Diana Riebold

Schistosoma mansoni: Schistosomicidal effect of mefloquine and primaquine in vitro

We investigated the effects of the anti-malarials mefloquine and primaquine against the juvenile and adult life stages of Schistosoma mansoniin vitro. Cercariae were incubated with 0.5 μg/ml, 1 μg/ml and 2 μg/ml mefloquine or primaquine and with 1 μg/ml praziquantel for 12h. Schistosomula, pre-adults and adults were incubated with 0.5 μg/ml, 1 μg/ml and 2 μg/ml mefloquine or primaquine and with 1 μg/ml praziquantel for 7 days. The viability status was classified as viable, damaged or dead and was checked every 3h for cercariae and every 12h for schistosomula, pre-adults and adults. Both, mefloquine and primaquine show time and dose-dependent schistosomicidal effects on the four life stages of S. mansoni. The promising in vitro effects on all stages of the blood fluke S. mansoni warrants further evaluation of both anti-malarials and their derivatives for their prophylactic and therapeutic values in early and late schistosomiasis in field trials.

High prevalence of Pneumocystis jirovecii colonization among patients with autoimmune inflammatory diseases and corticosteroid therapy

Background: Patients with autoimmune inflammatory diseases (AID) account for 13–36% of Pneumocystis pneumonia (PCP) cases in human immunodeficiency virus (HIV)-negative patients. Up to 88% of PCP cases in HIV-negative patients are associated with prior steroid treatment. Pulmonary colonization with Pneumocystis in HIV-negative patients is associated with corticosteroid therapy in up to 75% of cases. The aim of this study was to detect the prevalence and risk factors of pulmonary colonization with Pneumocystis jirovecii in patients with AID receiving corticosteroid therapy in comparison with healthy control persons. Methods: We investigated induced sputa of 102 patients with AID on current corticosteroid treatment and of 117 healthy controls for the presence of P. jirovecii using polymerase chain reaction (PCR). Results: Twenty-nine patients (28.5%) with AID were colonized with P. jirovecii compared to three healthy controls (2.6%) [p < 0.001, odds ratio (OR) 15.10, 95% confidence interval (CI) 4.43–51.38]. In patients with AID, age over 60 years was significantly associated with colonization (p = 0.015, OR 3.19, 95% CI 1.27–7.94). Multivariate analysis showed age to be independently associated with the colonization of P. jirovecii (95% CI 1.002–1.092). Neither duration nor dose of corticosteroid therapy nor immunosuppressive co-medication had a significant influence on P. jirovecii colonization. Conclusion: Patients with AID, especially those over 60 years of age, display a high prevalence of colonization with P. jirovecii. Clinicians should be aware of this and ensure that they consider the possibility of PCP when pulmonary symptoms arise in these patients.

Safety and immunogenicity of a trivalent single dose seasonal influenza vaccine containing pandemic A(H1N1) antigen in younger and elderly subjects: a phase III open-label single-arm study.

