ResearchPad - tuberculosis https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance]]> https://www.researchpad.co/article/elastic_article_15716 Meta-analyses on impact of isoniazid-resistant tuberculosis informed the World Health Organization recommendation of a levofloxacin-strengthened rifampicin-based regimen.We estimated the effect of initial rifampicin resistance (Rr) and/or isoniazid resistance (Hr) on treatment failure or relapse. We also determined the frequency of missed initial and acquired Rr to estimate the impact of true Hr.MethodsRetrospective analysis of 7291 treatment episodes with known initial isoniazid and rifampicin status obtained from individual patient databases maintained by the Damien Foundation Bangladesh over 20 years. Drug susceptibility test results were confirmed by the programme’s designated supra-national tuberculosis laboratory. To detect missed Rr among isolates routinely classified as Hr, rpoB gene sequencing was done randomly and on a sample selected for suspected missed Rr.ResultsInitial Hr caused a large recurrence excess after the 8-month regimen for new cases (rifampicin for two months), but had little impact on rifampicin-throughout regimens: (6 months, new cases; 3.8%; OR 0.8, 95%CI:0.3,2.8; 8 months, retreatment cases: 7.3%, OR 1.8; 95%CI:1.3,2.6). Rr was missed in 7.6% of randomly selected "Hr" strains. Acquired Rr was frequent among recurrences on rifampicin-throughout regimens, particularly after the retreatment regimen (31.9%). It was higher in mono-Hr (29.3%; aOR 3.5, 95%CI:1.5,8.5) and poly-Hr (53.3%; aOR 10.2, 95%CI 4.4,23.7) than in susceptible tuberculosis, but virtually absent after the 8-month new case regimen. Comparing Bangladesh (low Rr prevalence) with a high Rr prevalence setting,true Hr corrected for missed Rr caused only 2–3 treatment failures per 1000 TB cases (of whom 27% were retreatments) in both.ConclusionsOur analysis reveals a non-negligible extent of misclassifying as isoniazid resistance of what is actually missed multidrug-resistant tuberculosis. Recommending for such cases a “strengthened” regimen containing a fluoroquinolone provokes a direct route to extensive resistance while offering little benefit against the minor role of true Hr tuberculosis in rifampicin-throughout first-line regimen. ]]> <![CDATA[Confidential, accessible point-of-care sexual health services to support the participation of key populations in biobehavioural surveys: Lessons for Papua New Guinea and other settings where reach of key populations is limited]]> https://www.researchpad.co/article/elastic_article_14720 To achieve the UNAIDS 90-90-90 targets at a national level, many countries must accelerate service coverage among key populations. To do this, key population programs have adopted methods similar to those used in respondent-driven sampling (RDS) to expand reach. A deeper understanding of factors from RDS surveys that enhance health service engagement can improve key population programs. To understand the in-depth lives of key populations, acceptance of expanded point-of-care biological testing and determine drivers of participation in RDS surveys, we conducted semi-structured interviews with 111 key population participants (12–65 years) were purposefully selected from six biobehavioral surveys (BBS) in three cities in Papua New Guinea. Key populations were female sex workers, men who have sex with men, and transgender women. Four reasons motivated individuals to participate in the BBS: peer referrals; private, confidential, and stigma-free study facilities; “one-stop shop” services that provided multiple tests and with same-day results, sexually transmitted infection treatment, and referrals; and the desire to know ones’ health status. Biobehavioral surveys, and programs offering key population services can incorporate the approach we used to facilitate key population engagement in the HIV cascade.

