Unusual presentations of a severe type 2 leprosy reaction mimicking sepsis induced by helminth infection.

We describe an unusual case of type 2 leprosy reaction (T2R) with septic shock-like features induced by helminth infection in a 31-year-old Moluccan male patient with a history of completed treatment of WHO multidrug therapy (MDT)-multibacillary (MB) regimen 2 years before admission. During the course of illness, the patient had numerous complications, including septic shock, anemia, and disseminated intravascular coagulation (DIC). Nevertheless, antibiotic therapies failed to give significant results, and the source of infection could not be identified. Helminth infection was subsequently revealed by endoscopic examination followed by parasitological culture. Resolution of symptoms and normal level of organ function-specific markers were resolved within 3 days following anthelmintic treatment. This report demonstrated the challenge in the diagnosis and treatment of severe T2R. Given that helminth infections may trigger severe T2R that mimics septic shock, health professionals need to be aware of this clinical presentation, especially in endemic regions of both diseases.

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.

New features on the survival of human-infective Trypanosoma rangeli in a murine model: Parasite accumulation is observed in lymphoid organs.

Trypanosoma rangeli is a non-pathogenic protozoan parasite that infects mammals, including humans, in Chagas disease-endemic areas of South and Central America. The parasite is transmitted to a mammalian host when an infected triatomine injects metacyclic trypomastigotes into the host's skin during a bloodmeal. Infected mammals behave as parasite reservoirs for several months and despite intensive research, some major aspects of T. rangeli-vertebrate interactions are still poorly understood. In particular, many questions still remain unanswered, e.g. parasite survival and development inside vertebrates, as no parasite multiplication sites have yet been identified. The present study used an insect bite transmission strategy to investigate whether the vector inoculation spot in the skin behave as a parasite-replication site. Histological data from the skin identified extracellular parasites in the dermis and hypodermis of infected mice in the first 24 hours post-infection, as well as the presence of inflammatory infiltrates in a period of up to 7 days. However, qPCR analyses demonstrated that T. rangeli is eliminated from the skin after 7 days of infection despite being still consistently found on circulating blood and secondary lymphoid tissues for up to 30 days post-infection. Interestingly, significant numbers of parasites were found in the spleen and mesenteric lymph nodes of infected mice during different periods of infection and steady basal numbers of flagellates are maintained in the host's bloodstream, which might behave as a transmission source to insect vectors. The presence of parasites in the spleen was confirmed by fluorescent photomicrography of free and cell-associated T. rangeli forms. Altogether our results suggest that this organ could possibly behave as a T. rangeli maintenance hotspot in vertebrates.

Biliary ascariasis and severe bacterial outcomes: Report of three cases from a paediatric hospital in Brazil.

INTRODUCTION: Biliary ascariasis, although uncommon, can lead to infectious complications and severe outcomes. This study reported three patients with biliary ascariasis and who were admitted to a paediatric hospital in Salvador, Brazil. CASE REPORTS: Case 1: A 1-year-old boy, with HIV, hospitalised with diarrhoea, fever, pain, and abdominal distension. He underwent an exploratory laparotomy, which showed peritonitis secondary to a perforation of the hepatic duct by ascaris. Case 2: A 3-year-old boy admitted with fever, abdominal pain and jaundice. Imaging examination was suggestive of ascaris in the intrahepatic biliary tract and a hepatic abscess. Case 3: A 7-year-old boy who was hospitalised with a history of abdominal colic, jaundice and fever, with a suggestive image of ascaris in the biliary tract and evolution to sepsis. DISCUSSION: Three cases of biliary ascariasis were reported with severe infectious complications involving peritonitis, hepatic abscess and sepsis. CONCLUSION: In endemic regions, biliary ascariasis should be considered in cases with jaundice, abdominal pain and fever, due to its morbidity and risk of complications.

Distinct Biomarker Profiles Distinguish Malawian Children with Malarial and Non-malarial Sepsis.

Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 ß [IL-1ß], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1ß, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1ß compared with the other subgroups. IL-1ß best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.

The use of laser-based diagnostics for the rapid identification of infectious agents in human blood.

