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Natural Killer cells are key mediators of anti-tumour immunosurveillance and anti-viral immunity. Here, the authors map regulatory genetic variation in primary Natural Killer cells, providing new insights into their role in human health and disease.

Influenza pneumonia is a severe complication caused by inflammation of the lungs following infection with seasonal and pandemic strains of influenza A virus (IAV), that can result in lung pathology, respiratory failure, and death. There is currently no treatment for severe disease and pneumonia caused by IAV. Antivirals are available but are only effective if treatment is initiated within 48 h of onset of symptoms. Influenza complications and mortality are often associated with high viral load and an excessive lung inflammatory cytokine response. Therefore, we simultaneously targeted the virus and inflammation. We used the antiviral oseltamivir and the anti-inflammatory drug etanercept to dampen TNF signaling after the onset of clinical signs to treat pneumonia in a mouse model of respiratory IAV infection. The combined treatment down-regulated the inflammatory cytokines TNF, IL-1β, IL-6, and IL-12p40, and the chemokines CCL2, CCL5, and CXCL10. Consequently, combined treatment with oseltamivir and a signal transducer and activator of transcription 3 (STAT3) inhibitor effectively reduced clinical disease and lung pathology. Combined treatment using etanercept or STAT3 inhibitor and oseltamivir dampened an overlapping set of cytokines. Thus, combined therapy targeting a specific cytokine or cytokine signaling pathway and an antiviral drug provide an effective treatment strategy for ameliorating IAV pneumonia. This approach might apply to treating pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Most theories of International Relations (IR) are cautious, if not pessimistic, about the potential for change in IR. In this regard, the concept of ontological security holds promising yet oft-overlooked prospects. This article argues that applications of ontological security to IR theory thus far have been limited due to the narrow conceptualisations of practices and how they contribute to one’s attempts to preserve their ontological security. As such, this paper seeks to expand the theoretical framework through which ontological security is applied to IR, which involves a more comprehensive conceptualisation of practice that considers reflexivity as key. Accordingly, the theory demonstrates that a state, faced with threats to their sense of Self, can respond either by rigidising or changing their practices rather than being limited to the former. This allows one to account for change—especially big change—in world politics such as the increasingly inward-looking turn of the West.

Objectives: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p′-DDE, were related to genome-wide genetic and methylation variation in a population-based sample. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p,p′-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied. Results: Evidence for genome-wide significant association with p,p′-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allele was 192 ng/g lipid (p = 1.5 × 10−31). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19:41520351; p = 2.2 × 10−8).A whole-genome methylation analysis showed one significant relationship vs. p,p′-DDE levels (p = 6.2 × 10−9) located 7 kb downstream the CYP2B6 gene (cg27089200, position chr19:41531976). This CpG-site was also related to the lead SNP (p = 3.8 × 10−35), but mediated only 4% of the effect of the lead SNP on p,p′-DDE levels. Conclusion: Circulating levels of p,p′-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p,p′-DDE levels. Keywords: GWAS, CYP2B6, DDE, Metabolism, Methylation

Aberrant DNA methylation is an important cancer hallmark, yet the dynamics of DNA methylation changes in human carcinogenesis remain largely unexplored. Moreover, the role of DNA methylation for prediction of clinical outcome is still uncertain and confined to specific cancers. Here we perform the most comprehensive study of DNA methylation changes throughout human carcinogenesis, analysing 27,578 CpGs in each of 1,475 samples, ranging from normal cells in advance of non-invasive neoplastic transformation to non-invasive and invasive cancers and metastatic tissue. We demonstrate that hypermethylation at stem cell PolyComb Group Target genes (PCGTs) occurs in cytologically normal cells three years in advance of the first morphological neoplastic changes, while hypomethylation occurs preferentially at CpGs which are heavily Methylated in Embryonic Stem Cells (MESCs) and increases significantly with cancer invasion in both the epithelial and stromal tumour compartments. In contrast to PCGT hypermethylation, MESC hypomethylation progresses significantly from primary to metastatic cancer and defines a poor prognostic signature in four different gynaecological cancers. Finally, we associate expression of TET enzymes, which are involved in active DNA demethylation, to MESC hypomethylation in cancer. These findings have major implications for cancer and embryonic stem cell biology and establish the importance of systemic DNA hypomethylation for predicting prognosis in a wide range of different cancers.

Abstract Introduction Early diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed. Methods We conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard. Findings We analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4–96.7); for Isoniazid, 96.6 (95% CI, 92.1–98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8–99.7); for Amikacin, 96.6%; and (95% CI 92.1–98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%. Conclusion The Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.

