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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.

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.

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.

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 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.

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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., (© 2015 Blackwell Verlag GmbH.)

A 78-year-old woman presented to the acute medical unit with a productive cough, dyspnoea and decreased appetite of 4 days duration. Initial assessment supported a diagnosis of right-sided community-acquired pneumonia and she was started on antibiotics. In view of the clinical finding of splenomegaly, she had an ultrasound and, subsequently, a CT of the abdomen, which revealed a large splenic abscess. Pending cultures from a sample obtained from percutaneous drainage of the abscess, she was started on intravenous meropenem. The initial echocardiogram did not suggest any evidence of endocarditis. The pus drained from the abscess on cultures was subsequently positive for Staphylococcus aureus. An MRI of the spine excluded discitis as a source of infection. Owing to a high index of clinical suspicion a repeat echocardiogram was undertaken after 1-week, which confirmed acute endocarditis. The patient was treated with intravenous antibiotics for 6 weeks with improvement in clinical, radiological and biochemical parameters., (2015 BMJ Publishing Group Ltd.)

Brucella, the etiological agent of animal and human brucellosis, is a bacterium with the capacity to modulate the inflammatory response. Cyclic β-1,2-glucan (CβG) is a virulence factor key for the pathogenesis of Brucella as it is involved in the intracellular life cycle of the bacteria. Using comparative studies with different CβG mutants of Brucella, cgs (CβG synthase), cgt (CβG transporter) and cgm (CβG modifier), we have identified different roles for this polysaccharide in Brucella. While anionic CβG is required for bacterial growth in low osmolarity conditions, the sole requirement for a successful Brucella interaction with mammalian host is its transport to periplasmic space. Our results uncover a new role for CβG in promoting splenomegaly in mice. We showed that CβG-dependent spleen inflammation is the consequence of massive cell recruitment (monocytes, dendritics cells and neutrophils) due to the induction of pro-inflammatory cytokines such as IL-12 and TNF-α and also that the reduced splenomegaly response observed with the cgs mutant is not the consequence of changes in expression levels of the characterized Brucella PAMPs LPS, flagellin or OMP16/19. Complementation of cgs mutant with purified CβG increased significantly spleen inflammation response suggesting a direct role for this polysaccharide.

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., (© 2013 American College of Veterinary Radiology.)

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.

Streptococcus anginosus group is widely known for its ability to cause invasive pyogenic infections. There are very few reports of disseminated infections sustained by members of this streptococcal group. We report a case of a highly disseminated infection and analyse previous literature reports. Disseminated pyogenic infection has been defined as an infection affecting two or more of the following organs/systems: central nervous system, lung, liver and spleen. We performed a PubMed search using the terms: S. milleri, S. anginosus, brain abscess, pulmonary abscess, hepatic abscess, spleen abscess. We reviewed 12 case reports including the one presented in this paper. Underlying conditions such as dental infections, malignancy, gastrointestinal and respiratory tract disease accounted for 42% of cases. No definite endocarditis was encountered, even though positive blood cultures were found in 67% of patients. Concomitant brain-liver, brain-lung and brain-spleen involvement occurred in 50%, 42% and 8% of cases respectively. Ninety-one percent (91%) of patients were treated with β-lactams, and surgical procedures were performed in 67% of patients. Infections caused by S. anginosus group members are satisfactorily treated with penicillin G and cephalosporins. It is very important to associate surgery to antimicrobial chemotherapy in order to achieve a full or nearly full clinical recovery.

The diagnosis of enteric fever poses several problems due to the non-specific and wide array of clinical features. A five-year retrospective study enrolling 136 culture-proven cases of enteric fever was undertaken in order to estimate the clinical and laboratory characteristics, fever clearance time and outcome. The common symptoms and signs were: fever, vomiting, cough, anorexia, diarrhoea, abdominal pain, hepatomegaly, splenomegaly and coated tongue. Enteric fever should be considered in the differential diagnosis of febrile patients with abdominal symptoms.

