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BACKGROUND: The genotyping of Mycobacterium tuberculosis strains is important to have unique insights into the dissemination dynamics and evolutionary genetics of this pathogen and for TB control as it allows the detection of suspected outbreaks and the tracing of transmission chains. OBJECTIVE: To characterize M. tuberculois isolates collected from newly diagnosed pulmonary TB patients in Addis Ababa METHODS: One hundred and ninety two sputum samples were cultured on Löwenstein-Jensen (LJ) slants and isolates were heat killed for molecular genotyping. The isolates were characterized using spoligotyping and were compared with the International SpoIDB4 database. RESULT: T genotype constitutes the most predominant in our study (95, 49.5%) followed by the CAS genotype (42, 21.9%). Other genotypes found were Haarlem (H) (24, 12.5%), the LAM (3, 1.5%), the Beijing genotype (1, 0.5%); four (2.1%) isolates were designated as Unknown. CONCLUSION: All the isolates belong to the modern lineage and there is high clustering in the genotype of isolates which indicated the presence of recent TB transmission. Therefore, the Tuberculosis Control Programme needs to do more in advocating and strengthening the health system for early detection and treatment of active TB cases as delay in treatment is the key factor in disease transmission.
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Variación Genética , Genotipo , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Tuberculosis/prevención & control , Adolescente , Adulto , Anciano , Recuento de Linfocito CD4 , Análisis por Conglomerados , Etiopía/epidemiología , Femenino , Técnicas de Genotipaje/métodos , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Factores Socioeconómicos , Esputo/microbiología , Tuberculosis/microbiología , Adulto JovenRESUMEN
SETTING: Health centres in Awassa, southern Ethiopia. DESIGN: Consecutive patients visiting health centre laboratories for the evaluation of suspected pulmonary tuberculosis (TB) between June and September 2006 were investigated. On-the-spot, morning and second on-the-spot sputum samples were pooled for each patient. Direct smears were stained with hot Ziehl-Neelsen (ZN) technique and aliquots cultured for mycobacteria on Löwenstein-Jensen media. The remaining sputum was treated with household bleach, aliquoted and processed with short-term digestion, centrifugation and sedimentation techniques, and stained with ZN. RESULTS: Acid-fast bacilli were detected in respectively 126 (25%), 141 (28%), 169 (34%) and 198 (40%) of the 497 pooled sputum samples processed by the direct, short-term, sedimentation and centrifugation techniques (P < 0.001). The sensitivity of the direct, short-term, sedimentation and centrifugation techniques was respectively 51.1%, 53.2%, 57.6% and 63.6%. The difference between the direct smear and centrifugation (P < 0.001) or sedimentation (P < 0.005) methods was significant. The specificity of the direct, short-term digestion, sedimentation and centrifugation techniques was respectively 97%, 93%, 86.5% and 80.8%. CONCLUSIONS: Bleach treatment of sputum and centrifugation significantly improves the sensitivity of smear microscopy for the diagnosis of TB in a health centre in a high TB burden area. It is more sensitive, but possibly less specific, than other bleach methods.
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Mycobacterium tuberculosis/aislamiento & purificación , Manejo de Especímenes/métodos , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Técnicas Bacteriológicas , Centrifugación , Humanos , Sensibilidad y Especificidad , Hipoclorito de Sodio , Coloración y EtiquetadoRESUMEN
Background: In Ethiopia; little has been done to assess how Mycobacterium bovis has contributed to human tuberculosis; though the population routinely consumes unpasteurized milk and raw meat. The aim of this study was to determine the proportion of M. tuberculosis and M. bovis as etiological agents of tuberculous lymphadenitis (TBLN). Methods: Patients with lymphadenopathy (n = 171) were included in a cross-sectional study at Butajira Hospital; Southern Ethiopia. Lymph node biopsies were cultured. Patients' HIV status was identified. DNA from positive cultures was tested by PCR to identify M. bovis and M. tuberculosis. Isolates were genotyped by multiplex ligation-dependent probe amplification (MLPA) assay. Results: Among 171 patients; 156 had culture results. Of these; 107 (69) were positive for M. tuberculosis complex (MTC). Six of the 10 HIV-positive patients were culture positive. M. tuberculosis specific sequences were identified in the DNA of each of 100 samples as assessed by RD10 targeted PCR; and each of the 95 isolates exhibited the M. tuberculosis specific TbD1 deletion by MLPA analysis. No M. bovis was identified. These results indicate that all the isolates were modern M. tuberculosis strains. Furthermore; MLPA studies confirmed that 42of the isolates showed the Haarlem genotype and 12displayed sequences compatible with INH resistance. No mutations conferring resistance to ethambutol or rifampicin were detected. Conclusions: Our data showed that M. tuberculosis strains had common characteristics with strains causing pulmonary TB; which appears to be the main etiological agent of TBLN
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Ganglios Linfáticos/etiología , Mycobacterium bovis , TuberculosisRESUMEN
SETTING: Butajira, Southern Ethiopia. OBJECTIVE: To compare the diagnostic capacity of the clinical criteria for tuberculous lymphadenitis (TBLN) with histological and/or culture results and to assess the association of human immunodeficiency virus (HIV) with tuberculosis (TB) lymphadenitis. DESIGN: Patients (n=171) were included in the study from October 2005 until July 2006 at Butajira Hospital. Laboratory tests were performed to confirm TBLN. HIV status was identified in TBLN patients and retrospectively in 1608 healthy individuals. RESULT: A total of 136/161 (84.5%) patients were diagnosed with TBLN by histology. TBLN was culture-confirmed in 107/156 (68.6%) patients. The sensitivity, specificity, positive and negative predictive values of histology were respectively 92.5%, 49%, 79.8% and 75% when compared to culture as gold standard. Patients positive for TBLN by cytology and Ziehl-Neelsen (ZN) were also positive by histology and culture. Among the 143 confirmed TBLN patients, nine (6.3%) were HIV-positive. Of the 1608 healthy individuals, 77 (4.8%) were HIV-positive. Younger age (P=0.0001), female sex (P=0.016), not being married (P=0.0001) and illiteracy (P=0.016) showed a strong association with HIV in healthy individuals. CONCLUSION: Clinical criteria alone over-diagnosed TBLN by 15.4% compared to histological and/or bacteriological results. The HIV prevalence in TBLN patients and healthy individuals was the same.
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Infecciones por VIH/complicaciones , Seropositividad para VIH/complicaciones , Seroprevalencia de VIH , Tuberculosis Ganglionar/diagnóstico , Adolescente , Adulto , Anciano , Biopsia , Medios de Cultivo , Etiopía/epidemiología , Femenino , VIH , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Población Rural , Sensibilidad y Especificidad , Tuberculosis Ganglionar/epidemiología , Tuberculosis Ganglionar/patología , Tuberculosis Ganglionar/virologíaRESUMEN
SETTING: Private clinics and hospitals in Addis Ababa, Ethiopia. OBJECTIVES: To assess the knowledge of private practitioners (PPs) with regard to tuberculosis (TB) control and their practice of TB diagnosis, treatment and monitoring. DESIGN: A descriptive survey was conducted among PPs. A total of 120 responded to a self-administered questionnaire. RESULTS: According to 81.5% of the PPs, at least two to five TB cases were diagnosed in their clinic per week. The correct anti-tuberculosis treatment regimens recommended by the National Tuberculosis Programme (NTP) were mentioned by only 9.7% of the doctors, while 63% listed 68 regimens. The majority (41.0%) monitored treatment using chest X-ray (CXR) alone, while 21.0% use CXR in combination with another diagnostic tool. Eighty per cent of the PPs did not keep a TB register, and case holding was non-existent. CONCLUSIONS: PPs in Addis Ababa diagnose a high number of TB cases. However, there is a huge lack of information on anti-tuberculosis treatment. This shows the likely irrational use of the few available anti-tuberculosis drugs, which may favour the emergence and spread of drug resistance.
