Drug-resistant tuberculosis care and treatment outcomes over the last 15 years in Ethiopia: Results from a mixed-method review of trends.

BACKGROUND AND OBJECTIVES: Drug resistant tuberculosis (DR-TB) remains a global challenge with about a third of the cases are not detected. With the recent advances in the diagnosis and treatment follow-up of DR-TB, there have been improvements with treatment success rates. However, there is limited evidence on the successful models of care that have consistently registered good outcomes. Our aim was to assess Ethiopia's experience in scaling up an ambulatory, decentralized model of care while managing multiple regimen transition processes and external shocks. METHODS: This was a cross-sectional, mixed-method study. For the quantitative data, we reviewed routine surveillance data for the period 2009-2022 and collected additional data from publicly available reports. We then analyzed the data descriptively. Qualitative data were collected from program reports, quarterly presentations, minutes of technical working group meetings, and clinical review committee reports and analyzed thematically. RESULTS: The number of DR-TB treatment initiating centers increased from 1 to 67, and enrollment increased from 88 in 2010 to 741 in 2019, but declined to 518 in 2022. A treatment success rate (TSR) of over 70% was sustained. The decentralized and ambulatory service delivery remained the core service delivery model. The country successfully navigated multiple regimen transitions, including the recently introduced six-month short oral regimen. Several challenges remain, including the lack of strong and sustainable specimen transportation system, lack of established systems for timely tracing and linking of missed DR-TB cases, and data quality issues. CONCLUSIONS: Ethiopia scaled up a decentralized ambulatory model of care, kept up to date with recent developments in treatment regimens, and maintained a high TSR, despite the influence of multiple external challenges. The recent decline in case notification requires a deeper look into the underlying reasons. The feasibility of fully integrating DR-TB treatment and follow up at community level should be explored further.

TB-related catastrophic costs in Ethiopia.

OBJECTIVES: To measure the progress towards reducing TB-related catastrophic costs in 19 zones of Amhara, Oromia, SNNP (Southern Nations and Nationalities, and Peoples) and Sidama Regions of Ethiopia. METHODS: A baseline survey was conducted in randomly selected health facilities from all districts within the 19 zones from November 2020 to February 2021. Interventions targeting the major drivers of catastrophic costs identified in the baseline survey, such as installation of 126 GeneXpert and 13 Truenat machines, securing connectivity of 372 GeneXpert, establishing alternative specimen referral systems, and capacity-building of health workers, were implemented. A follow-up survey was conducted from October to December 2022. The WHO generic tool was used to collect data based on probability proportional to size. Data were entered into STATA software, and the proportion of catastrophic costs was calculated and compared between the two surveys. RESULTS: A total of 433 and 397 patients participated in the baseline and follow-up surveys, respectively. The proportion of catastrophic costs reduced from 64.7% to 43.8% (P < 0.0001). The share of direct non-medical costs decreased from 76.2% to 19.2%, while medical and indirect costs increased from 11.6% and 12.3% to 30.4% and 52.4 %. CONCLUSION: The proportion of households facing TB-related catastrophic costs has significantly reduced over the 2-year period. However, it remains unacceptably high and varies among regions. Further reducing the catastrophic costs requires multisectoral response, reviewing the TB service exemption policy, further decentralisation and improving the quality of TB services.

