Recent trends in tuberculosis in children in London.

BACKGROUND: Childhood tuberculosis (TB) represents a sentinel event of recent transmission and is an indication of the effectiveness of prevention and control interventions. We analysed the trends in the epidemiology of TB in children in London aged 0-14 years between 1999 and 2006. METHODS: Data were extracted from the Enhanced TB Surveillance System. RESULTS: Between 1999 and 2006, there were 1370 cases of TB in children. Incidence was higher in older children and in girls. The incidence rates in London Boroughs varied from 0.4/100,000 to 32.7/100,000. Between 1999 and 2006, Black-Africans comprised 49.2% of all TB cases in children, children from the Indian Subcontinent 21.8% and Whites 8.5%. The proportion of cases born in the UK averaged 52.4% during this period. Of non-UK-born children 79.3% were diagnosed with TB within 5 years of entry. CONCLUSIONS: Ethnicity, country of birth and age are important risk factors for development of. With an overall TB incidence in London exceeding 40/100,000, universal BCG immunization of all neonates should be considered across all London boroughs.

Viral Load in Spanish HIV patients: trends since the introduction of HAART.

The aim of this study is to describe trends in the percentage of samples with undetectable HIV viral load in Spain after the implementation of HAART. A descriptive observational study of HIV-VL measurements carried out in the microbiology department of the Hospital Clínico Universitario de Valladolid (HCUV) was conducted over a 9-year period (1996-2004). Regarding the trend over the study period, the 30-39 years age group accounted for most of the samples, although the percentage decreased from 65.5% to 59.6% over the study period. In contrast, the 40-49 years group increased from 9.1% to 14.5%. The preponderance of men, with percentages above 70%, was observed during the whole period. Although the purpose of this treatment is to maintain undetectable viral loads, since 1999 more than 60% of nonfirst samples had detectable levels. Based on the results of the VL trend among HIV/AIDS patients observed in this study, a large number of patients maintain elevated detectable VL years after HAART was implemented. Although different factors may be the cause of this and should be delimited in future studies, the phenomenon observed demonstrates the usefulness of monitoring VL and analyzing its time trend to gain further knowledge about the therapeutic results and care of HIV patients as a whole, also serving as the basis for corrective measures.

What is the best culture conversion prognostic marker for patients treated for multidrug-resistant tuberculosis?

INTRODUCTION: Identification of good prognostic marker for tuberculosis (TB) treatment response is a necessary step on the path towards a surrogate marker to reduce TB trial duration.METHODS: We performed a retrospective analysis on routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture conversion, defined as two consecutive negative cultures, was assessed, and performance of culture conversion at Month 2 and Month 6 to predict treatment success were explored. To explore factors associated with positive predicted value (PPV) and the specificity of culture conversion, a multinomial logistic regression was fitted.RESULTS: This study included 634 patients: 68.5% were males; the median age was 35 years, 75.2% were previously treated for TB, 59.4% were resistant only to isoniazid and rifampicin and 18.1% resistant to fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while specificity was much higher for culture conversion at Month 2: 91.3% (95%CI 86.1-95.1). PPV of culture conversion at Month 2 did not vary strongly according to patients' characteristics, while specificity was slightly higher among patients with fluoroquinolone-resistant strains.CONCLUSION: Culture conversion at Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the advantage of using an earlier marker, further evaluation as a surrogate marker is warranted to shorten TB trials.

Trend and seasonality of tuberculosis in Spain, 1996-2004.

This study aimed to analyse the trend and seasonality of tuberculosis (TB) in Spain over the past decade. Weekly TB incidence was calculated using data from the National Surveillance Network for the period 1996-2004. Secular trends and seasonal components were estimated using time-series analysis (least-squares method and Fourier transformation). A decline in incidence was observed, from 23.4 cases per 100,000 population in 1997 to 15.1 in 2004, and an annual cycle peaking in June was detected. Time-series analyses are necessary for detecting changes in the epidemiological pattern of TB in Spain, and it should be the first step towards the development of a predictive model.

Identification of patients who could benefit from bedaquiline or delamanid: a multisite MDR-TB cohort study.

