Trends in TB and HIV care and treatment cascade, Kenya, 2008-2018.

BACKGROUND: HIV infection is associated with high mortality among people with TB. Antiretroviral therapy (ART) reduces TB incidence and mortality among people living with HIV (PLHIV). Since 2005, Kenya has scaled up TB and HIV prevention, diagnosis and treatment. We evaluated the impact of these services on trends and TB treatment outcomes.METHODS: Using Microsoft Excel (2016) and Epi-Info 7, we analysed Kenya Ministry of Health TB surveillance data from 2008 to 2018 to determine trends in TB notifications, TB classification, HIV and ART status, and TB treatment outcomes.RESULTS: Among the 1,047,406 people reported with TB, 93% knew their HIV status, and 37% of these were HIV-positive. Among persons with TB and HIV, 69% received ART. Between 2008 and 2018, annual TB notifications declined from 110,252 to 96,562, and HIV-coinfection declined from 45% to 27%. HIV testing and ART uptake increased from 83% to 98% and from 30% to 97%, respectively. TB case fatality rose from 3.5% to 3.9% (P <0.018) among HIV-negative people and from 5.1% to 11.2% (P <0.001) among PLHIV on ART.CONCLUSION: TB notifications decreased in settings with suboptimal case detection. Although HIV-TB services were scaled-up, HIV-TB case fatality rose significantly. Concerted efforts are needed to address case detection and gaps in quality of TB care.

Can isoniazid preventive therapy be scaled up rapidly? Lessons learned in Kenya, 2014-2018.

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale-up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75-fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow-up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.

The effect of TB treatment on health-related quality of life for people with advanced HIV.

BACKGROUND: Study A5274 was an open-label trial of people with HIV (PLHIV) with CD4 cell count <50 cells/µL who were randomized to empirical TB treatment vs. isoniazid preventive therapy (IPT) in addition to antiretroviral therapy (ART). We evaluated health-related quality of life (HRQoL) by study arm, changes over time, and association with sociodemographic and clinical factors.METHODS: Participants aged >13 years were enrolled from outpatient clinics in 10 countries. HRQoL was assessed at Weeks 0, 8, 24 and 96 with questions about daily activity, hospital or emergency room visits, and general health status. We used logistic regression to examine HRQoL by arm and association with sociodemographic and clinical factors.RESULTS: Among 850 participants (424 empiric arm, 426 IPT arm), HRQoL improved over time with no difference between arms. At baseline and Week 24, participants with WHO Stage 3 or 4 events, or those who had Grade 3 or 4 signs/symptoms, were significantly more likely to report poor HRQoL using the composite of four HRQoL measures.CONCLUSION: HRQoL improved substantially in both arms during the study period. These findings show that ART, TB screening, and IPT can not only reduce mortality, but also improve HRQoL in PLHIV with advanced disease.

Performance of Xpert® MTB/RIF and Determine™ TB-LAM Ag in HIV-infected adults in peri-urban sites in Zambia.

SETTING: Peri-urban health facilities providing HIV and TB care in Zambia. OBJECTIVE: To evaluate 1) the impact of Xpert® MTB/RIF on time-to-diagnosis, treatment initiation, and outcomes among adult people living with HIV (PLHIV) on antiretroviral therapy (ART); and 2) the diagnostic performance of Xpert and Determine™ TB-LAM Ag assays. DESIGN: Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture. RESULTS: Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis (P = 0.018), and from evaluation to treatment initiation (P = 0.03) was significantly shorter for IP than for SOC. There was no difference in all-cause mortality (7.0% vs. 8.6%). TB-LAM Ag showed higher sensitivity with lower CD4 cell count: 81.8% at CD4 < 50 cells/mm3 vs. 31.7% overall. CONCLUSION: Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease.

Extensively drug-resistant tuberculosis 'hotspots' and sociodemographic associations in Durban, South Africa.

