Daniela Schmid

Interferon-γ Responses Are Associated with Resistance to Reinfection with Plasmodium falciparum in Young African Children

The contribution of T cell-mediated responses was studied with regard to resistance to reinfection in groups of Gabonese children participating in a prospective study of severe and mild malaria due to infection with Plasmodium falciparum. In those admitted with mild malaria, but not in those with severe malaria, production of IFN-gamma by peripheral blood mononuclear cells (PBMC) in response to either liver-stage or merozoite antigen peptides was associated with significantly delayed first reinfections and with significantly lower rates of reinfection. Proliferative or tumor necrosis factor responses to the same peptides showed no such associations. Production of interferon-gamma by PBMC in response to sporozoite and merozoite antigen peptides was observed in a higher proportion of those presenting with mild malaria. Differences in the Th1/Th2 cytokine balance may be linked to the ability to control parasite multiplication in these young children, helping to explain the marked differences observed in both susceptibility to infection as well as in clinical presentation.

Low Interleukin-12 Activity in Severe Plasmodium falciparum Malaria

ABSTRACT We compared interleukin-12 (IL-12) and other cytokine activities during and after an acute clinical episode in a matched-pair case-control study of young African children who presented with either mild or severe Plasmodium falciparum malaria. The acute-phase, pretreatment plasma IL-12 and alpha interferon (IFN-α) levels, as well as the acute-phase mitogen-stimulated whole-blood production capacity of IL-12, were significantly lower in children with severe rather than mild malaria. IL-12 levels, in addition, showed strong inverse correlations both with parasitemia and with the numbers of circulating malaria pigment-containing neutrophils. Acute-phase plasma tumor necrosis factor (TNF) and IL-10 levels were significantly higher in those with severe malaria, and the concentrations of both of these cytokines were positively correlated both with parasitemia and with the numbers of pigment-containing phagocytes in the blood. Children with severe anemia had the highest levels of TNF in plasma. In all the children, the levels in plasma and production capacities of all cytokines normalized when they were healthy and parasite free. The results indicate that severe but not mild P. falciparummalaria in young, nonimmune African children is characterized by down-regulated IL-12 activity, contrasting markedly with the up-regulation of both TNF and IL-10 in the same children. A combination of disturbed phagocyte functions resulting from hemozoin consumption, along with reduced IFN-γ responses, may contribute to these differential effects.

The Role of Red Blood Cell Polymorphisms in Resistance and Susceptibility to Malaria

In regions highly endemic for Plasmodium falciparum malaria, red cell polymorphisms that confer resistance to severe disease are widespread. Sickle cell trait, alpha-thalassemia, glucose-6-phosphate dehydrogenase deficiency, and blood groups were determined in 100 children from Gabon with severe malaria who were matched with 100 children with mild malaria and followed up for evaluation of reinfections. The sickle cell trait was significantly associated with mild malaria and blood group A with severe malaria. During follow-up, the original severe cases had significantly higher rates of reinfection than the original mild cases, with higher parasitemia and lower hematocrit values. Incidence rates did not differ in the context of erythrocyte polymorphisms, but patients with sickle cell trait presented with markedly lower levels of parasitemia than those without. Thus, the severity of malaria is partly determined by the presence of blood group A and the sickle cell trait. The different presentation of reinfections in severe versus mild cases probably reflects different susceptibility to malaria.

Malarial anaemia in African children associated with high oxygen-radical production.

Reactive oxygen intermediates are thought to be involved in both the illness and parasite destruction during malaria. We measured innately increased reactive oxygen intermediate production in Gabonese children with severe malaria and anaemia.

Frequency of Cytokine-Producing T Cells in Patients of Different Age Groups with Plasmodium falciparum Malaria

The frequency of cytokine-producing T cells was assessed in patients of different age groups (29 infants, aged 1-5 years; 30 schoolchildren, aged 6-14 years; 26 adults, aged >15 years) with acute Plasmodium falciparum malaria from Gabon. By using flow cytometry for the intracellular detection of cytokines, a striking expansion was seen, in adults compared with children, of CD4+ and CD8+ T cells with the following profiles of type 1 cytokine production: interleukin (IL)-2-/interferon (IFN)-gamma+, IL-2+/IFN-gamma+, and IL-2+/IFN-gamma-. Patients with hyperparasitemia had a significantly lower frequency of IL-2-/IFN-gamma+ CD4+ cells. Type 2 cytokine expression (IL-4+/IFN-gamma-, IL-13+/IFN-gamma-) and type 0 cytokine expression (IL-4+/IFN-gamma+, IL-13+/IFN-gamma+) were also increased in adults within the CD4+ subset. Frequencies of IL-5+/IL-4+, IL-10+/IFN-gamma-, and IL-10+/IFN-gamma+ cells were similar in all groups. The increased frequency of both type 1 and type 2 cytokine-producing T cells in adults is likely to be of significance in the protection against P. falciparum malaria.

