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Abstract Tuberculosis (TB) poses a significant global health threat, with high mortality rates if left untreated. Current sputum-based TB treatment monitoring methods face numerous challenges, particularly in relation to sample collection and analysis. This pilot study explores the potential of TB status assessment using DNA methylation (DNAm) signatures, which are gaining recognition as diagnostic and predictive tools for various diseases. We collected buccal swab samples from pulmonary TB patients at the commencement of TB treatment (n = 10), and at one, two, and six-month follow-up intervals. We also collected samples from healthy controls (n = 10) and individuals exposed to TB (n = 10). DNAm patterns were mapped using the Illumina Infinium Methylation EPIC 850 K platform. A DNAm profile distinct from controls was discovered in the oral mucosa of TB patients at the start of treatment, and this profile changed throughout the course of TB treatment. These findings were corroborated in a separate validation cohort of TB patients (n = 41), monitored at two and six months into their TB treatment. We developed a machine learning model to predict symptom scores using the identified DNAm TB profile. The model was trained and evaluated on the pilot, validation, and two additional independent cohorts, achieving an R2 of 0.80, Pearson correlation of 0.90, and mean absolute error of 0.13. While validation is needed in larger cohorts, the result opens the possibility of employing DNAm-based diagnostic and prognostic tools for TB in future clinical practice.

Abstract Background Gene drive-modified mosquitoes (GDMMs) have been promoted as one of the innovative technologies that may control and eliminate malaria and other mosquito-borne diseases. Several products are in early stages of development, targeting either population suppression or population modification of the mosquito vector. However, there is no direct experience of conducting risk assessment for environmental releases and subsequent policies regarding conditions for post-release. This study was carried out to gain additional insights on the possible post-release concerns that may arise, as they may inform future risk assessment and planning for deployment. Methods This study involved desktop reviews on post release monitoring experiences with previously released biological control products. Stakeholder consultations involving online surveys, and face to face workshop with experts from selected African countries from Eastern, Western, and Southern African regions was then carried out to establish post-release monitoring concerns for GDMMs. Results Review of genetic biocontrol technologies showed only limited lessons from post-release monitoring regimes with a focus largely limited to efficacy. For genetically modified organisms general surveillance and case-specific monitoring is expected in some of the regions. A number of post-release monitoring concerns in relation to the protection goals of human and animal health, biodiversity, and water quality were identified. Conclusion Based on established- protection goals, several post-release monitoring concerns have been identified. Subject to a rigorous risk assessment process for future GDMMs products, the concerns may then be prioritized for post-release monitoring.

Kenya is one of several Sub-Saharan African countries vulnerable to climate change, which severely impacts their small-holder farming (SHF) sectors. To build resilience and reduce SHFs’ vulnerability to the impact of climate change, there has been ongoing advocacy for an increase in adaptation funds disbursed to these African countries. However, the effectiveness of adaptation funds relies heavily on the quality of metrics used for tracking and assessing adaptation needs and actions developed by SHFs. This study, which set out to evaluate the impact of existing locally led adaptation (LLA) metrics relevant to Kenya’s SHFs, systematically searched grey and journal articles published between 2007 and 2023 and found that these sources did not reveal the impact of LLA metrics on resilience of SHFs, nor did they provide a framework for developing adaptation metrics relevant to SHFs. Kenya’s SHF sector is strategically vital for both rural and national economies and is the lifeblood of vulnerable communities. To mitigate the impact of climate change on this sector, the present study developed the first framework for locally led adaptation metrics for SHFs by drawing on the context knowledge of Kenya’s SHFs and lessons from the resilience and adaptation policy literature. This framework requires five steps: (1) to carry out gender intersectionality analysis to unravel the diverse typologies of SHFs in Kenya in order to identify their adaptation needs; (2) to co-develop metrics with stakeholders, including SHFs, periodically reviewing their relevance; (3) to complement metrics with contextual data; (4) to develop a knowledge brokering platform for cross-community and cross-country learning; and (5) to connect with government and decision makers. While this study has provided guidance on implementing the locally led adaptation metrics for Africa (LAMA) framework in real-world settings, there is a need to explore further how quantitative metrics can be complemented with contextual data.

Abstract African swine fever virus (ASFV) is a highly contagious and fatal hemorrhagic disease of domestic pigs, which poses a major threat to the swine industry worldwide. Studies have shown that indigenous African pigs tolerate ASFV infection better than European pigs. The porcine v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) encoding a p65 kD protein, a major subunit of the NF-kB transcription factor, plays important roles in controlling both innate and adaptive immunity during infection with ASFV. In the present study, RelA genes from ASFV-surviving and symptomatic pigs were sequenced and found to contain polymorphisms revealing two discrete RelA amino acid sequences. One was found in the surviving pigs, and the other in symptomatic pigs. In total, 16 nonsynonymous SNPs (nsSNPs) resulting in codon changes were identified using bioinformatics software (SIFT and Polyphen v2) and web-based tools (MutPre and PredictSNP). Seven nsSNPs (P374-S, T448-S, P462-R, V464-P, Q478-H, L495-E, and P499-Q) were predicted to alter RelA protein function and stability, while 5 of these (P374-S, T448-S, P462-R, L495-E, and Q499-P) were predicted as disease-related SNPs. Additionally, the inflammatory cytokine levels of IFN-α, IL-10, and TNF-α at both the protein and the mRNA transcript levels were measured using ELISA and Real-Time PCR, respectively. The resulting data was used in correlation analysis to assess the association between cytokine levels and the RelA gene expression. Higher levels of IFN-α and detectable levels of IL-10 protein and RelA mRNA were observed in surviving pigs compared to healthy (non-infected). A positive correlation of IFN-α cytokine levels with RelA mRNA expression was also obtained. In conclusion, 7 polymorphic events in the coding region of the RelA gene may contribute to the tolerance of ASFV in pigs.

Low- and middle-income countries are underresourced in subspecialist care. This study describes a unique maternal-fetal medicine clinical fellowship training program at Moi University School of Medicine and Moi Teaching and Referral Hospital in Eldoret, Western Kenya. The first of its kind in Eastern Africa, it has met with success in the retention of highly qualified practitioners providing complex pregnancy care to a population that has been heretofore underserved.

Building on an exercise that identified potential harms from simulated investigational releases of a population suppression gene drive for malaria vector control, a series of online workshops identified nine recommendations to advance future environmental risk assessment of gene drive applications.

