The phosphorylation landscape of infection-related development by the rice blast fungus.

Many of the world's most devastating crop diseases are caused by fungal pathogens that elaborate specialized infection structures to invade plant tissue. Here, we present a quantitative mass-spectrometry-based phosphoproteomic analysis of infection-related development by the rice blast fungus Magnaporthe oryzae, which threatens global food security. We mapped 8,005 phosphosites on 2,062 fungal proteins following germination on a hydrophobic surface, revealing major re-wiring of phosphorylation-based signaling cascades during appressorium development. Comparing phosphosite conservation across 41 fungal species reveals phosphorylation signatures specifically associated with biotrophic and hemibiotrophic fungal infection. We then used parallel reaction monitoring (PRM) to identify phosphoproteins regulated by the fungal Pmk1 MAPK that controls plant infection by M. oryzae. We define 32 substrates of Pmk1 and show that Pmk1-dependent phosphorylation of regulator Vts1 is required for rice blast disease. Defining the phosphorylation landscape of infection therefore identifies potential therapeutic interventions for the control of plant diseases.

Barley MLA3 recognizes the host-specificity effector Pwl2 from Magnaporthe oryzae.

Plant nucleotide-binding leucine-rich repeat (NLRs) immune receptors directly or indirectly recognize pathogen-secreted effector molecules to initiate plant defense. Recognition of multiple pathogens by a single NLR is rare and usually occurs via monitoring for changes to host proteins; few characterized NLRs have been shown to recognize multiple effectors. The barley (Hordeum vulgare) NLR gene Mildew locus a (Mla) has undergone functional diversification, and the proteins encoded by different Mla alleles recognize host-adapted isolates of barley powdery mildew (Blumeria graminis f. sp. hordei [Bgh]). Here, we show that Mla3 also confers resistance to the rice blast fungus Magnaporthe oryzae in a dosage-dependent manner. Using a forward genetic screen, we discovered that the recognized effector from M. oryzae is Pathogenicity toward Weeping Lovegrass 2 (Pwl2), a host range determinant factor that prevents M. oryzae from infecting weeping lovegrass (Eragrostis curvula). Mla3 has therefore convergently evolved the capacity to recognize effectors from diverse pathogens.

Bioengineering a plant NLR immune receptor with a robust binding interface toward a conserved fungal pathogen effector.

Bioengineering of plant immune receptors has emerged as a key strategy for generating novel disease resistance traits to counteract the expanding threat of plant pathogens to global food security. However, current approaches are limited by rapid evolution of plant pathogens in the field and may lack durability when deployed. Here, we show that the rice nucleotide-binding, leucine-rich repeat (NLR) immune receptor Pik-1 can be engineered to respond to a conserved family of effectors from the multihost blast fungus pathogen Magnaporthe oryzae. We switched the effector binding and response profile of the Pik NLR from its cognate rice blast effector AVR-Pik to the host-determining factor pathogenicity toward weeping lovegrass 2 (Pwl2) by installing a putative host target, OsHIPP43, in place of the native integrated heavy metal-associated domain (generating Pikm-1OsHIPP43). This chimeric receptor also responded to other PWL alleles from diverse blast isolates. The crystal structure of the Pwl2/OsHIPP43 complex revealed a multifaceted, robust interface that cannot be easily disrupted by mutagenesis, and may therefore provide durable, broad resistance to blast isolates carrying PWL effectors in the field. Our findings highlight how the host targets of pathogen effectors can be used to bioengineer recognition specificities that have more robust properties compared to naturally evolved disease resistance genes.

Zinc-finger (ZiF) fold secreted effectors form a functionally diverse family across lineages of the blast fungus Magnaporthe oryzae.

