Tuberculosis recurrence after completion treatment in a European city: reinfection or relapse?

BACKGROUND: Tuberculosis (TB) recurrence can be due to reinfection or relapse. The contribution of each to TB incidence and the factors associated with recurrence are not well known. Effectiveness of TB control programs is assessed in part by recurrence rates. The aim of this study was to establish the recurrence rate of TB in Barcelona, the associated risk factors and the role of reinfection. METHODS: A population-based retrospective longitudinal study was performed in Barcelona, Spain. TB patients with positive culture results who completed treatment between Jan 1(st), 2003 and Dec 31(st), 2006 were followed-up until December 31st, 2009 by the TB Control Program. The incidence rate of recurrence was calculated per person-year of follow-up (py). Kaplan-Meier and Cox regression methods were used for the survival analysis by calculating the hazard ratio (HR) with 95% confidence intervals (CI). RESULTS: Of the 1,823 TB cases identified, 971 fulfilled the inclusion criteria and 13 (1.3%) had recurrent TB. The recurrence rate was 341 cases per 100,000 py, 13 times higher than the TB incidence of the general population. Likelihood of TB recurrence at the 1st, 3rd and 5th year of follow-up was 0.1%, 1.4% and 1.6%, respectively. Factors associated with recurrence were HIV infection (HR: 4.7, CI: 1.4-15.7), living in the inner city district (HR: 3.9, CI: 1.3-11.8) and history of TB treatment (HR: 5.2, CI: 1.7-16.2). Genotyping results of recurrent cases were available for 6 patients (3 reinfections and 3 relapses). CONCLUSION: The rate of TB recurrence in Barcelona is low and most episodes occur within the first three years. Patients at higher risk of recurrence are co-infected with HIV, living in neighborhoods with high TB incidence or with a history of TB treatment. When available, genotyping results help determine whether the recurrence is due to reinfection or relapse.

Recurrences in tuberculosis in a cohort of human immunodeficiency virus-infected patients: The influence of highly active antiretroviral therapy

Background Little is known about recurrent tuberculosis (TB) among HIV-infected patients and the influence of highly active antiretroviral therapy (HAART).Methods A population-based retrospective longitudinal study was conducted on all HIV-infected TB patients in Barcelona (Spain) notified in 1987–2003, and followed up until 2005. TB recurrence and HAART influence were analysed according to calendar period. Results Patients with no-treatment and those in pre-HAART had more risk of TB recurrence (RR: 2.3; CI: 1–5.8 and RR: 4.8; CI: 2–12).Conclusions HAART decreases probability of TB recurrence and should be extended to all cases (AU)

Antecedentes Se conoce poco sobre recurrencias en tuberculosis (TB) en pacientes infectados por VIH y la influencia del tratamiento antiretroviral de gran actividad (HAART).Métodos Estudio poblacional longitudinal retrospectivo de todos los pacientes con TB infectados por VIH en Barcelona (España) notificados entre 1987-2003 y seguidos hasta 2005. Se analizó la influencia del HAART sobre las recurrencias en TB según el periodo calendario. Resultados Los pacientes sin antiretrovirales los del periodo pre-HAART tuvieron más riesgo de recurrencia en TB (RR:2.3;CI:1-5.8 y RR:4.8;CI:2-12).Conclusiones El HAART disminuye la probabilidad de recurrencia en TB por lo que debería extenderse su uso a nivel globa (AU)

Factors that influence current tuberculosis epidemiology.

According to WHO estimates, in 2010 there were 8.8 million new cases of tuberculosis (TB) and 1.5 million deaths. TB has been classically associated with poverty, overcrowding and malnutrition. Low income countries and deprived areas, within big cities in developed countries, present the highest TB incidences and TB mortality rates. These are the settings where immigration, important social inequalities, HIV infection and drug or alcohol abuse may coexist, all factors strongly associated with TB. In spite of the political, economical, research and community efforts, TB remains a major global health problem worldwide. Moreover, in this new century, new challenges such as multidrug-resistance extension, migration to big cities and the new treatments with anti-tumour necrosis alpha factor for inflammatory diseases have emerged and threaten the decreasing trend in the global number of TB cases in the last years. We must also be aware about the impact that smoking and diabetes pandemics may be having on the incidence of TB. The existence of a good TB Prevention and Control Program is essential to fight against TB. The coordination among clinicians, microbiologists, epidemiologists and others, and the link between surveillance, control and research should always be a priority for a TB Program. Each city and country should define their needs according to the epidemiological situation. Local TB control programs will have to adapt to any new challenge that arises in order to respond to the needs of their population.

Recurrences in tuberculosis in a cohort of human immunodeficiency virus-infected patients: the influence of highly active antiretroviral therapy.

