Subnational Projections of Lymphatic Filariasis Elimination Targets in Ethiopia to Support National Level Policy.

BACKGROUND: Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030. METHODS: Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level. RESULTS: Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets. CONCLUSIONS: The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions.

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. METHODS: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. RESULTS: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. CONCLUSIONS: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.

Effect of the Nonpathogenic Strain Fusarium oxysporum FO12 on Fe Acquisition in Rice (Oryza sativa L.) Plants.

Rice (Oryza sativa L.) is a very important cereal worldwide, since it is the staple food for more than half of the world's population. Iron (Fe) deficiency is among the most important agronomical concerns in calcareous soils where rice plants may suffer from this deficiency. Current production systems are based on the use of high-yielding varieties and the application of large quantities of agrochemicals, which can cause major environmental problems. The use of beneficial rhizosphere microorganisms is considered a relevant sustainable alternative to synthetic fertilizers. The main goal of this study was to determine the ability of the nonpathogenic strain Fusarium oxysporum FO12 to induce Fe-deficiency responses in rice plants and its effects on plant growth and Fe chlorosis. Experiments were carried out under hydroponic system conditions. Our results show that the root inoculation of rice plants with FO12 promotes the production of phytosiderophores and plant growth while reducing Fe chlorosis symptoms after several days of cultivation. Moreover, Fe-related genes are upregulated by FO12 at certain times in inoculated plants regardless of Fe conditions. This microorganism also colonizes root cortical tissues. In conclusion, FO12 enhances Fe-deficiency responses in rice plants, achieves growth promotion, and reduces Fe chlorosis symptoms.

Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice.

The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignant Pax5+/- B-cell precursors toward leukemia. Transcriptional profiling reveals that Myd88 is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction of Myd88 expression leads to a significant increase in leukemia incidence in Pax5+/-Myd88+/- mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development in Pax5+/- mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children.

Diversity and composition of beetle assemblages attracted to dung in cloud forests under active and passive restoration practices.

Ecosystem loss and degradation has become a worldwide concern. The implementation of ecological restoration plans has been proposed to facilitate the recovery of ecosystems. It is imperative that once restoration strategies have been implemented, the effects of these actions in the medium and long term be evaluated, particularly the structure and functioning of the ecosystem. Diversity (α- and ß-diversity) of beetles attracted to dung was assessed and compared in 3 habitat conditions (conserved forest, passive restoration, and active restoration) at 2 different seasons during the year (dry vs. rainy season) in cloud forest in San Luis Potosí (central Mexico). We found that the dry season was slightly richer than the rainy season, but the latter was significantly more diverse. Species diversity and composition in active restoration were more similar to passive restoration, and both differed greatly from the conserved forest. In contrast, conserved and passive restoration conditions exhibited similar patterns in ß-diversity of insects likely because they maintain more species associated with the original vegetation of the cloud forest. Beetle assemblages could be of more habitat generalists, as they actively distribute across the restoration sites. Beetles attracted to dung provide an overview of the effect of restoration in early faunal recovery, even though we monitored this entomofauna for a short period (31 months after the restoration plots were established). These beetles can be a useful indicator for exploring the main forces driving species diversity for the management and conservation status of cloud forests, a threatened ecosystem.

Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma.

The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK-MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials.

Preventable risk factors for type 2 diabetes can be detected using noninvasive spontaneous electroretinogram signals.

Given the ever-increasing prevalence of type 2 diabetes and obesity, the pressure on global healthcare is expected to be colossal, especially in terms of blindness. Electroretinogram (ERG) has long been perceived as a first-use technique for diagnosing eye diseases, and some studies suggested its use for preventable risk factors of type 2 diabetes and thereby diabetic retinopathy (DR). Here, we show that in a non-evoked mode, ERG signals contain spontaneous oscillations that predict disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome but not yet diabetes, using one single random forest-based model. Classification performance was both internally and externally validated, and correlation analysis showed that the spontaneous oscillations of the non-evoked ERG are altered before oscillatory potentials, which are the current gold-standard for early DR. Principal component and discriminant analysis suggested that the slow frequency (0.4-0.7 Hz) components are the main discriminators for our predictive model. In addition, we established that the optimal conditions to record these informative signals, are 5-minute duration recordings under daylight conditions, using any ERG sensors, including ones working with portative, non-mydriatic devices. Our study provides an early warning system with promising applications for prevention, monitoring and even the development of new therapies against type 2 diabetes.

Selecting tree species to restore forest under climate change conditions: Complementing species distribution models with field experimentation.

The long-term success of forest restoration programs can be improved using climate-based species distribution models (SDMs) to predict which tree species will tolerate climate change. However, as SDMs cannot estimate if species will recruit at these habitats, determining whether their predictions apply to early life-cycle stages of trees is critical to support such a usage. For this, we propose sowing seeds of the focal tree species under the current climate and simulated climate change conditions in target restoration sites. Thus, using of SDMs to design climate-adaptive forest restoration programs would be supported if the differences in habitat occupancy probabilities of species they predict between the current and future climate concurs with the observed differences in recruitment rates of species when sowed under the current climate and simulated climate change conditions. To test this hypothesis, we calibrated SDMs for Vachellia pennatula and Prosopis laevigata, two pioneer tree species widely recommended to restore human-degraded drylands in Mexico, and transferred them to climate change scenarios. After that, we applied the experimental approach proposed above to validate the predictions of SDMs. These models predicted that V. pennatula will decrease its habitat occupancy probabilities across Mexico, while P. laevigata was predicted to keep out their current habitat occupancy probabilities, or even increase them, in climate change scenarios. The results of the field experiment supported these predictions, as recruitment rates of V. pennatula were lower under simulated climate change than under the current climate, while no differences were found for the recruitment rates of P. laevigata between these environmental conditions. These findings demonstrate that SDMs provide meaningful insights for designing climate-adaptive forest restoration programs but, before applying this methodology, predictions of these models must be validated with field experiments to determine whether the focal tree species will recruit under climate change conditions. Moreover, as the pioneer trees used to test our proposal seem to be differentially sensitive to climate change, this approach also allows establishing what species must be prescribed to restore forests with a view to the future and what species must be avoided in these practices.

Responding to the cuts in UK AID to neglected tropical diseases control programmes in Africa.

The early termination of the Accelerating the Sustainable Control and Elimination of Neglected Tropical Diseases (Ascend) programme by the UK government in June 2021 was a bitter blow to countries in East and West Africa where no alternative source of funding existed. Here we assess the potential impact the cuts may have had if alternative funding had not been made available by new development partners and outline new strategies developed by affected countries to mitigate current and future disruptions to neglected tropical disease control programmes.

Geostatistical modelling of the distribution, risk and burden of podoconiosis in Kenya.

BACKGROUND: Understanding and accurately predicting the environmental limits, population at risk and burden of podoconiosis are critical for delivering targeted and equitable prevention and treatment services, planning control and elimination programs and implementing tailored case finding and surveillance activities. METHODS: This is secondary analysis of a nationwide podoconiosis mapping survey in Kenya. We combined national representative prevalence survey data of podoconiosis with climate and environmental data, overlayed with population figures in a geostatistical modelling framework, to predict the environmental suitability, population living in at-risk areas and number of cases of podoconiosis in Kenya. RESULTS: In 2020, the number of people living with podoconiosis in Kenya was estimated to be 9344 (95% uncertainty interval 4222 to 17 962). The distribution of podoconiosis varies by geography and three regions (Eastern, Nyanza and Western) represent >90% of the absolute number of cases. High environmental suitability for podoconiosis was predicted in four regions of Kenya (Coastal, Eastern, Nyanza and Western). In total, 2.2 million people live in at-risk areas and 4.2% of the total landmass of Kenya is environmentally predisposed for podoconiosis. CONCLUSIONS: The burden of podoconiosis is relatively low in Kenya and is mostly restricted to certain small geographical areas. Our results will help guide targeted prevention and treatment approaches through local planning, spatial targeting and tailored surveillance activities.

Estimating the burden of mycetoma in Sudan for the period 1991-2018 using a model-based geostatistical approach.

