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1.
Clin Microbiol Infect ; 26(6): 781.e9-781.e16, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31678231

RESUMO

OBJECTIVES: This study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cut-offs; (c) determine differences in immune response after different antibiotic treatments; and (d) determine appropriate diagnostic cut-off parameters for indirect immunofluorescence assay (IFA). METHODS: Sequential serum samples from 90 non-pregnant, adults were collected at seven time-points (days 0, 7, 14, 28, 90, 180 and 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal end-point titres against R. typhi and PCR. RESULTS: For all 90 individuals, reciprocal R. typhi IgM and IgG antibody titres ranged from <400 to ≥3200. The median half-life of R. typhi IgM was 126 days (interquartile range 36-204 days) and IgG was 177 days (interquartile range 134-355 days). Overall median patient titres for R. typhi IgM and IgG were significantly different (p < 0.0001) and at each temporal sample collection point (range p < 0.0001 to p 0.0411). Using Bayesian latent class model analysis, the optimal diagnostic cut-off reciprocal IFA titer on patient admission for IgM was 800 (78.6%, 95% CI 71.6%-85.2% sensitivity; 89.9%, 95% CI 62.5%-100% specificity), and for IFA IgG 1600 (77.3%; 95% CI 68.2%-87.6% sensitivity; 99%, 95% CI 95%-100% specificity). CONCLUSIONS: This study suggests suitable diagnostic cut-offs for local diagnostic laboratories and other endemic settings and highlights antibody persistence following acute infection. Further studies are required to validate and define cut-offs in other geographically diverse locations.


Assuntos
Anticorpos Antibacterianos/sangue , Imunidade Humoral , Rickettsia typhi/imunologia , Tifo Endêmico Transmitido por Pulgas/imunologia , Adulto , Antibacterianos/uso terapêutico , Teorema de Bayes , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Laos/epidemiologia , Estudos Longitudinais , Rickettsia typhi/efeitos dos fármacos , Rickettsia typhi/genética , Sensibilidade e Especificidade , Tifo Endêmico Transmitido por Pulgas/diagnóstico , Tifo Endêmico Transmitido por Pulgas/tratamento farmacológico
2.
Clin Microbiol Infect ; 24(8): 815-826, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29581051

RESUMO

BACKGROUND: Increasing evidence is becoming available on the aetiology and management of fevers in Asia; the importance of these fevers has increased with the decline in the incidence of malaria. AIMS: To conduct a narrative review of the epidemiology and management of fevers in South and South-East Asia and to highlight gaps in our knowledge that impair evidence-based health policy decisions. SOURCES: A narrative review of papers published since 2012 on developments in fever epidemiology, diagnosis and treatment in South and South-East Asia. The papers that the authors felt were pivotal, from their personal perspectives, are discussed. CONTENT: We identified 100 studies. Among the 30 studies (30%)-including both children and adults-that investigated three or more pathogens, the most frequently reported fever aetiology was dengue (reported by 15, 50%), followed by leptospirosis (eight, 27%), scrub typhus (seven, 23%) and Salmonella serovar Typhi (six, 20%). Among four studies investigating three or more pathogens in children, dengue and Staphylococcus aureus were the most frequent, followed by non-typhoidal Salmonella spp, Streptococcus pneumoniae, Salmonella serovar Typhi, and Orientia tsutsugamushi. Increased awareness is needed that rickettsial pathogens are common but do not respond to cephalosporins, and that alternative therapies, such as tetracyclines, are required. IMPLICATIONS: Many key gaps remain, and consensus guidelines for study design are needed to aid comparative understanding of the epidemiology of fevers. More investment in developing accurate and affordable diagnostic tests for rural Asia and independent evaluation of those already on the market are needed. Treatment algorithms, including simple biomarker assays, appropriate for empirical therapy of fevers in different areas of rural Asia should be a major aim of fever research. Enhanced antimicrobial resistance (AMR) surveillance and openly accessible databases of geography-specific AMR data would inform policy on empirical and specific therapy. More investment in innovative strategies facilitating infectious disease surveillance in remote rural communities would be an important component of poverty reduction and improving public health.


