RESUMEN
This prospective trial investigated the population pharmacokinetics of piperaquine given with dihydroartemisinin to treat uncomplicated malaria in 107 Ugandan children 6 months to 2 years old, an age group previously unstudied. Current weight-based dosing does not adequately address physiological changes in early childhood. Patients were administered standard 3-day oral doses and provided 1,282 capillary plasma concentrations from 218 malaria episodes. Less than 30% of treatments achieved 57 ng/mL on day 7. A three-compartment model with first-order absorption described the data well. Age had a statistically significant effect (P < 0.005) on clearance/bioavailability in a model that accounts for allometric scaling. Simulations demonstrated that higher doses in all children, but especially in those with lower weight for age, are required for adequate piperaquine exposure, although safety and tolerance will need to be established. These findings support other evidence that both weight- and age-specific guidelines for piperaquine dosing in children are urgently needed.
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Antimaláricos/farmacocinética , Artemisininas/uso terapéutico , Malaria/tratamiento farmacológico , Quinolinas/farmacocinética , Antimaláricos/sangre , Antimaláricos/uso terapéutico , Preescolar , Quimioterapia Combinada , Humanos , Lactante , Estudios Prospectivos , Quinolinas/sangre , Quinolinas/uso terapéutico , UgandaRESUMEN
BACKGROUND: It is unclear whether human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB) mainly through reactivation or following recent Mycobacterium tuberculosis (re)infection. Within a DNA fingerprint-defined cluster of TB cases, reactivation cases are assumed to be the source of infection for subsequent secondary cases. As HIV-positive TB cases are less likely to be source cases, equal or higher clustering in HIV-positives would suggest that HIV mainly increases the risk of TB following recent infection. METHODS: A systematic review was conducted to identify all studies on TB clustering and HIV infection in HIV-endemic populations. Available individual patient data from eligible studies were pooled to analyse the association between clustering and HIV. RESULTS: Of seven eligible studies, six contributed individual patient data on 2116 patients. Clustering was as, or more, likely in the HIV-positive population, both overall (summary OR 1.26, 95%CI 1.0-1.5), and within age groups (OR 1.50, 95%CI 0.9-2.3; OR 1.00, 95%CI 0.8-1.3 and OR 2.57, 95%CI 1.4-5.7) for ages 15-25, 26-50 and >50 years, respectively. CONCLUSIONS: Our results suggest that HIV infection mainly increases the risk of TB following recent M. tuberculosis transmission, and that TB control measures in HIV-endemic settings should therefore focus on controlling M. tuberculosis transmission rather than treating individuals with latent M. tuberculosis infection.
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Enfermedades Endémicas , Infecciones por VIH/epidemiología , Tuberculosis Latente/epidemiología , Mycobacterium tuberculosis/patogenicidad , Tuberculosis/epidemiología , Adolescente , Adulto , Factores de Edad , Análisis por Conglomerados , Enfermedades Endémicas/prevención & control , Femenino , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/microbiología , Tuberculosis Latente/transmisión , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Medición de Riesgo , Factores de Riesgo , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Tuberculosis/prevención & control , Tuberculosis/transmisión , Activación Viral , Adulto JovenRESUMEN
La "University of Miami Global Institute/Project Medishare" (UMGI/PM) a créé le premier hôpital de campagne à Port-au-Prince, en Haïti, après le séisme. Afin de caractériser les blessures et les interventions chirurgicales effectuées par l'UMGI/PM et d'évaluer les besoins spéciaux médicaux, chirurgicaux et de réadaptation, l'UMGI/PM et le "Centers for Disease Control and Prevention" (CDC) mènent une analyse rétrospective de tous les dossiers médicaux de malades disponibles pour la période du 13 janvier au 28 mai 2010. Le premier article de cette revue décrit les résultats de cette analyse et présente les données quantitatives obtenues.