OBJECTIFS: Mesurer les progrès accomplis dans la réduction des coûts catastrophiques liés à la TB dans 19 zones des régions d'Amhara, d'Oromia, de SNNP (Région des nations, nationalités et peuples du Sud) et de Sidama en Éthiopie. MÉTHODES: Une enquête de base a été menée dans des établissements de santé sélectionnés au hasard dans tous les districts des 19 zones de novembre 2020 à février 2021. Des interventions ciblant les principaux facteurs de coûts catastrophiques identifiés dans l'enquête de référence, telles que l'installation de 126 machines GeneXpert et 13 Truenat, la sécurisation de la connectivité de 372 GeneXpert, la mise en place de systèmes alternatifs d'orientation des échantillons et le renforcement des capacités des agents de santé, ont été mises en œuvre. Une enquête de suivi a été menée d'octobre à décembre 2022. L'outil générique de l'OMS a été utilisé pour recueillir des données fondées sur une probabilité proportionnelle à la taille. Les données ont été saisies dans le logiciel STATA, et la proportion des coûts catastrophiques a été calculée et comparée entre les deux enquêtes. RÉSULTATS: Au total, 433 et 397 patients ont participé respectivement à l'enquête de base et à l'enquête de suivi. La proportion des coûts catastrophiques est passée de 64,7% à 43,8% (P < 0,0001). La part des coûts non médicaux directs a diminué, passant de 76,2% à 19,2%, tandis que les coûts médicaux et indirects sont passés de 11,6% et 12,3% à 30,4% et 52,4%. CONCLUSION: La proportion de ménages confrontés à des coûts catastrophiques liés à la tuberculose a considérablement diminué au cours de la période de 2 ans. Cependant, il reste inacceptable et varie selon les régions. Pour réduire davantage les coûts catastrophiques, il faut une réponse multisectorielle, une révision de la politique d'exemption des services de lutte contre la TB, une décentralisation plus poussée et une amélioration de la qualité des services de lutte contre la TB.

Descriptors of multidrug-resistant TB deaths in Ethiopia.

Deaths related to multidrug-resistant TB among patients who had received a second-line anti-TB drugs in Ethiopia were analysed. Respectively 38/704 (5.4%) and 44/995 (4.4%) deaths were identified in two cohorts (2015 and 2022). In the 2015 cohort, severe malnutrition was less prevalent, previous treatment rates were three times higher, hypokalaemia was more frequent, and the use of the Xpert® MTB/RIF assay, respiratory failure and severe anaemia/pancytopenia were less common than in the 2022 cohort. We observed that there were variations in adverse events when different treatment regimens were used over different time periods. To ensure proper patient care, correct guidance must be consistently implemented.

Les décès liés à la TB multirésistante chez les patients ayant reçu des médicaments antituberculeux de seconde ligne en Éthiopie ont été analysés. Respectivement 38/704 (5,4%) et 44/995 (4,4%) décès ont été identifiés dans deux cohortes (2015 et 2022). Dans la cohorte 2015, la malnutrition sévère était moins fréquente, les taux de traitement antérieur étaient trois fois plus élevés, l'hypokaliémie était plus fréquente, et l'utilisation du test Xpert® MTB/RIF, l'insuffisance respiratoire et l'anémie/pancytopénie sévère étaient moins fréquentes que dans la cohorte 2022. Nous avons observé des variations dans les effets indésirables lorsque différents schémas thérapeutiques étaient utilisés sur différentes périodes. Pour garantir des soins adéquats aux patients, des consignes appropriées doivent être appliquées de manière régulière.

The yield of community-based tuberculosis and HIV among key populations in hotspot settings of Ethiopia: A cross-sectional implementation study.

