RESUMO
BACKGROUND: Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. METHODS: We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. RESULTS: Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2-53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17-0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17-50.60]; P = .004). CONCLUSIONS: Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease.
Assuntos
Antituberculosos/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Peru , Estudos Retrospectivos , Prevenção Secundária , Escarro/microbiologia , Fatores de Tempo , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto JovemRESUMO
BACKGROUND: The tuberculosis burden in children exposed at home to multidrug-resistant tuberculosis (MDR-TB) is unquantified. With limited access to MDR-TB treatment, likely millions of children share the experience of chronic exposure to an infectious patient. METHODS: We conducted a retrospective cohort study of child and adult household contacts of patients treated for MDR-TB in Lima, Peru, in 1996 to 2003. The primary outcome was TB disease. We estimated prevalence of TB disease when the index case began MDR-TB treatment and incidence of TB disease over the subsequent 4 years. RESULTS: Among 1299 child contacts, 67 were treated for TB. TB prevalence was 1771 (confidence interval [CI]: 1052-2489) per 100,000 children. In 4362 child-years of follow-up, TB incidence rates per 100,000 child-years were: 2079 (CI: 1302-2855) in year 1; 315 (CI: 6-624) in year 2; 634 (CI: 195-1072) in year 3; and 530 (CI: 66-994) in year 4. TB disease rates in children aged >1 year were not significantly different from those observed in adults. Children accounted for 20% of TB cases. Seven (87.5%) of 8 children tested had MDR-TB. Child contacts had TB disease rates approximately 30 times higher than children in the general population. CONCLUSIONS: Children were at high risk for TB disease when the index case started MDR-TB treatment and during the following year. These results highlight the need for implementing contact investigations and establishing systems for prompt referral and treatment of pediatric household contacts of MDR-TB patients, regardless of the age of the child.
Assuntos
Exposição Ambiental/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Busca de Comunicante , Farmacorresistência Bacteriana Múltipla , Características da Família , Feminino , Genótipo , Humanos , Incidência , Lactente , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Peru/epidemiologia , Prevalência , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
BACKGROUND: Partners In Health (PIH) works with the Ministry of Health to provide comprehensive health services in Haiti. Between 1994 and 2009, PIH recommended exclusive formula feeding in the prevention of mother-to-child transmission (PMTCT) of HIV program and provided support to implement this strategy. We conducted this study to assess HIV-free survival and prevalence of diarrhea and malnutrition among infants in our PMTCT program in rural Haiti where exclusive formula feeding was supported. METHODS: We reviewed medical charts of PMTCT mother-infant pairs at PIH between November 2004 and August 2006 through a retrospective longitudinal study and cross-sectional survey. We performed household surveys for each pair and at control households matched by infant's age and gender. RESULTS: 254 mother-infant pairs were included. 15.3% of infants were low birth weight; most births occurred at home (68.8%). 55.9% of households had no latrine; food insecurity was high (mean score of 18; scale 0-27, SD = 5.3). HIV-free survival at 18 months was 90.6%. Within the cohort, 9 children (3.5%) were HIV-infected and 17 (6.7%) died. Community controls were more likely to be breastfed (P = 0.003) and more likely to introduce food early (P = 0.003) than PMTCT-program households. There was no difference in moderate malnutrition (Z score ≤ 2 SD) between PMTCT and community groups after controlling for guardian's education, marital status, and food insecurity (OR = 1.05; 95% CI: 0.67, 1.64; P = 0.84). Diarrhea was 2.9 times more prevalent among community children than PMTCT infants (30.3% vs. 12.2%; P < 0.0001). CONCLUSIONS: In a PIH-supported program in rural Haiti that addressed socioeconomic barriers to ill-health, breast milk substitution was safe, acceptable and feasible for PMTCT for HIV-infected women choosing this option.
RESUMO
BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis have emerged as major global health threats. WHO recommends contact investigation in close contacts of patients with MDR and XDR tuberculosis. We aimed to assess the burden of tuberculosis disease in household contacts of such patients. METHODS: We undertook a retrospective cohort study of household contacts of patients treated for MDR or XDR tuberculosis in Lima, Peru, in 1996-2003. The primary outcome was active tuberculosis in household contacts at the time the index patient began MDR tuberculosis treatment and during the 4-year follow-up. We examined whether the occurrence of active tuberculosis in the household contacts differed by resistance pattern of the index patient: either MDR or XDR tuberculosis. FINDINGS: 693 households of index patients with MDR tuberculosis were enrolled in the study. In 48 households, the Mycobacterium tuberculosis isolate from the index patient was XDR. Of the 4503 household contacts, 117 (2·60%) had active tuberculosis at the time the index patient began MDR tuberculosis treatment-there was no difference in prevalence between XDR and MDR tuberculosis households. During the 4-year follow-up, 242 contacts developed active tuberculosis-the frequency of active tuberculosis was nearly two times higher in contacts of patients with XDR tuberculosis than it was in contacts of patients with MDR tuberculosis (hazard ratio 1·88, 95% CI 1·10-3·21). In the 359 contacts with active tuberculosis, 142 (40%) had had isolates tested for resistance against first-line drugs, of whom 129 (90·9%, 95% CI 85·0-94·6) had MDR tuberculosis. INTERPRETATION: In view of the high risk of disease recorded in household contacts of patients with MDR or XDR tuberculosis, tuberculosis programmes should implement systematic household contact investigations for all patients identified as having MDR or XDR tuberculosis. If shown to have active tuberculosis, these household contacts should be suspected as having MDR tuberculosis until proven otherwise. FUNDING: The Charles H Hood Foundation, the David Rockefeller Center for Latin American Studies at Harvard University, and the Bill & Melinda Gates Foundation.
Assuntos
Busca de Comunicante , Efeitos Psicossociais da Doença , Características da Família , Vigilância da População , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Criança , Estudos de Coortes , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Feminino , Humanos , Controle de Infecções/métodos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Peru/epidemiologia , Vigilância da População/métodos , Prevalência , Estudos Retrospectivos , Adulto JovemRESUMO
We estimated the proportion of recurrence within 2 years among adults cured by individualized multidrug-resistant tuberculosis regimens in Peru. Among 310 individuals with at least 24 months of follow-up, 16 experienced an episode of recurrent tuberculosis. If we assume the worst for treatment effectiveness-that all 16 episodes were caused by the original tuberculosis strain-then 5.2% (95% confidence interval, 3.0%-8.2%) experienced true relapse. This is an upper-bound estimate of relapse on which new regimens must improve.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Antituberculosos/uso terapêutico , Seguimentos , Humanos , Peru/epidemiologia , RecidivaRESUMO
BACKGROUND: Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS: A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS: Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS: Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis.