide an indication of the magnitude of HIV infection, provide a baseline for future monitoring, and may facilitate rational decision making regarding resource allocation. This paper includes a country-by-country listing of the estimated 1994 adult HIV prevalence rate per 100 population and the number of adult HIV infections, working estimates of adult HIV prevalence by subcontinent, and a case study (India) illustrating WHO's estimation technique.

Excreta disposal behaviour and latrine ownership in relation to the risk of childhood diarrhoea in Sri Lanka.

A case-control study of environmental and behavioural risk factors for childhood diarrhoea was conducted in Kurunegala district, Sri Lanka. From five hospitals, 2458 children aged less than 5 years and suffering from diarrhoea were recruited as clinic cases, and a further 4140 reporting with complaints other than diarrhoea were recruited as clinic controls. Community-based cross-sectional surveys were also conducted in three of the five areas served by these hospitals, and from these a further 1659 children were recruited as community controls. Children from households where excreta were reported to be disposed of in a latrine were less likely to have diarrhoea than children whose families improperly disposed of excreta. The results obtained from comparisons of cases with clinic controls (adjusted odds ratio [OR] 1.42, 95% confidence interval [CI] : 1.01-1.98), and of cases with community controls (OR 1.35, 95% CI : 0.85-2.13) were in agreement, suggesting that no important selection bias operated on this association. If the observed proportion (91%) of improper excreta disposal among the population could be reduced to 50%, 12% of childhood diarrhoea episodes would be prevented. Although latrine ownership may be a necessary condition for safe excreta disposal behaviour, diarrhoeal morbidity may only be reduced in Sri Lanka if behavioural changes take place concomitant with the construction of sanitation facilities.

Fatal outcome in a patient developing Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) without measurable disease.

A 51-year-old female patient in the first chronic phase of CML received an allogeneic PBSCT from a matched unrelated donor. The transplant was manipulated by CD34+ cell selection. On day +193 after transplantation the patient was readmitted to the hospital with recurrent fever of unknown origin and cough. Clinical, radiographic and sonographic evaluation revealed no characteristic findings besides a mild splenomegaly. Screening for EBV, CMV, RSV and HSV did not indicate an active infection. On day +203 the patient developed generalized seizures, respiratory failure and died within 24 h in multiorgan failure. The macroscopic postmortem was still not enlightening; the histological examination however, demonstrated diffuse organ infiltration by monoclonal lymphoblastoid cells due to EBV-LPD.