Recurrent parvovirus B19 viremia resulting in two episodes of hemophagocytic lymphohistiocytosis

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition with uncontrolled activation of lymphocytes and macrophages. Besides a primary (genetic) form, HLH can also be triggered by malignant, autoimmune and infectious diseases. HLH recurrences are rarely described, usually only in primary HLH. Parvovirus B19 (PVB19) Infection is one of the rare and rather benign causes of HLH. Since the infection usually results in long-lasting immunity, recurrent viremia is very uncommon. CASE PRESENTATION: We report an unusual case of a young female with recurrent PVB19 infection that led to repeated episodes of HLH. The first episode occurred at the age of 25 years with a three-week history of high fever and nonspecific accompanying symptoms. The diagnosis of HLH was confirmed by HLH-2004 criteria and HScore, PVB19 viremia was detected as underlying cause. Following guideline-based therapy, the patient was symptom-free for one year, before similar symptoms recurred in a milder form. Again, PVB19 was detected and HLH was diagnosed according to HScore. After successful treatment and a nine-month symptom-free interval, a third phase of hyperinflammation with low PVB19 viremia occurred; this time, treatment with a corticosteroid and intravenous immunoglobulin was initiated before the presence of clear diagnostic criteria for HLH. No further events occurred in the following three years. CONCLUSIONS: In the case of our patient, the recurrent viremia triggered three episodes of hyperinflammation, two of which were clearly diagnosed as HLH. To our knowledge, this is the first published case of recurrent HLH due to PVB19 infection. Therefore, the case gives new insights in triggering mechanisms for HLH

Prevalence of H. pylori among asymptomatic HIV-positive and negative individuals in Central Ethiopia and efficacy of eradication therapy

OBJECTIVES: Helicobacter pylori is a widespread pathogen and major contributor to dyspeptic disease and gastric cancer. Although the interaction between HIV and H. pylori infection is not well investigated, previous studies have suggested a decreased prevalence of H. pylori and limited efficacy of eradication therapy in HIV-positive individuals. Therefore, the objectives of this study were to describe the prevalence of H. pylori infection according to HIV status and analyze the efficacy of eradication therapy in Ethiopia. METHODS: A prospective, randomized, interventional study was performed involving HIV-positive and negative participants presenting to the Asella Referral and Teaching Hospital in Central Ethiopia between March and June 2017. A stool antigen test was used as a screening tool for H. pylori infection. Randomly selected patients received triple eradication therapy. RESULTS: The cumulative H. pylori prevalence was 77.3% (392/507): 78.8% (241/306) among HIV-positive individuals versus 75.1% (151/201) among HIV-negative individuals (P = 0.386). Twenty-five HIV-positive and 26 HIV-negative H. pylori-infected participants were randomized to receive standard triple therapy; three of them were lost to follow-up (one HIV-positive, two HIV-negative). The total eradication rate was 50.0%: 62.5% (15/24) among those HIV-negative versus 37.5% (9/24) among those HIV-positive [Au?1]. CONCLUSIONS: A high prevalence of H. pylori was observed among HIV-positive and negative individuals in Central Ethiopia. The efficacy of eradication therapy was low, with a trend towards lower efficacy in HIV-infected individuals

Development of International Educational Systems by Competence Networking based on Project Management

AbstractThe globalization demands new kinds of concepts and models to ensure the provision of skilled labor by international educational systems based on advanced competence networking. The success depends on the professional use of the latest project management theory, methodology, and practice. Multinational multi-projects fail and are aborted. A reason for that could be the deficiency of project readiness. The project management approach should be integrated into other management subsystems such as information, knowledge, competence, network management etc. One of the most important challenges is to ensure the communication and information transfer for competence balancing and sharing. A successful and efficient cooperation is only possible under equivalent partners. It creates the necessary trust. Beginning with the presentation of the need for cooperation and the exchange of knowledge for global and fair growth, the relationship between education, competence development and applied project management will be explained for educational transfer systems. Subsequently, the application of the approach will be illustrated by the planning, designing, implementing, and further developing of a large-scale Sino-German cooperation in higher education. The success of the project and the sustainability will be guaranteed. The roll-out to other network partners on a national and international scale is in progress

Risk-adjusted active tuberculosis case finding strategy in central Ethiopia

BACKGROUND: The World Health Organization recommends active case finding for tuberculosis (TB). Our study evaluated the targeted screening of household contacts (HHCs) of patients with contagious pulmonary tuberculosis (PTB) in Central Ethiopia. METHODS: The HHCs of patients with microbiologically confirmed PTB were screened for TB symptoms and risk factors for TB transmission. Symptomatic HHCs were subjected to secondary investigation. Antimicrobial resistance was investigated among study participants. RESULTS: Overall, 112 index patients with TB were included, and 289 HHCs from 89 households were screened. Multidrug-resistant-TB was detected in 2.7% (n=3) of index patients. The routine public health system process did not identify any TB suspects among HHCs. In total, 23.9% (n=69) of HHCs reported ≥1 TB symptom and PTB was confirmed in 2.1% (n=6). Reporting >1 TB symptom (relative risk [RR] 29.4, 95% CI 3.5−245.5, P<0.001) and night sweats (RR 27.1, 95% CI 3.2−226.6, P<0.001) were associated with the greatest relative risk. Regular alcohol consumption was identified as an individual risk factor for TB among HHCs (P=0.022). CONCLUSION: The MDR-TB rate among our patients was higher than recently reported for Ethiopia. Enhanced contact tracing using a risk-adjusted approach seems feasible and increases the case detection rate among HHCs of confirmed TB cases

Prevalence and characterization of antimicrobial resistance among gram-negative bacteria isolated from febrile hospitalized patients in central Ethiopia

BACKGROUND: Infectious diseases are among the leading causes of death in many low-income countries, such as Ethiopia. Without reliable local data concerning causative pathogens and antimicrobial resistance, empiric treatment is suboptimal. The objective of this study was to characterize gram-negative bacteria (GNB) as pathogens and their resistance pattern in hospitalized patients with infections in central Ethiopia. METHODS: Patients ≥ 1 year of age with fever admitted to the Asella Referral and Teaching Hospital from April 2016 to June 2018 were included. Blood and other appropriate clinical specimens were collected and cultured on appropriate media. Antibiotic susceptibility testing (AST) was performed using the Kirby–Bauer method and VITEK® 2. Species identification and detection of resistance genes were conducted using MALDI-ToF MS (VITEK® MS) and PCR, respectively. RESULTS: Among the 684 study participants, 54.2% were male, and the median age was 22.0 (IQR: 14–35) years. Blood cultures were positive in 5.4% (n = 37) of cases. Among other clinical samples, 60.6% (20/33), 20.8% (5/24), and 37.5% (3/8) of swabs/pus, urine and other body fluid cultures, respectively, were positive. Among 66 pathogenic isolates, 57.6% (n = 38) were GNB, 39.4% (n = 26) were gram-positive, and 3.0% (n = 2) were Candida species. Among the isolated GNB, 42.1% (16/38) were Escherichia coli, 23.7% (9/38) Klebsiella pneumoniae and 10.5% (4/38) Pseudomonas aeruginosa. In total, 27/38 gram-negative isolates were available for further analysis. Resistance rates were as follows: ampicillin/sulbactam, 92.6% (n = 25); cefotaxime, 88.9% (n = 24); ceftazidime, 74.1% (n = 20); cefepime, 74.1% (n = 20); gentamicin, 55.6% (n = 15); piperacillin/tazobactam, 48.1% (n = 13); meropenem, 7.4% (n = 2); and amikacin, 3.7% (n = 1). The bla(NDM-1) gene was detected in one K. pneumoniae and one Acinetobacter baumannii isolate, which carried an additional bla(OXA-51) gene. The ESBL enzymes were detected in 81.5% (n = 22) of isolates as follows: TEM, 77.2% (n = 17); CTX-M-1 group, 68.2% (n = 15); SHV group, 27.3% (n = 6); and CTX-M-9 group, 9.1% (n = 2). Based on the in vitro antimicrobial susceptibility results, empiric treatment initiated in 13 of 18 (72.2%) patients was likely ineffective. CONCLUSION: We report a high prevalence of ESBL-producing bacteria (81.5%) and carbapenem resistance (7.4%), with more than half of GNB carrying two or more ESBL enzymes resulting in suboptimal empiric antibiotic therapy. These findings indicate a need for local and national antimicrobial resistance surveillance and the strengthening of antimicrobial stewardship programs