Assuntos
Febre/epidemiologia , Febre/etiologia , Ásia/epidemiologia , Gerenciamento Clínico , Prática Clínica Baseada em Evidências , Febre/diagnóstico , Febre/terapia , Política de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Vigilância da População , Garantia da Qualidade dos Cuidados de Saúde
3.
Clin Microbiol Infect ; 24(9): 1017.e1-1017.e7, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29092789

RESUMO

OBJECTIVES: To compare two molecular assays (rrs quantitative PCR (qPCR) versus a combined 16SrRNA and LipL32 qPCR) on different sample types for diagnosing leptospirosis in febrile patients presenting to Mahosot Hospital, Vientiane, Laos. METHODS: Serum, buffy coat and urine samples were collected on admission, and follow-up serum ∼10 days later. Leptospira spp. culture and microscopic agglutination tests (MAT) were performed as reference standards. Bayesian latent class modelling was performed to estimate sensitivity and specificity of each diagnostic test. RESULTS: In all, 787 patients were included in the analysis: 4/787 (0.5%) were Leptospira culture positive, 30/787 (3.8%) were MAT positive, 76/787 (9.7%) were rrs qPCR positive and 20/787 (2.5%) were 16SrRNA/LipL32 qPCR positive for pathogenic Leptospira spp. in at least one sample. Estimated sensitivity and specificity (with 95% CI) of 16SrRNA/LipL32 qPCR on serum (53.9% (33.3%-81.8%); 99.6% (99.2%-100%)), buffy coat (58.8% (34.4%-90.9%); 99.9% (99.6%-100%)) and urine samples (45.0% (27.0%-66.7%); 99.6% (99.3%-100%)) were comparable with those of rrs qPCR, except specificity of 16SrRNA/LipL32 qPCR on urine samples was significantly higher (99.6% (99.3%-100%) vs. 92.5% (92.3%-92.8%), p <0.001). Sensitivities of MAT (16% (95% CI 6.3%-29.4%)) and culture (25% (95% CI 13.3%-44.4%)) were low. Mean positive Cq values showed that buffy coat samples were more frequently inhibitory to qPCR than either serum or urine (p <0.001). CONCLUSIONS: Serum and urine are better samples for qPCR than buffy coat, and 16SrRNA/LipL32 qPCR performs better than rrs qPCR on urine. Quantitative PCR on admission is a reliable rapid diagnostic tool, performing better than MAT or culture, with significant implications for clinical and epidemiological investigations of this global neglected disease.


Assuntos
Buffy Coat/microbiologia , Febre/microbiologia , Leptospira/isolamento & purificação , Leptospirose/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Soro/microbiologia , Urina/microbiologia , Adolescente , Adulto , Idoso , Proteínas da Membrana Bacteriana Externa/genética , Criança , DNA Bacteriano/genética , Feminino , Humanos , Laos , Leptospira/genética , Leptospirose/sangue , Leptospirose/urina , Lipoproteínas/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade , Adulto Jovem
4.
Sci Rep ; 7(1): 3031, 2017 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-28596557

RESUMO

Melioidosis, a severe infection with the environmental bacterium Burkholderia pseudomallei, is being recognised increasingly frequently. What determines its uneven distribution within endemic areas is poorly understood. We cultured soil from a rice field in Laos for B. pseudomallei at different depths on 4 occasions over a 13-month period. We also measured physical and chemical parameters in order to identify associated characteristics. Overall, 195 of 653 samples (29.7%) yielded B. pseudomallei. A higher prevalence of B. pseudomallei was found at soil depths greater than the 30 cm currently recommended for B. pseudomallei environmental sampling. B. pseudomallei was associated with a high soil water content and low total nitrogen, carbon and organic matter content. Our results suggested that a sampling grid of 25 five metre square quadrats (i.e. 25 × 25 m) should be sufficient to detect B. pseudomallei at a given location if samples are taken at a soil depth of at least 60 cm. However, culture of B. pseudomallei in environmental samples is difficult and liable to variation. Future studies should both rely on molecular approaches and address the micro-heterogeneity of soil when investigating physico-chemical associations with the presence of B. pseudomallei.