In KwaZulu-Natal, South Africa, the incidence of extensively drug-resistant tuberculosis (XDR-TB) is driven by the transmission of resistant strains. As data suggest that cases may be spatially clustered, we sought to identify 'hotspots' and describe these communities. We enrolled XDR-TB patients diagnosed from 2011 to 2014 in eThekwini. Global positioning system (GPS) coordinates for participant homes were collected and hotspots were identified based on population-adjusted XDR-TB incidence. The sociodemographic features of hotspots were characterised using census data. For a subset of participants, we mapped non-home XDR-TB congregate locations and compared these with results including only homes. Among 132 participants, 75 (57%) were female and 87 (66%) lived in urban or suburban locations. Fifteen of 197 census tracts were identified as XDR-TB hotspots with ≥95% confidence. Four spatial mapping methods identified one large hotspot in northeastern eThekwini. Hotspot communities had higher proportions of low educational attainment (12% vs. 9%) and unemployment (29.3% vs. 20.4%), and lower proportion of homes with flush toilets (36.4% vs. 68.9%). The case density shifted towards downtown Durban when congregate locations (e.g., workplaces) for 43 (33%) participants were mapped. In eThekwini, XDR-TB case homes were clustered into hotspots with more poverty indicators than non-hotspots. Prevention efforts targeting hotspot communities and congregate settings may be effective in reducing community transmission. .

Resource utilization for multidrug-resistant tuberculosis household contact investigations (A5300/I2003).

BACKGROUND: Current guidelines recommend evaluation of the household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB); however, implementation of this policy is challenging. OBJECTIVE: To describe the resource utilization and operational challenges encountered when identifying and characterizing adult MDR-TB index cases and their HHCs. DESIGN: Cross-sectional study of adult MDR-TB index cases and HHCs at 16 clinical research sites in eight countries. Site-level resource utilization was assessed with surveys. RESULTS: Between October 2015 and April 2016, 308 index cases and 1018 HHCs were enrolled. Of 280 index cases with sputum collected, 94 were smear-positive (34%, 95%CI 28-39), and of 201 with chest X-rays, 87 had cavitary disease (43%, 95%CI 37-50) after a mean duration of treatment of 8 weeks. Staff required 512 attempts to evaluate the 308 households, with a median time per attempt of 4 h; 77% (95%CI 73-80) of HHCs were at increased risk for TB: 13% were aged <5 years, 8% were infected with the human immunodeficiency virus, and 79% were positive on the tuberculin skin test/interferon-gamma release assay. One hundred and twenty-one previously undiagnosed TB cases were identified. Issues identified by site staff included the complexity of personnel and participant transportation, infection control, personnel safety and management of stigma. CONCLUSION: HHC investigations can be high yield, but are labor-intensive.

The California Multidrug-Resistant Tuberculosis Consult Service: a partnership of state and local programs.

Background: The US Centers for Disease Control and Prevention recommend expert consultation for multi-drug-resistant tuberculosis (MDR-TB) cases. In 2002, the California MDR-TB Service was created to provide expert MDR-TB consultations. We describe the characteristics, treatment outcomes and management of patients referred to the Service. Methods: Surveillance data were used for descriptive analysis of cases, with consultation during July 2002-December 2012. Clinical consultation data and modified World Health Organization indicators were used to assess the care and management of cases, with consultation from January 2009 to December 2012. Results: Of 339 MDR-TB patients, 140 received a consultation. The proportion of patients receiving a consultation increased from 12% in 2002 to 63% in 2012. There were 24 pre-extensively drug-resistant TB and 5 patients with extensively drug-resistant TB. The majority (n = 123, 88%) completed treatment, 5 (4%) died, 7 (5%) moved before treatment completion, 4 (3%) stopped treatment due to an adverse event and 1 (1%) had an unknown outcome. Indicator data showed that 86% underwent rapid molecular drug susceptibility testing, 98% received at least four drugs to which they had known or presumed susceptibility, and 93% culture converted within 6 months. Conclusions: Consultations with the MDR-TB Service increased over time. Results highlight successful treatment and indicator outcomes.