Retrospective clinical case series study in 2017 identifies Plasmodiumknowlesi as most frequent Plasmodium species in returning travellers from Thailand to Germany

Febrile illnesses are common in travellers returning from south-east Asia. However, malaria is a rare diagnosis in this population. A series of Plasmodium knowlesi infections was noted in German travellers returning from Thailand since 2012. Infectious disease and tropical medicine facilities registered by the German Society for Tropical Medicine and International Health were contacted in March 2017, and asked to report previous P. knowlesi cases. In addition, surveillance data from the Robert Koch-Institute were analysed. The facilities reported a total of six P. knowlesi-positive cases, all were returning travellers from Thailand. The P. knowlesi-positive cases made up 6/9 of all diagnosed malaria cases imported from Thailand in the time period 2012 to 2017. In 4/5 of cases where a malaria rapid diagnostic test had been applied it revealed a negative result. P. knowlesi is an important differential diagnosis in travellers returning from south-east Asia with itineraries that include Thailand. This study highlights the importance of this Plasmodium species in this patient subgroup. Whenever malaria is suspected in a returning traveller from Thailand, P. knowlesi should be taken into consideration and a differential PCR be executed as currently the unequivocal diagnosis of P. knowlesi is based on nuclear amplification techniques

Immune Evasion by Yersinia enterocolitica: Differential Targeting of Dendritic Cell Subpopulations In Vivo

CD4+ T cells are essential for the control of Yersinia enterocolitica (Ye) infection in mice. Ye can inhibit dendritic cell (DC) antigen uptake and degradation, maturation and subsequently T-cell activation in vitro. Here we investigated the effects of Ye infection on splenic DCs and T-cell proliferation in an experimental mouse infection model. We found that OVA-specific CD4+ T cells had a reduced potential to proliferate when stimulated with OVA after infection with Ye compared to control mice. Additionally, proliferation of OVA-specific CD4+ T cells was markedly reduced when cultured with splenic CD8α+ DCs from Ye infected mice in the presence of OVA. In contrast, T-cell proliferation was not impaired in cultures with CD4+ or CD4−CD8α− DCs isolated from Ye infected mice. However, OVA uptake and degradation as well as cytokine production were impaired in CD8α+ DCs, but not in CD4+ and CD4−CD8α− DCs after Ye infection. Pathogenicity factors (Yops) from Ye were most frequently injected into CD8α+ DCs, resulting in less MHC class II and CD86 expression than on non-injected CD8α+ DCs. Three days post infection with Ye the number of splenic CD8α+ and CD4+ DCs was reduced by 50% and 90%, respectively. The decreased number of DC subsets, which was dependent on TLR4 and TRIF signaling, was the result of a faster proliferation and suppressed de novo DC generation. Together, we show that Ye infection negatively regulates the stimulatory capacity of some but not all splenic DC subpopulations in vivo. This leads to differential antigen uptake and degradation, cytokine production, cell loss, and cell death rates in various DC subpopulations. The data suggest that these effects might be caused directly by injection of Yops into DCs and indirectly by affecting the homeostasis of CD4+ and CD8α+ DCs. These events may contribute to reduced T-cell proliferation and immune evasion of Ye