BACKGROUND: The World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome. OBJECTIVE: To identify patients at risk of unfavourable outcomes who may benefit from the new drugs. METHODS: Retrospective cohort study of treatment outcomes involving four to five effective drugs for 15-24 months in programmes in Uzbekistan, Georgia, Armenia, Swaziland and Kenya between 2001 and 2011. RESULTS: Of 1433 patients, 48.5% had body mass index (BMI) <18.5 kg/m(2), 72.9% had a high bacillary load, 16.7% were resistant to two injectables, 2.9% were resistant to ofloxacin (OFX) and 3.0% had extensively drug-resistant TB (XDR-TB). Treatment success ranged from 59.7% (no second-line resistance) to 27.0% (XDR-TB). XDR-TB (aOR 8.16, 95%CI 3.22-20.64), resistance to two injectables (aOR 1.90, 95%CI 1.00-3.62) or OFX (aOR 5.56, 95%CI 2.15-14.37), past incarceration (aOR 1.88, 95%CI 1.11-3.2), history of second-line treatment (aOR 3.24, 95%CI 1.53-6.85), low BMI (aOR 2.22, 95%CI 1.56-3.12) and high bacillary load (aOR 2.32, 95%CI 1.15-4.67) were associated with unfavourable outcomes. Patients started on capreomycin rather than kanamycin were more likely to have an unfavourable outcome (aOR 1.54, 95%CI 1.04-2.28). CONCLUSION: In our cohort, patients who may benefit from bedaquiline and delamanid represented up to two thirds of all MDR-TB patients.

Decontamination methods for samples preserved in cetylpyridinium chloride and cultured on thin-layer agar.

SETTING: Long transportation times of samples to culture laboratories can lead to higher contamination rates and significant loss of viability, resulting in lower culture positivity rates. Thin-layer agar (TLA) is a sensitive culture method for the isolation of Mycobacterium tuberculosis that has been optimised with N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) decontaminated samples. The combination of the TLA culture method and other decontamination procedures has not been extensively validated. DESIGN: Among 390 smear-positive samples, we compared the culture positivity of samples decontaminated using the Petroff method vs. NALC-NaOH neutralised with phosphate buffer (PBS), applied to samples preserved with cetylpyridinium chloride (CPC) or CPC-free, and then of CPC-preserved samples decontaminated with NALC-NaOH neutralised using Difco neutralising buffer. The sediments were inoculated on TLA, and then on MGIT 960 or Löwenstein-Jensen (LJ) as gold standards. RESULTS: Decontamination with NALC-NaOH yielded higher culture positivity in TLA than in the Petroff method, which was further enhanced by neutralising CPC with the Difco buffer. Surprisingly, culture positivity on LJ also increased after using Difco buffer, suggesting that CPC may not be completely neutralised in egg-based medium. CONCLUSIONS: After transportation in CPC, decontamination using NALC-NaOH followed by neutralisation using Difco buffer resulted in the best recovery rates for samples inoculated on TLA and on LJ.

Reasons for defaulting from drug-resistant tuberculosis treatment in Armenia: a quantitative and qualitative study.

SETTING: Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB). OBJECTIVE: To identify factors related to default from DR-TB treatment in Yerevan. DESIGN: Using a retrospective cohort design, we compared defaulters with patients who were cured, completed or failed treatment. Patients who initiated DR-TB treatment from 2005 to 2011 were included in the study. A qualitative survey was conducted including semi-structured interviews with defaulters and focus group discussions with care providers. RESULTS: Of 381 patients, 193 had achieved treatment success, 24 had died, 51 had failed treatment and 97 had defaulted. The number of drugs to which the patient was resistant at admission (aRR 1.16, 95%CI 1.05-1.27), the rate of treatment interruption based on patient's decision (aRR 1.03, 95%CI 1.02-1.05), the rate of side effects (aRR 1.18, 95%CI 1.09-1.27), and absence of culture conversion during the intensive phase (aRR 0.47, 95%CI 0.31-0.71) were independently associated with default from treatment. In the qualitative study, poor treatment tolerance, a perception that treatment was inefficient, lack of information, incorrect perception of being cured, working factors and behavioural problems were factors related to treatment default. CONCLUSION: In addition to economic reasons, poor tolerance of and poor response to treatment were the main factors associated with treatment default.

Multidrug- and isoniazid-resistant tuberculosis in three high HIV burden African regions.

SETTING: Despite major progress in the surveillance of drug-resistant tuberculosis (TB), data are lacking for many low-resource countries. World Health Organization estimates of multidrug-resistant TB (MDR-TB) rates in Africa are low, and based on very limited data from the African continent. OBJECTIVE: To measure MDR-TB prevalence in sub-Saharan African regions with a high prevalence of human immunodeficiency virus (HIV). METHOD: We conducted three anti-tuberculosis drug resistance surveys in sub-Saharan African regions with high HIV-TB coinfection prevalence: Homa Bay (Kenya), Chiradzulu (Malawi) and West Nile region (Uganda). RESULTS: The prevalence of MDR-TB in new patients was found to be low in the three regions: 1.4% (95%CI 0.2-2.6) in Homa Bay, 2.0% (95%CI 0.4-3.6) in Chiradzulu and 0.6% (95%CI 0.0-1.5) in the West Nile region. We found no significant association between MDR-TB and HIV infection. Nonetheless, ≥ 10% of the new cases surveyed were resistant to isoniazid (INH). CONCLUSION: The relatively high rate of resistance to INH highlights the need for rapid detection of INH resistance in addition to rifampicin (RMP) resistance, to allow rapid modification of treatment to avoid the acquisition of RMP resistance. Drug resistance should be monitored periodically.

