Tuberculosis and Sexual and Reproductive Health of Women in Four African Countries

Tuberculosis (TB) is a major reason of maternal mortality in low-income countries, and it increases the probability of adverse sexual and reproductive health (SRH) outcomes, including ectopic pregnancy and perinatal mortality. The data presented here is from the TB Sequel observational cohort conducted in four African countries. For this sub-study, we selected only female participants, who were diagnosed with drug susceptible TB and followed-up until the end of anti-TB treatment. The data collection included questionnaires, clinical examination and laboratory tests at TB diagnosis, day 14, month 2, 4 and 6. A total of 486 women, with 88.3% being 18-49 years old, were included in the analysis. Around 54.7% were HIV positive. Most of the participants (416/486;85.6%) in our cohort were considered cured at month 6. Only 40.4% of non-pregnant women of reproductive age used contraception at TB diagnosis. A total of 31 out of 486 women experienced pregnancy during TB treatment. Pregnancy outcomes varied between live birth (16/31;51.6%), induced abortion (6/31;19.4%), miscarriage (4/31;12.9%) and stillbirth (3/31;9.6%). Integration and linking of SRH services with TB programmes are vital to increase contraception use and protect women from obstetric risks associated with pregnancy during TB treatment

Health-related quality of life and psychological distress among adults in Tanzania: a cross-sectional study

Little data is available on health-related quality of life (HRQoL) and mental health of the general population in Tanzania. We aimed to describe HRQoL and level of psychological distress among adults in Mbeya and Songwe Regions of Tanzania. Methods We conducted a cross-sectional study between April and October 2019 in Mbeya and Songwe Regions. Data were collected using the Medical Outcomes Short Form-36 (SF-36) questionnaire and the Page Kessler Psychological Distress Scale (K10). We described demographic characteristics of participants and used log-binomial regression to identify participant characteristics associated with psychological distress (K10 score ≥ 20). Results A total of 393 adults were enrolled. The participants had a median age of 29 years (IQR 23–40) and 54.2% were male. Participants reported a physical component summary score (PCS) with a mean of 54.7 (SD7.1) and a mental component summary score (MCS) with a mean of 55.5 (SD5.1). Older participants (≥ 40 year) and those that were divorced/widowed reported lower physical functioning, energy/vitality and emotional well-being compared to their counterparts ( p < 0.05). In terms of psychological distress, majority of participants (78.4%; 305/389) reported that they were likely to be well (K10 score < 20), while 13.4% (52/389) reported to have mild (K10 score 20–24), 5.7% (22/389) moderate (K10 score 25–29), and 2.6% (10/389) severe (K10 score ≥ 30) psychological distress. Conclusions Physical function and mental well-being in this adult population from Tanzania were lower than that reported in other similar research in Tanzania and other African countries. This study provides valuable references for other research initiatives and clinical services in this region

Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment.

BACKGROUND: Despite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung recovery. Neutrophils are associated with lung pathology; however, CD16/CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype, and function of neutrophils following stimulation with Mycobacterium tuberculosis (Mtb) whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC) in relation to lung pathology. METHODS: Fresh blood from 42 adult, human immunodeficiency virus (HIV)-negative TB patients were analyzed pre- and post-therapy, with disease severity determined using chest radiography and bacterial load. Flow cytometry was used to monitor frequencies, phenotype, and function (generation of reactive oxygen species [ROS], together with CD11b, tumor necrosis factor, and interleukin 10 [IL-10] expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens. RESULTS: Total neutrophils decreased by post-treatment compared to baseline (P = .0059); however, CD16brCD62Lbr (segmented) neutrophils increased (P = .0031) and CD16dimCD62Lbr (banded) neutrophils decreased (P = .038). Banded neutrophils were lower in patients with severe lung damage at baseline (P = .035). Following WCL stimulation, ROS from segmented neutrophils was higher in patients with low Mtb loads even after adjusting for sex (P = .038), whereas IL-10-expressing CD16dimCD62Llo cells were higher in patients with mild damage (P = .0397) at baseline. CONCLUSIONS: High ROS generation, low levels of banded neutrophils, and high levels of IL-10-expressing CD16dimCD62Llo neutrophils are associated with reduced lung pathology at diagnosis. Hence, neutrophils are potential early indicators of TB severity and promising targets for TB host-directed therapy

Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients

Background: The inflammatory response to Mycobacterium tuberculosis results in variable degrees of lung pathology during active TB (ATB) with central involvement of neutrophils. Little is known about neutrophil-derived mediators and their role in disease severity at baseline and recovery upon TB treatment initiation. Methods: 107 adults with confirmed pulmonary TB were categorised based on lung pathology at baseline and following successful therapy using chest X-ray scores (Ralph scores) and GeneXpert bacterial load (Ct values). Plasma, sputum, and antigen-stimulated levels of MMP1, MMP3, MMP8, MMP9, MPO, S100A8/9, IL8, IL10, IL12/23(p40), GM-CSF, IFNγ, and TNF were analysed using multiplex cytokine arrays. Results: At baseline, neutrophil counts correlated with plasma levels of MMP8 (rho = 0.45, p = 2.80E-06), S100A8 (rho = 0.52, p = 3.00E-08) and GM-CSF (rho = 0.43, p = 7.90E-06). Levels of MMP8 (p = 3.00E-03), MMP1 (p = 1.40E-02), S100A8 (p = 1.80E-02) and IL12/23(p40) (p = 1.00E-02) were associated with severe lung damage, while sputum MPO levels were directly linked to lung damage (p = 1.80E-03), Mtb load (p = 2.10E-02) and lung recovery (p = 2.40E-02). Six months of TB therapy significantly decreased levels of major neutrophil-derived pro-inflammatory mediators: MMP1 (p = 4.90E-12 and p = 2.20E-07), MMP8 (p = 3.40E-14 and p = 1.30E-05) and MMP9 (p = 1.60E-04 and p = 1.50E-03) in plasma and sputum, respectively. Interestingly, following H37Rv whole cell lysate stimulation, S100A8 (p = 2.80E-02), MMP9 (p = 3.60E-02) and MPO (p = 9.10E-03) levels at month 6 were significantly higher compared to baseline. Sputum MMP1 (p = 1.50E-03), MMP3 (p = 7.58E-04), MMP9 (p = 2.60E-02) and TNF (p = 3.80E-02) levels were lower at month 6 compared to baseline in patients with good lung recovery. Conclusion: In this study, patients with severe lung pathology at baseline and persistent lung damage after treatment were associated with higher plasma and sputum levels of major pro-inflammatory neutrophil-derived mediators. Interestingly, low sputum MPO levels were associated with severe lung damage, higher Mtb burden and low recovery. Our data suggest that therapeutic agents which target these mediators should be considered for future studies on biomarkers and host-directed therapeutic approaches against TB-related lung pathology and/or lung recovery

Effects of pathogen dependency in a multi-pathogen infectious disease system including population level heterogeneity - a simulation study.

Increased computational resources have made individual based models popular for modelling epidemics. They have the advantage of incorporating heterogeneous features, including realistic population structures (like e.g. households). Existing stochastic simulation studies of epidemics, however, have been developed mainly for incorporating single pathogen scenarios although the effect of different pathogens might directly or indirectly (e.g. via contact reductions) effect the spread of each pathogen. The goal of this work was to simulate a stochastic agent based system incorporating the effect of multiple pathogens, accounting for the household based transmission process and the dependency among pathogens

Additional file 1: of Incidence and comparison of retrospective and prospective data on respiratory and gastrointestinal infections in German households

Definition of acute respiratory (ARI) and gastrointestinal infection (AGI) episodes. (DOCX 19 kb

Additional file 1: of Effects of pathogen dependency in a multi-pathogen infectious disease system including population level heterogeneity – a simulation study

Time taken to reach the peak prevalence varies according to the household size distribution in the cohort. Populations with larger households on an average experienced the epidemics at an accelerated rate compared to populations with smaller households on an average. (PNG 24 kb

A cross-sectional mixed-methods study of sexual and reproductive health knowledge, experiences and access to services among refugee adolescent girls in the Nakivale refugee settlement, Uganda

Abstract Background Humanitarian crises and migration make girls and women more vulnerable to poor sexual and reproductive health (SRH) outcomes. Nevertheless, there is still a dearth of information on SRH outcomes and access to SRH services among refugee girls and young women in Africa. We conducted a mixed-methods study to assess SRH experiences, knowledge and access to services of refugee girls in the Nakivale settlement, Uganda. Methods A cross-sectional survey among 260 adolescent girls 13–19 years old was conducted between March and May 2018. Concurrently, in-depth interviews were conducted among a subset of 28 adolescents. For both methods, information was collected regarding SRH knowledge, experiences and access to services and commodities. The questionnaire was entered directly on the tablets using the Magpi® app. Descriptive statistical analysis and multinomial logistic regression were performed. Qualitative data was transcribed and analysed using thematic content analysis. Results A total of 260 participants were interviewed, with a median age of 15.9 years. The majority of girls were born in DR Congo and Burundi. Of the 93% of girls who had experienced menstruation, 43% had ever missed school due to menstruation. Regarding SRH knowledge, a total of 11.7% were not aware of how HIV is prevented, 15.7% did not know any STI and 13.8% were not familiar with any method to prevent pregnancy. A total of 30 girls from 260 were sexually active, of which 11 had experienced forced sexual intercourse. The latter occurred during conflict, in transit or within the camp. A total of 27 of 260 participants had undergone female genital mutilation (FGM). The most preferred sources for SRH information was parents or guardians, although participants expressed that they were afraid or shy to discuss other sexuality topics apart from menstruation with parents. A total of 30% of the female adolescents had ever visited a SRH service centre, mostly to test for HIV and to seek medical aid for menstrual problems. Conclusions Adolescent refugee girls lack adequate SRH information, experience poor SRH outcomes including school absence due to menstruation, sexual violence and FGM. Comprehensive SRH services including sexuality education, barrier-free access to SRH services and parental involvement are recommended

Tuberculosis Treatment Response Monitoring by the Phenotypic Characterization of <em>MTB</em>-Specific <em>CD4+</em> T-Cells in Relation to HIV Infection Status

HIV infection causes systemic immune activation, impacts TB disease progression and hence may influence the diagnostic usability of Mycobacterium tuberculosis-specific T cell profiling. We investigated changes of activation and maturation markers on MTB-specific CD4+ T-cells after anti-tuberculosis treatment initiation in relation to HIV status and the severity of lung impairment. Thawed peripheral blood mononuclear cells from TB patients with (n = 27) and without HIV (n = 17) were analyzed using an intracellular IFN-γ assay and flow cytometry 2 and 6 months post-TB treatment initiation. H37Rv antigen was superior to the profile MTB-specific CD4+ T-cells phenotype when compared to PPD and ESAT6/CFP10. Regardless of HIV status and the severity of lung impairment, activation markers (CD38, HLA-DR and Ki67) on MTB-specific CD4+ T-cells declined after TB treatment initiation (p MTB-specific T cell phenotype before, during and after treatment completion was similar between people living with and without HIV, as well as between subjects with severe and mild lung impairment. These data suggest that the assessment of activation and maturation markers on MTB-specific CD4+ T-cells can be useful for TB treatment monitoring, regardless of HIV status and the severity of lung disease