OBJECTIVE: To determine the yield of tuberculosis (TB) and the prevalence of Human Immuno-deficiency virus (HIV) among key populations in the selected hotspot towns of Ethiopia. METHODS: We undertook a cross-sectional implementation research during August 2017-January 2018. Trained TB focal persons and health extension workers (HEWs) identified female sex workers (FSWs), health care workers (HCWs), prison inmates, homeless, internally displaced people (IDPs), internal migratory workers (IMWs) and residents in missionary charities as key and vulnerable popuaiton. They carried out health education on the importance of TB screening and HIV testing prior to recruitment of the study participants. Symptomatic TB screening and HIV testing was done. The yield of TB was computed per 100,000 background key population. RESULTS: A total of 1878 vulnerable people were screened, out of which 726 (38.7%) presumptive TB cases and 87 (4.6%) TB cases were identified. The yield of TB was 1519 (95% CI: 1218.1-1869.9). The highest proportion (19.5%) and yield of TB case (6,286 (95% CI: 3980.8-9362.3)) was among HCWs. The prevalence of HIV infection was 6%, 67 out of 1,111 tested. IMWs and FSWs represented 49.3% (33) and 28.4% (13) of the HIV infections, respectively. There was a statistically significant association of active TB cases with previous history of TB (Adjusted Odds Ratio (AOR): 11 95% CI, 4.06-29.81), HIV infection (AOR: 7.7 95% CI, 2.24-26.40), and being a HCW (AOR: 2.42 95% CI, 1.09-5.34). CONCLUSIONS: The prevalence of TB in key populations was nine times higher than 164/100,000 national estimated prevalence rate. The prevalence of HIV was five times higher than 1.15% of the national survey. The highest yield of TB was among the HCWs and the high HIV burden was detected among the FSWs and IMWs. These suggest a community and health facility based integrated and enhanced case finding approaches for TB and HIV in hotspot settings.

Prevalence of tuberculosis among mentally ill patients in conflict-stricken Afghanistan: A cross-sectional study.

OBJECTIVES: Tuberculosis (TB) and mental illness share underlying factors such as poverty, malnutrition, and stress. This study's objective was to determine the prevalence of TB among mentally ill patients in Afghanistan. METHODS: A cross-sectional study was conducted in five public and one private health facility. All patients in those centers were screened for TB, and the diagnosis of TB was made with GeneXpert or made clinically by a physician. RESULTS: Out of 8598 patients registered, 8324 (96.8%) were reached and 8073 (93.9%) were screened for TB, of whom 1703 (21.1%) were found to be presumptive TB patients. A total of 275 (16.7%) were diagnosed with all forms of TB, of whom 90.5% were women. Eighty-eight (32%) of them were bacteriologically confirmed and 187 (68%) were clinically diagnosed. The number needed to screen (NNS) was 29.3 and the number needed to test (NNT) was 6.1. The overall prevalence of TB among mentally ill patients was 3,567/100,000-20 times higher than the national incidence rate. TB was independently associated with married and widowed adults, young adults, females, and oral sleep drug users. CONCLUSIONS: TB among mentally ill patients is very high, and we recommend that TB care and prevention services be integrated into mental health centers.

Seasonal patterns of tuberculosis case notification in the tropics of Africa: A six-year trend analysis in Ethiopia.

OBJECTIVE: Seasonal variations affect the health system's functioning, including tuberculosis (TB) services, but there is little evidence about seasonal variations in TB case notification in tropical countries, including Ethiopia. This study sought to fill this gap in knowledge using TB data reported from 10 zones, 5 each from Amhara and Oromia regions. METHODS: Notified TB cases for 2010-2016 were analyzed using SPSS version 20. We calculated the quarterly and annual average TB case notification rates and the proportion of seasonal amplitudes. We applied Winters' multiplicative method of exponential smoothing to break down the original time series into seasonal, trend, and irregular components and to build a suitable model for forecasting. RESULTS: A total of 205,575 TB cases were identified (47.8% from Amhara, 52.2% from Oromia), with a male-to-female ratio of 1.2:1. The means of 8,200 (24%), 7,992 (23%), 8,849 (26%), and 9,222 (27%) TB cases were reported during July-September, October-December, January-March, and April-June, respectively. The seasonal component of our model indicated a peak in April-June and a trough in October-December. The seasonal amplitude in Amhara region is 10% greater than that of Oromia (p < 0.05). CONCLUSIONS: TB is shown to be a seasonal disease in Ethiopia, with a peak in quarter four and a low in quarter two of the fiscal year. The peak TB case notification rate corresponds with the end of the dry season in the two agrarian regions of Ethiopia. TB prevention and control interventions, such as efforts to increase community TB awareness about TB transmission and contact tracing, should consider seasonal variation. Regional variations in TB seasonality may require consideration of geographic-specific TB case-finding strategies. The mechanisms underlying the seasonal variation of TB are complex, and further study is needed.

