Barriers to the uptake of community-based curative child health services in Ethiopia.

BACKGROUND: Uptake of services to treat newborns and children has been persistently low in Ethiopia, despite being provided free-of-charge by Health Extension Workers (HEWs). In order to increase the uptake of these services, the Optimizing the Health Extension Project was designed to be implemented in four regions in Ethiopia. This study was carried out to identify barriers to the uptake of these services and potential solutions to inform the project. METHODS: Qualitative data were collected in October and November 2015 in 15 purposely selected districts in four regions. We conducted 90 focus group discussions and 60 in-depth interviews reaching a total of 664 participants. Thematic analysis was used to identify key barriers and potential solutions. RESULTS: Five demand-side barriers to utilization of health services were identified. Misconceptions about illness causation, compounded with preference for traditional healers has affected service uptake. Limited awareness of the availability of free curative services for children at health posts; along with the prevailing perception that HEWs were providing preventive services only had constrained uptake. Geographic challenge that made access to the health post difficult was the other barrier. Four supply-side barriers were identified. Health post closure and drug stock-out led to inconsistent availability of services. Limited confidence and skill among HEWs and under-resourced physical facilities affected the service delivery. Study participants suggested demand creation solutions such as increasing community awareness on curative service availability and educating them on childhood illness causation. Maintaining consistent supplies and ensuring service availability; along with regular support to build HEWs' confidence were the suggested supply-side solutions. Creating community feedback mechanisms was suggested as a way of addressing community concerns on the health services. CONCLUSION: This study explored nine demand- and supply-side barriers that decreased the uptake of community-based services. It indicated the importance of increasing awareness of new services and addressing prevailing barriers that deprioritize health services. At the same time, supply-side barriers would have to be tackled by strengthening the health system to uphold newly introduced services and harness sustainable impact.

Prevalence, severity, and associations of depression in people with epilepsy in Guinea: A single-center study.

BACKGROUND AND OBJECTIVE: Depression has long been recognized as a comorbidity of epilepsy in high-income countries, ranging from 17 to 49% of people with epilepsy (PWE). Of the limited studies from sub-Saharan Africa (SSA), where most people have uncontrolled seizures, an even higher prevalence of depression is reported among PWE at times exceeding 80%. We sought to assess the prevalence and severity of depression and its associated factors among PWE in Guinea, a sub-Saharan West African country where most PWE have poorly controlled seizures. METHODS: People with epilepsy from the community, age 16 years old and above, were consecutively recruited into a convenience cohort at the Ignace Deen Hospital in the capital city, Conakry, in summer 2018 as part of a larger study characterizing PWE in Guinea. Each participant was evaluated by a team of Guinean physicians and a U.S.-based neurologist to confirm the diagnosis of epilepsy. Inperson interviews were performed to measure demographic, clinical, socioeconomic, and related variables. Depression was measured via the Patient Health Questionniare-9 in the language of the participant's preference with a cutoff of 5 or more points being categorized as depressed. Regression analyses were performed to measure the associations between explanatory variables with the outcome of depression. RESULT: Of 140 PWE (age range: 16-66 years old; 64 female; 64% taking an antiseizure medication including 28% carbamazepine, 16% phenobarbital, and 14% valproic acid; duration of epilepsy: 11 years; 71% with one or more seizures in the past month; 17% never treated with an antiseizure medication; 90% with loss of consciousness during seizures; 10% without formal education; 31% with university level education; 62% using tap water; 48% with a serious seizure-related injury), the point prevalence of depression was 66% (95% confidence interval [CI]: 58%-74%): 43% of PWE had mild depression, 19% moderate, 4% moderate to severe, and 0.1% severe. In a multivariate analysis, the occurrence of a seizure in the past month (odds ratio: 3.03, 95% CI: 2.63-3.48, p = 0.01) was associated with depression, while gender, self-perceived stigma score, serious injuries, and the number of antiseizure medications taken were not statistically significantly associated (p > 0.05). Twenty-five percent of all participants endorsed thoughts of self-harm or suicidality. CONCLUSION: Two-thirds of PWE in Guinea had depression in this single-institution convenience cohort. The presence of a seizure in the last month was the factor most associated with depression and is modifiable in many PWE. The high prevalance of depression suggests that screening and addressing depressive symptoms should be incorporated into routine epilepsy care in Guinea.