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Víctimas de Desastres , Servicios de Salud , Atención Médica , Cirugía General , Hospitales , Haití , TerremotosRESUMEN
BACKGROUND: GB virus C (GBV-C) is an apathogenic virus that inhibits human immunodeficiency virus (HIV) replication in vitro. Mother-to-child transmission (MTCT) of GBV-C has been observed in multiple small studies. Our study examined the rate and correlates of MTCT of GBV-C in a large cohort of GBV-C-HIV-coinfected pregnant women in Thailand. METHODS: Maternal delivery plasma specimens from 245 GBV-C-HIV-infected women and specimens from their infants at 4 or 6 months of age were tested for GBV-C RNA. Associations with MTCT of GBV-C were examined using logistic regression. RESULTS: One hundred one (41%) of 245 infants acquired GBV-C infection. MTCT of GBV-C was independently associated with maternal antiretroviral therapy (adjusted odds ratio [AOR], 5.21 [95% confidence interval {CI}, 2.12-12.81]), infant HIV infection (AOR, 0.05 [95% CI, 0.01-0.26]), maternal GBV-C load (8.0 log(10) copies/mL: AOR, 86.77 [95% CI, 15.27-481.70]; 7.0-7.9 log(10) copies/mL: AOR, 45.62 [95% CI, 8.41-247.51]; 5.0-6.9 log(10) copies/mL: AOR, 9.07 [95% CI, 1.85-44.33]: reference, <5 log(10) viral copies/mL), and caesarean delivery (AOR, 0.26 [95% CI, 0.12-0.59]). CONCLUSIONS: Associations with maternal GBV-C load and mode of delivery suggest transmission during pregnancy and delivery. Despite mode of delivery being a common risk factor for virus transmission, GBV-C and HIV were rarely cotransmitted. The mechanisms by which maternal receipt of antiretroviral therapy might increase MTCT of GBV-C are unknown.
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Infecciones por Flaviviridae/transmisión , Virus GB-C , Infecciones por VIH/complicaciones , VIH , Hepatitis Viral Humana/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Adulto , Estudios de Cohortes , Femenino , Infecciones por Flaviviridae/complicaciones , Infecciones por Flaviviridae/virología , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/virología , Humanos , Recién Nacido , Embarazo , ARN Viral/sangre , Tailandia/epidemiología , Adulto JovenRESUMEN
Molecular methods for HIV-1 infection using dried blood-spot (DBS) for HIV-1 CRF01_AE subtypes have not been fully optimized. In this study assays for HIV-1 diagnosis or quantitation were evaluated using infant DBS from Thailand. Paired DBS and whole blood samples from 56 HIV-1 CRF01_AE or B'-infected infants were tested for infant diagnosis using modified Amplicor DNA PCR and NucliSens RNA NASBA and an in-house real-time PCR assay. The Amplicor Monitor viral load (VL) assay, with modifications for DBS, was also evaluated. DBS VL were hematocrit corrected. Stability studies were done on DBS stored at -70 degrees C to 37 degrees C for up to 1 year. The DBS diagnostic assays were 96-100% sensitive and 100% specific for HIV-1 diagnosis. DBS HIV-1 VL were highly correlated with plasma VL when corrected using the actual or an assumed hematocrit factor (r(c)=0.88 or 0.93, respectively). HIV-1 DNA in DBS appeared to be more stable than RNA and could be detected after up to 9 months at most temperatures. DBS VL could be consistently determined when stored frozen. These results show that DBS can be used accurately instead of whole blood for the diagnosis of HIV-1 infection and VL quantitation, particularly if samples are appropriately stored.
