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.

Cost-effectiveness of One Health intervention to reduce risk of human exposure and infection with non-typhoidal salmonellosis (NTS) in Nigeria.

Background: Non-typhoidal Salmonella infection (NTS) is an important foodborne zoonosis with underappreciated health and economic burdens, and low case fatality. It has global prevalence, with more burdens in under-resourced countries with poor health infrastructures. Using a cohort study, we determined the cost-effectiveness of NTS in humans in Nigeria for the year 2020. Methods: Using a customized Excel-based cost-effectiveness analysis tool, structured (One Health) and unstructured (episodic intervention against NTS) in Nigeria were evaluated. Input data on the disease burdens, costs surveillance, response and control of NTS were obtained from validated sources and the public health system. Results: The non-complicated and complicated cases were 309,444 (95%) and 16,287 (5%) respectively, and the overall programme cost was US$ 31,375,434.38. The current non-systematic episodic intervention costed US$ 14,913,480.36, indicating an additional US$ 16,461,954 to introduce the proposed intervention. The intervention will avert 4036.98 NTS DALYs in a single year. The non-complicated NTS case was US$ 60/person with significant rise in complicated cases. The cumulative costs of NTS with and without complications far outweighed the program cost for One Health intervention with an incremental cost-effectiveness ratio (ICER) of -US$ 221.30). Conclusions: Utilising structured One Health intervention is cost-effective against NTS in Nigeria, it carries additional mitigative benefits for other diseases and is less costly and more effective, indicative of a superior health system approach. Identified limitations must be improved to optimize benefits associated and facilitate policy discussions and resource allocation.

Efficacy of a Single Oral Dose of Artesunate plus Sulfalene-Pyrimethamineversus Praziquantel in the Treatment of Schistosoma mansoni in Kenyan Children: An Open-Label, Randomized, Exploratory Trial.

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.

Trends of non-vaccination, under-vaccination and missed opportunities for vaccination (2003-2014) amongst children 0-23 months in Kenya.

Vaccines are effective and cost-effective. Non-vaccination, under-vaccination, and missed opportunities for vaccination (MOV), have contributed to incomplete vaccination coverage in Kenya. Analyzing their trends is essential for targeting interventions and improvement strategies. This study aimed to assess trends of non-vaccination, under-vaccination, and MOV among children aged 0-23 months in Kenya using data obtained from the Kenya Demographic and Health Surveys (KDHS) conducted in 2003, 2008/09, and 2014. A two-stage, multi-stage, and stratified sampling technique was used. Weighted analysis was conducted to ensure generalizability to the full population. Using the KDHS sample size estimation process, the sample size was estimated for each indicator, with varying standard error estimates, level of coverage and estimated response rates. Final sample size was 2380 (2003), 2237 (2008/09) and 7380 (2014). To determine the level of non-vaccination, under-vaccination and MOV among children aged 0-23 months, a weighted descriptive analysis was used to estimate their prevalence, with 95% confidence intervals (CI) for each year. MOV was defined using an algorithm as a binary variable. Data coding and recoding were done using Stata (version 14; College Station, TX: StataCorp LP). Trends in proportions of non-vaccination, under-vaccination and MOV were compared between 2003, 2008/09, and 2014 using the Cochrane-Armitage trend test. All results with P≤0.05 were considered statistically significant. Trends in proportion of non-vaccination among children aged 0-23 months in Kenya was 13.2%, 6.1% and 3.2% in 2003, 2008/09 and 2014, respectively (P = 0.0001). Trends in proportion of under-vaccination among children aged 0-23 months in Kenya was 54.3%, 50% and 51.3% in 2003, 2008/09 and 2014, respectively (P = 0.0109). The trends in proportion of children who experienced MOV was 22.7% in 2003, 31.9% in 2008/09 and 37.6% in 2014 (P = 0.0001). In the study duration, non-vaccination decreased by 10%, under-vaccination remained relatively stable, and MOV increased by ~15%. There is need for the Government and partners to implement initiatives that improve vaccine access and coverage, particularly in regions with low coverage rates, and to address missed opportunities for vaccination.

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.

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.

SCHISTOACT: a protocol for an open-label, five-arm, non-inferiority, individually randomized controlled trial of the efficacy and safety of praziquantel plus artemisinin-based combinations in the treatment of Schistosoma mansoni infection.

