Leptospirosis as a cause of fever associated with jaundice in the Democratic Republic of the Congo.

BACKGROUND: Fever with jaundice is a common symptom of some infectious diseases. In public health surveillance within the Democratic Republic of the Congo (DRC), yellow fever is the only recognized cause of fever with jaundice. However, only 5% of the surveillance cases are positive for yellow fever and thus indicate the involvement of other pathogens. Leptospira spp. are the causative agents of leptospirosis, a widespread bacterial zoonosis, a known cause of fever with jaundice. This study aimed to determine the seropositivity of anti-Leptospira antibodies among suspected yellow fever cases and map the geographical distribution of possible leptospirosis in the DRC. METHODS: We conducted a retrospective study using 1,300 samples from yellow fever surveillance in the DRC from January 2017 to December 2018. Serum samples were screened for the presence of IgM against Leptospira spp. by a whole cell-based IgM ELISA (Patoc-IgM ELISA) at the Institut National de Recherche Biomedicale in Kinshasa (INRB) according to World Health Organization (WHO) guidance. Exploratory univariable and multivariable logistic regression analyses were undertaken to assess associations between socio-demographic factors and the presence of Leptospira IgM. RESULTS: Of the 1,300 serum samples screened, 88 (7%) showed evidence of IgM against Leptospira spp. Most positive cases (34%) were young adult males in the 20-29-year group. There were statistically significant associations between having Leptospira IgM antibodies, age, sex, and living area. Observed positive cases were mostly located in urban settings, and the majority lived in the province of Kinshasa. There was a statistically significant association between seasonality and IgM Leptospira spp. positivity amongst those living in Kinshasa, where most of the positive cases occurred during the rainy season. CONCLUSIONS: This study showed that leptospirosis is likely an overlooked cause of unexplained cases of fever with jaundice in the DRC and highlights the need to consider leptospirosis in the differential diagnosis of fever with jaundice, particularly in young adult males. Further studies are needed to identify animal reservoirs, associated risk factors, and the burden of human leptospirosis in the DRC.

Jaundice and Thrombocytopenia in an acute abdomen with concurrent Appendicitis and spontaneous Rectal perforation: An unusual presentation of human leptospirosis.

Leptospirosis, a bacterial infection attributed to the group leptospira, remains a globally emerging public-health issue in many endemic tropical, subtropical and temperate zones of the world. The burden is expected to inflate with population shifts related to violent storms and urban floods leading to poor housing and inadequate sanitation. Leptospirosis may mimic other illnesses such as influenza, dengue fever, typhoid and malaria due to its myriad presentation ranging from a mild, self-limiting febrile illness to hepatorenal dysfunction, myocarditis, pulmonary haemorrhage, meningitis, optic neuritis and rhabdomyolysis. The classical gastrointestinal manifestation of leptospirosis without hepatorenal dysfunction (Weil's disease) is a rare entity. We report a rare presentation of concurrent appendicitis and rectal perforation in a patient, whose jaundice and thrombocytopenia led to a suspicion of leptospirosis, confirmed by serology and fulfilment of parameters under the modified Faine's criteria. The patient was managed successfully and discharged in a stable condition.

Leptospirosis in French Historical Medical Literature: Weil's Disease or Kelsch's Disease?

Early names for leptospirosis often indicate occupational or environmental exposure. Leptospirosis is hard to identify in the tropical setting because of co-circulating diseases. This is not the case in the temperate setting, such as Europe, where the few historical differential diagnoses were malaria, typhoid, and viral hepatitis. Leptospirosis presumably caused community epidemics in Europe before 1900 and military epidemiologists carefully documented outbreaks in "constrained settings." Achille Kelsch (1841-1911) synthesized available military data and epidemiological perspectives to define "epidemic jaundice" as a nosological continuum, caused by an infectious agent found in muds and water. He viewed Weil's disease as being only one form of that now well-identified disease continuum. The causative pathogen and epidemiological determinants were identified years later. The role of soils and muds as intermediate reservoirs, as suggested by Kelsch, deserves further investigation.

Evidence of human leptospirosis cases in a cohort of febrile patients in Bangui, Central African Republic: a retrospective study, 2012-2015.