Effect of Antipyretic Drugs in Children with Malaria

A comparison of different antipyretics in children with malaria showed a small effect of naproxen, but not of metamizol, on the reduction of fever peaks. Antipyretic treatment had no effect on fever clearance and therefore should be used cautiously in the treatment of malaria.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges

Summary Definitions for a 4-stage continuum of HIV care were standardized and applied to HIV surveillance and national cohort data in 11 European Union countries. These countries are nearing the UNAIDS 90-90-90 target, although reducing the proportion undiagnosed remains challenging.

Shigellosis in refugees, Austria, July to November 2015.

We report on a cluster of shigellosis including 21 cases in refugees and two in local residents who worked in refugee transit centres, detected in Austria in 2015, between calendar weeks 29 and 47. The species isolated from the cluster cases, including one mixed infection, were S. sonnei (n = 13), S. flexneri (n = 10) and S. boydii (n = 1). Eleven of 18 tested isolates were extended spectrum beta-lactamase (ESBL)-positive, including five of six ciprofloxacin-resistant and three azithromycin-resistant isolates.

New HIV diagnoses among adults aged 50 years or older in 31 European countries, 2004–15: an analysis of surveillance data

BACKGROUND The HIV burden is increasing in older adults in the European Union (EU) and European Economic Area (EEA). We investigated factors associated with HIV diagnosis in older adults in the 31 EU/EEA countries during a 12 year period. METHODS In this analysis of surveillance data, we compared data from older people (aged ≥50 years) with those from younger people (aged 15-49 years). We extracted new HIV diagnoses reported to the European Surveillance System between Jan 1, 2004, and Dec 31, 2015, and stratified them by age, sex, migration status, transmission route, and CD4 cell count. We defined late diagnosis as CD4 count of less than 350 cells per μL at diagnosis and diagnosis with advanced HIV disease as less than 200 cells per μL. We compared the two age groups with the χ2 test for difference, and used linear regression analysis to assess temporal trends. FINDINGS During the study period 54 102 new HIV diagnoses were reported in older adults. The average notification rate of new diagnoses was 2·6 per 100 000 population across the whole 12 year period, which significantly increased over time (annual average change [AAC] 2·1%, 95% CI 1·1-3·1; p=0·0009). Notification rates for new HIV diagnoses in older adults increased significantly in 16 countries in 2004-15, clustering in central and eastern EU/EEA countries. In 2015, compared with younger adults, older individuals were more likely to originate from the reporting country, to have acquired HIV via heterosexual contact, and to present late (p<0·0001 for all comparisons). HIV diagnoses increased significantly over time among older men (AAC 2·2%, 95% CI 1·2-3·3; p=0·0006), women (1·3%, 0·2-2·4; p=0·025), men who have sex with men (5·8%, 4·3-7·5; p<0·0001), and injecting drug users (7·4%, 4·8-10·2; p<0·0001). INTERPRETATION Our findings suggest that there is a compelling need to deliver more targeted testing interventions for older adults and the general adult population, such as by increasing awareness among health-care workers and expanding opportunities for provider-initiated and indicator-condition-guided testing programmes. FUNDING European Centre for Disease Prevention and Control.

Elucidation of enterotoxigenic Bacillus cereus outbreaks in Austria by complementary epidemiological and microbiological investigations, 2013

Identifying Bacillus cereus as the causative agent of a foodborne outbreak still poses a challenge. We report on the epidemiological and microbiological investigation of three outbreaks of food poisoning (A, B, and C) in Austria in 2013. A total of 44% among 32 hotel guests (A), 22% among 63 employees (B) and 29% among 362 residents of a rehab clinic (C) fell sick immediately after meal consumption. B. cereus isolated from left overs or retained samples from related foods were characterized by toxin gene profiling, and molecular typing using panC sequencing and M13-PCR typing (in outbreak A and C). We identified two B. cereus strains in outbreak A, and six B. cereus strains, each in outbreak B and C; we also found Staphylococcus aureus and staphylococcal enterotoxins in outbreak A. The panC sequence based phylogenetic affiliation of the B. cereus strains, together with findings of the retrospective cohort analyses, helped determining their etiological role. Consumption of a mashed potatoes dish in outbreak A (RR: ∞), a pancake strips soup in outbreak B (RR 13.0; 95% CI 1.8-93.0) and for outbreak C of a fruit salad (RR 1.50; 95% CI 1.09-2.00), deer ragout (RR: 1.99; 95% CI 1.23-3.22) and a cranberry/pear (RR 2.46; 95% CI 1.50-4.03)were associated with increased risk of falling sick. An enterotoxigenic strain affiliated to the phylogenetic group with the highest risk of food poisoning was isolated from the crème spinach and the strawberry buttermilk, and also from the stool samples of the one B. cereus positive outbreak case-patient, who ate both. Our investigation of three food poisoning outbreaks illustrates the added value of a combined approach by using epidemiological, microbiological and genotyping methods in identifying the likely outbreak sources and the etiological B. cereus strains.