BACKGROUND: Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya. METHODS: The SCHISTOACT study is an open-label, head-to-head, five-arm, proof-of-concept, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-aged children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine, or artesunate-amodiaquine, or artesunate plus mefloquine, or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at - 10 for the risk difference in cure rates between praziquantel and the combined treatment. DISCUSSION: This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis and to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases. TRIAL REGISTRATION: Pan-African Clinical Trials Registry PACTR202001919442161 . Retrospectively registered on 6 January 2020.

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.

The effectiveness of combined approaches towards improving utilisation of adolescent sexual and reproductive health services in Kenya: a quasi-experimental evaluation.

Adolescent sexual and reproductive health (ASRH) services are key to improving the health of adolescents. This study aimed to establish the effectiveness of an intervention that combined activities in health facilities and communities in Kenya to increase utilisation of ASRH services. A quasi-experimental evaluation design was used to assess the effectiveness of the intervention. Using a stratified cluster sampling approach, two cross-sectional household surveys targeting girls aged 15-19 were conducted at baseline (September 2019) and endline (December 2020) in intervention and comparison. We combined the difference-in-difference approach to analyse the net change in outcomes between intervention and comparison arms of the study at baseline and endline and coarsened exact matching for variables that were significantly different to address the imbalance. There were a total of 1011 participants in the intervention arm and 880 in the comparison arm. Descriptive results showed a net increase of 12.7% in intervention sites in the knowledge of misconceptions about sex, pregnancy, and contraception, compared to 10.4% in the control site. In the multivariate regression analysis, two outcomes remained significant: decreases in adolescents' discomfort when seeking ASRH services because of either fear of parents (aPR = 0.58, 95% CI = 0.42-0.79, P = 0.001) or a lack of support from their partner (aPR = 0.25, 95% CI = 0.08-0.82, P = 0.023). The intervention combining a facility and community approach was not effective in increasing the use of ASRH information and services. Possible reasons for this are explored.

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.

Childhood mortality and associated factors in Migori County, Kenya: evidence from a cross-sectional survey.

OBJECTIVES: The under-five mortality (U5M) rate in Kenya (41 per 1000 live births) remains significantly above international goals (25 per 1000 live births). This is further exacerbated by regional inequalities in mortality. We aimed to describe U5M in Migori County, Kenya, and identify associated factors that can serve as programming targets. DESIGN: Cross-sectional observational survey. SETTING: Areas served by the Lwala Community Alliance and control areas in Migori County, Kenya. PARTICIPANTS: This study included 15 199 children born to respondents during the 18 years preceding the survey. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was mortality in the first 5 years of life. The survey was powered to detect a 10% change in various health metrics over time with 80% power. RESULTS: A total of 15 199 children were included in the primary analyses, and 230 (1.5%) were deceased before the fifth birthday. The U5M rate from 2016 to 2021 was 32.2 per 1000 live births. Factors associated with U5M included year of birth (HR 0.926, p<0.001), female sex (HR 0.702, p=0.01), parental marriage (HR 0.642, p=0.036), multiple gestation pregnancy (HR 2.776, p<0.001), birth spacing less than 18 months (HR 1.894, p=0.005), indoor smoke exposure (HR 1.916, p=0.027) and previous familial contribution to the National Hospital Insurance Fund (HR 0.553, p=0.009). The most common cause of death was malaria. CONCLUSIONS: We describe factors associated with childhood mortality in a Kenyan community using survival analyses of complete birth histories. Mortality rates will serve as the baseline for future programme evaluation as a part of a 10-year study design. This provides both the hyperlocal information needed to improve programming and generalisable conclusions for other organisations working in similar environments.

Examining the responsiveness of the National Health Insurance Fund to people living with hypertension and diabetes in Kenya: a qualitative study.

