Hemophagocytic lymphohistiocytosis-how common and how severe is it as a complication of malaria? Retrospective case series and review of the literature.

BACKGROUND: Infection-associated secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially life-threatening hyperinflammatory condition caused by various infectious diseases. Malaria has rarely been described as trigger. The aim of this study is to collect data on frequency, clinical spectrum, and outcome of sHLH induced by malaria. METHODS: We collected case numbers on malaria and malaria-associated sHLH from specialized centers in Germany from 2015 to 2022. In addition, we conducted a literature search on published cases of malaria-associated sHLH and systematically analyzed the literature regarding clinical and diagnostic criteria. RESULTS: We obtained data from 13 centers treating 1461 malaria cases with different Plasmodium species, of which 5 patients (0.34%) also were diagnosed with sHLH. The literature search revealed detailed case reports from further 51 patients and case series comprising the description of further 24 patients with malaria-associated sHLH. Most cases (48/80; 60%) were reported from Asia. The median time interval between onset of malaria symptoms and hospital admission was 7 days. Severe complications of sHLH were documented in 36% (20/56) of patients, including two patients with multiple organ failure in our case series. Only 41% (23/56) of patients received specific treatment for sHLH, nevertheless the mortality rate (CFR) of 5% is lower compared to the CFR reported for sHLH triggered by other infectious diseases (e.g., 25% in sHLH due to EBV infection). CONCLUSION: Malaria-associated sHLH appears to have a comparatively good prognosis but may still represent an underdiagnosed and potentially fatal complication of malaria, especially in resource-poor settings.

Early combination therapy of COVID-19 in high-risk patients.

PURPOSE: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect. METHODS: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 106 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 106 copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher's tests or Kaplan-Meier analysis and long-rank tests. Multivariable regression analysis was performed. RESULTS: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 106 copies/ml of 8.0 days (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2-9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment. CONCLUSION: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.

Disseminated Cryptococcosis Is a Common Finding among Human Immunodeficiency Virus-Infected Patients with Suspected Sepsis and Is Associated with Higher Mortality Rates.

Cryptococcosis is the leading cause of death among people with HIV in Sub-Saharan Africa. The lack of optimum diagnoses and medications significantly impair the management of the disease. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective study at (1) Adama Hospital Medical College and (2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult, HIV-infected patients presenting with suspected sepsis and assessed their 28-day survival rates. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years, and 61% were female. Overall, eleven (13%) had positive CrAg tests, of which five grew Cryptococcus in blood cultures. Despite high-dose fluconazole (1200 mg/d) monotherapy being given to those with positive CrAg tests, the 28-day mortality was 64% (7/11), with mortality being significantly higher than among the CrAg-negative patients (9% (6/71); p < 0.001). Cryptococcosis was the leading cause of mortality among HIV-infected sepsis patients in this Ethiopian cohort. The CrAg screening of HIV-infected patients attending an emergency department can minimize the number of missed cryptococcosis cases irrespective of the CD4 T cell count and viral load. These findings warrant the need for a bundle approach for the diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

Infectious mononucleosis is associated with an increased incidence of Crohn's disease: results from a cohort study of 31 862 outpatients in Germany.

OBJECTIVE: The pathogenesis of inflammatory bowel disease (IBD) has not been fully uncovered to date. Epstein-Barr-Virus (EBV) infection has recently been associated with the pathogenesis of multiple sclerosis, suggesting a general link between EBV and autoimmune diseases. However, data on an association between EBV and IBD have remained inconclusive. This study aims at evaluating an association between EBV and the development of IBD. METHODS: This retrospective cohort study included 15 931 patients with and 15 931 matched patients without infectious mononucleosis from the Disease Analyzer database (IQVIA) between 2000 and 2018. Incidences of Crohn's disease and ulcerative colitis were evaluated using Cox regression models. RESULTS: Within 5 years of the index date, the cumulative incidence of IBD was 124 and 90 cases per 100 000 person-years among patients with and without infectious mononucleosis, respectively (P = 0.040). In regression analyses, infectious mononucleosis was significantly associated with IBD [hazard ratios (HR), 1.35; 95% confidence interval (CI), 1.01-1.81]. Subgroup analyses revealed an association between infectious mononucleosis and Crohn's disease (HR, 1.93; 95% CI, 1.22-3.05) but not ulcerative colitis (HR, 1.03; 95% CI, 0.70-1.51). This association was strongest in patients between 14 and 20 years (HR, 4.50; 95% CI, 1.55-13.13) and was only observed in females (HR, 2.51; 95% CI, 1.39-4.53). CONCLUSION: Infectious mononucleosis is significantly associated with an increased incidence of Crohn's disease but not ulcerative colitis, especially in young female patients. Our data support the hypothesis of a pathophysiological involvement of EBV in the development of Crohn's disease and should trigger molecular research to further dissect the pathophysiology of IBD.

Rapid Selection of Sotrovimab Escape Variants in Severe Acute Respiratory Syndrome Coronavirus 2 Omicron-Infected Immunocompromised Patients.

BACKGROUND: Monoclonal antibodies (mAbs) that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly less effective against Omicron variants. Immunocompromised patients often experience prolonged viral shedding, resulting in an increased risk of viral escape. METHODS: In an observational, prospective cohort, 57 patients infected with Omicron variants who received sotrovimab alone or in combination with remdesivir were followed. The study end points were a decrease in SARS-CoV-2 RNA <106 copies/mL in nasopharyngeal swabs at day 21 and the emergence of escape mutations at days 7, 14, and 21 after sotrovimab administration. All SARS-CoV-2 samples were analyzed using whole-genome sequencing. Individual variants within the quasispecies were subsequently quantified and further characterized using a pseudovirus neutralization assay. RESULTS: The majority of patients (43 of 57, 75.4%) were immunodeficient, predominantly due to immunosuppression after organ transplantation or hematologic malignancies. Infections by Omicron/BA.1 comprised 82.5%, while 17.5% were infected by Omicron/BA.2. Twenty-one days after sotrovimab administration, 12 of 43 (27.9%) immunodeficient patients had prolonged viral shedding compared with 1 of 14 (7.1%) immunocompetent patients (P = .011). Viral spike protein mutations, some specific for Omicron (e.g., P337S and/or E340D/V), emerged in 14 of 43 (32.6%) immunodeficient patients, substantially reducing sensitivity to sotrovimab in a pseudovirus neutralization assay. Combination therapy with remdesivir significantly reduced emergence of escape variants. CONCLUSIONS: Immunocompromised patients face a considerable risk of prolonged viral shedding and emergence of escape mutations after early therapy with sotrovimab. These findings underscore the importance of careful monitoring and the need for dedicated clinical trials in this patient population.

Convalescent plasma treatment for SARS-CoV-2 infected high-risk patients: a matched pair analysis to the LEOSS cohort.

Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma (CP) has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. We performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with CP. Both cohorts had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality: UKD 60.9%, LEOSS 48.3%. In our cohort of COVID-19 patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched-pairs analysis. However, our data supports the concept that a reduction in mortality is achievable by early CP administration.

Immune response to third SARS-CoV-2 vaccination in seronegative kidney transplant recipients: Possible improvement by mycophenolate mofetil reduction.

Modification of vaccination strategies is necessary to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs). This multicenter observational study analyzed the effects of the third SARS-CoV-2 vaccination in previously seronegative KTRs with the focus on temporary mycophenolate mofetil (MMF) dose reduction within propensity matched KTRs. 56 out of 174 (32%) previously seronegative KTRs became seropositive after the third vaccination with only three KTRs developing neutralizing antibodies against the omicron variant. Multivariate logistic regression revealed that initial antibody levels, graft function, time after transplantation and MMF trough levels had an influence on seroconversion (P < .05). After controlling for confounders, the effect of MMF dose reduction before the third vaccination was calculated using propensity score matching. KTRs with a dose reduction of ≥33% showed a significant decrease in MMF trough levels to 1.8 (1.2-2.5) µg/ml and were more likely to seroconvert than matched controls (P = .02). Therefore, a MMF dose reduction of 33% or more before vaccination is a promising approach to improve success of SARS-CoV-2 vaccination in KTRs.

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 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.

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.

The implementation of the Kinyoun staining technique in a resource-limited setting is feasible and reveals a high prevalence of intestinal cryptosporidiosis in patients with HIV.

OBJECTIVES: In resource-limited settings, intestinal Cryptosporidial or coccidian infections are common causes of chronic diarrhea but usually remain undiagnosed by routine stool investigation. Here, the addition of the Kinyoun staining technique after stool concentration was evaluated as an easy and inexpensive method for diagnosis of intestinal parasitic infection in patients with HIV. METHODS: This cross-sectional study investigated patients with HIV with diarrhea and randomly selected patients with HIV without diarrhea as controls. Stool samples were examined by wet mount microscopy and Kinyoun staining after stool concentration. Clinical, sociodemographic, and behavioral data were collected. Statistical analysis was performed using chi-squared test and multivariate regression analysis. RESULTS: In total, 163 participants were included (62.0% female, mean age 38.2 [SD ± 10.7] years). Diarrhea was present in 52.1% (85/163). The prevalence of intestinal parasites was 18.4% (30/163). Cryptosporidial infections were more frequent among patients with diarrhea (12.9% [11/85] vs 1.3% [1/78], P = 0.005) and in patients with CD4+ cell count <200 cells/µl (25.9% [7/27] vs 3.7% [5/136], P = 0.001). Risk factors for intestinal parasitic infections were diarrhea and the habit of regularly eating uncooked food. Kinyoun staining was necessary for the detection of cryptosporidiosis. CONCLUSION: In our cohort, the prevalence of intestinal parasitic infection was high, especially after additional use of Kinyoun staining for detection of Cryptosporidia or intestinal coccidia. Considering its clinical relevance, particularly in individuals at risk, the implementation of this technique should be considered in resource-limited settings.

Myelitis with flaccid paralysis due to Japanese encephalitis: case report and review of the literature.

BACKGROUND: Japanese encephalitis is an arthropod-borne zoonotic flavivirus infection endemic to tropical and subtropical Asia. A minority of infections leads to a symptomatic course, but affected patients often develop life-threatening encephalitis with severe sequelae. LITERATURE REVIEW: Myelitis with flaccid paralysis is a rare complication of Japanese Encephalitis, which-according to our literature search-was reported in 27 cases, some of which were published as case reports and others as case series. Overall, there is a broad clinical spectrum with typically asymmetric manifestation and partly severe motor sequelae and partly mild courses. Lower limb paralysis appears to be more frequent than upper limb paralysis. An encephalitic component is not apparent in all cases CASE PRESENTATION: We herein add the case of a 29 year-old female who developed encephalitis and myelitis with flaccid paralysis during a long-time stay in Indonesia. Diagnostic workup in Indonesia did not clearly reveal an underlying cause. Upon clinical stabilization, the patient was evacuated to her home country Germany, where further diagnostics confirmed Japanese encephalitis virus as the causative agent. The patient has partly recovered, but still suffers from residual paralysis of the upper limb. CONCLUSION: Flaccid paralysis is a rare, and likely underdiagnosed complication of Japanese encephalitis, which, to the best of our knowledge, has never been diagnosed outside endemic areas before.

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 blaNDM-1 gene was detected in one K. pneumoniae and one Acinetobacter baumannii isolate, which carried an additional blaOXA-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.

Characterization of HIV-1 drug resistance among patients with failure of second-line combined antiretroviral therapy in central Ethiopia.

BACKGROUND: As a consequence of the improved availability of combined antiretroviral therapy (cART) in resource-limited countries, an emergence of HIV drug resistance (HIVDR) has been observed. We assessed the prevalence and spectrum of HIVDR in patients with failure of second-line cART at two HIV clinics in central Ethiopia. METHODS: HIV drug resistance was analysed in HIV-1-infected patients with virological failure of second-line cART using the geno2pheno application. RESULTS: Among 714 patients receiving second-line cART, 44 (6.2%) fulfilled the criteria for treatment failure and 37 were eligible for study inclusion. Median age was 42 years [interquartile range (IQR): 20-45] and 62.2% were male. At initiation of first-line cART, 23 (62.2%) were WHO stage III, mean CD4 cell count was 170.6 (range: 16-496) cells/µL and median (IQR) HIV-1 viral load was 30 220 (7963-82 598) copies/mL. Most common second-line cART regimens at the time of failure were tenofovir disoproxil fumarate (TDF)-lamivudine (3TC)-ritonavir-boosted atazanavir (ATV/r) (19/37, 51.4%) and zidovudine (ZDV)-3TC-ATV/r (9/37, 24.3%). Genotypic HIV-1 resistance testing was successful in 35 (94.6%) participants. We found at least one resistance mutation in 80% of patients and 40% carried a protease inhibitor (PI)-associated mutation. Most common mutations were M184V (57.1%), Y188C (25.7%), M46I/L (25.7%) and V82A/M (25.7%). High-level resistance against the PI ATV (10/35, 28.6%) and lopinavir (LPV) (5/35, 14.3%) was reported. As expected, no resistance mutations conferring integrase inhibitor resistance were detected. CONCLUSIONS: We found a high prevalence of resistance mutations, also against PIs (40%), as the national standard second-line cART components. Resistance testing before switching to second- or third-line cART is warranted.

