Biomedical subjects

A Llanos-Cuentas

Publications and source records attributed to A Llanos-Cuentas.

At least 19 recordsLinked to original sources

PubMed2005

Randomized, double-blind clinical trial of topical imiquimod 5% with parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru.

BACKGROUND: Current treatments for cutaneous leishmaniasis are limited by their toxicity, high cost, and discomfort and the emergence of drug resistance. New approaches, including combination therapies, are urgently needed. We performed a double-blind, randomized trial of therapy with parenteral antimony plus topical imiquimod, an innate immune-response modulator, versus therapy with antimony alone, in subjects with cutaneous leishmaniasis for whom an initial course of antimony therapy had failed. METHODS: Forty subjects with clinical resistance to antimony were recruited in Lima, Peru, between February 2001 and December 2002. All subjects received meglumine antimoniate (20 mg/kg/day im or iv) and were randomized to receive either topical imiquimod 5% cream (Aldara; 3M Pharmaceuticals) or vehicle control every other day for 20 days. Lesions and adverse events were evaluated during treatment and at 1, 2, 3, 6, and 12 months after the treatment period. RESULTS: The mean number of lesions was 1.2 per person; 71% of the lesions were facial and 76% were ulcerative. There were no major differences between the groups, and all but 2 subjects completed therapy. Mild adverse events were reported by 73% of the subjects, but only erythema occurred more commonly in the imiquimod group (P < or = .02). Lesions resolved more rapidly in the imiquimod group: 50% of the imiquimod group achieved cure at 1 month after the treatment period versus 15% of the vehicle cream group (P < or = .02); 61% of the imiquimod group at 2 months versus 25% of the vehicle cream group (P < or = .03); and 72% of the imiquimod group at 3 months versus 35% of the vehicle cream group (P < or = .02). Residual scarring in the imiquimod group was less prominent than in the vehicle cream group. CONCLUSIONS: Combined antimony plus imiquimod treatment was well tolerated, accelerated healing of lesions, and improved scar quality. This therapy may have particular advantages for subjects with facial lesions.

Adjuvants, Immunologic↗

PubMed2005

Differential polyadenylation of ribosomal RNA during post-transcriptional processing in Leishmania.

The protozoan parasite Leishmania belongs to the most ancient eukaryotic lineages and this is reflected in several distinctive biological features, such as eukaryotic polycistronic transcription and RNA trans-splicing. The disclosure of this organism's unusual characteristics leads to a better understanding of the origin and nature of fundamental biological processes in eukaryotes. Here we report another unusual phenomenon as we demonstrate that precursor ribosomal RNA can be extensively polyadenylated during post-transcriptional processingt. Furthermore, we demonstrate that the degree of precursor rRNA polyadenylation is variable in different strains and in the different life-stages of a strain.

3' Untranslated Regions↗

PubMed2004

A randomized, double-blind, parallel-group, dose-response study of micafungin compared with fluconazole for the treatment of esophageal candidiasis in HIV-positive patients.

BACKGROUND: Severely immunocompromised individuals are highly susceptible to Candida infection of the esophagus. This randomized, double-blind study assessed the dose-response relationship of the new echinocandin antifungal, micafungin, compared with that of standard fluconazole treatment. METHODS: A total of 245 patients (age, > or =18 years) with a prior diagnosis of acquired immunodeficiency syndrome/human immunodeficiency virus (HIV) infection and esophageal candidiasis, confirmed by endoscopy and culture, were randomized to receive micafungin (50, 100, or 150 mg per day) or fluconazole (200 mg per day). Both agents were administered once per day by a 1-h intravenous infusion for 14-21 days. The primary efficacy end point was endoscopic cure rate, defined as endoscopy grade of 0 at the end of therapy. RESULTS: The endoscopic cure rate (grade 0) was dose-dependent with 50, 100, and 150 mg of micafungin per day at 68.8%, 77.4%, and 89.8%, respectively. Symptoms improved or resolved rapidly (3-7 days of treatment in the majority of patients). The endoscopic cure rate for 100 and 150 mg of micafungin per day (83.5%) was comparable to that for 200 mg of fluconazole per day (86.7%; 95% confidence interval for the difference in endoscopic cure rate, -14.0% to 7.7%). The overall safety and tolerability was acceptable, with no important differences between micafungin (all doses) and fluconazole. CONCLUSIONS: The dose-response findings demonstrate a greater efficacy with micafungin at 100 and 150 mg per day than at 50 mg per day. This study also indicates that the efficacy of micafungin (at dosages of 100 and 150 mg per day) was comparable to that of fluconazole, suggesting that micafungin represents a valuable new treatment option for esophageal candidiasis in HIV-positive patients.

