Infectious diseases in paediatric pathology: experience from a developing country

Infectious and parasitic diseases have always challenged man. Although many of them are typically seen in some areas of the world and can be adequately managed by just improving socioeconomic status and sanitary conditions, they are still quite prevalent and may sometimes be seen outside their original geographical areas. Human migration due to different reasons, tourism, blood transfusion and solid organ transplantation has created new concerns for health professionals all over the world. If not for diagnostic purposes, at least these tropical and infectious diseases should be largely known because their epidemiology, pathogenesis, host/parasite interaction, inflammatory and reparative responses are quite interesting and teach us about human biology. Curiosity is inherent to pathology practice and so we are compelled to look for things other than tumours or degenerative diseases. This review focuses on infectious and parasitic diseases found in a developing country and brings up-to-date information on diseases caused by viruses (dengue, yellow fever), bacteria (typhoid fever, leprosy), parasites (Chagas` disease, cutaneous and visceral leishmaniasis, amoebiasis, Capillaria hepatica, schistosomiasis, cysticercosis) and caused by fungi (paracoccidioidomycosis, cryptococcosis, histoplasmosis) that may be useful for pathologists when facing somewhat strange cases from developing countries.

SEROLOGIC SURVEY FOR SELECTED INFECTIOUS DISEASES IN FREE-RANGING BRAZILIAN TAPIRS (TAPIRUS TERRESTRIS) IN THE CERRADO OF CENTRAL BRAZIL

From September 2000 to January 2002, a serologic survey was conducted in a population of free-ranging Brazilian tapirs (Tapirus terrestris) inhabiting Emas National Park and surrounding areas in Goias state. central Brazil, as part of an ecologic study. Ten tapirs were immobilized with a tiletamine-zolazepam combination. and blood samples were collected. All sera were negative for Leptospira spp.. Brucella abortus, and equine infectious anemia; and one of 10 animals was positive for Toxoplasma goudii. This report represents the first serologic survey for selected infectious diseases in a free-ranging population or Brazilians tapirs in central Brazil.

Infectious endocarditis caused by Nocardia sp.: histological morphology as a guide for the specific diagnosis

Nocardia is a rare opportunistic agent, which may affect immunocompromised individuals causing lung infections and exceptionally infective endocarditis (IE). There are few reports of IE caused by Nocardia sp., usually involving biological prostheses but rarely in natural valves. Its accurate microbiological identification may be hampered by the similarity with Rhodococcus equi and Corynebacterium spp. Here we report a case of native mitral valve IE caused by this agent in which the clinical absence of response to vancomycin and the suggestion of Nocardia sp. by histology pointed to the misdiagnosis of Corynebacterium spp. in blood cultures. The histological morphology can advise on the need for expansion of cultivation time and use of extra microbiological procedures that lead to the differential diagnosis with Corynebacterium spp. and other agents, which is essential to establish timely specific treatment, especially in immunocompromised patients.

Fatal adenoviral necrotizing bronchiolitis case in a post-cardiac surgery intensive care unit

We report a case of a 67 year-old-male patient admitted to the intensive care unit in the post-coronary bypass surgery period who presented cardiogenic shock, acute renal failure and three episodes of sepsis, the latter with pulmonary distress at the 30th post-operative day. The patient expired within five days in spite of treatment with vancomycin, imipenem, colistimethate and amphotericin B. At autopsy severe adenovirus pneumonia was found. Viral pulmonary infections following cardiovascular surgery are uncommon. We highlight the importance of etiological diagnosis to a correct treatment approach.