BACKGROUND During the pandemic of the 2009 A(H1N1) influenza virus strain, 20-40% of the population in some areas were infected. Infection with A(H1N1) may be mild, with an average case fatality rate below 0.25%, but severe disease is not limited to patients with underlying medical conditions. Since A(H1N1) is expected to continue to circulate it is included in the seasonal influenza vaccines for the 2010-2011 winter season. We investigated the immunogenicity and safety of a preservative-free non-adjuvanted seasonal trivalent influenza vaccine. METHODS We conducted a single center single-arm study involving 142 subjects (77 adults of 18-60 years and 65 subjects 61 years and above) to test the immunogenicity, safety, and tolerability of a trivalent split influenza vaccine. The vaccine contained 15μg of hemagglutinin of each of the virus strains recommended for the 2010-2011 northern hemisphere winter season (A/California/7/2009 (H1N1)-like strain; A/Perth/16/2009 (H3N2)-like strain; B/Brisbane/60/2008-like strain) in a non-adjuvanted preservative-free formulation. Antibody response to each antigen was measured by hemagglutination inhibition (HI) 21 days after immunization. Subject diary cards and additional telephone interviews were used to assess the safety profile. RESULTS By day 21 after the vaccination, seroconversion, or a 4-fold antibody increase in HI antibody titers, was detectable against A(H1N1) in 84% and 75% of younger and older adults, against A(H3N2) in 80% and 57%, and against the B influenza strain in 61% and 33%. HI antibody titers of 40 or more were observed against A(H1N1) in 99% and 90% of younger and older adults, against A(H3N2) in 100% and 90%, and against the B influenza strain in 91% and 78%. Pre-vaccination antibody titers were protective against A(H1N1), A(H3N2), and B in 26%, 44% and 33%, respectively of the adults below 61 years and in 27%, 54% and 44% of the subjects of 61 years and above. Local and systemic reactions were more common in younger than in older subjects and the most frequently reported reactions were pain at the injection site (36%), myalgia (24%), and fatigue (15%). Five percent elderly subjects and 1% of younger subjects had mild or moderate unsolicited adverse events such as prolonged ecchymosis or night sweats that resolved within 7 days after vaccination. CONCLUSIONS This single dose trivalent seasonal influenza vaccine generated protective antibodies to all three viral strains and had an acceptable safety profile in both younger and older adults (ClinicalTrials.gov identifier: NCT01147081).

Pneumocystis jirovecii colonization among renal transplant recipients

Renal transplant recipients are at risk of developing Pneumocystis pneumonia (PcP), especially in the first 2 years after transplantation, with a mortality rate of up to 50%. No data are available on pulmonary colonization with Pneumocystis jirovecii in renal transplant recipients. The aim of this study was to determine the prevalence of pulmonary colonization with Pneumocystis jirovecii in renal transplant recipients and to find related risk factors.

Schistosomula, pre-adults and adults of Schistosoma mansoni ingest fluorescence-labelled albumin in vitro and in vivo: implication for a drug-targeting model.

SUMMARY OBJECTIVE Bilharziosis is one of the most important helminthal infections in humans and is caused by blood flukes of the genus Schistosoma. Three different life stages of the parasite occur within the mammalian host: schistosomula located in the skin, pre-adults located in the lung and adult worms located in the portal venous system. Erythrocytes are a major source of nutrient supply for adults. However, sources of nutrition for the developing stages are still unclear. METHODS To investigate whether schistosomula, pre-adults and adults of Schistosoma mansoni ingest human serum albumin (HSA) in vitro, these life stages were incubated with aminofluorescein-labelled human serum albumin (Afl-HSA) for 5 h. To test the uptake of albumin in vivo, the albumin conjugate was given intravenously to S. mansoni infected NMRI mice 24 h before harvesting the 3 life stages. RESULTS In comparison to the control group schistosomula, pre-adults, and adults showed an accumulation of Afl-HSA within the oesophagus and intestinal caecum in vitro and in vivo. CONCLUSION Our findings suggest that albumin seems to be a major source of energy supply for the early schistosomal life stages and an additive energy support for adult worms. Since albumin has been used successfully as a drug carrier for chemotherapeutic substances against malignant disorders, further studies will focus on albumin as a carrier for anthelminthics in a drug-targeting model.

Imbalance of pro- and antifibrogenic genes and bile duct injury in murine Schistosoma mansoni infection–induced liver fibrosis

Objectives  The murine model of Schistosoma mansoni infection is characterized by strong fibrosis and little hepatocellular injury. The objective of this study was to evaluate the potential link between hepatic schistosomiasis and bile duct injury in relation to the expression of profibrotic cytokines and fibrosis‐related genes.