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Competencia Clínica , Pautas de la Práctica en Medicina , Tuberculosis/diagnóstico , Tuberculosis/prevención & control , Adulto , Anciano , Etiopía , Femenino , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Práctica Privada , Tuberculosis/tratamiento farmacológicoRESUMEN
Two randomized, double-blind, placebo-controlled trials, in which levamisole (2.5 mg/kg) was given alone or co-administered with ivermectin (200 microg/kg) or albendazole (400 mg), were conducted. In Trial 1, safety and drug-drug interaction were explored in 42 healthy male volunteers. During Trial 2, the safety of the same treatment regimens and their efficacy against the adult worms and microfilariae of Onchocerca volvulus were investigated in 66 infected subjects of both sexes. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. The pharmacokinetic parameters for levamisole alone and the combinations were determined in Trial 1 and then compared with historical data for ivermectin and albendazole, given as single agents, to determine if drug-drug interaction had occurred. The level of efficacy against the adult worms was determined by the examination of histology sections of nodules excised 6 months posttreatment and from the changes seen in the levels of microfilaridermia within a year of treatment. Microfilaricidal efficacy was estimated from the reductions in the levels of microfilaridermia between day 0 (1 day pre-treatment) and day 30. Although the regimens were generally well tolerated, there were unexpected adverse effects in both healthy volunteers and infected subjects. Clinically significant drug-drug interactions resulted in an increase in the bio-availability of ivermectin but a reduction in that of albendazole when these drugs were co-administered with levamisole. Levamisole given alone or with albendazole had little effect on O. volvulus. The combination of levamisole with ivermectin was neither macrofilaricidal nor more effective against the microfilariae and the adult worms than ivermectin alone. The pathogenesis of the adverse events and the drug-drug interactions are discussed.
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Albendazol/efectos adversos , Antinematodos/efectos adversos , Ivermectina/efectos adversos , Levamisol/efectos adversos , Oncocercosis/tratamiento farmacológico , Adolescente , Adulto , Albendazol/farmacocinética , Albendazol/uso terapéutico , Animales , Anticestodos/efectos adversos , Anticestodos/farmacocinética , Anticestodos/uso terapéutico , Antinematodos/farmacocinética , Antinematodos/uso terapéutico , Método Doble Ciego , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Humanos , Ivermectina/farmacocinética , Ivermectina/uso terapéutico , Levamisol/farmacocinética , Levamisol/uso terapéutico , Masculino , Microfilarias/efectos de los fármacos , Persona de Mediana Edad , Onchocerca volvulus/efectos de los fármacos , Resultado del TratamientoRESUMEN
Having established previously that prematurity in The Gambia is associated with impaired maternofetal transfer of some specific antibodies, we investigated the influence of low birthweight and prematurity on placental transfer of IgG subclasses in 180 Gambian mothers and their newborn babies. A physician-blinded, cross-sectional study of 180 mother-baby pairs was carried out in the labour ward of Bansang Hospital, The Gambia. Paired maternal and cord serum samples were collected from mothers and their newborns. Serum IgG subclass levels were measured by laser nephelometry. Placental transfer of all IgG subclasses was significantly reduced in preterm newborns compared with term newborns (p < 0.01). In low birthweight (LBW) babies, the transfer of IgG1 (p = 0.03) and IgG2 (p < 0.01) subclasses, but not IgG3 and IgG4, was significantly reduced. In preterm neonates with an adequate birthweight and term neonates with a low birthweight, all IgG subclasses were transferred with reduced efficiency, but IgG1 and IgG2 subclasses were transferred with significantly less efficiency than IgG3 and IgG4. These results confirm that prematurity and low birthweight are associated with impaired placental transfer of IgG1 and IgG2 subclasses in this Gambian population. This impairment might explain the susceptibility of these newborns to certain polysaccharide-encapsulated organisms.
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Inmunoglobulina G/sangre , Recién Nacido de Bajo Peso/sangre , Recien Nacido Prematuro/sangre , Intercambio Materno-Fetal/inmunología , Adolescente , Adulto , Estudios Transversales , Femenino , Sangre Fetal/inmunología , Gambia , Humanos , Inmunoglobulina G/inmunología , Recién Nacido de Bajo Peso/inmunología , Recién Nacido , Recien Nacido Prematuro/inmunología , Masculino , Persona de Mediana Edad , EmbarazoRESUMEN
BACKGROUND: RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. METHODS: 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol. FINDINGS: 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037). INTERPRETATION: RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.