Assuntos
Betaproteobacteria , Microbiologia Ambiental , Oryza , Microbiologia do Solo , Carga Bacteriana , Fenômenos Químicos , Estações do Ano , Solo/química
5.
Epidemiol Infect ; 144(8): 1770-3, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26645633

RESUMO

Epidemiological data regarding group A streptococcal (GAS) infections in South East Asia are scarce with no information from Laos. We characterized emm types, emm clusters and the antibiotic resistance profile of 124 GAS isolates recovered in Laos during 2004-2013. Most strains were recovered from skin and invasive infections (76% and 19%, respectively). Thirty-four emm types were identified as belonging to 12 emm clusters and no novel emm types were identified. No significant differences were observed in the distribution of emm types or emm clusters according to age or site of recovery (skin or invasive infections). There was moderate strain diversity in this country but considerable differences in emm-type distribution between Laos, Thailand and Cambodia. Vaccine coverage was high for the J8 vaccine candidate. The theoretical coverage for the 30-valent vaccine candidate needs further investigation. Antibiotic resistance was moderate to erythromycin and chloramphenicol (8% and 7%, respectively) and low to ofloxacin (<1%).


Assuntos
Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/classificação , Streptococcus pyogenes/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Transporte/genética , Criança , Pré-Escolar , Análise por Conglomerados , Farmacorresistência Bacteriana , Feminino , Variação Genética , Genótipo , Humanos , Lactente , Recém-Nascido , Laos/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/administração & dosagem , Streptococcus pyogenes/genética , Vacinação/estatística & dados numéricos , Adulto Jovem
7.
New Microbes New Infect ; 2(6): 170-2, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25566395

RESUMO

Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are major aetiological agents of hand, foot and mouth disease in Asia. We established the first genomic characterization of strains isolated in 2011 from Lao patients. Isolates were related to EV-A71 genotype C4 and CV-A16 genotype B1a that circulated in neighbouring countries during the same period. This confirms the regional character of hand, foot and mouth disease epidemiology and makes plausible the occurrence of severe disease in the Lao population.

8.
Clin Microbiol Infect ; 19(10): E466-72, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23738720

RESUMO

We investigated whether dried cerebrospinal fluid (CSF) conserved on filter paper can be used as a substrate for accurate PCR diagnosis of important causes of bacterial meningitis in the Lao PDR. Using mock CSF, we investigated and optimized filter paper varieties, paper punch sizes, elution volumes and quantities of DNA template to achieve sensitive and reliable detection of bacterial DNA from filter paper specimens. FTA Elute Micro Card™ (Whatman, Maidstone, UK) was the most sensitive, consistent and practical variety of filter paper. Following optimization, the lower limit of detection for Streptococcus pneumoniae from dried mock CSF spots was 14 genomic equivalents (GE)/µL (interquartile range 5.5 GE/µL) or 230 (IQR 65) colony forming units/mL. A prospective clinical evaluation for S. pneumoniae, S. suis and Neisseria meningitidis was performed. Culture and PCR performed on fresh liquid CSF from patients admitted with a clinical diagnosis of meningitis (n = 73) were compared with results derived from dried CSF spots. Four of five fresh PCR-positive CSF samples also tested PCR positive from dried CSF spots, with one patient under the limit of detection. In a retrospective study of S. pneumoniae samples (n = 20), the median (IQR; range) CSF S. pneumoniae bacterial load was 1.1 × 10(4) GE/µL (1.2 × 10(5) ; 1 to 6.1 × 10(6) DNA GE/µL). Utilizing the optimized methodology, we estimate an extrapolated sensitivity of 90%, based on the range of CSF genome counts found in Laos. Dried CSF filter paper spots could potentially help us to better understand the epidemiology of bacterial meningitis in resource-poor settings and guide empirical treatments and vaccination policies.