Addressing tuberculosis control in fragile states: Urban DOTS experience in Kabul, Afghanistan, 2009-2015.

Tuberculosis (TB) is a major public health problem in Afghanistan, but experience in implementing effective strategies to prevent and control TB in urban areas and conflict zones is limited. This study shares programmatic experience in implementing DOTS in the large city of Kabul. We analyzed data from the 2009-2015 reports of the National TB Program (NTP) for Kabul City and calculated treatment outcomes and progress in case notification using rates, ratios, and confidence interval. Urban DOTS was implemented by the NTP in partnership with United States Agency for International Development (USAID)-funded TB projects, the World Health Organization (WHO), and the private sector. Between 2009 and 2015, the number of DOTS-providing centers in Kabul increased from 22 to 85. In total, 24,619 TB patients were enrolled in TB treatment during this period. The case notification rate for all forms of TB increased from 59 per 100,000 population to 125 per 100,000. The case notification rate per 100,000 population for sputum-smear-positive TB increased from 25 to 33. The treatment success rate for all forms of TB increased from 31% to 67% and from 47% to 77% for sputum-smear-positive TB cases. The treatment success rate for private health facilities increased from 52% in 2010 to 80% in 2015. In 2013, contact screening was introduced, and the TB yield was 723 per 100,000-more than two times higher than the estimated national prevalence of 340 per 100,000. Contact screening contributed to identifying 2,509 child contacts of people with TB, and 76% of those children received isoniazid preventive therapy. The comprehensive urban DOTS program significantly improved service accessibility, TB case finding, and treatment outcomes in Kabul. Public- and private-sector involvement also improved treatment outcomes; however, the treatment success rate remains higher in private health facilities. While the treatment success rate increased significantly, it remains lower than the national average, and more efforts are needed to improve treatment outcomes in Kabul. We recommend that the urban DOTS approach be replicated in other countries and cities in Afghanistan with settings similar to Kabul.

Tuberculosis along the continuum of HIV care in a cohort of adolescents living with HIV in Ethiopia.

SETTING: Eight health facilities in Ethiopia. OBJECTIVE: To determine tuberculosis (TB) incidence rates and associated factors among adolescents living with the human immunodeficiency virus (ALHIV). DESIGN: This was a retrospective cohort study. Adolescents enrolled in HIV care between January 2005 and 31 December 2013 constituted the study population. The main outcome variable was TB diagnosis during follow-up. Baseline World Health Organization (WHO) clinical stage, CD4 count, previous history of TB and use of isoniazid preventive therapy (IPT) were the main independent variables. We estimated TB incidence rates as incident cases per 100 person-years of observation (PYO). Cox regression analysis was used to control for confounders. RESULTS: Of the 1221 adolescents screened, 1072 were studied; 60.1% were girls. TB incidence rate was 16.32 per 100 PYO during pre-antiretroviral therapy (pre-ART) follow-up but declined to 2.25 per 100 PYO after initiation of ART. Advanced WHO clinical stage (adjusted hazard ratio [aHR] 2.71, 95%CI 1.69-4.33) and CD4 count <350 cells/µl (aHR 2.28, 95%CI 1.10-4.81) predicted TB incidence in the pre-ART cohort. IPT use was associated with a significant reduction in TB incidence in the ART cohort, but not in the pre-ART group. CONCLUSION: Although TB was a significant problem in ALHIV, timely administration of ART and IPT had a significant protective effect.

The yield of a tuberculosis household contact investigation in two regions of Ethiopia.