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Vacunas contra la Malaria/administración & dosificación , Malaria Falciparum/prevención & control , Plasmodium falciparum/inmunología , Proteínas Recombinantes , Vacunas Sintéticas/administración & dosificación , Adulto , Animales , Anticuerpos Antiprotozoarios/análisis , Gambia/epidemiología , Humanos , Inmunización , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Masculino , Modelos de Riesgos Proporcionales , Proteínas Protozoarias , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare the survival of children born to HIV-1 or HIV-2 seropositive mothers with that of children born to HIV-seronegative mothers and to evaluate risk factors for mortality. DESIGN: Physician-blinded prospective study. METHODS: One hundred and one HIV-1-seropositive, 243 HIV-2-seropositive pregnant women, and 468 HIV-seronegative women (control group) matched by age, parity, and health centre, were followed up in a study of mother-to-child transmission of HIV. Mothers and children were seen at 2 and 6 months of age and subsequently followed at 3-monthly intervals up to 18 months of age. HIV infection in children was diagnosed by polymerase chain reaction at 2, 9 or 18 months and by antibody assays at 18 months. RESULTS: Fifteen per cent of children born to HIV-1-infected mothers died compared with 7% of children born to HIV-2-infected mothers [hazard ratio, 2.3; 95% confidence interval (CI), 1.1-4.7; P = 0.02], and 6% of HIV-seronegative mothers (hazard ratio, 2.6; 95% CI, 1.4-5.0; P = 0.003). Six of the 17 children known to be HIV-1 infected died compared with none among the eight HIV-2-infected children (P = 0.13). High proviral load in the babies, high antenatal maternal RNA plasma viral load, and maternal death increased child mortality significantly. CONCLUSIONS: More children born to HIV-1-infected mothers died in comparison with those born to HIV-2-infected mothers or to mothers from the control group. This effect was due to excess death in HIV-1-infected infants which was associated with a high viral load in the affected mother and child.
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Infecciones por VIH/mortalidad , VIH-1/aislamiento & purificación , VIH-2/aislamiento & purificación , Complicaciones Infecciosas del Embarazo , Tasa de Supervivencia , Femenino , Gambia/epidemiología , Infecciones por VIH/transmisión , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Madres , Evaluación de Resultado en la Atención de Salud , Embarazo , Resultado del Embarazo , Carga ViralRESUMEN
OBJECTIVES: To determine the rates of, and risk factors for, mother-to-child transmission (MCT) of HIV-1 and HIV-2 infection in The Gambia. DESIGN: A blinded, prospective, community-based cohort study of 29.549 pregnant women attending the eight largest antenatal clinics in The Gambia. METHODS: Women were tested for HIV-1 and HIV-2 infection. Infected subjects and a group of HIV-seronegative women were followed with their babies until 18 months after delivery. Maternal CD4 cell count percentages were measured before and 18 months after delivery, and the antenatal plasma viral load was determined. Babies were tested for HIV by the polymerase chain reaction and/or serology at 2, 9 and 18 months of age. RESULTS: The study enrolled 144 women positive for HIV-1 and 294 for HIV-2 plus 565 seronegative pregnant women: the mean antenatal percentage CD4 cell counts of 96 HIV-1-positive, 223 HIV-2-positive and 125 HIV-seronegative mothers were 31% [95% confidence interval (CI) 28-33], 41% (95% CI 39-42) and 47% (95% CI 45-49), respectively. The geometric mean antenatal plasma viral load of 94 HIV-1-infected women was 15,100 copies x 10(3) ml (95% CI 10,400-19,000) which was much higher than that of 60 randomly selected HIV-2-infected women, which was 410 copies x 10(3) ml (95% CI 150-910) (P < 0.001). The estimated transmission rate of HIV-1 was 24.4% (95% CI 14.6-33.9) and that of HIV-2 was 4.0% (95% CI 1.9-7.4). Five of 17 HIV-1-positive and three of eight HIV-2-positive babies were infected after 2 months of age. Birth in the rainy season [odds ratio (OR) 2.9; 95% CI 1.2-7.2], a low postnatal CD4 cell percentage (OR for a 10% fall 2.4; 95% CI 1.1-5.1) and a high maternal plasma viral load (OR for a 10-fold increase 2.9; 95% CI 1.1-7.8) were risk factors for transmission that applied equally to both viruses. CONCLUSION: Low maternal HIV-2 RNA levels, which on average are 37-fold less than in HIV-1 infection, relate to the low MCT rate of HIV-2.