AIMS: To investigate the use of a laser-based method of detection as a potential diagnostic test for the rapid identification of infectious agents in human blood. METHODS AND RESULTS: In this study, the successful differentiation of blood spiked with viruses, bacteria or protozoan parasites to clinically relevant levels is demonstrated using six blood types (O+, O-, AB+, A+, A-, B+) using blood from different individuals with blood samples prepared in two different laboratories. Experiments were performed using various compositions of filters, experimental set-ups and experimental parameters for spectral capture. CONCLUSIONS: The potential for developing a laser-based diagnostic instrument to detect the presence of parasites, bacteria and viruses in human blood capable of providing analysis results within minutes was demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY: There is an ongoing need for clinical diagnostics to adapt to newly emerging agents and to screen simultaneously for multiple infectious agents. A laser-based approach can achieve sensitive, multiplex detection with minimal sample preparation and provide rapid results (within minutes). These properties along with the flexibility to add new agent detection by simply adjusting the detection programming make it a promising tool for clinical diagnosis.

Identifying risk factors for the development of sepsis during adult severe malaria.

BACKGROUND: Severe falciparum malaria can be compounded by bacterial sepsis, necessitating antibiotics in addition to anti-malarial treatment. The objective of this analysis was to develop a prognostic model to identify patients admitted with severe malaria at higher risk of developing bacterial sepsis. METHODS: A retrospective data analysis using trial data from the South East Asian Quinine Artesunate Malaria Trial. Variables correlating with development of clinically defined sepsis were identified by univariable analysis, and subsequently included into a multivariable logistic regression model. Internal validation was performed by bootstrapping. Discrimination and goodness-of-fit were assessed using the area under the curve (AUC) and a calibration plot, respectively. RESULTS: Of the 1187 adults with severe malaria, 86 (7.3%) developed clinical sepsis during admission. Predictors for developing sepsis were: female sex, high blood urea nitrogen, high plasma anion gap, respiratory distress, shock on admission, high parasitaemia, coma and jaundice. The AUC of the model was 0.789, signifying modest differentiation for identifying patients developing sepsis. The model was well-calibrated (Hosmer-Lemeshow Chi squared = 1.02). The 25th percentile of the distribution of risk scores among those who developed sepsis could identify a high-risk group with a sensitivity and specificity of 70.0 and 69.4%, respectively. CONCLUSIONS: The proposed model identifies patients with severe malaria at risk of developing clinical sepsis, potentially benefiting from antibiotic treatment in addition to anti-malarials. The model will need further evaluation with more strictly defined bacterial sepsis as outcome measure.

Considerations for Systemic and Topical Treatment of Morganella morganii Septicemia Arising from Maggot Infestation.

INTRODUCTION: Live maggot infestation (myiasis) of wounds can present a host of ailments. Loosely associated with maggot excreta, Morganella morganii is a widespread, gram-negative rod bacterium commonly found in the intestinal tracts of humans. M morganii has been observed as being pathogenic, particularly in nosocomial and postoperative environments, as well as in immunosuppressed and elderly populations. CASE REPORT: Herein, the authors present a rare, previously unreported case of M morganii septicemia (as confirmed by positive blood culture), secondary to myiasis of the lower extremities. The patient was successfully treated with both systemic and topical interventions. Posttreatment examination revealed resolution of myiasis and negative blood cultures. CONCLUSIONS: Myiasis can be invasive, leading to severe systemic infection. In these cases, a broad-spectrum antibiotic combined with systemic and topical antiparasitic therapy should be considered.

Post-treatment haemolysis in African children with hyperparasitaemic falciparum malaria; a randomized comparison of artesunate and quinine.

BACKGROUND: Parenteral artesunate is the treatment of choice for severe malaria. Recently, haemolytic anaemia occurring 1 to 3 weeks after artesunate treatment of falciparum malaria has been reported in returning travellers in temperate countries. METHODS: To assess these potential safety concerns in African children, in whom most deaths from malaria occur, an open-labelled, randomized controlled trial was conducted in Kinshasa, Democratic Republic of Congo. 217 children aged between 6 months and 14 years with acute uncomplicated falciparum malaria and parasite densities over 100,000/µL were randomly allocated to intravenous artesunate or quinine, hospitalized for 3 days and then followed for 42 days. RESULTS: The immediate reduction in haemoglobin was less with artesunate than with quinine: median (IQR) fall at 72 h 1.4 g/dL (0.90-1.95) vs. 1.7 g/dL (1.10-2.40) (p = 0.009). This was explained by greater pitting then recirculation of once infected erythrocytes. Only 5% of patients (in both groups) had a ≥ 10% reduction in haemoglobin after day 7 (p = 0.1). One artesunate treated patient with suspected concomitant sepsis had a protracted clinical course and required a blood transfusion on day 14. CONCLUSIONS: Clinically significant delayed haemolysis following parenteral artesunate is uncommon in African children hospitalised with acute falciparum malaria and high parasitaemias. TRIAL REGISTRATION: ClinicalTrials.gov ; Identifier: NCT02092766 (18/03/2014).