Abstract Extrapulmonary tuberculosis (EPTB) has received less attention than pulmonary tuberculosis due to its non-contagious nature. EPTB can affect any organ and is more prevalent in people living with HIV. Low- and middle-income countries are now facing the double burden of non-communicable diseases (NCDs) and HIV, complicating the management of patients with symptoms that could be compatible with both EPTB and NCDs. Little is known about the risk of death of patients presenting with symptoms compatible with EPTB. We included patients with a clinical suspicion of EPTB from a tertiary level hospital in Mbeya, Tanzania, to assess their risk of dying. A total of 113 (61%) patients were classified as having EPTB, and 72 (39%) as having non-TB, with corresponding mortality rates of 40% and 41%. Associated factors for mortality in the TB groups was hospitalization and male sex. Risk factors for hospitalization was having disease manifestation at any site other than lymph nodes, and comorbidities. Our results imply that NCDs serve as significant comorbidities amplifying the mortality risk in EPTB. To strive towards universal health coverage, focus should be on building robust health systems that can tackle both infectious diseases, such as EPTB, and NCDs.

Background: The composting process of peri-urban household wastes, changes that occur during composting, and the properties of the composting products that are of importance for use as soil amendments were studied. Seven different composting mixtures were made in large piles consisting of fallen tree leaves and fresh vegetable leaves mixed with grass or maize straw (0%, 10%, 30% and 50% w/w), wastes common in peri-urban areas of Harare. Results: The highest temperature peaks of the mixtures with 0% and 10% straw were in the range of 68°C to 72°C. Mixtures with 30% straw had temperature peaks of 50°C (maize) and 52°C (grass). The mixture with 50% grass straw reached a peak of 50°C, while the corresponding mixture with maize straw did not reach thermophilic temperatures. pH ranged from between 6.2 and 6.8 before composting to between 7.4 and 7.8 after composting. The ammonium concentration peaked at various times but declined to negligible concentrations at day 140. The concentration of nitrates increased with composting up to day 97 and decreased gradually thereafter. There was a general increase in nitrogen concentration from 0.9% to 2.3% as composting progressed. Decreases in organic C% and C/N ratio with composting were also observed, signifying mass loss. Conclusion: The results of this study indicated that household wastes with 50% straw or less can be composted but with measures being taken to achieve temperatures greater than 55°C for at least 3 days to destroy weed seeds and pathogens. The composts with 30% straw mixture had the greatest potential as a soil amendment in peri-urban areas of Harare as they effectively reduced nitrogen losses.

Extrapulmonary Tuberculosis (EPTB) poses challenges from patient and health system perspectives. The cost-effectiveness analysis of the Xpert MTB/RIF (Xpert) test to diagnose pulmonary tuberculosis is documented. However, there are no economic evaluations for EPTB. Considering the reported better diagnostic sensitivity of the MPT64 test, this study explored its cost-effectiveness as an alternative diagnostic test. We conducted this economic evaluation to assess the cost-effectiveness of the MPT64 test compared to Xpert and ZN microscopy for EPTB adult patients. We utilised a Markov modelling approach to capture short- and long-term costs and benefits from a health system perspective. For the model inputs, we combined data from our cohort studies in Tanzania and peer-reviewed EPTB literature. We calculated the Incremental Cost Effectiveness Ratio (ICER) by comparing the cost (in USD) of each diagnostic test and Quality Adjusted Life Years (QALYs) as health gain. We found the MPT64 test cost-effective for EPTB diagnosis and absolutely dominated ZN microscopy and Xpert using the baseline model inputs. A scenario analysis showed that the Xpert test might be the most cost-effective at its higher test sensitivity, which corresponds to using it to diagnose lymph node aspirates. The prevalence of HIV among EPTB cases, their probability of treatment, costs of ART, and the probability of the MPT64 test in detecting EPTB patients were the main parameters associated with the highest impact on ICER in one-way deterministic analysis. The most cost-effective option for EPTB at the baseline parameters was the MPT64 diagnostic test. Including the MPT64 test in EPTB diagnostic pathways for previously untreated patients can lead to better resource use. The Xpert test was the most cost-effective diagnostic intervention at a higher diagnostic test sensitivity in scenario analyses based on different sites of infection, such as for the lymph node aspirates.

BackgroundTanzania is 1 of 20 countries where the majority of unvaccinated and undervaccinated children reside. Prior research identified substantial rural-urban disparities in the coverage and timeliness of childhood vaccinations in Tanzania, with children in rural settings being more likely to receive delayed or no vaccinations. Further research is necessary to identify effective and scalable interventions that can bridge rural-urban gaps in childhood vaccination while accounting for multifaceted barriers to vaccination. ObjectiveThis protocol describes a type 1 effectiveness-implementation hybrid study to evaluate Chanjo Kwa Wakati (timely vaccination in Kiswahili), a community-based digital health intervention to improve vaccination timeliness. The intervention combines human resources (community health workers), low-cost digital strategies (electronic communication, digital case management, and task automation), a vaccination knowledge intervention, and insights from behavioral economics (reminders and incentives) to promote timely childhood vaccinations. MethodsThe study will be conducted in 2 predominantly rural regions in Tanzania with large numbers of unvaccinated or undervaccinated children: Shinyanga and Mwanza. Forty rural health facilities and their catchment areas (clusters) will be randomized to an early or delayed onset study arm. From each cluster, 3 cohorts of mother-child dyads (1 retrospective cohort and 2 prospective cohorts) will be enrolled in the study. The timeliness and coverage of all vaccinations recommended during the first year of life will be observed for 1200 children (n=600, 50% intervention group children and n=600, 50% nonintervention group children). The primary effectiveness outcome will be the timeliness of the third dose of the pentavalent vaccine (Penta3). Quantitative surveys, vaccination records, study logs, fidelity checklists, and qualitative interviews with mothers and key informants will inform the 5 constructs of the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. The results will be used to develop an implementation blueprint to guide future adaptations and scale-up of Chanjo Kwa Wakati. ResultsThe study was funded in August 2022. Data collection is expected to last from February 2024 to July 2027. ConclusionsThis study will address the lack of rigorous evidence on the effectiveness of community-based digital health interventions for promoting vaccination coverage and timeliness among children from sub-Saharan Africa and identify potential implementation strategies to facilitate the deployment of vaccination promotion interventions in low- and middle-income countries. Trial RegistrationClinicalTrials.gov NCT06024317; https://www.clinicaltrials.gov/study/NCT06024317 International Registered Report Identifier (IRRID)PRR1-10.2196/52523