BACKGROUND: In spite of a local favorable environment, leptospirosis has never been described in Central African Republic so far mainly because of the weakness of diagnostic tests and differential diagnostic strategy for febrile jaundice cases negative for yellow fever virus. Here we bring a complementary insight to conclusions of Gadia CLB et al. regarding the presence of leptospirosis in Central African Republic in YFV-negative febrile icteric patients. METHODS: Our study included 497 individuals presenting with fever and jaundice but negative for yellow fever infection, retrospectively selected from the national surveillance biobank for yellow fever in Institut Pasteur de Bangui, Central African Republic. A combination of serological (ELISA, agglutination) and molecular biology techniques (quantitative real-time polymerase chain reaction) was used to identify Leptospira or the patient's immune response to the bacteria. Statistical analyses were done using the non parametric Mann-Withney U test with a 5% statistical threshold. RESULTS: ELISA test results showed 46 positive serum samples while 445 were negative and 6 remains equivocal. In addition, the reference microscopic agglutination test for leptospirosis diagnostic confirmed that 7 out of 32 samples tested were positive. Unfortunately, all 497 serum samples tested for leptospirosis were negative using the molecular techniques. CONCLUSIONS: Unlike Gadia et al., we confirmed that leptospirosis is circulating in Central African Republic and therefore may be responsible for some of the unexplained cases of febrile jaundice in the country. Thus, leptospirosis needs to be investigated to improve identification of aetiological pathogens. Our study also suggests a need to improve sample transportation and storage conditions.

Leptospirosis as Cause of Febrile Icteric Illness, Burkina Faso.

Patients in Burkina Faso who sought medical attention for febrile jaundice were tested for leptospirosis. We confirmed leptospirosis in 27 (3.46%) of 781 patients: 23 (2.94%) tested positive using serologic assays and 4 (0.51%) using LipL32 PCR. We further presumed leptospirosis in 16 (2.82%) IgM-positive specimens.

Syphilitic jaundice: a rare manifestation of the secondary stage presenting a missed opportunity to prevent ocular syphilis.

The classical presentation of secondary syphilis comprises skin rashes, mucosal ulceration and lymphadenopathy. However, this disseminated stage can also present with symptoms and signs of ocular, neurological, pulmonary, renal, musculoskeletal and digestive tract disease. We report the case of a gay man who presented with icteric hepatitis. Although he underwent an exhaustive series of investigations (some of which were invasive), syphilis was not initially considered in the differential diagnosis. His jaundice resolved spontaneously, but he subsequently developed an acute optic neuritis. Early syphilis is relatively common in men who have sex with men (MSM). Prompt diagnosis and treatment in this case would have prevented ocular involvement. Syphilis testing should be considered in all MSM presenting with unexplained symptoms and signs.

Case Report: A Cluster of Three Leptospirosis Cases in a New York City Abattoir and an Unusual Complication in the Index Case.

We report the case of a 46-year-old male abattoir worker who developed myalgias, shortness of breath, and irritability 2 weeks after sustaining a laceration to the hand with a knife at work. During his hospital evaluation for septic shock he was noted to be febrile, hypotensive, profoundly jaundiced with aseptic meningitis, and renal failure, and was diagnosed with Leptospirosis interrogans infection confirmed by serum and urine polymerase chain reaction. After standard antibiotic therapy and recovery from severe clinical illness, he developed unilateral orchitis with pyuria secondary to leptospirosis, a well-established complication in the veterinary literature, but of which we offer the first report in humans in the English literature. The case presented was also the index case that uncovered a cluster outbreak of leptospirosis in New York City during the winter of 2016-2017, involving a total of three patients who lived or worked within a block of the abattoir. Two patients survived whereas the third died of pulmonary hemorrhage shortly after seeking medical care.

Scrub Typhus - The Most Common Cause of Febrile Jaundice in a Tertiary Care Hospital of Himalayan State.

BACKGROUND: Most common cause of jaundice in south east Asia is of infective etiology. Combination of fever with jaundice can cause diagnostic problem as this duo is present in many infective diseases. Timely diagnosis by simple laboratory investigations can save a lot of time and prevent morbidity and mortality. Our main aim was to determine the most common etiology of infectious jaundice in a tertiary care hospital of Himalayan state and to study their clinical profile. METHODOLOGY: This was a prospective observational study done in one year. All the patients more than 18 years of age presenting with jaundice with bilirubin >1.5mg/dl were taken. The clinical profile was observed and investigations for etiology were done. RESULTS: Total number of patients studied were 170. Maximum number of patients were 50 (39.4%) in age group less than 30 years and females outnumbered males with 1.8:1 ratio (64.7% v/s 35.3%). Fever was the most common presenting complaint in 127 (74.7%) patients and most common etiology was scrub typhus with 103 patients (60.6%) followed by hepatitis E in 36 patients (21.2%) and leptospirosis in 9 patients (5.3%). CONCLUSIONS: Scrub typhus is the commonest cause of febrile jaundice in Himachal Pradesh. The general physicians should be sensitized for the early diagnosis to reduce mortality.

A new model of self-resolving leptospirosis in mice infected with a strain of Leptospira interrogans serovar Autumnalis harboring LPS signaling only through TLR4.

Leptospirosis is an emerging worldwide zoonosis caused by pathogenic Leptospira spp. Our understanding of leptospirosis pathogenesis and host immune response remains limited, while mechanistic studies are hindered by a lack of proper animal models and immunological reagents. Here we established a murine model of acute and self-resolving leptospirosis by infecting 10-week-old C57BL/6 mice with Leptospira interrogans serovar Autumnalis strain 56606v, with characteristic manifestations including jaundice as well as subcutaneous and pulmonary bleeding, but no kidney lesions. We also verified that the lipopolysaccharide (LPS) of strain 56606v signaled through a TLR4-dependent pathway in murine bone marrow-derived macrophages (BMDMs), rather than the previously reported TLR2. In addition, upon infection with Leptospira strain 56606v, TLR4-/- C57BL/6 mice presented more severe jaundice and liver injury as well as higher bacterial loads than WT mice but milder pulmonary hemorrhaging. Molecular studies showed that leptospirosis-related bleeding coincides with the temporal kinetics of iNOS production, while jaundice and liver injury are probably due to insufficiently controlled bacterial loads in the liver. These results suggested that TLR4 is essential in mediating host leptospiral clearance and, to some extent, is associated with pulmonary and subcutaneous hemorrhage, probably through downstream inflammatory mediators, iNOS in particular. Overall, our murine model using immunocompetent mice might facilitate future studies into the pathogenesis of jaundice and bleeding in leptospirosis. Meanwhile, our study suggests the prospect of combining antibiotics and immunosuppressants in the treatment of severe leptospirosis presenting with pulmonary hemorrhage.

Pressor support during a Jarisch Herxheimer reaction after initiation of treatment for Weil's disease.

We present a case of Weil's disease complicated by a Jarisch-Herxheimer reaction (JHR) after initiation of antibiotics while in the emergency department requiring invasive monitoring and vasopressor support. The case is followed by a brief review of the JHR which is rarely observed with treatment of leptospirosis. A healthy 28-year-old female who recently returned from the Caribbean presented to the emergency department with flu-like symptoms. The patient appeared jaundiced with conjunctival suffusion and was ultimately treated with the appropriate antibiotics for leptospirosis in the ED. She decompensated subsequently, requiring supplemental oxygen, central and arterial line placement, and vasopressor support with norepinephrine. Although rarely encountered and not well reported throughout the literature, initiation of antibiotics can cause a JHR reaction given that Leptospira interrogans is a spirochete. This JHR may be self-limited and of short duration, or it can be prolonged and severe, requiring invasive therapies such as central line placement for vasopressor support and intubation. It is suggested that patients started on antibiotics for leptospirosis/Weil's disease should be monitored in the emergency department for a short duration prior to discharge or transfer to a regular medical floor for observation given the possibility for decompensation.

Clonal structure in Ichthyobacterium seriolicida, the causative agent of bacterial haemolytic jaundice in yellowtail, Seriola quinqueradiata, inferred from molecular epidemiological analysis.

Bacterial haemolytic jaundice caused by Ichthyobacterium seriolicida has been responsible for mortality in farmed yellowtail, Seriola quinqueradiata, in western Japan since the 1980s. In this study, polymorphic analysis of I. seriolicida was performed using three molecular methods: amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST) and multiple-locus variable-number tandem repeat analysis (MLVA). Twenty-eight isolates were analysed using AFLP, while 31 isolates were examined by MLST and MLVA. No polymorphisms were identified by AFLP analysis using EcoRI and MseI, or by MLST of internal fragments of eight housekeeping genes. However, MLVA revealed variation in repeat numbers of three elements, allowing separation of the isolates into 16 sequence types. The unweighted pair group method using arithmetic averages cluster analysis of the MLVA data identified four major clusters, and all isolates belonged to clonal complexes. It is likely that I. seriolicida populations share a common ancestor, which may be a recently introduced strain.

Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin in the treatment of secondary hemophagocytic lymphohistiocytosis with classical Hodgkin lymphoma: a case report and review of the literature.

BACKGROUND: Hemophagocytic lymphohistiocytosis is becoming an increasingly recognized disorder in adults. Classical Hodgkin lymphoma is a relatively uncommon etiology of hemophagocytic lymphohistiocytosis and may complicate treatment options. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin are discussed here as a treatment regimen. CASE PRESENTATION: A 66-year-old Hispanic man previously in good health presented with a 1-month history of recurrent fevers, chills, and night sweats and a 3-week history of new onset jaundice. A bone marrow biopsy revealed a normocellular bone marrow with increased histiocytes with areas of hemophagocytic activity. He met five out of eight criteria for hemophagocytic lymphohistiocytosis diagnosis including fevers, pancytopenia, hemophagocytosis, ferritin of 23,292 ng/mL (>500 ng/mL), and soluble-CD25 of 15,330 pg/mL (>1033 pg/mL). A right cervical lymph node biopsy revealed CD15, CD30, MUM-1, and Epstein-Barr virus-encoded small ribonucleic acid-positive cells with morphologic findings of classical Hodgkin lymphoma, lymphocyte-rich subtype. He completed 2 weeks of hemophagocytic lymphohistiocytosis-directed therapy with etoposide and dexamethasone, but then was switched to rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin due to minimal improvement in his pancytopenia and hepatic impairment. He completed one full cycle of rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin with notable improvement in serial hepatic function panels and had an undetectable Epstein-Barr virus viral load. However, he eventually died due to complications of Enterococcus faecalis bacteremia and colonic microperforation in the setting of persistent pancytopenia. CONCLUSIONS: This case discusses the challenges facing treatment of adult malignancy-associated hemophagocytic lymphohistiocytosis. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin may be a viable option for patients with secondary hemophagocytic lymphohistiocytosis and Hodgkin lymphoma who cannot tolerate standard therapies due to hepatic impairment. Targeted therapy and immunotherapy are promising new areas of developing treatments.

A case report of inhalation anthrax acquired naturally.

BACKGROUND: Anthrax is a zoonotic occupational disease caused by Bacillus anthracis, a rod-shaped immobile aerobic gram-positive bacteria with spore. Anthrax occurs in humans randomly and with low frequency. Most cases of anthrax are acquired through contact with infected animals or contaminated animal products. This old disease became particularly important since 2001 that the biological spores were exploited in America. Depending on the transmission method of the disease, clinical manifestations occur in three classes: Cutaneous, respiratory, and gastrointestinal anthrax. The respiratory form is considered as the most fatal and a rare form of anthrax intending to show complicated and unusual manifestations. CASE PRESENTATION: In this case report a rare case of inhalation anthrax acquired naturally in southeast of Iran is presented. A blind 65-year-old man, living in a rural area, was admitted with respiratory infection, fever, dyspnea, loss of appetite, and myalgia. The patient was treated with outpatient antibiotics a week ago. After admission, the patient was again treated for pneumonia, but there was no improvement despite treatment and the patient was suffering from septicemia symptoms. Radiographic images showed wide mediastinum. Bacillus anthracis was isolated from blood and sputum culture and the results were confirmed by colony morphology, biochemical reactions and PCR. The treatment was changed to ciprofloxacin, clindamycin, and penicillin. On the second day of anthrax treatment, the patient was complicated with jaundice, elevation of liver enzymes, and a significant drop in hemoglobin, hematocrit, and platelet despite lack of obvious bleeding and was complicated with respiratory distress and sepsis and died a week after treatment. CONCLUSIONS: We could discover no specific exposure associated with anthrax infection for this patient. However, due to being located in an endemic and enzootic area, it is proposed that the exposure occurred through contact with infected airborne dust or an unknown contaminated item. Despite many advances in preventing anthrax, still some rare cases of respiratory and complicated anthrax are emerging. With regard to the threat of bioterrorism, medical staff's sensitivity to the clinical syndrome, methods of prophylaxis and treatment of anthrax must be raised. Fast diagnosis and successful treatment the lethal cases of this infection are of utmost important.

Ichthyobacterium seriolicida gen. nov., sp. nov., a member of the phylum 'Bacteroidetes', isolated from yellowtail fish (Seriola quinqueradiata) affected by bacterial haemolytic jaundice, and proposal of a new family, Ichthyobacteriaceae fam. nov.

A novel Gram-stain-negative, rod-shaped (0.3 × 4-6 µm), non-flagellated, aerobic strain with gliding motility, designated JBKA-6T, was isolated in 1991 from a yellowtail fish, Seriola quinqueradiata, showing symptoms of bacterial haemolytic jaundice. 16S rRNA gene sequence analysis showed that strain JBKA-6T was related most closely to members of the family Flavobacteriaceae in the phylum 'Bacteroidetes'. Furthermore, based on gyrB gene sequence analysis, JBKA-6T was classified into a single clade within the order Flavobacteriales, which was distinct from the known clades of the families Flavobacteriaceae, Blattabacteriaceae and Cryomorphaceae. The predominant isoprenoid quinone was identified as MK-6 (97.9 %), and the major cellular fatty acids (>10 %) were C14 : 0 and iso-C15 : 0. The main polar lipids were phosphatidylethanolamine, three unidentified phospholipids, two unidentified aminophospholipids and two unidentified polar lipids. The DNA G+C content of JBKA-6T, as derived from its whole genome, was 33.4 mol%. The distinct phylogenetic position and phenotypic traits of strain JBKA-6T distinguish it from all other described species of the phylum 'Bacteroidetes', and therefore it was concluded that strain JBKA-6T represents a new member of the phylum 'Bacteroidetes', and the name Ichthyobacterium seriolicida gen. nov., sp. nov. is proposed. The type strain of Ichthyobacterium seriolicida is JBKA-6T ( = ATCC BAA-2465T = JCM 18228T). We also propose that Icthyobacterium gen. nov. is the type genus of a novel family, Ichthyobacteriaceae fam. nov.

A first report of leptospirosis after liver transplantation.

Leptospirosis has been rarely reported in solid organ transplant recipients. We report the first case to our knowledge of leptospirosis in a liver transplant recipient who developed jaundice and renal insufficiency. We describe his favorable clinical progression and discuss the possible mechanisms involved in the more benign disease course. We also review the previously published cases of leptospirosis in solid organ transplant recipients. Although this disease does not appear to present any particularities in this context, we highlight the importance of clinical suspicion in this setting, particularly after liver transplantation.

Fever, jaundice and acute renal failure.

Leptospirosis is an uncommon infectious disease that has protean clinical manifestations ranging from an innocuous 'flu-like' illness to potentially life-threatening multi-organ failure. Here we describe a case of Weil's disease that presented on the acute medical take with fever, jaundice and acute renal failure. We highlight the importance of careful history taking at the time of admission and how understanding the epidemiology and pathophysiology of leptospirosis enables a definitive diagnosis to be reached.

Congenital jaundice in bovine aborted foetuses: an emerging syndrome in southern Belgium.

Southern Belgium faces an unusual recent increase of icteric bovine aborted foetuses. In the necropsy room, the majority of foetuses presented jaundice and splenomegaly. Despite a wide range of analyses, no definitive cause of abortion has yet been established but some analysis results support the leptospirosis hypothesis. This first description of cases will help veterinary practitioners to recognize more cases and to conduct those to the laboratory for future investigations.