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Recolección de Muestras de Sangre/métodos , ADN Viral/sangre , Infecciones por VIH/diagnóstico , VIH-1/aislamiento & purificación , ARN Viral/sangre , Carga Viral , Adulto , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , VIH-1/fisiología , Humanos , Lactante , Reacción en Cadena de la Polimerasa/métodos , Juego de Reactivos para Diagnóstico , Replicación de Secuencia Autosostenida , Sensibilidad y Especificidad , Manejo de Especímenes , TailandiaRESUMEN
Similar to other mycobacterial diseases, susceptibility to Buruli ulcer (Mycobacterium ulcerans infection) may be determined by host genetic factors. We investigated the role of SLC11A1 (NRAMP1) in Buruli ulcer because of its associations with both tuberculosis and leprosy. We enrolled 182 Buruli ulcer patients (102 with positive laboratory confirmation) and 191 healthy neighbourhood-matched controls in Ghana, and studied three polymorphisms in the SLC11A1 gene: 3' UTR TGTG ins/del, D543N G/A, and INT4 G/C. Finger prick blood samples from study subjects were dried on filter papers (FTA) and processed. D543N was significantly associated with Buruli ulcer: the odds ratio (adjusted for gender, age, and region of the participant) of the GA genotype versus the GG genotype was 2.89 (95% confidence intervals (CI): 1.41-5.91). We conclude that a genetic polymorphism in the SLC11A1 gene plays a role in susceptibility to develop Buruli ulcer, with an estimated 13% population attributable risk.
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Proteínas de Transporte de Catión/genética , Predisposición Genética a la Enfermedad , Infecciones por Mycobacterium no Tuberculosas/genética , Mycobacterium ulcerans , Úlcera Cutánea/genética , Úlcera Cutánea/microbiología , Adolescente , Adulto , Sustitución de Aminoácidos , Asparagina/química , Asparagina/genética , Ácido Aspártico/química , Ácido Aspártico/genética , Niño , Femenino , Frecuencia de los Genes , Humanos , Masculino , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Polimorfismo GenéticoRESUMEN
Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.
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Dengue/diagnóstico , Leptospirosis/diagnóstico , Vigilancia de la Población/métodos , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Dengue/etiología , Diagnóstico Diferencial , Femenino , Humanos , Incidencia , Lactante , Leptospirosis/etiología , Leptospirosis/mortalidad , Masculino , Registros Médicos , Persona de Mediana Edad , Puerto Rico/epidemiología , Factores de RiesgoRESUMEN
Leptospirosis is a zoonosis that can cause severe multisystem disease. While host gene-environment interactions likely modify infectious disease susceptibility, including for leptopsirosis, this has not been documented. In a 1998 leptospirosis outbreak investigation among triathletes in a lake swim, swallowing lake-water was a disease risk-factor. We used genomic DNA from 85 anonymized blood-sample remainders from that investigation to examine the association of laboratory-confirmed leptospirosis with gene polymorphisms (TNF-alpha alleles and serologically defined genotypes for HLA-DRB1 and HLA-DQB1). HLA-DQ6-positive triathletes had increased risk of laboratory-confirmed leptospirosis (OR=2.8, P=0.04) compared to DQ6-negatives. DQ6-positive triathletes swallowing lake-water had greatest risk (OR 8.46, P< or =0.001). This first report of a genetic risk-factor affecting susceptibility to leptospirosis is also the first documented gene-environment interaction (DQ6 and swallowed water) affecting infectious disease susceptibility. Based on these preliminary findings, we hypothesize a role for superantigens in leptospirosis and underscore the importance of outbreak investigations for understanding infectious disease gene-environment interactions.
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Brotes de Enfermedades , Antígenos HLA-DQ/genética , Leptospira/aislamiento & purificación , Leptospirosis/epidemiología , Leptospirosis/genética , Microbiología del Agua , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Cohortes , ADN/sangre , ADN/genética , Ambiente , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-DQ/metabolismo , Cadenas beta de HLA-DQ , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Cadenas HLA-DRB1 , Humanos , Leptospirosis/microbiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Abastecimiento de AguaRESUMEN
SETTING: In countries with high HIV rates, diagnosis of lower respiratory disease etiology is both challenging and clinically important. OBJECTIVE: To determine the etiology of lower respiratory tract disease among persons with suspected tuberculosis (TB) and abnormal chest X-rays in a setting with very high HIV seroprevalence. DESIGN: Cross-sectional prevalence data from a prospective cohort of predominantly hospitalized adults with suspected TB in Botswana, January-December 1997. RESULTS: Of 229 patients, 86% were HIV-positive and 71% had a pathogen identified. TB was confirmed in 52%, 17% had acute mycoplasma pneumonia, 3% had Pneumocystis carinii, 27% grew a bacterial pathogen from sputum and 8% from blood. Ninety-four per cent of TB diagnoses were made through expectorated sputum and only 5% of TB cases were diagnosed by sputum induction alone. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis had positive and negative predictive values of 94% and 59%, respectively. Male sex, cough < 2 weeks, and tuberculin skin test > or = 5 mm were independently associated with culture-positive TB among persons with negative acid-fast bacilli smears. Co-infection with two or more pathogens occurred in 25%. CONCLUSIONS: Mycoplasma pneumoniae infection was quite common despite clinical suspicion of TB, and sputum induction and PCR did not significantly improve our ability to diagnose TB, although clinical presentation had some predictive value.