AIDS-Related Opportunistic Infections↗

PubMed2004

The influence of climate on the epidemiology of bartonellosis in Ancash, Peru.

The aim of this study was to evaluate the association between bartonellosis and selected climatic factors during the time periods 1983-1988 and 1995-99, which included two events of the El Niño phenomenon (1986-88, 1997-98), and to identify a reliable climate parameter to be used as an alert indicator for bartonellosis outbreaks in Ancash. The study site was Ancash and its province Carhuaz, Peru. Time-series cross-correlation analysis was used to assess the association between bartonellosis and climate parameters. A higher, almost 4-fold, monthly bartonellosis incidence risk in Ancash department was observed during the El Niño events of 1986-88 and 1997-98. At a regional (Ancash department) and local level (Carhuaz, Ancash), the best correlation was observed between bartonellosis and sea-surface temperature (SST). The results indicate that SST would be the best climate parameter to be used as an alert indicator for bartonellosis outbreaks in Ancash.

Bartonella Infections↗

PubMed2002

Environmental factors as determinants of malaria risk. A descriptive study on the northern coast of Peru.

We conducted a series of studies on the northern Pacific coast of Peru to determine environmental risk factors for malaria. We report in this paper the results of both a descriptive study of incidence and a prevalence survey of malaria. Both studies showed that the area was at low risk for malaria. The malaria incidence rate was 40/1000 p.a. during the study period, and the prevalence of infection was 0.9% (95% CI: 0.4-1.7) before and 1.4% (95% CI: 0.8-2.2) after the high incidence period. However, the risk of malaria varied according to season, village and even house within a single village. Incidence rates increased from February (2.6/1000 p.a.) to May (12.9/1000 p.a.) and decreased during the second part of the year. Most of the cases were clustered in four villages that constituted only 21% of the total population of the area. Houses where multiple cases were recorded were often located near a source of water. Our observations suggested that environmental factors, and particularly the presence of water for irrigation around villages and houses, played a major role in determining the risk of malaria. These observations were extended through an entomological study and a case-control study, to be published elsewhere.

Adolescent↗

PubMed2001

Successful treatment of drug-resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator.

Treatment failures for leishmaniasis with pentavalent antimonials, including meglumine antimonate, are increasingly common in many endemic areas. Imiquimod (Aldara; 3M Pharmaceuticals) is a novel immune response-activating compound, approved by the United States Food and Drug Administration, that is currently used to treat cervical warts and has been shown to activate macrophage killing of Leishmania species. Therefore, an open-label, prospective study was conducted of combined imiquimod plus meglumine antimonate therapy in 12 patients with cutaneous leishmaniasis who had previously not responded to meglumine antimonate therapy. All of the patients responded well to this combination therapy, and 90% were found to be cured at the 6-month follow-up period.

Adjuvants, Immunologic↗

PubMed2001

Atovaquone and proguani hydrochloride compared with chloroquine or pyrimethamine/sulfodaxine for treatment of acute Plasmodium falciparum malaria in Peru.

The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (Malarone) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9) or atovaquone/proguanil as before (n=5) (phase 2). In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] vs. 8% [1/13], P<0.0001). In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]). There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.

Adolescent↗

PubMed1999

Survey of Bartonella species infecting intradomicillary animals in the Huayllacallán Valley, Ancash, Peru, a region endemic for human bartonellosis.

The natural cycle of Bartonella bacilliformis remains uncertain, and the suspected existence of animal reservoirs for the bacterium has never been convincingly demonstrated. We conducted a survey of Bartonella species infecting intradomicillary animals in a bartonellosis-endemic region of Peru, obtaining blood from 50 animals living in the homes of 11 families whose children had recently had bartonellosis. Bartonella-like bacteria were recovered from four of nine small rodents included in the study, but from none of the 41 domesticated animals. Identification and comparison of these isolates, and two Bartonella-like isolates obtained from Phyllotis mice in a different endemic region of Peru using serologic and genotypic methods indicated that although none were strains of B. bacilliformis, five were probably representatives of three previously unrecognized Bartonella species and one was a likely strain of the pathogenic species B. elizabethae.

Animals↗

PubMed1998

Short report: detection of Leishmaniavirus in human biopsy samples of leishmaniasis from Peru.

Leishmaniavirus is a double-stranded RNA virus that persistently infects some strains of the protozoan parasite Leishmania. There is considerable interest in the possibility that the presence of this virus alters parasite phenotype and may affect disease pathogenesis. If so, the virus marker could provide a valuable prognostic indicator for human leishmaniasis, particularly in those cases caused by New World parasite strains. The virus has been detected in cultured L. braziliensis, L. b. guyanensis, and L. major. To date there has been no information as to the extent of infection in samples prior to culturing in the laboratory. This study demonstrates, through the reverse transcription-polymerase chain reaction, that Leishmaniavirus exists in human biopsy samples of leishmaniasis prior to manipulation in culture.

Animals↗

PubMed1998

The gp63 gene locus, a target for genetic characterization of Leishmania belonging to subgenus Viannia.

In the present study the gp63 gene locus was used as a target for genetic characterization of Leishmania parasites by 2 methods: (i) RFLP analysis with several restriction enzymes (gp63-RFLP), and (ii) intra-genic PCR amplification coupled with restriction analysis (PCR-RFLP). Both methods were applied to a large number of natural isolates belonging to 4 species of the subgenus Viannia, namely L. (V.) braziliensis, L. (V.) peruviana, L. (V.) guyanensis and L. (V.) lainsoni; reference stocks of subgenus Leishmania were included as outgroups. Multilocus isoenzyme typing (MLEE) was used as a reference. On the one hand gp63-RFLP evidenced an extensive polymorphism and revealed specific markers for subgenus, species and geographical populations: congruence with MLEE was demonstrated statistically. The particular interest of gp63-RFLP was illustrated by infra-specific polymorphism, because of the possible relationship with phenotype diversity. On the other hand intra-genic amplification was less resolutive than gp63-RFLP, but also allowed discrimination of the 2 subgenera (PCR alone) and all the species tested in the subgenus Viannia (PCR-RFLP). PCR-RFLP presents an important operational advantage as it allows genetic characterization of minute amounts of parasites, using Leishmania specific primers. The polymorphism revealed by gp63-RFLP and PCR-RFLP illustrates the very high genomic and genetic plasticity of gp63 genes.

Animals↗

PubMed1997

Efficacy of sodium stibogluconate alone and in combination with allopurinol for treatment of mucocutaneous leishmaniasis.

A randomized, open, controlled clinical trial was designed to evaluate the efficacy, tolerance, and safety of sodium stibogluconate plus allopurinol and sodium stibogluconate alone as treatment of patients with mucocutaneous leishmaniasis. In phase 1 of the study, all 22 patients with severe disease had improvement of their lesions, but only two had clinical cure (both of these patients received sodium stibogluconate alone). In phase 2, which included 59 patients with moderate disease, the cure rate among sodium stibogluconate recipients was 75% (21 of 28) compared with 63.6% (14 of 22) among the sodium stibogluconate plus allopurinol recipients. The rates of clinical adverse events were similar among both groups. Thrombocytopenia was more frequent in the sodium stibogluconate plus allopurinol recipients, but the difference was not statistically significant. Eight patients (two sodium stibogluconate recipients and six sodium stibogluconate plus allopurinol recipients) withdrew from the study because of severe thrombocytopenia. In this study, the addition of allopurinol to sodium stibogluconate provided no clinical benefit as treatment of mucocutaneous leishmaniasis.

Adult↗

PubMed1997

Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection): combined experience from phase I and phase II studies.

Amphotericin B (AmB) has been the most effective systemic antifungal agent, but its use is limited by the dose-limiting toxicity of the conventional micellar dispersion formulation (Fungizone). New formulations with better and improved safety profiles are being developed and include ABELCET (formerly ABLC), but their dispositions have not been well characterized; hence, the reason for their improved profiles remains unclear. This report details the pharmacokinetics of ABELCET examined in various pharmacokinetic and efficacy studies by using whole-blood measurements of AmB concentration performed by high-pressure liquid chromatography. The data indicated that the disposition of AmB after administration of ABELCET is different from that after administration of Fungizone, with a faster clearance and a larger volume of distribution. It exhibits complex and nonlinear pharmacokinetics with wide interindividual variability, extensive distribution, and low clearance. The pharmacokinetics were unusual. Clearance and volume of distribution were increased with dose, peak and trough concentrations after multiple dosings increased less than proportionately with dose, steady state appeared to have been attained in 2 to 3 days, despite an estimated half-life of up to 5 days, and there was no evidence of significant accumulation in the blood. The data are internally consistent, even though they were gathered under different conditions and circumstances. The pharmacokinetics of ABELCET suggest that lower concentrations in blood due to higher clearance and greater distribution may be responsible for its improved toxicity profile compared to those of conventional formulations.

Amphotericin B↗

PubMed1995

Putative Leishmania hybrids in the Eastern Andean valley of Huanuco, Peru.

During an outbreak of tegumentary leishmaniasis that developed in the 1990s in the Eastern Andean valley of Huanuco, Peru, the coexistence of Andean (uta) and sylvatic leishmaniases was suspected for ecological and geographical reasons, and sympatric sampling was carried out. Seven human isolates of Leishmania were characterized by multilocus enzyme electrophoresis, random amplification of polymorphic DNA and molecular karyotyping. The three methods identified 3 isolates as L. braziliensis, and 4 isolates as putative hybrids with characters of L. braziliensis and L. peruviana. Data from Huanuco are compared to previous results from other areas endemic for uta. Biological and epidemiological implications are discussed.

Animals↗

PubMed1995

Extensive polymorphism at the Gp63 locus in field isolates of Leishmania peruviana.

Genetic diversity within and between tandemly arrayed copies of the Gp63 gene occurs in laboratory isolates of Leishmania spp., but the extent to which this represents natural genetic diversity has not been assessed. Here, the Gp63 locus is examined in 58 fresh isolates of L. peruviana, and clones derived from them, collected throughout the Peruvian Andes. Extensive polymorphism is observed, both in size of Gp63 containing chromosomes, and for restriction-fragment-length polymorphisms (RFLPs) at the Gp63 locus. All clones within an isolate are identical, including those with two distinct Gp63-hybridising chromosomal-sized pulsed-field gel electrophoresis (PFGE) bands, consistent with diploidy but with size differences in homologous chromosomes. For RFLP analysis, three enzymes were selected to cut within the coding region (PstI), in the intergenic region (SalI) and outside (EcoRI) the Gp63 gene cluster. PstI gave identical banding patterns across all isolates/clones. For EcoRI and SalI, all clones within an isolate were identical, but isolates were polymorphic for fragments at 13 (2-30 kb) and 8 (2.6-8.8 kb) different molecular mass locations generating 19 and 16 distinct RFLP patterns or genotypes for each enzyme, respectively. EcoRI restriction patterns, analysed by PFGE, were consistent with the presence of two clusters of Gp63 genes on each homologous chromosome, one contained within EcoRI fragments large enough to carry from 3 to 10 copies of the Gp63 gene, the second on fragments which could carry 1 or 2 copies of the gene. SalI patterns indicated variable restriction sites within clusters, but not within every intergenic region. A hierarchical analysis of variance of allele frequencies, expressed in terms of Wright's F-statistic, indicated significant barriers to gene flow at all levels, valleys within regions (north/south), villages within valleys, and individuals within villages. This extreme polymorphism at the Gp63 locus of L. peruviana demonstrates the great potential for generation of genetic diversity in parasite populations.

Animals↗

PubMed1995

Karyotype plasticity in neotropical Leishmania: an index for measuring genomic distance among L. (V.) peruviana and L. (V.) braziliensis populations.

A method for phenetic analysis of karyotype data has been developed for Leishmania populations. Measurement of size difference between chromosomes recognized by a given DNA probe in different isolates led to the formulation of a Chromosome Size Difference Index (CSDI). The method was applied to phenetic analysis of 4 sets of chromosomes--each set being recognized by a different probe--in 37 L. (Viannia) peruviana isolates sampled along a North-South transect through the Peruvian Andes and, in 11 L. (V.) braziliensis isolates from the Amazonian forest (Peru, Bolivia and Brazil). Karyotype variability was better accounted for by CSDI than by a method based on disjunctive encoding of karyotype data. CSDI evidenced the nature of relationships between L. braziliensis and L. peruviana and it provided a coherent picture of geographical and genomic differentiation among parasite populations. The latter did cluster according to their geographical origin. L. braziliensis was found karyotypically more homogeneous than L. peruviana. Within L. peruviana, Northern populations were closer to L. braziliensis than to Southern L. peruviana populations. The validity of karyotypic populations, or karyodemes, was sustained.

