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Biomedical subjects

K Mansinho

Publications and source records attributed to K Mansinho.

18 recordsLinked to original sources

Detection of Pneumocystis jirovecii dihydropteroate synthase polymorphisms in patients with Pneumocystis pneumonia.

In the present study, in order to improve the detection of Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations in pulmonary specimens of HIV-infected patients with P. jirovecii pneumonia, we evaluated a microfiltration procedure for the removal of human cell contamination and a nested-PCR method, for amplification in specimens with low parasite load. In the studied population, PCR amplification of the DHPS gene was more successful in unfiltered than in filtered specimens, with both touchdown-PCR and nested-PCR procedures (p<0.05 and p<0.001, respectively), but the amount of host DNA in the samples analysed seems to be inversely related with the successful PCR parasite detection. Amplification of P. jirovecii DHPS gene with nested-PCR was achieved in 77.5% of the specimens studied, demonstrating that this is a useful method for the identification of mutations in pulmonary specimens, including samples with low parasite loads, and will facilitate the evaluation of the relationship between the P. jirovecii DHPS polymorphisms and clinical resistance to sulfa drugs.

Bronchoalveolar Lavage Fluid↗

Identification and characterization of HIV-2 strains obtained from asymptomatic patients that do not use CCR5 or CXCR4 coreceptors.

In vivo, human immunodeficiency virus type 2 (HIV-2) infection reveals several unique characteristics when compared to HIV-1 infection, the most remarkable of which is the extraordinarily long asymptomatic period. Here we describe two HIV-2 primary isolates, obtained from asymptomatic individuals, which do not infect any coreceptor-expressing cell lines tested. In those cells, we show that the absence of replication is directly related to cell entry events. Furthermore, productive infection observed in peripheral blood mononuclear cells (PBMC) was not inhibited by natural ligands and monoclonal antibodies directed to CCR5 and CXCR4. Finally, viral entry efficiency and viral progeny production of these viruses are markedly impaired in PBMC, indicating a reduced replicative fitness of both viruses. In conclusion, our data suggest that in some HIV-2 asymptomatic individuals, the circulating viruses are unable to use the major coreceptors to infect PBMC. This fact should have important implications in HIV-2 pathogenesis and transmission.

CD4 Antigens↗

Emergence of drug resistance mutations in human immunodeficiency virus type 2-infected subjects undergoing antiretroviral therapy.

The reverse transcriptase (RT) and protease genes from 12 human immunodeficiency virus type 2 (HIV-2)-infected individuals who had been exposed to antiretroviral drugs for longer than 6 months were examined for the presence of mutations which could be involved in drug resistance. Four individuals carried virus genotypes with amino acid substitutions potentially associated with resistance to nucleoside analogues: two at codon 70 (K-->R) and two at codon 184 (M-->V). Moreover, the latter two patients harbored a codon Q151M mutation which is associated to multidrug resistance in HIV-1, and one of these subjects carried some of the typically linked mutations at codons 65 and 69. With regard to the protease inhibitors, substitutions associated with resistance to protease inhibitors at codon 46 were observed in all individuals. Moreover, minor resistance mutations, as well as new ones of unknown meaning, were often seen in the protease gene. In conclusion, amino acid changes in the HIV-2 RT and protease genes which could be associated with drug resistance seem to occur at positions identical to those for HIV-1.

Adolescent↗

Human immunodeficiency virus type 2 (HIV-2) in Portugal: clinical spectrum, circulating subtypes, virus isolation, and plasma viral load.