Modulation of CrbS-Dependent Activation of the Acetate Switch in Vibrio cholerae.

Vibrio cholerae controls the pathogenicity of interactions with arthropod hosts via the activity of the CrbS/R two-component system. This signaling pathway regulates the consumption of acetate, which in turn alters the relative virulence of interactions with arthropods, including Drosophila melanogaster CrbS is a histidine kinase that links a transporter-like domain to its signaling apparatus via putative STAC and PAS domains. CrbS and its cognate response regulator are required for the expression of acetyl coenzyme A (acetyl-CoA) synthetase (product of acs), which converts acetate to acetyl-CoA. We demonstrate that the STAC domain of CrbS is required for signaling in culture; without it, acs transcription is reduced in LB medium, and V. cholerae cannot grow on acetate minimal media. However, the strain remains virulent toward Drosophila and expresses acs similarly to the wild type during infection. This suggests that there is a unique signal or environmental variable that modulates CrbS in the gastrointestinal tract of Drosophila Second, we present evidence in support of CrbR, the response regulator that interacts with CrbS, binding directly to the acs promoter, and we identify a region of the promoter that CrbR may target. We further demonstrate that nutrient signals, together with the cAMP receptor protein (CRP)-cAMP system, control acs transcription, but regulation may occur indirectly, as CRP-cAMP activates the expression of the crbS and crbR genes. Finally, we define the role of the Pta-AckA system in V. cholerae and identify redundancy built into acetate excretion pathways in this pathogen.IMPORTANCE CrbS is a member of a unique family of sensor histidine kinases, as its structure suggests that it may link signaling to the transport of a molecule. However, mechanisms through which CrbS senses and communicates information about the outside world are unknown. In the Vibrionaceae, orthologs of CrbS regulate acetate metabolism, which can, in turn, affect interactions with host organisms. Here, we situate CrbS within a larger regulatory framework, demonstrating that crbS is regulated by nutrient-sensing systems. Furthermore, CrbS domains may play various roles in signaling during infection and growth in culture, suggesting a unique mechanism of host recognition. Finally, we define the roles of additional pathways in acetate flux, as a foundation for further studies of this metabolic nexus point.

Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up in countries.

Universal coverage of essential interventions would reduce neonatal deaths by an estimated 71%, benefit women and children after the first month, and reduce stillbirths. However, the packages with the greatest effect (care around birth, care of small and ill newborn babies), have low and inequitable coverage and are the most sensitive markers of health system function. In eight of the 13 countries with the most neonatal deaths (55% worldwide), we undertook a systematic assessment of bottlenecks to essential maternal and newborn health care, involving more than 600 experts. Of 2465 bottlenecks identified, common constraints were found in all high-burden countries, notably regarding the health workforce, financing, and service delivery. However, bottlenecks for specific interventions might differ across similar health systems. For example, the implementation of kangaroo mother care was noted as challenging in the four Asian country workshops, but was regarded as a feasible aspect of preterm care by respondents in the four African countries. If all high-burden countries achieved the neonatal mortality rates of their region's fastest progressing countries, then the mortality goal of ten or fewer per 1000 livebirths by 2035 recommended in this Series and the Every Newborn Action Plan would be exceeded. We therefore examined fast progressing countries to identify strategies to reduce neonatal mortality. We identified several key factors: (1) workforce planning to increase numbers and upgrade specific skills for care at birth and of small and ill newborn babies, task sharing, incentives for rural health workers; (2) financial protection measures, such as expansion of health insurance, conditional cash transfers, and performance-based financing; and (3) dynamic leadership including innovation and community empowerment. Adapting from the 2005 Lancet Series on neonatal survival and drawing on this Every Newborn Series, we propose a country-led, data-driven process to sharpen national health plans, seize opportunities to address the quality gap for care at birth and care of small and ill newborn babies, and systematically scale up care to reach every mother and newborn baby, particularly the poorest.

Conditional permeabilization of the P. falciparum plasma membrane in infected cells links cation influx to reduced membrane integrity.

