Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors.

Robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV) outbreak in Gulu, Uganda (2000-2001). Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections

Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome.

BACKGROUND: Human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fungal burden and limited leukocyte trafficking to cerebrospinal fluid (CSF). The immunopathogenesis of CM immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy at the site of infection is poorly understood. METHODS: We characterized the lineage and activation status of mononuclear cells in blood and CSF of HIV-infected patients with noncryptococcal meningitis (NCM) (n = 10), those with CM at day 0 (n = 40) or day 14 (n = 21) of antifungal therapy, and those with CM-IRIS (n = 10). RESULTS: At diagnosis, highly activated CD8(+) T cells predominated in CSF in both CM and NCM. CM-IRIS was associated with an increasing frequency of CSF CD4(+) T cells (increased from 2.2% to 23%; P = .06), a shift in monocyte phenotype from classic to an intermediate/proinflammatory, and increased programmed death ligand 1 expression on natural killer cells (increased from 11.9% to 61.6%, P = .03). CSF cellular responses were distinct from responses in peripheral blood. CONCLUSIONS: After CM, T cells in CSF tend to evolve with the development of IRIS, with increasing proportions of activated CD4(+) T cells, migration of intermediate monocytes to the CSF, and declining fungal burden. These changes provide insight into IRIS pathogenesis and could be exploited to more effectively treat CM and prevent CM-IRIS

Adubo de liberação lenta Basacote® na produção de mudas de pinheira (Annona squamosa L.).

Em sistemas de produção intensivos da pinha (Annona squamosa L.), a utilização de mudas com elevado padrão de qualidade morfofisiológica e fitossanitária na implantação de pomares é decisiva para viabilização do sistema de produção. A utilização de fertilizantes de liberação controlada pode propiciar maior eficiência do processo de produção de mudas, uma vez que podem favorecer o rápido desenvolvimento das plantas, reduzindo seu tempo de permanência no viveiro. Assim, objetivou-se com esse trabalho avaliar o efeito de doses de um adubo de liberação lenta (ALL) no desenvolvimento de mudas de pinheira

Effect of Schistosoma mansoni infection and its treatment on antibody responses to measles catch-up immunisation in pre-school children: A randomised trial.

BACKGROUND: Schistosoma infection is associated with immune modulation that can influence responses to non-schistosome antigens. Vaccine responses may be impaired in S. mansoni-infected individuals. We investigated effects of S. mansoni infection on responses to childhood measles catch-up immunisation and of praziquantel treatment on this outcome in a randomised trial. METHODOLOGY: The Immune Modulation and Childhood Immunisation (IMoChI) study was based in Entebbe, Uganda. Children aged 3-5 years (193 S. mansoni-infected and 61 uninfected) were enrolled. Infected children were randomised in a 1:1:1 ratio to receive praziquantel 2 weeks before, at time of, or 1 week after, measles catch-up immunisation. Plasma anti-measles IgG was measured at enrolment, 1 week and 24 weeks after measles immunisation. Primary outcomes were IgG levels and percentage of participants with levels considered protective against measles. RESULTS: Anti-measles IgG levels increased following immunisation, but at 1 week post-immunisation S. mansoni-infected, compared to uninfected, children had lower levels of anti-measles IgG (adjusted geometric mean ratio (aGMR) 0.4 [95% CI 0.2-0.7]) and the percentage with protective antibody levels was also lower (adjusted odds ratio 0.1 [0-0.9]). Among S. mansoni-infected children, anti-measles IgG one week post-immunisation was higher among those treated with praziquantel than among those who were not yet treated (treatment before immunisation, aGMR 2.3 [1.5-4.8]; treatment at immunisation aGMR 1.8 [1.1-3.5]). At 24 weeks post-immunisation, IgG levels did not differ between the trial groups, but tended to be lower among previously-infected children who were still S mansoni stool-positive than among those who became stool-negative. CONCLUSIONS AND SIGNIFICANCE: Our findings suggest that S. mansoni infection among pre-school children is associated with a reduced antibody response to catch-up measles immunisation, and that praziquantel treatment improves the response. S. mansoni infection may contribute to impaired vaccine responses in endemic populations; effective schistosomiasis control may be beneficial for vaccine efficacy. This should be further explored. TRIAL REGISTRATION: ISRCTN87107592

Monitoring changes in malaria epidemiology and effectiveness of interventions in Ethiopia and Uganda: Beyond Garki Project baseline survey.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: Scale-up of malaria interventions seems to have contributed to a decline in the disease but other factors may also have had some role. Understanding changes in transmission and determinant factors will help to adapt control strategies accordingly. METHODS: Four sites in Ethiopia and Uganda were set up to monitor epidemiological changes and effectiveness of interventions over time. Here, results of a survey during the peak transmission season of 2012 are reported, which will be used as baseline for subsequent surveys and may support adaptation of control strategies. Data on malariometric and entomological variables, socio-economic status (SES) and control coverage were collected. RESULTS: Malaria prevalence varied from 1.4 % in Guba (Ethiopia) to 9.9 % in Butemba (Uganda). The most dominant species was Plasmodium vivax in Ethiopia and Plasmodium falciparum in Uganda. The majority of human-vector contact occurred indoors in Uganda, ranging from 83 % (Anopheles funestus sensu lato) to 93 % (Anopheles gambiae s.l.), which is an important factor for the effectiveness of insecticide-treated nets (ITNs) or indoor residual spraying (IRS). High kdr-L1014S (resistance genotype) frequency was observed in A. gambiae sensu stricto in Uganda. Too few mosquitoes were collected in Ethiopia, so it was not possible to assess vector habits and insecticide resistance levels. ITN ownership did not vary by SES and 56-98 % and 68-78 % of households owned at least one ITN in Ethiopia and Uganda, respectively. In Uganda, 7 % of nets were purchased by households, but the nets were untreated. In three of the four sites, 69-76 % of people with access to ITNs used them. IRS coverage ranged from 84 to 96 % in the three sprayed sites. Half of febrile children in Uganda and three-quarters in Ethiopia for whom treatment was sought received diagnostic tests. High levels of child undernutrition were detected in both countries carrying important implications on child development. In Uganda, 7-8 % of pregnant women took the recommended minimum three doses of intermittent preventive treatment. CONCLUSION: Malaria epidemiology seems to be changing compared to earlier published data, and it is essential to have more data to understand how much of the changes are attributable to interventions and other factors. Regular monitoring will help to better interpret changes, identify determinants, modify strategies and improve targeting to address transmission heterogeneity.UK aid (PPA

The Italian arm of the PREPARE study: an international project to evaluate and license a maternal vaccine against group B streptococcus.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries. MAIN BODY: The term "PREPARE" designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls). SHORT CONCLUSION: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease

Correction to: Monitoring changes in malaria epidemiology and effectiveness of interventions in Ethiopia and Uganda: Beyond Garki Project baseline survey

This is the final version. Available on open access from BMC via the DOI in this recordThe article to which this is the correction is available in ORE at http://hdl.handle.net/10871/19983Correction to: Malar J (2015) 14:337 https://doi.org/10.1186/s12936-015-0852-7 Please be advised that one of the author names is incorrectly spelled in the published article: ‘Irene Kyomuhagi’ should be ‘Irene Kyomuhangi’. The corrected name can be found in the author list of this article