Neutrophil activity in sepsis: a systematic review.

The neutrophil is an important cell in host defense against infections, acting as the first line of microorganism control. However, this cell exhibits dysregulated activity in sepsis and may contribute to the pathogenesis of the disease. This systematic review aimed to highlight the major scientific findings regarding neutrophil activity in sepsis reported in clinical and experimental research published in the last 10 years. The search was conducted in the Virtual Health Library of PAHO-WHO (BVS) and PubMed databases, and articles published between January 2007 and May 2017 in Portuguese, English, and Spanish were eligible. Article selection was carried out independently by two reviewers (CB and IB). A total of 233 articles were found, of which 87 were identified on PubMed and 146 on BVS. Eighty-two articles were duplicates. Of the remaining 151 articles, 19 met the inclusion criteria after title, abstract, and full-text analysis. Overall, research in clinical samples and animal models of sepsis showed reduced capacity of neutrophils to migrate and delayed apoptosis, but there was no consensus on the phagocytic activity of neutrophils in sepsis. Molecules, such as pentraxin 3 (PTX3), have been analyzed as potential diagnostic markers in sepsis but the diversity of soluble molecules detected in blood samples of sepsis patients did not enable further understanding of the correlation of these circulating molecules with neutrophil activity during sepsis. Optimal understanding of the function of neutrophils in sepsis remains a challenge that, if overcome, would eventually allow targeted therapeutic interventions in patients affected by this severe syndrome.

Neutrophil activity in sepsis: a systematic review

The neutrophil is an important cell in host defense against infections, acting as the first line of microorganism control. However, this cell exhibits dysregulated activity in sepsis and may contribute to the pathogenesis of the disease. This systematic review aimed to highlight the major scientific findings regarding neutrophil activity in sepsis reported in clinical and experimental research published in the last 10 years. The search was conducted in the Virtual Health Library of PAHO-WHO (BVS) and PubMed databases, and articles published between January 2007 and May 2017 in Portuguese, English, and Spanish were eligible. Article selection was carried out independently by two reviewers (CB and IB). A total of 233 articles were found, of which 87 were identified on PubMed and 146 on BVS. Eighty-two articles were duplicates. Of the remaining 151 articles, 19 met the inclusion criteria after title, abstract, and full-text analysis. Overall, research in clinical samples and animal models of sepsis showed reduced capacity of neutrophils to migrate and delayed apoptosis, but there was no consensus on the phagocytic activity of neutrophils in sepsis. Molecules, such as pentraxin 3 (PTX3), have been analyzed as potential diagnostic markers in sepsis but the diversity of soluble molecules detected in blood samples of sepsis patients did not enable further understanding of the correlation of these circulating molecules with neutrophil activity during sepsis. Optimal understanding of the function of neutrophils in sepsis remains a challenge that, if overcome, would eventually allow targeted therapeutic interventions in patients affected by this severe syndrome.

Morte súbita causada por ruptura de aneurisma em aorta em ruminantes / Sudden death caused by aortic aneurysm rupture in ruminants

De um total de 2.088 ruminantes necropsiados no Laboratório de Patologia Animal da Universidade Federal de Campina Grande durante o período de janeiro de 2003 a dezembro de 2015, 803 (38,45%) eram bovinos, 651 (31,18%) ovinos e 634 (30,37%) caprinos. Desses, dois caprinos (0,31%), um ovino (0,15%) e um bovino (0,12%) foram diagnosticados com ruptura de artéria aorta devido à presença de aneurismas, correspondendo a 0,19% das causas de morte em ruminantes. O caso 1 ocorreu em um caprino que apresentava bom estado corporal e foi encontrado morto pelo proprietário; o caso 2, em um caprino com diagnóstico clínico presuntivo de linfadenite caseosa; o caso 3, em um ovino que foi encontrado morto pelo proprietário; e o caso 4, em um bovino com histórico de timpanismo recidivante. Em todos os casos, a morte ocorreu rapidamente por choque hipovolêmico. Os principais achados macroscópicos na necropsia foram hemotórax ou hemoperitônio e a ruptura na artéria aorta. Nos caprinos, abscessos foram visualizados microscopicamente e estavam associados à presença de bactérias, o que sugere infecção por Corynebacterium pseudotuberculosis. No ovino, não foram observadas lesões que pudessem elucidar a causa do aneurisma, por isso foi considerado de provável origem idiopática. No bovino, não foi possível estabelecer a causa, mas a presença do aneurisma dificultava a eructação dos gases da fermentação ruminal, caracterizando um quadro de timpanismo secundário. Aneurismas ocorrem de forma esporádica em caprinos, ovinos e bovinos e devem ser considerados como uma importante causa de morte súbita.(AU)