The intracellular human malaria parasite, Plasmodium falciparum, uses the PfATP4 cation pump to maintain Na+ and H+ homeostasis in parasite cytosol. PfATP4 is the target of advanced antimalarial leads, which produce many poorly understood metabolic disturbances within infected erythrocytes. Here, we expressed the mammalian ligand-gated TRPV1 ion channel at the parasite plasma membrane to study ion regulation and examine the effects of cation leak. TRPV1 expression was well-tolerated, consistent with negligible ion flux through the nonactivated channel. TRPV1 ligands produced rapid parasite death in the transfectant line at their activating concentrations, but were harmless to the wild-type parent. Activation triggered cholesterol redistribution at the parasite plasma membrane, reproducing effects of PfATP4 inhibitors and directly implicating cation dysregulation in this process. In contrast to predictions, TRPV1 activation in low Na+ media accentuated parasite killing but a PfATP4 inhibitor had unchanged efficacy. Selection of a ligand-resistant mutant revealed a previously uncharacterized G683V mutation in TRPV1 that occludes the lower channel gate, implicating reduced permeability as a mechanism for parasite resistance to antimalarials targeting ion homeostasis. Our findings provide key insights into malaria parasite ion regulation and will guide mechanism-of-action studies for advanced antimalarial leads that act at the host-pathogen interface.

Addressing Equity in Global Medical Education During the COVID-19 Pandemic: The Global Medical Education Collaborative.

PROBLEM: The COVID-19 pandemic has presented a unique set of challenges to medical education globally. Low- and middle-income countries (LMICs) have faced unique barriers in transitioning to virtual modalities, and many medical students in LMICs experienced dramatically reduced educational time. The authors created the Global Medical Education Collaborative (GMEC) to address this problem by providing free, online, case-based tutorials to medical students in LMICs during the pandemic. APPROACH: The authors developed a needs assessment to gauge students' educational requirements, which informed GMEC's 2 primary goals: to provide free access to interactive online tutorials for students in LMICs and to bridge the physical distance between educators and learners via an online platform. A pilot program in Nigeria (April 26-May 26, 2020) helped inform the current strategy and logistics. Tutors and students were recruited via social media and medical education networks at the authors' home institutions. OUTCOMES: Within the first 2 months (April 26-June 26, 2020), 324 students representing 12 countries and 20+ medical schools joined GMEC. Additionally, 95 physicians and trainees joined as tutors and, collectively, delivered 52 tutorials. Students responded to a needs assessment querying confidence in various clinical domains, interest in covering clinical topics, barriers to virtual learning, and the effect of the pandemic on their education. Tutors held 1-hour, interactive tutorials over Zoom covering a variety of clinical topics. According to surveys, 91% of students (71 of 78) felt more confident in the material related to the tutorial's topic after participating. NEXT STEPS: GMEC will continue to engage students, tutors, and collaborators to facilitate the delivery of innovative, high-quality tutorials to students affected by COVID-19 in LMICs. To ensure that the platform is sustainable and aligned with GMEC's mission to promote equity in global medical education, the collaborative will need to be agile and responsive.

Barriers to the utilization of community-based child and newborn health services in Ethiopia: a scoping review.

The Ethiopian Federal Ministry of Health and partners have scaled up integrated community case management (iCCM) and community-based newborn care (CBNC), allowing health extension workers (HEWs) to manage the major causes of child and newborn death at the community level. However, low service uptake remains a key challenge. We conducted a scoping review of peer-reviewed and grey literature to assess barriers to the utilization of HEW services and to explore potential solutions. The review, which was conducted to inform the Optimizing the Health Extension Program project, which aimed to increase the utilization of iCCM and CBNC services, included 24 peer-reviewed articles and 18 grey literature documents. Demand-side barriers to utilization included lack of knowledge about the signs and symptoms of childhood illnesses and danger signs; low awareness of curative services offered by HEWs; preference for home-based care, traditional care, or religious intervention; distance, lack of transportation and cost of care seeking; the need to obtain husband's permission to seek care and opposition of traditional or religious leaders. Supply-side barriers included health post closures, drug stockouts, disrespectful care and limited skill and confidence of HEWs, particularly with regard to the management of newborn illnesses. Potential solutions included community education and demand generation activities, finding ways to facilitate and subsidize transportation to health facilities, engaging family members and traditional and religious leaders, ensuring consistent availability of services at health posts and strengthening supervision and supply chain management. Both demand generation and improvement of service delivery are necessary to achieve the expected impact of iCCM and CBNC. Key steps for improving utilization would be carrying out multifaceted demand generation activities, ensuring availability of HEWs in health posts and ensuring consistent supplies of essential commodities. The Women's Development Army has the potential to improving linkages between HEWs and communities, but this strategy needs to be strengthened to be effective.

Prevalence and factors associated with hepatitis B in a cohort of HIV-infected children in the Pediatric Department at Donka National Hospital, Guinea.

INTRODUCTION: children pay a heavy price for infection with the hepatitis B virus (HBV). The objective of this work was to determine the prevalence of hepatitis B and describe the associated factors in children at the pediatric department of Donka Hospital. METHODS: this was a cross-sectional study of a cohort of children in the pediatric department of Donka Hospital. HBsAg was performed by using an immunochromatographic method. The analysis of the data was done with software R. The proportions were compared using the Chi-square test or the Fisher test at the significance level of 5%. A logistic regression model was used to explain the prevalence of hepatitis B. RESULTS: one hundred and forty-nine children were recruited between February and July 2017. HBsAg was present in 12 children, i.e. 8.16% (95% CI: 4.29-13.82). The average age was 93.32 months (IQR: 6-180). Male children were the most affected (n = 11, P <0.05), with a sex ratio of 1.01. The majority (51.35%) were on AZT + 3TC + NVP pediatric form and 25% were on AZT + 3TC + NVP adult form and 23.65% on TDF + FTC + EFV. In univariate analysis, ALT, HBsAg positivity, and maternal HBV vaccination status were associated with the prevalence of HBsAg (P <0.05). CONCLUSION: the prevalence of co-infection in children and adults is almost identical in our context. Hence the importance of strengthening preventive measures at all levels, especially the vaccination of children and mothers.

Regulation of acetyl-CoA synthetase transcription by the CrbS/R two-component system is conserved in genetically diverse environmental pathogens.

The CrbS/R two-component signal transduction system is a conserved regulatory mechanism through which specific Gram-negative bacteria control acetate flux into primary metabolic pathways. CrbS/R governs expression of acetyl-CoA synthase (acsA), an enzyme that converts acetate to acetyl-CoA, a metabolite at the nexus of the cell's most important energy-harvesting and biosynthetic reactions. During infection, bacteria can utilize this system to hijack host acetate metabolism and alter the course of colonization and pathogenesis. In toxigenic strains of Vibrio cholerae, CrbS/R-dependent expression of acsA is required for virulence in an arthropod model. Here, we investigate the function of the CrbS/R system in Pseudomonas aeruginosa, Pseudomonas entomophila, and non-toxigenic V. cholerae strains. We demonstrate that its role in acetate metabolism is conserved; this system regulates expression of the acsA gene and is required for growth on acetate as a sole carbon source. As a first step towards describing the mechanism of signaling through this pathway, we identify residues and domains that may be critical for phosphotransfer. We further demonstrate that although CrbS, the putative hybrid sensor kinase, carries both a histidine kinase domain and a receiver domain, the latter is not required for acsA transcription. In order to determine whether our findings are relevant to pathogenesis, we tested our strains in a Drosophila model of oral infection previously employed for the study of acetate-dependent virulence by V. cholerae. We show that non-toxigenic V. cholerae strains lacking CrbS or CrbR are significantly less virulent than are wild-type strains, while P. aeruginosa and P. entomophila lacking CrbS or CrbR are fully pathogenic. Together, the data suggest that the CrbS/R system plays a central role in acetate metabolism in V. cholerae, P. aeruginosa, and P. entomophila. However, each microbe's unique environmental adaptations and pathogenesis strategies may dictate conditions under which CrbS/R-mediated acs expression is most critical.

Cost-effectiveness of trachoma control in seven world regions.

