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.

[The "Black Death" : Crimean-Congo hemorrhagic fever]. / Der "schwarze Tod" : Krim-Kongo-Hämorrhagisches-Fieber.

The Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease that has been known for centuries. In the last years more frequent cases reflect the effects of climate change, globalization and the increasing encroachment of humans into previously unexploited areas. Humans acquire the infection by tick bites or through the slaughtering and processing of infected animals. The course of the disease can be severe and the average mortality reaches up to 30 %. It is transmissible from human to human and there is no causal treatment. Thus, CCHF meets the criteria for a highly contagious life-threatening disease. In the following current data on the virus, its vector, the distribution and transmission will be presented, as well as information on the diagnosis, the disease, the underlying pathophysiology and consequences in dealing with patients and deceased.

Increased detection of invasive enteropathogenic bacteria in pre-incubated blood culture materials by real-time PCR in comparison with automated incubation in Sub-Saharan Africa.

BACKGROUND: Invasive enteropathogenic bacteria can cause systemic infections. Data from studies with PCR detection suggest, at least for Salmonella enterica, that blood culture may lead to underestimation in the tropics. Corresponding data are lacking for other invasive enteropathogenic bacteria. We compared classical blood culture and molecular methods for the diagnosis of blood infections. METHODS: A real-time multiplex PCR for Salmonella spp., Shigella spp./entero- invasive Escherichia coli (EIEC), Yersinia spp., and Campylobacter jejuni was applied to 2321 retained blood culture samples from Ghanaian patients, after enrichment by automated culture. RESULTS: PCR detected Salmonella DNA in 56 out of 58 pre-incubated Ghanaian blood cultures with growth of S. enterica. In 2 samples molecular diagnosis was only possible after 1:10 dilution. Twenty-two samples negative by blood culture and 1 positive with Micrococcus spp. were PCR-positive for Salmonella spp. In addition, 3 Shigella spp./EIEC, 2 Yersinia spp., and 1 C. jejuni were detected by PCR but not by culture growth. CONCLUSIONS: Real-time PCR was more sensitive in identifying invasive enteropathogenic bacteria than automated blood culture, which is hampered by a lack of evidence-based standardization of pre-analytic conditions in the tropics. Primary agar culture and Gram-staining prior to automated blood culture is advisable in cases where transportation times are long.

Effects of COVID-19-Associated Infection Control on the Pattern of Infections Imported by German Soldiers and Police Officers Returning from Predominantly Tropical Deployment Sites.

In response to the COVID-19 pandemic, German public health authorities launched various infection control procedures. In line with this, anti-pandemic infection control was also implemented for German military and police deployments. The presented study assessed the impact of this increased infection control effort on deployment-associated infections in a holistic approach. To do so, the results of post-deployment assessments offered to German soldiers and police officers at the Department of Tropical Medicine and Infectious Diseases of the Bundeswehr Hospital Hamburg obtained during the pandemic period were compared to the results recorded during the pre-pandemic period in an exploratory, hypothesis-forming comparative study. In total, data from 1010 military deployments and 134 police deployments, predominantly to the African or the Eastern Mediterranean WHO regions, were included in the analyses. In the main results, a significant decrease in gastroenteritis in deployed soldiers (20.1% versus 61.3%, p < 0.0001) and at least a trend in the same direction in deployed police officers (25.7% versus 35.4%, p = 0.4026) were shown for the pandemic period, while no consistent tendency into the one or the other direction was detectable for febrile illness on deployment. In contrast to the finding of less frequently reported deployment-associated gastroenteritis, the detection rates of enteric microorganisms after deployment, including poor hygiene-related colonization with apathogenic protozoa, remained unchanged. Regarding non-enteric infections, the numbers of serologically confirmed malaria cases on deployment and as expected, due to increased airway protection, Mycobacterium tuberculosis-specific immune-conversion dropped significantly with p = 0.0037 and p = 0.009, respectively. As a side finding, soldiers and police officers with post-deployment medical assessments were more likely to be older and male during the pandemic compared to the pre-pandemic period. In summary, only minor changes in deployment-associated infection and colonization rates were seen in response to the increased infection control procedures during the pandemic period, apart from respiratory infections. In particular, the clinical finding of less gastroenteritis on deployment was not matched by a concordant decline in poor hygiene-related enteric colonization with apathogenic protozoa in the soldiers' guts, indicating that the fecal-oral transmission risk remained basically the same.