Abstract Background Food insecurity is a major predicament for rural populations, especially mothers and children, whose livelihoods are often dependent on rain-fed agriculture. Indigenous foods have the potential of mitigating food insecurity as they can thrive in poor agro-ecological conditions. However, the associations between indigenous food production and food security status of mothers and children drawn from rural contexts has not been expansively assessed. Food insecurity evident by high food poverty rates remain high in Kisumu County due to over-reliance on food imports from other counties. The objective of the study was to assess seasonality in associations between production of selected indigenous foods (kidney beans, soya beans, millet, cassava, sweet potatoes, groundnuts, green grams, cow peas, amaranth leaves, spider plant leaves, black night shade leaves, mangoes, guavas, lime, and tamarind) and food security status of mothers and children during planting and harvesting seasons. Methods We used a longitudinal study design adopting both quantitative and qualitative data collection methods. A structured questionnaire assessed production of selected indigenous foods in the sampled households, Household Food Insecurity Access Scale for mother’s food security status and Prevalence of Underweight for children’s food security status. Ordinal logistic regression was used to derive odds ratio (OR), which assessed strength of associations between dependent variables (mother’s and children’s food security status) and independent variables (production of selected indigenous foods). Significance was determined at α ≤ 0.05. Results Results demonstrated that during planting season, production of kidney beans decreased the odds of mothers being severely food insecure by 53% (OR = 0.469, 95% CI = 0.228–0.964, p = 0.039). In the same season, sorghum production demonstrated 3.5 times increase in odds of children being severely food insecure (OR = 3.498, 95% CI = 1.454–8.418, p = 0.005). During harvesting season, production of kidney beans was associated with a 62% reduction in the odds of children being severely food insecure (OR = 0.379, 95% CI = 0.190–0.754, p = 0.006). Conclusions Production of some of the selected indigenous foods demonstrated significant odds of predicting mother’s and children’s food security status across both study seasons. An intervention-based study approach that would best establish causal associations of indigenous food production and food security status is recommended.

Background: Cervical cancer is one of the leading causes of cancer mortality among women in Kenya due to late presentations, poor access to health care, and limited resources. Across many low- and middle-income countries infrastructure and human resources for cervical cancer management are currently insufficient to meet the high population needs therefore patients are not able to get appropriate treatment. Objective: This study aimed to describe the clinicopathological characteristics and the treatment profiles of cervical cancer cases seen at Moi Teaching and Referral Hospital (MTRH) Methods: This was a retrospective cross-sectional study conducted at MTRH involving the review of the electronic database and medical charts of 1541 patients with a histologically confirmed diagnosis of cervical cancer between January 2012 and December 2021. Results: Of the 1541 cases analyzed, 91% were squamous cell carcinomas, 8% were adenocarcinomas, and 1% were other histological types. Thirty-eight percent of the patients were HIV infected and less than 30% of the women had health insurance. A majority (75%) of the patients presented with advanced-stage disease (stage IIB-IV). Only 13.9% received chemoradiotherapy with curative intent; of which 33.8% received suboptimal treatment. Of the 13% who received surgical treatment, 45.3% required adjuvant therapy, of which only 27.5% received treatment. Over 40% of the women were lost to follow-up. Conclusion: Most of the patients with cervical cancer in Kenya present at advanced stages with only a third receiving the necessary treatment while the majority receive only palliative treatment or supportive care.

Abstract Background Cervical cancer is caused by oncogenic human papillomaviruses (HR-HPV) and is common among Kenyan women. Identification of factors that increase HR-HPV persistence is critically important. Kenyan women exposed to aflatoxin have an increased risk of HR-HPV detection in cervical specimens. This analysis was performed to examine associations between aflatoxin and HR-HPV persistence. Methods Kenyan women were enrolled in a prospective study. The analytical cohort for this analysis included 67 HIV-uninfected women (mean age 34 years) who completed at least two of three annual study visits and had an available blood sample. Plasma aflatoxin was detected using ultra-high pressure liquid chromatography (UHPLC)-isotope dilution mass spectrometry. Annual cervical swabs were tested for HPV (Roche Linear Array). Ordinal logistic regression models were fitted to examine associations of aflatoxin and HPV persistence. Results Aflatoxin was detected in 59.7% of women and was associated with higher risk of persistent detection of any HPV type (OR = 3.03, 95%CI = 1.08–8.55, P = 0.036), HR-HPV types (OR = 3.63, 95%CI = 1.30-10.13, P = 0.014), and HR-HPV types not included in the 9-valent HPV vaccine (OR = 4.46, 95%CI = 1.13–17.58, P = 0.032). Conclusions Aflatoxin detection was associated with increased risk of HR-HPV persistence in Kenyan women. Further studies, including mechanistic studies are needed to determine if aflatoxin synergistically interacts with HR-HPV to increase cervical cancer risk.

The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer, and to encourage collaborations between researchers in North America and East African countries. To date, studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on the persistence of HPV, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP. It will now be determined how HPV testing fits into cervical cancer screening programs in Kenya and Uganda, how aflatoxin influences immunological control of HIV, how HPV alters certain genes involved in the growth of tumours in HIV-infected women. Although there have been challenges in performing this research, with time, this work should help to reduce the burden of cervical cancer and other cancers related to HIV infection in people living in sub-Saharan Africa, as well as optimized processes to better facilitate research as well as patient autonomy and safety. KEY MESSAGESThe East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer.Collaborations have been established between researchers in North America and East African countries for these studies.Studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on HPV detection, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP.

The liver is the site of first pass metabolism, detoxifying and metabolizing blood arriving from the hepatic portal vein and hepatic artery. It is made up of multiple cell types, including macrophages. These are either bona fide tissue-resident Kupffer cells (KC) of embryonic origin, or differentiated from circulating monocytes. KCs are the primary immune cells populating the liver under steady state. Liver macrophages interact with hepatocytes, hepatic stellate cells, and liver sinusoidal endothelial cells to maintain homeostasis, however they are also key contributors to disease progression. Generally tolerogenic, they physiologically phagocytose foreign particles and debris from portal circulation and participate in red blood cell clearance. However as immune cells, they retain the capacity to raise an alarm to recruit other immune cells. Their aberrant function leads to the development of non-alcoholic fatty liver disease (NAFLD). NAFLD refers to a spectrum of conditions ranging from benign steatosis of the liver to steatohepatitis and cirrhosis. In NAFLD, the multiple hit hypothesis proposes that simultaneous influences from the gut and adipose tissue (AT) generate hepatic fat deposition and that inflammation plays a key role in disease progression. KCs initiate the inflammatory response as resident immune effectors, they signal to neighbouring cells and recruit monocytes that differentiated into recruited macrophages in situ. Recruited macrophages are central to amplifying the inflammatory response and causing progression of NAFLD to its fibro-inflammatory stages. Given their phagocytic capacity and their being instrumental in maintaining tissue homeostasis, KCs and recruited macrophages are fast-becoming target cell types for therapeutic intervention. We review the literature in the field on the roles of these cells in the development and progression of NAFLD, the characteristics of patients with NAFLD, animal models used in research, as well as the emerging questions. These include the gut-liver-brain axis, which when disrupted can contribute to decline in function, and a discussion on therapeutic strategies that act on the macrophage-inflammatory axis.