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Infecciones por VIH/complicaciones , VIH-1 , Neumonía por Mycoplasma/etiología , Tuberculosis Pulmonar/complicaciones , Adulto , Antibióticos Antituberculosos/uso terapéutico , Botswana , Estudios Transversales , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Neumonía por Mycoplasma/diagnóstico , Neumonía por Mycoplasma/tratamiento farmacológico , Reacción en Cadena de la Polimerasa , Prevalencia , Esputo/microbiología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
SETTING: A provincial referral hospital in northern Thailand, where a cross-sectional study from 1995-1996 reported on the occupational risk of Mycobacterium tuberculosis transmission. OBJECTIVE: To assess the impact of acid-fast bacilli sputum smear-positive results notification to improve tuberculosis (TB) services by documenting the location of sputum collection, completing the TB register immediately, and minimising delays between hospital admission and treatment initiation. DESIGN: The cohort of smear-positive TB patients identified through laboratory microscopy record reviews from 1994-1999. Time from admission to hospital, laboratory diagnosis of TB, registration for treatment, and initiation of therapy were determined during the implementation of enhancing the laboratory results notification system. RESULTS: The number of unregistered TB patients fell from 44 cases in 1994 to none in 1999. The time elapsed from admission to treatment initiation decreased from a mean of 5.6 days in 1997 (n = 162) to 3.1 days in 1999 (n = 136) (P < 0.001). This decrease was attributed to a reduction in time between laboratory diagnosis and treatment from 2.7 days in 1997 to 0.6 days in 1999 (P < 0.001). CONCLUSION: Prompt identification, isolation and treatment of TB patients occurred through an enhanced laboratory notification system. Such systems are inexpensive, improve TB care services and may reduce nosocomial transmission of M. tuberculosis.
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Notificación de Enfermedades , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Humanos , Laboratorios de Hospital , Tailandia , Factores de Tiempo , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/transmisiónRESUMEN
SETTING: A provincial referral hospital in northern Thailand, where a cross-sectional study during 1995-1996 reported on the occupational risk of Mycobacterium tuberculosis transmission. OBJECTIVE: To describe the effectiveness of prevention strategies for nosocomial tuberculosis (TB). DESIGN: A prospective study among health care workers (HCW) including annual tuberculin skin test (TST) screening and active TB surveillance. Following a comprehensive risk assessment, preventive interventions were implemented targeting HCWs, hospitalised patients, and the hospital environment. RESULTS: The number of pulmonary TB cases diagnosed increased steadily from 102 in 1990 to 356 in 1999. The TST conversion rate was 9.3 (95% CI 3.3-15) per 100 person-years (py) in 1995-1997, but declined steadily to 2.2 (95% CI 0.0-5.1) in 1999. HCWs first screened within 12 months of employment had higher TST conversion rates (adjusted RR = 9.5, 95% CI 1.8-49.5) compared to those employed for longer than 12 months. The annual rate of active TB per 100 000 HCWs was 536 in 1995-1999. CONCLUSION: These HCWs were exposed to active TB patients and were at risk for M. tuberculosis infection, particularly during their first 12 months of employment. Implementation of nosocomial TB control measures in 1996 was followed by declining TST conversion rates, despite increasing exposure to active TB patients.