Real-time multiplex PCR for simultaneous detection of Campylobacter jejuni, Salmonella, Shigella and Yersinia species in fecal samples.

Diarrheal diseases due to notifiable bacterial infections require rapid diagnosis of the causative pathogens. To facilitate detection, a real-time multiplex PCR was developed that identifies common diarrhea-causing bacteria in fecal samples. On the basis of published sequence data, sets of primers and probes were designed that were specific for Campylobacter jejuni, Salmonella, Shigella/enteroinvasive Escherichia coli EIEC, and Yersinia species, suitable for use in a one-tube PCR assay. The assay was assessed using a list of 137 well-defined intestinal bacterial strains or isolates. Furthermore, 393 routine clinical stool samples were analyzed, and the results of real-time multiplex PCR were compared with those obtained by established microbiological methods. The PCR yielded results within 3h including DNA purification. No false-positive signals or cross-reactions were observed. The analytical sensitivity was 10(3)cfumL(-1) for Campylobacter jejuni, 10(4)cfumL(-1) for Salmonella, and 10(5)cfumL(-1) for Shigella/EIEC and Yersinia, respectively. Compared with culture, PCR detected 79 out of 81 Campylobacter jejuni (97.5%), 71 out of 74 Salmonella (96%), 8 out of 8 Shigella (100%), and 10 out of 10 Yersinia-positive (100%) clinical samples. In culture-negative samples (n=192), PCR additionally detected 2 Shigella, 1 Salmonella, and 5 Campylobacter jejuni infections. Thus, the new real-time multiplex PCR provides reliable results within a short time and might be useful as an additional diagnostic tool whenever time is important in the diagnosis of enteropathogenic bacteria.

Surveillance of enteropathogenic bacteria, protozoa and helminths in travellers returning from the tropics.

Diarrhoea is a frequent symptom associated with travelling to tropical regions, but the cause is often not found. Epidemiology was assessed including up-to-date real-time PCR approaches.We analysed datasets of 528 patients who presented at the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, between 2006 and 2010 for screening purposes or because of diarrhoea. Stool samples were obtained and investigated by microscopy, bacterial culture, two PCR assays targeting Entamoeba histolytica, Entamoeba dispar, Giardia duodenalis, and Cryptosporidium parvum, or Salmonella spp., Shigella/EIEC spp., Campylobacter jejuni, and Yersinia spp.Among patients with gastrointestinal symptoms, 51% tested positive for bacteria or parasites, of which 66% had a known enteropathogenic potential. In patients without diarrhoea, 53% (n = 80) were positive, and 33% of these cases harboured agents of pathogenic potential. Association with clinical symptoms was primarily found for bacterial infections. Blastocystis hominis, however, was more frequent in asymptomatic than in symptomatic travellers.In conclusion, the study stresses the etiological relevance of bacterial gastroenteritis in travellers returning from the tropics, the need for molecular approaches to increase diagnostic sensitivity and demonstrates that asymptomatic carriage of enteropathogens after prolonged stays in the tropics is similarly frequent compared with symptomatic infections in travellers.

Screening for Carbapenemases in Ertapenem-Resistant Enterobacteriaceae Collected at a Tunisian Hospital Between 2014 and 2018.