BACKGROUND: Little is known about recurrent tuberculosis (TB) among HIV-infected patients and the influence of highly active antiretroviral therapy (HAART). METHODS: A population-based retrospective longitudinal study was conducted on all HIV-infected TB patients in Barcelona (Spain) notified in 1987-2003, and followed up until 2005. TB recurrence and HAART influence were analysed according to calendar period. RESULTS: Patients with no-treatment and those in pre-HAART had more risk of TB recurrence (RR: 2.3; CI: 1-5.8 and RR: 4.8; CI: 2-12). CONCLUSIONS: HAART decreases probability of TB recurrence and should be extended to all cases.

Community health workers improve contact tracing among immigrants with tuberculosis in Barcelona.

BACKGROUND: The important increase in immigration during recent years has changed the epidemiology and control strategies for tuberculosis (TB) in many places. This study evaluates the effectiveness of intervention with community health workers (CHW) to improve contact tracing among immigrants. METHODS: The study included all TB cases detected by the Barcelona TB Program from 2000 to 2005 and compared a period without CHW intervention (2000-2002) to a period with CHW intervention (2003-2005). The influence on contact tracing of sex, age, hospital of diagnosis, district of residence, birthplace, HIV, homeless and CHW intervention was analysed by logistic regression. Odds ratio (OR) and 95% confidence intervals (CI) were calculated. RESULTS: 960 foreign born TB cases were detected, 388 in the intervention period. Contact tracing was performed on 65,7% of 201 smear-positive cases during the pre-intervention period compared to 81.6% of 152 smear-positive TB cases during the intervention period (p < 0.001). Risk factors associated with incomplete contact tracing of smear-positive index cases included being diagnosed in two hospitals without contact tracing TB unit (OR = 3.5; CI:1.4-8.9) and (OR = 4.6; CI:1.6-13.5) respectively, birth place in India-Pakistan (OR = 4.4; CI:1.9-10.3) or North Africa (OR = 4.3; CI:1.8-10.5), having an unknown residence (OR = 5.4; CI:1.6-18.0), being HIV-infected (OR = 6.1; CI:2.5-14.8) or homeless (OR = 3.3; CI:1.3-8.2), and the absence of CHW intervention (OR = 2.4; CI:1.3-4.3). CONCLUSIONS: The effectiveness of contact tracing for TB control in areas with high immigration can be improved by incorporating CHWs who act as translators, cultural mediators and facilitators who accompany cases and contacts through treatment and follow-up.

Incidence of infectious diseases and survival among the Roma population: a longitudinal cohort study.

BACKGROUND: Roma ethnicity is greatly affected by tuberculosis (TB), AIDS, injecting drugs use (IDU) and imprisonment. METHODS: We assessed the incidence of several health problems by means of a retrospective cohort study performed in Camp de la Bota, Barcelona (Spain). The 380 individuals included in the 1985 TB outbreak investigation were followed-up until 31 December 2008. One hundred ninety-two subjects (50.5%) were men and 188 (49.5%) women. Information sources included questionnaires taken at the time of this outbreak, a population census and other registries from Barcelona and Catalonia. Cox proportional hazards mixed models were employed in the multivariate survival analysis. RESULTS: By the end of the follow-up, the survival rate was 79.4%; 50 persons (13.1%) had deceased and 28 (7.3%) had emigrated. The incidence of AIDS was 104 cases per 100 000 person-years of follow-up (pyf), IDU was 240 cases pyf, imprisonment was 642 cases pyf and that of TB was 91 cases pyf. Male survival was lower [hazard ratio (HR) 4.22], when the effect of family was taken into account, than when it was not taken into account (HR 3.67). CONCLUSIONS: High incidences of AIDS, TB, IDU, imprisonment and poor survival rates have been observed among Roma. Family was found to be an important factor influencing the survival rates: when not considered, the risk of death among men was underestimated.

Epidemiology of imported malaria among children and young adults in Barcelona (1990-2008).

BACKGROUND: Increasing international travel and migration is producing changes in trends in infectious diseases, especially in children from many European cities. The objective of this study was to describe the epidemiology and determine the trends of imported malaria in patients under 20 years old in the city of Barcelona, Spain, during an 18-year period. METHODS: The study included malaria cases that were laboratory confirmed and reported to the malaria register at the Public Health Agency of Barcelona from 1990 to 2008, residing in Barcelona and less than 20 years old. Patients were classified as natives (born in Spain) or immigrants. Differences in the distribution of demographic, clinical characteristics, and incidence per 100,000 person-year evolution were analysed. Natives and immigrants were compared by logistic regression by calculating the odds ratio (OR) with a 95% confidence interval (CI) and Chi-square for a linear trend (p<0.05). RESULTS: Of the total 174 cases, 143 (82.1%) were immigrants, 100 (57.5%) were female, 121 (69.5%) Plasmodium falciparum, and 108 (62.1%) were visiting friends and relatives (VFR) as the reason for travel. Among the immigrants, 99 (67.8%) were from Equatorial Guinea. Immigrant cases more frequently travelled to Africa than natives (p=0.02). The factors associated with imported malaria among immigrant residents was travelling for VFR (OR: 6.2 CI 1.9-20.2) and age 15-19 (OR: 3.7 CI 1-13.3). The incidence increased from 1990 to 1999 (p<0.001) and decreased from 2000 to 2008 (p=0.01), although the global linear trend was not statistically significant (p=0.41). The fatality rate was 0.5%. CONCLUSIONS: The majority of cases of malaria in population less than 20 years in Barcelona were immigrants, travelling to Africa for VFR and Plasmodium falciparum was most frequently detected. The trend analysis of the entire study period did not show a statistically significant decline. It is recommended to be aware of malaria, especially among children of immigrants who travel to their parent's home country for VFR. Better access to pre travel advice should be provided.