Abstract Building on an exercise that identified potential harms from simulated investigational releases of a population suppression gene drive for malaria vector control, a series of online workshops identified nine recommendations to advance future environmental risk assessment of gene drive applications.

Information and communication technologies (ICTs) have been touted as being potentially powerful tools that can be used to facilitate the implied educational change and reform. Implementation of ICT in higher education learning environments is a complex task. Teachers and students, but also management, administration and ICT support are affected by and affect the implementation. To facilitate the change processes better the first step is to actually understand what problems and challenges implementation of ICT leads to and how it affects practice. Although classical instructional methods will continue to be used in the teaching-learning process, it is also true that Information Communication Technologies (ICTs) can be harnessed to become powerful pedagogical tools. Proceeding from the premise that there are many ways to use new technologies for teaching and learning, the paper presents literature on the possibilities and challenges of integrating ICT into teaching-learning, the rationale for adopting and using ICTs for learning-teaching, as well as the key factors that influence the adoption and use of ICTs in teaching and learning both from a general perspective and in a technical education context. The paper then outlines and discusses findings of a study designed to investigate the possibilities and challenges of using Information Communication Technology (ICT) in teaching-learning procedures in primary school institutions in Kenya using data obtained from a Tinderet District school in the Rift valley region of Kenya. It examines views in pertinent literature as well as teachers' perceptions of the benefits of integrating ICT into teaching-learning, the success factors and obstacles encountered in their endeavours to do this. Conclusions are drawn and suggestions made to address the challenges and improve on the use of ICT for teaching-learning in teaching institutions.

BackgroundHIV-associated Kaposi sarcoma (KS), among the most frequent cancers seen in sub-Saharan Africa, is associated with a high prevalence of lymphedema. Lymphedema causes progressive functional impairment marked by swelling, physical discomfort, disfiguring changes, skin hardening from fibrosis, poor wound healing, and recurrent skin infection. While compression therapy is considered a major component of lymphedema management, this intervention has never been evaluated in HIV-associated KS lymphedema.Methods/designThe Kenyan Improvised Compression for Kaposi Sarcoma (KICKS) study is a randomized, controlled trial. Due to variable lymphedema stage, we will use block randomization with a 1:1 allocation to assign participants to one of two groups: "Immediate compression" or "Delayed compression." Those randomized to "Immediate compression" intervention arm will receive weekly two-component compression bandages while receiving chemotherapy, whereas those in the "Delayed compression" control arm will be followed during chemotherapy and then receive compression after chemotherapy is completed. The primary outcome is change in Lower Extremity Lymphedema Index from enrollment at Week 0 to blinded outcome assessment at Week 14 between intervention and control arms. Secondary outcomes are change in leg lymphedema-specific quality of life (LYMQOL) and change in overall health quality of life in cancer (EORTC QLQ C30).DiscussionThis represents the first study in sub-Saharan Africa to assess a lymphedema-directed intervention for KS, and the intervention-locally sourced two-component compression bandages-is affordable and available. Thus, the KICKS study is an important step towards developing an evidence-based path for regionally relevant management of HIV-associated KS lymphedema.Trial registrationThis trial was registered at ClinicalTrials.gov on January 19, 2018: identifier NCT03404297.

IntroductionCompression therapy is well-established standard of care for chronic leg ulcers from venous disease and lymphedema. Chronic leg ulcers and lymphedema have a significant impact on quality of life, driven by pain, foul odor, and restricted mobility. Provision of layered compression therapy in resource-limited settings, as in Western Kenya and other regions of sub-Saharan Africa, is a major challenge due to several barriers: availability, affordability, and access to healthcare facilities. When wound care providers from an Academic Model Providing Access to Healthcare (AMPATH) health center in Western Kenya noted that a donated, finite supply of two-component compression bandages was helping to heal chronic leg ulcers, they began to explore the potential of finding a local, sustainable solution. Dermatology and pharmacy teams from AMPATH collaborated with health center providers to address this need.MethodsFollowing a literature review and examination of ingredients in prepackaged brand-name kits, essential components were identified: elastic crepe, gauze, and zinc oxide paste. All of these materials are locally available and routinely used for wound care. Two-component compression bandages were made by applying zinc oxide to dry gauze for the inner layer and using elastic crepe as the outer layer. Feedback from wound clinic providers was utilized to optimize the compression bandages for ease of use.ResultsAdjustments to assembly of the paste bandage included use of zinc oxide paste instead of zinc oxide ointment for easier gauze impregnation and cutting the inner layer gauze in half lengthwise to facilitate easier bandaging of the leg, such that there were two rolls of zinc-impregnated gauze each measuring 5 inches × 2 m. Adjustments to use of the compression bandage have included increasing the frequency of bandage changes from 7 to 3 days during the rainy seasons, when it is difficult to keep the bandage dry. Continuous local acquisition of all components led to lower price quotes for bulk materials, driving down the production cost and enabling a cost to the patient of 200 KSh (2 USD) per two-component compression bandage kit. Wound care providers have provided anecdotal reports of healed chronic leg ulcers (from venous stasis, trauma), improved lymphedema, and patient tolerance of compression.ConclusionsLow-cost locally sourced two-component compression bandages have been developed for use in Western Kenya. Their use has been initiated at an AMPATH health center and is poised to meet the need for affordable compression therapy options in Western Kenya. Studies evaluating their efficacy in chronic leg ulcers and Kaposi sarcoma lymphedema are ongoing. Future work should address adaptation of compression bandages for optimal use in Western Kenya and evaluate reproducibility of these bandages in similar settings, as well as consider home- or community-based care delivery models to mitigate transportation costs associated with accessing healthcare facilities.

Antigen-specific CD4 and CD8 T cells are important components of the immune response to Mycobacterium tuberculosis, yet little information is currently known regarding how the breadth, specificity, phenotype, and function of M. tuberculosis-specific T cells correlate with M. tuberculosis infection outcome in humans. To facilitate evaluation of human M. tuberculosis-specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60 M. tuberculosis Ags. Using IFN-γ production as a readout of Ag specificity, the assay can be conducted using 50 μl of blood per test condition and can be expanded to accommodate additional Ags. We evaluated the intra- and interassay variability, and implemented testing of the assay in diverse cohorts of M. tuberculosis-unexposed healthy adults, foreign-born adults with latent M. tuberculosis infection residing in the United States, and tuberculosis household contacts with latent M. tuberculosis infection in a tuberculosis-endemic setting in Kenya. The M. tuberculosis-specific T cell response spectrum assay further enhances the immunological toolkit available for evaluating M. tuberculosis-specific T cell responses across different states of M. tuberculosis infection, and can be readily implemented in resource-limited settings. Moreover, application of the assay to longitudinal cohorts will facilitate evaluation of treatment- or vaccine-induced changes in the breadth and specificity of Ag-specific T cell responses, as well as identification of M. tuberculosis-specific T cell responses associated with M. tuberculosis infection outcomes.