BACKGROUND: Carbapenem-resistance is frequently detected in Enterobacteriaceae isolated from patients in Tunisia. The study was performed to identify frequent carbapenemases in Tunisian isolates. METHODS: Between May 2014 and January 2018, 197 ertapenem-resistant Enterobacteriaceae were isolated at the microbiological department of the Military Hospital of Tunis. The strains were phenotypically characterized and then subjected to in-house polymerase chain reaction (PCR) targeting the carbapenemase genes blaIMP, blaVIM, blaNDM, blaSPM, blaAIM, blaDIM,blaGIM, blaSIM, blaKPC, blaBIC , and blaOXA-48. RESULTS: The assessed 197 ertapenem-resistant Enterobacteriaceae from Tunis comprised 170 Klebsiella pneumoniae, 19 Enterobacter cloacae, 6 Escherichia coli, 1 Citrobacter sedlakii, and 1 Enterobacter asburiae. Thereby, 55 out of 197 isolates (27.9%) were from blood cultures, suggesting a systemic disease. The carbapenemase gene blaOXA-48 quantitatively dominated by far with 153 detections, followed by blaNDM with 14 detections, which were distributed about the whole study interval. In contrast, blaBIC and blaVIM were only infrequently identified in 5 and 3 cases, respectively, while the other carbapenamases were not observed. CONCLUSIONS: The carbapenemase gene blaOXA-48 was identified in the vast majority of ertapenem-resistant Tunisian Enterobacteriaceae while all other assessed carbapenemases were much less abundant. In a quantitatively relevant minority of isolates, the applied PCR-based screening approach did not identify any carbapenemases.

Loop-mediated isothermal amplification-based detection of typhoid fever on an automated Genie II Mk2 system - A case-control-based approach.

Typhoid fever, caused by the bacterium Salmonella enterica subsp. enterica serovar Typhi, is an important cause of blood stream infections in the tropics, for which easy-to-apply molecular diagnostic approaches are desirable. The diagnostic performance of a newly introduced and a previously described loop-mediated isothermal amplification (LAMP) approach using different primer sets on a Genie II Mk2 device for the identification of Salmonella enterica ssp. enterica ser. Typhi was evaluated with well-characterized residual materials from the tropics in a case control-based approach. After in-vitro confirmation of binding characteristics of both LAMP primer sets with culture isolates (n = 112), sensitivity and specificity were 100% for the newly designed new LAMP primer set 1 with incubated blood culture materials, while specificity was reduced to 97.1% for primer set 2. For 170 EDTA blood samples, sensitivity and specificity were 10% and 98.3% for primer set 1 as well as 38.0% and 83.3% for primer set 2, respectively; qPCR from EDTA blood did not score much better with 10% sensitivity and 100% specificity. LAMP using a Genie II Mk2 device is suitable for the identification of Salmonella enterica spp. enterica ser. Typhi from incubated blood culture materials. Sensitivity and specificity were insufficient for diagnosis directly from EDTA blood samples but LAMP showed similar sensitivity as qPCR.

Pharmaceutical interactions between antiretroviral and antimalarial drugs used in chemoprophylaxis.

Human immunodeficiency virus (HIV) is the causative agent of the Acquired Immunodeficiency Syndrome (AIDS). The pandemic is believed to have originated within the Northern Congo basin covering large parts of the Democratic Republic of Congo, the Republic of Congo, the Central African Republic, Cameroon and Gabon. Although over decades, HIV-1 has spread throughout the World leaving no country unaffected, sub-Saharan Africa remains the region with more than 80% of all infected individuals. The HIV-2 epidemic has largely remained restricted to West Africa along the Upper Guinean forests. Co-incident with these regions of highest HIV distribution is a part of the malaria belt and therefore, co-infections are common. In this review we carve out the consequences of HIV transmission prevention and synchronous malaria prophylaxis during occupational or leisure travelling activities within this World region. In particular, we elaborate on considering pre-existing drug resistances of both, the malaria parasites and the immunodeficiency viruses, when determining a combination for prophylactic and, if necessary, post-expositional measures with a focus on the compatibility of both medications.

Microbiological screenings for infection control in unaccompanied minor refugees: the German Armed Forces Medical Service's experience.