From a total of 2,088 necropsied ruminants in the Laboratory of Animal Pathology of Federal University of Campina Grande during the period from January 2003 to December 2015, 803 (38.45%) were cattle, 651 (31.18%) sheep, and 634 (30.37%) goats. Of these, two goats (0.31%), one sheep (0.15%) and one bovine (0.12%) were diagnosed with rupture of aorta due to the presence of aneurysms, corresponding to 0.19% of causes of death in ruminants. Case 1 occurred in a goat that had good body condition and was found dead by the owner, case 2 occurred in a goat that had clinical presumptive diagnosis of caseous lymphadenitis, case 3 occurred in a sheep who was found dead by the owner, and case 4 occurred in a cow with a history of recurrent bloating. In all cases, death occurred rapidly by hypovolemic shock. The macroscopic findings at necropsy were hemothorax or hemoperitoneum and the rupture in the aorta artery. In goats, abscesses were viewed microscopically and they were associated with the presence of bacteria, suggesting for Corynebacterium pseudotuberculosis infection. In the sheep, lesions that could explain the cause of the aneurysm were not observed, so we consider the aneurisma as idiopathic. In the cow, it was not possible to establish the cause, but the presence of the aneurysm hampered eructation of ruminal gases, causing secondary bloat. Aneurysms occur sporadically in goats, sheep and cattle and must be regarded as an important cause of sudden death.(AU)

Use of inflammatory molecules to predict the occurrence of fever in onco-hematological patients with neutropenia.

Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM) may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-α), soluble TNF-α I and II receptors (sTNFRI and sTNFRII), monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif) ligand 2 (CCL2)], macrophage inflammatory protein-1α (MIP-1α or CCL3), eotaxin (CCL11), interleukin-8 (IL-8 or CXCL8), and interferon-inducible protein-10 (IP-10 or CXCL10) in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24 h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group) and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15) before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02). Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both) in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients.

Use of inflammatory molecules to predict the occurrence of fever in onco-hematological patients with neutropenia

Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM) may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-α), soluble TNF-α I and II receptors (sTNFRI and sTNFRII), monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif) ligand 2 (CCL2)], macrophage inflammatory protein-1α (MIP-1α or CCL3), eotaxin (CCL11), interleukin-8 (IL-8 or CXCL8), and interferon-inducible protein-10 (IP-10 or CXCL10) in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24 h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group) and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15) before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02). Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both) in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients.

Candida parapsilosis endocarditis: a comparative review of the literature.

Fungal endocarditis (FE) is an uncommon disease, and while accounting for only 1.3-6% of all cases of infectious endocarditis, it carries a high mortality risk. Although Candida albicans represents the main etiology of FE, C. parapsilosis is the most common non-albicans species. We report the case of a 32-year-old man with a history of prior intravenous drug (IVD) use hospitalized with endocarditis due to C. parapsilosis and review all 71 additional cases documented in the literature. A retrospective analysis of the 72 C. parapsilosis cases compared to 52 recently reviewed cases of C. albicans endocarditis was conducted to identify organism-specific clinical peculiarities. The most common predisposing factor for C. parapsilosis endocarditis (41/72; 57.4%) involved prosthetic valves followed by IVD use (12/72; 20%). Peripheral embolic and/or hemorrhagic events occurred in 28/64 (43.8%) patients, mostly in cerebral and lower limb territories. Overall mortality was 41.7%. Combined surgical and clinical treatment was associated with a lower mortality. Few patients received the newer antifungal agents, and it would appear that more experience is required for their use in the treatment of C. parapsilosis endocarditis.

Neurohistologic and ultrastructural lesions in cattle experimentally intoxicated with the plant Prosopis juliflora.