Mycetoma is widespread in tropical and subtropical regions favouring arid areas with low humidity and a short rainy season. Sudan is one of the highly endemic countries for mycetoma. Estimating the population at risk and the number of cases is critical for delivering targeted and equitable prevention and treatment services. In this study, we have combined a large dataset of mycetoma cases recorded by the Mycetoma Research Centre (MRC) in Sudan over 28 years (1991-2018) with a collection of environmental and water and hygiene-related datasets in a geostatistical framework to produce estimates of the disease burden across the country. We developed geostatistical models to predict the number of cases of actinomycetoma and eumycetoma in areas considered environmentally suitable for the two mycetoma forms. Then used the raster dataset (gridded map) with the population estimates for 2020 to compute the potentially affected population since 1991. The geostatistical models confirmed this heterogeneous and distinct distribution of the estimated cases of eumycetoma and actinomycetoma across Sudan. For eumycetoma, these higher-risk areas were smaller and scattered across Al Jazirah, Khartoum, White Nile and Sennar states, while for actinomycetoma a higher risk for infection is shown across the rural districts of North and West Kurdufan. Nationally, we estimated 63,825 people (95%CI: 13,693 to 197,369) to have been suffering from mycetoma since 1991 in Sudan,51,541 people (95%CI: 9,893-166,073) with eumycetoma and 12,284 people (95%CI: 3,800-31,296) with actinomycetoma. In conclusion, the risk of mycetoma in Sudan is particularly high in certain restricted areas, but cases are ubiquitous across all states. Both prevention and treatment services are required to address the burden. Such work provides a guide for future control and prevention programs for mycetoma, highly endemic areas are clearly targeted, and resources are directed to areas with high demand.

Prevalence and distribution pattern of malaria and soil-transmitted helminth co-endemicity in sub-Saharan Africa, 2000-2018: A geospatial analysis.

BACKGROUND: Limited understanding exists about the interactions between malaria and soil-transmitted helminths (STH), their potential geographical overlap and the factors driving it. This study characterised the geographical and co-clustered distribution patterns of malaria and STH infections among vulnerable populations in sub-Saharan Africa (SSA). METHODOLOGY/PRINCIPAL FINDINGS: We obtained continuous estimates of malaria prevalence from the Malaria Atlas Project (MAP) and STH prevalence surveys from the WHO-driven Expanded Special Project for the Elimination of NTDs (ESPEN) from Jan 1, 2000, to Dec 31, 2018. Although, MAP provides datasets on the estimated prevalence of Plasmodium falciparum at 5km x 5km fine-scale resolution, we calculated the population-weighted prevalence of malaria for each implementation unit to ensure that both malaria and STH datasets were on the same spatial resolution. We incorporated survey data from 5,935 implementation units for STH prevalence and conducted the prevalence point estimates before and after 2003. We used the bivariate local indicator of spatial association (LISA analysis) to explore potential co-clustering of both diseases at the implementation unit levels among children aged 2-10 years for P. falciparum and 5-14 years for STH, living in SSA. Our analysis shows that prior to 2003, a greater number of SSA countries had a high prevalence of co-endemicity with P.falciparium and any STH species than during the period from 2003-2018. Similar prevalence and distribution patterns were observed for the co-endemicity involving P.falciparum-hookworm, P.falciparum-Ascaris lumbricoides and P.falciparum-Trichuris trichiura, before and after 2003. We also observed spatial variations in the estimates of the prevalence of P. falciparum-STH co-endemicity and identified hotspots across many countries in SSA with inter-and intra-country variations. High P. falciparum and high hookworm co-endemicity was more prevalent in West and Central Africa, whereas high P. falciparum with high A. lumbricoides and high P. falciparum with high T. trichiura co-endemicity were more predominant in Central Africa, compared to other sub-regions in SSA. CONCLUSIONS/SIGNIFICANCE: Wide spatial heterogeneity exists in the prevalence of malaria and STH co-endemicity within the regions and within countries in SSA. The geographical overlap and spatial co-existence of malaria and STH could be exploited to achieve effective control and elimination agendas through the integration of the vertical control programmes designed for malaria and STH into a more comprehensive and sustainable community-based paradigm.

Assessing the effect of environmental and socio-economic factors on skin melanoma incidence: an island-wide spatial study in Gran Canaria (Spain), 2007-2018.

INTRODUCTION: Skin melanoma incidence has risen in the last decades becoming a major public health problem in many regions of the world. Geographic variation of rates is not well understood. PURPOSE: To assess the spatial distribution of skin melanoma in Gran Canaria Island (Canary Islands, Spain) and to evaluate the role of environmental, socio-economic, and demographic factors in this distribution. METHODS: We performed a small-area study with disease mapping at the census-tract level (CT) in Gran Canaria between 2007 and 2018. After testing for spatial autocorrelation, we integrated individual-level health data with census-based demographic and socio-economic indicators, and satellite-based environmental data. Finally, we assessed the role of demographic, socio-economic and environmental factors on skin melanoma incidence using a Bayesian analytical framework, with options for non-spatial and spatial random effects. RESULTS: 1058 patients were diagnosed with invasive skin melanoma in the study period and geolocated to a CT (number of CT in Gran Canaria = 565). We found evidence of global spatial autocorrelation in skin melanoma incidence (Moran's I = 0.09, pseudo p-value = 0.001). A few hotspots were detected, fundamentally in urban northern tracts. A radial pattern of high values was also observed in selected ravines with historical isolation. Multivariable conditional autoregressive models identified urbanicity, percent of females, and a high socio-economic status as risk factors for disease. Solar radiation did not show a significant role. CONCLUSION: Urbanicity and a high socio-economic status were identified as the main risk factors for skin melanoma. These associations might reflect differential melanoma susceptibilities or be explained by health inequalities in detection. This study also uncovered high-risk areas in particular ravines. Future targeted research in these regions might help better understand the role of genetic and toxic factors in melanoma pathogenesis.

Childhood B-Cell Preleukemia Mouse Modeling.

Leukemia is the most usual childhood cancer, and B-cell acute lymphoblastic leukemia (B-ALL) is its most common presentation. It has been proposed that pediatric leukemogenesis occurs through a "multi-step" or "multi-hit" mechanism that includes both in utero and postnatal steps. Many childhood leukemia-initiating events, such as chromosomal translocations, originate in utero, and studies so far suggest that these "first-hits" occur at a far higher frequency than the incidence of childhood leukemia itself. The reason why only a small percentage of the children born with such preleukemic "hits" will develop full-blown leukemia is still a mystery. In order to better understand childhood leukemia, mouse modeling is essential, but only if the multistage process of leukemia can be recapitulated in the model. Therefore, mouse models naturally reproducing the "multi-step" process of childhood B-ALL will be essential to identify environmental or other factors that are directly linked to increased risk of disease.

Single-Nucleotide Polymorphisms in the Beta-Tubulin Gene and Its Relationship with Treatment Response to Albendazole in Human Soil-Transmitted Helminths in Southern Mozambique.

Soil-transmitted helminth (STH) cornerstone control strategy is mass drug administration (MDA) with benzimidazoles. However, MDA might contribute to selection pressure for anthelmintic resistance, as occurred in livestock. The aim of this study is to evaluate the treatment response to albendazole and the relationship with the presence of putative benzimidazole resistance single-nucleotide polymorphisms (SNPs) in the ß-tubulin gene of STH in Southern Mozambique. After screening 819 participants, we conducted a cohort study with 184 participants infected with STH in Manhiça district, Southern Mozambique. A pretreatment and a posttreatment stool samples were collected and the STH infection was identified by duplicate Kato-Katz and quantitative polymerase chain reaction (qPCR). Cure rate and egg reduction rates were calculated. Putative benzimidazole resistance SNPs (F167Y, F200T, and E198A) in Trichuris trichiura and Necator americanus were assessed by pyrosequencing. Cure rates by duplicate Kato-Katz and by qPCR were 95.8% and 93.6% for Ascaris lumbricoides, 28% and 7.8% for T. trichiura, and 88.9% and 56.7% for N. americanus. Egg reduction rate by duplicate Kato-Katz was 85.4% for A. lumbricoides, 34.9% for T. trichiura, and 40.5% for N. americanus. Putative benzimidazole resistance SNPs in the ß-tubulin gene were detected in T. trichiura (23%) and N. americanus (21%) infected participants at pretreatment. No statistical difference was observed between pretreatment and posttreatment frequencies for none of the SNPs. Although treatment response to albendazole was low, particularly in T. trichiura, the putative benzimidazole resistance SNPs were not higher after treatment in the population studied. New insights are needed for a better understanding and monitoring of human anthelmintic resistance.

Cattle-related risk factors for malaria in southwest Ethiopia: a cross-sectional study.

BACKGROUND: Despite the low to moderate intensity of malaria transmission present in Ethiopia, malaria is still a leading public health problem. Current vector control interventions, principally long-lasting insecticidal nets and indoor residual spraying, when deployed alone or in combination, are insufficient to control the dominant vector species due to their exophagic and exophilic tendencies. Zooprophylaxis presents a potential supplementary vector control method for malaria; however, supporting evidence for its efficacy has been mixed. METHODS: To identify risk factors of malaria and to estimate the association between cattle and Anopheles vector abundance as well as malaria risk, a cross-sectional study was conducted in a village near Arba Minch, Ethiopia. Epidemiological surveys (households = 95, individuals = 463), mosquito collections using CDC light traps and a census of cattle and human populations were conducted. To capture environmental conditions, land cover and water bodies were mapped using satellite imagery. Risk factor analyses were performed through logistic, Poisson, negative binomial, and spatial weighted regression models. RESULTS: The only risk factor associated with self-reported malaria illness at an individual level was being a child aged 5 or under, where they had three times higher odds than adults. At the household level, variables associated with malaria vector abundance, especially those indoors, included socioeconomic status, the proportion of children in a household and cattle population density. CONCLUSIONS: Study results are limited by the low abundance of malaria vectors found and use of self-reported malaria incidence. Environmental factors together with a household's socioeconomic status and host availability played important roles in the risk of malaria infection in southwest Ethiopia. Cattle abundance in the form of higher cattle to human ratios may act as a protective factor against mosquito infestation and malaria risk. Humans should remain indoors to maximize potential protection against vectors and cattle kept outside of homes.

Evaluation of antibody serology to determine current helminth and Plasmodium falciparum infections in a co-endemic area in Southern Mozambique.

BACKGROUND: Soil-transmitted helminths (STH), Schistosoma spp. and Plasmodium falciparum are parasites of major public health importance and co-endemic in many sub-Saharan African countries. Management of these infections requires detection and treatment of infected people and evaluation of large-scale measures implemented. Diagnostic tools are available but their low sensitivity, especially for low intensity helminth infections, leaves room for improvement. Antibody serology could be a useful approach thanks to its potential to detect both current infection and past exposure. METHODOLOGY: We evaluated total IgE responses and specific-IgG levels to 9 antigens from STH, 2 from Schistosoma spp., and 16 from P. falciparum, as potential markers of current infection in a population of children and adults from Southern Mozambique (N = 715). Antibody responses were measured by quantitative suspension array Luminex technology and their performance was evaluated by ROC curve analysis using microscopic and molecular detection of infections as reference. PRINCIPAL FINDINGS: IgG against the combination of EXP1, AMA1 and MSP2 (P. falciparum) in children and NIE (Strongyloides stercoralis) in adults and children had the highest accuracies (AUC = 0.942 and AUC = 0.872, respectively) as markers of current infection. IgG against the combination of MEA and Sm25 (Schistosoma spp.) were also reliable markers of current infection (AUC = 0.779). In addition, IgG seropositivity against 20 out of the 27 antigens in the panel differentiated the seropositive endemic population from the non-endemic population, suggesting a possible role as markers of exposure although sensitivity could not be assessed. CONCLUSIONS: We provided evidence for the utility of antibody serology to detect current infection with parasites causing tropical diseases in endemic populations. In addition, most of the markers have potential good specificity as markers of exposure. We also showed the feasibility of measuring antibody serology with a platform that allows the integration of control and elimination programs for different pathogens.

Neighbors' use of water and sanitation facilities can affect children's health: a cohort study in Mozambique using a spatial approach.

BACKGROUND: Impact evaluation of most water, sanitation and hygiene (WASH) interventions in health are user-centered. However, recent research discussed WASH herd protection - community WASH coverage could protect neighboring households. We evaluated the effect of water and sanitation used in the household and by household neighbors in children's morbidity and mortality using recorded health data. METHODS: We conducted a retrospective cohort including 61,333 children from a district in Mozambique during 2012-2015. We obtained water and sanitation household data and morbidity data from Manhiça Health Research Centre surveillance system. To evaluate herd protection, we estimated the density of household neighbors with improved facilities using a Kernel Density Estimator. We fitted negative binomial adjusted regression models to assess the minimum children-based incidence rates for every morbidity indicator, and Cox regression models for mortality. RESULTS: Household use of unimproved water and sanitation displayed a higher rate of outpatient visit, diarrhea, malaria, and anemia. Households with unimproved water and sanitation surrounded by neighbors with improved water and sanitation high coverage were associated with a lower rate of outpatient visit, malaria, anemia, and malnutrition. CONCLUSION: Household and neighbors' access to improve water and sanitation can affect children's health. Accounting for household WASH and herd protection in interventions' evaluation could foster stakeholders' investment and improve WASH related diseases control. Distribution of main water and sanitation facilities used during study period.

Transient Inhibition of the JAK/STAT Pathway Prevents B-ALL Development in Genetically Predisposed Mice.

Preventing development of childhood B-cell acute lymphoblastic leukemia (B-ALL), a disease with devastating effects, is a longstanding and unsolved challenge. Heterozygous germline alterations in the PAX5 gene can lead to B-ALL upon accumulation of secondary mutations affecting the JAK/STAT signaling pathway. Preclinical studies have shown that this malignant transformation occurs only under immune stress such as exposure to infectious pathogens. Here we show in Pax5+/- mice that transient, early-life administration of clinically relevant doses of ruxolitinib, a JAK1/2 inhibitor, significantly mitigates the risk of B-ALL following exposure to infection; 1 of 29 animals treated with ruxolitinib developed B-ALL versus 8 of 34 untreated mice. Ruxolitinib treatment preferentially targeted Pax5+/- versus wild-type B-cell progenitors and exerted unique effects on the Pax5+/- B-cell progenitor transcriptional program. These findings provide the first in vivo evidence for a potential strategy to prevent B-ALL development. SIGNIFICANCE: JAK/STAT inhibition suppresses tumorigenesis in a B-ALL-susceptible mouse model, presenting a novel approach to prevent B-ALL onset.

Recruitment of pioneer trees with physically dormant seeds under climate change: the case of Vachellia pennatula (Fabaceae) in semiarid environments of Mexico.

Most tree species native to arid and semiarid ecosystems produce seeds with physical dormancy, which have impermeable coats that protect them from desiccation and prevent germination when the environmental conditions are unfavorable for seedling establishment. This dormancy mechanism may confer some degree of tolerance to seeds facing warmer and drier conditions, as those expected in several regions of the world because of climate change. Scarification of these seeds (removal of protective coats) is required for stimulating germination and seedling development. However, as scarification exposes seeds to the external environmental conditions, it can promote desiccation and viability loss in the future. To test these hypotheses, we performed field experiments and sowed scarified and unscarified seeds of a pioneer tree native to semiarid ecosystems of Mesoamerica (Vachellia pennatula) under the current climate and simulated climate change conditions. The experiments were conducted at abandoned fields using open-top chambers to increase temperature and rainout shelters to reduce rainfall. We measured microenvironmental conditions within the experimental plots and monitored seedling emergence and survival during a year. Air temperature and rainfall in climate change simulations approached the values expected for the period 2041-2080. Seedling emergence rates under these climatic conditions were lower than under the current climate. Nevertheless, emergence rates in climate change simulations were even lower for scarified than for unscarified seeds, while the converse occurred under the current climate. On the other hand, although survival rates in climate change simulations were lower than under the current climate, no effects of the scarification treatment were found. In this way, our study suggests that climate change will impair the recruitment of pioneer trees in semiarid environments, even if they produce seeds with physical dormancy, but also indicates that these negative effects will be stronger if seeds are scarified.