BACKGROUND: The German Military Medical Service contributed to the medical screening of unaccompanied minor refugees (UMRs) coming to Germany in 2014 and 2015. In this study, a broad range of diagnostic procedures was applied to identify microorganisms with clinical or public health significance. Previously, those tests had only been used to screen soldiers returning from tropical deployments. This instance is the first time the approach has been studied in a humanitarian context. METHODS: The offered screenings included blood cell counts, hepatitis B serology and microscopy of the stool to look for protozoa and worm eggs as well as PCR from stool samples targeting pathogenic bacteria, protozoa and helminths. If individuals refused certain assessments, their decision to do so was accepted. A total of 219 apparently healthy male UMRs coming from Afghanistan, Egypt, Somalia, Eritrea, Syria, Ghana, Guinea, Iran, Algeria, Iraq, Benin, Gambia, Libya, Morocco, Pakistan, and Palestine were assessed. All UMRs who were examined at the study department were included in the assessment. RESULTS: We detected decreasing frequencies of pathogens that included diarrhoea-associated bacteria [Campylobacter (C.) jejuni, enteropathogenic Escherichia (E.) coli (EPEC), enterotoxic E. coli (ETEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC)/Shigella spp.), Giardia (G.) duodenalis, helminths (comprising Schistosoma spp., Hymenolepis (H.) nana, Strongyloides (S.) stercoralis] as well as hepatitis B virus. Pathogenic microorganisms dominated the samples by far. While G. duodenalis was detected in 11.4% of the assessed UMRs, the incidence of newly identified cases in the German population was 4.5 cases per 100,000 inhabitants. CONCLUSIONS: We conclude that the applied in-house PCR screening systems, which have proven to be useful for screening military returnees from tropical deployments, can also be used for health assessment of immigrants from the respective sites. Apparently healthy UMRs may be enterically colonized with a broad variety of pathogenic and apathogenic microorganisms. Increased colonization rates, as shown for G. duodenalis, can pose a hygiene problem in centralized homes for asylum seekers.

Colonization with Multidrug-Resistant Bacteria - On the Efficiency of Local Decolonization Procedures.

The effectiveness of a disinfectant-based decolonization strategy for multidrug-resistant bacteria like extended spectrum ß-lactamase (ESBL)-positive Gram-negative bacteria with or without additional fluoroquinolon and carbapenem resistance as well as vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus was assessed. Between 2011 and 2015, 25 patients from Libya, Syria, and the Ukraine with war traumata were treated at the Bundeswehr hospital Hamburg. The patients were heavily colonized and infected with multidrug-resistant bacteria, altogether comprising 371 distinct combinations of pathogens and isolation sites. Local disinfection was assessed for effectiveness regarding successful decolonization of multidrug-resistant bacteria. Altogether, 170 cases of successful decolonization were observed, comprising 95 (55.8%) such events at sampling sites that were accessible to disinfecting procedures. The remaining 75 (44.2%) decolonization events had to be considered as spontaneous. In contrast, 95 out of 172 (55.2%) colonized isolation sites that were accessible to disinfection procedures were successfully decolonized. Patient compliance with the enforced hygiene procedures was associated with decolonization success. Systemic antibiotic therapy did not relevantly affect isolation time. Disinfecting washing moderately supports local decolonization of multidrug-resistant pathogens in comparison with spontaneous decolonization rates if the patients' compliance with the applied hygiene procedures is ensured.

Low Enteric Colonization with Multidrug-Resistant Pathogens in Soldiers Returning from Deployments- Experience from the Years 2007-2015.

