In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

Morphological changes in the digestive system of 93 human immunodeficiency virus positive patients: an autopsy study

Involvement of the digestive system in patients with acquired immunodeficiency syndrome (AIDS) is frequent and many changes in these patients are diagnosed only at autopsy. There are few studies of autopsy with detailed analysis of this system and only one was conducted in Brazil. We evaluated each segment of the digestive system in 93 consecutive autopsies of patients infected with human immunodeficiency virus (HIV) and the importance of these lesions to death. Of these, 90 (96.8%) patients had AIDS. We reviewed medical records, autopsy reports and histological sections from tongue to rectum stained with hematoxylin-eosin. When necessary, we analyzed special stains and immunohistochemistry to investigate infections. There was damage to the digestive system in 73 (78.5%) cases. The most common infections were candidiasis (42%), cytomegalovirus (29%), histoplasmosis (11.8%), toxoplasmosis (9.7%) and mycobacterial infection (9.7%). Malignancies were rare, present in four (4.3%) cases (two Kaposi's sarcoma, one adenocarcinoma and one metastatic embryonal carcinoma). All segments showed lesions: tongue (48.6%), esophagus (44.8%), stomach (44.7%), colon (43.2%) and small intestine (28.9%). The lesions found were immediate cause of death in five (5.4%) cases. In another 36 (38.7%) cases the basic disease was systemic and also compromised the digestive system.

MENINGOENCEPHALITIS DUE TO VARICELLA ZOSTER VIRUS IN AIDS PATIENTS. REPORT OF ELEVEN CASES AND REVIEW OF THE LITERATURE

Neurological complications of varicella-zoster virus (VZV) are infrequent and include various clinical pictures. The reactivation of VZV in patients with AIDS is generally associated with an acute and severe meningoencephalitis. We report the epidemiological, clinical and virological data from 11 consecutive patients with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to VZV. All patients were male and seropositive for HIV. The primary risk factor for HIV infection was unprotected sexual contact. The median of CD4 T cell count was 142 cells/µL. All of them presented signs and symptoms of meningoencephalitis. Six patients (54.5%) presented pleocytosis; they all showed high CSF protein concentrations with a median of 2.1 g/dL. Polymerase chain reaction of cerebrospinal fluid specimen was positive for VZV in all of them and they were treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall survival was 63% (7 of 11 patients). The four dead patients had low cellular counts in CSF, below the median of this parameter. VZV should be included among the opportunistic pathogens that can involve CNS with a diffuse and severe meningoencephalitis in patients with advanced HIV/AIDS disease.

LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts.

MALARIA DIAGNOSIS BY LOOP-MEDIATED ISOTHERMAL AMPLIFICATION (LAMP) IN THAILAND

The loop-mediated isothermal amplification method (LAMP) is a recently developed molecular technique that amplifies nucleic acid under isothermal conditions. For malaria diagnosis, 150 blood samples from consecutive febrile malaria patients, and healthy subjects were screened in Thailand. Each sample was diagnosed by LAMP, microscopy and nested polymerase chain reaction (nPCR), using nPCR as the gold standard. Malaria LAMP was performed using Plasmodiumgenus and Plasmodium falciparum specific assays in parallel. For the genus Plasmodium, microscopy showed a sensitivity and specificity of 100%, while LAMP presented 99% of sensitivity and 93% of specificity. For P. falciparum, microscopy had a sensitivity of 95%, and LAMP of 90%, regarding the specificity; and microscopy presented 93% and LAMP 97% of specificity. The results of the genus-specific LAMP technique were highly consistent with those of nPCR and the sensitivity of P. falciparum detection was only marginally lower.

