Longer delays in diagnosis and treatment ofpulmonary tuberculosis in pastoralist setting, Eastern Ethiopia

Purpose: This study aimed to assess the extent of patient, health system and total delays in diagnosis and treatment of pulmonary tuberculosis (TB) in Somali pastoralist setting, Ethiopia. Patients and Methods: A cross-sectional study among 444 confirmed new pulmonary TB patients aged ≥15 years in 5 TB care units was conducted between December 2017 and October 2018. Data were collected using a structured questionnaire and record review. We measured delays from symptom onset to provider visit, provider visit to diagnosis and diagnosis to treatment initiation. Delays were summarized using median days. Mann- Whitney and Kruskal-Wallis tests were used to compare delays between categories of explanatory variables. The Log-binomial regression model was used to reveal factors associated with health system delay ≥15 days, presented in adjusted prevalence ratio (APR) with 95% confidence interval (CI). Results: The median age of patients was 30 years, ranged from 15 to 82. The majority (62.4%) were male, and nearly half (46.4%) were pastoralists. The median patient, health system and total delays were 30 (19-48.5), 14 (4.5-29.5) and 50 (35-73.5) days, respec-tively. The median patient delay (35.5 days) and total delay (58.5 days) among pastoralists were substantially higher than the equivalent delays among non-pastoralists [p<0.001]. Of all, 3.8% of patients (16 of 18 were pastoralists) delayed longer than 6 months without initiating treatment. Factors associated with health system delay ≥15 days were mild symptoms [APR (95% CI) = 1.4 (1.1-1.7)], smear-negativity [APR (95% CI) = 1.2 (1.01- 1.5)], first visit to health centers [APR (95% CI) = 1.6 (1.3-2.0)] and multiple provider contacts [APR (95% CI) = 5.8 (3.5-9.6)]. Conclusion: Delay in diagnosis and treatment remains a major challenge of tuberculosis control targets in pastoralist settings of Ethiopia. Efforts to expand services tailored to transhumance patterns and diagnostic capacity of primary healthcare units need to be prioritized. © 2020 Getnet et al.Purpose: This study aimed to assess the extent of patient, health system and total delays in diagnosis and treatment of pulmonary tuberculosis (TB) in Somali pastoralist setting, Ethiopia. Patients and Methods: A cross-sectional study among 444 confirmed new pulmonary TB patients aged ≥15 years in 5 TB care units was conducted between December 2017 and October 2018. Data were collected using a structured questionnaire and record review. We measured delays from symptom onset to provider visit, provider visit to diagnosis and diagnosis to treatment initiation. Delays were summarized using median days. Mann- Whitney and Kruskal-Wallis tests were used to compare delays between categories of explanatory variables. The Log-binomial regression model was used to reveal factors associated with health system delay ≥15 days, presented in adjusted prevalence ratio (APR) with 95% confidence interval (CI). Results: The median age of patients was 30 years, ranged from 15 to 82. The majority (62.4%) were male, and nearly half (46.4%) were pastoralists. The median patient, health system and total delays were 30 (19-48.5), 14 (4.5-29.5) and 50 (35-73.5) days, respec-tively. The median patient delay (35.5 days) and total delay (58.5 days) among pastoralists were substantially higher than the equivalent delays among non-pastoralists [p<0.001]. Of all, 3.8% of patients (16 of 18 were pastoralists) delayed longer than 6 months without initiating treatment. Factors associated with health system delay ≥15 days were mild symptoms [APR (95% CI) = 1.4 (1.1-1.7)], smear-negativity [APR (95% CI) = 1.2 (1.01- 1.5)], first visit to health centers [APR (95% CI) = 1.6 (1.3-2.0)] and multiple provider contacts [APR (95% CI) = 5.8 (3.5-9.6)]. Conclusion: Delay in diagnosis and treatment remains a major challenge of tuberculosis control targets in pastoralist settings of Ethiopia. Efforts to expand services tailored to transhumance patterns and diagnostic capacity of primary healthcare units need to be prioritized. © 2020 Getnet et al

Challenges in delivery of tuberculosis services in Ethiopian pastoralist settings: clues for reforming service models and organizational structures