This assessment describes the enteric colonization of German soldiers 8-12 weeks after returning from mostly but not exclusively subtropical or tropical deployment sites with third-generation cephalosporin-resistant Enterobacteriaceae, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). Between 2007 and 2015, 828 stool samples from returning soldiers were enriched in nonselective broth and incubated on selective agars for Enterobacteriaceae expressing extended-spectrum beta-lactamases (ESBL), VRE and MRSA. Identification and resistance testing of suspicious colonies was performed using MALDI-TOF-MS, VITEK-II and agar diffusion gradient testing (bioMérieux, Marcy-l'Étoile, France). Isolates with suspicion of ESBL were characterized by ESBL/ampC disc-(ABCD)-testing and molecular approaches (PCR, Sanger sequencing). Among the returnees, E. coli with resistance against third-generation cephalosporins (37 ESBL, 1 ESBL + ampC, 1 uncertain mechanism) were found in 39 instances (4.7%). Associated quinolone resistance was found in 46.2% of these isolates. Beta-lactamases of the blaCTX-M group 1 predominated among the ESBL mechanisms, followed by the blaCTX-M group 9, and blaSHV. VRE of vanA-type was isolated from one returnee (0.12%). MRSA was not isolated at all. There was no clear trend regarding the distribution of resistant isolates during the assessment period. Compared with colonization with resistant bacteria described in civilians returning from the tropics, the colonization in returned soldiers is surprisingly low and stable. This finding, together with high colonization rates found in previous screenings on deployment, suggests a loss of colonization during the 8- to 12-week period between returning from the deployments and assessment.

Surveillance of Food- and Smear-Transmitted Pathogens in European Soldiers with Diarrhea on Deployment in the Tropics: Experience from the European Union Training Mission (EUTM) Mali.

Introduction. Since 2013, European soldiers have been deployed on the European Union Training Mission (EUTM) in Mali. From the beginning, diarrhea has been among the most "urgent" concerns. Diarrhea surveillance based on deployable real-time PCR equipment was conducted between December 2013 and August 2014. Material and Methods. In total, 53 stool samples were obtained from 51 soldiers with acute diarrhea. Multiplex PCR panels comprised enteroinvasive bacteria, diarrhea-associated Escherichia coli (EPEC, ETEC, EAEC, and EIEC), enteropathogenic viruses, and protozoa. Noroviruses were characterized by sequencing. Cultural screening for Enterobacteriaceae with extended-spectrum beta-lactamases (ESBL) with subsequent repetitive sequence-based PCR (rep-PCR) typing was performed. Clinical information was assessed. Results. Positive PCR results for diarrhea-associated pathogens were detected in 43/53 samples, comprising EPEC (n = 21), ETEC (n = 19), EAEC (n = 15), Norovirus (n = 10), Shigella spp./EIEC (n = 6), Cryptosporidium parvum (n = 3), Giardia duodenalis (n = 2), Salmonella spp. (n = 1), Astrovirus (n = 1), Rotavirus (n = 1), and Sapovirus (n = 1). ESBL-positive Enterobacteriaceae were grown from 13 out of 48 samples. Simultaneous infections with several enteropathogenic agents were observed in 23 instances. Symptoms were mild to moderate. There were hints of autochthonous transmission. Conclusions. Multiplex real-time PCR proved to be suitable for diarrhea surveillance on deployment. Etiological attribution is challenging in cases of detection of multiple pathogens.

Food and drinking water hygiene and intestinal protozoa in deployed German soldiers.

This report analyzes the occurrence of Cryptosporidium spp., E. histolytica, and G. intestinalis in stool of returnees from military deployments and the impact of hygiene precautions. Between 2007 and 2010, stool samples of 830 returnees that were obtained 8-12 weeks after military deployments in Afghanistan, Uzbekistan, the Balkans, Democratic Republic of the Congo/Gabonese Republic, and Sudan and 292 control samples from non-deployed soldiers were analyzed by PCR for Cryptosporidium spp., E. histolytica, G. intestinalis, and the commensal indicator of fecal contamination E. dispar. Data on hygiene precautions were available. The soldiers were questioned regarding gastrointestinal and general symptoms. Among 1122 stool samples, 18 were positive for G. intestinalis, 10 for E. dispar, and no-one for Cryptosporidium spp. and E. histolytica. An increased risk of acquiring chronic parasitic infections in comparison with non-deployed controls was demonstrated only for G. intestinalis in Sudan, where standardized food and drinking water hygiene precautions could not be implemented. Standard food and drinking water hygiene precautions in the context of screened military field camps proved to be highly reliable in preventing food-borne and water-borne chronic infections and colonization by intestinal protozoa, leading to detection proportions similar to those in non-deployed controls.