This study aimed to evaluate whether a psychoeducational intervention provided to older Chinese immigrant foster grandparents (FGs) would improve their knowledge, skills, confidence, coping skills, and mental health outcomes when working with children who have special needs. Pre and posttests with standardized measures were conducted among older Chinese immigrant FGs (N ​= ​18). Non-parametric Wilcoxon signed rank tests were conducted to examine whether the main outcome measures were significantly different after the intervention. Results showed that FGs experienced improvement in grandparenting empowerment, caregiving mastery skills, perceived social support, negative social interaction, as well as life satisfaction after the intervention. However, the results did not show improvement in measurements of stress, knowledge of formal services, and coping skills after the psychoeducational intervention. Overall, the result suggests that this psychoeducational intervention is a promising one for older Chinese immigrant FGs with implications for other minority populations. Recommendations and strategies for enhancing interprofessional collaboration to address the needs of FGs are also provided.

Abstract Meat from wildlife species (bushmeat) represents a major source of dietary protein in low- and middle-income countries where humans and wildlife live in close proximity. Despite the occurrence of zoonotic pathogens in wildlife, their prevalence in bushmeat remains unknown. To assess the risk of exposure to major pathogens in bushmeat, a total of 3784 samples, both fresh and processed, were collected from three major regions in Tanzania during both rainy and dry seasons, and were screened by real-time PCR for the presence of DNA signatures of Bacillus anthracis (B. anthracis), Brucella spp. (Brucella) and Coxiella burnetii (Coxiella). The analysis identified DNA signatures of B. anthracis (0.48%), Brucella (0.9%), and Coxiella (0.66%) in a total of 77 samples. Highest prevalence rates of B. anthracis, Brucella, and Coxiella were observed in wildebeest (56%), dik-dik (50%), and impala (24%), respectively. Fresh samples, those collected during the rainy season, and samples from Selous or Serengeti had a greater relative risk of being positive. Microbiome characterization identified Firmicutes and Proteobacteria as the most abundant phyla. The results highlight and define potential risks of exposure to endemic wildlife diseases from bushmeat and the need for future investigations to address the public health and emerging infectious disease risks associated with bushmeat harvesting, trade, and consumption.

This paper examined the effect of bullying victimization on suicidal ideation and suicide attempt among adolescents in Ghana. Data on 1,633 students ages 14-18 years (50.6% males) were analyzed using logistic regression. We found that 17% of the 1,633 adolescents examined reported experiencing suicidal thoughts and about 21% of the 1,633 adolescents attempted suicide at some point during the past year. Prevalence of bullying was reported among 40% of the adolescents. Importantly, we found that the experience of bullying victimization was a significant predictor of both suicidal ideation and suicide attempt. While factors such as loneliness, anxiety, and use of illicit substances were positively associated with suicidal behaviors, participating in physical activity, having friends, and parental support reduced the likelihood of experiencing suicidal ideation. We make several policy recommendations, including educational programs on suicidal behaviors, antibullying interventions, and social support programs within schools and other social settings.

Infection with Mycobacterium tuberculosis (Mtb) in people with HIV (PWH) is associated with depletion of Mtb-specific CD4 T cell responses, increased risk of progression to active tuberculosis (TB) disease, and increased immune activation. Although higher HIV viral loads have been reported in Mtb/HIV co-infection, the extent to which Mtb infection and TB disease impact the frequency and phenotype of HIV-specific T cell responses has not been well described. We enrolled a cohort of PWH in Kenya across a spectrum of Mtb infection states, including those with no evidence of Mtb infection, latent Mtb infection (LTBI), and active pulmonary TB disease, and evaluated the frequency, immune activation, and cytotoxicity phenotype of HIV-specific CD4 and CD8 T cell responses in peripheral blood by flow cytometry. We found evidence of depletion of HIV-specific CD4 and CD8 T cells in people with TB, but not with LTBI. Expression of the immune activation markers human leukocyte antigen-DR isotype (HLA-DR) and Ki67 and of the cytotoxic molecules granzyme B and perforin were increased in total CD4 and CD8 T cell populations in individuals with TB, although expression of these markers by HIV-specific CD4 and CD8 T cells did not differ by Mtb infection status. These data suggest that TB is associated with overall increased T cell activation and cytotoxicity and with depletion of HIV-specific CD4 and CD8 T cells, which may contribute to further impairment of T cell–mediated immune control of HIV replication in the setting of TB. [ABSTRACT FROM AUTHOR]

Objectives: Centralized programs have been ineffective in reducing the burden of cervical cancer among Kenyan women. A community-based pilot study was initiated to screen Kenyan women for cervical cancer and to vaccinate their children against human papillomavirus (HPV). Methods: Women were educated about cervical cancer prevention at community meetings. Women then provided self-collected vaginal swabs for oncogenic HPV testing using the Roche Cobas Assay. All women were then referred to the local clinic for Visual Inspection with Acetic Acid (VIA). Women were offered the quadrivalent HPV vaccine for their children if and when it became available for the study. Results: Women in western Kenya were invited to participate in community meetings. A total of 200 women were enrolled: 151 (75.5%) were HIV-uninfected and 49 (24.5%) were HIV-infected; the median age for all women was 42 years. High-risk (HR)-HPV types were detected in 49 of swabs from all 200 participants (24.5%) including 20.5% of HIV-uninfected women and 36.7% of HIV-infected women (P = .022). VIA was performed on 198 women: 192 had normal examinations and six had abnormal examinations. Five cervical biopsies revealed two cases of CIN 2 and one CIN 3. Although all mothers were willing to have their children (N = 432) vaccinated, the HPV vaccine could not be delivered to Kenya during the study period. Conclusions: Kenyan women were willing to attend community meetings to learn about prevention of cervical cancer, to provide self-collected vaginal swabs for HPV testing, to travel to the Webuye Clinic for VIA following the collection of swabs, and to have their children vaccinated against HPV. HR-HPV was prevalent, especially in HIV-infected women. As a result of this pilot study, this community-based strategy to prevent cervical cancer will be continued in western Kenya.