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Infección Hospitalaria/epidemiología , Enfermedades Profesionales/epidemiología , Tuberculosis Pulmonar/epidemiología , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Personal de Hospital , Estudios Prospectivos , Factores de Riesgo , Tailandia/epidemiologíaRESUMEN
OBJECTIVE: To identify risk factors for transmission of Mycobacterium tuberculosis from patients with tuberculosis and human immunodeficiency virus (HIV) infection in Botswana. DESIGN: Transmission was studied in 210 children aged <10 years (contacts) of unknown HIV status exposed to 51 adults with tuberculosis (index cases), including 41/49 (83.7%) with HIV infection. METHODS: Data collected on index cases included demographics, clinical and social characteristics, sputum, HIV, and CD4 lymphocyte results. Tuberculin skin testing was performed on contacts, and their parent or guardian was interviewed. A positive test was defined as > or = 10 mm induration. Skin test results were compared with results obtained from a population survey of children of similar age from the same community. RESULTS: A positive skin test was found in 12.1% of exposed children compared with 6.2% in the community (P = 0.005). Of the infected children, 22 (78.6%) were contacts of a close female relative. The risk of transmission increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases (10.8% if smear 0+, 9.3% if smear 1+,29.4% if smear 2+, 44% if smear 3+, P < 0.001). In multivariate analysis, severe immunodeficiency (CD4 lymphocyte count <200 cells/mm3) among HIV-infected index cases was protective against transmission (OR 0.08, 95%CI 0.01-0.5, P = 0.006). CONCLUSION: The intensity of exposure to tuberculosis patients and the degree of sputum smear positivity for acid-fast bacilli remain important risk factors for transmission of M. tuberculosis during the era of HIV. However, tuberculosis patients with advanced AIDS may be less infectious than patients in earlier stages of AIDS.
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Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/complicaciones , Tuberculosis/transmisión , Adolescente , Adulto , Botswana , Recuento de Linfocito CD4 , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tuberculosis/inmunologíaRESUMEN
BACKGROUND: Little is known about causes of death in countries of southern Africa seriously affected by the HIV/AIDS epidemic. METHODS: After obtaining informed consent, autopsies were performed on 128 mainly hospitalised adults in Francistown, Botswana, between July 1997 and June 1998. Criteria for case selection included those who died before a diagnosis could be established, those whose condition deteriorated unexpectedly during hospitalization, and those who had respiratory disease. This represented 14% of adult medical patients who died in hospital during the study period. RESULTS: Of the 128 patients, 104 (81%) were HIV-positive. Among HIV-positive patients, the most common pathologic findings were tuberculosis (TB) (40%), bacterial pneumonia (23%), Pneumocystis carinii pneumonia (11%), and Kaposi's sarcoma (11%); these conditions were the cause of death in 38%, 14%, 11%, and 6%, respectively. Of the 40 pulmonary TB cases, 90% also had disseminated extra-pulmonary TB. Chest radiology could not reliably distinguish the pathologies pre-mortem. CONCLUSIONS: TB was the leading cause of death in our series of HIV-positive adults in Botswana, selected towards those with chest disease; in most, it was widely disseminated. Bacterial pneumonia also played an important role in mortality. Pneumocystis carinii pneumonia was present, but relatively uncommon.
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Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Infecciones Oportunistas Relacionadas con el SIDA/patología , Causas de Muerte , Infecciones por VIH/mortalidad , Infecciones por VIH/patología , Tuberculosis Pulmonar/mortalidad , Tuberculosis Pulmonar/patología , Adolescente , Adulto , Autopsia , Botswana/epidemiología , Distribución de Chi-Cuadrado , Femenino , Humanos , Inmunohistoquímica , Masculino , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Estadísticas no ParamétricasRESUMEN
Leptospirosis, a disease acquired by exposure to contaminated water, is characterized by fever accompanied by various symptoms, including abdominal pain. An acute febrile illness occurred in athletes who participated in an Illinois triathlon in which the swimming event took place in a freshwater lake. Of 876 athletes, 120 sought medical care and 22 were hospitalized. Two of the athletes had their gallbladders removed because of abdominal pain and clinical suspicion of acute cholecystitis. We applied an immunohistochemical test for leptospirosis to these gallbladders and demonstrated bacterial antigens staining (granular and filamentous patterns) around blood vessels of the serosa and muscle layer. Rare intact bacteria were seen in 1 case. These results show that leptospirosis can mimic the clinical symptoms of acute cholecystitis. If a cholecystectomy is performed in febrile patients with suspicious environmental or animal exposure, pathologic studies for leptospirosis on formalin-fixed, paraffin-embedded tissues may be of great value.
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Colecistitis/diagnóstico , Fiebre de Origen Desconocido/diagnóstico , Leptospirosis/diagnóstico , Enfermedad Aguda , Adulto , Antígenos Bacterianos/análisis , Colecistectomía , Colecistitis/microbiología , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Femenino , Vesícula Biliar/microbiología , Humanos , Inmunohistoquímica , Leptospira/inmunología , Leptospira/aislamiento & purificación , Leptospirosis/microbiología , Masculino , Persona de Mediana Edad , DeportesRESUMEN
Global control and prevention of meningococcal disease depends on the further development of vaccines that overcome the limitations of the current polysaccharide vaccines. Protein-polysaccharide conjugate vaccines likely will address the marginal protective antibody responses and short duration of immunity in young children derived from the A, C, Y, and W-135 capsular polysaccharides, but they will be expensive to produce and purchase, and may not offer a practical solution to the countries with greatest need. In addition, OMP vaccines have been tested extensively in humans and hold some promise in the development of a serogroup B vaccine, but are limited by the antigenic variability of these subcapsular antigens and the resulting strain-specific protection. Elimination of meningococcal disease likely will require a novel approach to vaccine development, ideally incorporating a safe and effective antigen or antigens common to all meningoccocal serogroups. As a solely human pathogen, however, N. meningitidis has developed many tools with which to evade the human immune system, and likely will pose a formidable challenge for years to come.
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Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas , Vacunación , Adolescente , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Ensayos Clínicos como Asunto , Humanos , Infecciones Meningocócicas/microbiología , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/inmunología , Neisseria meningitidis/inmunología , Factores de Riesgo , EstudiantesRESUMEN
Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.
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Epidemiología Molecular , Mycobacterium tuberculosis/genética , Vigilancia de la Población , Tuberculosis Pulmonar/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adulto , Botswana/epidemiología , Dermatoglifia del ADN/métodos , Elementos Transponibles de ADN , Femenino , Humanos , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Estudios Prospectivos , Tuberculosis Pulmonar/microbiologíaRESUMEN
Little is known about the clinical outcomes of patients with primary multidrug-resistant (MDR) tuberculosis. Clinical outcomes among 46 patients in Estonia with primary MDR tuberculosis and 46 patients with pansusceptible tuberculosis were compared. Patients with MDR tuberculosis were more likely than those with pansensitive tuberculosis to have treatment failure (odds ratio, 8.9; 95% confidence interval [CI], 3.0-26.3) after adjusting for medical problems and weeks of effective treatment, often with second-line drugs. Ten patients (22%) with MDR tuberculosis and 2 (4%) with susceptible tuberculosis died of tuberculosis (P=.03). MDR tuberculosis (hazard ratio [HR], 7.8; 95% CI, 1.6-37.4), number of medical problems (HR, 2.5; 95% CI, 1.5-4.4), and male sex (HR, 5.8; 95% CI, 1.1-29.6) were associated with death due to tuberculosis in multivariable analysis. Human immunodeficiency virus test results were negative for all 55 patients tested. These findings underscore the urgent need for increased attention to prevention and treatment of MDR tuberculosis globally.
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Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Adulto , Antituberculosos/farmacología , Estudios de Cohortes , Farmacorresistencia Bacteriana Múltiple , Estonia/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Entrevistas como Asunto , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Oportunidad Relativa , Sistema de Registros , Estudios Retrospectivos , Factores Sexuales , Esputo/microbiología , Factores de Tiempo , Insuficiencia del Tratamiento , Tuberculosis/epidemiología , Tuberculosis/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaRESUMEN
The porin proteins of Neisseria meningitidis are important components of outer membrane protein (OMP) vaccines. The class 3 porin gene, porB, of a novel serogroup B, serotype 4, 15 isolate from Chile (Ch501) was found to be VR1-4, VR2-15, VR3-15 and VR4-15 by porB variable region (VR) typing. Rabbit immunization studies using outer membrane vesicles revealed immunodominance of individual PorB (class 3) VR epitopes. The predominant anti-Ch501 PorB response was directed to the VR1 epitope. Anti-PorB VR1 mediated killing was suggested by the bactericidal activity of Ch501 anti-sera against a type 4 strain not expressing PorA or class 5 OMPs. Studies that examine the molecular epidemiology of individual porB VRs, and the immune responses to PorB epitopes, may contribute to the development of broadly protective group B meningococcal vaccines.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/inmunología , Neisseria meningitidis/inmunología , Porinas , Animales , Anticuerpos Monoclonales , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/aislamiento & purificación , Secuencia de Bases , Western Blotting , Epítopos , Femenino , Datos de Secuencia Molecular , Neisseria meningitidis/genética , Reacción en Cadena de la Polimerasa , Conejos , Alineación de Secuencia , Análisis de Secuencia de ADN , Serotipificación , VacunaciónRESUMEN
SETTING: Gaborone, the capital of Botswana. OBJECTIVE: To determine the time from positive sputum smear microscopy for acid-fast bacilli (AFB) to initiation of therapy, and to identify risk factors for delays. DESIGN: Retrospective cohort study of medical records and surveillance data for patients with positive smear microscopy and newly diagnosed tuberculosis (TB) from January to May 1997. Treatment delay was defined as more than 2 weeks from the first positive sputum smear to the initiation of TB treatment. RESULTS: Of 127 patients identified, 15 (11.8%) had treatment delay, 13 (10.2%) had an incomplete workup (only one smear performed) and were not registered for TB treatment, and six (4.5%) had two or more positive smears but were not registered for TB treatment. Risk factors for treatment delay or non-registration included TB patients who had been diagnosed in a hospital outpatient setting vs. a clinic (RR 2.9, 95% CI 1.2-3.6, P = 0.02), or in a high volume vs. low volume clinic (RR 2.2, 95% CI 1.2-5.3, P = 0.01). CONCLUSION: More than a quarter of the smear-positive TB patients identified had treatment delay or no evidence of treatment initiation. Proper monitoring of laboratory sputum results and suspect TB patient registers could potentially reduce treatment delays and patient loss.
Asunto(s)
Antituberculosos/administración & dosificación , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Antituberculosos/uso terapéutico , Botswana , Esquema de Medicación , Femenino , Humanos , Masculino , Cooperación del Paciente , Factores de Riesgo , Pruebas Serológicas , Factores de Tiempo , Tuberculosis Pulmonar/diagnóstico , Listas de EsperaRESUMEN
DNA fingerprinting may be useful to elucidate tuberculosis (TB) transmission in community settings, but its utility is limited if only few fingerprint patterns are observed or band numbers are low. We performed DNA fingerprinting on a national, population-based sample of Mycobacterium tuberculosis isolates from Botswana. During 1995-1996, a random sample of 213 isolates, representing 5% of all smear-positive TB cases, underwent DNA fingerprinting using restriction fragment length polymorphism (RFLP) IS6110 analysis. Eighty-two (38%) of the 213 isolates belonged to one of 18 clusters, with 2-9 isolates/cluster. The median number of bands was 10 (range 1-19); 183 (86%) had six or more bands. Sixty-three (49%) of 128 patients tested were infected with the human immunodeficiency virus (HIV). The degree of RFLP pattern heterogeneity and high band number support the feasibility of a prospective DNA fingerprinting study in Botswana.