Expression of mycobacterium tuberculosis induced SOCS3 and STAT3 and the implications on innate immunity in TB patients vs healthy contacts in high TB/HIV endemic setting: A cross-sectional analytical study.

BACKGROUND: Mycobacterium tuberculosis (TB) remains a disease of global health concern and a leading cause of mortality arising from an infectious agent. Protective immunity to TB remains unclear. Suppressor of cytokine signaling-3 (SOCS3) and signal transduction and activator of transcription-3 (STAT3) genes have shown potential to influence innate immunity. We, therefore, explored the expression of SOCS3 and STAT3 and their implications on the innate immunity in TB patients and their healthy close contacts. METHODS: We recruited 72 TB patients and 62 healthy contacts from a high TB and HIV endemic setting (Lusaka, Zambia). We used RT-PCRT and flow cytometry to quantify the expression of SOCS, STAT3 and cytokines respectively. Data was analysed Stata version 14.0 and figures were developed in GraphPad prism version 9.1.0 (221). Assessment for associations for categorical and continuous variables was analysed using the Chi-square test and Mann-Whitney test respectively. Spearman's rank correlation was used to evaluate the relationship between SOCS3 and IL-6. A p-value < 0.05 was considered statistically significant. RESULTS: Healthy contacts markedly expressed SOCS3 in both unstimulated and stimulated whole blood in comparison to TB patients (p <0.0001). STAT3 was elevated in TB patients in TB patients in stimulated blood only. IL-6 (P = < 0.0001) and IL-10 (P = <0.0001), were significantly expressed in Healthy contacts in comparison to TB patients. TNF-α (p = 0.044) were markedly elevated in TB patients in comparison to healthy contacts. IL-6 and SOCS3 correlated significantly in healthy contacts only (r = 0.429, p = 0.02). CONCLUSIONS: Both SOCS3 and STAT3 are genes of importance in mounting protective innate immunity against TB. We propose that SOCS3 stimulation and inhibition of STAT3 as possible approaches in gene therapy and vaccine development for TB.

Immune correlates of Mycobacterium Tuberculosis patients in Zambia stratified by HIV serostatus and level of immunity-a cross-sectional analytical laboratory based study.

BACKGROUND: People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count. RESULTS: We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28-42) years and 31(25-36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465-702.5 cells/mm3] vs 345 [157-483 cell/mm3] in HIV negative vs HIV positive respectively p = <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827-23,686 pg/ml] vs. 9,508 [5,514-15,008 pg/ml], respectively; p = 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3 for both cohorts. 21,953 [8,990-24,206 pg/ml] vs 9,505 [5,400-15,313 pg/ml], p value = 0.0585 in patients with CD4 count < 500 cell/mm3 and 13,168 [7,087-22,584 pg/ml] vs 10,413 [7,397-14,806 pg/ml], p value = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36-0.72; p < 0.0001) and r = 0.48 (95% CI 0.15-0.68; p = 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0-0.28] vs 0.007 [0-0.32] respectively; p = 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99, p value 0.007. CONCLUSIONS: This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.

A comparison of vitamin D and cathelicidin (LL-37) levels between patients with active TB and their healthy contacts in a high HIV prevalence setting: a prospective descriptive study.

BACKGROUND: Studies from Asia and Europe indicate an association between vitamin D deficiency and susceptibility to TB. We performed an observational case-control study to determine vitamin D and cathelicidin (LL-37) levels and their association with active TB in newly diagnosed and microbiologically confirmed adult TB patients in Zambia, a high HIV prevalence setting. METHODS: Both total vitamin D and LL-37 were measured using ELISA from serum and supernatant isolated from cultured whole blood that was stimulated with heat-killed Mycobacterium tuberculosis. Statistical analysis was performed using STATA statistical software version 12. RESULTS: The median vitamin D in TB patients and healthy contacts was 28.7 (19.88-38.64) and 40.8 (31.2-49.44) ng/ml, respectively (p<0.001). The median LL-37 in TB patients compared with healthy contacts was 1.87 (2.74-8.93) and 6.73 (5.6-9.58) ng/ml, respectively (p=0.0149). Vitamin D correlation with LL-37 in healthy contacts was R2=0.7 (95% CI 0.566 to 0.944), p<0.0001. Normal vitamin D significantly predicted a healthy status (OR 4.06, p=0.002). CONCLUSIONS: Significantly lower levels of vitamin D and LL-37 are seen in adults with newly diagnosed active TB. Longitudinal studies across various geographical regions are required to accurately define the roles of vitamin D and LL-37 in preventive and TB treatment outcomes.

Impact of mHealth on contraceptive use among women and men of reproductive age in low- and middle-income countries: a systematic review and meta-analysis.