Filamentous plant pathogens deliver effector proteins into host cells to suppress host defence responses and manipulate metabolic processes to support colonization. Understanding the evolution and molecular function of these effectors provides knowledge about pathogenesis and can suggest novel strategies to reduce damage caused by pathogens. However, effector proteins are highly variable, share weak sequence similarity and, although they can be grouped according to their structure, only a few structurally conserved effector families have been functionally characterized to date. Here, we demonstrate that Zinc-finger fold (ZiF) secreted proteins form a functionally diverse effector family in the blast fungus Magnaporthe oryzae. This family relies on the Zinc-finger motif for protein stability and is ubiquitously present in blast fungus lineages infecting 13 different host species, forming different effector tribes. Homologs of the canonical ZiF effector, AVR-Pii, from rice infecting isolates are present in multiple M. oryzae lineages. Wheat infecting strains of the fungus also possess an AVR-Pii like allele that binds host Exo70 proteins and activates the immune receptor Pii. Furthermore, ZiF tribes may vary in the proteins they bind to, indicating functional diversification and an intricate effector/host interactome. Altogether, we uncovered a new effector family with a common protein fold that has functionally diversified in lineages of M. oryzae. This work expands our understanding of the diversity of M. oryzae effectors, the molecular basis of plant pathogenesis and may ultimately facilitate the development of new sources for pathogen resistance.

The transcriptional landscape of plant infection by the rice blast fungus Magnaporthe oryzae reveals distinct families of temporally co-regulated and structurally conserved effectors.

The rice blast fungus Magnaporthe oryzae causes a devastating disease that threatens global rice (Oryza sativa) production. Despite intense study, the biology of plant tissue invasion during blast disease remains poorly understood. Here we report a high-resolution transcriptional profiling study of the entire plant-associated development of the blast fungus. Our analysis revealed major temporal changes in fungal gene expression during plant infection. Pathogen gene expression could be classified into 10 modules of temporally co-expressed genes, providing evidence for the induction of pronounced shifts in primary and secondary metabolism, cell signaling, and transcriptional regulation. A set of 863 genes encoding secreted proteins are differentially expressed at specific stages of infection, and 546 genes named MEP (Magnaportheeffector protein) genes were predicted to encode effectors. Computational prediction of structurally related MEPs, including the MAX effector family, revealed their temporal co-regulation in the same co-expression modules. We characterized 32 MEP genes and demonstrate that Mep effectors are predominantly targeted to the cytoplasm of rice cells via the biotrophic interfacial complex and use a common unconventional secretory pathway. Taken together, our study reveals major changes in gene expression associated with blast disease and identifies a diverse repertoire of effectors critical for successful infection.

Genomic surveillance uncovers a pandemic clonal lineage of the wheat blast fungus.

Wheat, one of the most important food crops, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America and to guide preemptive wheat breeding for blast resistance.

Pattern and determinants of contraceptive use among the muslim women in Wajir and Lamu counties in Kenya: a cross-sectional study.

BACKGROUND: Improving access to family planning (FP) is associated with positive health benefits that includes averting nearly a third of all maternal deaths and 10% of childhood deaths. Kenya has made great strides in improving access to family planning services. However, amid this considerable progress, regional variation has been noted which begs the need for a clearer understanding of the the patterns and determinants that drive these inconsistencies. METHODS: We conducted a cross-sectional study that involved 663 Muslim women of reproductive age (15-49 years) from Wajir and Lamu counties in Kenya between March and October 2018.The objective of this study was to understand patterns and determinants of contraceptive use in two predominantly Muslim settings of Lamu and Wajir counties that have varying contraceptive uptake. Eligible women were interviewed using a semi-structured questionnaire containing socio-demographic information and history of family planning use. Simple and multiple logistic regression were used to identify determinants of family planning use. The results were presented as Crude Odds Ratio (COR) and Adjusted Odds Ratio (AOR) ratios at 95% confidence interval. A p-value of 0.05 was considered statistically significant. RESULTS: Of the 663 Muslim women of reproductive age consenting to participate in the study, 51.5%, n = 342 and 48.5%, n = 321 were from Lamu and Wajir County, respectively. The prevalence of women currently using contraceptive was 18.6% (n = 123). In Lamu, the prevalence was 32.8%, while in Wajir, it was 3.4%. The determinants of current contraceptive use in Lamu include; marital status, age at marriage, employment status, discussion with a partner on FP, acceptability of FP in culture, and willingness to obtain information on FP. While in Wajir, determinants of current contraceptive use were education, and the belief that family planning is allowed in Islam. CONCLUSIONS: Our study found moderately high use of contraceptives among Muslim women of reproductive age in Lamu county and very low contraceptive use among women in Wajir. Given the role of men in decision making, it is critical to design male involvement strategy particularly in Wajir where the male influence is very prominent. It is critical for the government to invest in women and girls' education to enhance their ability to make informed decisions; particularly in Wajir where FP uptake is low with low education attainment. Further, our findings highlight the need for culturally appropriate messages and involvement of religious leaders to demystify the myths and misconception around family planning and Islam particularly in Wajir.