Contexte : Les Centers for Disease Control and Prevention des Etats Unis recommandent de consulter un expert en cas de tuberculose multirésistante (TB-MDR). En 2002, le California MDR-TB Service a été créé afin de fournir une consultation d'experts en TB-MDR. Nous décrivons les caractéristiques, les résultats du traitement et la prise en charge des patients référés vers ce service.Méthode : Les données de surveillance ont été utilisées pour une analyse descriptive des cas ayant eu une consultation entre juillet 2002 et décembre 2012. Les données de consultation clinique et les indicateurs modifiés de l'Organisation Mondiale de la Santé ont été utilisés afin d'évaluer la prise en charge des cas qui ont bénéficié d'une consultation entre janvier 2009 et décembre 2012.Résultats : Sur 339 patients TB-MDR, 140 ont bénéficié d'une consultation. Cette proportion est passée de 12% en 2002 à 63% en 2012. Il y a eu 24 patients TB pré-ultrarésistante et 5 patients TB ultrarésistante. La majorité (n = 123 ; 88%) a achevé le traitement, 5 (4%) sont décédés, 7 (5%) ont déménagé avant la fin du traitement, 4 (3%) ont arrêté le traitement à cause d'un effet secondaire et 1 (1%) a eu un résultat inconnu. Les indicateurs ont montré que 86% avaient bénéficié d'un test de pharmacosensibilité moléculaire rapide, que 98% avaient reçu au moins quatre médicaments avec une sensibilité connue ou présumée et que 93% ont eu une conversion de culture dans les 6 mois.Conclusion : Les consultations au service de TB-MDR ont augmenté dans le temps. Nous avons mis en lumière les bons résultats du traitement et des indicateurs.

Marco de referencia: Los Centros para el Control y la Prevención de Enfermedades de los Estados Unidos recomiendan que se recurra a la consulta con expertos en los casos de tuberculosis multirresistente (TB-MDR). En el 2002, se creó el California MDR-TB Service en California, con el objeto de proveer consultas de expertos en la materia. En el presente estudio se describen las características, los desenlaces terapéuticos y el tratamiento de los pacientes remitidos a este servicio.Métodos: Se utilizaron los datos de la vigilancia en el análisis descriptivo de los casos que consultaron el Servicio de julio del 2002 a diciembre del 2012. A partir de la base de datos de la consulta y los indicadores modificados de la Organización Mundial de la Salud se evaluó la atención y el tratamiento de los casos que consultaron de enero del 2009 a diciembre del 2012.Resultados: De los 339 pacientes con diagnóstico de TB-MDR, 140 obtuvieron la consulta de expertos. La proporción de pacientes con una consulta aumentó de un 12% en el 2002 al 63% en el 2012. Se atendieron 24 pacientes con TB pre-ultrarresistente y cinco pacientes con TB ultrarresistente. La mayoría completó el tratamiento (n = 123; 88%), 5 pacientes fallecieron (4%), 7 se mudaron antes de haber completado el tratamiento (5%), 4 interrumpieron el tratamiento debido a una reacción adversa (3%) y se desconoció el desenlace de 1 paciente (1%). Según los datos de los indicadores, en 86% de los casos se practicaron pruebas moleculares rápidas de sensibilidad a los medicamentos, el 98% de pacientes recibió como mínimo cuatro fármacos con sensibilidad confirmada o supuesta y el 93% de los pacientes había convertido el cultivo en un lapso de 6 meses.Conclusión: Las consultas al Servicio de expertos en TB-MDR han aumentado con el transcurso del tiempo. Los resultados del estudio ponen de manifiesto la eficacia del tratamiento y revelan indicadores de evolución muy favorables.

Toward a generation free of tuberculosis: TB disease and infection in individuals of college age in the United States.

OBJECTIVES: To assess the magnitude of active TB disease and latent TB infection (LTBI) in young adults of college age. PARTICIPANTS: Individuals who were aged 18-24 years in 2011 were used as a proxy for college students. METHODS: Active TB cases reported to the 2011 US National TB Surveillance System (NTSS) were included. LTBI prevalence was calculated from the 2011-2012 National Health and Nutrition Examination Survey. The 2011 American Community Survey was used to calculate population denominators. Analyses were stratified by nativity. RESULTS: Active TB disease incidence among persons aged 18-24 years was 2.82/100,000, 18.8/100,000 among foreign-born individuals and 0.9/100,000 among US-born individuals. In 2011, 878 TB cases were reported; 629 (71.6%) were foreign-born. LTBI prevalence among persons of 18-24 years was 2.5%: 8.7% and 1.3% among foreign-born and US-born, respectively. CONCLUSION: Active screening and treatment programs for foreign-born young adults could identify TB cases earlier and provide an opportunity for prevention efforts.

HIV testing uptake among the household contacts of multidrug-resistant tuberculosis index cases in eight countries.