Predictors of death among patients who completed tuberculosis treatment: a population-based cohort study.

BACKGROUND: Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. METHODS: A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995-1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). RESULTS: Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 41-60 years old (HR: 3.5; CI:2.1-5.7), age greater than 60 years (HR: 14.6; CI:8.9-24), alcohol abuse (HR: 1.7; CI:1.2-2.4) and HIV-infected IDU (HR: 7.9; CI:4.7-13.3). CONCLUSIONS: The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival.

Transmission Of childhood tuberculosis risk factors associated with an unidentified index case and outbreak evolution in Barcelona (1987-2007).

The objective of the study was to examine the factors associated with unidentified tuberculosis (TB) index cases (1987-2007) and to describe outbreaks (2000-2007) of childhood TB cases in Barcelona, Spain. Contact tracing seems to be fundamental in index case identification, but improvement could be made among older children and cases of extrapulmonary TB or pulmonary TB with sputum microscopy results.

Imported malaria among African immigrants: is there still a relationship between developed countries and their ex-colonies?

BACKGROUND: The objective of this study was to compare cases of imported malaria originating from the Spanish ex-colony of Equatorial Guinea (EG) with those originating from the rest of Africa (RA). METHODS: All the African cases detected in Barcelona between 1989 and 2007 were investigated in a retrospective analysis. Clinical-epidemiological variables such as sex, age, visiting friends and relatives (VFR), species, hospital admission and chemo-prophylaxis were compared. Data were analysed by logistic regression, calculating the Odds Ratio (OR) and 95% Confidence Intervals (95% CI). RESULTS: Of the 489 African patients, 279 (57,1%) had been born in EG and 210 (42,9%) in the rest of Africa. The cumulative incidence of imported malaria among those from EG was 179.6 per thousand inhabitants, while in those from the RA it was 33.7 per thousand (p < 0.001). Compliance with chemoprophylaxis (CP) was very low, but there were no differences between the two groups. Comparing those from EG to those from RA, the former were characterized by having more patients in the visiting friends and relatives (VFR) category, and more individuals younger than 15 years or older than 37 years, and more women. They also visited a traveller's health centre more often, had fewer hospital admissions and were less likely to reside in the inner city. CONCLUSION: Cases of imported malaria originating in Africa, are more likely to come from the Spanish ex-colony of EG, and VFR are more likely to be affected. It is recommended that developed countries promote prevention programmes, such as CP advice directed at African immigrants, and develop programmes of cooperation against malaria in their ex-colonies.

Imported malaria in a cosmopolitan European city: a mirror image of the world epidemiological situation.

BACKGROUND: International travel and migration have been related with an increase of imported malaria cases. There has been considerable immigration to Barcelona from low-income countries (LIC) in recent years. The objective is to describe the epidemiology and to determine the trends of the disease in Barcelona. METHODS: Analysis of the cases notified among city residents between 1989 and 2005. Patients were classified as: tourists, voluntary workers, resident immigrants (visiting friends and relatives, VFR) and recently arrived immigrants. An analysis was conducted using the chi2 test and comparison of means. As a measure of association we calculated the Relative Risk (RR) and Odds Ratio (OR) with a Confidence Interval of 95% (CI) and carried out a trends analysis. RESULTS: Of the total of 1,579 imported cases notified, 997 (63.1%) lived in Barcelona city, and 55.1% were male. The mean age of patients was 32.7 years. The incidence increased from 2.4 cases/100,000 in 1989 to 3.5 cases/100,000 in 2005 (RR 1.46 CI:1.36-1.55). This increase was not statistically significant (trends analysis, p = 0.36). In terms of reason for travelling, 40.7% were VFR, 33.6% tourists, 12.1% voluntary workers and 13.6% were recently arrived immigrants. The most frequent species found was Plasmodium falciparum (71.3%), mainly in visitors to Africa (OR = 2.3, CI = 1.7-3.2). The vast majority (82.2%) had had some contact with Africa (35.9% with Equatorial Guinea, a Spanish ex-colony) and 96.6% had not completed chemoprophylaxis. Six deaths were observed, all tourists who had travelled to Africa and not taken chemoprophylaxis (3.9% fatality rate). CONCLUSION: Over the period studied there is an increase in malaria incidence, however the trend is not statistically significant. Lack of chemoprophylaxis compliance and the association between Africa and P. falciparum are very clear in the imported cases. Most of the patients with malaria did not take chemoprophylaxis.