Vancomycin use in a brazilian teaching hospital: comparison with the Hospital Infection Controlpractices Advisory Committee Guidelines (HICPAC)

This study describes vancomycin prescribing patterns in an average complexity hospital and compare the guidelines proposed by the Hospital Infection Control Practices Advisory Committee (HICPAC). The study was conducted in a 256-bed secondary-care hospital. Data were collected of all patients given vancomycin from March 2003 to February 2004, using a standardized chart-extraction form designed. Appropriate and inappropriate use was reviewed according to the Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines on prudent vancomycin use. Out of 118 prescriptions, 95 (80.5%) were considered appropriate. Out of these 95 orders, 77 (81.1%) were administered for empiric treatment of suspected Gram-positive infections, 17 (17.9%) were administered for treatment of proven Gram-positive infections (76.5% identified as Staphyloccocus aureus-like agents) and 1 (1.0%) for beta-lactam allergy. The majority of the patients (96.6%) had recently used an antimicrobial medication (3 months). The mean pre-treatment hospitalization period was 11±10 days. Out of the 118 treatments, 67 (56.8%) were for nosocomial infections. The more frequent indications for vancomycin use were pneumonia (48.3%) and primary sepsis (18.6%), accounting for more than 66% of all treatments. No restriction policy was suggested because vancomycin use was considered adequate in the majority of the treatment cases. The broad empiric use of this antimicrobial was greater than expected in the institution and its use should be revised.

Carbapenem stewardship: positive impact on hospital ecology

INTRODUCTION: Excessive group 2 carbapenem use may result in decreased bacterial susceptibility. OBJECTIVE: We evaluated the impact of a carbapenem stewardship program, restricting imipenem and meropenem use. METHODS: Ertapenem was mandated for ESBL-producing Enterobacteriaceae infections in the absence of non-fermenting Gram-negative bacilli (GNB) from April 2006 to March 2008. Group 2 carbapenems were restricted for use against GNB infections susceptible only to carbapenems and suspected GNB infections in unstable patients. Cumulative susceptibility tests were done for nosocomial pathogens before and after restriction using Clinical and Laboratory Standards Institute (CLSI) guide-lines.Vitek System or conventional identification methods were performed and susceptibility testing done by disk diffusion according to CLSI.Antibiotic consumption (t-test) and susceptibilities (McNemar's test) were determined. RESULTS: The defined daily doses (DDD) of group 2 carbapenems declined from 61.1 to 48.7 DDD/1,000 patient-days two years after ertapenem introduction (p = 0.027). Mean ertapenem consumption after restriction was 31.5 DDD/1,000 patient-days. Following ertapenem introduction no significant susceptibility changes were noticed among Gram-positive cocci. The most prevalent GNB were P. aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp. There was no change in P. aeruginosa susceptibility to carbapenems. Significantly improved P. aeruginosa and K. pneumoniae ciprofloxacin susceptibilities were observed, perhaps due to decreased group 2 carbapenem use. K. pneumoniae susceptibility to trimethoprim-sulfamethoxazole improved. CONCLUSION: Preferential use of ertapenem resulted in reduced group 2 carbapenem use, with a positive impact on P. aeruginosa and K. pneumoniae susceptibility.

Economic impact of treatment for surgical site infections in cases of total knee arthroplasty in a tertiary public hospital in Brazil

The aim of this study was to estimate the additional cost of treatment of a group of nosocomial infections in a tertiary public hospital. A retrospective observational cohort study was conducted by means of analyzing the medical records of 34 patients with infection after total knee arthroplasty, diagnosed in 2006 and 2007, who met the criteria for nosocomial infection according to the Centers for Disease Control and Prevention. To estimate the direct costs of treatment for these patients, the following data were gathered: length of hospital stay, laboratory tests, imaging examinations, and surgical procedures performed. Their costs were estimated from the minimum values according to the Brazilian Medical Association. The estimated cost of the antibiotics used was also obtained. The total length of stay in the ward was 976 days, at a cost of US$ 18,994.63, and, in the intensive care unit, it was 34 days at a cost of US$ 5,031.37. Forty-two debridement procedures were performed, at a cost of US$ 5,798.06, and 1965 tests (laboratory and imaging) were also performed, at a cost of US$ 15,359.25. US$ 20,845.01 was spent on antibiotics and US$ 1,735.16 on vacuum assisted closure therapy, microsurgical flaps, implant removal, spacer use, and surgical revision. The total additional cost of these cases of hospital infection in 2006 and 2007 was of US$ 91,843.75. Based on that, we demonstrate that the high cost of treatment for hospital infections emphasizes the importance of taking measures to prevent and control hospital infection.