Background: The main pediatric (0–18 years) gynecologic cancers include stromal carcinomas (juvenile granulosa cell tumors and Sertoli-Leydig cell tumors), genital rhabdomyosarcomas and ovarian germ cell. Outcomes depend on time of diagnosis, stage, tumor type and treatment which can have long-term effects on the reproductive career of these patients. This study seeks to analyze the trends in clinical-pathologic presentation, treatment and outcomes in the cases seen at our facility. This is the first paper identifying these cancers published from sub-Saharan Africa. Method: Retrospective review of clinico-pathologic profiles and treatment outcomes of pediatric gynecologic oncology patients managed at MTRH between 2010 and 2020. Data was abstracted from gynecologic oncology database and medical charts. Results: Records of 40 patients were analyzed. Most, (92.5%, 37/40) of the patients were between 10 and 18 years. Ovarian germ cell tumors were the leading histological diagnosis in 72.5% (29/40) of the patients; with dysgerminomas being the commonest subtype seen in 12 of the 37 patients (32.4%). The patients received platinum-based chemotherapy in 70% of cases (28/40). There were 14 deaths among the 40 patients (35%) Conclusion: Surgery remains the main stay of treatment and fertility-sparing surgery with or without adjuvant platinum-based chemotherapy are the standard of care with excellent prognosis following early detection and treatment initiation. LMICs face several challenges in access to quality care and that affects survival of these patients. Due to its commonality, ovarian germ cell cancers warrant a high index of suspicion amongst primary care providers attending to adnexal masses in this age group.

Background: Dietary intake of HIV-seropositive persons remains a major concern across various settings around the globe. Inadequate dietary intake, infections and stage of disease progression elicit malnutrition among HIV-seropositive individuals, which hastens progression of HIV to full-blown AIDS. Aim: The study sought to determine the dietary intake of HIV-seropositive clients attending Longisa County Hospital Comprehensive Care Clinic, Bomet County, Kenya. Methods: A cross-sectional analytical study design was administered on a comprehensive sample of 210 patients. A 24-hour dietary recall questionnaire and Food Frequency Questionnaire (FFQ) were used by the researcher to collect data on the dietary intake of the respondents. The 24-hour dietary recall data were analysed using NutriSurvey whereas data obtained from the FFQ were analysed manually. Results: Study respondents comprised more females (61.6%) than males (38.6%). Adequacy in energy intake amongst the respondents was average as males attained 47.4% of recommended energy intake, whereas females attained 50.0%. Intakes for selected nutrients, vitamin A, B1, B2, C, were adequate for males and females. Iron intake was significantly low among female respondents as 89.3% did not meet the RDA. Similarly, zinc intake among male respondents was low as only 28.9% met the RDA. The mean number of meals consumed by the respondents was 3.8 ± 0.1. Consumption frequency of legumes, fruits, other vegetables, meats, eggs and fish was irregular. Conclusion: The dietary intake of the respondents was not satisfactory as evidenced by inadequacies in intake of certain nutrients and low number of meals consumed on a daily basis. Inadequate dietary intake is detrimental to HIV and AIDS management and treatment modalities, hence resulting in poor treatment outcomes. Care and treatment modalities at HIV and AIDS clinics should encompass provision of clear and concise information on the importance of adequate dietary intake as a means of optimising positive treatment outcomes.

The composition of the neutron stars from its surface region, outer-core, inner-core, and to its center is still being investigated. One can only surmise on the properties of neutron stars from the spectroscopic data that may be available from time to time. A few models have suggested that the matter at the surface region of the neutron star is composed of atomic nuclei that get crushed under extremely large pressure and gravitational stress, and this leads to the creation of solid lattice with a sea of electrons, and perhaps some protons, flowing through the gaps between them. Nuclei with high mass numbers, such as ferrous, gold, platinum, uranium, may exist in the surface region or in the outer-core region. It is found that the structure of the neutron star changes very much as one goes from the surface to the core of the neutron star. The surface region is extremely hard and very smooth. Surface irregularities are hardly of the order of 5 mm, whereas the interior of the neutron star may be superfluid and composed of neutron-degenerate matter. However, the neutron star is highly compact crystalline systems, and in terrestrial materials under pressure, many examples of incommensurate phase transitions have been discovered. Consequently, the properties of incommensurate crystalline neutron star have been studied. The composition of the neutron stars in the super dense state remains uncertain in the core of the neutron star. One model describes the core as superfluid neutron-degenerate matter, mostly, composed of neutrons , and a small percentage of protons and electrons More exotic forms of matter are possible, including degenerate strange matter. It could also be incommensurate crystalline neutron matter that could be BCC or HCP. Using principles of quantum statistical mechanics, the specific heat and entropy of the incommensurate crystalline neutron star has been calculated assuming that the temperature of the star may vary between to . Two values for the temperature T that have been arbitrarily chosen for which the calculations have been done are and . The values of specific heat and entropy decrease as the temperature increases, and also, their magnitudes are very small. This is in line with the second law of thermodynamics.

In this work, the potential of utilizing of dried Cabbage Waste Powder (CWP) as an agro-waste biosorbent for the removal of noxious Congo Red (CR) dye was successfully investigated. FTIR spectroscopic analysis found multiple functional groups on CWP and their interactive effects played important roles in dye removal. Batch experiments were carried out to determine adsorption kinetics and isotherms. Experimental results showed that the rate of adsorption increased with increase in adsorbent weight, dye concentration, pH and decrease in particle size. However, the CR dye removal declined with increased in temperature indicating an endothermic process. Adsorption equilibrium was achieved within 3 h with efficiency of up to 91% at equilibrium. Langmuir adsorption isotherm model, Elovich equation and pseudo-second-order kinetics gave a good fit to the experimental data. Results furnish evidence that CWP is an efficacious, eco-friendly, bio renewable and affordable biomaterial for dye removal from industrial effluents.

PURPOSEEvaluate the effectiveness of compression while receiving chemotherapy compared with chemotherapy alone in the treatment of HIV-associated Kaposi sarcoma (KS) lymphedema.METHODSA randomized controlled trial was conducted in a single oncology clinic in western Kenya (NCT03404297). A computer-generated randomization schedule was used to allocate treatment arms. Randomized block design was used for stratification by lymphedema stage. Participants were HIV positive adults age ≥ 18 years on antiretroviral therapy with biopsy-proven KS associated with leg lymphedema and being initiated on chemotherapy. The intervention was 10 weeks of weekly clinic-based application of two-component paste compression bandages. The primary outcome was change in the Lower Extremity Lymphedema Index (LELI) score from week 0 to week 14. The secondary outcomes were change in the Lymphedema Quality of Life measure (LYMQOL) and change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 score from week 0 to week 14. Blinded outcome assessments were conducted.RESULTSOf 30 participants randomly assigned, 25 eligible patients (chemotherapy [control], n = 13; compression plus chemotherapy [intervention], n = 12) returned at week 14. Change in LELI, LYMQOL, and EORTC QLQ-C30 scores between week 14 and week 0 did not significantly differ by arm. The mean (standard deviation) change in LELI score was –25.9 (34.6) for the control arm compared with –13.3 (29.5) for the intervention arm, P = .340. The difference (95% CI) in the change in LELI score was –12.6 (–39.3 to 14.1).CONCLUSIONFuture studies evaluating a 14-week change in LELI for KS lymphedema should assume a standard deviation of approximately 30. Lessons learned from this pilot trial should inform the development of a larger, multicenter trial to evaluate the effectiveness of compression for KS lymphedema.

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with clinical manifestation cases that are almost similar to those of common respiratory viral infections. This study determined the prevalence of SARS-CoV-2 and other acute respiratory viruses among patients with flu-like symptoms in Bukavu city, Democratic Republic of Congo. We screened 1352 individuals with flu-like illnesses seeking treatment in 10 health facilities. Nasopharyngeal swab specimens were collected to detect SARS-CoV-2 using real-time reverse transcription-polymerase chain reaction (RT-PCR), and 10 common respiratory viruses were detected by multiplex reverse transcription-polymerase chain reaction assay. Overall, 13.9% (188/1352) of patients were confirmed positive for SARS-CoV-2. Influenza A 5.6% (56/1352) and Influenza B 0.9% (12/1352) were the most common respiratory viruses detected. Overall, more than two cases of the other acute respiratory viruses were detected. Frequently observed symptoms associated with SARS-CoV-2 positivity were shivering (47.8%; OR = 1.8; CI: 0.88–1.35), cough (89.6%; OR = 6.5, CI: 2.16–28.2), and myalgia and dizziness (59.7%; OR = 2.7; CI: 1.36–5.85). Moreover, coinfection was observed in 12 (11.5%) specimens. SARS-CoV-2 and influenza A were the most cooccurring infections, accounting for 33.3% of all positive cases. This study demonstrates cases of COVID-19 infections cooccurring with other acute respiratory infections in Bukavu city during the ongoing outbreak of COVID-19. Therefore, testing for respiratory viruses should be performed in all patients with flu-like symptoms for effective surveillance of the transmission patterns in the COVID-19 affected areas for optimal treatment and effective disease management.

ABSTRACT: Porcine Parvovirus (PPV) is one of the major pathogens responsible for reproductive failure in sows. However, the information on its frequency in the Democratic Republic of Congo (DRC) is largely unknown. Thus, the present study was carried out to detect and genetically characterize some of known Parvovirus namely porcine parvovirus 1, 2, 3, 4, porcine bocavirus (PBoV) 1, and porcine bocavirus-like virus (PBolikeV) in 80 randomly selected archive pig farm samples during an African swine fever (ASF) survey in South Kivu, eastern DRC by polymerase chain reaction (PCR). The majority of animals analyzed (82.5%) were local breeds, and most of them (87.5%) were adults (above one year old). The majority of the animals (65%) were from the free range farms. The PCR result indicated that only PPV3 was detected in 14/80 pigs. Seven swine herds (8.7%) were co-infected with PPV3 and ASFV. Morever, a significantly high PPV3 infection rate was observed in the spleen (66.7%, P

Abstract Background One of the major challenges facing investigators in the microbiome field is turning large numbers of reads generated by next-generation sequencing (NGS) platforms into biological knowledge. Effective analytical workflows that guarantee reproducibility, repeatability, and result provenance are essential requirements of modern microbiome research. For nearly a decade, several state-of-the-art bioinformatics tools have been developed for understanding microbial communities living in a given sample. However, most of these tools are built with many functions that require an in-depth understanding of their implementation and the choice of additional tools for visualizing the final output. Furthermore, microbiome analysis can be time-consuming and may even require more advanced programming skills which some investigators may be lacking. Results We have developed a wrapper named iMAP (Integrated Microbiome Analysis Pipeline) to provide the microbiome research community with a user-friendly and portable tool that integrates bioinformatics analysis and data visualization. The iMAP tool wraps functionalities for metadata profiling, quality control of reads, sequence processing and classification, and diversity analysis of operational taxonomic units. This pipeline is also capable of generating web-based progress reports for enhancing an approach referred to as review-as-you-go (RAYG). For the most part, the profiling of microbial community is done using functionalities implemented in Mothur or QIIME2 platform. Also, it uses different R packages for graphics and R-markdown for generating progress reports. We have used a case study to demonstrate the application of the iMAP pipeline. Conclusions The iMAP pipeline integrates several functionalities for better identification of microbial communities present in a given sample. The pipeline performs in-depth quality control that guarantees high-quality results and accurate conclusions. The vibrant visuals produced by the pipeline facilitate a better understanding of the complex and multidimensional microbiome data. The integrated RAYG approach enables the generation of web-based reports, which provides the investigators with the intermediate output that can be reviewed progressively. The intensively analyzed case study set a model for microbiome data analysis.

Abstract Background Cervical cancer is caused by oncogenic human papillomaviruses (HPV) and is one of the most common malignancies in women living in sub-Saharan Africa. Women infected with the human immunodeficiency virus (HIV) have a higher incidence of cervical cancer, but the full impact on HPV detection is not well understood, and associations of biological and behavioral factors with oncogenic HPV detection have not been fully examined. Therefore, a study was initiated to investigate factors that are associated with oncogenic HPV detection in Kenyan women. Methods Women without cervical dysplasia were enrolled in a longitudinal study. Data from enrollment are presented as a cross-sectional analysis. Demographic and behavioral data was collected, and HPV typing was performed on cervical swabs. HIV-uninfected women (n = 105) and HIV-infected women (n = 115) were compared for demographic and behavioral characteristics using t-tests, Chi-square tests, Wilcoxon sum rank tests or Fisher’s exact tests, and for HPV detection using logistic regression or negative binomial models adjusted for demographic and behavioral characteristics using SAS 9.4 software. Results Compared to HIV-uninfected women, HIV-infected women were older, had more lifetime sexual partners, were less likely to be married, were more likely to regularly use condoms, and were more likely to have detection of HPV 16, other oncogenic HPV types, and multiple oncogenic types. In addition to HIV, more lifetime sexual partners was associated with a higher number of oncogenic HPV types (aIRR 1.007, 95% CI 1.007–1.012). Greater travel distance to the clinic was associated with increased HPV detection (aOR for detection of ≥ 2 HPV types: 3.212, 95% CI 1.206–8.552). Older age (aOR for HPV 16 detection: 0.871, 95% CI 0.764–0.993) and more lifetime pregnancies (aOR for detection of oncogenic HPV types: 0.706, 95% CI, 0.565–0.883) were associated with reduced detection. Conclusion HIV infection, more lifetime sexual partners, and greater distance to health-care were associated with a higher risk of oncogenic HPV detection, in spite of ART use in those who were HIV-infected. Counseling of women about sexual practices, improved access to health-care facilities, and vaccination against HPV are all potentially important in reducing oncogenic HPV infections.

African swine fever (ASF) is a notifiable contagious disease caused by the African swine fever virus (ASFV), leading to a serious socio-economic impact, constraining pig industry, and affecting food security worldwide. This study aimed to detect and characterize ASFV strains from suspected infected domestic pigs in two South-Kivu province districts of the Democratic Republic of the Congo (DRC). A total of 155 pig samples were screened for viral DNA and sequencing at multiple loci. An infection rate of 5.2% (8/155) was recorded from a total of 155 blood samples with the highest ASFV infection rate of 8% for Uvira (6/75) and mostly in female pigs 5 (7.6%). Most ASF associated clinical signs were redness on the skin and snout at 49% (95% CI: 21–34), followed by the unwillingness of pigs to stand at 29 % (95%, CI: 19–35). Phylogenetic analysis of partial B646L (p72) and the full-length E183 (p54) gene sequences revealed the circulation of genotypes IX and X, which clustered with previously reported viruses in the same region, Uganda, Kenya, and Tanzania. Intragenotypic resolution of the CVR region clustered the viruses into two subgroups: the genotype X strain subgroup (10 repeats, AAAABNAABA) and the genotype IX strain subgroup (11 repeats, AAAAAAAAAAF). This finding provides additional evidence that genetically similar ASFV strains may be circulating within South Kivu province and highlights the need for improved coordination to prevent the spread of the disease in non-infected areas.

INTRODUCTION: Opportunistic fungal infections due to immunosuppression coupled with antifungal drug resistance are an emerging challenge globally. The present study examined the antifungal susceptibility of yeasts and molds from sputum of tuberculosis retreatment and relapse patients at selected reference facilities in Kenya. METHODS: a total of 340 sputa samples from patients who gave written informed consent were examined. Fungal culture was done on sabouraud dextrose agar (SDA). Molds were identified by macroscopic and microscopic features while yeasts were inoculated on CHROMTMagar Candida and confirmed using API 20C AUXTM. Itraconazole (ICZ), voriconazole (VCZ), fluconazole (FCZ) and amphotericin B (AMB) were tested using broth micro-dilution methods according to Clinical and Laboratory Standards Institute (CLSI). RESULTS: out of the 340 samples, 14.4% (n=49) and 15.6% (n=53) were positive for yeasts and molds respectively. Candida albicans and C. krusei were the most predominant isolates constituting 49.0% (n=24) and 20.4% (n=10) of the total yeasts respectively. Aspergillus spp. were the most frequent (22.6%) molds and isolates with MICs 4μg/ml on the antifungal agents were noted. All the molds except two (n=2) isolates of Scedosporium aspiopermum exhibited MICs 4μg/ml for fluconazole. Overall, molds were more sensitive to AMB and VCZ.Candida albicans had MIC50 0.06μg/ml, and MIC 904μg/ml. There was a statistically significant difference (F=3.7, P=0.004=0.05) in the overall sensitivity pattern of molds for the four antifungal agents while there was no significant difference (F=1.7, P=0.154=0.05) in sensitivity exhibited by the yeasts. CONCLUSION: the study demonstrates the significance of fungal colonization in presumptive tuberculosis retreatment or relapse with evidence of triazole resistance. There is need to strengthen fungal diagnostic and clinical management capabilities in susceptible populations.

Availability of medicines for treatment of cardiovascular disease (CVD) is low in low-income and middle-income countries (LMIC). Supply chain models to improve the availability of quality CVD medicines in LMIC communities are urgently required. Our team established contextualised revolving fund pharmacies (RFPs) in rural western Kenya, whereby an initial stock of essential medicines was obtained through donations or purchase and then sold at a small mark-up price sufficient to replenish drug stock and ensure sustainability. In response to different contexts and levels of the public health system in Kenya (eg, primary versus tertiary), we developed and implemented three contextualised models of RFPs over the past decade, creating a network of 72 RFPs across western Kenya, that supplied 22 categories of CVD medicines and increased availability of essential CVD medications from

Schistosoma mansoni (SM) is a parasitic helminth that infects over 200 million people and causes severe morbidity. It undergoes a multi-stage life cycle in human hosts and as such stimulates a stage-specific immune response. The human T cell response to SM is complex and varies throughout the life cycle of SM. Relative to the wealth of information regarding the immune response to SM eggs, little is known about the immune response to the adult worm. In addition, while a great deal of research has uncovered mechanisms by which co-infection with helminths modulates immunity to other pathogens, there is a paucity of data on the effect of pathogens on immunity to helminths. As such, we sought to characterize the breadth of the T cell response to SM and determine whether co-infection with Mycobacterium tuberculosis (Mtb) modifies SM-specific T cell responses in a cohort of HIV-uninfected adults in Kisumu, Kenya. SM-infected individuals were categorized into three groups by Mtb infection status: active TB (TB), Interferon-γ Release Assay positive (IGRA+), and Interferon-γ Release Assay negative (IGRA-). U.S. adults that were seronegative for SM antibodies served as naïve controls. We utilized flow cytometry to characterize the T cell repertoire to SM egg and worm antigens. We found that T cells had significantly higher proliferation and cytokine production in response to worm antigen than to egg antigen. The T cell response to SM was dominated by γδ T cells that produced TNFα and IFNγ. Furthermore, we found that in individuals infected with Mtb, γδ T cells proliferated less in response to SM worm antigens and had higher IL-4 production compared to naïve controls. Together these data demonstrate that γδ T cells respond robustly to SM worm antigens and that Mtb infection modifies the γδ T cell response to SM.

Objectives: Cervical cancer is caused by persistent infection with oncogenic, or “high-risk” types of human papillomaviruses, and is the most common malignancy in Kenyan women. A longitudinal study was initiated to investigate factors associated with persistent human papillomavirus detection among HIV-infected and HIV-uninfected Kenyan women without evidence of cervical dysplasia. Methods: Demographic/behavioral data and cervical swabs were collected from HIV-uninfected women (n = 82) and HIV-infected women (n = 101) at enrollment and annually for 2 years. Human papillomavirus typing was performed on swabs (Roche Linear Array). Logistic regression models of human papillomavirus persistence were adjusted for demographic and behavioral characteristics. Results: HIV-infected women were older and less likely to be married and to own a home and had more lifetime sexual partners than HIV-uninfected women. All HIV-infected women were receiving anti-retroviral therapy at enrollment and had satisfactory CD4 cell counts and HIV viral loads. One- and two-year persistent human papillomavirus detection was significantly associated with HIV infection for any human papillomavirus, high-risk human papillomavirus, International Agency for the Research on Cancer-classified high-risk human papillomavirus, and non-oncogenic “low-risk” human papillomavirus. Conclusion: Persistent detection of oncogenic and non-oncogenic human papillomavirus was strongly associated with HIV infection in Kenyan women with re-constituted immune systems based on satisfactory CD4 cell counts. In addition to HIV infection, factors associated with an increased risk of human papillomavirus persistence included a higher number of lifetime sex partners. Factors associated with decreased risk of human papillomavirus persistence included older age and being married. Further studies are needed to identify the immunological defects in HIV-infected women that allow human papillomavirus persistence, even in women receiving effective anti-retroviral therapy. Further studies are also needed to determine the significance of low-risk human papillomavirus persistence in HIV-infected women.

