Cellular and Cytokine Responses in the Granulomas of Asymptomatic Cattle naturally infected with Mycobacterium bovis in Ethiopia

Cells (CD3+ T cell and CD68+ macrophages), cytokines (IFN-γ+ and TNF-α+) and effector molecule (iNOS+) responses were evaluated in the lymph nodes and tissue of cattle naturally infected with Detailed post mortem and immunohistochemical examinations of lesions were performed on 16 cows positive for single intradermal cervical comparative tuberculin (SICCT) test which were identified from dairy farms located around the Addis Ababa City. The severity of the gross lesion was significantly higher (p=0.003) in culture positive (n=12) cows than in culture negative (n=4). Immunohistochemical techniques showed that in culture positive cows, the mean immunolabeling fraction of CD3+ T cells decreased as the stage of granuloma increased from stage I to stage IV (p<0.001). In contrast, the immunolabelling fraction of CD68+ macrophages, IFN-γ+, TNF-α+ and iNOS+ increased from stage I to stage IV (p< 0.001). In culture negative cows, early stages showed a significantly higher fraction of CD68+ macrophages (p=0.03) and iNOS+ (p=0.007) when compared to culture positive cows. Similarly, at advanced granuloma stages, culture negative cows demonstrated significantly higher mean proportions of CD3+ T cells (p< 0.001) compared to culture positive cows. Thus, this study demonstrates that following natural infection of cows with , as the stage of granuloma increases from stage I to stage IV, the immunolabelling fraction of CD3+ cells decreases while the immunolabeling fraction of CD68+ macrophages, IFN-γ+, TNF-α+ and iNOS+ increases. [Abstract copyright: Copyright © 2020 Tulu et al.

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

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

BACKGROUND: The 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. METHODS: In 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. FINDINGS: We 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 (<10 g/dL), body-mass index (<18·5 kg/m2), 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. INTERPRETATION: C-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. FUNDING: World Health Organization

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

IMPACT OF CATTLE KEEPING ON HUMAN BITING RATE OF ANOPHELINE MOSQUITOES AND MALARIA TRANSMISSION AROUND ZIWAY, ETHIOPIA

Objective: To assess the impact of livestock keeping on the human biting rate (HBR)of anopheline mosquitoes and malaria transmission around Ziway in the middle courseof the Ethiopian Rift Valley.Design: As a passive experiment, man landing captures were done in homesteads withmixed dwelling, separate cattle shed and without livestock; and as an active experiment,captures were in experimental tukuls (huts) of cattle, goats, and without livestock.Parasite and spleen rates of children were compared among those residents undervariable living conditions mentioned for passive experiment.Subjects: For entomological study, human-baits were used for man-landing captures ofmosquitoes. Study subjects for parasitological and clinical studies were children below10 years old.Main outcome measures: Human-biting rate (HBR) of anopheline mosquitoes; and theparasite and spleen rates of the study subjects in different living conditions.Results: In the passive experiment, the mean HBR of Anopheles arabiensis in mixeddwelling, separate cattle shed and without livestock was 8.45, 4.64 and 5.97, respectively.Similarly, the HBR of An. pharoensis was 2.88, 1.79 and 1.61, respectively. In the activeexperiment, the mean HBR of An. arabiensis in tukuls with cattle, goats, and withoutlivestock was 3.50, 3.38 and 1.43 respectively; while that of An. pharoensis was 0.37,0.70 and 0.55 respectively. Parasitologically, mean parasite rates of 26.67%, 15.05% and23.85% were, respectively, recorded from children living under the above conditionsstated for passive experiment. Similarly, the mean spleen rates of 50.0%, 26.9%, and47.37% were recorded, respectively.Conclusion: These observations in the present study indicate that the presence of cattlein homesteads tends to increase the man biting rate of An. arabiensis, althoughdifferences in the mean HBR of vector mosquitoes were not statistically significant forall groups. In contrast, cattle keeping in separate cattle sheds outside of the humandwellings tends to reduce the man biting rate of An. arabiensis and malaria transmissionin the study area