Microbiota-induced peritrophic matrix regulates midgut homeostasis and prevents systemic infection of malaria vector mosquitoes.

Manipulation of the mosquito gut microbiota can lay the foundations for novel methods for disease transmission control. Mosquito blood feeding triggers a significant, transient increase of the gut microbiota, but little is known about the mechanisms by which the mosquito controls this bacterial growth whilst limiting inflammation of the gut epithelium. Here, we investigate the gut epithelial response to the changing microbiota load upon blood feeding in the malaria vector Anopheles coluzzii. We show that the synthesis and integrity of the peritrophic matrix, which physically separates the gut epithelium from its luminal contents, is microbiota dependent. We reveal that the peritrophic matrix limits the growth and persistence of Enterobacteriaceae within the gut, whilst preventing seeding of a systemic infection. Our results demonstrate that the peritrophic matrix is a key regulator of mosquito gut homeostasis and establish functional analogies between this and the mucus layers of the mammalian gastrointestinal tract.

Disseminated tungiasis in a 78-year-old woman from Tanzania: a case report.

BACKGROUND: Tungiasis is one of the neglected tropical diseases; it affects up to 40% of individuals living in societies with poor housing and sanitation standards. In endemic areas, Tunga infestation, which predominantly affects the periungual areas of the lower limbs in humans, is associated with considerable morbidity and poor quality of life. CASE PRESENTATION: A 78-year-old woman of African descent presented with pain, inflammation, suppuration, ulceration, and deformation of digits of all four limbs. She had a total of 1146 embedded sand fleas: 812 in lower limbs and 334 in her hands. She was febrile; her full blood count revealed pancytopenia and blood cultures were positive for Staphylococcus aureus and Streptococcus pyogenes isolates. Furthermore, she had severe hyponatremia. We applied 20% salicylated petroleum jelly followed by the manual removal of embedded sand fleas with a sterile needle. Intravenously administered piperacillin-tazobactam, topical ivermectin, ferrous sulfate, folic acid, tolvaptan, albendazole, multivitamins, and tetanus prophylaxis were instituted. She was discharged home after 16 days of hospitalization. CONCLUSIONS: Tungiasis is a neglected disease of concern in underprivileged societies that is preventable and curable. Early recognition and prompt treatment is crucial to prevent complications in this disease which may potentially mimic other conditions resulting in erroneous management.

Donor-Derived Strongyloidiasis Infection in Solid Organ Transplant Recipients: A Review and Pooled Analysis.

BACKGROUND: Donor-derived Strongyloides stercoralis infection in solid organ transplant (SOT) recipients is uncommon. Immunosuppressed SOT recipients are at risk of developing severe forms of strongyloidiasis infection through transmission from an infected donor allograft. METHODS: PubMed was searched for English-written articles published up to April 2015. Articles that reported cases of donor-derived strongyloidiasis infection in SOT recipients were reviewed for a pooled analysis. RESULTS: A total of 27 cases were identified from various SOT recipients. Donors were mostly from Strongyloides endemic regions (23 cases). No transplant recipients received prophylaxis against strongyloidiasis infection. Median age was 53 years. Median time of presenting symptoms after the solid organ transplantation was 72 days. The most common presenting symptoms were gastrointestinal (GI) symptoms (19 cases; 70.4%). Diagnosis of strongyloidiasis infection was mainly made by the confirmation of Strongyloides larvae or worm in GI samples (19 cases) and respiratory samples (14 cases). Donor-derived strongyloidiasis infection was evidenced by serology test results in 17 cases and epidemiological risk assessment analysis in 10 cases. Ivermectin was the most commonly used medication with use of a combination of iverrmectin and albendazole or thiabendazole in 15 cases. Death was noted in 9 cases (34.6%) of 26 cases with known outcomes. Presence of sepsis or bacteremia was a predictor of mortality because it was seen in 9 patients who died (100.0%) and in 4 patients who survived (23.5%; P < .001). CONCLUSIONS: Donor-derived strongyloidiasis infection in SOT recipients has high mortality. Effective donor screening and prophylaxis in high-risk SOT recipients may help to decrease morbidity and mortality associated with donor-derived strongyloidiasis.