SETTING: Amhara and Oromia regions, Ethiopia. OBJECTIVE: To determine the yield of a household contact investigation for tuberculosis (TB) under routine programme conditions. DESIGN: Between April 2013 and March 2014, TB clinic officers conducted symptom-based screening for household contacts (HHCs) of 6015 smear-positive TB (SS+ TB) index cases. Based on quarterly reported programme data, we calculated the yield in terms of number needed to screen (NNS) and number needed to test (NNT). RESULTS: Of 15,527 HHCs screened, 6.1% had presumptive TB (8.5% in Oromia vs. 3.9% in Amhara). All forms of TB and SS+ TB were diagnosed in respectively 2.5% (Oromia 3.9% vs. Amhara 1.2%) and 0.76% (Oromia 0.98% vs. Amhara 0.55%) of contacts. The NNS to detect a TB case all forms and SS+ TB was respectively 40 and 132. The NNT to diagnose a TB case all forms and SS+ TB was respectively 2.4 and 8. Of 1687 eligible children aged <5 years, 323 were started on isoniazid preventive therapy. CONCLUSIONS: The yield of the household contact investigation was over 10 times higher than the estimated prevalence in the general population; household contact investigations can serve as an entry point for childhood TB care.

Scaling up TB DOTS in a fragile state: post-conflict Afghanistan.

SETTING: Afghanistan. OBJECTIVE: To describe the results of rapid expansion of the DOTS strategy in a post-conflict environment, with a focus on the experience of the Rural Expansion of Afghanistan's Community-based Healthcare (REACH) Program. RESULTS: Despite the destruction of the National Tuberculosis Program (NTP) and basic health services by war and an uncertain security situation, the NTP, with assistance from many partners and REACH, increased the number of patients receiving DOTS by 136% in 4 years (from 9261 cases in 2001 to 21851 in 2005), with an 86% treatment success rate. By focusing on rapidly expanding the number of facilities capable of providing tuberculosis (TB) diagnostic and treatment services and involving community health workers in case detection, referrals and home-based DOTS, REACH showed a 10-fold rise in the number of facilities providing TB services and a 380% increase in the number of sputum smear-positive pulmonary TB cases detected in 2 years (from 251/month in 2004 to 818/month in 2006) in 13 provinces. CONCLUSION: At the current rate of expansion, case detection and successful treatment of TB cases in Afghanistan will continue to expand rapidly. The NTP and REACH have demonstrated that expansion of TB services in Afghanistan is possible despite the challenges.

The dynamics of tuberculosis in response to 10 years of intensive control effort in Peru.

Improved tuberculosis (TB) case detection and cure rates are expected to accelerate the decline in incidence of TB and to reduce TB-associated deaths. Time series analyses of case reports in Peru showed that the per capita TB incidence rate was probably steady before 1991. Case reports increased between 1990 and 1992 as a result of improved case detection. Although diagnostic efforts have continued to increase since 1993, the incidence of new pulmonary TB cases has declined in every department of the country, with a national rate of decline > or =5.8% per year (range, 1.9%-9.7%). This elevated rate of decline suggests that 27% (19%-34%) of cases (158,000) and 70% (63%-77%) of deaths (91,000) among smear-positive patients were averted between 1991 and 2000. This is the first demonstration that a significant number of TB cases can be prevented through intensive short-course chemotherapy in a high-burden country.

Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries.

CONTEXT: No large-scale study has investigated the impact of multidrug-resistant tuberculosis (TB) on the outcome of standard short-course chemotherapy under routine countrywide TB control program conditions in the World Health Organization's (WHO) directly observed treatment short-course strategy for TB control. OBJECTIVE: To assess the results of treatment with first-line drugs for patients enrolled in the WHO and the International Union Against Tuberculosis and Lung Disease's global project on drug-resistance surveillance. DESIGN AND SETTING: Retrospective cohort study of patients with TB in the Dominican Republic, Hong Kong Special Administrative Region (People's Republic of China), Italy, Ivanovo Oblast (Russian Federation), the Republic of Korea, and Peru. PATIENTS: New and retreatment TB cases who received short-course chemotherapy with isoniazid, rifampicin, pyrazinamide, and either ethambutol or streptomycin between 1994 and 1996. MAIN OUTCOME MEASURE: Treatment response according to WHO treatment outcome categories (cured; died; completed, defaulted, or failed treatment; or transferred). RESULTS: Of the 6402 culture-positive TB cases evaluated, 5526 (86%) were new cases and 876 (14%) were retreatment cases. A total of 1148 (20.8%) new cases and 390 (44.5%) retreatment cases were drug resistant, including 184 and 169 cases of multidrug-resistant TB, respectively. Of the new cases 4585 (83%) were treated successfully, 138 (2%) died, and 151 (3%) experienced short-course chemotherapy failure. Overall, treatment failure (relative risk [RR], 15.4; 95% confidence interval [CI], 10.6-22.4; P<.001) and mortality (RR, 3.73; 95% CI, 2.13-6.53; P<.001) were higher among new multidrug-resistant TB cases than among new susceptible cases. Even in settings using 100% direct observation, cases with multidrug resistance had a significantly higher failure rate than those who were susceptible (9/94 [10%] vs 8/1410 [0.7%]; RR, 16.9; 95% CI, 6.6-42.7; P<.001). Treatment failure was also higher among patients with any rifampicin resistance (n=115) other than multidrug resistance (RR, 5.48; 95% CI, 3.04-9.87; P<.001), any isoniazid resistance (n=457) other than multidrug resistance (RR, 3. 06; 95% CI, 1.85-5.05; P<.001), and among patients with TB resistant to rifampicin only (n=76) (RR, 5.47; 95% CI, 2.68-11.2; P<.001). Of the retreatment cases, 497 (57%) were treated successfully, 51 (6%) died, and 124 (14%) failed short-course chemotherapy treatment. Failure rates among retreatment cases were higher in those with multidrug-resistant TB, with any isoniazid resistance other than multidrug resistance, and in cases with TB resistant to isoniazid only. CONCLUSIONS: These data suggest that standard short-course chemotherapy, based on first-line drugs, is an inadequate treatment for some patients with drug-resistant TB. Although the directly observed treatment short-course strategy is the basis of good TB control, the strategy should be modified in some settings to identify drug-resistant cases sooner, and to make use of second-line drugs in appropriate treatment regimens. JAMA. 2000;283:2537-2545

Meningoencefalitis bacteriana en pediatría / Bacterial meningoencephalitis in pediatrics

La menigoencefalitis bacteriana es una patología que ha aumentado su incidencia en los últimos años. Se ha realizado un estudio prospectivo, previa elaboración de un protocolo para determinar la incidencia de esta patología, germen causal, clínica tratamiento, secuelas y mortalidad. En el Servicio de Pediatría del Hospital Central SSFP, durante el período de 1985-1988 se hospitalizaron 3604 pacientes, de los cuales 670 (18.5%) correspondieron a la Unidad de Cuidados Intensivos Pediátricos, diagnosticándose dentro del segundo grupo 20 casos de meningoencefalitis bacteriana, lo que equivalen al 2.9% de los pacientes intensivos. De los 20 casos analizados, se aislaron ocho de Neisseria meningitidis seis casos con Heamophyllus influenzae, uno con E. coli y en cinco no se aisló germen causal. En el grupo estudiado: 16 pacientes fueron de sexo masculino, 4 de sexo femenino. El grupo etario más afectado fue el de lactantes (40%). Entre los síntomas y signos comunes estuvieron: fiebre, vómitos, irritebilidad y signos meníngeos. El tratamiento antibiótico fue doble y la mortalidad alcanzó el 15% de los casos estudiados. Se enfatiza la necesidad de un diagnóstico etiológico rápido y el inicio de un tratamiento adecuado y oportuno para evitar secuelas posteriores y disminuir la mortalidad por esta patología