Distribution of HLA-DQ risk genotypes for celiac disease in Ethiopian children

Most patients with celiac disease are positive for either HLA-DQA1*05:01-DQB1*02 (DQ2.5) or DQA1*03:01-DQB1*03:02 (DQ8). Remaining few patients are usually DQA1*02:01-DQB1*02 (DQ2.2) carriers. Screenings of populations with high frequencies of these HLA-DQA1-DQB1 haplotypes report a 1% to 3% celiac disease prevalence. The aim was to determine the prevalence of HLA-DQ risk haplotypes for celiac disease in Ethiopian children. Dried blood spots collected from 1193 children from the Oromia regional state of Ethiopia were genotyped for HLA-DQA1 and DQB1 genotyping using an asymmetric polymerase chain reaction (PCR) and a subsequent hybridization of allele-specific probes. As references, 2000 previously HLA-genotyped children randomly selected from the general population in Sweden were included. DQ2.2 was the most common haplotype and found in 15.3% of Ethiopian children, which was higher compared with 6.7% of Swedish references (P P trans genotype encoded by DQA1*05-DQB1*03:01 in combination with DQ2.2 occurred in 3.6% of Ethiopian children, which was higher compared with 1.3% of Swedish references (P P = .3504). The frequency of HLA risk haplotypes for celiac disease is very similar in Ethiopian and Swedish children. This finding of importance will be useful in future screening of children for celiac disease in Ethiopia

Serological evidence for a decline in malaria transmission following major scale-up of control efforts in a setting selected for Plasmodium vivax and Plasmodium falciparum malaria elimination in Babile district, Oromia, Ethiopia.

BACKGROUND: Following successful malaria control during the last decade, Ethiopia instituted a stepwise malaria elimination strategy in selected low-transmission areas. METHODS: Cross-sectional surveys were conducted in Babile district, Oromia, Ethiopia from July to November 2017 to evaluate malaria infection status using microscopy and nested polymerase chain reaction (nPCR) and serological markers of exposure targeting Plasmodium falciparum and Plasmodium vivax apical membrane antigen-1 (AMA-1). RESULTS: Parasite prevalence was 1.2% (14/1135) and 5.1% (58/1143) for P. falciparum and 0.4% (5/1135) and 3.6% (41/1143) for P. vivax by microscopy and nPCR, respectively. Antibody prevalence was associated with current infection by nPCR for both P. falciparum (p<0.001) and P. vivax (p=0.014) and showed an age-dependent increase (p<0.001, for both species). Seroconversion curves indicated a decline in malaria exposure 15 y prior to sampling for P. falciparum and 11.5 y prior to sampling for P. vivax, broadly following malaria incidence data from district health offices, with higher antibody titres in adults than children for both species. CONCLUSIONS: Malaria transmission declined substantially in the region with continuing heterogeneous but measurable local transmission, arguing in favour of continued and tailored control efforts to accelerate the progress towards elimination efforts

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BackgroundThe WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population.MethodsIn this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895.FindingsWe identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively.InterpretationC-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications.FundingWorld Health Organization

Establishing health biotech and enhancing local manufacturing of pharmaceuticals in Sub-Saharan Africa

Although many nations in Sub-Saharan Africa (SSA) have recently recorded impressive economic growth, and several countries could attain middle-income status in the next decade, there is no or little concurrent advance in health biotech with little capabilities for manufacturing of medicines, medical supplies, and health commodities in the region. They import majority of medicines, medical supplies, and health commodities used in national programs including immunization, family planning, tuberculosis, HIV, and malaria that drive health outcomes and population-level impact with supports mainly obtained from high-income countries, multilateral agencies, or philanthropies. Nevertheless, there is a growing global debate that countries should graduate from receiving development assistance which goes to the most important health programs like immunization when nations transition from low-income to middle-income economic status. Since sudden withdrawal of all or partial development assistance could send a shock to the health care and dent the trajectory toward achieving the health Sustainable Development Goal, it is imperative to urgently establish or strengthen health biotech and enhance manufacturing of pharmaceuticals in SSA