Epidemiology of internal contamination with polonium-210 in the London incident, 2006.

BACKGROUND: More than 700 UK residents were tested for possible contamination with polonium-210 ((210)Po) following the alleged poisoning of Mr Alexander Litvinenko in London in November 2006. This paper describes the epidemiology of internal contamination with the radionuclide in this group. METHODS: 11 locations in London had been identified as sufficiently environmentally contaminated with (210)Po to present a health risk to people associated with them. Public health consultant teams identified individuals at risk and offered 24-h urine testing for (210)Po excretion. Prevalence of internal contamination was estimated, and a retrospective cohort analysis was completed for each location. RESULTS: Overall 139 individuals (prevalence 0.19 (95% CI 0.13 to 0.27)) showed evidence of internal contamination with (210)Po, although none with uptakes likely to cause adverse health effects. Substantial prevalence was seen among specific hotel service staff, customers, staff and other users of a hotel bar, office and hospital staff, staff of one restaurant and residents of and visitors to the family home. Increased risks of contamination were seen for a hotel bar in association with occupational, behavioural and temporal factors. Occupational and guest exposure to contaminated areas of hotels were also associated with increased contamination risk. Nurses were more likely to become contaminated than other staff involved in direct patient care. CONCLUSIONS: Uptake of trace amounts of radionuclide in this incident was frequent. Occupational, behavioural and temporal gradients in contamination risk were mostly consistent with a priori site risk assessments. Utility of the investigation methods and findings for future accidental or deliberate environmental contamination incidents are discussed.

Viral Load in Spanish HIV patients: trends since the introduction of HAART

The aim of this study is to describe trends in the percentageof samples with undetectable HIV viral load in Spain afterthe implementation of HAART. A descriptive observationalstudy of HIV-VL measurements carried out in themicrobiology department of the Hospital Clínico Universitariode Valladolid (HCUV) was conducted over a 9-year period(1996-2004).Regarding the trend over the study period, the 30-39years age group accounted for most of the samples, althoughthe percentage decreased from 65.5 % to 59.6%over the study period. In contrast, the 40-49 years group increasedfrom 9.1 % to 14.5 %. The preponderance of men,with percentages above 70 %, was observed during thewhole period.Although the purpose of this treatment is to maintainundetectable viral loads, since 1999 more than 60% of nonfirstsamples had detectable levels.Based on the results of the VL trend among HIV/AIDSpatients observed in this study, a large number of patientsmaintain elevated detectable VL years after HAART was implemented.Although different factors may be the cause ofthis and should be delimited in future studies, the phenomenonobserved demonstrates the usefulness of monitoringVL and analyzing its time trend to gain furtherknowledge about the therapeutic results and care of HIVpatients as a whole, also serving as the basis for correctivemeasures (AU)

en el porcentaje de muestras con carga viral(CV) de VIH indetectable en una serie española, despuésde la introducción de la terapia antirretroviral de altaeficacia (HAART). Se ha llevado a cabo un estudio descriptivoobservacional de las determinaciones de CV deVIH realizadas en el departamento de microbiología delHospital Clínico Universitario de Valladolid (HCUV) duranteun período de 9 años (1996-2004). Las muestrasprocedentes de individuos cuya categoría de edad se encontrabaen el intervalo de 30-39 años fueron las masnumerosas, y la proporción de CV indetectables en estegrupo disminuyó del 65,5% al 59,6% durante el períodode estudio. Al contrario en el grupo de 40-49 años aumentódel 9,1% al 14,5%. Los varones, con porcentajesencima del 70%, fueron el grupo preponderante duranteel período entero.De acuerdo con nuestros hallazgos un porcentaje importantede pacientes (más del 60%) mantiene niveles deCV detectable en las muestras de seguimiento, a pesarde la introducción de las terapias «HAART» desde 1999.La presente aportación demuestra la utilidad de monitorizarla CV y su tendencia en el tiempo, como indicadorde la eficiencia terapéutica; aunque sean necesariosestudios futuros que pueden matizar los factores involucradosen este hecho de cara a optimizar los cuidados yla terapia de los pacientes con infección VIH (AU)