Design of Inhibitors That Target the Menin-Mixed-Lineage Leukemia Interaction.

The prognosis of mixed-lineage leukemia (MLL) has remained a significant health concern, especially for infants. The minimal treatments available for this aggressive type of leukemia has been an ongoing problem. Chromosomal translocations of the KMT2A gene are known as MLL, which expresses MLL fusion proteins. A protein called menin is an important oncogenic cofactor for these MLL fusion proteins, thus providing a new avenue for treatments against this subset of acute leukemias. In this study, we report results using the structure-based drug design (SBDD) approach to discover potential novel MLL-mediated leukemia inhibitors from natural products against menin. The three-dimensional (3D) protein model was derived from Protein Databank (Protein ID: 4GQ4), and EasyModeller 4.0 and I-TASSER were used to fix missing residues during rebuilding. Out of the ten protein models generated (five from EasyModeller and I-TASSER each), one model was selected. The selected model demonstrated the most reasonable quality and had 75.5% of residues in the most favored regions, 18.3% of residues in additionally allowed regions, 3.3% of residues in generously allowed regions, and 2.9% of residues in disallowed regions. A ligand library containing 25,131 ligands from a Chinese database was virtually screened using AutoDock Vina, in addition to three known menin inhibitors. The top 10 compounds including ZINC000103526876, ZINC000095913861, ZINC000095912705, ZINC000085530497, ZINC000095912718, ZINC000070451048, ZINC000085530488, ZINC000095912706, ZINC000103580868, and ZINC000103584057 had binding energies of -11.0, -10.7, -10.6, -10.2, -10.2, -9.9, -9.9, -9.9, -9.9, and -9.9 kcal/mol, respectively. To confirm the stability of the menin-ligand complexes and the binding mechanisms, molecular dynamics simulations including molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) computations were performed. The amino acid residues that were found to be potentially crucial in ligand binding included Phe243, Met283, Cys246, Tyr281, Ala247, Ser160, Asn287, Asp185, Ser183, Tyr328, Asn249, His186, Leu182, Ile248, and Pro250. MI-2-2 and PubChem CIDs 71777742 and 36294 were shown to possess anti-menin properties; thus, this justifies a need to experimentally determine the activity of the identified compounds. The compounds identified herein were found to have good pharmacological profiles and had negligible toxicity. Additionally, these compounds were predicted as antileukemic, antineoplastic, chemopreventive, and apoptotic agents. The 10 natural compounds can be further explored as potential novel agents for the effective treatment of MLL-mediated leukemia.

Inclusivity in Occupational Participation: Life Stories of Bangladeshi With Spinal Cord Injury.

This research aimed to describe the process of occupational participation among persons with spinal cord injury (SCI) discharged from the only SCI rehabilitation hospital in Bangladesh. We analyzed seven participants' interview transcripts and observations using the trajectory equifinality model. Study participants demonstrated the following occupational participation trajectories: (a) employing a strategy or difficulty in occupational participation; (b) performing solidarity or experiencing deprivation; (c) creating identity or divergence; and (d) being included in or excluded from everyday life. There are four pathways: (I) discouraging conditions that minimized daily performance; (II) reinforcing obligatory connections to optimization of daily performance; (III) reciprocity to facilitate social activities; and (IV) manipulating mastery in occupational participation. Occupational therapists can consider the trajectory phases and pathways of occupational participation when facilitating the inclusion of service users after discharge from the hospital.

Experience of Occupational Participation Among Persons With Spinal Cord Injury: Life Story Analysis With Trajectory Equifinality Model (TEM)Persons with spinal cord injury (SCI) in Bangladesh demonstrated inadequate skills in community integration because of limited access to health care follow-ups and unfavorable sociocultural conditions. This research focuses on occupational participation experiences among seven persons with SCI living in the community. We used trajectory equifinality model (TEM) to analyze semi-structured interview and observation data to understand human experiences in an irreversible timeline from a starting point to an endpoint. Data analysis revealed a conceptualization of four periods of occupational participation and four common types of non-linear pathways. Participants optimized shared occupational participation and used mastery over occupations to minimize the experience of occupational deprivation. These findings could assist in developing independent peer-led occupation-based health care programs with few skilled occupational therapists and limited financial resources. These 3 years of interviews and follow-up reports with participants who were selected purposively do not necessarily reflect how actual participation unfolded over time.

Habit Formation Intervention to Improve Type 2 Diabetes Self-Management Behaviors: A Feasibility Study.

IMPORTANCE: Self-management of lifestyle behaviors is the recommended focus for interventions to address Type 2 diabetes. Habit formation is an effective approach to changing personal behaviors, but evidence of success for Type 2 diabetes is limited. OBJECTIVE: To examine the feasibility and preliminary effectiveness of occupation-based habit formation interventions for improving diabetes self-management behaviors. DESIGN: Single-subject design with multiple participants providing 4 wk of baseline data followed by 10 wk of intervention data. SETTING: Individual telehealth sessions. PARTICIPANTS: Eight adults (ages 29-75 yr) with Type 2 diabetes, who had access to a telephone and who were not involved in other diabetes-related education or interventions voluntarily, enrolled into the study. INTERVENTION: Participants engaged in 10 wk of habit formation intervention focused on four diabetes self-management domains: nutrition, blood glucose monitoring, medication management, and physical activity. OUTCOMES AND MEASURES: Data gathered included findings on measures of diabetes self-care behaviors and habit formation. RESULTS: There was a significant change in self-care behaviors for 6 of the 8 participants (p < .05 for 1 participant, and p < .01 for 5 participants). Group changes were statistically significant (p < .001). Habit strength significantly improved for all areas of diabetes self-management (p < .001 for nutrition, blood glucose monitoring, and medication management and p = .001 for physical activity). CONCLUSIONS AND RELEVANCE: Findings suggest that the occupation-based intervention was feasible and showed promise for developing self-management behaviors. What This Article Adds: Habits are considered foundational to occupations, yet application of the science of habit formation is often not well understood by occupational therapists. This study considered the theoretical components of habit formation that have been neglected by prior studies and demonstrates the feasibility and preliminary effect estimates of a habit formation intervention when used with people with Type 2 diabetes.

Occupational therapy gender imbalance; revisiting a lingering issue.

BACKGROUND: Recently, it has been suggested that gender disparity in Occupational Therapy has to do with segregated gendered job norms that position female dominated professions as a 'step down' for many males. Interestingly, this suggestion was not underpinned by experiences of males in the profession. AIMS AND METHODS: Thirteen male Occupational Therapists with a variety of backgrounds were invited to this Round Table research, focussing on the broader issue of the existing gender imbalance in Occupational Therapy. RESULTS: Two themes emerged: 'The core values of the profession', and 'Broadening the scope of the profession'; none of them suggesting that male/female imbalance was necessarily the most pressing issue. CONCLUSIONS: A gender-unrelated approach to everyday problem-solving was put forward to achieve increased diversity in Occupational Therapists' backgrounds, better reflecting the people they serve. By broadening the scope and the way the profession is presented, and encouraging innovative and more entrepreneurially driven approaches, diversity in the workforce could be further facilitated. These findings are discussed within the context of 'The mutual constitution of cultures and selves' model. SIGNIFICANCE: Diversity in the Occupational therapy workforce could be further facilitated with a shift in focus away from the male/female perspective to an intersectional approach.

Establishing an Antimicrobial Stewardship Program in Sierra Leone: A Report of the Experience of a Low-Income Country in West Africa.

Antimicrobial Resistance (AMR) is a growing global health challenge that threatens to undo gains in human and animal health. Prevention and control of AMR requires functional antimicrobial stewardship (AMS) program, which is complex and often difficult to implement in low- and middle-income countries. We aimed to describe the processes of establishing and implementing an AMS program at Connaught Hospital in Sierra Leone. The project involved the setting up of an AMS program, capacity building and performing a global point prevalence survey (GPPS) at Sierra Leone's national referral hospital. Connaught Hospital established a multidisciplinary AMS subcommittee in 2021 to provide AMS services such as awareness campaigns, education and training and review of guidelines. We performed a GPPS on 175 patients, of whom more than half (98, 56.0%) were prescribed an antibiotic: 63 (69.2%) in the surgical wards and 53 (51.2%) in the medical wards. Ceftriaxone (60, 34.3%) and metronidazole (53, 30.3%) were the most common antibiotics prescribed to patients. In conclusion, it is feasible to establish and implement an AMS program in low-income countries, where most hospitalized patients were prescribed an antibiotic.