Rates of antimicrobial resistance in latin america (2004-2007) and in vitro activity of the glycylcycline tigecycline and of other antibiotics

As a part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.), Gram-positive and Gram-negative bacterial isolates were collected from 33 centers in Latin America (centers in Argentina, Brazil, Chile, Colombia, Guatemala, Honduras, Jamaica, Mexico, Panama, Puerto Rico, and Venezuela) from January 2004 to September 2007. Argentina and Mexico were the greatest contributors of isolates to this study. Susceptibilities were determined according to Clinical Laboratory Standards Institute guidelines. Resistance levels were high for most key organisms across Latin America: 48.3% of Staphylococcus aureus isolates were methicillin-resistant while 21.4% of Acinetobacter spp. isolates were imipenem-resistant. Extended-spectrum β-lactamase were reported in 36.7% of Klebsiella pneumoniae and 20.8% of E. coli isolates. Tigecycline was the most active agent against Gram-positive isolates. Tigecycline was also highly active against all Gram-negative organisms, with the exception of Pseuodomonas aeruginosa, against which piperacillin-tazobactam was the most active agent tested (79.3% of isolates susceptible). The in vitro activity of tigecycline against both Gram-positive and Gram-negative isolates indicates that it may be an useful tool for the treatment of nosocomial infections, even those caused by organisms that are resistant to other antibacterial agents.

Experimental infections with Paracoccidioides brasiliensis obtained from armadillos: comparison to clinical isolates

Paracoccidioides brasiliensis causes paracoccidioidomycosis (PCM) that is one of the most prevalent systemic human mycoses in Latin America. Armadillos show a high incidence of PCM infection and could, therefore, be a natural reservoir for this fungus. In this study were compared the virulence profiles of isolates obtained from nine-banded armadillos (Dasypus novemcinctus) (PbT1 and PbT4) and isolates from PCM patients (Pb265 and Bt83). Pathogenicity was evaluated by fungal load and analysis of colony morphology. Immunity against the fungus was tested by delayed type hypersensitivity test (DTH) and antibody quantification by ELISA. The higher virulence of PbT1 and PbT4 was suggested by higher fungal load in spleen and lungs. Armadillo isolates and Bt83 presented a cotton-like surface contrasting with the cerebriform appearance of Pb265. All isolates induced cellular and humoral immune responses in infected BALB/c mice. DTH reactions were similarly induced by the four isolates, however, a great variability was observed in specific antibody levels, being the highest ones induced by Bt83 and PbT4. The present work confirms that armadillos harbor P. brasiliensis, whose multiplication and induced immunity in experimentally infected mice are heterogeneous, resembling the behavior of isolates from human PCM. This study reinforces the possibility that armadillos play an important role in the biological cycle of this pathogen.

Descriptor-and fragment-based QSAR models for a series of Schistosoma mansoni purine nucleoside inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the treatment of major parasitic infectious diseases, with special emphasis on its role in the discovery of new drugs against schistosomiasis, a tropical disease that affects millions of people worldwide. In the present work, we have determined the inhibitory potency and developed descriptor- and fragment-based quantitative structure-activity relationships (QSAR) for a series of 9-deazaguanine analogs as inhibitors of SmPNP. Significant statistical parameters (descriptor-based model: r² = 0.79, q² = 0.62, r²pred = 0.52; and fragment-based model: r² = 0.95, q² = 0.81, r²pred = 0.80) were obtained, indicating the potential of the models for untested compounds. The fragment-based model was then used to predict the inhibitory potency of a test set of compounds, and the predicted values are in good agreement with the experimental results