SETTING: The household contacts (HHCs) of multidrug-resistant tuberculosis (MDR-TB) index cases are at high risk of tuberculous infection and disease progression, particularly if infected with the human immunodeficiency virus (HIV). HIV testing is important for risk assessment and clinical management. METHODS: This was a cross-sectional, multi-country study of adult MDR-TB index cases and HHCs. All adult and child HHCs were offered HIV testing if never tested or if HIV-negative >1 year previously when last tested. We measured HIV testing uptake and used logistic regression to evaluate predictors. RESULTS: A total of 1007 HHCs of 284 index cases were enrolled in eight countries. HIV status was known at enrolment for 226 (22%) HHCs; 39 (4%) were HIV-positive. HIV testing was offered to 769 (98%) of the 781 remaining HHCs; 544 (71%) agreed to testing. Of 535 who were actually tested, 26 (5%) were HIV-infected. HIV testing uptake varied by site (median 86%, range 0-100%; P < 0.0001), and was lower in children aged <18 years than in adults (59% vs. 78%; adjusted for site P < 0.0001). CONCLUSIONS: HIV testing of HHCs of MDR-TB index cases is feasible and high-yield, with 5% testing positive. Reasons for low test uptake among children and at specific sites-including sites with high HIV prevalence-require further study to ensure all persons at risk for HIV are aware of their status.

One-pump fiber optical parametric amplifier in presence of dispersion fluctuations: impact of fourth-order dispersion coefficient.

The impact of random dispersion fluctuations on the gain and saturation behavior of a one-pump fiber optical parametric amplifier (1-P FOPA) in the presence of fourth-order dispersion coefficient (ß4) is investigated. Three coupled amplitude equations with fiber losses are solved numerically for the calculation of the pump, signal, and idler. The performances of 1-P FOPA are also analyzed with variation of dispersion fluctuation amplitude (σ) and correlation length (Lc). Based on the numerical results, it is found that the gain spectra and saturation curves exhibit some differences when ß4 is considered. In comparison with the case where ß4 is ignored, the peak gain remains the same, but the 3 dB bandwidth increases when ß4 exists. Another notable difference is that the saturation power is shifted to lower or higher values, depending on the σ and Lc parameters. In general, the peak gain reduces as σ increases, and the peak gain reduction is greater for the case of shorter Lc. The numerical analysis is probably useful, especially for the case where the signal wavelength is detuned far from the pump wavelength.

Tuberculosis, human rights and ethics considerations along the route of a highly vulnerable migrant from sub-Saharan Africa to Europe.

Migrant health is a critical public health issue, and in many countries attention to this topic has focused on the link between migration and communicable diseases, including tuberculosis (TB). When creating public health policies to address the complex challenges posed by TB and migration, countries should focus these policies on evidence, ethics, and human rights. This paper traces a commonly used migration route from sub-Saharan Africa to Europe, identifying situations at each stage in which human rights and ethical values might be affected in relation to TB care. This illustration provides the basis for discussing TB and migration from the perspective of human rights, with a focus on the right to health. We then highlight three strands of discussion in the ethics and justice literature in an effort to develop more comprehensive ethics of migrant health. These strands include theories of global justice and global health ethics, the creation of 'firewalls' to separate enforcement of immigration law from protection of human rights, and the importance of non-stigmatization to health justice. The paper closes by reflecting briefly on how TB programs can better incorporate human rights and ethical principles and values into public health practice.

Latent tuberculous infection testing among HIV-infected persons in clinical care, United States, 2010-2012.

SETTING: Current guidelines recommend latent tuberculous infection (LTBI) testing at the time of human immunodeficiency virus (HIV) diagnosis and annually thereafter for persons at high risk of LTBI. OBJECTIVES: To estimate LTBI testing prevalence and describe the characteristics of HIV-infected persons who would benefit from annual LTBI testing. DESIGN: We estimated the proportions of LTBI testing among a nationally representative sample of HIV-infected adults in care between 2010 and 2012, and compared the patient characteristics of those with a positive LTBI test result to those with a negative result using χ2 tests. RESULTS: Among 2772 patients, 68.8% had been tested for LTBI at least once since HIV diagnosis, and 39.4% had been tested during the previous 12 months. Among patients tested at least once, 6.9% tested positive, 80.7% tested negative, and 12.4% had an indeterminate or undocumented result. Patients with a positive test were significantly more likely to be foreign-born, have lower educational attainment, and a household income at or below the federal poverty level. CONCLUSIONS: More than 30% of HIV-infected patients had never been tested for LTBI. Providers should test all patients for LTBI at the time of HIV diagnosis. The patient characteristics associated with a positive LTBI test result may guide provider decisions about annual testing.

Primary Sjogren's syndrome presenting as hypokalemic paralysis: A case series.