TIPS and splenorenal shunt for complications of portal hypertension in chronic hepatosplenic schistosomiasis-A case series and review of the literature.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) and shunt surgery are established treatment options for portal hypertension, but have not been systematically evaluated in patients with portal hypertension due to hepatosplenic schistosomiasis (HSS), one of the neglected tropical diseases with major impact on morbidity and mortality in endemic areas. METHODS: In this retrospective case study, patients with chronic portal hypertension due to schistosomiasis treated with those therapeutic approaches in four tertiary referral hospitals in Germany and Italy between 2012 and 2020 were included. We have summarized pre-interventional clinical data, indication, technical aspects of the interventions and clinical outcome. FINDINGS: Overall, 13 patients with confirmed HSS were included. 11 patients received TIPS for primary or secondary prophylaxis of variceal bleeding due to advanced portal hypertension and failure of conservative management. In two patients with contraindications for TIPS or technically unsuccessful TIPS procedure, proximal splenorenal shunt surgery in combination with splenectomy was conducted. During follow-up (mean follow-up 23 months, cumulative follow-up time 31 patient years) no bleeding events were documented. In five patients, moderate and transient episodes of overt hepatic encephalopathy were observed. In one patient each, liver failure, portal vein thrombosis and catheter associated sepsis occurred after TIPS insertion. All complications were well manageable and had favorable outcomes. CONCLUSIONS: TIPS implantation and shunt surgery are safe and effective treatment options for patients with advanced HSS and sequelae of portal hypertension in experienced centers, but require careful patient selection.

Multicentric Castleman's disease in HIV patients: a single-center cohort diagnosed from 2008 to 2018.

PURPOSE: Castleman's disease (CD) is a well-established entity but there is a lack of available data regarding the management and therapy of HIV- and HHV-8-positive multicentric CD (MCD). We provide our own single-center experience with HIV-associated MCD. METHODS: We performed a retrospective, descriptive study on a cohort of patients with MCD, diagnosed and admitted to the infectious diseases or intensive care unit in the University Hospital Düsseldorf between 2008 and 2018. Included patients had a previous or new HIV diagnosis and clinical signs resembling MCD with evidence of HHV-8 replication or histological diagnosis for MCD. RESULTS: Nine male patients were included in the study. All patients were treated with Rituximab after diagnosis of MCD, with six of them acquiring resolution of symptoms. Three patients received tocilizumab additionally. Other treatment options included: splenectomy (2/9), valganciclovir (2/9), vincristine and siltuximab (1/9), ruxolitinib and Cytosorb® (2/9). The relapse rate was 44% (4/9) and the survival rate 87.5% after 1 year (8/9) and 71.4% after 3 years (5/7). CONCLUSION: The most effective first-line therapy and retreatment option remains rituximab. The effectiveness of other treatment options like splenectomy or different immunotherapeutic approaches requires confirmation in larger-scale studies.

Tick species from cattle in the Adama Region of Ethiopia and pathogens detected.

Ticks will diminish productivity among farm animals and transmit zoonotic diseases. We conducted a study to identify tick species infesting slaughter bulls from Adama City and to screen them for tick-borne pathogens. In 2016, 291 ticks were collected from 37 bulls in Adama, which were ready for slaughter. Ticks were identified morphologically. Total genomic DNA was extracted from ticks and used to test for Rickettsia spp. with real-time PCR. Species identification was done by phylogenetic analysis using sequencing that targeted the 23S-5S intergenic spacer region and ompA genes. Four tick species from two genera, Amblyomma and Rhipicephalus, were identified. Amblyomma cohaerens was the dominant species (n = 241, 82.8%), followed by Amblyomma variegatum (n = 22, 7.5%), Rhipicephalus pulchellus (n = 19, 6.5%), and Rhipicephalus decoloratus (n = 9, 3.0%). Among all ticks, 32 (11%) were positive for Rickettsia spp. and 15 (5.2%) of these were identified as R. africae comprising at least two genetic clades, occurring in A. variegatum (n = 10) and A. cohaerens (n = 5). The remainder of Rickettsia-positive samples could not be amplified due to low DNA yield. Furthermore, another 15 (5.2%) samples carried other pathogenic bacteria: Ehrlichia ruminantium (n = 9; 3.1%) in A. cohaerens, Ehrlichia sp. (n = 3; 1%) in Rh. pulchellus and A. cohaerens, Anaplasma sp. (n = 1; 0.5%) in A. cohaerens, and Neoehrlichia mikurensis (n = 2; 0.7%) in A. cohaerens. All ticks were negative for Bartonella spp., Babesia spp., Theileria spp., and Hepatozoon spp. We reported for the first time E. ruminatium, N. mikurensis, Ehrlichia sp., and Anaplasma sp. in A. cohaerens. Medically and veterinarily important pathogens were mostly detected from A. variegatum and A. cohaerens. These data are relevant for a One-health approach for monitoring and prevention of tick-borne disease transmission.

Diagnosis and clinical management of hepatosplenic schistosomiasis: A scoping review of the literature.

BACKGROUND: Hepatosplenic schistosomiasis (HSS) is a disease caused by chronic infection with Schistosma spp. parasites residing in the mesenteric plexus; portal hypertension causing gastrointestinal bleeding is the most dangerous complication of this condition. HSS requires complex clinical management, but no specific guidelines exist. We aimed to provide a comprehensive picture of consolidated findings and knowledge gaps on the diagnosis and treatment of HSS. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed relevant original publications including patients with HSS with no coinfections, published in the past 40 years, identified through MEDLINE and EMBASE databases. Treatment with praziquantel and HSS-associated pulmonary hypertension were not investigated. Of the included 60 publications, 13 focused on diagnostic aspects, 45 on therapeutic aspects, and 2 on both aspects. Results were summarized using effect direction plots. The most common diagnostic approaches to stratify patients based on the risk of variceal bleeding included the use of ultrasonography and platelet counts; on the contrary, evaluation and use of noninvasive tools to guide the choice of therapeutic interventions are lacking. Publications on therapeutic aspects included treatment with beta-blockers, local management of esophageal varices, surgical procedures, and transjugular intrahepatic portosystemic shunt. Overall, treatment approaches and measured outcomes were heterogeneous, and data on interventions for primary prevention of gastrointestinal bleeding and on the long-term follow-up after interventions were lacking. CONCLUSIONS: Most interventions have been developed on the basis of individual groups' experiences and almost never rigorously compared; furthermore, there is a lack of data regarding which parameters can guide the choice of intervention. These results highlight a dramatic need for the implementation of rigorous prospective studies with long-term follow-up in different settings to fill such fundamental gaps, still present for a disease affecting millions of patients worldwide.

Clinical and microbiological characterization of sepsis and evaluation of sepsis scores.

BACKGROUND: Despite the necessity of early recognition for an optimal outcome, sepsis often remains unrecognized. Available tools for early recognition are rarely evaluated in low- and middle-income countries. In this study, we analyzed the spectrum, treatment and outcome of sepsis at an Ethiopian tertiary hospital and evaluated recommended sepsis scores. METHODS: Patients with an infection and ≥2 SIRS criteria were screened for sepsis by SOFA scoring. From septic patients, socioeconomic and clinical data as well as blood cultures were collected and they were followed until discharge or death; 28-day mortality was determined. RESULTS: In 170 patients with sepsis, the overall mortality rate was 29.4%. The recognition rate by treating physicians after initial clinical assessment was low (12.4%). Increased risk of mortality was significantly associated with level of SOFA and qSOFA score, Gram-negative bacteremia (in comparison to Gram-positive bacteremia; 42.9 versus 16.7%), and antimicrobial regimen including ceftriaxone (35.7% versus 19.2%) or metronidazole (43.8% versus 25.0%), but not with an increased respiratory rate (≥22/min) or decreased systolic blood pressure (≤100mmHg). In Gram-negative isolates, extended antimicrobial resistance with expression of extended-spectrum beta-lactamase and carbapenemase genes was common. Among adult patients, sensitivity and specificity of qSOFA score for detection of sepsis were 54.3% and 66.7%, respectively. CONCLUSION: Sepsis is commonly unrecognized and associated with high mortality, showing the need for reliable and easy-applicable tools to support early recognition. The established sepsis scores were either of limited applicability (SOFA) or, as in the case of qSOFA, were significantly impaired in their sensitivity and specificity, demonstrating the need for further evaluation and adaptation to local settings. Regional factors like malaria endemicity and HIV prevalence might influence the performance of different scores. Ineffective empirical treatment due to antimicrobial resistance is common and associated with mortality. Local antimicrobial resistance statistics are needed for guidance of calculated antimicrobial therapy to support reduction of sepsis mortality.