The human immunodeficiency virus type 2 (HIV-2) is responsible for 4. 5% of AIDS cases in Portugal. Six HIV-2 subtypes have been described so far, subtype A being proposed as more pathogenic than the rest. The relationship between the clinical status and levels of both cellular and plasma HIV-2 viraemia is not well known, nor their modifications under antiretroviral therapy. Thirty-two consecutive HIV-2 infected persons (17 men, 15 women) attending two different hospitals in Lisbon in 1997 were enrolled prospectively in the study. All but 4 individuals most likely acquired the infection through heterosexual contact. More than half of the study population was of African origin, mainly from Guinea-Bissau. Eleven (34.4%) patients had developed clinical manifestations included within the B or C groups of the CDC classification system for HIV infection, with the rest being asymptomatic. Half of the population was undergoing antiretroviral treatment at the time of the study. HIV-2 subtypes were investigated using a new Nef-based restriction fragment length polymorphism (RFLP) method that allows differentiation of the main two variants, A and B. Plasma viral load was quantified using a new quantitative competitive reverse transcriptase polymerase chain reaction (QcRT-PCR) procedure as well as the Amp-RT assay. Virus isolation was attempted from peripheral blood mononuclear cells. All but one person carried HIV-2 subtype A. Plasma viraemia examined by QcRT-PCR was measurable in 15 (50%) of 30 subjects, yielding in all instances values below 20,000 HIV-2 RNA copies per ml. Plasma RT activity could be detected in only 10 (33%) of 30 subjects, a rate much lower than that seen in HIV-1 infection. Virus was isolated from 16 (53.3%) of 30 patients. A significant correlation was found between CD4+ counts, clinical status, rate of virus isolation, and plasma viral load by both QcRT-PCR and Amp-RT. In conclusion, HIV-2 subtype A is the predominant variant circulating in Portugal among both natives and immigrants. A lower cellular and plasma viral load with respect to HIV-1 was seen in persons without immunosuppression, from whom the rate of virus recovery was extremely low.

Female↗

[Human immunodeficiency virus type 2 infection].

The isolation of a second retrovirus, HIV-2, led to fears that a second AIDS pandemic, similar in scope and magnitude to that caused by HIV-1, might ensue. However, the peculiar biologic properties of HIV-2, namely the lower transmissibility of this virus through both sexual and vertical routes, contributed to a more regionalized distribution of the virus, which became endemic in West Africa. HIV-2 is genetically more closely related to SIV than to HIV-1. When it comes to clinical disease, the spectrum of opportunistic infections and tumors (except for Kaposi sarcoma) are similar to that observed with HIV-1. Controlled longitudinal studies suggest that the rate of progression to advanced HIV related disease and mortality are far lower for HIV-2 than for HIV-1. Understanding how, immunologically and virologically, HIV-2 behaves differently from HIV-1 may provide some insight into the mechanisms governing HIV-1 pathogenesis.

HIV Infections↗

Evidence of Nef truncation in human immunodeficiency virus type 2 infection.

Human immunodeficiency virus (HIV)-2 differs from HIV-1 in its relative lower transmissibility and pathogenicity. To understand the virologic basis of these differences, the nef gene from HIV-2-seropositive persons was analyzed because of its importance for disease progression in the genetically related simian immunodeficiency virus (SIV[MAC]). Proviral nef sequences from 60 HIV-2-infected persons were amplified from peripheral blood lymphocytes, and nef open-reading frames were screened by a transcription and translation assay for the presence of full-length (32- to 36-kDa) or truncated (<32 kDa) Nef proteins. Overall, 6 (10%) of 60 persons had truncated Nef proteins; of these, 5 were among the 36 asymptomatic subjects (13.9%) and only 1 was among the 24 symptomatic subjects (4.2%) (P =.23). The results of this study document the presence of defective nef genes in HIV-2 infections with a prevalence higher than that previously seen in HIV-1-infected cohorts of long-term nonprogressors or patients with AIDS.

Amino Acid Sequence↗

[The acquired immunodeficiency syndrome, hypertrophic myocardiopathy and multivalvular infectious endocarditis. Apropos a clinical case].

We present a clinical case of a 33 years old young male, gypsy, intravenous drug abuser with heroine and cocaine and AIDS diagnosis. The clinical anamnesis was mainly fever and systolic heart murmur in a clinical scenario of AIDS. The two-dimensional echocardiographic study was clearly diagnostic of an hypertrophic obstructive cardiomyopathy of the left ventricle. This study showed also the presence of multiple vegetations of the mitral, aortic and pulmonic valves in a clinical setting of an acute Streptococcus Viridans infective endocarditis. In this case report we discuss the incidence of this type of multiple cardiac lesions and particularly the presence of this specific pathogenic agent in this high risk group of patients with intravenous drug abuse and systemic immunosuppression. We pointed out the rarity of these findings of left side valvular vegetations associated with this type of cardiomyopathy and the different factors related to infective endocarditis.

AIDS-Related Opportunistic Infections↗

[Immunologic profile of HIV-2 seropositive African individuals (follow-up)].

In the geographic distribution of HIV-2, it is known that this infection is most prevalent in West Africa. Since 1986 we have studied seropositive and seronegative clusters, in Guinea-Bissau with follow-ups in 1988, 1989, 1990 and 1991. Analysis of the results show the high incidence of this infection. 8.51% of the 4,372 people of the general population studied were seropositive, showing the high predominance of HIV-2 infection. Only 4 cases were exclusively reactive to HIV-1 and a slow evolution of HIV-1 infections. In the seroconversions of HIV-2 infections the antibodies appeared first to the core components and secondly to the surface glycoproteins. Some of the laboratory parameters affected in the evolution of the infection include a gradual increase in immunoglobulins and a decrease in CD4 lymphocytes and in the CD4/CD8 ratio. A comparison of these variations in HIV-2 infected people, with or without cross-reactivity to HIV-1, reveals that they are much more evident in exclusively HIV-2 positive people. This fact can indicate that the variants responsible for the cross-reactions are less pathogenic and phylogenetically less developed.

Africa, Western↗

Six new isolates of human immunodeficiency virus type 2 (HIV-2) and the molecular characterization of one (HIV-2CAM2).

We report the isolation of human immunodeficiency virus type 2 (HIV-2) from each of six West Africans with AIDS-related complex or AIDS. One isolate (HIV-2CAM2) was molecularly cloned and shown by restriction mapping to differ in seven out of 22 sites from the prototype HIV-2ROD. Nevertheless, by a number of serological criteria these isolates are all clearly HIV-2.

AIDS-Related Complex↗

Human immunodeficiency virus type 2 infection associated with AIDS in West Africa.

We recently reported the isolation of a new retrovirus, termed human immunodeficiency virus type 2 (HIV-2), from two West African patients with the acquired immunodeficiency syndrome (AIDS). This virus is related to but distinct from the well-characterized AIDS retrovirus, human immunodeficiency virus type 1 (HIV-1). We report here evidence of infection with HIV-2 in 30 patients, almost all from West Africa. Seventeen of them had a clinical syndrome indistinguishable from AIDS (7 of these 17 died). Others had either the AIDS-related complex or no HIV-related symptoms. All patients had serum antibodies reacting with HIV-2 in an indirect immunofluorescence assay. All serum tested contained antibodies reacting with the envelope glycoprotein of the virus in an immunoprecipitation assay. Cross-reactivity of serum antibodies with HIV-1 was detected in a minority of patients and varied according to the assay used. Retroviral isolates were obtained from the blood lymphocytes of 11 patients and were all identified as HIV-2 by nucleic acid hybridization; none hybridized with an HIV-1 probe. These findings indicate that some cases of AIDS in West Africa may be caused by HIV-2, but the extent of the spread of this virus and its clinical correlates will require careful epidemiologic investigation.

AIDS-Related Complex↗

[Cutaneous infection with the cytomegalovirus virus in AIDS patients].

Cutaneous cytomegalovirus (CMV) infection has been observed in a variety of nonspecific skin lesions. Because of this fact, its diagnosis is rare and frequently accidental. The presence of the virus has also been observed in apparently normal skin, from both a clinical and histological point of view. In this context, skin biopsy and immunohistochemistry are often the first means of diagnosis of systemic CMV infection. In 180 skin biopsies carried out on HIV patients in the Infectious and Parasitic Diseases Unit, typical histopathological findings of CMV infection in a nonspecific skin lesion were observed in only one patient. Although the patient showed no extracutaneous manifestations at this time, she died soon after this diagnosis. Because of this fact, we review the literature and discuss the difficulties and implications of the diagnosis of cutaneous CMV infection in AIDS patients.

AIDS-Related Opportunistic Infections↗

[Verrucous herpes zoster in AIDS patients].

The authors describe a case of disseminated Herpes-Zoster (VZV) in an HIV 1 positive patient with AIDS. Hyperkeratotic characteristics, acyclovir resistance and sensitivity to foscarnet of cutaneous lesions are the most important features of this example. From the casuistics of the department, the authors describe two similar cases and review the medical literature with emphasis on etiopathogenic, diagnostic and therapeutic factors of lesions caused by DNA Virus in immunocompromised hosts.

AIDS-Related Opportunistic Infections↗