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IntroductionSupport groups for people living with HIV (PLHIV) are essential for increasing adherence, retention, addressing their psychosocial needs and improving patient literacy. However, factors that influence participation of caregivers living with HIV (LHIV) in these groups are scarcely documented, particularly for those caring for orphans and vulnerable children (OVC).MethodsThis study used baseline data collected between 1st October 2021 and 30th September 2022 from the PEPFAR/USAID-funded Adolescents and Children HIV Incidence Reduction, Empowerment and Virus Elimination (ACHIEVE) project in Tanzania to investigate factors that affect participation of caregivers LHIV in support groups for PLHIV. A total of 74,249 HIV-positive OVC caregivers who were already receiving antiretroviral therapy (ART) and had a confirmed care and treatment centre identification number were included in the analysis. Factors affecting group participation were identified through multilevel analysis using multivariable mixed-effects logistic regression.ResultsResults showed that 84.2% of the caregivers were participants in the support groups for PLHIV. Their mean age was 36 years, and the majority (82.1%) were female. Multivariable analysis revealed that participation in the groups was more likely among caregivers living in urban areas (aOR = 1.39 [1.24, 1.55]), with primary education (aOR = 1.17 [1.07, 1.28]), and without disabilities (aOR = 0.62 [0.47, 0.82]). However, participation was less likely among widowed (aOR = 0.91 [0.84, 0.999]), single or unmarried (aOR = 0.86 [0.78, 0.95]), and those with secondary education or higher levels than never attended (aOR = 0.69 [0.60, 0.80]), moderate hunger (aOR = 0.86 [0.79, 0.93]), and those aged 30 years or older (p< 0.001).DiscussionA sizeable proportion (15.8%) of the caregivers were not in support groups for PLHIV, ranging from 12.3% among those in households with severe hunger to 29.7% among disabled ones. The study highlights the need for tailored interventions to increase participation in support groups for PLHIV, particularly for caregivers who are disabled, live in rural areas, are older, widowed, and/or unmarried, and those in poor households.

IntroductionIn Tanzania, only 66% children 0–14 years living with HIV know their HIV status, 66% are on treatment while 47% of children on ART are virally suppressed. Although retention on ART and poor adherence remain a challenge for children living with HIV, orphans and vulnerable children (OVC) face a greater limitation of access to and utilization of comprehensive HIV care and treatment. In response to this, the current study assessed the determinants of viral load suppression (VLS) among OVC aged 0–14 years living with HIV enrolled in HIV interventions.MethodsThis was a cross-sectional study that used secondary data collected by the USAID Kizazi Kipya project in 81 district councils of Tanzania. Included in this study are 1,980 orphans and vulnerable children living with HIV (OVCLHIV) (0–14 years) enrolled and served by the project for 24 months. Data analysis involved multivariable logistic regression, with viral load suppression as the outcome of interest and HIV interventions as the main independent variables.ResultsThe overall VLS rate among the OVCLHIV was 85.3%. This rate increased from 85.3, 89.9, 97.6 to 98.8% after 6, 12, 18, and 24 months of retention on ART, respectively. Similar rates were observed as the duration of adherence to ART increased. In the multivariable analysis, OVCLHIV attending people living with HIV (PLHIV) support groups were 411 times more likely to be virally suppressed than those not attending (aOR = 411.25, 95% CI 168.2–1,005.4). OVCLHIV with health insurance were 6 times more likely to achieve viral suppression than those without (aOR = 6.05, 95% CI 3.28–11.15). OVCLHIV with >95% adherence to ART were 149 times more likely to be virally suppressed than those not adherent to ART (aOR = 148.96, 95% CI 42.6–520.6, p < 0.001). Other significant factors included food security and family size. OVCLHIV reached by the different HIV community-based interventions were more likely to be virally suppressed than those who were not.DiscussionTo advance viral suppression, efforts should be made to ensure that all OVCLHIV are reached by community-based interventions as well as integrating food support in HIV treatment interventions.