Assuntos
Bactérias/classificação , DNA Bacteriano/líquido cefalorraquidiano , Meningites Bacterianas/líquido cefalorraquidiano , Tipagem Molecular/instrumentação , Papel , Adolescente , Bactérias/genética , Bactérias/isolamento & purificação , Carga Bacteriana/instrumentação , Carga Bacteriana/métodos , Criança , Pré-Escolar , DNA Bacteriano/química , DNA Bacteriano/genética , Humanos , Lactente , Laos , Limite de Detecção , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/microbiologia , Tipagem Molecular/métodos , Estudos Prospectivos
10.
Clin Microbiol Infect ; 18(12): 1221-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22192733

RESUMO

Scrub typhus (caused by Orientia tsutsugamushi) and murine typhus (caused by Rickettsia typhi) cause up to 28% of febrile episodes in Thailand and Laos. The current understanding of coagulation and inflammation in the pathogenesis of these clinically very similar vasculotropic diseases is limited. This study compared human in vivo changes in 15 coagulation, inflammation and endothelial activation markers in prospectively collected admission and follow-up samples of 121 patients (55 scrub typhus, 55 murine typhus, and 11 typhus-like illness) and 51 healthy controls from Laos. As compared with controls, all but one of the markers assessed were significantly affected in typhus patients; however, the activation patterns differed significantly between scrub and murine typhus patients. The levels of markers of coagulation activation and all inflammatory cytokines, except for interleukin-12, were significantly higher in patients with scrub typhus than in those with murine typhus. In patients with murine typhus, however, the levels of endothelium-derived markers were significantly higher. Anticoagulant factors were inhibited in both typhus patient groups. This is the first study demonstrating that, in scrub typhus, in vivo coagulation activation is prominent and is related to a strong proinflammatory response, whereas in murine typhus, changes in coagulant and fibrinolytic pathways are suggestive of endothelial cell perturbation. These data suggest that, although late-stage endothelial infection is common in both diseases, the in vivo pathogenic mechanisms of R. typhi and O. tsutsugamushi could differ in the early phase of infection and may contribute to disease differentiation.


Assuntos
Tifo por Ácaros/patologia , Tifo Endêmico Transmitido por Pulgas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Coagulação Sanguínea , Criança , Pré-Escolar , Feminino , Humanos , Inflamação/patologia , Laos , Masculino , Pessoa de Meia-Idade , Orientia tsutsugamushi/patogenicidade , Estudos Prospectivos , Rickettsia typhi/patogenicidade , Adulto Jovem
12.
Eur J Clin Nutr ; 63(3): 323-31, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18000519

RESUMO

BACKGROUND/OBJECTIVE: To assess the traditional postpartum practices, mother and child nutritional status and associated factors. SUBJECTS/METHODS: A cross-sectional study in 41 randomly selected villages on the outskirts of Vientiane capital city, Lao PDR (Laos). 300 pairs of infants (< 6 months of age) and their mothers were enrolled. Information was collected about pregnancy, delivery and traditional practices through a standardized questionnaire. Dietary intake and food frequency were estimated using the 24 h recall method, calibrated bowls and FAO food composition tables. Mothers' and infants' anthropometry was assessed and multivariate analysis performed. RESULTS: Contrasting with a high antenatal care attendance (91%) and delivery under health professional supervision (72%), a high prevalence of traditional practices was found, including exposure to hot beds of embers (97%), use of traditional herb tea as the only beverage (95%) and restricted diets (90%). Twenty-five mothers (8.3%) were underweight. Mothers had insufficient intake of calories (55.6%), lipids (67.4%), iron (92.0%), vitamins A (99.3%) and C (45%), thiamin (96.6%) and calcium (96.6%). Chewed glutinous rice was given to infants as an early (mean 34.6, 95% CI:29.3-39.8 days) complementary food by 53.7% of mothers, and was associated with stunting in 10% children (OR=1.35, 95% CI:1.04-1.75). CONCLUSION: The high prevalence of traditional postpartum restricted diets and practices, and inadequate maternal nutritional intake in urban Laos, suggest that antenatal care may be an important opportunity to improve postpartum diets.