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<![CDATA[High prevalence of phenotypic pyrazinamide resistance and its association with <i>pncA</i> gene mutations in <i>Mycobacterium tuberculosis</i> isolates from Uganda]]> https://www.researchpad.co/article/elastic_article_14718 Susceptibility testing for pyrazinamide (PZA), a cornerstone anti-TB drug is not commonly done in Uganda because it is expensive and characterized with technical difficulties thus resistance to this drug is less studied. Resistance is commonly associated with mutations in the pncA gene and its promoter region. However, these mutations vary geographically and those conferring phenotypic resistance are unknown in Uganda. This study determined the prevalence of PZA resistance and its association with pncA mutations.Materials and methodsUsing a cross-sectional design, archived isolates collected during the Uganda national drug resistance survey between 2008–2011 were sub-cultured. PZA resistance was tested by BACTEC Mycobacterial Growth Indicator Tube (MGIT) 960 system. Sequence reads were downloaded from the NCBI Library and bioinformatics pipelines were used to screen for PZA resistance–conferring mutations.ResultsThe prevalence of phenotypic PZA resistance was found to be 21%. The sensitivity and specificity of pncA sequencing were 24% (95% CI, 9.36–45.13%) and 100% (73.54% - 100.0%) respectively. We identified four mutations associated with PZA phenotypic resistance in Uganda; K96R, T142R, R154G and V180F.ConclusionThere is a high prevalence of phenotypic PZA resistance among TB patients in Uganda. The low sensitivity of pncA gene sequencing confirms the already documented discordances suggesting other mechanisms of PZA resistance in Mycobacterium tuberculosis. ]]> <![CDATA[Early cell-autonomous accumulation of neutral lipids during infection promotes mycobacterial growth]]> https://www.researchpad.co/article/elastic_article_14614 Lipids represent an important source of nutrition for infecting mycobacteria, accumulating within the necrotic core of granulomas and present in foamy macrophages associated with mycobacterial infection. In order to better understand the timing, process and importance of lipid accumulation, we developed methods for direct in vivo visualization and quantification of this process using the zebrafish-M. marinum larval model of infection. We find that neutral lipids accumulate cell-autonomously in mycobacterium-infected macrophages in vivo during early infection, with detectable levels of accumulation by two days post-infection. Treatment with ezetimibe, an FDA-approved drug, resulted in decreased levels of free cholesterol and neutral lipids, and a reduction of bacterial growth in vivo. The effect of ezetimibe in reducing bacterial growth was dependent on the mce4 operon, a key bacterial determinant of lipid utilization. Thus, in vivo, lipid accumulation can occur cell-autonomously at early timepoints of mycobacterial infection, and limitation of this process results in decreased bacterial burden.

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<![CDATA[Predicting the impact of patient and private provider behavior on diagnostic delay for pulmonary tuberculosis patients in India: A simulation modeling study]]> https://www.researchpad.co/article/elastic_article_14543 India contributes more than a quarter of the 10 million global tuberculosis (TB) cases every year.Several studies capture long, circuitous care pathways followed by TB patients until their diagnosis. However, these studies do not quantify the link between diagnostic delay and underlying patient and provider behavior characteristics.What did the researchers do and find?We developed a quantitative simulation model to estimate the impact of behavioral characteristics of patients and providers on diagnostic delay and estimated the parameters of this model using data from detailed interviews of 76 patients from Mumbai and 64 patients from Patna.We found that earlier test ordering by providers would yield a much larger reduction in diagnostic delay than increasing their diagnostic accuracy.What do these findings mean?Policy-makers and implementing agencies should encourage early test ordering behavior by providers to reduce diagnostic delay, and, consequently, to reduce disease transmission. ]]> <![CDATA[Disseminated Histoplasmosis: Fighting a neglected killer of patients with advanced HIV disease in Latin America]]> https://www.researchpad.co/article/elastic_article_14538 <![CDATA[Health profile of adult special immigrant visa holders arriving from Iraq and Afghanistan to the United States, 2009–2017: A cross-sectional analysis]]> https://www.researchpad.co/article/elastic_article_13850 Between 2,000 and 19,000 Special Immigrant Visa holders (SIVH) from Iraq and Afghanistan have resettled in the United States annually since 2008.Per the Immigration and Nationality Act, SIVH, like other immigrants and refugees, must be examined by a physician before arriving in the US. Results of these overseas examinations are transmitted by the Centers for Disease Control and Prevention (CDC) to US state and local health departments via CDC’s Electronic Disease Notification system (EDN).Increasing provider knowledge about the health conditions most commonly encountered in SIVH as well as any differences in health conditions between SIVH from Iraq and Afghanistan may facilitate diagnostic screening, examination, and referrals to additional healthcare providers in the US.Information about the health of SIV populations is limited and would be beneficial for US clinicians who see SIVH in their clinics.What did the researchers do and find?In this cross-sectional analysis, we analyzed overseas medical exam data in CDC’s EDN for 19,167 SIV Iraqi and Afghan adults who resettled to the United States from April 2009 through December 2017.Among all SIVH, 56.5% were overweight or had obesity, 2.4% reported hypertension, 1.1% reported diabetes, and 19.4% reported current or previous tobacco use.In general, Iraqi SIVH were more likely to have obesity, diabetes, and be current or former smokers than Afghan SIVH.What do these findings mean?State public health agencies and clinicians screening SIVH should consider screening for diabetes among those with risk factors and prompt referral and management of obesity, hypertension, and smoking.Behavioral risk factor counseling and referral to culturally appropriate chronic disease prevention programs can be initiated at screening visits and subsequently reemphasized with primary care providers and other healthcare professionals.Limitations include the inability to obtain all SIVH records, self-reported medical history of NCDs, and underdiagnosis of NCDs such as hypertension and diabetes because formal laboratory testing for NCDs is not used during overseas medical exams. ]]> <![CDATA[Patients infected with <i>Mycobacterium africanum</i> versus <i>Mycobacterium tuberculosis</i> possess distinct intestinal microbiota]]> https://www.researchpad.co/article/elastic_article_13847 Mycobacterium africanum (MAF) is a hypovirulent mycobacterium species that is co-endemic with Mycobacterium tuberculosis (MTB) in West Africa and is selectively responsible for up to half the tuberculosis cases in this region. Why some individuals become infected with MAF versus MTB is unclear but has been suggested to be determined by differential host immune competency. Since the microbiome has now been implicated in numerous studies to generally influence host resistance to disease, we investigated whether differences in the intestinal microbiota might associate with MAF as compared with MTB infection. This report presents the first analysis of the intestinal microbiome of MAF-infected subjects as well as a comparison with the microbiota of co-endemic MTB patients and reveals that the microbiota of individuals with MAF infection display both decreased diversity and distinct differences in microbial taxa when compared to both MTB-infected and healthy controls. Furthermore, our data reveal for the first time in TB patients a correlation between the abundance of certain taxa and host blood transcriptional changes related to immune function. Our study also establishes that antibiotic treatment induces parallel changes in the gut microbiota of MAF- and MTB-infected patients. Although not directly addressed in the present study, the findings presented here raise the possibility that the microbiota or other host physiologic or immune factors closely associated with it may be a factor underlying the differential susceptibility of West Africans to MAF infection. In addition, the data identify certain commensal taxa that could be tested in future studies as specific determinants of this association.

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<![CDATA[Interaction between host genes and <i>Mycobacterium tuberculosis</i> lineage can affect tuberculosis severity: Evidence for coevolution?]]> https://www.researchpad.co/article/elastic_article_13824 Susceptibility to tuberculosis (TB) is affected by genetic variation in both the human host and the causative bacterium, Mycobacterium tuberculosis. However, prior studies of the genetics of each species have not explained a large part of TB risk. The possibility exists that risk can be better estimated from patterns of variation in the two species as a unit, such that some combinations provide increased risk, or in the presence of TB, increased disease severity. We hypothesized that alleles in the two species that have co-existed for long periods are more likely to reduce disease severity so as to promote prolonged co-occurrence. We tested this by studying TB severity in two patient cohorts from Uganda for which paired MTB-human DNA were available. We examined severity, as measured by the Bandim TBscore, and assessed whether there was an interaction between MTB lineage and SNPs in the host with this metric. Our results indicate that the most recent TB lineage (L4.6/Uganda) when found together with an ancestral allele in SLC11A1 resulted in more severe disease. This finding is consistent with the conclusion that MTB and human have coevolved to modulate TB severity.

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<![CDATA[Mortality estimates by age and sex among persons living with HIV after ART initiation in Zambia using electronic medical records supplemented with tracing a sample of lost patients: A cohort study]]> https://www.researchpad.co/article/elastic_article_13858 Despite many studies demonstrating differences in HIV-related outcomes between men and women on antiretroviral therapy (ART) in sub-Saharan Africa, few studies use a probability sample that would enable them to offer regionally representative estimates.Many studies taken from routine service delivery settings are unable to account for outcomes among individuals lost to follow-up, which may threaten the validity of estimates comparing mortality in men and women.Furthermore, whether differences in survival between men and women vary across other important sociodemographic characteristics (such as age) remains underexplored.What did the researchers do and find?We used a multistage sampling approach to enumerate an analysis population of HIV-positive patients visiting public health facilities in 4 provinces in Zambia (Lusaka, Southern, Eastern, and Western).We estimated the association between sex and mortality overall and by age, adjusting for other sociodemographic and clinical characteristics.Of 49,129 adults newly initiating ART, the mortality rate was almost twice as high in men compared to women.Analysis of age-by-sex interactions revealed particularly elevated mortality among young males (as compared to females of the same age). While mortality rates appeared to fall with age among men, mortality rates rose with age among women, and by 50 years of age, women had a 2–3 times higher rate of death compared to women under 30.What do these findings mean?Among adults living with HIV in Zambia, men on average experience greater mortality compared to women, but this difference varies markedly by age, even after adjustment for other sociodemographic and clinical characteristics (e.g., baseline level of immunosuppression).Additional means of engaging and supporting younger men in HIV care is urgently needed and may include improved access to self-testing, use of financial incentives, and male-friendly services that feature flexible hours, an integrated multi-disease care model, and reduced visit frequency.Rising mortality associated with age in women greater than would be expected in the general population suggests that health services targeting women of reproductive age may be in part responsible for good clinical outcomes in younger women, but also highlights the need for specific programs to engage older women in care. ]]> <![CDATA[Mobilising community networks for early identification of tuberculosis and treatment initiation in Cambodia: an evaluation of a seed-and-recruit model]]> https://www.researchpad.co/article/elastic_article_12762 A tuberculosis active case finding model that mobilises community networks using a seed-and-recruit approach is associated with early identification and treatment of TB, and is also more likely to find bacteriologically confirmed TB cases in Cambodia https://bit.ly/33PWqyR

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<![CDATA[Systematic Review and Meta-Analysis of Sex Differences in Social Contact Patterns and Implications for Tuberculosis Transmission and Control]]> https://www.researchpad.co/article/Nee18d789-0b3b-40b1-b66a-3ae64454cf7f

Social contact patterns might contribute to excess burden of tuberculosis in men. We conducted a study of social contact surveys to evaluate contact patterns relevant to tuberculosis transmission. Available data describe 21 surveys in 17 countries and show profound differences in sex-based and age-based patterns of contact. Adults reported more adult contacts than children. Children preferentially mixed with women in all surveys (median sex assortativity 58%, interquartile range [IQR] 57%–59% for boys, 61% [IQR 60%–63%] for girls). Men and women reported sex-assortative mixing in 80% and 95% of surveys (median sex assortativity 56% [IQR 54%–58%] for men, 59% [IQR 57%–63%] for women). Sex-specific patterns of contact with adults were similar at home and outside the home for children; adults reported greater sex assortativity outside the home in most surveys. Sex assortativity in adult contacts likely contributes to sex disparities in adult tuberculosis burden by amplifying incidence among men.

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<![CDATA[A Neighbor-Based Approach to Identify Tuberculosis Exposure, the Kopanyo Study ]]> https://www.researchpad.co/article/N03a08efc-2a80-4951-a22c-371beaa39189

Contact investigation is one public health measure used to prevent tuberculosis by identifying and treating persons exposed to Mycobacterium tuberculosis. Contact investigations are a major tenet of global tuberculosis elimination efforts, but for many reasons remain ineffective. We describe a novel neighbor-based approach to reframe contact investigations.

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<![CDATA[Pretreatment Out-of-Pocket Expenses for Presumptive Multidrug-Resistant Tuberculosis Patients, India, 2016–2017]]> https://www.researchpad.co/article/Nf6638d43-464e-405c-a78e-d1fda6d13cb9

In India, under the National Tuberculosis Elimination Programme, the government provides free treatment for multidrug-resistant tuberculosis; however, many patients seek care elsewhere, which is costly. To determine those out-of-pocket expenses, we interviewed 40 presumptive patients and found that they spent more than their median annual income before registering for the government program.

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<![CDATA[Clustered micronodules as predominant manifestation on CT: A sign of active but indolently evolving pulmonary tuberculosis]]> https://www.researchpad.co/article/N48b20e2f-c3ed-4c3c-a251-c583ed3c8c8a

Objective

To investigate the prevalence, patient characteristics, and natural history of clustered micronodules (CMs) in active pulmonary tuberculosis.

Materials and methods

From January 2013 through July 2018, 833 consecutive patients with bacteriologically or polymerase chain reaction–proven active pulmonary tuberculosis were retrospectively evaluated. CMs were defined as a localized aggregation of multiple dense discrete micronodules, which primarily distributed around small airways distal to the level of the segmental bronchus: small airways surrounded by CMs maintained luminal patency and the CMs might coalesce into a larger nodule. The patients were dichotomized according to whether the predominant computed tomography (CT) abnormalities were CMs. We analyzed radiologic and pathologic findings in patients whose predominant diagnostic CT abnormalities were CMs, along with those of incidental pre-diagnostic CT scans, if available. Chi-square, McNemar, Student t-test and Wilcoxon-signed rank test were performed.

Results

CMs were the predominant CT abnormality in 2.6% of the patients (22/833, 95% CI, 1.8–4.0%) with less sputum smear-positivity (4.8% vs 31.0%; p = .010) and a similar proportion of immunocompromised status (40.9% vs 46.0%; p = .637) than those without having CMs as the predominant CT abnormality. The time interval for minimal radiologic progression was 6.4 months. The extent of CMs increased with disease progression, frequently accompanied by consolidation and small airway wall thickening. Pathologically, smaller CMs were non-caseating granulomas confined to the peribronchiolar interstitium, whereas larger CMs were caseating granulomas involving lung parenchyma. Two of the five patients with a pre-diagnostic CT scan obtained more than 50 months pre-diagnosis showed an incipient stage of CMs, in which they were small peribronchiolar nodules.

Conclusion

Active pulmonary tuberculosis manifested predominantly as CMs in 2.6% of patients, with scarce of acid-fast bacilli smear-positivity and no association with impaired host immunity. CMs indolently progressed, accompanied by consolidation and small airway wall thickening, and originated from small nodules.

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<![CDATA[Risk factors associated to a high Mycobacterium tuberculosis complex seroprevalence in wild boar (Sus scrofa) from a low bovine tuberculosis prevalence area]]> https://www.researchpad.co/article/Nfbbd03ef-7cb8-4d82-b605-16cf8ee0d77e

Animal tuberculosis is a worldwide zoonotic disease caused principally by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC). In southern Iberian Peninsula, wild reservoirs such as the wild boar, among other factors, have prevented the eradication of bovine tuberculosis. However, most of the studies have been focused on south-central Spain, where the prevalence of tuberculosis is high among wild ungulates and cattle herds. In northern regions, where wild boar density and bovine tuberculosis prevalence are lower, fewer studies have been carried out and the role of this species is still under debate. The aim of this study was to describe the temporal and spatial distribution of antibodies against MTC in wild boar from the Basque Country, northern Spain. Sera from 1902 animals were collected between 2010 and 2016. The seroprevalence was determined with an in house enzyme-linked immunosorbent assay and the search of risk factors was assessed by Generalized Linear Models. Overall, 17% of wild boars (326/1902; 95%CI, [15.5%–18.9%]) showed antibodies against MTC. Risk factors associated with seropositivity were the year and location of sampling, the number of MTC positive cattle, the distance to positive farms and the percentage of shrub cover. Younger age classes were associated with increased antibody titres among seropositive individuals. The seroprevalence detected was higher than those previously reported in neighbouring regions. Hence, further studies are needed to better understand the role of wild boar in the epidemiology of tuberculosis in low tuberculosis prevalence areas and consequently, its relevance when developing control strategies.

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<![CDATA[Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions]]> https://www.researchpad.co/article/N5c16b8fb-2363-48af-bce8-dbbca8329b25

Mycobacterium tuberculosis is the causative agent of tuberculosis and has evolved an ability to survive in hostile host environments. M. tuberculosis is thought to utilize the rTCA cycle to sustain its latent growth during infection, but the enzymatic characteristics and physiological function for the key citrate lyase of the rTCA cycle, MtbCitE, in the important pathogen remain unclear. In this study, we investigated the function of MtbCitE based on its structural properties and sequence comparisons with other bacterial citrate lyase subunits. We showed that several amino acid residues were important for the citrate cleavage activity of MtbCitE. Strikingly, the citrate cleavage activity of MtbCitE was inhibited by ATP, indicating that energy metabolism might couple with the regulation of MtbCitE activity, which differed from other CitEs. More interestingly, deletion of citE from Mycobacterium bovis BCG decreased the mycobacterial survival rate under hypoxic conditions, whereas complementation with citE restored the phenotype to wild-type levels. Consistently, three key rTCA cycle enzymes were positively regulated under hypoxic conditions in mycobacteria. Therefore, we characterized a unique citrate lyase MtbCitE from M. tuberculosis and found that the CitE protein significantly contributed to mycobacterial survival under hypoxic conditions.

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<![CDATA[High Incidence of Active Tuberculosis in Asylum Seekers from Eritrea and Somalia in the First 5 Years after Arrival in the Netherlands]]> https://www.researchpad.co/article/Nc8af2d48-d8ba-4dff-a071-b7ce5fd281b7

Three quarters of tuberculosis (TB) patients in the Netherlands are foreign-born; 26% are from Eritrea or Somalia. We analyzed TB incidence rates in asylum seekers from Eritrea and Somalia in the first 5 years after arrival in the Netherlands (2013–2017) and performed survival analysis with Cox proportional hazards regression to analyze the effect of age and sex on the risk for TB. TB incidence remained high 5 years after arrival in asylum seekers from Eritrea (309 cases/100,000 person-years) and Somalia (81 cases/100,000 person-years). Age >18 years was associated with a higher risk for TB in asylum seekers from Eritrea (3.4 times higher) and Somalia (3.7 times higher), and male sex was associated with a 1.6 times higher risk for TB in asylum seekers from Eritrea. Screening and treating asylum seekers from high-incidence areas for latent TB infection upon arrival would further reduce TB incidence in the Netherlands.

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<![CDATA[Predictors of loss to follow-up of tuberculosis cases under the DOTS programme in Namibia]]> https://www.researchpad.co/article/N1182245d-6786-4993-b29c-d79f6eba7ce3

Background

In Namibia, one out of every 25 cases of tuberculosis (TB) is “lost to follow-up” (LTFU). This has impacted negatively on national efforts to end the disease by 2035. The aim of this study was to determine the trends and predictors of LTFU under the directly observed treatment short-course (DOTS) programme in Namibia.

Methods

The study involved a retrospective longitudinal analysis of a nationwide cohort of TB cases registered under the DOTS programme in Namibia from 2006 to 2015. The trends and predictors of LTFU among cases in the National Electronic TB Register of the National TB and Leprosy Program were respectively determined by interrupted time series and multivariate logistic regression analyses using R-Studio software.

Results

Out of 104 203 TB cases, 3775 (3.6%) were LTFU. A quarter (26%) of cases with poor outcomes were due to LTFU. The annual decline in cases of LTFU was significant between the first (2005–2010) and second (2010–2015) medium-term plan period for TB programme implementation (p=0.002). The independent predictors of LTFU were male sex (p=0.004), 15–24 years age group (p=0.03), provider of treatment (p<0.001), intensive phase (p=0.047) and living in border/transit regions (p<0.001). HIV co-infection and TB regimen were not significant predictors of LTFU.

Conclusions

There were declining trends in LTFU in Namibia. DOTS programmes should integrate socioeconomic interventions for young and middle-aged adult male TB cases to reduce LTFU.

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<![CDATA[Factors associated with delay in treatment initiation for pulmonary tuberculosis]]> https://www.researchpad.co/article/Neb9702ea-2763-45b1-96fd-d08576360256

Background

Delays in treatment initiation for tuberculosis (TB) may lead to worse clinical outcomes and increased transmission. We aimed to determine factors associated with treatment delays, to guide public health action.

Methods

We extracted data on clinical characteristics and documented potential barriers to treatment from all pulmonary TB cases with clinical case review data from 2011 to 2015 and linked these to TB surveillance data. We described the distribution of delays from symptom onset to first presentation (“presentation delay”) and from presentation to treatment (“healthcare delay”). We calculated time ratios (TRs) to determine the association between sociodemographic and clinical factors and delay outcomes.

Results

Median presentation delay was 30 days (interquartile range (IQR) 11–72 days). Language barriers were associated with 40% longer presentation delay (TR 1.40, 1.01–1.94). Median healthcare delay was 40 days (IQR 13–89 days), and mostly consisted of the time taken before deciding to refer to TB specialists (median 26 days, IQR 4–73 days). Shorter healthcare delay was associated with positive sputum smear (TR 0.58, 0.47–0.70), UK residency <2 years (TR 0.47, 0.32–0.67), male sex (TR 0.74, 0.60–0.91) and secondary care referral (TR 0.63, 0.51–0.78).

Conclusions

Our findings support continued initiatives to enable access to care for migrant populations to minimise presentation delay. Multifaceted approaches to increase clinician awareness of TB clinical presentations, to implement systems enabling early case recognition, to maximise the yield from sputum smear investigations and to ensure rapid diagnosis of smear negative cases are required to achieve further TB control.

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