Intoxication by pods of Prosopis juliflora (mesquite beans) causes an impairment of cranial nerve function in cattle and goats. In goats, vacuolation of neurons in the trigeminal motor nuclei has been reported. To study the lesions in cattle caused by consumption of P. juliflora pods and dry ground pods, eight 6- to 12-month-old male cattle were divided into 4 groups: group 1 was fed a ration containing 50% of pods; groups 2 and 3 received a ration containing 50 and 75% of dry ground pods, respectively; group 4 was the control. After 200 days, all cattle were killed and sampled for histologic evaluation. Samples of the trigeminal motor nucleus were examined by electron microscopy. All cattle from groups 1, 2, and 3 showed clinical signs resulting from impaired function of cranial nerves V, IX, X, and XII, starting 45-75 days after consumption of the plant. The main histologic lesions were vacuolation and loss of neurons in trigeminal motor nuclei and other motor cranial nerve nuclei with Wallerian-like degeneration in the cranial nerves. Mild denervation atrophy was observed in the masseter and other masticatory muscles. On electron microscopy, neurons of the trigeminal nuclei had markedly swollen mitochondria, with the mitochondrial cristae displaced peripherally, disoriented and disintegrating. Intoxication by P. juliflora seems to have a novel pathogenesis, characterized by a selective, primary, chronic, and progressive injury to mitochondria of neurons of the trigeminal and other cranial nerve nuclei. Cranial nerve degeneration and denervation atrophy of the muscles occurs as a consequence of the neuronal lesion.

Acute intoxication by Crotalaria retusa in sheep.

Acute intoxication by seeding Crotalaria retusa occurred during the dry season, in a flock of 80 sheep, in the semi-arid region of the state of Paraiba, northeastern Brazil. Anorexia, severe depression, mild jaundice, incoordination and recumbence were observed in 16 sheep that died within 12 h. At necropsy the liver had a nutmeg appearance. Seeds of C. retusa were found in large amounts in the rumen of the dead animals. Histologic lesions of the liver were characterized by centrilobular necrosis. Seeds of C. retusa were given to six sheep at doses of 2.5 (two sheep), 5, 10, 20 and 40 g/kg bw (one sheep for each dose). Sheep ingesting 5-40 g/kg bw were killed when moribund, 38-120 h after the start of the administration. Clinical signs and gross and histologic lesions were similar to those observed in field outbreak. The seeds used in the experiment contained 1.4% of monocrotaline. It is concluded that hungry sheep can be affected spontaneously by acute monocrotaline intoxication when they ingest large amounts of C. retusa seeds in a short period of time.

Outbreaks of pythiosis in two flocks of sheep in northeastern Brazil.

Two outbreaks of cutaneous pythiosis caused by Pythium insidiosum were diagnosed in two herds of crossbred hair wool sheep of different ages in the semiarid region of Northeastern Brazil. In one herd of 120 sheep, 40 were affected. The other outbreak affected six sheep out of 80. Local swellings with ulcerative lesions were observed in the limbs and abdominal and prescapular regions. Three sheep were necropsied. Two of them had lung metastasis characterized by multifocal nodules measuring 0.5-2 cm. In one animal, the prescapular lymph node was also affected. In another, the cutaneous lesion extended to the sesamoid bone. Microscopically, there were multifocal granulomas with intralesional P. insidiosum hyphae and Splendore-Hoeppli material surrounding the hyphae. The diagnosis was based on the histologic lesions, immunohistochemical identification, and culture of the etiologic agent. One sheep treated with potassium iodide recovered. Standing in swampy water for long periods in a warm aquatic environment seems to be the reason for the high prevalence of the disease.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: report on 23 cases.

Schistosoma mansoni infection is likely to be responsible for a significant proportion of cases of myelopathy occurring in areas where schistosomiasis is endemic. The aim of this study is to describe the clinical, laboratory and therapeutic data of 23 patients with schistosomal myeloradiculopathy. The medical records of 23 patients with schistosomal myelopathy admitted to two general hospitals of Belo Horizonte (MG), in Brazil, from 1995 to 1999, were reviewed retrospectively. Seventeen patients were male (74%). The mean age for the whole group was 27 years. Lower limb weakness and associated lumbar and/or lower limb pain were reported by 20 patients (87%), and 16 (70%) were unable to walk. All individuals presented urinary retention and 19 (83%) complained of intestinal dysfunction. The treatment was based on the association of antischistosomal drugs and corticosteroids. Five patients (22%) presented a full response to treatment, 13 (57%) partial response without functional limitations and 4 (17%) partial improvement with limitations or no response. Three out of the 4 patients who stopped steroids before 45 days of treatment developed recurrence of the symptoms and signs of myelopathy. Our cases demonstrate the severe presentation of the disease and the data disclosed here suggest that treatment with steroids should be kept for months after clinical improvement.

Schistosomiasis mansoni is associated with pyogenic liver abscesses in the state of Minas Gerais, Brazil.