[Small bowel obstruction secondary to massive hookworm infestation complicated by fatal plurimicrobial bacteriemia]. / Occlusion iléale par infestation massive par des ankylostomes responsable d'une septicémie plurimicrobienne d'évolution fatale.

INTRODUCTION: Intestinal symptoms (cramping, flatulence) and iron deficient anemia are classical presenting manifestations of duodenal hookworm infestation in patients living in endemic area. CASE REPORT: We report a 45-year-old immunocompetent metropolitan man who presented with intestinal obstruction secondary to massive hookworm infestation complicated by fatal plurimicrobial bacteriemia with refractory septic shock. CONCLUSION: We report a case of acute surgical abdominal presentation with septicemia and refractory shock syndrome due to ileal translocation secondary to massive hookworm infestation. To the best of our knowledge, such a case has not yet been reported.

Characterization of Prototheca wickerhamii isolated from disseminated algaemia of kidney transplant patient from Malaysia.

Prototheca wickerhamii isolated from blood of 61-year-old kidney transplant patient was described. Although it is classified as an alga (genus Chlorella), the disease, protothecosis, is included under mycoses because of its clinical pathological presentations. Colony characteristics of P. wickerhamii are indistinguishable from other yeast-like organisms like Cryptococcus and Candida. Fortunately, commercial identification system for yeast can be used to identify this organism to the species level. Electron microscopy demonstrated "morula" or daisy-like appearance of its endosporulating sporangia. The organism was sensitive to amphotericin B by E test method. Even though human protothecosis is uncommon, it cannot be ignored because it is emerging as an opportunistic infection in immunosuppressed individuals. To our knowledge, this is the first reported case of disseminated algaemia due to P. wickerhamii in Malaysia.

MIF participates in Toxoplasma gondii-induced pathology following oral infection.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is essential for controlling parasite burden and survival in a model of systemic Toxoplasma gondii infection. Peroral T. gondii infection induces small intestine necrosis and death in susceptible hosts, and in many aspects resembles inflammatory bowel disease (IBD). Considering the critical role of MIF in the pathogenesis of IBD, we hypothesized that MIF participates in the inflammatory response induced by oral infection with T. gondii. METHODOLOGY/PRINCIPAL FINDINGS: Mif deficient (Mif(-/-)) and wild-type mice in the C57Bl/6 background were orally infected with T. gondii strain ME49. Mif(-/-) mice had reduced lethality, ileal inflammation and tissue damage despite of an increased intestinal parasite load compared to wt mice. Lack of MIF caused a reduction of TNF-α, IL-12, IFN-γ and IL-23 and an increased expression of IL-22 in ileal mucosa. Moreover, suppressed pro-inflammatory responses at the ileal mucosa observed in Mif(-/-) mice was not due to upregulation of IL-4, IL-10 or TGF-ß. MIF also affected the expression of matrix metalloproteinase-9 (MMP-9) but not MMP-2 in the intestine of infected mice. Signs of systemic inflammation including the increased concentrations of inflammatory cytokines in the plasma and liver damage were less pronounced in Mif(-/-) mice compared to wild-type mice. CONCLUSION/SIGNIFICANCE: In conclusion, our data suggested that in susceptible hosts MIF controls T. gondii infection with the cost of increasing local and systemic inflammation, tissue damage and death.

Neonatal umbilical myiasis with sepsis.

The authors report a 9-day old neonate from a rural area with umbilical myiasis caused by fly larvae of Cochliomyia hominivorax. The blowfly causing this infestation belongs to the family Calliphoridae (Diptera) and the genus Cochliomyia that usually infests only open wounds of animals. The new-world screw-worm fly Cochliomyia hominivorax, is an obligate ectoparasite of domestic and wild animals, and in some cases may affect humans. This is the rare reported case of neonatal umbilical myiasis with sepsis in the world literature.