Perceptions of Occupational Therapy Educators about the Educational Preparation of Occupational Therapists for Designation as Qualified Mental Health Professionals.

This study investigated educators' perspectives on whether occupational therapists were educationally prepared for designation as Qualified Mental Health Professionals (QMHPs) using a cross-sectional survey design followed by interviews to gather qualitative data. Fifty-two educators responded to an electronic survey questionnaire. Six of the 52 participants volunteered for follow-up interviews. Most educators (64.58%) thought that occupational therapists were prepared for designation as QMHPs (p=.04). Interview data indicated that educational programs prepared students for psychosocial practice using various content delivery methods. Occupational therapists need to advocate for recognition as significant contributors to the treatment of people with mental health challenges.

Tocopherol Enhances the Antioxidant Defense System and Histomorphometric Parameters in The Gastrointestinal Tract of Rats Treated with Sodium Arsenite.

Arsenic compromises the gastrointestinal integrity and function via the body's anti-oxidative system breakdown.  Hence, this study aimed to investigate the effects of tocopherol on redox imbalance and histoarchitectural alterations in rats' gastrointestinal tract exposed to sodium arsenite. Sodium arsenite and graded doses of tocopherol were administered orally into experimental rats assigned to different groups for four weeks concurrently. Redox status assay was done in homogenized samples by spectrophotometry. Parietal cell mass and mucous cell density (stomach), villus height and crypt depth (ileum), goblet cells count, and crypt depth (colon) were evaluated by histomorphometry. Inflammatory cells infiltration was also assessed using a semi-quantitative procedure. Sodium arsenite caused a significant increase in Malondialdehyde and Myeloperoxidase but, decreased Superoxide dismutase, Catalase, Nitric oxide, Glutathione peroxidase, Glutathione, and Glutathione-S-Transferase. Tocopherol treatment reversed the changes (p<0.05) though not largely dose-dependent. Furthermore, tocopherol annulled sodium arsenite-induced increase in parietal cell mass and decrease in mucous cell density in the stomach, decrease in villus height and villus height/crypt depth ratio in the ileum, and decrease in goblets cells and increase in crypt depth in the colon. Moreover, activated inflammatory cell infiltration by sodium arsenite was mitigated by tocopherol. Sodium arsenite provokes not only marked inflammatory cellular infiltration but a focal loss of glands, hyperplasia of crypts, atrophic villi, and hypertrophy of Peyer's patches in the intestines, which are all lessened with tocopherol treatment.  These findings underscore the anti-oxidative properties of tocopherol as a potent dietary factor against sodium arsenite toxicity in the gastrointestinal tract. Keywords: Tocopherol, arsenic, stomach, ileum, colon.

Malaria surveillance amongst pregnant women attending antenatal care in private hospitals in Onitsha metropolis, South Eastern Nigeria.

Background: Recent reports suggest that pregnant women living in holoendemic regions of sub-Sahara Africa die in great numbers annually due to malaria disease resulting from their higher susceptibility, reduced immunity and demographic associated factors. This work investigated the prevalence of Plasmodium falciparum in pregnant women attending antenatal care (ANC) in selected private hospitals in Onitsha metropolis South East Nigeria. Methods: Venous blood samples were collected from 270 pregnant women during ANC visits between October 2016 and December 2017. A questionnaire was used to collect demographic data, gestational age, knowledge of malaria and preventive measures while clinical presentations and symptoms were extracted from the physician's clerking form. Laboratory diagnosis was done using microscopy. The effect of the demographic variables and other associated factors on prevalence and parasite densities was studied using Chi-square and ANOVA tests. Results: The overall P. falciparum prevalence was 42.6%. Prevalence varied with the maternal age, gestational age, preventive measures adopted by the pregnant women and clinical presentations. 27.8 % of the infected women were highly parasitized (>5000 parasites/µl); 67% had a moderate parasite density (1,000-4,999 parasites/µl) and 5.2% showed a low parasite density (1-999 parasites/µl). We observed that 35.2%, 30%, 18.9% and 5.2% of the study cohorts preferred and used treated bed nets, insecticides, windows and door screening and non-treated bed nets respectively as malaria preventive measures. 5.9% did not use any protection. Conclusions: The findings of this study revealed high prevalence of malaria among pregnant women living in Onitsha metropolis with high mean parasite densities despite strong adherence to use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy (IPTp) and other malaria preventive measures.

Genetic diversity and allelic frequency of antigenic markers in Plasmodium falciparum isolates from Nnewi district in Nigeria.

INTRODUCTION: The genetic diversity of Plasmodium falciparum poses a threat to the development and implementation of malaria control strategies. Thus, there is a need for continuous surveillance of its genetic diversity, especially amongst the parasite's reservoir's asymptomatic population. METHODOLOGY: Three cohorts comprising children under ten years old, pregnant women and other adults were recruited into this study. Blood sample was collected from all consenting individuals and screened by the polymerase chain reaction (PCR) method. The genetic diversity of P. falciparum was determined by genotyping the merozoite surface protein-1 (msp-1), merozoite surface protein-2 (msp-2) and glutamate-rich protein (glurp). The size of alleles was visualized on the agarose gel. The multiplicity of infection (MOI) and expected heterozygosity (He) were determined. RESULTS: The majority of the patients showed polyclonal infections, while the multiplicity of infection with msp-2 and glurp of isolates from pregnant women were 2.5 and 1.8, respectively. Children and adults were 2.3 and 1.1; 2.4 and 1.3, respectively. The estimated number of genotypes was 10 msp-1 (4 KI; 4 MAD; 2 RO33), 27 msp-2 (14 FC27; 13 IC/3D7) and 8 glurp. K1 (36/100) was more frequent than the MAD20 (22.33/100) allele, which was, in turn, more frequent than the RO33 (13.59/100). The samples with the 3D7 allele (53.40/100) of msp-2 occurred more frequently than the FC27 type (45.63/100). Polymorphism in the glurp gene occurred most frequently (72.82/100). CONCLUSION: The study samples exhibited a high degree of genetic polymorphism in msp-2 allele typing with multiple clones, reflecting the complexity of parasite populations.

Geospatial approach to investigate spatial clustering and hotspots of blood lead levels in children within Kabwe, Zambia.

BACKGROUND: Communities around Kabwe, Zambia are exposed to lead due to deposits from an old lead (Pb) and zinc (Zn) mining site. Children are particularly more vulnerable than adults, presenting with greatest risk of health complications. They have increased oral uptake due to their hand to mouth activities. Spatial analysis of childhood lead exposure is useful in identifying specific areas with highest risk of pollution. The objective of the current study was to use a geospatial approach to investigate spatial clustering and hotspots of blood lead levels in children within Kabwe. METHODS: We analysed existing data on blood lead levels (BLL) for 362 children below the age of 15 from Kabwe town. We used spatial autocorrelation methods involving the global Moran's I and local Getis-Ord Gi*statistic in ArcMap 10.5.1, to test for spatial dependency among the blood lead levels in children using the household geolocations. RESULTS: BLL in children from Kabwe are spatially autocorrelated with a Moran's Index of 0.62 (p < 0.001). We found distinct hotspots (mean 51.9 µg/dL) in communities close to the old lead and zinc-mining site, lying on its western side. Whereas coldspots (mean 7 µg/dL) where observed in areas distant to the mine and traced on the eastern side. This pattern suggests a possible association between observed BLL and distance from the abandoned lead and zinc mine, and prevailing winds. CONCLUSION: Using geocoded data for households, we found clustering of childhood blood lead and identified distinct hotspot areas with high lead levels for Kabwe town. The geospatial approach used is especially valuable in resource-constrained settings like Zambia, where the precise identification of high risk locations allows for the initiation of targeted remedial and treatment programs.

Efficiency and Improved Profitability of Insect-Based Aquafeeds for Farming Nile Tilapia Fish (Oreochromis niloticus L.).

In Sub-Saharan Africa, Nile tilapia (Oreochromis niloticus L.) make up over 80% of aquaculture production. However, the local aquaculture farmers are restricted by the unavailability and expensive cost of formulated rations. To reduce reliance on the scarce and expensive fishmeal used in fish feeds, alternative insect protein has been successfully utilized in many aquafeeds. However, data on the influence of insect-based feed on the growth and economic benefit of feeding tilapia with the emerging insect-based diet are scanty. This study investigated the effect of partially and completely substituting fishmeal with black soldier fly larval meal (BM) on growth and economic parameters of tilapia. The O. niloticus was fed a standard commercial diet as a control (100% FM; 0% BM), BM33 (67% FM; 33% BM), BM67 (33% FM; 67% BM) and BM100 (0% FM; 100% BM) for 20 weeks in randomly assigned cages mounted in an 800 m2 earthen pond. Results from this study showed that diet type significantly (p < 0.05) affected the feed intake of the fish as well as weight gain. The feed conversion ratio and survival rate of O. niloticus did not vary across the different diets. Fish fed Diet1 had a 15% increase in weight when compared to fish fed the control diet. Return on investment and the cost-benefit ratio was similar across the diets, suggesting that BM is a suitable and cost-equivalent dietary supplement of FM up to 100% in aquafeed for growing tilapia fish in earthen ponds for the market.

Evaluation of macrofilaricidal and microfilaricidal activities against Onchocerca ochengi and cytotoxicity of some synthesized azo compounds containing thiophene backbone.

Control and treatment of onchocerciasis, a devastating tropical filarial disease caused by Onchocerca volvulus, rely solely on the community directed treatment with ivermectin. However, ivermectin is only microfilaricidal with evidence of resistance of the parasite among other limitations, which necessitate the search for new efficacious and safe filaricides. Ten synthetic thienylazoryl dyes were screened in vitro against adult and microfilariae worm stages of Onchocerca ochengi based on worm motility and MTT formazan assay. Cytotoxicity of active compounds was assessed on monkey kidney epithelial cells (LLC-MK2) using the MTT formazan assay. Seven (7) compounds showed both macrofilaricidal activity against adult male worms and microfilaricidal activity among which three 4a, 4c and 4e recorded the highest activity (IC50 = 4.2 to 8.8µM) against adult male worms, comparable to some standard anthelmintics. Five compounds showed rapid activity against microfilariae with 100% inhibition after 24-h incubation. The active compounds were nontoxic on monkey kidney cells (CC50> 4µg/mL), but their selectivity index values were relatively low (≤ 3). The thienylazoaryls with both macrofilaricidal and microfilaricidal activities may yield molecules which could be used for eradication of onchocerciasis following further medicinal chemistry modification of their structures to enhance their selectivity.

Article 3: 1-year impact of supervision, performance assessment, and recognition strategy (SPARS) on prescribing and dispensing quality in Ugandan health facilities.

BACKGROUND: To strengthen appropriate medicine use (AMU) including the prescribing and dispensing quality at public sector health facilities in Uganda, the Ministry of Health introduced a multipronged approach known as the Supervision, Performance Assessment, and Recognition Strategy (SPARS). This paper assesses the impact of the first year of SPARS implementation on key AMU indicators. METHODS: District-based health workers trained as supervisors provide in-service training in medicines management complemented by indicator-based performance assessment and targeted supervision during each SPARS facility visit. From 2010 to 2013, health facilities that started the SPARS intervention were assessed during the first and last visit during a period of 12 months of implementing SPARS. This study examines 12 AMU indicators with 57 individual outcomes covering prescribing and dispensing quality. We also explored factors influencing 1-year improvement. RESULTS: We found an overall increase in AMU indicators of 17 percentage points (p < 0.000) between the first and last visit during a period of 12 months of supervisions, which was significant in all levels of health care facilities and in both government and private not-for-profit faith-based sectors. Appropriate dispensing (25 percentage points, p < 0.005) improved more than appropriate prescribing (12 percentage points, p = 0.13). Specific facilities that reached an average score of over 75% across all AMU measures within the first year of supervision improved from 3 to 41% from the first visit (baseline). The greatest overall impact on AMU occurred in lower-level facilities; the level of improvement varied widely across indicators, with the greatest improvements seen for the lowest baseline measures. Supervision frequency had a significant impact on level of improvement in the first year, and private not-for-profit faith-based health facilities had notably higher increases in several dispensing and prescribing indicator scores than public sector facilities. CONCLUSIONS: The multipronged SPARS approach was effective in building appropriate medicine use capacity, with statistically significant improvements in AMU overall and almost all prescribing and dispensing quality measures after 12 months of supervision. We recommend broad dissemination of the SPARS approach as an effective strategy to strengthen appropriate medicine use in low-income countries.

Education for sustainable health care: From learning to professional practice.

A number of planetary boundaries, including climate change as a result of greenhouse gas emissions, has already been exceeded. This situation has deleterious consequences for public health. Paradoxically, 4.4% of these emissions are attributable to the healthcare sector. These problems have not been sufficiently acknowledged in health professions curricula. This paper addresses two main issues, humanistic learning and the application of knowledge acquisition to clinical practice. Humanistic learning principles can be used to emphasize learner-centered approaches, including knowledge acquisition and reflection to increase self-awareness. Applying humanistic principles in everyday life and clinical practice can encourage stewardship, assisting students to become agents for change. In terms of knowledge and skills application to clinical practice, an overview of varied and novel approaches of how sustainable education can be integrated at different stages of training across several health care professions is provided. The Health and Environment Adaptive Response Taskforce (HEART) platform as an example of creating empowered learners, the NurSusTOOLKIT, a multi-disciplinary collaboration offering free adaptable educational resources for educators and the Greener Anaesthesia and Sustainability Project (GASP), an example of bridging the transition to clinical practice, are described.

Elimination of Simulium neavei-Transmitted Onchocerciasis in Wambabya-Rwamarongo Focus of Western Uganda.

Wambabya-Rwamarongo onchocerciasis focus is one of the eight foci Uganda verified using the WHO verification guidelines. The approach for elimination was twice yearly treatment with ivermectin for every round, treating at least 90% of all the eligible population. This was in combination with vector elimination using Abate® (BASF SE, Limburgerhof, Germany) since elimination nationwide policy was launched. From 2008 to 2013, the program distributed ivermectin with a mean treatment coverage of the ultimate treatment goal (UTG) or eligible population of 91.2%, with a range of 85-96%. In 2009, vector elimination based on ground larviciding had a dramatic impact on the Simulium vectors, as the last fly was observed in October 2009. No more Simulium vectors were observed during a period of at least 7 years, including the 3-year posttreatment surveillance (PTS) until the focus was reclassified as eliminated in August 2017. During the PTS period, none of the 10,578 trapped crabs were found infested with the aquatic stages of the vector. The last infested crab was observed in March 2010, and for at least 7 years, no infested crabs were observed. Serological surveys showed that of 2,978 young children examined in 2013, only one was OV16 positive (0.0%; 95% CI: 0-0.21). In 2017, after the PTS period, all 3,079 young children examined were negative for OV16 (95% CI: 0-0.16). Therefore, entomological and serological results provided evidence that resulted in the reclassification of Wambabya-Rwamarongo focus from "transmission interrupted" to "transmission eliminated" with no possibility of recrudescence.

Historical Elimination of Onchocerciasis from Victoria Nile Focus in Central Uganda Verified Using WHO Criteria.

Uganda has verified elimination of seven onchocerciasis foci since 2007 when the nationwide onchocerciasis elimination policy was launched. However, the Victoria Nile focus (which was eliminated in the early 1970s) had not been verified. The objective of this study was to verify this focus to the WHO verification guidelines and bring it in line with recently eliminated foci. Vector control with dichlorodiphenyltrichloroethane was the main intervention used at the Victoria Nile from the 1950s to the 1970s. Historical fly collection sites along River Nile were identified for recent fly collection. Relevant health workers near the sites were trained to supervise fly collection activity. With support from communities, fly collectors were identified, trained, and equipped to collect Simulium flies for at least a year. A total of 854 Simulium flies were collected and analyzed by polymerase chain reaction to detect Onchocerca volvulus DNA. The communities and their leaders provided consent for the collection of dry blood spots (DBS) from children younger than 10 years for investigation of recent exposure to the disease. A total of 2,953 DBS were collected and analyzed by OV16 ELISA to detect the presence of IgG4 antibodies recognizing the OV16 antigen. The results showed that none of the flies carried O. volvulus DNA. Similarly, all the children were OV16 negative, showing no exposure to onchocerciasis. All the flies collected were identified as Simulium adersi, which is not a known vector for O. volvulus. The results confirmed that onchocerciasis and its vector Simulium damnosum had been eliminated in the Victoria Nile focus.