Clinical Trial to Evaluate the Safety and Immunogenicity of a Trivalent Surface Antigen Seasonal Influenza Vaccine Produced in Mammalian Cell Culture and Administered to Young and Elderly Adults with and without A(H1N1) Pre-Vaccination

Vaccination against influenza is an important means of reducing morbidity and mortality in subjects at risk. The prevalent viral strains responsible for seasonal epidemics usually change annually, but the WHO recommendations for the 2011/2012-season in the Northern hemisphere included the same antigens as for the previous season. We conducted a single-center, single-arm study involving 62 younger (18–60 years) and 64 older (>60 years) adults to test the immunogenicity, safety and tolerability of a trivalent surface antigen, inactivated influenza vaccine produced in mammalian cell-culture. The vaccine contained 15 µg hemagglutinin of each of the virus strains recommended for the 2011–2012 Northern hemisphere winter season (A/California/7/09 (H1N1)-; A/Perth/16/09 (H3N2)-; B/Brisbane/60/08-like strain) in a non-adjuvanted preservative-free formulation. Antibody response was measured by hemagglutination inhibition 21 days after immunization. Adverse events and safety were assessed using subject diary cards and telephone interviews. Seroconversion or a 4-fold antibody increase in antibody titers was detectable against A(H1N1) in 68% of both younger and older adults, against A(H3N2) in 53% and 27%, and against the B influenza strain in 35% and 17%. Antibody titers of 40 or more were observed against A(H1N1) in 87% and 90% of younger and older adults, against A(H3N2) in 98% and 98%, and against the B influenza strain in 93% and 90%. Pre-vaccination antibody titers were protective against A(H1N1), A(H3N2) and B in 38%, 58% and 58%, respectively, of younger and in 43%, 88% and 70% of older adults. Among subjects with previous A(H1N1) vaccination only 48% of younger and 47% of older adults had protective A(H1N1) antibodies at inclusion. Adverse reactions were generally mild. The most frequently reported reactions were pain at the injection site, myalgia and fatigue. The vaccine generated protective antibodies against all three viral strains and had an acceptable safety profile in both younger and older adults. Trial Registration ClinicalTrials.gov NCT01422512

Pneumocystis jiroveci Dihydropteroate Synthase Gene Mutations at Codon 171 but Not at Codons 55 or 57 Detected in Germany

NOTE. PR, present report; TMP-SMZ, trimethoprim-sulfamethoxazole. in Missouri and other areas where the disease is not endemic needs review. The national Lyme disease surveillance case definition was developed nearly 10 years ago [3], and a great amount of relevant new scientific evidence regarding Lyme disease and southern tick–associated rash illness has accumulated since that time. The findings of Wormser et al. [6, 9] argue in favor of establishing more rigorous inclusion criteria for patients who present with erythema migrans–like lesions in areas where Lyme disease is not endemic.

Pneumocystis jirovecii colonisation in HIV‐positive and HIV‐negative subjects in Cameroon

To determine the prevalence of Pneumocystis pneumonia (PCP), a major opportunistic infection in AIDS patients in Europe and the USA, in Cameroon.

Pneumocystis pneumonia in an alcoholic patient with prolonged mechanical ventilation

infection affecting the adrenalglands has been described in an immunocompetent adult[2]. PcP has also been reported in HIV-negative infantswith comorbidities, such as respiratory syncytial virus, cy-tomegalovirus, adenovirus, influenza virus, chronic bron-chitis, bronchial asthma, and cystic fibrosis [3], and it hasbeen associated with sudden infant death syndrome [4].Reported here is a case of PcP that occurred in an immuno-competent alcoholic patient.A 65-year-old man presented with suspected cerebralcontusion and severe right-sided chest pain after a house-hold accident. Physical examination revealed mild cerebralcontusion, fractures of the sixth and seventh ribs on theright side, and a small laceration of the right eyebrow. Thelower abdomen was tender with signs of peritonitis, and aninguinal hernia was palpable on the right side. The patienthad a 7-year history of alcohol abuse (2–3 l beer and 3–4alcoholicdrinksperday),buttherewasnootherunderlyingdisease or drug intake.