The association between pyogenic liver abscesses and schistosomiasis has been confirmed by clinical and experimental studies. In this retrospective study of 78 patients with pyogenic liver abscesses the association with schistosomiasis has been investigated. Pyodermitis, a known focus of bacteremia, was observed in 19 patients (24%). Blood eosinophilia was observed in 30 patients (39%). Staphylococcus aureus was cultured from abscesses in 17 out of 38 patients (45%). Forty-one out of 57 patients (53%) had stool examination. Schistosoma mansoni was the main parasite identified. Eggs of S. mansoni were also identified in liver biopsies in 7 out of 19 patients who did the exam. The large number of young patients with liver abscesses described here is different from what has been observed in developed countries. This clinical study provide support for the concept that granulomas of S. mansoni in the liver are foci for colonization with S. aureus, which in presence of staphylococcal bacteremia can form liver abscesses.

Hepatosplenic schistosomiasis in field-based studies: a combined clinical and sonographic definition.

A combined clinical and sonographic classification of hepatosplenic schistosomiasis mansoni to be used in field-based studies is proposed herein. Seven hundred forty one individuals out of 892 (83%), living in an area endemic for schistosomiasis in Brazil, have been submitted to clinical and ultrasound examinations. Based on two stool examinations the overall prevalence for schistosomiasis in this area was 73%. Abdominal palpation was performed with patients in dorsal decubit, during deep breath, by two experienced physicians and a portable ultrasound was used for the evaluation of liver fibrosis, portal collaterals and spleen size. Four groups of individuals were identified using data obtained by abdominal palpation and ultrasound examination: (1) palpable spleen and intense periportal thickening in 9 individuals (1.2%); (2) spleen not palpable and intense periportal thickening in 15 (2%); (3) palpable spleen with light to moderate periportal thickening in 32 (4.3%), and (4) palpable spleen with a normal liver on ultrasound in 30 (4%). The definition of hepatosplenic schistosomiasis in field-based studies as the finding of Schistosoma mansoni eggs in the stools in an individual with splenomegaly is not acceptable anymore. Abdominal ultrasound should be combined with clinical examination to accurately identify hepatosplenics in endemic areas for schistosomiasis.

Pyogenic abscesses and parasitic diseases.

Parasitic diseases which during their course in the host switch the immune system from a T helper 1 to a T helper 2 response may be detrimental to the host, contributing to granuloma formation, eosinophilia, hyper-IgE, and increased susceptibility to bacterial and fungal infections. Patients and animals with acute schistosomiasis and hyper-IgE in their serum develop pyogenic liver abscess in the presence of bacteremia caused by Staphylococcus aureus. The Salmonella-S. mansoni association has also been well documented. The association of tropical pyomyositis (pyogenic muscle abscess) and pyogenic liver abscess with Toxocara infection has recently been described in the same context. In tropical countries that may be an interesting explanation for the great morbidity of bacterial diseases. If the association of parasitic infections and pyogenic abscesses and/or fungal diseases are confirmed, there will be a strong case in favor of universal treatment for parasitic diseases to prevent or decrease the morbidity of superinfection with bacteria and fungi.

Human toxocariasis and pyogenic liver abscess: a possible association.

OBJECTIVES: To study the role of human toxocariasis in the pathogenesis of pyogenic liver abscess. METHODS: We compared the serology for toxocariasis and serum levels of IgE in 16 patients with pyogenic liver abscess to those in 32 matched (age and gender) controls to define the possible association between these two entities. RESULTS: The serology for toxocariasis was positive in 10 of 16 patients compared with 4 of 32 controls. The relative odds and 95% confidence interval (conditional logistic regression), comparing cases and matched controls, was significant (1.4; 95% confidence interval, 1.1-1.7) for Toxocara serology. Regarding IgE serum levels, there was no difference between cases and controls. CONCLUSIONS: Human toxocariasis can be one of the predisposing causes of pyogenic liver abscess, especially in tropical countries in which this parasitic disease is common. Treatment of human toxocariasis may prevent morbid complications like hepatic abscess and should be considered in patients with clinical and/or serological evidence of Toxocara infection.

[Dengue: a new approach]. / Dengue: uma nova abordagem.