The effects of nitric oxide on the immune response during giardiasis

Nitric oxide (NO) is a free radical synthesized from L-arginine by different isoforms NO-synthases. NO possesses multiple and complex biological functions. NO is an important mediator of homeostasis, and changes in its generation or actions can contribute or not to pathological states. The knowledge of effects of NO has been not only important to our understanding of immune response, but also to new tools for research and treatment of various diseases. Knowing the importance of NO as inflammatory mediator in diverse infectious diseases, we decided to develop a revision that shows the participation/effect of this mediator in immune response induced against Giardia spp. Several studies already demonstrated the participation of NO with microbicidal and microbiostatic activity in giardiasis. On the other hand, some works report that Giardia spp. inhibit NO production by consuming the intermediate metabolite arginine. In fact, studies in vitro showed that G. lamblia infection of human intestinal epithelial cells had reduced NO production. This occurs due to limited offer of the crucial substrate arginine (essential aminoacid for NO production), consequently reducing NO production. Therefore, the balance between giardial arginine consumption and epithelial NO production could contribute to the variability of the duration and severity of infections by this ubiquitous parasite.

Estimating HIV-1 incidence using the serologic testing algorithm for recent HIV infections at HIV counseling and testing centers in the city of São Paulo, Brazil

The network of HIV counseling and testing centers in São Paulo, Brazil is a major source of data used to build epidemiological profiles of the client population. We examined HIV-1 incidence from November 2000 to April 2001, comparing epidemiological and socio-behavioral data of recently-infected individuals with those with long-standing infection. A less sensitive ELISA was employed to identify recent infection. The overall incidence of HIV-1 infection was 0.53/100/year (95% CI: 0.31-0.85/100/year): 0.77/100/year for males (95% CI: 0.42-1.27/100/year) and 0.22/100/ year (95% CI: 0.05-0.59/100/year) for females. Overall HIV-1 prevalence was 3.2% (95% CI: 2.8-3.7%), being 4.0% among males (95% CI: 3.3-4.7%) and 2.1% among females (95% CI: 1.6-2.8%). Recent infections accounted for 15% of the total (95% CI: 10.2-20.8%). Recent infection correlated with being younger and male (p = 0.019). Therefore, recent infection was more common among younger males and older females.

Histological response study of chronic viral hepatitis C patients treated with interferon alone or combined with ribavirin

Chronic hepatitis C is often a progressive, fibrotic disease that can lead to cirrhosis and other complications. The recommended therapy is a combination of interferon and ribavirin. Besides its antiviral action, interferon is considered to have antifibrotic activity. We examined the outcome of hepatic fibrosis and inflammation in chronic hepatitis C patients who were non-responders to interferon. We made a case series, retrospective study, based on revision of medical records and reassessment of liver biopsies. For inclusion, patients should have been treated with interferon alone or combined with ribavirin, with no virological response (non responders and relapsers) and had a liver biopsy before and after treatment. Histological evaluation included: i-outcome of fibrosis and necroinflammation; ii-annual fibrosis progression rate evaluation, before and after treatment. Seventy-five patients were included. Fifty-seven patients (76%) did not show progression of fibrosis after treatment, compared to six (8%) before treatment (p < 0.001). The mean annual fibrosis progression rate was significantly reduced after treatment (p = 0.036). Inflammatory activity improved in 19 patients (25.3%). The results support the hypothesis of an antifibrotic effect of interferon-based therapy, in non-responder patients. There was evidence of anti-inflammatory effects of treatment in some patients.

A coronavirus detected in the vampire bat Desmodus rotundus

This article reports on the identification of a group 2 coronavirus (BatCoV DR/2007) in a Desmodus rotundus vampire bat in Brazil. Phylogenetic analysis of ORF1b revealed that BatCoV DR/2007 originates from a unique lineage in the archetypical group 2 coronaviruses, as described for bat species elsewhere with putative importance in Public Health.