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), which leads to an estimated 1. 5 million deaths worldwide each year. Although the immune correlates of protection against Mtb infection and TB disease have not been well-defined, natural killer (NK) cells are increasingly recognized as a key component of the innate immune response to Mtb and as a link between innate and adaptive immunity. In this study, we evaluated NK cell phenotypic and functional profiles in QuantiFERON-TB (QFT)+ and QFT− adults in a TB endemic setting in Kisumu, Kenya, and compared their NK cell responses to those of Mtb-naïve healthy adult controls in the U.S. We used flow cytometry to define the phenotypic profile of NK cells and identified distinct CD56dim NK cell phenotypes that differentiated the Kenyan and U.S. groups. Additionally, among Kenyan participants, NK cells from QFT+ individuals with latent Mtb infection (LTBI) were characterized by significant downregulation of the natural cytotoxicity receptor NKp46 and the inhibitory receptor TIGIT, compared with QFT− individuals. Moreover, the distinct CD56dim phenotypic profiles in Kenyan individuals correlated with dampened NK cell responses to tumor cells and diminished activation, degranulation, and cytokine production following stimulation with Mtb antigens, compared with Mtb-naïve U.S. healthy adult controls. Taken together, these data provide evidence that the phenotypic and functional profiles of NK cells are modified in TB endemic settings and will inform future studies aimed at defining NK cell-mediated immune correlates that may be protective against acquisition of Mtb infection and progression to TB disease.

Mycobacterium tuberculosis (Mtb) is a serious public health concern, infecting a quarter of the world and leading to 10 million cases of tuberculosis (TB) disease and 1. 5 million deaths annually. An effective type 1 CD4 T cell (TH1) immune response is necessary to control Mtb infection and defining factors that modulate Mtb-specific TH1 immunity is important to better define immune correlates of protection in Mtb infection. Helminths stimulate type 2 (TH2) immune responses, which antagonize TH1 cells. As such, we sought to evaluate whether co-infection with the parasitic helminth Schistosoma mansoni (SM) modifies CD4 T cell lineage profiles in a cohort of HIV-uninfected adults in Kisumu, Kenya. Individuals were categorized into six groups by Mtb and SM infection status: healthy controls (HC), latent Mtb infection (LTBI) and active tuberculosis (TB), with or without concomitant SM infection. We utilized flow cytometry to evaluate the TH1/TH2 functional and phenotypic lineage state of total CD4 T cells, as well as CD4 T cells specific for the Mtb antigens CFP-10 and ESAT-6. Total CD4 T cell lineage profiles were similar between SM+ and SM− individuals in all Mtb infection groups. Furthermore, in both LTBI and TB groups, SM infection did not impair Mtb-specific TH1 cytokine production. In fact, SM+ LTBI individuals had higher frequencies of IFNγ+ Mtb-specific CD4 T cells than SM− LTBI individuals. Mtb-specific CD4 T cells were characterized by expression of both classical TH1 markers, CXCR3 and T-bet, and TH2 markers, CCR4, and GATA3. The expression of these markers was similar between SM+ and SM− individuals with LTBI. However, SM+ individuals with active TB had significantly higher frequencies of GATA3+ CCR4+ TH1 cytokine+ Mtb-specific CD4 T cells, compared with SM− TB individuals. Together, these data indicate that Mtb-specific TH1 cytokine production capacity is maintained in SM-infected individuals, and that Mtb-specific TH1 cytokine+ CD4 T cells can express both TH1 and TH2 markers. In high pathogen burden settings where co-infection is common and reoccurring, plasticity of antigen-specific CD4 T cell responses may be important in preserving Mtb-specific TH1 responses.

METHODS:We evaluated therapeutic TAT for a tertiary hospital in Western Kenya, using a time-motion study focusing specifically on common hematology and biochemistry orders. The aim was to determine significant bottlenecks in diagnostic testing processes at the institution. RESULTS:A total of 356 (155 hematology and 201 biochemistry) laboratory tests were fully tracked from the time of ordering to availability of results to care providers. The total therapeutic TAT for all tests was 21.5 ± 0.249 hours (95% CI). The therapeutic TAT for hematology was 20.3 ± 0.331 hours (95% CI) while that for biochemistry tests was 22.2 ± 0.346 hours (95% CI). Printing, sorting and dispatch of the printed results emerged as the most significant bottlenecks, accounting for up to 8 hours of delay (Hematology-8.3 ± 1.29 hours (95% CI), Biochemistry-8.5 ± 1.18 hours (95% CI)). Time of test orders affected TAT, with orders made early in the morning and those in the afternoon experiencing the most delays in TAT. CONCLUSION:Significant inefficiencies exist at multiple steps in the turnaround times for routine laboratory tests at a large referral hospital within an LMIC setting. Multiple opportunities exist to improve TAT and streamline processes around diagnostic testing in this and other similar settings.

Background: HIV-associated Kaposi sarcoma (KS), among the most frequent cancers seen in sub-Saharan Africa, is associated with a high prevalence of lymphedema. Lymphedema causes progressive functional impairment marked by swelling, physical discomfort, disfiguring changes, skin hardening from fibrosis, poor wound healing, and recurrent skin infection. While compression therapy is considered a major component of lymphedema management, this intervention has never been evaluated in HIV-associated KS lymphedema. Methods/design: The Kenyan Improvised Compression for Kaposi Sarcoma (KICKS) study is a randomized, controlled trial. Due to variable lymphedema stage, we will use block randomization with a 1:1 allocation to assign participants to one of two groups: “Immediate compression” or “Delayed compression.” Those randomized to “Immediate compression” intervention arm will receive weekly two-component compression bandages while receiving chemotherapy, whereas those in the “Delayed compression” control arm will be followed during chemotherapy and then receive compression after chemotherapy is completed. The primary outcome is change in Lower Extremity Lymphedema Index from enrollment at Week 0 to blinded outcome assessment at Week 14 between intervention and control arms. Secondary outcomes are change in leg lymphedema-specific quality of life (LYMQOL) and change in overall health quality of life in cancer (EORTC QLQ C30). Discussion: This represents the first study in sub-Saharan Africa to assess a lymphedema-directed intervention for KS, and the intervention—locally sourced two-component compression bandages—is affordable and available. Thus, the KICKS study is an important step towards developing an evidence-based path for regionally relevant management of HIV-associated KS lymphedema. Trial registration: This trial was registered at ClinicalTrials.gov on January 19, 2018: identifier NCT03404297. Keywords: Kaposi sarcoma, Lymphedema, Compression, Unna boot, Paste bandage, Randomized controlled trial