Impact of on-site Xpert on TB diagnosis and mortality trends in Uganda.

SETTING: Since 2012, Uganda expanded the Xpert® MTB/RIF network for diagnosis of TB. OBJECTIVES: We compared TB care cascades at health facilities with on-site Xpert vs. facilities that accessed the assay through specimen referral. DESIGN: We analysed secondary aggregate data of the National TB and Leprosy Program (NTLP) from 2016 to 2019. We computed the proportions of notified TB cases and mortality ratios in relation to the estimated TB burden. RESULTS: TB case notifications per annum increased from 24,287 in 2016 to 30,739 in 2019, and the proportion of cases diagnosed at facilities with on-site Xpert testing increased from 62% (15,070/24,287) to 81% (24,829/30,739) (P < 0.001). TB mortality at facilities with on-site Xpert decreased from 8.6% (1,302/15,070) to 7.8% (1,938/24,829) (P = 0.41), while it increased at facilities without on-site Xpert from 6.9% (638/9,217) to 8.8% (521/5,910) (P = 0.23). Furthermore, mortality among TB-HIV co-infected patients at facilities with on-site Xpert dropped from 5.0% (760/15,070) in 2016 to 4.8% (1,187/24,826) in 2019 (P = 0.84) compared to 4.4% (407/9,217) in 2016 to 5.3% (315/5,910) in 2019 (P = 0.57). CONCLUSION: Wider installation and decentralisation of Xpert leads to increased case-finding. However, the impact on reduction in mortality remains limited. Interventions to address TB-related mortality in addition to Xpert roll-out are required.

CONTEXTE: Depuis 2012, l'Ouganda a élargi son réseau de tests Xpert® MTB/RIF destinés au diagnostic de la TB. Nous avons comparé les cascades de soins de la TB dans des centres en mesure de réaliser les tests Xpert « sur place ¼ et dans des centres ayant accès à ces tests par un système d'adresse des prélèvements. MÉTHODES: Nous avons analysé les données agrégées secondaires du programme national de lutte contre la TB (NTLP) de 2016 à 2019. Nous avons calculé les pourcentages de cas de TB ayant fait l'objet d'une notification et les taux de mortalité par rapport au poids sanitaire estimé de la TB. RÉSULTATS: Les notifications annuelles de cas de TB ont augmenté de 24 287 en 2016 à 30 739 en 2019, et la proportion de cas diagnostiqués dans les centres avec tests Xpert sur place a augmenté de 62% (15 070/24 287) à 81% (24 829/30 739) ; P < 0,001. La mortalité liée à la TB dans les centres avec tests Xpert sur place a diminué de 8,6% (1 302/15 070) à 7,8% (1 938/24 829) (P = 0,41), alors qu'elle a augmenté dans les centres sans tests Xpert sur place, de 6,9% (638/9 217) à 8,8% (521/5 910) (P = 0,23). Par ailleurs, la mortalité des patients coinfectés par la TB et le VIH dans les centres avec tests Xpert sur place a diminué de 5,0% (760/15 070) en 2016 à 4,8% (1 187/24 826) en 2019 (P = 0,84), contre une hausse de 4,4% (407/9 217) en 2016 à 5,3% (315/5 910) en 2019 (P = 0,57) dans les centres sans tests Xpert sur place. CONCLUSIONS: La décentralisation et l'élargissement du déploiement des tests Xpert a permis d'accroître le nombre de cas détectés. Toutefois, l'impact sur la réduction de la mortalité reste limité. Des interventions visant à réduire la mortalité liée à la TB, audelà du déploiement des tests Xpert, sont nécessaires.

Isolation of luteal endothelial cells and functional interactions with T lymphocytes.

The objectives of this study were to optimize the isolation of luteal endothelial cells (LEC) and examine their functional interactions with autologous T lymphocytes. Analysis by flow cytometry showed that the purity of LEC isolated by filtration was nearly 90% as indicated by Bandeiraea simplicifolia (BS)-1 lectin binding. LEC expressed mRNA for progesterone receptor (PGR), prostaglandin receptors (PTGFR, PTGER2 and 4, and PTGIR), tumor necrosis factor receptors (TNFRSF1A&B) and interleukin (IL) 1B receptors (IL1R1&2). LEC were pretreated with either vehicle, progesterone (P4; 0-20 µM), prostaglandin (PG) E2 or PGF2α (0-0.2 µM), and further treated with or without TNF and IL1B (50 ng/mL each). LEC were then incubated with autologous T lymphocytes in an adhesion assay. Fewer lymphocytes adhered to LEC after exposure to high compared to low P4 concentrations (cubic response; P < 0.05). In contrast, 0.2 µM PGE2 and PGF2α each increased T lymphocyte adhesion in the absence of cytokines (P < 0.05). LEC induced IL2 receptor alpha (CD25) expression and proliferation of T lymphocytes. In conclusion, filtration is an effective way of isolating large numbers of viable LEC. It is proposed that PGs and P4 modulate the ability of endothelial cells to bind T lymphocytes, potentially regulating extravasation, and that LEC activate T lymphocytes migrating into or resident in the CL.

Effects of dietary Capsicum oleoresin on productivity and immune responses in lactating dairy cows.

This study investigated the effect of Capsicum oleoresin in granular form (CAP) on nutrient digestibility, immune responses, oxidative stress markers, blood chemistry, rumen fermentation, rumen bacterial populations, and productivity of lactating dairy cows. Eight multiparous Holstein cows, including 3 ruminally cannulated, were used in a replicated 4×4 Latin square design experiment. Experimental periods were 25 d in duration, including a 14-d adaptation and an 11-d data collection and sampling period. Treatments included control (no CAP) and daily supplementation of 250, 500, or 1,000 mg of CAP/cow. Dry matter intake was not affected by CAP (average 27.0±0.64 kg/d), but milk yield tended to quadratically increase with CAP supplementation (50.3 to 51.9±0.86 kg/d). Capsicum oleoresin quadratically increased energy-corrected milk yield, but had no effect on milk fat concentration. Rumen fermentation variables, apparent total-tract digestibility of nutrients, and N excretion in feces and urine were not affected by CAP. Blood serum ß-hydroxybutyrate was quadratically increased by CAP, whereas the concentration of nonesterified fatty acids was similar among treatments. Rumen populations of Bacteroidales, Prevotella, and Roseburia decreased and Butyrivibrio increased quadratically with CAP supplementation. T cell phenotypes were not affected by treatment. Mean fluorescence intensity for phagocytic activity of neutrophils tended to be quadratically increased by CAP. Numbers of neutrophils and eosinophils and the ratio of neutrophils to lymphocytes in peripheral blood linearly increased with increasing CAP. Oxidative stress markers were not affected by CAP. Overall, in the conditions of this experiment, CAP did not affect feed intake, rumen fermentation, nutrient digestibility, T cell phenotypes, and oxidative stress markers. However, energy-corrected milk yield was quadratically increased by CAP, possibly as a result of enhanced mobilization of body fat reserves. In addition, CAP increased neutrophil activity and immune cells related to acute phase immune response.

Immune and production responses of dairy cows to postruminal supplementation with phytonutrients.

This study investigated the effect of phytonutrients (PN) supplied postruminally on nutrient utilization, gut microbial ecology, immune response, and productivity of lactating dairy cows. Eight ruminally cannulated Holstein cows were used in a replicated 4×4 Latin square. Experimental periods lasted 23 d, including 14-d washout and 9-d treatment periods. Treatments were control (no PN) and daily doses of 2g/cow of either curcuma oleoresin (curcumin), garlic extract (garlic), or capsicum oleoresin (capsicum). Phytonutrients were pulse-dosed into the abomasum of the cows, through the rumen cannula, 2 h after feeding during the last 9 d of each experimental period. Dry matter intake was not affected by PN, although it tended to be lower for the garlic treatment compared with the control. Milk yield was decreased (2.2 kg/d) by capsicum treatment compared with the control. Feed efficiency, milk composition, milk fat and protein yields, milk N efficiency, and 4.0% fat-corrected milk yield were not affected by treatment. Rumen fermentation variables, apparent total-tract digestibility of nutrients, N excretion with feces and urine, and diversity of fecal bacteria were also not affected by treatment. Phytonutrients had no effect on blood chemistry, but the relative proportion of lymphocytes was increased by the capsicum treatment compared with the control. All PN increased the proportion of total CD4(+) cells and total CD4(+) cells that co-expressed the activation status signal and CD25 in blood. The percentage of peripheral blood mononuclear cells (PBMC) that proliferated in response to concanavalin A and viability of PBMC were not affected by treatment. Cytokine production by PBMC was not different between control and PN. Expression of mRNA in liver for key enzymes in gluconeogenesis, fatty acid oxidation, and response to reactive oxygen species were not affected by treatment. No difference was observed due to treatment in the oxygen radical absorbance capacity of blood plasma but, compared with the control, garlic treatment increased 8-isoprostane levels. Overall, the PN used in this study had subtle or no effects on blood cells and blood chemistry, nutrient digestibility, and fecal bacterial diversity, but appeared to have an immune-stimulatory effect by activating and inducing the expansion of CD4 cells in dairy cows. Capsicum treatment decreased milk yield, but this and other effects observed in this study should be interpreted with caution because of the short duration of treatment.

Physiology and Endocrinology Symposium: role of immune cells in the corpus luteum.

The immune system is essential for optimal function of the reproductive system. The corpus luteum (CL) is an endocrine organ that secretes progesterone, which is responsible for regulating the length of the estrous cycle, and for the establishment and maintenance of pregnancy in mammals. This paper reviews literature that addresses 2 areas; i) how immune cells are recruited to the CL, and ii) how immune cells communicate with luteal cells to affect the formation, development, and regression of the CL. Immune cells, primarily recruited to the ovulatory follicle from lymphoid organs after the LH surge, facilitate ovulation and populate the developing CL. During the luteal phase, changes in the population of macrophages, eosinophils, neutrophils, and T lymphocytes occur at critical functional stages of the CL. In addition to their role in facilitating ovulation, immune cells may have an important role in luteal function. Evidence shows that cytokines secreted by immune cells modulate both luteotropic and luteolytic processes. However, the decision to pursue either function may depend on the environment provided by luteal cells. It is suggested that understanding the role immune cells play could lead to identification of new strategies to improve fertility in dairy cattle and other species.