Aim: This pilot study’s aim was to determine the feasibility of examining the effects of an environmental variable (i.e., tree canopy coverage) on mental health after sustaining a brain injury. Methods: A secondary data analysis was conducted leveraging existing information on mental health after moderate to severe traumatic brain injury (TBI) from the TBI Model System. Mental health was measured using PHQ-9 (depression) and GAD-7 (anxiety) scores. The data were compared with data on tree canopy coverage in the state of Texas that was obtained from the Multi-Resolution Land Characteristics (MRLC) Consortium using GIS analysis. Tree canopy coverage as an indicator of neighborhood socioeconomic status was also examined using the Neighborhood SES Index. Results: Tree canopy coverage had weak and non-significant correlations with anxiety and depression scores, as well as neighborhood socioeconomic status. Data analysis was limited by small sample size. However, there is a higher percentage (18.8%) of participants who reported moderate to severe depression symptoms in areas with less than 30% tree canopy coverage, compared with 6.6% of participants who endorsed moderate to severe depression symptoms and live in areas with more than 30% tree canopy coverage (there was no difference in anxiety scores). Conclusion: Our work confirms the feasibility of measuring the effects of tree canopy coverage on mental health after brain injury and warrants further investigation into examining tree canopy coverage and depression after TBI. Future work will include nationwide analyses to potentially detect significant relationships, as well as examine differences in geographic location.

Abstract Introduction Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care. Objective We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up. Methods A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed. Results The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma. Conclusion The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.

Abstract Background The standard face-to-face training for the integrated management of childhood illness (IMCI) continues to be plagued by concerns of low coverage of trainees, the prolonged absence of trainees from the health facility to attend training and the high cost of training. Consequently, the distance learning IMCI training model is increasingly being promoted to address some of these challenges in resource-limited settings. This paper examines participants’ accounts of the paper-based IMCI distance learning training programme in three district councils in Mbeya region, Tanzania. Methods A cross-sectional qualitative descriptive design was employed as part of an endline evaluation study of the management of possible serious bacterial infection in Busokelo, Kyela and Mbarali district councils of Mbeya Region in Tanzania. Key informant interviews were conducted with purposefully selected policymakers, partners, programme managers and healthcare workers, including beneficiaries and training facilitators. Results About 60 key informant interviews were conducted, of which 53% of participants were healthcare workers, including nurses, clinicians and pharmacists, and 22% were healthcare administrators, including district medical officers, reproductive and child health coordinators and programme officers. The findings indicate that the distance learning IMCI training model (DIMCI) was designed to address concerns about the standard IMCI model by enhancing efficiency, increasing outputs and reducing training costs. DIMCI included a mix of brief face-to-face orientation sessions, several weeks of self-directed learning, group discussions and brief face-to-face review sessions with facilitators. The DIMCI course covered topics related to management of sick newborns, referral decisions and reporting with nurses and clinicians as the main beneficiaries of the training. The problems with DIMCI included technological challenges related to limited access to proper learning technology (e.g., computers) and unfriendly learning materials. Personal challenges included work-study-family demands, and design and coordination challenges, including low financial incentives, which contributed to participants defaulting, and limited mentorship and follow-up due to limited funding and transport. Conclusion DIMCI was implemented successfully in rural Tanzania. It facilitated the training of many healthcare workers at low cost and resulted in improved knowledge, competence and confidence among healthcare workers in managing sick newborns. However, technological, personal, and design and coordination challenges continue to face learners in rural areas; these will need to be addressed to maximize the success of DIMCI.

Invasive Salmonella infection, which can cause typhoid/paratyphoid fever and invasive non-typhoidal salmonellosis, is a public health burden in Africa. Accurate diagnosis and etiological characterization are required to conduct prevalence and risk estimations for Salmonella infection; however, the utilization of optimal techniques and surveillance data are still insufficient. In this study, we performed a laboratory-based survey in Freetown, which is the biggest city in Sierra Leone with a high burden of typhoid fever, by using blood culture and molecular methods but not the Widal test, to estimate the prevalence and aetiology of invasive Salmonella infection among fever patients. We found a very low prevalence of typhoid fever in patients with fever during the investigation period, and this prevalence was clearly overestimated by the Widal test. Genome sequencing of the S. Typhi isolate from this work revealed that the strain carried multiple antibiotic resistance genes, and an epidemic clone that has existed in West Africa for years was also detected in Sierra Leone. By using metagenomic sequencing, one patient with invasive non-typhoidal salmonellosis was identified as having bacterial co-infections. Our data highlight that Salmonella surveillance based on accurate laboratory diagnosis and genome sequencing needs to be strengthened to provide a better estimation of the real epidemics and enable potential risk assessment by etiological analysis in Africa. Even in a laboratory with only basic equipment, it is possible to conduct next-generation sequencing for pathogen discovery in bloodstream infections and to determine the etiological characteristics of pathogene without complex combinations of laboratory methods.

Abstract Background In nature and in cultivated fields, plants encounter multiple stress factors. Nonetheless, our understanding of how plants actively respond to combinatorial stress remains limited. Among the least studied stress combination is that of flooding and herbivory, despite the growing importance of these stressors in the context of climate change. We investigated plant chemistry and gene expression changes in two heirloom tomato varieties: Cherokee Purple (CP) and Striped German (SG) in response to flooding, herbivory by Spodoptera exigua, and their combination. Results Volatile organic compounds (VOCs) identified in tomato plants subjected to flooding and/or herbivory included several mono- and sesquiterpenes. Flooding was the main factor altering VOCs emission rates, and impacting plant biomass accumulation, while different varieties had quantitative differences in their VOC emissions. At the gene expression levels, there were 335 differentially expressed genes between the two tomato plant varieties, these included genes encoding for phenylalanine ammonia-lyase (PAL), cinnamoyl-CoA-reductase-like, and phytoene synthase (Psy1). Flooding and variety effects together influenced abscisic acid (ABA) signaling genes with the SG variety showing higher levels of ABA production and ABA-dependent signaling upon flooding. Flooding downregulated genes associated with cytokinin catabolism and general defense response and upregulated genes associated with ethylene biosynthesis, anthocyanin biosynthesis, and gibberellin biosynthesis. Combining flooding and herbivory induced the upregulation of genes including chalcone synthase (CHS), PAL, and genes encoding BAHD acyltransferase and UDP-glucose iridoid glucosyltransferase-like genes in one of the tomato varieties (CP) and a disproportionate number of heat-shock proteins in SG. Only the SG variety had measurable changes in gene expression due to herbivory alone, upregulating zeatin, and O-glucosyltransferase and thioredoxin among others. Conclusion Our results suggest that both heirloom tomato plant varieties differ in their production of secondary metabolites including phenylpropanoids and terpenoids and their regulation and activation of ABA signaling upon stress associated with flooding. Herbivory and flooding together had interacting effects that were evident at the level of plant chemistry (VOCs production), gene expression and biomass markers. Results from our study highlight the complex nature of plant responses to combinatorial stresses and point at specific genes and pathways that are affected by flooding and herbivory combined.

Background: Tuberculosis (TB) prevalence is increasing among women of reproductive age (WRA) in sub-Saharan Africa, yet undiagnosed and untreated cases remain rather high with serious health and socio-economic consequences. We aimed to assess the prevalence and predictors of TB in WRA seeking health care for acute respiratory symptoms. Methods: We consecutively enrolled outpatient WRA with acute respiratory symptoms seeking care at four healthcare facilities in Ethiopia between July 2019 and December 2020. Data on sociodemographic characteristics and clinical information were collected using a structured questionnaire administered by trained nurses. Posteroanterior chest X-ray was performed in non-pregnant WRA and interpreted independently by two radiologists. Sputum samples were collected from all patients and tested for pulmonary TB using Xpert MTB/RIF and/or smear microscopy. Predictors of bacteriologically confirmed TB cases were determined using binary logistic regression, with clinically relevant variables included in the final Firth’s multivariate-penalized logistic regression model. Results: We enrolled 577 participants, of whom 95 (16%) were pregnant, 67 (12%) were living with HIV, 512 (89%) had cough of less than 2 weeks, and 56 (12%) had chest-x-ray findings suggestive of TB. The Overall prevalence of TB was 3% (95% CI: 1.8%-4.7%) with no significant difference observed between patient groups categorized by duration of cough or HIV serostatus (P-value = 0.9999). In multivariable analysis, TB-suggestive CXR abnormality (AOR 18.83 [95% CI, 6.20–57.18]) and history of weight loss (AOR 3.91 [95% CI, 1.25–12.29]) were associated with bacteriologically-confirmed TB cases. Conclusions: We found a high TB prevalence among low-risk women of reproductive age with acute respiratory symptoms. Routine CXR may improve early case detection and thereby TB treatment outcomes.

Abstract Background: Cyclophosphamide (CP) is an anticancer agent, but its chronic administration induces ovarian toxicity. Objective: We evaluated the effects of aqueous extract (AE) and methanol extract (ME) of Amaranthus hybridus (A. hybridus) on CP-induced ovarian toxicity in rats. Materials and Methods: 40 female Wistar rats (10 wk, 170-200 gr) were distributed into 8 groups (n = 5/each) as follows: 1) healthy control; 2) CP+distilled water (10 ml/kg/d); 3) CP+3%-tween 80 (10 mL/kg/d); 4) CP+clomiphene citrate (2 mg/kg/d); 5, 6) CP+AE of A. hybridus (55 and 110 mg/kg/d); and 7, 8) CP+ME of A. hybridus (55 and 110 mg/kg/d). After 28 days of treatment, estrus cyclicity, ovarian and uterine weights as well as estradiol levels and ovarian histology were determined. Results: CP induced ovarian toxicity after 28 days of exposure. More specifically, CP disturbed the estrus cycle, decreased ovary and uterus weights (p = 0.04), and the 17-β estradiol level (p = 0.04), and induced severe ovarian damages. Remarkably, A. hybridus significantly increased (p = 0.03) the ovarian weight (AE and ME at all doses) and uterus weight (ME at 110 mg/kg/d), compared with the CP-treated rats. Moreover, the 17-β estradiol level was significantly elevated (p = 0.02) in rats given clomiphene citrate and A. hybridus (AE 110 mg/kg/d; ME 55 mg/kg/d). Finally, the ovaries of rats given plant extracts had many corpus luteum and normal follicles, and no cystic follicles. Conclusion: A. hybridus prevented the detrimental effects of CP on ovarian function, which could support its traditional use as a fertility enhancer.

Background: Globally, approximately 19.7 million children remain under-vaccinated; many more receive delayed vaccinations. Sustained progress towards global vaccination targets requires overcoming, or compensating for, incrementally greater barriers to vaccinating hard-to-reach and hard-to-vaccinate children. We prospectively assessed pregnant women’s valuations of routine childhood vaccinations and preferences for alternative incentives to inform interventions aiming to increase vaccination coverage and timeliness in southern Tanzania. Methods: Between August and December 2017, 406 women in their last trimester of pregnancy were enrolled from health facilities and communities in the Mtwara region of Tanzania and asked contingent valuation questions about their willingness to vaccinate their child if they were (a) given an incentive, or (b) facing a cost for each vaccination. Interval censored regressions assessed correlates of women’s willingness to pay (WTP) for timely vaccinations. Participants were asked to rank monetary and non-monetary incentive options for the timely vaccination of their children. Findings: All women expected to get their children vaccinated according to the recommended schedule, even without incentives. Nearly all women (393; 96.8 %) were willing to pay for vaccinations. The average WTP was Tanzania Shilling (Tsh) 3,066 (95 % confidence interval Tsh 2,523–3,610; 1 USD ∼ Tsh 2,200) for each vaccination. Women’s valuations of timely vaccinations varied significantly with vaccine-related knowledge and attitudes, economic status, and rural vs urban residence. Women tended to prefer non-monetary over monetary incentives for the timely vaccination of their children. Interpretation: Women placed a high value on timely childhood vaccinations, suggesting that unexpected system-level barriers rather than individual-level demand factors are likely to be the primary drivers of missed vaccinations. Systematic variation in the value of vaccinations across women reflects variation in perceived benefits and opportunity costs. In this setting, nonmonetary incentives and other interventions to increase demand and compensate for system-level barriers hold significant potential for improving vaccination coverage and timeliness. ClinicalTrials.gov Protocol: NCT03252288.

Research background: Beans form a substantial part of the household diet in East and Central Africa and are consumed by most households. They are alternative low-cost proteins for less endowed people in a society and can contribute towards nutrition, food security, and employment. In Homa Bay County, beans are staple food grown by a vast majority of farmers. Choice of market outlet is the most significant decision for farm households to sell their produce to the different market outlets, which has a more substantial impact on household income. Purpose of the article: Factors influencing the choice of market outlets among smallholder bean farmers in Homa Bay County, Kenya Methods: Data collected were analyzed using a Multivariate Probit. Multi-stage sampling was used to collect data from 362 farmers, which constituted 181 participants and 181 non-participants of Public-private partnerships (PPPs); data was collected using a pretested semi-structured questionnaire. Findings & value added & novelty: The market outlet choices available in the study area for sales of beans included consumers, brokers, retailers, and wholesalers; however, retailers and wholesalers constituted more than half of the market outlets. Experience in bean farming, farm size, access to training, credit, and partnership participation positively and significantly influenced selling to these market outlets. Farmers who participated in PPP participated more in bean farming than non-participants; this might be attributed to the benefit acquired from partnerships, such as training farm inputs, among others. Thus, PPP could be an effective way of improving smallholder livelihood; policies that include mechanisms that create or secure markets for smallholder farmers will see to it that they get increased returns.

Colibri® a commercial formulation of Imidacloprid severely impairs the reproductive function. This study aimed at evaluating the preventive effects of Amaranthus hybridus on the reproductive toxicity of colibri® in female rats. Eighty rats (n = 10/group) were orally treated with colibri® (22.5 mg/kg) and co-administered with either aqueous or methanolic extracts of A. hybridus (55 or 110 mg/kg) within four weeks. Control animals received either distilled water (10 ml/kg), clomiphene citrate or vitamin E. Starting from day 18 of treatment till the end, half of animals in each group (n = 5) was used for the fertility test whereas the remaining rats were kept under treatment until sacrifice. Blood, ovaries, uterus and vagina were collected after sacrifice for measurement of sexual hormones, oxidative stress markers and histological assessment. Exposure of female rats to colibri® was followed by a significant reduction (p

Abstract Background Stigma and masculinity represent persistent barriers in delivering successful HIV interventions to men. Our study examined community perceptions of HIV and anti-retroviral therapy (ART) and their implications for men on ART across the life course in Blantyre, Malawi. Methods Our qualitative study is based on 72 face-to-face semi-structured interviews. Participants were selected purposively and included men on ART (with suppressed and unsuppressed viral loads), adult male community members irrespective of HIV status and other HIV stakeholders such as health personnel and program implementers. Interviews were conducted in Chichewa and English, transcribed verbatim and analyzed thematically in NVivo 12. We applied the socio-ecological model as our theoretical framework as well as a “life-course” perspective. Results Our findings highlight lingering negative perceptions towards ART in general and towards PLHIV irrespective of viral load suppression. With intersecting notions of masculinity and stigma, men’s descriptions of anticipated stigma in their relationships and when visiting health facilities dominated. Stigma was experienced at the personal, interpersonal, facility and community level. Yet, men living with HIV were perceived differently throughout the life-course, with young sexually active men seen as the most stigmatized group and older men seen as drawing resilience from a greater range of masculine norms. Some men of all ages displayed “transformative” masculinities independent of stigma and community expectations. Conclusions We propose the “life-course” as a useful concept for studies on masculinity, HIV and stigma. Considering gendered constructions of “respectable” midlife-older age vis-à-vis younger age, and how they influence stigma as well as uptake and adherence to ART might lead to more targeted services for men that build on “transformative masculinities”.

Abstract This study examined the perceived effects of examination special centres on teaching and learning of English language and the quality of education in Nsukka Local Government Area, Enugu State, Nigeria. The study employed a descriptive survey design. All the 123 English language teachers (PPMB Statistics, 2020) from 31 secondary schools, five secondary school principals, three religious priests and three traditional leaders in Nsukka Local Government Area of Enugu State, Nigeria were sampled for the study. The researchers developed a 15-item-structured questionnaire for data collection from the 31 teachers; while 3 structured interview questions were used to elicit responses from the principals, religious priests and traditional leaders. Mean and standard deviation were used to analyse the data collected with questionnaire; while the oral interview was analysed qualitatively through thematic analysis. The study revealed that examination special centres have detrimental effect on the teaching and learning of English language in secondary schools and the quality of education in Nsukka Local Government Area, Enugu State, Nigeria. It was recommended among others that private and public secondary schools, and tutorial centres that have been turned into examination special centres should be closed down by Enugu State Ministry of Education.

Abstract Background The potential shift of major causes of febrile illnesses from malaria to non-malarial febrile illnesses, including arboviral diseases such as chikungunya and dengue, is of concern. The last outbreaks of these infections were reported in 2018 and 2019 for chikungunya in Zanzibar and dengue in Dar es Salaam. We conducted a cross-sectional study that involved serological testing of stored blood samples from the blood banks in Temeke Referral Hospital in Dar es Salaam and the National Blood Bank Unit in Zanzibar. The samples were collected from Zanzibar and Dar es Salaam donors in May and June 2020, respectively. A total of 281 samples were included in the study, and their demographic information extracted from the registers. The samples were then transported to Muhimbili University of Health and Allied Sciences at the Microbiology Laboratory. They were subjected to an indirect ELISA to detect IgG and IgM against dengue and chikungunya viruses. Results Seropositive IgM samples from Dar es Salaam were 3/101 (2.97%) for chikungunya and 1/101 (0.9%) for dengue, while samples from Zanzibar were all IgM negative for both viruses. Chikungunya IgG seropositivity was significantly higher (p ≤ 0.05) in Dar es Salaam 21/101 (21.2%) than Zanzibar 22/180 (12.2%). There was no difference in dengue IgG seropositivity between Dar es Salaam 44/101 (43.5%) and Zanzibar 68/180 (37.8%). Similarly, dual IgG seropositivity for both dengue and chikungunya viruses were not different between Dar es Salaam 13/101 (12.9%) and Zanzibar 11/180 (6.1%). Conclusion Detection of IgM for dengue and chikungunya in Dar es Salaam indicates recent or ongoing transmission of the two viruses in the absence of a reported outbreak. These findings suggest the possibility of transmission of the two infections through blood transfusion. Detection of IgG antibodies for dengue and chikungunya viruses might be contributed by both; the ongoing infections and residual responses caused by preceding infections in the country. Results from blood banks may represent the tip of the iceberg. Further studies are needed to gain insight into the actual burden of the two diseases in Tanzania.

Abstract Pediatric extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. A new immunochemistry based MPT64 antigen detection test has shown improved sensitivity compared to current laboratory tests. The aim of this study was to implement and validate the test performance in a resource limited African setting. Presumptive pediatric (0–18 y) EPTB patients were prospectively enrolled at Mbeya Zonal Referral Hospital, and followed to the end of treatment or until a final diagnosis was reached. Specimens from suspected sites of infection were subject to routine diagnostics, GeneXpert MTB/RIF assay and the MPT64 test. The performance of the tests was assessed using mycobacterial culture as well as a composite reference standard. 30 patients were categorized as TB cases, 31 as non-TB cases and 2 were uncategorized. In the TB group, the three most common infections were adenitis (30%), peritonitis (30%) and meningitis (20%). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 92%, 88%, 87%, 92% and 90%, respectively. Mortality was equally high among TB/non-TB cases (23% vs 21%), and malnutrition was the main comorbidity among TB cases. The MPT64 test was implementable in the routine diagnostics in a low-resource setting and improved the diagnosis of pediatric EPTB.

Agricultural crop productivity relies on the application of chemical pesticides to reduce pest and pathogen damage. However, chemical pesticides also pose a range of ecological, environmental and economic penalties. This includes the development of pesticide resistance by insect pests and pathogens, rendering pesticides less effective. Alternative sustainable crop protection tools should therefore be considered. Semiochemicals are signalling molecules produced by organisms, including plants, microbes, and animals, which cause behavioural or developmental changes in receiving organisms. Manipulating semiochemicals could provide a more sustainable approach to the management of insect pests and pathogens across crops. Here, we review the role of semiochemicals in the interaction between plants, insects and microbes, including examples of how they have been applied to agricultural systems. We highlight future research priorities to be considered for semiochemicals to be credible alternatives to the application of chemical pesticides.

Background Sustainable Development Goal (SDG) 3.1 target is to reduce the global maternal mortality ratio (MMR) to less than 70 maternal deaths per 100 000 live births by 2030. In the Ending Preventable Maternal Mortality strategy, a supplementary target was added, that no country has an MMR above 140 by 2030. We conducted two cross-sectional reproductive age mortality surveys to analyse changes in Zimbabwe’s MMR between 2007–2008 and 2018–2019 towards the SDG target.Methods We collected data from civil registration, vital statistics and medical records on deaths of women of reproductive ages (WRAs), including maternal deaths from 11 districts, randomly selected from each province (n=10) using cluster sampling. We calculated weighted mortality rates and MMRs using negative binomial models, with 95% CIs, performed a one-way analysis of variance of the MMRs and calculated the annual average reduction rate (ARR) for the MMR.Results In 2007–2008 we identified 6188 deaths of WRAs, 325 pregnancy-related deaths and 296 maternal deaths, and in 2018–2019, 1856, 137 and 130, respectively. The reproductive age mortality rate, weighted by district, declined from 11 to 3 deaths per 1000 women. The MMR (95% CI) declined from 657 (485 to 829) to 217 (164 to 269) deaths per 100 000 live births at an annual ARR of 10.1%.Conclusions Zimbabwe’s MMR declined by an annual ARR of 10.1%, against a target of 10.2%, alongside declining reproductive age mortality. Zimbabwe should continue scaling up interventions against direct maternal mortality causes to achieve the SDG 3.1 target by 2030.

Background: Dyslipidaemia is a key comorbid condition of type 2 diabetes mellitus that increases the risk of cardiovascular disease. This study describes the pattern of dyslipidaemia and factors associated with elevated levels of non-high density lipoprotein cholesterol (HDL-C) among patients with type 2 diabetes mellitus in Ho. Methods: This hospital-based cross-sectional study enrolled 210 patients with type 2 diabetes mellitus from Ho municipality. A semi-structured questionnaire was used to obtain demographic and other relevant parameters. Anthropometric, haemodynamic, and biochemical variables were obtained using standard methods. Dyslipidaemia was defined according to the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria while elevated levels of non-HDL-C was defined as non-HDL-C level ≥3.37 mmol/L. A Chi-square test and multivariate logistic regression analyses were performed to determine factors associated with elevated non-HDL-C levels. Results: Overall, dyslipidaemia and elevated levels of non-HDL-C prevalence was 67.1% and 64.3%, respectively. The frequency of atherogenic, isolated, and mixed dyslipidaemias were 10.5%, 58.09% and 53.33 %, respectively. Females were four times more likely to develop elevated levels of non-HDL-C after adjustment for age (AOR: 4.07; CI: 2.20–7.51; p < 0.0001). Likewise, overweight (AOR: 3.1; CI: 1.45–6.61; p = 0.0035), grade 1 obesity (AOR: 2.8; CI: 1.20–6.49; p = 0.0168), and truncal obesity (AOR: 3.09; CI: 1.54–6.19; p < 0.0001) were three times each more likely to develop elevated levels of non HDL-C after adjustment for age and gender. However, alcohol intake was 66% unlikely to develop elevated levels of non-HDL-C (COR: 0.34; CI: 0.16–0.73; p = 0.006). Conclusion: Dyslipidaemia and elevated levels of non-HDL-C were common in our study participants. Hypercholesterolaemia and co-occurrence of high TG and high LDL-C levels were the most prevalent isolated and mixed dyslipidaemias, respectively. The female gender, overweight, grade 1 obesity and truncal obesity, as well as alcohol intake were significant predictors of elevated levels of non-HDL-C.

Low sexual desire disorder is a recurrent deficiency in desire for sexual activity which impairs lifestyle. It is a frequent problem in women with limited therapeutic options. Phyllanthus muellerianus (Kuntze) Exell is a plant used by traditional healers to boost libido in women. This study aimed at evaluating the aphrodisiac properties of root barks extracts of this plant on a model of Low Sexual Desire Disorder (LSDD) in female rats. Low sexual desire was induced by ovariectomy plus low steroid hormones supplementations. Thirty ovariectomized rats were treated for 21 days with either distilled water, aqueous or methanol extracts (60 or 372 mg/kg) of P. muellerianus. All animals were supplemented with a low dose of 17β-estradiol and progesterone prior to sexual behavior test. Sexual behavior test was performed each week by pairing each female rat with a sexually experienced male. Sexual motivation (approach, ear wiggling, hops and darts, anogenital presentation and aggressive behavior frequency) and sexual receptivity parameters (lordosis frequency and quotient) were recorded. At the end of treatments, animals were sacrificed, uteri and vagina collected, weighed and conserved for total uterine proteins assay and histology. LSDD was characterized by significant inhibition of sexual motivation parameters and lordosis frequency compared to a normal control. Moreover, poor reproductive tissues growth characterized by low total uterine proteins, uterine wet weight and uterine epithelia size was noted in LSDD group compared to normal control. Interestingly, plant extracts significantly improved sexual motivation parameters (p

Background: One-third of tuberculosis (TB) cases are missed each year and delays in the diagnosis of TB are hampering the whole cascade of care. Early chest X-ray (CXR) in patients with cough irrespective of duration may reduce TB diagnostic and treatment delays and increase the number of TB patients put into TB care. We aimed to evaluate the impact of CXR on delay in the diagnosis of pulmonary tuberculosis (PTB) among people with cough of any duration. Methods: A facility-based cross-sectional study was conducted in four selected health facilities from two regions and two city administrations of Ethiopia. Patients who sought health care were screened for cough of any duration, and those with cough underwent CXR for PTB and their sputum specimens were tested for microbiological confirmation. Delays were followed up and calculated using median and inter-quartile range (IQR) to summarize (first onset of cough to first facility visit, ≥15 days), diagnosis delay (first facility visit to date of PTB diagnosis, >7 days), and total delay (first onset of cough to date of PTB diagnosis, >21 days). Kruskal–Wallis and Mann–Witney tests were used to compare the delays among independent variables. Results: A total of 309 PTB cases were consecutively diagnosed of 1853 presumptive TB cases recruited in the study that were identified from 2647 people who reported cough of any duration. The median (IQR) of patient delay, diagnosis delay, and the total delay was 30 (16–44), 1 (0–3), and 31 (19–48) days, respectively. Patients' delay contributed a great role in the total delay, 201/209 (96.2%). Median diagnosis delay was higher among those that visited health center, diagnosed at a facility that had no Xpert mycobacterium tuberculosis (MTB)/RIF assay, radiologist, or CXR (P < 0.05). Factors associated with patients delay were history of previous TB treatment (adjusted prevalence ratio [aPR] = 0.79, 95% confidence interval [CI]: 0.63–0.99) and history of weight loss (aPR = 1.12; 95% CI: 1.0–1.25). Early CXR screening for cough of

Abstract Background Vaccine hesitancy has been recognized as an important barrier to timely vaccinations around the world, including in sub-Saharan Africa. In Tanzania, 1 in 4 children is not fully vaccinated. The objective of this mixed methods study was to describe and contextualize parental concerns towards vaccines in Tanzania. Methods Between 2016 and 2017, we conducted a cross-sectional survey (n = 134) and four focus group discussions (FGDs, n = 38) with mothers of children under 2 years of age residing in Mtwara region in Southern Tanzania. The survey and FGDs assessed vaccination knowledge and concerns and barriers to timely vaccinations. Vaccination information was obtained from government-issued vaccination cards. Results In the cross-sectional survey, 72% of mothers reported missed or delayed receipt of vaccines for their child. Although vaccine coverage was high, timeliness of vaccinations was lower and varied by vaccine. Rural mothers reported more vaccine-related concerns compared to urban mothers; literacy and access to information were identified as key drivers of the difference. Mothers participating in FGDs indicated high perceived risk of vaccine-preventable illnesses, but expressed concerns related to poor geographic accessibility, unreliability of services, and missed opportunities for vaccinations resulting from provider efforts to minimize vaccine wastage. Conclusions Findings from our cross-sectional survey indicate the presence of vaccination delays and maternal concerns related to childhood vaccines in Tanzania. In FGDs, mothers raised issues related to convenience more often than issues related to vaccine confidence or complacency. Further research is necessary to understand how these issues may contribute to the emergence and persistence of vaccine hesitancy and to identify effective mitigation strategies.