Evaluating the effectiveness of the National Health Insurance Fund in providing financial protection to households with hypertension and diabetes patients in Kenya.

BACKGROUND: Non-communicable diseases (NCDs) can impose a substantial financial burden to households in the absence of an effective financial risk protection mechanism. The national health insurance fund (NHIF) has included NCD services in its national scheme. We evaluated the effectiveness of NHIF in providing financial risk protection to households with persons living with hypertension and/or diabetes in Kenya. METHODS: We carried out a prospective cohort study, following 888 households with at least one individual living with hypertension and/or diabetes for 12 months. The exposure arm comprised households that are enrolled in the NHIF national scheme, while the control arm comprised households that were not enrolled in the NHIF. Study participants were drawn from two counties in Kenya. We used the incidence of catastrophic health expenditure (CHE) as the outcome of interest. We used coarsened exact matching and a conditional logistic regression model to analyse the odds of CHE among households enrolled in the NHIF compared with unenrolled households. Socioeconomic inequality in CHE was examined using concentration curves and indices. RESULTS: We found strong evidence that NHIF-enrolled households spent a lower share (12.4%) of their household budget on healthcare compared with unenrolled households (23.2%) (p = 0.004). While households that were enrolled in NHIF were less likely to incur CHE, we did not find strong evidence that they are better protected from CHE compared with households without NHIF (OR = 0.67; p = 0.47). The concentration index (CI) for CHE showed a pro-poor distribution (CI: -0.190, p < 0.001). Almost half (46.9%) of households reported active NHIF enrolment at baseline but this reduced to 10.9% after one year, indicating an NHIF attrition rate of 76.7%. The depth of NHIF cover (i.e., the share of out-of-pocket healthcare costs paid by NHIF) among households with active NHIF was 29.6%. CONCLUSION: We did not find strong evidence that the NHIF national scheme is effective in providing financial risk protection to households with individuals living with hypertension and/diabetes in Kenya. This could partly be explained by the low depth of cover of the NHIF national scheme, and the high attrition rate. To enhance NHIF effectiveness, there is a need to revise the NHIF benefit package to include essential hypertension and/diabetes services, review existing provider payment mechanisms to explicitly reimburse these services, and extend the existing insurance subsidy programme to include individuals in the informal labour market.

Essential emergency and critical care as a health system response to critical illness and the COVID19 pandemic: what does it cost?

Essential Emergency and Critical Care (EECC) is a novel approach to the care of critically ill patients, focusing on first-tier, effective, low-cost, life-saving care and designed to be feasible even in low-resourced and low-staffed settings. This is distinct from advanced critical care, usually conducted in ICUs with specialised staff, facilities and technologies. This paper estimates the incremental cost of EECC and advanced critical care for the planning of care for critically ill patients in Tanzania and Kenya.The incremental costing took a health systems perspective. A normative approach based on the ingredients defined through the recently published global consensus on EECC was used. The setting was a district hospital in which the patient is provided with the definitive care typically provided at that level for their condition. Quantification of resource use was based on COVID-19 as a tracer condition using clinical expertise. Local prices were used where available, and all costs were converted to USD2020.The costs per patient day of EECC is estimated to be 1 USD, 11 USD and 33 USD in Tanzania and 2 USD, 14 USD and 37 USD in Kenya, for moderate, severe and critical COVID-19 patients respectively. The cost per patient day of advanced critical care is estimated to be 13 USD and 294 USD in Tanzania and USD 17 USD and 345 USD in Kenya for severe and critical COVID-19 patients, respectively.EECC is a novel approach for providing the essential care to all critically ill patients. The low costs and lower tech approach inherent in delivering EECC mean that EECC could be provided to many and suggests that prioritizing EECC over ACC may be a rational approach when resources are limited.