Experimental chemotherapy of Schistosomiasis III: laboratory and clinical trials with trichlorphone, an organophosphorus compound

Oogram studies have been carried out on mice, hamsters, and Cebus morikeys experimentally infected with Schistosoma mansoni and treated with trichlorphone (0,0-dimethyl 1-hydroxy-2, 2, 2-trichloroethylphosphonate). In mice, despite a slight hepatic shift of schistosomes, all animais presented oogram changes when dosed, per os, at the schedules of 200, and 100 mg/kg/day × 7. In hamsters, antischistosomal activity could be detected only at toxic leveis. In monkeys, trichlorphone showed insignificant action even after oral administration of 30 mg/kg/day for 10 consecutive days. In 5 volunteers, a sharp drop in cholinesterase plasma level was observed 24 hours after a single oral dose of 7.5 mg/kg. However, cholinesterase levels returned to the initial values within a period of 11 to 27 days. Trichlorphone was then administered to 12 schistosome patients (7.5 mg/kg/day, every fort- night, × 5). One month after therapy, interruption of egg laying was observed in 6 patients. Late parasitological control showed that all treated patients continued to pass viable S. mansoni eggs with their stools.

Cerebrospinal fluid syndromes in HIV-positive patients with acute consciousness compromise

We reviewed the cerebrospinal fluid (CSF) syndromes of 100 consecutive HIV-positive patients presenting acute consciousness compromise in emergency rooms, and correlated them with clinical data. The most frequent CSF syndromes were: absolute protein-cytological dissociation (21), viral (19), neurocryptococcosis (7), relative protein-cytological dissociation (6) and septic (4), moderate hypoglycorrachia (4), severe hypoglycorrachia (4) and hydroelectrolytic disturbance (3). One fifth of the patients had CSF syndromes considered sufficient for diagnosis or an immediate clinical decision. The most common clinical data were infective and neurological. There was little correlation between the clinical data and the CSF syndromes. We conclude that in HIV-positive individuals presenting acute consciousness disturbances there are frequently non-specific results in the CSF analysis that must be weighed against a detailed history and thorough physical examination. Taking this into account, in about one fifth of cases the CSF analysis can offer useful information for treatment.

Tegumentary leishmaniasis in Northern Argentina: distribution of infection and disease, in three municipalities of Salta, 1990-1992

This work describes the epidemiological pattern of tegumentary leishmaniasis in an area north of Salta, Argentina. The prevalence and incidence were estimated by means of a cross-sectional study and two follow-up studies during two consecutive years. The Montenegro Skin Test (MST) was administered to 7336 subjects at baseline. The prevalence and incidence between 1990 and 1992 of infection (MST reactive) was 38‰ persons and 4.5‰ persons/year respectively. The prevalence and incidence of tegumentary leishmaniasis (presence of clinical signs) was 1.8‰ and 0.8‰ persons/year, respectively. A physical examination performed on 264 patients with MST reactive during three years revealed that 130 cases (49.2%) had some evident sign of infection (scar and/or lesion), with a clinical presentation compatible with leishmaniasis. Our study demonstrated that after the epidemic outbreak of 1985 the transmission in the study area returned to endemic levels in 1992, and also demonstrated the presence of the asymptomatic infection in the area.

An intermittent schedule is better than continuous regimen of antimonial therapy for cutaneous leishmaniasis in the municipality of Rio de Janeiro, Brazil

This study reviews a series of cutaneous leishmaniasis cases diagnosed and treated in outpatient units in the municipality of Rio de Janeiro, where the intermittent schedule of antimonial therapy was replaced by the continuous regimen. Both schedules were based on daily intramuscular injections of pentavalent antimonial. Forty-nine subjects received the intermittent regimen, consisting of three ten-day series alternated with ten-day rest intervals whereas seventy-one patients received the continuous regimen during 20 consecutive days. The study groups had similar composition regarding age, sex and clinical condition. The cure rate was significantly higher in the group receiving the intermittent schedule than in the group receiving continuous therapy (89.8% vs 63.3%). Moreover, loss to follow-up was significantly more frequent in the group receiving continuous therapy (19.7% vs 4.1% in the intermittent therapy). Under field conditions, the intermittent regimen provided higher effectiveness and adherence than the continuous schedule.

Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis C virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin

Comorbidities in human immunodeficiency virus infection are of great interest due to their association with unfavorable outcomes and failure of antiretroviral therapy. This study evaluated the prevalence of coinfection by human immunodeficiency virus and viral hepatitis in an endemic area for hepatitis B in the Western Amazon basin. Serological markers for hepatitis B virus, hepatitis C virus and hepatitis D virus were tested in a consecutive sample of all patients referred for treatment of human immunodeficiency virus or acquired immunodeficiency syndrome. The variables sex, age, origin and exposure category were obtained from medical records and from the sexually transmitted diseases and acquired immunodeficiency syndrome surveillance database. Among 704 subjects, the prevalence of chronic hepatitis B carriage was 6.4% and past infection 40.2%. The presence of hepatitis B was associated with birth in hyperendemic areas of the Amazon basin, male sex and illegal drug use. The overall prevalence of hepatitis C was 5% and was associated with illegal drug use. The prevalence of hepatitis B and C among human immunodeficiency virus or acquired immunodeficiency syndrome patients in the Western Amazon basin was lower than seen elsewhere and is probably associated with the local epidemiology of these viruses and the degree of overlap of their shared risk factors. An opportunity presents itself to evaluate the prevention of hepatitis C through harm reduction policies and hepatitis B through vaccination programs among human immunodeficiency virus or acquired immunodeficiency syndrome patients.

Comparative study of survivor and nonsurvivor sepsis patients in a university hospital

To determine parameters associated with the evolution of sepsis, a five-year retrospective study was conducted in a university hospital. One hundred and four consecutive sepsis patients were evaluated, of whom 55.8% were men. The mortality was 68.3% and was associated with older age (p<0.05). Chronic comorbidities and infection site were not associated with prognosis. Gram-positive bacteria were more frequently identified in survivors (p<0.05), while non-detection of the germ was associated with mortality (p<0.01). Appropriate use of antibiotics (germ sensitive to at least one drug administered) was associated with survival (p<0.0001) while inappropriate use (p<0.05) or empirical use (p<0.01) were more frequent in nonsurvivors. Leukocytosis was the main abnormality (54.8%) detected on diagnosis, from the leukocyte count. During the evolution, normal leukocyte count was associated with survival (p<0.01) and leukocytosis with mortality (p<0.05). In conclusion, mortality was associated with nondetection of the pathogen, leukocytosis during the evolution of the sepsis and inappropriate or empirical use of antimicrobials. Evidence-based treatment that is directed towards modifiable risk factors might improve the prognosis for sepsis patients.

Clinical and epidemiological profile of blood donors with positive serology for viral hepatitis in southern Brazil

INTRODUCTION: Positive serological tests for hepatitis viruses B and C at blood banks are an important reason for blood deferral. Additionally, high residual risk for transfusing hepatitis-contaminated blood has been estimated in southern Brazil. This study aimed to identify risk factors for positive serological tests for viral hepatitis (VH) in blood donors (BD). METHODS: A case-control study included consecutive BD with positive serology for VH, between 2008 and 2009. Cases and controls (BD with negative serology for VH) were paired 1:1 by sex and donation date. Assessment of clinical and epidemiological characteristics related to viral hepatitis was conducted. RESULTS: Among 1,282 blood donors (641 cases and 641 controls), those with positive serology for viral hepatitis had higher mean age (p<0.001); higher proportion of replacement donation (p<0.001); first donation (p<0.001); and interviewer deferment (p=0.037), compared to controls. Furthermore, donors with positive tests were less regular donors (p<0.001), had less previous history of rejection (p=0.003) and showed lower hematocrit median before donation (p=0.019). Multivariate analysis demonstrated that age (OR=1.056, 95%CI 1.042-1.069, p<0.001), replacement donation (OR=1.545, 95%CI 1.171-2.038, p=0.002) and first donation (OR=9.931, 95%CI 7.486-13.173, p<0.001) were independently associated with positivity of serological tests for viral hepatitis. CONCLUSIONS: Specific characteristics of blood donors were associated with positive serology for viral hepatitis. These peculiarities should be taken into account when assessing candidates for blood donation.

Phlebotomine sandflies (Diptera: Psychodidae) in São Vicente Férrer, a sympatric area to cutaneous and visceral leishmaniasis in the state of Pernambuco, Brazil

INTRODUCTION: In the last decades, a considerable geographic expansion of the leishmaniases in all regions of Brazil has been observed. The present study was carried out to identify the composition of the phlebotomine sandfly fauna and verify the seasonal variation of the main species after environmental changes occurred in São Vicente Férrer Municipality, State of Pernambuco, Brazil. METHODS: Captures were carried out during four consecutive nights of each month using Centers for Disease Control and Prevention light traps from September 2009 to September 2010. The correlation between the number of phlebotomine sandflies captured and climatic factors (temperature and rainfall) was evaluated. RESULTS: A total of 13,872 specimens belonging to 20 species were captured, of which, 6,247 (45%) were females, and 7,625 (55%) were males. Lutzomyia migonei was the most abundant species with 9,964 (71.8%) specimens, being predominant in the intradomicile and peridomicile areas with 108 (86.4%) and 9,746 (97%), respectively. In the forest remnants, Lutzomyia complexa 2,395 (65%) and Lutzomyia sordellii 770 (20.8%) predominated. The correlation analysis between the total number of sandflies captured and climatic factors did not show a significant influence on population density. CONCLUSIONS: The high abundance of Lutzomyia migonei and Lutzomyia complexa indicates the possibility of new cases of cutaneous leishmaniasis (CL).

Slow clinical improvement after treatment initiation in Leishmania/HIV coinfected patients

INTRODUCTION: In Brazil there is a large area of overlap of visceral leishmaniasis (VL) and HIV infection, which favored a increased incidence of coinfection Leishmania/HIV. METHODS: This study evaluated 65 consecutive patients with VL and their clinical response to treatment in two health care settings in Belo Horizonte, Brazil. RESULTS: At baseline, the clinical picture was similar between both groups, although diarrhea and peripheral lymphadenomegaly were more frequent in HIV-infected subjects. HIV-positive patients had lower median blood lymphocyte counts (686/mm³ versus 948/mm³p = 0.004) and lower values of alanine aminotransferase (ALT) (48IU/L versus 75.6IU/L p = 0.016) than HIV-negative patients. HIV-positive status (hazard ratio = 0.423, p = 0.023) and anemia (HR = 0.205, p = 0.002) were independent negative predictors of complete clinical response following antileishmanial treatment initiation. CONCLUSIONS: This study reinforces that all patients with VL should be tested for HIV infection, regardless of their clinical picture. This practice would allow early recognition of coinfection with initiation of antiretroviral therapy and, possibly, reduction in treatment failure.

Echocardiographic parameters associated with pulmonary congestion in outpatients with Chagas' cardiomyopathy and non-chagasic cardiomyopathy

INTRODUCTION: Despite significant left ventricular (LV) systolic dysfunction and cardiomegaly, pulmonary congestion does not seem to be a major finding in Chagas' cardiomyopathy (CC). This study sought to identify echocardiographic parameters associated with pulmonary congestion in CC and in dilated cardiomyopathy of other etiologies, such as non-CC (NCC), and to compare pulmonary venous hypertension between the two entities. METHODS: A total of 130 consecutive patients with CC and NCC, with similar echocardiographic characteristics, were assessed using Doppler echocardiography and chest radiography. Pulmonary venous vessel abnormalities were graded using a previously described pulmonary congestion score, and this score was compared with Doppler echocardiographic parameters. RESULTS: NCC patients were older than CC patients (62.4 ± 13.5 × 47.8 ± 11.2, p = 0.00), and there were more male subjects in the CC group (66.2% × 58.5%, p = 0.4). Pulmonary venous hypertension was present in 41 patients in the CC group (63.1%) and in 63 (96.9%) in the NCC group (p = 0.0), the mean lung congestion score being 3.2 ± 2.3 and 5.9 ± 2.6 (p = 0.0), respectively. On linear regression multivariate analysis, the E/e' ratio (β = 0.13; p = 0.0), LV diastolic diameter (β = 0.06; p = 0.06), left atrial diameter (β = 0.51; p = 0.08), and right ventricular (RV) end-diastolic diameter (β = 0.02; p = 0.48) were the variables that correlated with pulmonary congestion in both groups. CONCLUSIONS: Pulmonary congestion was less significant in patients with CC. The degree of LV of systolic and diastolic dysfunction and the RV diameter correlated with pulmonary congestion in both groups. The E/e' ratio was the hallmark of pulmonary congestion in both groups.