Data-driven modelling and spatial complexity supports heterogeneity-based integrative management for eliminating Simulium neavei-transmitted river blindness.

Concern is emerging regarding the challenges posed by spatial complexity for modelling and managing the area-wide elimination of parasitic infections. While this has led to calls for applying heterogeneity-based approaches for addressing this complexity, questions related to spatial scale, the discovery of locally-relevant models, and its interaction with options for interrupting parasite transmission remain to be resolved. We used a data-driven modelling framework applied to infection data gathered from different monitoring sites to investigate these questions in the context of understanding the transmission dynamics and efforts to eliminate Simulium neavei- transmitted onchocerciasis, a macroparasitic disease that causes river blindness in Western Uganda and other regions of Africa. We demonstrate that our Bayesian-based data-model assimilation technique is able to discover onchocerciasis models that reflect local transmission conditions reliably. Key management variables such as infection breakpoints and required durations of drug interventions for achieving elimination varied spatially due to site-specific parameter constraining; however, this spatial effect was found to operate at the larger focus level, although intriguingly including vector control overcame this variability. These results show that data-driven modelling based on spatial datasets and model-data fusing methodologies will be critical to identifying both the scale-dependent models and heterogeneity-based options required for supporting the successful elimination of S. neavei-borne onchocerciasis.

Diversity, above-ground biomass, and vegetation patterns in a tropical dry forest in Kimbi-Fungom National Park, Cameroon.

RESEARCH HIGHLIGHTS: This study is one of few detailed analyses of plant diversity and vegetation patterns in African dry forests. We established permanent plots to characterize plant diversity, above-ground biomass, and vegetation patterns in a tropical dry forest in Kimbi-Fungom National Park, Cameroon. Our results contribute to long-term monitoring, predictions, and management of dry forest ecosystems, which are often vulnerable to anthropogenic pressures. BACKGROUND AND OBJECTIVES: Considerable consensus exists regarding the importance of dry forests in species diversity and carbon storage; however, the relationship between dry forest tree species composition, species richness, and carbon stock is not well established. Also, simple baseline data on plant diversity are scarce for many dry forest ecosystems. This study seeks to characterize floristic diversity, vegetation patterns, and tree diversity in permanent plots in a tropical dry forest in Northwestern Cameroon (Kimbi-Fungom National Park) for the first time. MATERIALS AND METHODS: We studied associations between above-ground biomass and species composition, and how different vegetation types vary in terms of species composition, diversity, and carbon storage, in a dry forest in Kimbi-Fungom National Park, Cameroon. Vegetation was inventoried in 17 permanent 1-ha plots. Allometric equations were used to calculate above-ground biomass and carbon. RESULTS: We found an average of 269.8 tree stems ha-1 and 43.1 species ha-1. Five vegetation types: semi-deciduous, gallery, mixed vegetation, secondary and the grassland/woody savanna forest were classified using TWINSPAN analysis. The five vegetation types had an average above-ground biomass of 149.2 t ha-1 and 74.6 tC ha-1 of carbon in the 17 ha analyzed. Canonical correspondence analysis (CCA) showed the importance of semi-deciduous forest over grassland/woody savanna forest. CONCLUSIONS: This study demonstrated that the forest of the Kimbi-Fungom National Park is poor in plant diversity, biomass, and carbon, highlighting the need to implement efficient management practices. Fine-scale inventory data of species obtained in this study could be useful in developing predictive models for efficient management of tropical dry forests.

The Galabat-Metema cross-border onchocerciasis focus: The first coordinated interruption of onchocerciasis transmission in Africa.

BACKGROUND: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. METHODS/PRINCIPLE FINDINGS: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission. CONCLUSION: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed.