Brucellosis in pregnancy: results of multicenter ID-IRI study.

Brucellosis in pregnant women is reported to be associated with obstetric complications (OCs), and adequate data for human brucellosis during pregnancy are largely lacking. We performed this multicenter retrospective cross-sectional study to evaluate the epidemiology, clinical course, treatment responses, and outcomes of brucellosis among pregnant women. The study period comprised a 14-year period from January 2002 to December 2015. All consecutive pregnant women diagnosed with brucellosis in 23 participating hospitals were included. Epidemiological, clinical, laboratory, therapeutic, and outcome data along with the assessment data of the neonate were collected using a standardized questionnaire. Data of 242 patients were analyzed. The OC rate was 14.0% (34/242) in the cohort. Of the 242 women, 219 (90.5%) delivered at term, 3 (1.2%) had preterm delivery, 15 (6.2%) aborted, and 5 (2.1%) had intrauterine fetal demise. Seventeen (7.0%) of the newborns were considered as low birth weight. Spontaneous abortion (6.1%) was the commonest complication. There were no maternal or neonatal deaths and pertinent sequelae or complications were not detected in the newborns. Splenomegaly (p = 0.019), nausea and/or vomiting (p < 0.001), vaginal bleeding (p < 0.001), anemia (blood hemoglobin < 11 g/dL; p < 0.001), high level of serum aspartate aminotransferase (> 41 IU/L; p = 0.025), oligohydramnios on ultrasonography (p = 0.0002), history of taking medication other than Brucella treatment during pregnancy (p = 0.027), and Brucella bacteremia (p = 0.029) were the significant factors associated with OCs. We recommend that pregnant women with OC or with fever should be investigated for brucellosis if they live in or have traveled to an endemic area.

[Periodic fever and pancytopenia in a 35-year-old patient]. / Periodisches Fieber und Panzytopenie bei einem 35­jährigen Patienten.

MEDICAL HISTORY AND INITIAL PRESENTATION: A 35-year-old patient with a previous history of persistent episodic fever, sore throat, myalgia, and cephalgia presented for evaluation of pancytopenia. He had no recent travel history, except for a stay in Italy 1 year prior to admission and in Spain several years in the past. DIAGNOSTIC WORKUP: Laboratory evaluation confirmed pancytopenia, agranulocytosis, and elevated infection parameters without indicative serological results en par with lymphadenitis colli. Computed tomography scanning revealed cervical lymphadenopathy, hepatosplenomegaly, and colitis with occult perforation of the sigmoid colon. Bone marrow biopsy showed an infiltration of polyclonal plasma cells. Lymph node biopsy was compatible with necrotizing lymphadenitis. DIAGNOSIS: Polymerase chain reaction analysis of a lymph node specimen confirmed the presence of Leishmania species, thereby enabling the diagnosis of visceral Leishmania. THERAPY COURSE: Treatment with liposomal amphotericin B was initiated. Both fever and lymphadenopathy quickly resolved. CONCLUSION: VL is a clinically pleiotropic, severe disease with fatal outcome if left untreated. It often presents with distinct similarities to hematologic malignancies. Exacerbation can occasionally occur as fulminant macrophage activation syndrome. Disease incidence is globally increasing and has not peaked as yet. A complex interplay between pathogen and the immune system is the key pathophysiological mechanism.

Ultrasound presentation of abdominal tuberculosis in a German tertiary care center.

OBJECTIVE: Abdominal tuberculosis (TB) is a relatively rare disease in most of Europe and the typical clinical and sonographic findings in this setting have not been studied. We aimed to define sonographic findings that should alert an examiner to the possibility of abdominal TB in a low endemic region. METHODS: Case records of 17 patients with proven (n = 11) or highly likely (n = 6) abdominal TB detected in the gastrointestinal ultrasound unit at a German tertiary care center in 2003-2013 were analyzed retrospectively. Findings were compared with reported series from high-prevalence regions. RESULTS: While 76% of patients had an immigrant background, only 35% had a condition associated with immunosuppression. Lymphadenopathy was present in all cases of abdominal TB, while it was absent in 28% of patients from a control group with proven abdominal sarcoidosis. Moreover, retroperitoneal lymphadenopathy was significantly more common in TB. Other findings in patients with abdominal TB in descending order of frequency were ascites, altered hepatic texture, splenomegaly, splenic lesions, peritoneal thickening, intestinal wall lesions, hepatic lesions and hepatomegaly. 76% of abdominal TB patients had 2 or more pathological findings. CONCLUSIONS: Multiple pathological intra-abdominal findings including lymphadenopathy should alert the examiner to the possibility of abdominal TB.

Ultrasonographic appearance of histoplasmosis identified in the spleen in 15 cats.

Histoplasmosis is the second most common fungal infection reported in the cat. The disseminated form involving lung, liver, lymph nodes, spleen, and bone marrow is a frequent manifestation of the disease. Limited information is available in the literature regarding the ultrasonographic appearance of the spleen in cats with disseminated or splenic histoplasmosis. A retrospective review of splenic ultrasound images from 15 cats confirmed to have histoplasmosis by splenic aspirates was performed. Size, echotexture, echogenicity, margin appearance, presence of nodules, and the overall shape of the spleen were reported in each case. Splenomegaly was documented in all cases (15/15) and a hypoechoic appearance of the spleen was documented in 14/15 of cases. The spleen was diffusely and uniformly affected in 14/15 (six homogenous and eight with a subtle mottled appearance) and had discrete nodules in 1/15 cats. Histoplasmosis should be included in the differential list for an enlarged and hypoechoic spleen in cats with consistent clinical findings. Additionally, ultrasound guided splenic aspirate may be a useful method to obtain a cytology sample for diagnosis.

Innate immune activation during Salmonella infection initiates extramedullary erythropoiesis and splenomegaly.

Systemic Salmonella infection commonly induces prolonged splenomegaly in murine or human hosts. Although this increase in splenic cellularity is often assumed to be due to the recruitment and expansion of leukocytes, the actual cause of splenomegaly remains unclear. We monitored spleen cell populations during Salmonella infection and found that the most prominent increase is found in the erythroid compartment. At the peak of infection, the majority of spleen cells are immature CD71(-)Ter119(+) reticulocytes, indicating that massive erythropoiesis occurs in response to Salmonella infection. Indeed, this increase in RBC precursors corresponded with marked elevation of serum erythropoietin (EPO). Furthermore, the increase in RBC precursors and EPO production required innate immune signaling mediated by Myd88/TRIF. Neutralization of EPO substantially reduced the immature RBC population in the spleen and allowed a modest increase in host control of infection. These data indicate that early innate immunity to Salmonella initiates marked splenic erythropoiesis and may hinder bacterial clearance.

Identification of cytokeratin 18 as a biomarker of mouse and human hepatosplenic schistosomiasis.

Previously, we demonstrated unique protein expression patterns in 20-week-Schistosoma mansoni-infected CBA/J mice with moderate splenomegaly syndrome (MSS) or hypersplemomegaly syndrome (HSS). To better understand the development of severe pathology, we compared the two-dimensional differential in-gel electrophoresis (2D-DIGE) proteomic signatures of livers from uninfected mice and mice infected for 6, 8, 12, or 20 weeks and found significant changes in collagen isoforms, interleukin-2 (IL-2), cytokeratin 18, hydroxyproline, S. mansoni phosphoenolpyruvate carboxykinase, major urinary protein isoforms, and peroxiredoxin 6. Cytokeratin 18, hydroxyproline, and connective tissue growth factor (CTGF) were chosen for analysis in mouse and human sera using targeted biochemical assays. Consistent with the liver analysis, cytokeratin 18, CTGF, and hydroxyproline were significantly elevated in sera from mice with HSS compared to those from uninfected mice or mice with MSS. Moreover, cytokeratin 18 and CTGF were found to be markers for subjects with hepatosplenic and intestinal schistosomiasis, respectively, while serum hydroxyproline was a strong indicator of fibrosis for severe HS. These findings indicate that schistosome-associated changes to the liver can be detected in the serum and reveal the potential for cytokeratin 18 to be used as a diagnostic marker for early detection of hepatosplenic schistosomiasis.

Bacteremia, fever, and splenomegaly caused by a newly recognized bartonella species.

Bartonella species cause serious human infections globally, including bacillary angiomatosis, Oroya fever, trench fever, and endocarditis. We describe a patient who had fever and splenomegaly after traveling to Peru and also had bacteremia from an organism that resembled Bartonella bacilliformis, the causative agent of Oroya fever, which is endemic to Peru. However, genetic analyses revealed that this fastidious bacterium represented a previously uncultured and unnamed bartonella species, closely related to B. clarridgeiae and more distantly related to B. bacilliformis. We characterized this isolate, including its ability to cause fever and sustained bacteremia in a rhesus macaque. The route of infection and burden of human disease associated with this newly described pathogen are currently unknown.

Congenital brucellosis: case report.

A 6-hour-old infant was admitted with severe respiratory distress and hepatosplenomegaly. Her mother had arthralgia for 4 weeks in the 7/8th month of pregnancy and the infant was born at 31 weeks. Brucella spp was detected in blood culture and serology in mother and infant, supporting the diagnosis of brucellosis with presumed transplacental transmission.

Myelofibrosis: An unusual presentation of disseminated tuberculosis.

Disseminated tuberculosis (DTB) often presents with protean clinical manifestations that often leads to potential diagnostic dilemmas. The nonspecific features may include pyrexia of unknown origin, hepatosplenomegaly, lymphadenopathy, meningitis, and a variety of hematological abnormalities, namely anemia, pancytopenia, and leukemoid reaction. Tuberculosis is one of the nonhematopoietic diseases that has been reported in conjunction with myelofibrosis. We, hereby, report a case of DTB with massive splenomegaly, severe pancytopenia, and marrow fibrosis.

Septicemic melioidosis complicating undiagnosed chronic kidney disease and beta-thalassemia minor in a Bangladeshi farmer.

Melioidosis is an emerging infectious disease in many countries including Bangladesh. Patients with diabetes mellitus are at increased risk for infection by Burkholderia pseudomallei, the causative agent for melioidosis. Here, we report an autochthonous case of septicemic melioidosis occurring in a middle-aged non-diabetic Bangladeshi farmer who presented with prolonged pyrexia and splenomegaly. Diagnostic workup revealed splenic micro-abscesses, previously undetected chronic kidney disease (CKD) and beta-thalassemia minor. This case stresses the importance of searching for less common risk factors for melioidosis such as CKD and hemolytic anemia.

Leptospirosis mimicking hemolytic uremic syndrome: a case report.

Leptospirosis was diagnosed in a child presenting with acute kidney injury, anemia, and thrombocytopenia. Initial symptoms included abdominal pain and nonbloody diarrhea, followed by fever, vomiting, and skin rash. Leptospirosis was suspected and eventually confirmed. Although leptospirosis is uncommon in temperate climates, it is occurring in increasing numbers of participants in water sports, making it a consideration in the differential diagnosis of hemolytic uremic syndrome.

Lack of pathogenicity and toxicity of the mycoinsecticide Metarhizium anisopliae var. acridum following acute gastric exposure in mice.

Metarhizium anisopliae var. acridum, monospore culture EH-502/8 (CNRCB MaPL40), isolated in Mexico from Schistocerca piceifrons ssp. piceifrons (Orthoptera: Acrididae) was tested for acute oral intragastric pathogenicity and toxicity in CD-1 mice. Animals were inoculated with one dose (10(8) conidia/animal) of viable (72 mice), non-viable (24 mice) conidia and compared to 18 control mice. Clinical observations were done daily; mycological and histological tests were performed during necropsies after the inoculation. No mice showed clinical symptoms of illness or died during the study. The fungus was able to persist in some organs until day 3, but did not cause any damage to the host. The gross pathology observed was splenomegaly in mice inoculated with viable and non-viable conidia. Non-germinated conidia, observed in several organs, suggest hematogenous spread, but without any histopathological tissue reaction. Results support the non-pathogenic and non-toxic status of this fungal strain when administered in a single intragastric dose to mice.

Case Report: Scrub Typhus and Q Fever Coinfection.

A 56-year-old female goat herder had scrub typhus that persisted after receiving doxycycline for 5 days. Her symptoms continued, prompting us to perform further examinations that revealed coinfection of Q fever and scrub typhus via molecular and serological testing. We also isolated Orientia tsutsugamushi using BALB/c mice and L929 cells.

Hepatosplenic brucella abscesses on computed tomography and magnetic resonance imaging: Case series.

INTRODUCTION: Because of its infrequent and the lack of clinical data and image finding, the management of acute infections with the hepatosplenic brucella abscesses is challenging. METHODS: There were 10 serologically diagnosed cases with this brucella infection. All patients had fever, 50% patients had upper abdominal pain. Ninety percent patients lived in an urban environment. The localization of lesions included: 30% hepatosplenic, 30% liver, and 40% spleen. RESULTS: Abdominal computed tomography (CT) scans and magnetic resonance imaging (MRI) demonstrated hepatosplenomegaly, with multiple small abscess lesions of various sizes in the acute stage of brucellosis, with the largest diameter of 1.5 cm in the liver. After contrast-enhanced CT and MRI findings, the arterial phase in which the enhancing area of lesions was thick, revealed multifocal hypodense or hypointense lesions of various sizes. These lesions manifested distinct boundary, which was intensified obviously in portal venous phase. CONCLUSION: Our results indicate that early CT or MRI dynamic contrast enhancement of suspected cases could improve rapid diagnosis. However, diagnostic criteria remain problematic and diagnosis is mostly based on a combination of clinical suspicion, serologic markers, and radiologic findings.

A comparison of cecal colonization of Salmonella enterica serotype Typhimurium in white leghorn chicks and Salmonella-resistant mice.

BACKGROUND: Salmonellosis is one of the most important bacterial food borne illnesses worldwide. A major source of infection for humans is consumption of chicken or egg products that have been contaminated with Salmonella enterica serotype Typhimurium, however our knowledge regarding colonization and persistence factors in the chicken is small. RESULTS: We compared intestinal and systemic colonization of 1-week-old White Leghorn chicks and Salmonella-resistant CBA/J mice during infection with Salmonella enterica serotype Typhimurium ATCC14028, one of the most commonly studied isolates. We also studied the distribution of wild type serotype Typhimurium ATCC14028 and an isogenic invA mutant during competitive infection in the cecum of 1-week-old White Leghorn chicks and 8-week-old CBA/J mice. We found that although the systemic levels of serotype Typhimurium in both infected animal models are low, infected mice have significant splenomegaly beginning at 15 days post infection. In the intestinal tract itself, the cecal contents are the major site for recovery of serotype Typhimurium in the cecum of 1-week-old chicks and Salmonella-resistant mice. Additionally we show that only a small minority of Salmonellae are intracellular in the cecal epithelium of both infected animal models, and while SPI-1 is important for successful infection in the murine model, it is important for association with the cecal epithelium of 1-week-old chicks. Finally, we show that in chicks infected with serotype Typhimurium at 1 week of age, the level of fecal shedding of this organism does not reflect the level of cecal colonization as it does in murine models. CONCLUSION: In our study, we highlight important differences in systemic and intestinal colonization levels between chick and murine serotype Typhimurium infections, and provide evidence that suggests that the role of SPI-1 may not be the same during colonization of both animal models.

[Hyperactive malarious splenomegaly: diagnosis and therapeutic problems in adults]. / Splénomégalie palustre hyperactive: problèmes diagnostiques et thérapeutiques chez l'adulte.

The chronic forms of malaria are scarce. We report a case of an hyperactive malarious splenomegaly. This case concerns a 69 year-old man residing in a village of Côte d'Ivoire. He had massive splenomegaly type IV. He was admitted in hospital for progressive loss of weight and moderate fever He presented also asthenia, anaemia and regular hepatomegaly. The haematological, biochemical, immunological and radiological exams ruled out trypanosomiasis, visceral leishmaniasis, tuberculosis, bilharziasis diseases and neoplasia process. His age, the massive splenomegaly, the anaemia, the high antimalarial IgM antibodies in immunofluorescence and the favourable response to the prolonged administration of antimalarial treatment led to the diagnosis of hyperactive malarious splenomegaly despite the detection of Plasmodium falciparum in blood. This observation allows to underline the frequency of this possible underestimated chronic form of malaria in Africa and shows the necessity to consider it seriously when facing massive splenomegaly.

Disseminated histoplasmosis mimicking relapsed chronic lymphocytic leukaemia.

Histoplasma microconidia when inhaled are presented in antigenic form to T cells, limiting the extent of infection; however, defects in cellular immunity results in disseminated disease. Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disorder resulting in functionally impaired lymphocytes, predisposing patients to various opportunistic infections. The author reports a recently treated patient with CLL presenting with constitutional symptoms accompanied by hepatosplenomegaly and diffuse adenopathy. Considering the recent diagnosis and treatment of CLL, initial suspicion was relapsed disease. However, considering the immune deficiency associated with CLL and its treatment, infectious aetiologies were strongly considered. Further investigation revealed a case of disseminated histoplasmosis mimicking CLL in this reported patient. Considering appropriate diagnosis and timely therapy, the reported patient had good prognosis despite being diagnosed with disseminated histoplasmosis. This case highlights consideration of disseminated histoplasmosis in patients presenting with diffuse adenopathy along with hepatomegaly and/or splenomegaly in the right clinical setting.

Septicemic listeriosis: An emerging food-borne illness in India?

Listeriosis is a food borne illness of significant public health concern, caused by consumption of food contaminated by gram negative bacilli, Listeria monocytogenes. Clinical listeriosis is relatively rare and it has varying spectrum of presentation, ranging from severe sepsis in immune-compromised individuals, febrile gastroenteritis and meningo-encephalitis in infants and adults. This disease is under reported in developing nations due to the lack of awareness and inadequate laboratory facilities to promptly isolate and identify the organism. We report a case of sporadic food-borne listeriosis, in an otherwise healthy individual presenting with meningo-encephalitis. Prompt identification and appropriate antibiotic therapy led to a favorable outcome.

Attenuated Coxiella burnetii phase II causes a febrile response in gamma interferon knockout and Toll-like receptor 2 knockout mice and protects against reinfection.

Coxiella burnetii is a highly infectious obligate intracellular bacterium. The phase I form is responsible for Q fever, a febrile illness with flu-like symptoms that often goes undiagnosed. The attenuated C. burnetii phase II (having a truncated "O" chain of its lipopolysaccharide) does not cause disease in immunocompetent animals; however, phase II organisms remain infectious, and we questioned whether disease could be produced in immunodeficient mice. To study C. burnetii phase II infections, febrile responses in gamma interferon knockout (IFN-gamma(-/-)), BALB/c, Toll-like receptor 2 knockout (TLR2(-/-)), and C57BL/6 mice were measured using the Nine Mile phase II (NMII) strain of C. burnetii. Immunocompetent mice showed minimal febrile responses, unlike those obtained with IFN-gamma(-/-) and TLR2(-/-) mice, which showed elevated rectal temperatures that were sustained for approximately 15 days with transient increases in splenic weights. Reinfection of IFN-gamma(-/-) and TLR2(-/-) mice with C. burnetii NMII 30 days after primary infection protected mice as evident by reduced febrile responses and a lack of splenic inflammation. Although minimal detection of Coxiella in TLR2(-/-) mouse spleens was observed, greater colonization was evident in the IFN-gamma(-/-) mice. Cytokine analysis was performed on infected peritoneal macrophages isolated from these mice, and immunocompetent macrophages showed robust tumor necrosis factor alpha, IFN-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) but no interleukin-12 (IL-12) responses. IFN-gamma(-/-) macrophages produced elevated levels of IL-6, IL-10, and IL-12, while TLR2(-/-) macrophages produced GM-CSF, IL-12, and minimal IL-10. To distinguish immunity conferred by innate or adaptive systems, adoptive transfer studies were performed and showed that immune lymphocytes obtained from immunocompetent mice protected against a subsequent challenge with NMII, indicating that adaptive immunity mediates the observed protection. Thus, our data show that NMII is capable of eliciting disease in immunocompromised mice, which may help in evaluation of vaccine candidates as well as the study of host-pathogen interactions.