Despite the global progress in response to HIV and AIDS, notable challenges remain for children, especially identification, linkage, and retention in HIV care and treatment services. To succeed in pediatric HIV programming requires the linkage and retention of the children in those services over time. This study assessed the level of retention to antiretroviral therapy (ART) and its associated factors among orphans and vulnerable children living with HIV (OVCLHIV) in Tanzania. Data were obtained from the USAID Kizazi Kipya project that collected pediatric ART data from October 2017 to October 2019 in 81 district councils of Tanzania. Community-based volunteers supported the linkage and retention of the OVCLHIV on ART. Analysis of on-ART status was conducted in a cohort of OVCLHIV aged 0–20 years enrolled in the project and monitored for 24 months. OVCLHIV who remained on ART until the end of the follow-up period were referred to as “retained,” otherwise, “not retained”. Multivariable analysis was conducted using logistic regression, adjusting for baseline characteristics. Of the 5,304 OVCLHIV analyzed, the mean age was 13.1 years, 51.5% were female, and 72.2% were living with female caregivers. Their overall rate of retention on ART over the 24 months was 86.7%. Multivariable analysis showed that as the higher frequency of home visit by the project staff increased, the likelihood of retention increased by 8% [adjusted odds ratio (aOR) = 1.08, 95% CI 1.06–1.11, p < 0.001]. Membership in people living with HIV (PLHIV) support groups was associated with a higher likelihood of retention compared to nonmembership (aOR = 3.31, 95% CI 2.60–4.21, p < 0.001). Children in larger family size were 22% less likely to sustain ART (aOR = 0.78, 95% CI 0.72–0.84, p < 0.001). Urban OVCLHIV were 18% less likely to remain on ART than their rural counterparts (aOR = 0.82, 95% CI 0.69–0.98, p = 0.030). Remaining on ART was 49% more likely for OVC in economically better-off households than those in destitute households (aOR = 1.49, 95% CI 1.22–1.81, p < 0.001). Male OVC were 17% less likely to be retained on ART than their female counterparts (aOR = 0.83, 95% CI 0.71–0.99, p = 0.033). Community-based OVC support resulted in a high pediatric retention rate over the 24 months of follow-up. While key enablers of retention were higher frequency of home visits by the project volunteer, participation in PLHIV support groups, and better economic status, large family sizes, urban place of residence, and male gender of the OVC were barriers. This study brings useful evidence to inform strategies for advancing retention of OVCLHIV on ART for their better health outcomes and overall wellbeing.

Abstract Background HIV status disclosure facilitates access to HIV-related prevention and treatment services and increases opportunities for social support, HIV risk reduction with partners, and index testing for sexual partners or children. This study assessed the effect of a program model of community-based social welfare volunteers on HIV status disclosure among caregivers of orphans and vulnerable children (OVC). Methods This was a longitudinal study, which was based on OVC caregivers who were beneficiaries of the USAID Kizazi Kipya project in Tanzania. They were enrolled (baseline) by community social welfare volunteers during 2017–2018, received services, and reassessed at midline in 2019. Caregivers who reported having been HIV tested, were asked to voluntarily report the status in order for the volunteers to establish and provide needed services. Those who reported their HIV status as negative or positive were grouped as “disclosed”, and those who knew their status but did not report it were documented as “undisclosed”. McNemar’s tests compared disclosure rates at baseline and midline. Multivariable analysis was conducted using generalized estimating equation (GEE). Results The study analyzed 140,664 caregivers (72% female) from 81 district councils of Tanzania. Their mean age at enrollment was 47.4 years. Overall, 81.3% of the caregivers disclosed their HIV status to the project staff at baseline; this increased significantly to 96.1% at midline (p 0.05). In the multivariable analysis, caregivers’ likelihood of HIV status disclosure was nearly 6 times higher at midline than at baseline, when baseline characteristics were adjusted for (OR = 5.76, 95% CI 5.59–5.94, p

Abstract Background Utilization of antiretroviral therapy (ART) is crucial for better health outcomes among people living with the human immunodeficiency virus (PLHIV). Nearly 30% of the 1.6 million PLHIV in Tanzania are not on treatment. Since HIV positive status is the only eligibility criterion for ART use, it is critical to understand the obstacles to ART access and uptake to reach universal coverage of ART among PLHIV. For the caregivers of orphans and vulnerable children (OVC) LHIV and not on ART, attempts to identify them and ensure that they initiate and continue using ART is critical for their wellbeing and their ability to care for their children. Methods Data are from the community-based, United States Agency for International Development (USAID)-funded Kizazi Kipya project that aims at scaling up the uptake of HIV/AIDS and other health and social services by orphans and vulnerable children (OVC) and their caregivers. HIV positive caregivers of OVC who were enrolled in the USAID Kizazi Kipya project between January 2017 and June 2018 were included in this cross-sectional study. The caregivers were drawn from 11 regions: Arusha, Iringa, Katavi, Kigoma, Mara, Mbeya, Morogoro, Ruvuma, Simiyu, Singida, and Tanga. The outcome variable was ART status (either using or not), which was enquired of each OVC caregiver LHIV at enrollment. Data analysis involved multivariable analysis using random-effects logistic regression to identify correlates of ART use. Results In total, 74,999 caregivers living with HIV with mean age of 44.4 years were analyzed. Of these, 96.4% were currently on ART at enrollment. In the multivariable analysis, ART use was 30% lower in urban than in rural areas (adjusted odds ratio (OR) = 0.70, 95% confidence interval (CI) 0.61–0.81). Food security improved the odds of being on ART (OR = 1.29, 95% CI 1.15–1.45). Disabled caregivers were 42% less likely than non-disabled ones to be on ART (OR = 0.58, 95% CI 0.45–0.76). Male caregivers with health insurance were 43% more likely than uninsured male caregivers to be on ART (OR = 1.43, 95% CI 1.11–1.83). Caregivers aged 40–49 years had 18% higher likelihood of being on ART than the youngest ones. Primary education level was associated with 26% increased odds of being on ART than no education (OR = 1.26, 95% CI 1.13–1.41). Conclusions Although nearly all the caregivers LHIV in the current study were on ART (96.4%), more efforts are needed to achieve universal coverage. The unreached segments of the population LHIV, even if small, may lead to worse health outcomes, and also spur further spread of the HIV epidemic due to unachieved viral suppression. Targeting caregivers in urban areas, food insecure households, who are uninsured, and those with mental or physical disability can improve ART coverage among caregivers LHIV.

Abstract Background HIV status disclosure facilitates receipt of HIV prevention and treatment services. Although disclosure to sexual partners, family members or friends has been extensively studied, disclosure to community-based HIV programs is missing. This study assesses the magnitude of, and factors associated with undisclosed HIV status to a community-based HIV prevention program among caregivers of orphans and vulnerable children (OVC) in Tanzania. Methods Data are from the USAID-funded Kizazi Kipya project that seeks to increase uptake of HIV, health, and social services by OVC and their caregivers in Tanzania. Data on OVC caregivers who were enrolled in the project during January–March 2017 in 18 regions of Tanzania were analyzed. Caregivers included were those who had complete information on their HIV status disclosure, household socioeconomic status, and sociodemographic characteristics. HIV status was self-reported, with undisclosed status representing all those who knew their HIV status but did not disclose it. Multilevel mixed-effects logistic regression, with caregivers’ HIV status disclosure being the outcome variable was conducted. Results The analysis was based on 59,683 OVC caregivers (mean age = 50.4 years), 71.2% of whom were female. Of these, 37.2% did not disclose their HIV status to the USAID Kizazi Kipya program at the time of enrollment. Multivariate analysis showed that the likelihood of HIV status non-disclosure was significantly higher among: male caregivers (odds ratio (OR) = 1.22, 95% confidence interval (CI) 1.16–1.28); unmarried (OR = 1.12, 95% CI 1.03–1.23); widowed (OR = 1.12, 95% CI 1.07–1.18); those without health insurance (OR = 1.36, 95% CI 1.28–1.45); age 61 + years (OR = 1.72, 95% CI 1.59–1.88); those with physical or mental disability (OR = 1.14, 95% CI 1.04–1.25); and rural residents (OR = 1.58, 95% CI 1.34–1.86). HIV status non-disclosure was less likely with higher education (p

Abstract Background Tanzania has met only 50.1% of the 90% target for diagnosing HIV in children. The country’s pediatric case finding strategy uses global best practices of index testing, provider-initiated counselling and testing, and targeted community testing of at-risk populations to find about 50,000 children living with HIV (CLHIV) who are undiagnosed. However, context-specific strategies are necessary to find the hidden children to meet the full 90% target. This study assesses whether sex of the caregiver is associated with HIV status of orphans and vulnerable children (OVC) as a valuable strategy for enhanced pediatric case findings. Methods Data originate from the community-based, United States Agency for International Development (USAID)-funded Kizazi Kipya Project, which works towards increasing OVC’s and their caregivers’ uptake of HIV/AIDS and other health and social services in Tanzania. Included in this study are 39,578 OVC ages 0–19 years who the project enrolled during January through March 2017 in 18 regions of Tanzania and who voluntarily reported their HIV status. Data analysis involved multi-level logistic regression, with OVC HIV status as the outcome of interest and caregiver’s sex as the main independent variable. Results Three-quarters (74.3%) of the OVC included in the study had female caregivers, and their overall HIV prevalence was 7.1%. The prevalence was significantly higher (p

The association between hunger and adherence to antiretroviral therapy (ART) is less known especially in vulnerable populations receiving HIV care and treatment services. Caregivers of orphans and vulnerable children (OVC) are vulnerable and likely to experience hunger due to additional economic pressure in caring for OVC. Using data from the community–based, USAID–funded Kizazi Kipya project, this study assesses the association between hunger and ART adherence among caregivers of OVC in Tanzania. HIV positive caregivers enrolled in the project from January to July 2017 were analyzed. The outcome variable was adherence to ART, defined as “not having missed any ART dose in the last 30 days,” and household hunger, measured using the Household Hunger Scale (HHS), was the main independent variable. Data analysis included multivariable logistic regression. The study analyzed 11,713 HIV positive caregivers who were on ART at the time of enrollment in the USAID Kizazi Kipya project in 2017. Aged 48.2 years on average, 72.9% of the caregivers were female. While 34.6% were in households with little to no hunger, 59.4 and 6.0% were in moderate hunger and severe hunger households, respectively. Overall, 90.0% of the caregivers did not miss any ART dose in the last 30 days. ART adherence rates declined as household hunger increased (p < 0.001). Multivariable analysis showed that the odds of adhering to ART was significantly lower by 42% among caregivers in moderate hunger households than those in little to no hunger households (OR = 0.58, 95% CI 0.50–0.68). The decline increased to 47% among those in severe hunger households (OR = 0.53, 95% CI 0.41–0.69). Hunger is an independent and a significant barrier to ART adherence among caregivers LHIV in Tanzania. Improving access to adequate food as part of HIV care and treatment services is likely to improve ART adherence in this population.

About 2 billion people worldwide suffer moderate or severe forms of food insecurity, calling for correctional measures involving economic strengthening interventions. This study assessed the impact of household economic strengthening (HES) intervention on food security among caregivers of orphans and vulnerable children (OVC) in Tanzania. The study was longitudinal in design, based on OVC caregivers' baseline (2017-2018) and midline (2019) data from the USAID Kizazi Kipya project. Food security, the outcome, was measured using the Household Hunger Scale (HHS) in three categories: little to no hunger (food secure), moderate hunger, and severe hunger. Membership in the USAID Kizazi Kipya-supported economic strengthening intervention (i.e. WORTH Yetu) was the main independent variable. Data analysis involved generalized estimating equation (GEE) for multivariate analysis. With mean age of 50.3 years at baseline, the study analyzed 132,583 caregivers, 72.2% of whom were female. At midline, 7.6% of all caregivers enrolled at baseline were members in WORTH Yetu. Membership in WORTH Yetu was significantly effective in reducing household hunger among the caregivers: severe hunger dropped from 9.4% at baseline to 4.1% at midline; moderate hunger dropped from 65.9% at baseline to 62.8% at midline; and food security (i.e., little to no hunger households) increased from 25.2% at baseline to 33.1% at midline. In the multivariate analysis, membership in WORTH Yetu reduced the likelihood of severe hunger by 47% (OR = 0.53, 95% CI 0.48-0.59), and moderate hunger by 21% (OR = 0.79, 95% CI 0.76-0.83), but increased the likelihood of food security by 45% (OR = 1.45, 95% CI 1.39-1.51). The USAID Kizazi Kipya's model of household economic strengthening for OVC caregivers was effective in improving food security and reducing household hunger in Tanzania. This underscores the need to expand WORTH Yetu coverage. Meanwhile, these results indicate a potential of applying the intervention in similar settings to address household hunger.

Background. The Tanzanian national guideline for pediatric HIV disclosure recommends beginning disclosure as early as age 4–6 years; full disclosure is recommended at the age of 8–10 years. Despite clear procedures, the disclosure rate in Tanzania remains relatively low. This study assessed the factors associated with HIV status disclosure to orphans and vulnerable children living with HIV (OVCLHIV). Methods. Data for this analysis come from the USAID-funded Kizazi Kipya program in Tanzania that provides health and social services to OVC and caregivers of HIV-affected households. Data were collected between January 2018 and March 2019. Disclosure status was self-reported by caregivers of children aged 8 years or above. Beneficiary characteristics were included as independent variables. Generalized estimating equations took into account the clustering effect of the study design. Results. Of the 10673 OVCLHIV, most were females (52.43%), and 80.67% were enrolled in school. More than half (54.89%) were from households in rural areas. Caregivers were mostly females (70.66%), three quarters were between 31 and 60 years old and had a complete primary education (67.15%), and 57.75% were HIV-infected. Most of the OVCLHIV (87.31%) had a disclosed HIV status. Greater OVCLHIV age p

Pengabdian kepada masyarakat ini merupakan bentuk penerapan ilmu desain interior dengan tujuan memberikan kontribusi kepada masyarakat Indonesia sesuai bidang ilmu dosen interior. Objek Gereja Batak Karo Protestan (GBKP) Bandung Barat menjadi proyek dalam menerepakan keilmuan desain interior. Etnis Karo merupakan salah satu Etnis yang ada di Pulau Sumatera, Etnis Karo kaya akan budaya lokal baik Tangible maupun Intagible dengan pengabdian ini Universitas Kristen Maranatha berperan serta untuk turut usaha pelatihan budaya Etnis Karo. Pengabdian ini merupakan hasil Kerjasama Universitas Kristen Maranatha dengan Gereja Batak Karo Protestan khususnya kepada Program Sarjana Desain Interior agar dilakukanya redesign interior GBKP sehingga jemaat dapat beribadah, melayani Tuhan dengan nyaman dan kyusuk. Dengan redesign interior gereja diharapkan kualitas suara, kualitas warna pada interior menjadi lebih baik untuk digunakkan, kegiatan pengabdian ini dinilai memiliki nilai positif bagi kedua belah pihak, khususnya program sarjana desain interior memiliki peran nyata yang dirasakan oleh masyarakat terutama jemaat Gereja Batak Karo Protestan. Kata kunci: Batak Karo, Desain Gereja, Gereja Karo, Interior, Redesign

Species belonging to the Mycobacterium kansasii complex (MKC) are frequently isolated from humans and the environment and can cause serious diseases. The most common MKC infections are caused by the species M. kansasii ( sensu stricto ), leading to tuberculosis-like disease. However, a broad spectrum of virulence, antimicrobial resistance and pathogenicity of these non-tuberculous mycobacteria (NTM) are observed across the MKC. Many genomic aspects of the MKC that relate to these broad phenotypes are not well elucidated. Here, we performed genomic analyses from a collection of 665 MKC strains, isolated from environmental, animal and human sources. We inferred the MKC pangenome, mobilome, resistome, virulome and defence systems and show that the MKC species harbours unique and shared genomic signatures. High frequency of presence of prophages and different types of defence systems were observed. We found that the M. kansasii species splits into four lineages, of which three are lowly represented and mainly in Brazil, while one lineage is dominant and globally spread. Moreover, we show that four sub-lineages of this most distributed M. kansasii lineage emerged during the twentieth century. Further analysis of the M. kansasii genomes revealed almost 300 regions of difference contributing to genomic diversity, as well as fixed mutations that may explain the M. kansasii 's increased virulence and drug resistance.

Different and contrasting trends related to human migration and the implementation of health control programmes influence the spread of drug-resistant tuberculosis (TB). We analysed the Mycobacterium tuberculosis population structure in Estonia, a high-priority EU country for TB control, to detect the dynamic changes and underlying factors. The study collection included 278 M. tuberculosis isolates recovered in 1999 and 2014-2015. The isolates were subjected to drug susceptibility testing, genotyping and analysis of sublineage/cluster-specific markers and drug resistance mutations. The Beijing genotype was the most prevalent, and its rate increased from 28.6% in 1999 to 38.5% in 2015 (p = .09). The non-Beijing strains represented Euro-American lineage (Latin American Mediterranean [LAM], Ural, Haarlem, T, X genotypes) and Indo-Oceanic lineage (one EAI-IND isolate). The proportion of isolates resistant to two or more drugs increased from 22.4% to 29.1% (p = .1). The pre-XDR/XDR isolates were identified only within the Beijing genotype. In contrast, the drug resistance rate decreased in the LAM genotype from 42.1% to 11.8% (p = .05). The Beijing B0/W148-cluster ('successful Russian strain') included only MDR, pre-XDR or XDR isolates. All B0/W148-cluster isolates were resistant to two or more drugs compared to 28% of the Beijing 94-32-cluster (p = .0002). The Beijing genotype was not identified in the isolates from patients born in Estonia before 1940 compared to its 35.2% rate among other patients. In summary, the circulation of the highly drug-resistant isolates of the Beijing B0/W148 subtype, the increased prevalence of the Beijing genotype among HIV-coinfected patients and the increased number of patients with alcohol abuse (47.5%) present major challenges of the current TB control in Estonia. The Beijing genotype was likely brought to Estonia after 1945 due to the massive human influx from the Soviet Union. In contrast, the main genotypes of the Euro-American lineage were likely endemic in Estonia during all 20th century., (© 2020 Wiley-VCH GmbH.)

Objectives: We assessed the genetic structure of the Mycobacterium tuberculosis population in Estonia with a special focus on major epidemic/endemic clones and drug resistance determinants. We investigated the hypothesis of the decisive impact of massive human influx on the locally circulating genotypes. Estonia received a mass immigration from Russia during 1945-90 followed by enhanced interaction with the EU since 1991., Methods: The study sample included M. tuberculosis isolates from patients newly diagnosed with TB in 2014 in North Estonia (including the capital Tallinn). The isolates were subjected to first- and second-line drug susceptibility testing, detection of mutations in rpoB, katG, inhA, rrs, embB and gyrA and lineage/clone-specific genotyping., Results: Of the M. tuberculosis isolates, 39.8% were assigned to the Beijing genotype; 56.8% of them were MDR. In contrast, all three major non-Beijing genotypes (LAM, Haarlem and Ural) were mainly drug susceptible. MDR was more prevalent among Beijing B0/W148-cluster isolates (81.8%) compared with other Beijing isolates (20.0%; P = 0.0007). The pre-XDR phenotype was found in eight isolates, of which six belonged to Beijing B0/W148. All rifampicin-resistant and ofloxacin-resistant and 97% of isoniazid-resistant isolates harboured resistance mutations in rpoB, gyrA and katG. The rpoB S531L, katG S315T and embB M306V mutations were the most prevalent., Conclusions: The major pool of the Beijing isolates was brought to Estonia before 1990. However, an active circulation of the most hazardous MDR-associated Beijing B0/W148-cluster started only in the last 20 years and its significantly increased circulation presents the major threat to TB control in Estonia. The overwhelming prevalence of the rpoB531 and katG315 mutations in the MDR-associated Beijing isolates requires attention., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined., Methods: Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens., Results: Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome., Conclusions: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance., (Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are associated with worse treatment outcomes for patients, including higher mortality, than for drug-sensitive tuberculosis. Delamanid (OPC-67683) is a novel anti-TB medication with demonstrated activity against multidrug-resistant disease. Patients who participated in the previously reported randomised, placebo-controlled trial of delamanid and the subsequent open-label extension trial were eligible to participate in a 24-month observational study designed to capture treatment outcomes. Treatment outcomes, as assessed by clinicians and defined by the World Health Organization, were categorised as favourable and unfavourable. Delamanid treatment groups were combined for analysis, based on their duration of treatment. In total, for 421 (87.5%) out of 481 patients from the original randomised controlled trial, consent was granted for follow-up assessments. Favourable outcomes were observed in 143 (74.5%) out of 192 patients who received delamanid for ≥6 months, compared to 126 (55%) out of 229 patients who received delamanid for ≤2 months. Mortality was reduced to 1.0% among those receiving long-term delamanid versus short-term/no delamanid (8.3%; p<0.001). Treatment benefit was also seen among patients with extensively drug-resistant TB. This analysis suggests that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.