Salmonella enterica serovars are intracellular bacteria capable of causing typhoid fever and gastroenteritis of significant morbidity and mortality worldwide. Current prophylactic and therapeutic treatment is hampered by the emergence of multidrug-resistant (MDR) strains of Salmonella, and vaccines provide only temporal and partial protection in vaccinees. To develop more effective Salmonella vaccines, it is important to understand the development of protective adaptive immunity to virulent Salmonella. Here we report the identification of novel CD4(+) T cell peptide epitopes, which are conserved among Salmonella serovars. Immunization of Salmonella-infected mice with these peptide epitopes reduces the burden of Salmonella disease. Furthermore, we show that distinct polyfunctional (interferon-γ(+), tumor necrosis factor(+), and interleukin-2(+)) Salmonella-specific CD4(+) T cell responses develop with respect to magnitude and kinetics. Moreover, we found that CD4(+) T cell responses against immunodominant epitopes are predictive for active Salmonella disease. Collectively, these data could contribute to improved diagnosis of Salmonella-related diseases and rational design of Salmonella vaccines.

Objectives: To determine risk factors in children for the acquisition of Brucella, clinical presentation, treatment, and disease outcomes., Methods: A retrospective multicenter chart review was undertaken of children identified with brucellosis from 1986 to 2008 at three tertiary care centers in Chicago, Illinois, USA. The charts were reviewed for data regarding risk factors for acquisition, clinical presentation, and outcomes., Results: Twenty-one charts were available for review. The median age was 6.5 years (range 2-14 years); 62% were female. Ethnic background was 67% Hispanic and 24% Arabic. Risk factors included travel to an endemic area (86%), particularly Mexico, and consumption of unpasteurized milk products (76%). Common findings included fever (95%), bacteremia (86%), elevated liver transaminases (80%), constitutional symptoms (76%), splenomegaly (60%), and hepatomegaly (55%). Relapse occurred in three of six subjects started on single drug treatment, but in only one of 15 subjects who started on two or more drugs (p=0.053). No relapses occurred in children whose initial therapy included rifampin or those administered three-drug regimens., Conclusions: Brucella is an infrequent pathogen but should be considered in children with compatible epidemiologic and clinical characteristics. Blood cultures should be obtained, and initial therapy with two or more drugs may decrease the risk of relapse., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A 62 year-old woman who presented with an atraumatic acute abdomen was discovered to have haemoperitoneum with splenic rupture on urgent computed tomography and was immediately referred for life-saving emergency splenectomy. Histopathological examination revealed secondary splenic amyloidosis. The patient was later found to be suffering from infective endocarditis secondary to her permanent cardiac pacemaker. This report describes a patient who could have suffered from a long-standing infected vegetation on a permanent cardiac pacemaker, which led to splenic amyloidosis and spontaneous splenic rupture.

Here, we report a case of multidrug-resistant tuberculosis (TB) presenting as a solitary splenic mass in a 60-year-old immunocompetent patient. Splenic TB is unusual and, when present, is usually associated with disseminated disease in immunocompromised patients. A high level of suspicion is required for diagnosis, and, as occurred in our case, it may be an unexpected finding following surgery. Diagnosis was made by polymerase chain reaction, which showed the presence of Mycobacterium tuberculosis DNA. Interestingly, rifampicin- and isoniazid-resistant genes were detected in our analysis. Splenic TB diagnosis and treatment are reviewed., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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.

The extrapulmonary tuberculosis (TB) includes all the sites excepting lung, its origin being in the hematogenous disseminating foci within the main infection. The case of a woman, aged 36, is presented suffering of second degree obesity and type II diabetes mellitus under diet. She was admitted in the Surgery Clinics I of Emergency "Floreasca" Hospital (October 21, 2008) for discontinuous pains, relatively strong in the left hypocondrium, vesperal fever, perspirations, symptoms being present for 5 months. The investigations carried out before and after the admission show the presence of a splenomegaly (stage I-WHO), the absence of hypersplenism, portal hypertension, or other objective elements--excepting those mentioned at admittance--as well as the imaging changes (thoracic abdominal CT: spleen with an axis of 17 cm length, multiple solid hypodense lesions with a diameter of 5 cm). The surgical intervention is undergone (laparoscopic splenectomy). The morphological-pathological diagnosis was tuberculosis of the spleen. Considerations are made on this TB rare site.