Assuntos
Características Culturais , Dieta , Cuidado Pós-Natal , Adulto , Estatura , Aleitamento Materno , Estudos Transversais , Inquéritos sobre Dietas , Ingestão de Energia , Feminino , Humanos , Incidência , Lactente , Transtornos da Nutrição do Lactente/epidemiologia , Laos/epidemiologia , Mães , Gravidez , Magreza/epidemiologia , Adulto Jovem
13.
Clin Exp Immunol ; 153(1): 63-7, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18505434

RESUMO

Scrub typhus is responsible for a large proportion of undifferentiated fevers in south-east Asia. The cellular tropism and pathophysiology of the causative agent, Orientia tsutsugamushi, remain poorly understood. We measured endothelial and leucocyte activation by soluble cell adhesion molecule enzyme-linked immunosorbent assays in 242 Lao and Thai patients with scrub or murine typhus, leptospirosis, dengue, typhoid and uncomplicated falciparum malaria on admission to hospital. Soluble E-selectin (sE-selectin) levels were lowest in dengue, sL-selectin highest in scrub typhus with a high sE-selectin to sL-selectin ratio in leptospirosis patients. In scrub typhus patients elevated sL-selectin levels correlated with the duration of skin rash (P = 0.03) and the presence of eschar (P = 0.03), elevated white blood cell (WBC) count (P = 0.007), elevated lymphocyte (P = 0.007) and neutrophil counts (P = 0.015) and elevated levels of sE-selectin correlated with the duration of illness before admission (P = 0.03), the presence of lymphadenopathy (P = 0.033) and eschar (P = 0.03), elevated WBC (P = 0.005) and neutrophil counts (P = 0.0003). In comparison, soluble selectin levels in murine typhus patients correlated only with elevated WBC counts (P = 0.03 for sE-selectin and sL-selectin). Soluble intercellular adhesion molecule-1 and soluble vascular adhesion molecule-1 levels were not associated significantly with any clinical parameters in scrub or murine typhus patients. The data presented suggest mononuclear cell activation in scrub typhus. As adhesion molecules direct leucocyte migration and induce inflammatory and immune responses, this may represent O. tsutsugamushi tropism during early dissemination, or local immune activation within the eschar.


Assuntos
Células Endoteliais/parasitologia , Leucócitos/imunologia , Orientia tsutsugamushi/fisiologia , Tifo por Ácaros/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Dengue/imunologia , Diagnóstico Diferencial , Selectina E/sangue , Células Endoteliais/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Selectina L/sangue , Laos , Leptospirose/imunologia , Contagem de Leucócitos , Malária Falciparum/imunologia , Orientia tsutsugamushi/imunologia , Selectina-P/sangue , Estatísticas não Paramétricas , Tailândia , Tifo Endêmico Transmitido por Pulgas/imunologia , Tifo Epidêmico Transmitido por Piolhos/imunologia
14.
Trop Med Int Health ; 11(8): 1157-65, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16903879