Previous definition of classic dengue, with or without bleeding, and of dengue hemorrhagic fever (DHF) that may evolve without bleeding and with or without dengue shock syndrome (DSS) are reviewed here. The classical approach to the diagnosis and treatment of dengue, although useful in the past, nowadays breeds confusion and adds a burden to the physician's task of decision-making regarding the treatment of patients with severe forms of the disease. The classification of dengue proposed in this paper, and summarized in a diagram, incorporates new concepts about sepsis, systemic inflammatory response syndrome (SIRS), and acute respiratory distress syndrome (ARDS). This new approach, in our view, is a useful guide to initial evaluation and treatment of the disease. It also approximates the dengue syndrome to other protocols and medical procedures routinely used in intensive care units, making it easier to be followed by the health personnel working in areas subject to epidemic bursts.

Schistosoma mansoni: assessment of morbidity before and after control.

The literature on the assessment of morbidity due to Schistosoma mansoni infection is updated. Imaging techniques such as ultrasonography, echodoppler cardiography, computerized tomography (CT scan) and magnetic resonance imaging (MRI) introduced a new perspective, and expanded our knowledge on morbidity. Three well-defined syndromes caused by schistosomiasis mansoni have been described: the stage of invasion, acute schistosomiasis (Katayama fever), and chronic schistosomiasis. Complications of the acute and chronic syndromes have also been reported: pulmonary hypertension, neuroschistosomiasis, association with Salmonella, association with Staphylococci, viral hepatitis B, glomerulonephritis. In most individuals with hepatosplenic schistosomiasis the spleen is increased in size. Hepatosplenic schistosomiasis can, however, occur without splenomegaly. The definition of hepatosplenic schistosomiasis in endemic areas as the finding of S. mansoni eggs in the stools in an individual with hepatosplenomegaly is not satisfactory anymore. Many aspects of morbidity are expected to change after schistosomiasis control. Some are expected to change quickly (worm burden, Salmonella bacteremia, hepatosplenic schistosomiasis in children) whereas others shall remain for years (pulmonary hypertension, glomerulonephritis, neuroschistosomiasis). Intestinal schistosomiasis in individuals with low worm burdens is very difficult to diagnose and therefore laborious to control.

Visceral larva migrans syndrome complicated by liver abscess.

We describe a case of visceral larva migrans syndrome complicated by liver abscess, pericardial effusion and ascites. To our knowledge, these findings have not been reported previously. The structural and immunological alterations caused by visceral larva migrans are thought to lead to the development of visceral abscesses.

Fever of undetermined origin in patients with the acquired immunodeficiency syndrome in Brazil: report on 55 cases.

The medical records of patients with AIDS admitted to a general hospital in Brazil from 1989 to 1997 were reviewed retrospectively with the aim at defining the frequency and etiology of fever of undetermined origin (FUO) in HIV-infected patients of a tropical country and to evaluate the usefulness of the main diagnostic procedures. 188 (58.4%) out of 322 patients reported fever at admission to hospital and 55 (17.1%) had FUO. Those with FUO had a mean CD4+ cell count of 98/ml. A cause of fever was identified for 45 patients (81.8%). Tuberculosis (32.7%), Pneumocystis carinii pneumonia (10.9%), and Mycobacterium avium complex (9.1%) were the most frequent diagnoses. Other infectious diseases are also of note, such as cryptococcal meningitis (5.5%), sinusitis (3.6%), Salmonella-S. mansoni association (3.6%), disseminated histoplasmosis (3.6%), neurosyphilis (1.8%), and isosporiasis (1.8%). Four patients had non-Hodgkin's lymphoma (7.3%). We conclude that an initial aggressive diagnostic approach should be always considered because biopsies (lymph node, liver and bone marrow) produced the highest yield in the diagnosis of FUO and the majority of the diagnosed diseases are treatable. The association of diseases is common and have contributed to delay the final diagnosis of FUO in most cases. In our study area the routine request of hemocultures for Salmonella infection and the investigation of cryptococcal antigen in the serum should be considered.

Abortion due to equine herpesvirus in southern Brazil.

We report an outbreak of abortion due to equine herpesvirus (EHV) in 5 mares between 9 and 11 months of gestation, from a herd of 22 Thoroughbred mares. Equine herpesvirus was isolated from extracts of the liver, spleen and thymus but not from the lungs of a 9-month fetus grown in Rabbit Kidney (RK13) cells. The virus was identified by electron microscopy, where virus particles could be seen in the nucleus of infected cells, and by the fluorescent antibody technique with polyclonal antibodies against the whole virus. Anamnesis, necropsy, histopathology, bacteriology, and virology data suggest that the abortions reported in this paper were due to equine herpesvirus.