Background: The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries., Methods: From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis., Findings: Among 1278 patients, 43·7% showed resistance to at least one second-line drug, 20·0% to at least one second-line injectable drug, and 12·9% to at least one fluoroquinolone. 6·7% of patients had XDR tuberculosis (range across study sites 0·8-15·2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries., Interpretation: Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies., Funding: US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In the first attempt to establish a quality assurance programme for susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones, 20 strains with different fluoroquinolone susceptibility patterns were distributed by the Supranational Reference Laboratory in Stockholm to the other mycobacterial reference laboratories of the Nordic and Baltic countries. Susceptibility testing to fluoroquinolones was performed according to routine procedures in each laboratory. Results were compared to sequence analysis of the gyrA gene and minimal inhibitory concentration determination. Most laboratories found identical susceptibility patterns. The two resistant strains were correctly identified by all laboratories, but three laboratories each falsely reported one susceptible strain as resistant. These results indicate that the participating laboratories yield reliable results in detection of fluoroquinolone-resistant strains, although the need for a standardised quality assurance programme for drug susceptibility testing for fluoroquinolones is stressed by the strains falsely reported as resistant.

It is generally thought that there is full cross-resistance in Mycobacterium tuberculosis between the aminoglycoside drugs kanamycin and amikacin. However, kanamycin resistance and amikacin susceptibility were seen in 43 of 79 (54%) multidrug-resistant Estonian isolates, indicating that there might be a need to test the resistance of M. tuberculosis isolates to both drugs.

Restriction fragment length polymorphism (RFLP) analysis of 209 Mycobacterium tuberculosis clinical isolates obtained from newly detected pulmonary tuberculosis patients (151 male and 58 female; mean age, 41 years) in Estonia during 1994 showed that 61 isolates (29%) belonged to a genetically closely related group of isolates, family A, with a predominant IS6110 banding pattern. These strains shared the majority of their IS6110 DNA-containing restriction fragments, representing a predominant banding pattern (similarity, >65%). This family A comprised 12 clusters of identical isolates, and the largest cluster comprised 10 strains. The majority (87.5%) of all multidrug-resistant (MDR) isolates, 67.2% of all isolates with any drug resistance, but only 12% of the fully susceptible isolates of M. tuberculosis belonged to family A. These strains were confirmed by spoligotyping as members of the Beijing genotype family. The spread of Beijing genotype MDR M. tuberculosis strains was also frequently seen in 1997 to 1999. The members of this homogenous group of drug-resistant M. tuberculosis strains have contributed substantially to the continual emergence of drug-resistant tuberculosis all over Estonia.

The Central Europe forms a buffer zone between the countries of the European West reporting tuberculosis notification rates lower than 20 per 100,000, the cut-off set between low and high incidence areas, and the Eastern European countries including the republics of the former USSR, Russia and the Baltic States. The Czech Republic holds an intermediate place between these two territories with the total notification rate of tuberculosis cases 18.8, 9.7 bacteriologically verified and 5.7 positive in direct smear per 100,000 in 1996. Data on drug resistance obtained from the WHO/IUATLD Global Project on Anti-Tuberculosis Drug Resistance Surveillance were available from the Czech Republic, the only Central European country participating in the Project. The prevalence of resistant cases was here low: 2% primary and 13% acquired, and MDR cases were recorded in 1% of untreated and in 6% of repeatedly treated patients. The first microepidemic of MDR cases comprising 21 individuals was characterized by DNA fingerprinting. This outbreak pointed out the MDR tuberculosis as a new, extremely serious phenomenon in the epidemiology of tuberculosis. Corresponding data from Estonia and Latvia showed incomparably higher values in the drug resistance pattern: from 28 to 34% primary and 46 to 74% acquired resistance. MDR strains were reported in 9 to 14% of untreated and in 19 to 54% of repeatedly treated patients.

Setting: The incidence of drug resistant tuberculosis in Estonia has increased rapidly during the last five to six years., Objective: To investigate the drug resistance patterns of Mycobacterium tuberculosis isolated from tuberculosis patients in Estonia., Results: In 1994, 623 cases of tuberculosis were diagnosed in Estonia, 518 new cases with no previous history of tuberculosis, and 105 with a history of previous treatment for tuberculosis. All pulmonary M. tuberculosis isolates from 1994 were analysed for drug susceptibility. Of the 302 new cases (58.3%) that were culture verified, 28% had isolates resistant to one or more of the four drugs tested (isoniazid, rifampicin, streptomycin, ethambutol), and 9% had multi-drug resistant (resistant to at least isoniazid and rifampicin) strains., Conclusion: The incidence of drug resistance in M. tuberculosis is high in Estonia.