Characterization of Blast Resistance in a Diverse Rice Panel from Sub-Saharan Africa.

There is a recent unparalleled increase in demand for rice in sub-Saharan Africa, yet its production is affected by blast disease. Characterization of blast resistance in adapted African rice cultivars can provide important information to guide growers and rice breeders. We used molecular markers for known blast resistance genes (Pi genes; n = 21) to group African rice genotypes (n = 240) into similarity clusters. We then used greenhouse-based assays to challenge representative rice genotypes (n = 56) with African isolates (n = 8) of Magnaporthe oryzae which varied in virulence and genetic lineage. The markers grouped rice cultivars into five blast resistance clusters (BRC) which differed in foliar disease severity. Using stepwise regression, we found that the Pi genes associated with reduced blast severity were Pi50 and Pi65, whereas Pik-p, Piz-t, and Pik were associated with increased susceptibility. All rice genotypes in the most resistant cluster, BRC 4, possessed Pi50 and Pi65, the only genes that were significantly associated with reduced foliar blast severity. Cultivar IRAT109, which contains Piz-t, was resistant against seven African M. oryzae isolates, whereas ARICA 17 was susceptible to eight isolates. The popular Basmati 217 and Basmati 370 were among the most susceptible genotypes. These findings indicate that most tested genes were not effective against African blast pathogen collections. Pyramiding genes in the Pi2/9 multifamily blast resistance cluster on chromosome 6 and Pi65 on chromosome 11 could confer broad-spectrum resistance capabilities. To gain further insights into genomic regions associated with blast resistance, gene mapping could be conducted with resident blast pathogen collections. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Quality of life and factors associated among caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo, a cross-sectional study.

BACKGROUND: Ebola virus disease is a medical condition whose consequent effects on quality of life of patients. In the history of infectious diseases, there have been pathologies that have had significant repercussions for caregivers, healthcare providers and the community. OBJECTIVES: This study investigate determinants of quality of life among caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo. METHODS: This was a cross sectional study. The study sites were the two health districts of Beni and Katwa, in North-Kivu province in the Eastern part of Democratic Republic of the Congo. The study period was from April to August 2022. Participants of the study were caregivers of adolescents and young adult Ebola virus survivors. Simple random sampling technique was used to select the 68 study participants. A questionnaire was administered. Data was collected using pretested questionnaire of WHO quality of life Bref (WHOQOL-BREF) and CommCare by Dimagi.Inc. lastest Version 2.52.1 and  a sum of score of 78 or higher indicated a high level of life quality. To determine the quality of life of caregivers of adolescents and young adult EVD survivors, descriptive analysis was used. The Pearson correlation coefficient was utilized to check whether the predictor variables are multicollinear. The regression analysis produced the crude odds ratio (COR), adjusted odds ratio (aOR), 95% confidence interval (CI), and p-value. Statistical significance was defined as a p-value 0.05. The final multivariate model contained variables that were significant in the bivariate analysis. Prior to data collection, a research permit from National Ethical Committee of Research in Democratic Republic of the Congo was obtained. Written informed consents from literate or illiterate caregivers of adolescent and young adult Ebola survivors were obtained. Throughout the study, participants' privacy and confidentiality were respected. RESULTS: A total of 68 care givers participated in the study, with a majority 54/68(79.41%) having poor quality of life. Men were 3.17 times more likely to record good quality of life than women (p = 0.02); OR:(95% CI), 3.17: (1.2 - 8.36), With regards to place of residence, caregivers who lived in town were less likely to have good quality of life compared to those in rural (p = 0.01); OR: (95%CI), 0.25: (0.09 - 0.72). CONCLUSION: The quality of life of caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo is poor. To be woman caregiver and to live in town are determinants associated with poor quality of life among caregivers of adolescent and young adult Ebola survivors.

Prevalence and determinants of contraception utilization over time in Migori County, Kenya: Repeated cross-sectional household surveys.

Contraception use and family planning have been shown to save lives and benefit women, their families, and their communities. We conducted a cross-sectional study analyzing data from a 2021 survey that was conducted across eight different regions in Migori County, Kenya to examine the potential role that different factors play in meeting family planning targets. Comparisons are made to data collected in 2018/2019 in order to estimate the change over time of contraception uptake. Descriptive statistics were calculated, the Cochran-Mantel-Haenszel test was used to compare contraception use over time, and multivariable logistic regression was used to model determinants of contraceptive use. Sixty-four percent of respondents in 2021 reported that they currently use some form of contraception, and implants are the most popular contraceptive method. Factors associated with higher contraception usage were region, ages 25-34 years, and marital status. Contraception uptake increased significantly in East Kamagambo following a community-driven sexual and reproductive health intervention by the Lwala Community Alliance, suggesting that increased investment in family planning may be influential. We recommend targeted outreach to population groups with low uptake of contraception and investment in both demand- and supply-side interventions to increase contraceptive uptake. Additional research, especially for populations under 18, is needed to further inform effective investment and policy.

Comparing travel behaviour characteristics and correlates between large and small Kenyan cities (Nairobi versus Kisumu).

Understanding urban travel behaviour is crucial for planning healthy and sustainable cities. Africa is urbanising at one of the fastest rates in the world and urgently needs this knowledge. However, the data and literature on urban travel behaviour, their correlates, and their variation across African cities are limited. We aimed to describe and compare travel behaviour characteristics and correlates of two Kenyan cities (Nairobi and Kisumu). We analysed data from 16,793 participants (10,000 households) in a 2013 Japan International Cooperation Agency (JICA) household travel survey in Nairobi and 5790 participants (2760 households) in a 2016 Institute for Transportation and Development Policy (ITDP) household travel survey in Kisumu. We used the Heckman selection model to explore correlations of travel duration by trip mode. The proportion of individuals reporting no trips was far higher in Kisumu (47% vs 5%). For participants with trips, the mean number [lower - upper quartiles] of daily trips was similar (Kisumu (2.2 [2-2] versus 2.4 [2-2] trips), but total daily travel durations were lower in Kisumu (65 [30-80] versus 116 [60-150] minutes). Walking was the most common trip mode in both cities (61% in Kisumu and 42% in Nairobi), followed by motorcycles (17%), matatus (minibuses) (11%), and cars (5%) in Kisumu; and matatus (28%), cars (12%) and buses (12%) in Nairobi. In both cities, females were less likely to make trips, and when they did, they travelled for shorter durations; people living in households with higher incomes were more likely to travel and did so for longer durations. Gender, income, occupation, and household vehicle ownership were associated differently with trip making, use of transport modes and daily travel times in cities. These findings illustrate marked differences in reported travel behaviour characteristics and correlates within the same country, indicating setting-dependent influences on travel behaviour. More sub-national data collection and harmonisation are needed to build a more nuanced understanding of patterns and drivers of travel behaviour in African cities.

Efficacy of 3-day low dose quinine plus clindamycin versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children (CLINDAQUINE): an open-label randomized trial.

BACKGROUND: The World Health Organization recommends quinine plus clindamycin as first-line treatment of malaria in the first trimester of pregnancy and as a second-line treatment for uncomplicated falciparum malaria when artemisinin-based drug combinations are not available. The efficacy of quinine plus clindamycin was compared with that of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in children below 5 years of age. METHODS: An open-label, phase 3, randomized trial was conducted in western Kenya. Children aged 6-59 months with uncomplicated falciparum malaria were randomly assigned (1:1) via a computer-generated randomization list to receive 3 days of twice a day treatment with either oral quinine (20 mg/kg/day) plus clindamycin (20 mg/kg/day) or artemether-lumefantrine (artemether 20 mg, lumefantrine 120 mg) as one (for those weighing 5-14 kg) or two (for those weighing 15-24 kg) tablets per dose. The primary outcome was a PCR-corrected rate of adequate clinical and parasitological response (ACPR) on day 28 in the per-protocol population. RESULTS: Of the 384 children enrolled, 182/192 (94.8%) receiving quinine plus clindamycin and 171/192 (89.1%) receiving artemether-lumefantrine completed the study. The PCR-corrected ACPR rate was 44.0% (80 children) in the quinine plus clindamycin group and 97.1% (166 children) in the artemether-lumefantrine group (treatment difference - 53.1%, 95% CI - 43.5% to - 62.7%). At 72 h after starting treatment, 50.3% (94 children) in the quinine plus clindamycin group were still parasitaemic compared with 0.5% (1 child) in the artemether-lumefantrine group. Three cases of severe malaria were recorded as serious adverse events in the quinine plus clindamycin group. CONCLUSIONS: The study found no evidence to support the use of a 3-day low dose course of quinine plus clindamycin in the treatment of uncomplicated falciparum malaria in children under 5 years of age in Kenya, where artemether-lumefantrine is still effective. TRIAL REGISTRATION: This trial is registered with the Pan-African Clinical Trials Registry, PACTR20129000419241.

Comparison of household socioeconomic status classification methods and effects on risk estimation: lessons from a natural experimental study, Kisumu, Western Kenya.

INTRODUCTION: Low household socioeconomic status is associated with unhealthy behaviours including poor diet and adverse health outcomes. Different methods leading to variations in SES classification has the potential to generate spurious research findings or misinform policy. In low and middle-income countries, there are additional complexities in defining household SES, a need for fieldwork to be conducted efficiently, and a dearth of information on how classification could impact estimation of disease risk. METHODS: Using cross-sectional data from 200 households in Kisumu County, Western Kenya, we compared three approaches of classifying households into low, middle, or high SES: fieldworkers (FWs), Community Health Volunteers (CHVs), and a Multiple Correspondence Analysis econometric model (MCA). We estimated the sensitivity, specificity, inter-rater reliability and misclassification of the three methods using MCA as a comparator. We applied an unadjusted generalized linear model to determine prevalence ratios to assess the association of household SES status with a self-reported diagnosis of diabetes or hypertension for one household member. RESULTS: Compared with MCA, FWs successfully classified 21.7% (95%CI = 14.4%-31.4%) of low SES households, 32.8% (95%CI = 23.2-44.3) of middle SES households, and no high SES households. CHVs successfully classified 22.5% (95%CI = 14.5%-33.1%) of low SES households, 32.8% (95%CI = 23.2%-44.3%) of middle SES households, and no high SES households. The level of agreement in SES classification was similar between FWs and CHVs but poor compared to MCA, particularly for high SES. None of the three methods differed in estimating the risk of hypertension or diabetes. CONCLUSIONS: FW and CHV assessments are community-driven methods for SES classification. Compared to MCA, these approaches appeared biased towards low or middle SES households and not sensitive to high household SES. The three methods did not differ in risk estimation for diabetes and hypertension. A mix of approaches and further evaluation to refine SES classification methodology is recommended.

Trends and determinants of adolescent pregnancy: Results from Kenya demographic health surveys 2003-2014.

BACKGROUND: Adolescent pregnancy increases the risk of disability and death due to unsafe abortion, prolonged labour and delivery, and complications after birth. Availability of accurate data is important to guide decision-making related to adolescent sexual reproductive health (ASRH). This study analyses the trends in prevalence and factors associated with adolescent pregnancy in Kenya using data from three national Demographic Health Surveys (2003, 2008/2009, 2014). METHODS: Our analysis focused on a subsample of data collected from women aged 20 to 24 years. A trend analysis was performed to establish a change in the rate of adolescent pregnancy in 2003, 2008/2009, and 2014 survey data points. Binary Logistic regression and pooled regression analysis were used to explore factors associated with adolescent pregnancy. RESULTS: The percentage of women aged 20 to 24 years who reported their first pregnancy between ages 15 and 19 years was 42% in 2003 and 42.2% in 2009 but declined to 38.9% in 2014. Using regression analyses, we established that education status, marital status, religion and wealth quintile were associated with adolescent pregnancy. Trend analysis shows that there was an overall decreasing trend in adolescent pregnancy between 2003 and 2014. CONCLUSION: Although Kenya has made strides in reducing the prevalence of adolescent pregnancy in the last decade, much more needs to be done to further reduce the burden, which remains high. DEFINITION: Adolescents: Although WHO defines the adolescence period as being 10-19 years, this paper focuses on the late adolescent period, 15-19 years, here in referred to as adolescents.

Navigating the local foodscape: qualitative investigation of food retail and dietary preferences in Kisumu and Homa Bay Counties, western Kenya.

INTRODUCTION: Non-communicable diseases have risen markedly over the last decade. A phenomenon that was mainly endemic in high-income countries has now visibly encroached on low and middle-income settings. A major contributor to this is a shift towards unhealthy dietary behavior. This study aimed to examine the complex interplay between people's characteristics and the environment to understand how these influenced food choices and practices in Western Kenya. METHODS: This study used semi-structured guides to conduct in-depth interviews and focus group discussions with both male and female members of the community, across various socioeconomic groups, from Kisumu and Homa Bay Counties to further understand their perspectives on the influences of dietary behavior. Voice data was captured using digital voice recorders, transcribed verbatim, and translated to English. Data analysis adopted an exploratory and inductive analysis approach. Coded responses were analyzed using NVIVO 12 PRO software. RESULTS: Intrapersonal levels of influence included: Age, the nutritional value of food, occupation, perceived satiety of some foods as opposed to others, religion, and medical reasons. The majority of the participants mentioned location as the main source of influence at the community level reflected by the regional staple foodscape. Others include seasonality of produce, social pressure, and availability of food in the market. Pricing of food and distance to food markets was mentioned as the major macro-level influence. This was followed by an increase in population and road infrastructure. CONCLUSION: This study demonstrated that understanding dietary preferences are complex. Future interventions should not only consider intrapersonal and interpersonal influences when aiming to promote healthy eating among communities but also need to target the community and macro environments. This means that nutrition promotion strategies should focus on multiple levels of influence that broaden options for interventions. However, government interventions in addressing food access, affordability, and marketing remain essential to any significant change.

Impact of Community-Based Mass Testing and Treatment on Malaria Infection Prevalence in a High-Transmission Area of Western Kenya: A Cluster Randomized Controlled Trial.

BACKGROUND: Global gains toward malaria elimination have been heterogeneous and have recently stalled. Interventions targeting afebrile malaria infections may be needed to address residual transmission. We studied the efficacy of repeated rounds of community-based mass testing and treatment (MTaT) on malaria infection prevalence in western Kenya. METHODS: Twenty clusters were randomly assigned to 3 rounds of MTaT per year for 2 years or control (standard of care for testing and treatment at public health facilities along with government-sponsored mass long-lasting insecticidal net [LLIN] distributions). During rounds, community health volunteers visited all households in intervention clusters and tested all consenting individuals with a rapid diagnostic test. Those positive were treated with dihydroartemisinin-piperaquine. Cross-sectional community infection prevalence surveys were performed in both study arms at baseline and each year after 3 rounds of MTaT. The primary outcome was the effect size of MTaT on parasite prevalence by microscopy between arms by year, adjusted for age, reported LLIN use, enhanced vegetative index, and socioeconomic status. RESULTS: Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage across the 3 annual rounds ranged between 75.0% and 77.5% in year 1, and between 81.9% and 94.3% in year 2. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (95% confidence interval [CI], .79-1.08) and 0.92 (95% CI, .76-1.10) after year 1 and year 2, respectively. CONCLUSIONS: MTaT performed 3 times per year over 2 years did not reduce malaria parasite prevalence in this high-transmission area. CLINICAL TRIALS REGISTRATION: NCT02987270.

Piperaquine Pharmacokinetics during Intermittent Preventive Treatment for Malaria in Pregnancy.

Dihydroartemisinin-piperaquine (DP) is a long-acting artemisinin combination treatment that provides effective chemoprevention and has been proposed as an alternative antimalarial drug for intermittent preventive therapy in pregnancy (IPTp). Several pharmacokinetic studies have shown that dose adjustment may not be needed for the treatment of malaria in pregnancy with DP. However, there are limited data on the optimal dosing for IPTp. This study aimed to evaluate the population pharmacokinetics of piperaquine given as IPTp in pregnant women. Pregnant women were enrolled in clinical trials conducted in Kenya and Indonesia and treated with standard 3-day courses of DP, administered in 4- to 8-week intervals from the second trimester until delivery. Pharmacokinetic blood samples were collected for piperaquine drug measurements before each treatment round, at the time of breakthrough symptomatic malaria, and at delivery. Piperaquine population pharmacokinetic properties were investigated using nonlinear mixed-effects modeling with a prior approach. In total, data from 366 Kenyan and 101 Indonesian women were analyzed. The pharmacokinetic properties of piperaquine were adequately described using a flexible transit absorption (n = 5) followed by a three-compartment disposition model. Gestational age did not affect the pharmacokinetic parameters of piperaquine. After three rounds of monthly IPTp, 9.45% (95% confidence interval [CI], 1.8 to 26.5%) of pregnant women had trough piperaquine concentrations below the suggested target concentration (10.3 ng/ml). Translational simulations suggest that providing the full treatment course of DP at monthly intervals provides sufficient protection to prevent malaria infection. Monthly administration of DP has the potential to offer optimal prevention of malaria during pregnancy. (This study has been registered at ClinicalTrials.gov under identifier NCT01669941 and in the ISRCTN under number ISRCTN34010937.).

Chitosan inhibits septin-mediated plant infection by the rice blast fungus Magnaporthe oryzae in a protein kinase C and Nox1 NADPH oxidase-dependent manner.

Chitosan is a partially deacetylated linear polysaccharide composed of ß-1,4-linked units of d-glucosamine and N-acetyl glucosamine. As well as a structural component of fungal cell walls, chitosan is a potent antifungal agent. However, the mode of action of chitosan is poorly understood. Here, we report that chitosan is effective for control of rice blast disease. Chitosan application impairs growth of the blast fungus Magnaporthe oryzae and has a pronounced effect on appressorium-mediated plant infection. Chitosan inhibits septin-mediated F-actin remodelling at the appressorium pore, thereby preventing repolarization of the infection cell. Chitosan causes plasma membrane permeabilization of M. oryzae and affects NADPH oxidase-dependent synthesis of reactive oxygen species, essential for septin ring formation and fungal pathogenicity. We further show that toxicity of chitosan to M. oryzae requires the protein kinase C-dependent cell wall integrity pathway, the Mps1 mitogen-activated protein kinase and the Nox1 NADPH oxidase. A conditionally lethal, analogue (PP1)-sensitive mutant of Pkc1 is partially remediated for growth in the presence of chitosan, while ∆nox1 mutants increase their glucan : chitin cell wall ratio, rendering them resistant to chitosan. Taken together, our data show that chitosan is a potent fungicide which requires the cell integrity pathway, disrupts plasma membrane function and inhibits septin-mediated plant infection.