Primary Sjögren's syndrome (pSS) primarily involves exocrine glands, and renal tubular acidosis (RTA) is seen in one-third of the cases. RTA with hypokalemic paralysis as a presenting feature of pSS is described in few case reports in literature. We report 13 cases who presented as hypokalemic paralysis, and on evaluation were diagnosed to be pSS, as per the diagnostic criteria laid by the Sjögren's International Collaborative Clinical Alliance (2012). All patients were female, with a mean age at presentation being 33.1 ± 8.22 years (range, 25-48 years). Eleven patients had a complete distal RTA and two patients had incomplete distal RTA at the time of presentation. 62% (8/13) of patients had no signs and symptoms of exocrine gland involvement. All the cases were managed with oral alkali therapy, and six patients received additional immunomodulating agents. No improvement in renal tubular dysfunction (in the form of a reduction in the alkali dose) after immunomodulating therapy was observed over a mean follow-up of 2.8 years. Renal tubular dysfunction can be the presenting manifestation of pSS. It is important to consider the possible presence of this disorder in adults with otherwise unexplained distal RTA or hypokalemia.

Malnutrition associated with unfavorable outcome and death among South African MDR-TB and HIV co-infected children.

SETTING: Pediatric multidrug-resistant tuberculosis (MDR-TB) is complicated by difficult diagnosis, complex treatment, and high mortality. In South Africa, these challenges are amplified by human immunodeficiency virus (HIV) co-infection; however, evidence on treatment outcomes among co-infected children is limited. OBJECTIVE: Using conventional and new pediatric definitions, to describe treatment outcomes and identify risk factors for unfavorable outcome and mortality in children aged <15 years with MDR-TB or extensively drug-resistant TB (XDR-TB) in KwaZulu-Natal, South Africa. DESIGN: Retrospective cohort study in a regional TB referral hospital. RESULTS: From January 2009 to June 2010, 84 children (median age 8 years, IQR 4-12) with MDR-TB (n = 78) or XDR-TB (n = 6) initiated treatment. Sixty-four (77%) were HIV-positive and 62 (97%) received antiretroviral therapy. Sixty-six (79%) achieved favorable treatment outcomes. Overall mortality was 11% (n = 9) at 18 months after initiation of treatment. Malnutrition (aOR 27.4, 95%CI 2.7-278.7) and severe radiographic findings (aOR 4.68, 95%CI 1.01-21.9) were associated with unfavorable outcome. New pediatric outcome definitions increased the proportion classified as cured. CONCLUSION: It is possible to successfully treat pediatric MDR-TB-HIV even in resource-poor settings. Malnutrition is a marker for severe TB-HIV disease, and is a potential target for future interventions in these patients.

Epidemiology of smear-negative pulmonary tuberculosis in the United States, 1993-2008.

BACKGROUND: Smear-negative tuberculosis (TB) is difficult to diagnose and has been associated with poor treatment outcomes and excessive mortality, particularly in high human immunodeficiency virus (HIV) prevalent settings. However, few studies have used mycobacterial culture to rigorously confirm all smear-negative TB cases in a population-based cohort. DESIGN: We included all culture-confirmed, pulmonary TB cases reported to the US National TB Surveillance System from 1993 to 2008. We analyzed smear-negative TB risk factors and survival, as compared to smear-positive TB. We calculated prevalence ratios (PRs) and adjusted for confounders (aPR). RESULTS: From 1993 to 2008, 159,121 cases of culture-confirmed pulmonary TB were reported in the United States, of which 58,786 (37%) were sputum smear-negative. Smear-negative TB cases were more likely to be foreign-born (aPR 1.10, 95%CI 1.08-1.12), incarcerated (aPR 1.52, 95%CI 1.48-1.56) or HIV-infected (aPR 1.27, 95%CI 1.24-1.30). Hispanics and non-Hispanic Blacks were less likely to have smear-negative TB (respectively aPR 0.87, 95%CI 0.85-0.89 and aPR 0.90, 95%CI 0.89-0.92). Smear-negative TB cases had lower mortality (aRR 0.78, 95%CI 0.74-0.81), independent of HIV status. CONCLUSION: Smear-negative TB represents a large proportion of TB cases in the United States, and occurs more often among persons in groups more likely to undergo TB screening. The lower mortality may indicate earlier TB detection, and underscores the need for continued vigilance in screening of high-risk persons.