RESUMO

OBJECTIVE: To determine the efficacy and safety of oral dihydroartemisinin-piperaquine (DP, Artekin) in the treatment of uncomplicated Plasmodium falciparum malaria in southern Laos. METHODS: An open, randomized clinical trial of oral artesunate-mefloquine (AM) vs. DP in 220 patients with acute uncomplicated falciparum malaria in Savannakhet Province, Laos. RESULTS: The 42-day cure rates (95% CI), as determined by survival analysis and adjusted for reinfection, were excellent and similar for the two groups [99 (94-100)% and 100 (100-100)% for AM and DP, respectively]. The median (range) fever and parasite clearance times for the AM and DP groups were also similar [20 (4-63) h and 2 (1-4) days vs. 20 (7-57) and 2 (1-4) days, logrank P = 0.4 and 0.17, respectively]. There were more patients with at least one potential side effect following treatment in the AM group when compared with the DP group [64/110 (58%) vs. 48/110 (44%), respectively, P = 0.031]. CONCLUSION: Dihydroartemisinin-piperaquine did not have superior efficacy to AM for the treatment of uncomplicated falciparum malaria in Laos but was associated with fewer adverse effects.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/tratamento farmacológico , Mefloquina/administração & dosagem , Quinolinas/administração & dosagem , Sesquiterpenos/administração & dosagem , Administração Oral , Adolescente , Adulto , Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Artesunato , Criança , Quimioterapia Combinada , Feminino , Humanos , Laos/epidemiologia , Malária Falciparum/epidemiologia , Masculino , Mefloquina/efeitos adversos , Parasitemia/tratamento farmacológico , Parasitemia/epidemiologia , Quinolinas/efeitos adversos , Quinolinas/sangue , Recidiva , Sesquiterpenos/efeitos adversos , Falha de Tratamento , Resultado do Tratamento
15.
Trop Med Int Health ; 9(12): 1241-6, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15598255

RESUMO

OBJECTIVE: To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia. DESIGN: Cross-sectional survey. SETTING: Pharmacies and shops selling antimalarial drugs in Myanmar (Burma), Lao PDR, Vietnam, Cambodia and Thailand. MAIN OUTCOME MEASURES: Proportion of artemisinin derivatives or mefloquine containing drugs of substandard quality. RESULTS: Of the 188 tablet packs purchased which were labelled as 'artesunate' 53% did not contain any artesunate. All counterfeit artesunate tablets were labelled as manufactured by 'Guilin Pharma', and refinements of the fake blisterpacks made them often hard to distinguish from their genuine counterparts. No other artemisinin derivatives were found to be counterfeited. Of the 44 mefloquine samples, 9% contained <10% of the expected amount of active ingredient. CONCLUSIONS: An alarmingly high proportion of antimalarial drugs bought in pharmacies and shops in mainland SE Asia are counterfeit, and the problem has increased significantly compared with our previous survey in 1999-2000. This is a serious threat to public health in the region.


Assuntos
Antimaláricos/provisão & distribuição , Fraude/estatística & dados numéricos , Malária/prevenção & controle , Automedicação/normas , Antimaláricos/química , Antimaláricos/normas , Artemisininas/análise , Artemisininas/normas , Artesunato , Sudeste Asiático , Estudos Transversais , Rotulagem de Medicamentos/normas , Humanos , Mefloquina/análise , Mefloquina/normas , Sesquiterpenos/análise , Sesquiterpenos/normas
16.
Thorax ; 58(2): 185-6, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12554907

RESUMO

We present a patient who collapsed with chest pain and dyspnoea on a transatlantic flight. She was found to have Pneumocystis carinii pneumonia (PCP) and human immunodeficiency virus infection. Platypnoea and orthodeoxia, which have not been previously reported in association with PCP, were major features of her illness. The PCP predominantly affected her lung bases and it is likely that gravity increased intrapulmonary blood flow through poorly ventilated lung bases with failure of pulmonary vasoconstriction to increase upper zone perfusion, exacerbating desaturation on sitting up. The partial DNA sequence of the infecting P carinii was identical to previously described isolates.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Pleurisia/complicações , Pneumonia por Pneumocystis/complicações , Dispneia/etiologia , Evolução Fatal , Feminino , Humanos , Hipóxia/etiologia , Pessoa de Meia-Idade , Postura/fisiologia
17.
Br J Clin Pharmacol ; 52(6): 655-61, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11736876