OBJECTIVE: Around the world, the use of modern contraceptives has risen significantly, but the quality and reach of sexual and reproductive health services remains weak in the poorest countries. To address the high unmet need, an opportunity arises for mobile health technology (mHealth) to empower both clients and providers. However, evidence that mHealth is effective in increasing modern contraceptive use is limited and mixed, and we set out to assess its impact. METHODS: A systematic literature search from seven electronic databases was conducted using key search terms. Individually randomised controlled trials that compared modern contraceptive use in women and men using phone message interventions and those without the intervention were included. Stata was used to calculate pooled estimates of effect under the random-effects model, as well as produce the risk of bias using the Egger's regression method. GRADEpro GDT was used to assess the quality of individual studies. RESULTS: A pooled estimate of all of the studies showed a positive association between phone messages and contraception use, but no clear evidence of benefit (OR 1.12; 95% CI 0.97-1.29). Notably, pooled results of studies that reported modern contraceptive use as the primary outcome showed that mobile phone messaging was associated with an increase in the use of modern contraception (OR 1.22; 95% CI 1.01-1.47). CONCLUSIONS: The finding of this systematic review suggests that mobile phone message interventions utilising a behavioural change technique are an effective method of increasing modern contraceptive use among men and women of reproductive age in low- and middle-income countries though the effect is small.

OBJECTIF: Partout dans le monde, l'utilisation de contraceptifs modernes a considérablement augmenté, mais la qualité et la portée des services de santé sexuelle et reproductive restent faibles dans les pays les plus pauvres. Pour répondre à cet important besoin non satisfait, une opportunité se présente avec la technologie de la santé mobile (mHealth) permettant d'autonomiser à la fois les patients et les prestataires. Cependant, les preuves que mHealth est efficace pour augmenter l'utilisation de la contraception moderne sont limitées et mitigées, et nous avons entrepris d'évaluer son impact. MÉTHODES: Une recherche systématique de la littérature dans 7 bases de données électroniques a été menée à l'aide de termes de recherche clés. Des essais contrôlés randomisés individuels comparant l'utilisation de la contraception moderne chez les femmes et les hommes utilisant des interventions via des messages téléphoniques et ceux sans intervention ont été inclus. Stata a été utilisé pour calculer des estimations d'effet poolées selon le modèle à effets aléatoires, ainsi que pour produire le risque de biais à l'aide de la méthode de régression d'Egger. GRADEpro GDT a été utilisé pour évaluer la qualité des études individuelles. RÉSULTATS: Une estimation poolée de toutes les études a montré une association positive entre les messages téléphoniques et l'utilisation de la contraception, mais aucune preuve claire de bénéfice (OR 1,12; IC95%: 0,97­1,29). Notamment, les résultats poolés des études qui rapportaient sur l'utilisation de la contraception moderne comme critère principal ont montré que la messagerie par téléphone mobile était associée à une augmentation de l'utilisation de la contraception moderne (OR 1,22; IC95%: 1,01­1,47). CONCLUSIONS: Les résultats de cette revue systématique suggèrent que les interventions de messagerie par téléphone mobile utilisant une technique de changement de comportement sont une méthode efficace pour augmenter l'utilisation de la contraception moderne chez les hommes et les femmes en âge de procréer dans les pays à revenu faible ou intermédiaire, bien que l'effet soit faible.

Design and Development Process of a Youth Depression Screening m-Health Application for Primary Health Care Workers in South Africa and Zambia: An Overview of the MEGA Project.

Literature indicates a high prevalence and burden of mental illness in youths world-wide, which may be even higher in low- and middle-income countries (LMIC), such as South Africa and Zambia. Additionally, there is a lack of knowledge regarding youth depression amongst many primary health care (PHC) practitioners. The principal goal of the MEGA project is to provide youth with better access to mental health services and appropriate care, by developing a mental health screening mobile application tool to be used in PHC settings in South Africa and Zambia. In this study, we will use a mixed methods multi-center study design. In phase one, we will investigate the mental health literacy of PHC practitioners to identify areas in need of development. Based on the needs identified, we will develop and test a mobile health application to screen for common youth mental health problems in phase two. In phase three, we will implement and evaluate a tiered education and training program in the use of the m-health application. In the final phase, we will evaluate the acceptability and feasibility of the m-health application in PHC centres across South Africa and Zambia. Evidence suggests that PHC practitioners should routinely consider mental illness when assessing youth. However, common psychiatric disorders remain largely undetected and untreated in PHC settings. By identifying limitations in PHC workers knowledge with regard to youth mental health, we aspire to improve the depression care provided to youth in Southern Africa and Zambia by developing and implementing a locally relevant m-health application.

Interactions between Schistosoma haematobium and human immunodeficiency virus type 1: the effects of coinfection on treatment outcomes in rural Zambia.

A prospective cohort study was conducted in two villages in Zambia to compare the efficacy of praziquantel in the treatment of schistosomiasis haematobium in people with and without concomitant infection with human immunodeficiency virus (HIV). Five hundred seven individuals with infected with Schistosoma haematobium were enrolled and followed-up for as long as 12 months after treatment with a single dose of praziquantel. Seventy-three were coinfected with HIV. The study demonstrated that praziquantel is still very effective in the treatment and control of S. haematobium even when there is coinfection with HIV (without symptoms and signs of acquired immunodeficiency syndrome [AIDS]/HIV disease). Resistance to reinfection with S. haematobium is not altered in subjects coinfected with HIV (without symptoms and signs of AIDS/HIV disease). Individuals with coinfection excreted fewer eggs and complained less of hematuria than those without HIV infection, and the sensitivity and positive predictive value of reported hematuria as an indication of heavy infection were lower in the group coinfected with HIV. This observation may have implications for the use of hematuria as an indicator for rapid diagnosis of schistosomiasis in areas where HIV is prevalent.