Animals↗

PubMed1995

From population to genome: ecogenetics of Leishmania (Viannia) braziliensis and L. (V.) peruviana.

The size polymorphism of nine chromosomes, recognized by specific probes, was analysed in populations of Leishmania (Viannia) braziliensis and L. (V.) peruviana from various Peruvian biogeographical units. Interpretation of the polymorphism, by statistical and phenetic methods, led to the identification of five consensus (alpha- and beta-tubulin) and four variable chromosomes. The dynamics of the variable chromosomes were studied. The promoter role of the environment on their polymorphism was indicated by: (1) the discrimination of L. braziliensis (forest) and L. peruviana (Andes) by the size of the chromosome containing the gp63 genes; and (2) the fact that, within L. peruviana, the polymorphism of the variable chromosomes revealed a strong eco-geographical structuring of parasite populations, accompanied by increasing chromosomal dissimilarity along a cline from north to south. The adaptative significance of the polymorphism of the variable chromosomes was suggested by: (1) a correlation between chromosomal polymorphism and phenotype variability (lesion type in patients and virulence in vitro); and (2) the association between the decrease in size of the gp63-containing chromosome from L. braziliensis to L. peruviana, and a rearrangement of the gp63 genes, probably accompanied by a decrease in their copy number. As chromosomal variation was shown to be more dependant on eco-geographical differences than isoenzymatic variation, chromosome variation and enzyme variation probably differ in adaptative significance.

Adaptation, Biological↗

PubMed1995

The relationship between CDC light-trap and human-bait catches of endophagic sandflies (Diptera: Psychodidae) in the Peruvian Andes.

A study was carried out in the Peruvian Andes to test the suitability of CDC light traps for monitoring changes in the human-landing rate of endophagic phlebotomine sandflies, following house-spraying with pyrethroid insecticide. On four pairs of consecutive nights, sandflies were caught inside eight sprayed and eight unsprayed houses, either by human bait or by CDC light traps. The sandflies collected were Lutzomyia verrucarum (97%) and Lu.peruensis (3%), both probable vectors of Leishmania peruviana, and the species composition was unaffected by house-spraying. A non-linear relationship was detected between light-trap and human-bait catches, but the relationship did not diverge significantly from linearity within the range of sandfly abundance found in most houses in the endemic area (i.e. between 3 and 200 sandflies/house-night), and did not differ significantly between sprayed and unsprayed houses. However, light trap catches had a significantly lower proportion of blood-fed females in sprayed than in unsprayed houses, probably due to an insecticidal effect on post-blood-feeding behaviour. The proportion of Lu. verrucarum was significantly higher in light trap than in human bait catches, indicating that Lu.peruensis is either more anthropophilic or less phototropic than Lu.verrucarum.

Animals↗

PubMed1995

An association between phlebotomine sandflies and aphids in the Peruvian Andes.

As the composition of natural sugars in the diet of adult sandflies (Diptera: Psychodidae: Phlebotominae) may affect the development of Leishmania (Kinetoplastida: Trypanosomatidae) in sandfly guts, and so play an important role in the epidemiology of leishmaniasis, there is increasing interest in the sources of sugars for wild sandflies. Advanced chromatography techniques have provided indirect evidence that wild sandflies feed on honeydew, a substance released by aphids (Hemiptera: Aphididae) when feeding. Our objective was to determine whether sandfly density can be influenced directly by the local density of aphids. Aphid density was determined by counting absolute numbers of aphids on alfalfa stems in Purisima Valley, Peru, where sandflies transmit Leishmania peruviana causing Andean cutaneous leishmaniasis (uta). Sandfly relative abundance was measured using sticky trap sampling repeatedly in alfalfa fields. Lutzomyia verrucarum accounted for 92% of the total sandflies collected. As there was a female bias in sandflies collected close to houses, only the numbers of male sandflies were used in analysis. Most of the adult aphids found feeding on alfalfa were either Therioaphis trifolii forma maculata (97%) or Acyrthosiphon pisum (3%). By regression analysis, a significant relationship was found between the density of Lu.verrucarum males and the density of adults of both aphid species. This is the first ecological study to support the hypothesis that aphid honeydew may be a source of sugar for sandflies.

Animals↗