Outcome of tuberculosis treatment in HIV-positive adults diagnosed through active versus passive case-finding

Background: The World Health Organization strongly recommends regular screening for tuberculosis (TB) in HIV-positive individuals. Objective: To compare the outcome of anti-tuberculosis treatment (ATT) in HIV-positive adults diagnosed with TB through active case-finding (ACF) or passive case-finding (PCF). Design: Antiretroviral therapy (ART)-naïve adults diagnosed with TB were included from two prospective cohort studies conducted in Ethiopia between September 2010 and March 2013. The PCF cohort was based at out-patient TB clinics, whereas participants in the ACF cohort were actively screened for TB by bacteriological sputum testing (smear microscopy, Xpert MTB/RIF assay, and liquid culture) without pre-selection on the basis of symptoms and signs. Outcomes of ATT were compared between participants in the two cohorts; characteristics at diagnosis and predictors of adverse outcomes were analysed. Results: Among 439 TB/HIV co-infected participants, 307 and 132 belonged to PCF and ACF cohorts, respectively. Compared with the ACF participants, hemoptysis, conjunctival pallor, bedridden status, and low mid upper-arm circumference (MUAC) were significantly more common in participants identified through PCF. Sputum smear-positivity rates among pulmonary TB cases were 44.2% and 21.1% in the PCF and ACF cohorts, respectively (p<0.001). Treatment success was ascertained in 247 (80.5%) of the participants in the PCF cohort and 102 (77.2%) of the participants in the ACF cohorts (p=0.223). Low MUAC (p=0.001) independently predicted mortality in the participants in both cohorts. Conclusion: Although patients identified through ACF had less advanced TB disease, ATT outcome was similar to the patients identified through PCF. To achieve a better outcome, case management in ACF strategy should be strengthened through enhanced patient-centred counselling and adherence support

Hydrological Simulation in a Rift-Bounded Lake System and Implication of Water Abstraction: Central Rift Valley Lakes Basin, Ethiopia

The Katar and Meki subbasins play a significant role in supporting the livelihoods of people in the region. However, the subbasins are currently under heavy human pressures, mainly associated with the ever-increasing human population and the subsequent intensification of irrigated agricultural activities. The aims of this study are to quantify the water balance components of the Katar and Meki rivers using the Soil and Water Assessment Tool (SWAT) model and to assess the implication of water abstraction on river hydrology. The Katar and Meki subbasins were discretized into 107 and 87 micro-subbasins, which were then subdivided further into Hydrologic Response Units (HRUs) of 683 and 658, respectively. Hydro-meteorological data from 1997 to 2014 were used for model setup, calibration, and validation. Nash–Sutcliffe Efficiency (NSE), coefficient of determination (R2), and Percent Bias (PBIAS) were used for model performance evaluation. The results of the simulation revealed NSE = 0.68–0.83, R2 = 0.72–0.85, and PBIAS = 1.6–22.7 during calibration and validation. More than 65% of the simulated flow was bracketed with the 95PPU for both subbasins, with the thickness of the 95PPU in the range of 0.90 to 1.41 calibration and 1.15 to 1.31 validation, which indicates that the overall performance of the water balance model can be rated as “very good”. The results of the water balance show that evapotranspiration (ET), surface runoff (Qs), and groundwater discharge (Qgw) were large in the Meki subbasin, while percolation (PERC) and water yield (WYLD) were large in the Katar subbasin. The model estimated 140 and 111 mm of average annual WYLD for the Katar and Meki subbasins, respectively, and the Katar subbasin is a major contributor of water to Lake Ziway. A total volume of 19.41 million cubic meters (MCM) of water is abstracted from Katar and Meki rivers for irrigation and domestic use, which significantly reduces Lake Ziway’s level by 4.5 cm (m). If the current trend of development continues, 149.92 MCM water will be abstracted each year from the lake environment and will reduce the lake level by 1.72 m. It is suspected that the Katar and Meki rivers are likely to cease to exist after a few decades and that Lake Ziway will also dry out