RESUMO

AIMS: Artesunate and artemether are the two most widely used artemisinin derivatives in the treatment of uncomplicated Plasmodium falciparum malaria, but there is little information on their comparative pharmacokinetics. The aim of this study was to examine the relative oral antimalarial bioavailability and pharmacokinetics of the two derivatives. METHODS: The pharmacokinetic properties of oral artesunate and artemether (4 mg kg(-1)) were compared in a randomized cross-over study of 14 adult patients in western Thailand with acute uncomplicated Plasmodium falciparum malaria. Antimalarial activity was compared using a previously validated, sensitive bioassay. RESULTS: Despite a 29% lower molar dose, oral artesunate administration resulted in significantly larger mean area under the plasma antimalarial activity time curve and median maximum plasma antimalarial activity than after oral artemether (P

Assuntos
Antimaláricos/farmacocinética , Artemisininas , Malária Falciparum/metabolismo , Sesquiterpenos/farmacocinética , Doença Aguda , Administração Oral , Adolescente , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Área Sob a Curva , Artemeter , Artesunato , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Humanos , Malária Falciparum/tratamento farmacológico , Masculino , Modelos Biológicos , Sesquiterpenos/administração & dosagem , Sesquiterpenos/uso terapêutico , Tailândia , Fatores de Tempo
18.
Trans R Soc Trop Med Hyg ; 95(5): 519-23, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11706665

RESUMO

In some areas clinicians have combined parenteral artesunate and quinine in the belief that the 2 drugs would be additive or synergistic in severe malaria. A randomized comparison of the effectiveness of intravenous (i.v.) artesunate versus i.v. artesunate and i.v. quinine together on parasite clearance was conducted in 1998/99 amongst 69 patients with uncomplicated and severe Plasmodium falciparum malaria in western Thailand. The parasite clearance time did not differ significantly between the 2 treatment groups (P = 0.12), but adverse events were significantly more frequent in the artesunate plus quinine group (P = 0.05). Quinine did not have a significant antipyretic effect and artesunate did not affect the electrocardiographic QTc interval. There is no benefit evident from combining parenteral administration of these 2 antimalarial drugs in the acute phase of treatment.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas , Malária Falciparum/tratamento farmacológico , Quinina/administração & dosagem , Sesquiterpenos/administração & dosagem , Doença Aguda , Adolescente , Adulto , Idoso , Artesunato , Sinergismo Farmacológico , Quimioterapia Combinada , Ecocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade
19.
Blood ; 98(2): 450-7, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11435316

RESUMO

Ring-infected erythrocyte surface antigen (RESA)-positive, Plasmodium falciparum-negative red blood cells (RBCs) are cells from which the malaria parasite has been removed by the host without the destruction of the erythrocyte ("pitting"). The survival of RESA-RBCs in vivo was assessed in 14 severe and 6 uncomplicated falciparum malaria patients. The mean RESA-RBC life of 183 hours (95% confidence interval [CI], 136-246) was longer than the median parasite clearance time of 66 hours (range, 30-108 hours) but shorter than the mean red cell life of 1027 hours (95% CI, 840-1213) (P =.0004), with a median ratio of 0.2:1.0 (range, 0.1-0.7). The estimated median percentage of parasites pitted/body transit was 0.003% (range, 0.001%-0.05%). The rate of rise of the RESA-RBC count during the first 24 hours after antimalarial treatment was significantly faster (P =.036) and the subsequent RESA-RBC survival significantly shorter (P =.017) after treatment with an artemisinin derivative than after treatment with quinine. Parasitization of red cells leads to changes in the erythrocyte that shorten their survival even if the parasite is removed subsequently.


Assuntos
Antígenos de Protozoários/sangue , Envelhecimento Eritrocítico , Eritrócitos/parasitologia , Malária Falciparum/sangue , Plasmodium falciparum/imunologia , Proteínas de Protozoários/sangue , Adolescente , Adulto , Idoso , Animais , Contagem de Eritrócitos , Eritrócitos/imunologia , Humanos , Cinética , Malária Falciparum/parasitologia , Pessoa de Meia-Idade , Mianmar/etnologia , Tailândia
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