BACKGROUND: The End-TB strategy aims to see a world free of tuberculosis (TB) by the coming decade through detecting and treating all cases irrespective of socioeconomic inequalities. However, case detections and treatment outcomes have not been as they should be in Somali pastoral settings of Ethiopia. Hence, this study aimed to explore the challenges that hinder the delivery and utilization of TB services in pastoral areas. METHODS: A qualitative study was conducted between December 2017 and October 2018 among pastoralist patients with delay of >/=2 months in seeking healthcare, healthcare providers and programme managers. Data were collected from different sources using 41 in-depth interviews, observations of facilities and a review meeting of providers from 50 health facilities. The data were transcribed, coded and analyzed to identify pre-defined and emerging sub-themes. ATLAS.ti version 7.0 was used for coding data, categorizing codes, and visualizing networks. RESULTS: Poor knowledge of TB and its services, limited accessibility (unreachability, unavailability and unacceptability), pastoralism, and initial healthcare-seeking at informal drug vendors that provide improper medications were the key barriers hindering the uptake of TB medical services. Inadequate infrastructure, shortage of trained and enthused providers, interruptions of drugs and laboratory supplies, scarce equipment, programme management gaps, lack of tailored approach, low private engagement, and cross-border movement were the major challenges affecting the provision of TB services for pastoral communities. The root factors were limited potential healthcare coverage, lack of zonal and district TB units, mobility and drought, strategy and funding gaps, and poor development infrastructure. CONCLUSION: In pastoral settings of Ethiopia, the major challenges of TB services are limited access, illicit medication practices, inadequate resources, structural deficits, and lack of tailored approaches. Hence, for the pastoral TB control to be successful, mobile screening and treatment modalities and engaging rural drug vendors will be instrumental in enhancing case findings and treatment compliance; whereas, service expansion and management decentralization will be essential to create responsive structures for overcoming challenges

Linking Social Protection Schemes: The Joint Effects of a Public Works and a Health Insurance Programme in Ethiopia

In developing countries and in particular in sub-Saharan Africa, social protection schemes tend to operate in silos. However, schemes targeting the same geographical areas may have synergies that have not yet been examined, and which are worth scrutinising. This paper contributes to this knowledge gap by examining the joint impacts of two social protection programmes in Ethiopia, that is, the Productive Safety Net Programme and a Community Based Health Insurance Scheme. Based on three rounds of individual level panel data and several rounds of qualitative interviews, we find that individuals covered by both programmes, as opposed to neither or only one of the two programmes, provide greater labour supply, have larger livestock holdings, and have a lower amount of outstanding loans. Furthermore, joint participation is associated with greater use of modern health care facilities as compared to participating only in the safety net programme. These results show that bundling of interventions enhances protection against multiple risks and that linking social protection schemes yields more than the sum of their individual effects

Factors related to discontinued clinic attendance by patients with podoconiosis in southern Ethiopia: a qualitative study

Background Podoconiosis is a lymphoedema of non-infectious cause which results in long-term ill health in affected individuals. Simple, effective treatment is available in certain parts of Ethiopia, but evidence indicates that not all patients continue collecting treatment supplies from clinic sites once started. We used qualitative techniques to explore factors related to discontinued attendance at outreach clinics of a non-government organization in southern Ethiopia. Methods A cross-sectional qualitative study was conducted in four clinic sites through unstructured in-depth interviews, key informant interviews and focus group discussions with the involvement of 88 study subjects. Results Discontinuation of clinic visits is common among podoconiosis patients. The reasons were: remoteness from the clinic sites, unrealistic expectation of ‘special’ aid, worry about increasing stigma, illness and misconceptions about treatment. Conclusions Several of these factors are remediable through community and individual information and education. Appropriate routes to deliver this information must be identified. Certain factors (such as distance to clinic sites and stigma) require substantial expansion of services or liaison with village-level government health services

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Helios Expression Is a Marker of T Cell Activation and Proliferation

Foxp3+ T-regulatory cells (Tregs) normally serve to attenuate immune responses and are key to maintenance of immune homeostasis. Over the past decade, Treg cells have become a major focus of research for many groups, and various functional subsets have been characterized. Recently, the Ikaros family member, Helios, was reported as a marker to discriminate naturally occurring, thymic-derived Tregs from those peripherally induced from naïve CD4+ T cells. We investigated Helios expression in murine and human T cells under resting or activating conditions, using well-characterized molecules of naïve/effector/memory phenotypes, as well as a set of Treg-associated markers. We found that Helios-negative T cells are enriched for naïve T cell phenotypes and vice versa. Moreover, Helios can be induced during T cell activation and proliferation, but regresses in the same cells under resting conditions. We demonstrated comparable findings using human and murine CD4+Foxp3+ Tregs, as well as in CD4+ and CD8+ T cells. Since Helios expression is associated with T cell activation and cellular division, regardless of the cell subset involved, it does not appear suitable as a marker to distinguish natural and induced Treg cells

MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity

International audienceMiddle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal-human interface

Children with Moderate Acute Malnutrition with No Access to Supplementary Feeding Programmes Experience High Rates of Deterioration and No Improvement: Results from a Prospective Cohort Study in Rural Ethiopia

Background: Children with moderate acute malnutrition (MAM) have an increased risk of mortality, infections and impaired physical and cognitive development compared to well-nourished children. In parts of Ethiopia not considered chronically food insecure there are no supplementary feeding programmes (SFPs) for treating MAM. The short-term outcomes of children who have MAM in such areas are not currently described, and there remains an urgent need for evidence-based policy recommendations. Methods: We defined MAM as mid-upper arm circumference (MUAC) of ≥11.0cm and <12.5cm with no bilateral pitting oedema to include Ethiopian government and World Health Organisation cut-offs. We prospectively surveyed 884 children aged 6–59 months living with MAM in a rural area of Ethiopia not eligible for a supplementary feeding programme. Weekly home visits were made for seven months (28 weeks), covering the end of peak malnutrition through to the post-harvest period (the most food secure window), collecting anthropometric, socio-demographic and food security data. Results: By the end of the study follow up, 32.5% (287/884) remained with MAM, 9.3% (82/884) experienced at least one episode of SAM (MUAC <11cm and/or bilateral pitting oedema), and 0.9% (8/884) died. Only 54.2% of the children recovered with no episode of SAM by the end of the study. Of those who developed SAM half still had MAM at the end of the follow up period. The median (interquartile range) time to recovery was 9 (4–15) weeks. Children with the lowest MUAC at enrolment had a significantly higher risk of remaining with MAM and a lower chance of recovering. Conclusions: Children with MAM during the post-harvest season in an area not eligible for SFP experience an extremely high incidence of SAM and a low recovery rate. Not having a targeted nutrition-specific intervention to address MAM in this context places children with MAM at excessive risk of adverse outcomes. Further preventive and curative approaches should urgently be considered

Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients

BACKGROUND: Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI) has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB) co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001), higher plasma efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036), baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1 3435TT genotype (p = 0.001). CONCLUSION: We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI

The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017 : a systematic analysis for the Global Burden of Disease study 2017

Background: Stomach cancer is a major health problem in many countries. Understanding the current burden of stomach cancer and the differential trends across various locations is essential for formulating effective preventive strategies. We report on the incidence, mortality, and disability-adjusted life-years (DALYs) due to stomach cancer in 195 countries and territories from 21 regions between 1990 and 2017. Methods: Estimates from GBD 2017 were used to analyse the incidence, mortality, and DALYs due to stomach cancer at the global, regional, and national levels. The rates were standardised to the GBD world population and reported per 100 000 population as age-standardised incidence rates, age-standardised death rates, and age-standardised DALY rates. All estimates were generated with 95% uncertainty intervals (UIs). Findings: In 2017, more than 1·22 million (95% UI 1·19–1·25) incident cases of stomach cancer occurred worldwide, and nearly 865 000 people (848 000–885 000) died of stomach cancer, contributing to 19·1 million (18·7–19·6) DALYs. The highest age-standardised incidence rates in 2017 were seen in the high-income Asia Pacific (29·5, 28·2–31·0 per 100 000 population) and east Asia (28·6, 27·3–30·0 per 100 000 population) regions, with nearly half of the global incident cases occurring in China. Compared with 1990, in 2017 more than 356 000 more incident cases of stomach cancer were estimated, leading to nearly 96 000 more deaths. Despite the increase in absolute numbers, the worldwide age-standardised rates of stomach cancer (incidence, deaths, and DALYs) have declined since 1990. The drop in the disease burden was associated with improved Socio-demographic Index. Globally, 38·2% (21·1–57·8) of the age-standardised DALYs were attributable to high-sodium diet in both sexes combined, and 24·5% (20·0–28·9) of the age-standardised DALYs were attributable to smoking in males. Interpretation: Our findings provide insight into the changing burden of stomach cancer, which is useful in planning local strategies and monitoring their progress. To this end, specific local strategies should be tailored to each country's risk factor profile. Beyond the current decline in age-standardised incidence and death rates, a decrease in the absolute number of cases and deaths will be possible if the burden in east Asia, where currently almost half of the incident cases and deaths occur, is further reduced. Funding: Bill & Melinda Gates Foundation