Distribution of HLA-DQ risk genotypes for celiac disease in Ethiopian children

Most patients with celiac disease are positive for either HLA-DQA1*05:01-DQB1*02 (DQ2.5) or DQA1*03:01-DQB1*03:02 (DQ8). Remaining few patients are usually DQA1*02:01-DQB1*02 (DQ2.2) carriers. Screenings of populations with high frequencies of these HLA-DQA1-DQB1 haplotypes report a 1% to 3% celiac disease prevalence. The aim was to determine the prevalence of HLA-DQ risk haplotypes for celiac disease in Ethiopian children. Dried blood spots collected from 1193 children from the Oromia regional state of Ethiopia were genotyped for HLA-DQA1 and DQB1 genotyping using an asymmetric polymerase chain reaction (PCR) and a subsequent hybridization of allele-specific probes. As references, 2000 previously HLA-genotyped children randomly selected from the general population in Sweden were included. DQ2.2 was the most common haplotype and found in 15.3% of Ethiopian children, which was higher compared with 6.7% of Swedish references (P <.0001). Opposed to this finding, DQ2.5 and DQ8 occurred in 9.7% and 6.8% of Ethiopian children, which were less frequent compared with 12.8% and 13.1% of Swedish references, respectively (P <.0001). The DQ2.5-trans genotype encoded by DQA1*05-DQB1*03:01 in combination with DQ2.2 occurred in 3.6% of Ethiopian children, which was higher compared with 1.3% of Swedish references (P <.0001). However, when children with moderate high to very high-risk HLA genotypes were grouped together, there was no difference between Ethiopian children and Swedish references (27.4% vs 29.0%) (P =.3504). The frequency of HLA risk haplotypes for celiac disease is very similar in Ethiopian and Swedish children. This finding of importance will be useful in future screening of children for celiac disease in Ethiopia

Drug Resistance in HIV-Positive Adults During the Initial Year of Antiretroviral Treatment at Ethiopian Health Centers

BACKGROUND: The increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition.METHODS: Participants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis.RESULTS: Among 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis.CONCLUSIONS: Among adults receiving health center-based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition

Development of a clinical scoring system for assessment of immunosuppression in patients with tuberculosis and HIV infection without access to CD4 cell testing - results from a cross-sectional study in Ethiopia

Background: Currently, antiretroviral therapy (ART) is recommended for all HIV-positive patients with tuberculosis (TB). The timing of ART during the course of anti-TB treatment is based on CD4 cell counts. Access to CD4 cell testing is not universally available; this constitutes an obstacle for the provision of ART in low-income countries. Objective: To determine clinical variables associated with HIV co-infection in TB patients and to identify correlations between clinical variables and CD4 cell strata in HIV/TB co-infected subjects, with the aim of developing a clinical scoring system for the assessment of immunosuppression. Design: Cross-sectional study of adults with TB (with and without HIV co-infection) recruited in Ethiopian outpatient clinics. Clinical variables potentially associated with immunosuppression were recorded using a structured questionnaire, and they were correlated to CD4 cell strata used to determine timing of ART initiation. Variables found to be significant in multivariate analysis were used to construct a scoring system. Results: Among 1,116 participants, the following findings were significantly more frequent in 307 HIV-positive patients compared to 809 HIV-negative subjects: diarrhea, odynophagia, conjunctival pallor, herpes zoster, oral candidiasis, skin rash, and mid-upper arm circumference (MUAC) less than20 cm. Among HIV-positive patients, conjunctival pallor, MUAC less than20 cm, dyspnea, oral hairy leukoplakia (OHL), oral candidiasis, and gingivitis were significantly associated with less than350 CD4 cells/mm(3). A scoring system based on these variables had a negative predictive value of 87% for excluding subjects with CD4 cell counts less than100 cells/mm(3); however, the positive predictive value for identifying such individuals was low (47%). Conclusions: Clinical variables correlate with CD4 cell strata in HIV-positive patients with TB. The clinical scoring system had adequate negative predictive value for excluding severe immunosuppression. Clinical scoring systems could be of use to categorize TB/HIV co-infected patients with regard to the timing of ART initiation in settings with limited access to laboratory facilities