OBJECTIVES: To assess the responsiveness of the National Health Insurance Fund (NHIF) Supa Cover benefit package to the needs of individuals with diabetes and hypertension in Kenya. DESIGN, SETTING AND PARTICIPANTS: We carried out a qualitative study and collected data using key informant interviews (n=39) and focus group discussions (n=4) in two purposively selected counties in Western Kenya. Study participants were drawn from NHIF officials, county government officials, health facility managers, healthcare workers and individuals with hypertension and diabetes who were enrolled in NHIF. We analysed data using a thematic approach. RESULTS: Study participants reported that the NHIF Supa Cover benefit package expanded access to services for people living with hypertension and diabetes. However, the NHIF members and healthcare workers had inadequate awareness of the NHIF service entitlements. The NHIF benefit package inadequately covered the range of services needed by people living with hypertension and diabetes and the benefits package did not prioritise preventive and promotive services. Sometimes patients were discriminated against by healthcare providers who preferred cash-paying patients, and some NHIF-empanelled health facilities had inadequate structural inputs essential for quality of care. Study participants felt that the NHIF premium for the general scheme was unaffordable, and NHIF members faced additional out-of-pocket costs because of additional payments for services not available or covered. CONCLUSION: Whereas NHIF has reduced financial barriers for hypertension and diabetes patients, to enhance its responsiveness to patient needs, NHIF should implement mechanisms to increase benefit package awareness among members and providers. In addition, preventive and promotive services should be included in NHIF's benefits package and mechanisms to monitor and hold contracted providers accountable should be strengthened.

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.

Impact, cost-effectiveness, and budget implications of HPV vaccination in Kenya: A modelling study.

BACKGROUND: Sub-Saharan Africa has the highest rate of cervical cancer cases and deaths worldwide. Kenya introduced a quadrivalent HPV vaccine (GARDASIL, hereafter referred to as GARDASIL-4) for ten-year-old girls in late 2019 with donor support from Gavi, the Vaccine Alliance. As Kenya may soon graduate from Gavi support, it is important to evaluate the potential cost-effectiveness and budget impact of the current HPV vaccine, and potential alternatives. METHODS: We used a proportionate outcomes static cohort model to evaluate the annual budget impact and lifetime cost-effectiveness of vaccinating ten-year-old girls over the period 2020-2029. We included a catch-up campaign for girls aged 11-14 years in 2020. We estimated cervical cancer cases, deaths, disability adjusted life years (DALYs), and healthcare costs (government and societal perspective) expected to occur with and without vaccination over the lifetimes of each cohort of vaccinated girls. For each of the four products available globally (CECOLIN©, CERVARIX©, GARDASIL-4©, and GARDASIL-9 ©), we estimated the cost (2021 US$) per DALY averted compared to no vaccine and to each other. Model inputs were obtained from published sources, as well as local stakeholders. RESULTS: We estimated 320,000 cases and 225,000 deaths attributed to cervical cancer over the lifetimes of the 14 evaluated birth cohorts. HPV vaccination could reduce this burden by 42-60 %. Without cross-protection, CECOLIN had the lowest net cost and most attractive cost-effectiveness. With cross-protection, CERVARIX was the most cost-effective. Under either scenario the most cost-effective vaccine had a 100 % probability of being cost-effective at a willingness-to-pay threshold of US$ 100 (5 % of Kenya's national gross domestic product per capita) compared to no vaccination. Should Kenya reach its target of 90 % coverage and graduate from Gavi support, the undiscounted annual vaccine program cost could exceed US$ 10 million per year. For all three vaccines currently supported by Gavi, a single-dose strategy would be cost-saving compared to no vaccination. CONCLUSION: HPV vaccination for girls is highly cost-effective in Kenya. Compared to GARDASIL-4, alternative products could provide similar or greater health benefits at lower net costs. Substantial government funding will be required to reach and sustain coverage targets as Kenya graduates from Gavi support. A single dose strategy is likely to have similar benefits for less cost.

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.

Cost Effectiveness of Strategies for Caring for Critically Ill Patients with COVID-19 in Tanzania.

BACKGROUND: The resources for critical care are limited in many settings, exacerbating the significant morbidity and mortality associated with critical illness. Budget constraints can lead to choices between investing in advanced critical care (e.g. mechanical ventilators in intensive care units) or more basic critical care such as Essential Emergency and Critical Care (EECC; e.g. vital signs monitoring, oxygen therapy, and intravenous fluids). METHODS: We investigated the cost effectiveness of providing EECC and advanced critical care in Tanzania in comparison with providing 'no critical care' or 'district hospital-level critical care' using coronavirus disease 2019 (COVID-19) as a tracer condition. We developed an open-source Markov model ( https://github.com/EECCnetwork/POETIC_CEA ) to estimate costs and disability-adjusted life-years (DALYs) averted, using a provider perspective, a 28-day time horizon, patient outcomes obtained from an elicitation method involving a seven-member expert group, a normative costing study, and published literature. We performed a univariate and probabilistic sensitivity analysis to assess the robustness of our results. , RESULTS: EECC is cost effective 94% and 99% of the time when compared with no critical care (incremental cost-effectiveness ratio [ICER] $37 [-$9 to $790] per DALY averted) and district hospital-level critical care (ICER $14 [-$200 to $263] per DALY averted), respectively, relative to the lowest identified estimate of the willingness-to-pay threshold for Tanzania ($101 per DALY averted). Advanced critical care is cost effective 27% and 40% of the time, when compared with the no critical care or district hospital-level critical care scenarios, respectively. CONCLUSION: For settings where there is limited or no critical care delivery, implementation of EECC could be a highly cost-effective investment. It could reduce mortality and morbidity for critically ill COVID-19 patients, and its cost effectiveness falls within the range considered 'highly cost effective'. Further research is needed to explore the potential of EECC to generate even greater benefits and value for money when patients with diagnoses other than COVID-19 are accounted for.

The Effectiveness of Interactive Text Messaging and Structured Psychosocial Support Groups on Developmental Milestones of Children From Adolescent Pregnancies in Kenya: Quasi-Experimental Study.

BACKGROUND: In sub-Saharan Africa, one-quarter of all pregnancies occur in adolescents. Children born to adolescent mothers have poorer physical and socio-cognitive development. One reason may be inadequate knowledge on childcare and psychosocial support during pregnancy and post partum, since adolescent mothers have less antenatal care attendance and overall interaction with the health care system. Mobile health technology has been used to relay health information to special groups; however, psychosocial support commonly requires physical interaction. OBJECTIVE: We aimed to assess the efficacy of an interactive mobile text messaging platform and support groups in improving adolescent mothers' knowledge and practices as well as infant growth and development. METHODS: This was a quasi-experimental study, conducted among adolescent mothers with infants younger than 3 months, in Homa Bay County, Kenya. Five of the 8 subcounties in Homa Bay County were purposively selected as study clusters. Four subcounties were assigned as intervention clusters and 1 as a control cluster. Adolescent mothers from 2 intervention subcounties received interactive text messaging only (limited package), whereas those from the other 2 subcounties received text messaging and weekly support groups, moderated by a community health extension worker and a counselor (full package); the control cluster only received the end-line evaluation (posttest-only control). The follow-up period was 9 months. Key outcomes were maternal knowledge on childcare and infant development milestones assessed using the Developmental Milestones Checklist (DMC III). Knowledge and DMC III scores were compared between the intervention and control groups, as well as between the 2 intervention groups. RESULTS: We recruited 791 mother-infant pairs into the intervention groups (full package: n=375; limited package: n=416) at baseline and 220 controls at end line. Attrition from the intervention groups was 15.8% (125/791). Compared with the control group, adolescent mothers receiving the full package had a higher knowledge score on infant care and development (9.02 vs 8.01; P<.001) and higher exclusive breastfeeding rates (238/375, 63.5% vs 112/220, 50.9%; P=.004), and their infants had higher average DMC III scores (53.09 vs 48.59; P=.01). The limited package group also had higher knowledge score than the control group (8.73 vs 8.01; P<.001); this group performed better than the full package group on exclusive breastfeeding (297/416, 71.4% vs 112/220, 50.9%; P<.001) and DMC III scores (58.29 vs 48.59; P<.001) when compared with the control group. We found a marginal difference in knowledge scores between full and limited package groups (9.02 vs 8.73; P=.048) but no difference in DMC III scores between the 2 groups (53.09 vs 58.29; P>.99). CONCLUSIONS: An interactive text messaging platform improved adolescent mothers' knowledge on nurturing infant care and the development of their children, even without physical support groups. Such platforms offer a convenient avenue for providing reproductive health information to adolescents. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201806003369302; https://tinyurl.com/kkxvzjse.

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.

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.