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.

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.

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.

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., (Copyright 2007 Massachusetts Medical Society.)

T-dependent Ab responses are characterized by parallel extrafollicular plasmablast growth and germinal center (GC) formation. This study identifies that, in mice, the Ab response against Salmonella is novel in its kinetics and its regulation. It demonstrates that viable, attenuated Salmonella induce a massive early T-dependent extrafollicular response, whereas GC formation is delayed until 1 mo after infection. The extrafollicular Ab response with switching to IgG2c, the IgG2a equivalent in C57BL/6 mice, is well established by day 3 and persists through 5 wk. Switching is strongly T dependent, and the outer membrane proteins are shown to be major targets of the early switched IgG2c response, whereas flagellin and LPS are not. GC responses are associated with affinity maturation of IgG2c, and their induction is associated with bacterial burden because GC could be induced earlier by treating with antibiotics. Clearance of these bacteria is not a consequence of high-affinity Ab production, for clearance occurs equally in CD154-deficient mice, which do not develop GC, and wild-type mice. Nevertheless, transferred low- and high-affinity IgG2c and less efficiently IgM were shown to impede Salmonella colonization of splenic macrophages. Furthermore, Ab induced during the infection markedly reduces bacteremia. Thus, although Ab does not prevent the progress of established splenic infection, it can prevent primary infection and impedes secondary hemogenous spread of the disease. These results may explain why attenuated Salmonella-induced B cell responses are protective in secondary, but not primary infections.

The presence of Tropheryma whippelii was demonstrated in the PAS-negative mesenteric granulomatous lymph nodes of a patient affected by Whipple disease. Ultrastructurally a few bacteria, enclosed by a membrane characteristic of Tropheryma whippelii, were found in the extracellular spaces and remnants of bacteria were found in the phagocytic vacuoles of macrophages. The scarce number of bacilli, probably due to the fact that the disease was at an initial phase, could explain the absence of PAS positivity. This case confirms the role of the electron microscopy in the diagnosis of Whipple disease, especially for extra-intestinal lesions and at the initial phase of the disease, when the characteristic PAS-positive macrophages can be absent.

The case of a woman with splenic abscess due to Brucella is reported. There was no response with antibiotics and surgical treatment was required. On the basis of this case and the literature review we consider that surgical treatment must be considered in patients with splenic abscess due to Brucella infection.

A 47-year-old fishmonger presented with a history of weight loss and lethargy. On investigation he was found to have myeloma. He presented again before follow up, with a 3-day history of fever and a maculopapular rash. He was admitted to the haematology ward and treated with broad-spectrum antibiotics. Blood cultures were found to be positive for Erysipelothrix rhusiopathiae. Penicillin treatment was given, and he made a good recovery. The importance of occupational illness in an already immunocompromised patient and of taking a proper social and occupational history from patients on admission is illustrated through this case.

Treponema denticola is a consensus periodontal pathogen that has recently been associated with endodontic pathology. In this study, the effect of mono-infection of the dental pulp with T. denticola and with polymicrobial "red-complex" organisms (RC) (Porphyromonas gingivalis, Tannerella forsythia, and T. denticola) in inducing disseminating infections in wild-type (WT) and severe-combined-immunodeficiency (SCID) mice was analyzed. After 21 days, a high incidence (5/10) of orofacial abscesses was observed in SCID mice mono-infected with T. denticola, whereas abscesses were rare in SCID mice infected with the red-complex organisms or in wild-type mice. Splenomegaly was present in all groups, but only mono-infected SCID mice had weight loss. T. denticola DNA was detected in the spleen, heart, and brain of mono-infected SCID mice and in the spleen from mono-infected wild-type mice, which also had more periapical bone resorption. The results indicate that T. denticola has high pathogenicity, including dissemination to distant organs, further substantiating its potential importance in oral and linked systemic conditions.

Objectives: to evaluate the diagnostic value of clinical symptoms and signs in enteric fever and to propose a clinical diagnostic criterion., Design: Prospective observational study., Setting: Kathmandu Medical College, Teaching Hospital, Kathmandu, Nepal., Materials and Methods: febrile patients with clinical diagnosis of enteric fever were included in the study with the aim of confirming diagnosis with blood culture, or bone marrow culture and evaluating the diagnostic accuracy of various clinical signs and symptoms., Results: 64% of the clinically diagnosed cases had blood/ bone marrow culture positive. The diagnostic accuracy of the various symptoms and signs excluding fever was between 42%-75.5%. Majority of the symptom and sign did not have very high diagnostic accuracy. Hence a diagnostic criterion was proposed and clinical features with diagnostic accuracy more than 50% were taken into consideration. Major criteria included fever with diagnostic accuracy of 64%, headache with accuracy of 75.5% and relative bradycardia with an accuracy of 66%. Minor criteria included vomiting, diarrhoea, Splenomegaly, chills and abdominal pain /discomfort with diagnostic accuracy of 57%, 55%, 55%, 53% and 51% respectively. Finally after combination of various major and minor criteria a final diagnostic criterion was proposed having an accuracy of 66% and including both major and minor clinical symptom and sign., Conclusion: clinical diagnosis of enteric fever will be very helpful in a country like ours. Though none of the clinical symptoms and sign have very high diagnostic accuracy a diagnostic criteria may be helpful. Criteria including both major and minor signs and symptoms would be the most appropriate diagnostic tool as it includes the important abdominal symptoms and signs of enteric fever.

Tumor necrosis factor-alpha (TNF-alpha) is suggested to play multiple roles in immune and pathologic responses in tuberculosis. In this study, we have developed a system for the expression of recombinant guinea pig TNF-alpha (rgpTNF-alpha). Using rgpTNF-alpha along with neutralizing anti-rgpTNF-alpha antiserum, we tested the effect of modulating the levels of TNF-alpha on antigen-specific T cell proliferation in splenocytes. By neutralizing TNF-alpha in the supernatant of PPD-pulsed splenocytes with anti-rgpTNF-alpha, we observed hyperproliferation. Conversely, the addition of rgpTNF-alpha resulted in a significant suppression of PPD-induced lymphoproliferation. In addition, when unvaccinated and BCG-vaccinated guinea pigs were treated with polyclonal rgpTNF-alpha antiserum throughout the first 3 weeks following low-dose, pulmonary infection with Mycobacterium tuberculosis H37Rv, we observed splenomegaly in BCG-vaccinated guinea pigs. We also detected higher levels of splenic granuloma organization in the non-vaccinated group as well as a significant number of plasma cells associated with granulomata from the BCG-vaccinated group. These results suggest that modulating the availability of TNF-alpha in BCG-vaccinated guinea pigs can lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of humoral immunity. Conversely, abrogating TNF-alpha activity in the context of a hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue them from immunopathological consequences of overproducing TNF-alpha.

A 28-year-old woman from Sudan who had lived for 9 years in Victoria, Australia, was diagnosed with falciparum malaria 2 months after splenectomy for massive splenomegaly of unknown cause. Chronic falciparum malaria can occasionally present years after leaving endemic areas in partially immune patients. It should be considered in such patients with presentations possibly related to malaria, including splenomegaly, anaemia, or a long history of intermittent fevers and chills.

Objective: To determine the contribution of a blood culture service to the diagnosis of fever in a resource-poor setting and to identify clinical predictors of specific bloodstream infections (BSI)., Methods: In a descriptive, prospective study at the Medical Wards at Queen Elizabeth Central Hospital, Blantyre, Malawi, we tried to identify a specific cause of fever in febrile patients, comparing the use of routinely available diagnostic methods with the same methods plus blood culture. Clinical predictors of specific BSIs were sought., Results: A total of 352 patients admitted with fever (axillary temperature > or =37.4 degrees C) or a history of fever within the last 4 days were enrolled. Tuberculosis (TB) was the diagnosis most commonly suspected initially on clinical grounds (28%), followed by lower respiratory tract infection (16%), malaria (12%) and gastroenteritis (5%). Blood cultures were positive in 128 patients (36%); Mycobacterium tuberculosis was the most commonly isolated organism (57 patients). In most cases the diagnosis of TB had already been made using routinely available diagnostic methods, including chest radiography. In all 16 cases of Streptococcus pneumoniae bacteraemia, infection with this agent was clinically suspected, usually on the basis of pulmonary symptoms and signs. In contrast, in 30 of 65 patients (65%) with non-typhi salmonellae (NTS) bacteraemia, there were no symptoms or signs specifically suggestive of this diagnosis. Fever > or =39 degrees C and splenomegaly predicted NTS bacteraemia with an odds ratio of 8.4 (95% confidence interval 3.4-20.6, P < 0.001)., Conclusion: BSIs are common among patients admitted with fever. While BSI with mycobacteraemia and S. pneumoniae can usually be predicted on clinical grounds and with routinely available diagnostic methods, NTS bacteraemia often presents as a primary BSI without localizing symptoms and signs. Splenomegaly in this population indicates NTS bacteraemia rather than malaria.

Our aim was to evaluate the efficacy of abdominal US and fine-needle aspiration biopsy (FNAB) in the diagnosis of disseminated mycobacteriosis (DM) in patients with Acquired Immunodeficiency Syndrome (AIDS). We reviewed the US and clinical records of 18 AIDS patients (12 males; 22-43 years) with DM studied with abdominal US. 18 patients underwent fine-needle aspiration biopsy of enlarged abdominal lymphnodes and 11 underwent FNAB of the spleen. All aspirates were studied with acid-fast stain for fast examination and cultures for isolation of mycobacteria. Abdominal US showed: enlarged abdominal lymphnodes (diameter range: 5-35 mm; mean 17 mm) splenomegaly (spleen diameter range: 14-22 cm; mean: 16.2 cm) and hepatomegaly (right hepatic lobe thickness range: 14.5-18.5 cm) in all patients; multiple splenic abscesses (diameter range: 3-20 mm) in 11 patients; small intestine wall thickening in 5 patients (maximum bowel wall thickness range: 7-15 mm); mild to moderate ascites in 8 patients; pleural effusion in 4 patients; hyperechogenicity of the kidney cortex in 5 patients; peritoneal abscesses in one and a retroperitoneal abscess in one patient. fast-acid-stain of spleen and/or lymphnode FNAB specimens allowed early diagnosis of mycobateriosis in 18/18 cases (100%). Cultures of lymphnode aspirates grew mycobacteria in 10/18 patients (56%). Spleen aspirates grew mycobacteria in 11/11 patients (100%) Blood cultures were positive in 6/18 patients (33%). Diagnosis of species was M. tuberculosis in 9 and M. avium in 6 patients. In 3/18 patients (17%) all cultures were negative. In conclusion, abdominal US features suggest DM in AIDS patients. Spleen and/or lymphnode FNAB allows a specific diagnosis in 100% of the patients.

Chronic diseminated candidiasis--mainly its hepatosplenic form- is one of the most characteristic invasive infection due to Candida in haematological patients. A case is presented of a 31 year old man admitted to the Clinical Department with acute mieloid leukosis M2, showing febrile neutropenia after induction and consolidation chemotherapy. Hepatoesplenic candidiasis was diagnosed and confirmed by computered axial tomography (CAT) and hepatic biopsy; amphotericin B followed by liposome encapsuled amphotericin B up to complete a total dose of 4 g was used for treatment. The patient was discharged waiting for bone marrow transplantation. Early suspicion of hepatosplenic candidiasis helps to select a rapid diagnosis method and an effective treatment.