BACKGROUND/AIMS: The fight against blinding trachoma is being addressed with an integrated strategy of surgery, antibiotics, hygiene promotion, and environmental improvement-the SAFE strategy, but its cost-effectiveness is largely unknown. This paper estimates the cost effectiveness of surgery and antibiotics in trachoma-endemic areas in seven world regions. METHODS: A population model was applied to follow the lifelong impact on individuals receiving trachoma control. Intervention costs and effectiveness estimates were based on a combination of primary data collection and literature review. RESULTS: Providing trichiasis surgery to 80% of those who need it would avert over 11 million DALYs per year globally, with cost effectiveness ranging from I$13 to I$78 per DALY averted across regions. Mass antibiotic treatment of all children using azythromycin at prevailing market prices would avert more than 4 million DALYs per year globally with cost-effectiveness ranging between I$9,000 and I$65,000 per DALY averted. The intervention is only cost-effective if azythromycin is donated or becomes available at reduced prices. Mass treatment of all children with tetracycline and targeted treatment with azythromycin are not cost-effective. CONCLUSIONS: As individual components of the SAFE strategy, trichiasis surgery for trachoma is a cost-effective way of restoring sight in all epidemiological sub-regions considered, as is the use of azythromycin, if donated or at reduced prices. Large study uncertainties do not change study conclusions. The results should be interpreted in the context of the overall SAFE strategy to address issues of sustainability.

Community case management of childhood illness in sub-Saharan Africa - findings from a cross-sectional survey on policy and implementation.

BACKGROUND: Community case management (CCM) involves training, supporting, and supplying community health workers (CHWs) to assess, classify and manage sick children with limited access to care at health facilities, in their communities. This paper aims to provide an overview of the status in 2013 of CCM policy and implementation in sub-Saharan African countries. METHODS: We undertook a cross-sectional, descriptive, quantitative survey amongst technical officers in Ministries of Health and UNICEF offices in 2013. The survey aim was to describe CCM policy and implementation in 45 countries in sub-Saharan Africa, focusing on: CHW profile, CHW activities, and financing. RESULTS: 42 countries responded. 35 countries in sub-Saharan Africa reported implementing CCM for diarrhoea, 33 for malaria, 28 for pneumonia, 6 for neonatal sepsis, 31 for malnutrition and 28 for integrated CCM (treatment of 3 conditions: diarrhoea, malaria and pneumonia) - an increase since 2010. In 27 countries, volunteers were providing CCM, compared to 14 countries with paid CHWs. User fees persisted for CCM in 6 countries and mark-ups on commodities in 10 countries. Most countries had a national policy, memo or written guidelines for CCM implementation for diarrhoea, malaria and pneumonia, with 20 countries having this for neonatal sepsis. Most countries plan gradual expansion of CCM but many countries' plans were dependent on development partners. A large group of countries had no plans for CCM for neonatal sepsis. CONCLUSION: 28 countries in sub-Saharan Africa now report implementing CCM for pneumonia, diarrhoea and malaria, or "iCCM". Most countries have developed some sort of written basis for CCM activities, yet the scale of implementation varies widely, so a focus on implementation is now required, including monitoring and evaluation of performance, quality and impact. There is also scope for expansion for newborn care. Key issues include financing and sustainability (with development partners still providing most funding), gaps in data on CCM activities, and the persistence of user fees and mark-ups in several countries. National health management information systems should also incorporate CCM activities.

Community health workers providing government community case management for child survival in sub-Saharan Africa: who are they and what are they expected to do?

We describe community health workers (CHWs) in government community case management (CCM) programs for child survival across sub-Saharan Africa. In sub-Saharan Africa, 91% of 44 United Nations Children's Fund (UNICEF) offices responded to a cross-sectional survey in 2010. Frequencies describe CHW profiles and activities in government CCM programs (N = 29). Although a few programs paid CHWs a salary or conversely, rewarded CHWs purely on a non-financial basis, most programs combined financial and non-financial incentives and had training for 1 week. Not all programs allowed CHWs to provide zinc, use timers, dispense antibiotics, or use rapid diagnostic tests. Many CHWs undertake health promotion, but fewer CHWs provide soap, water treatment products, indoor residual spraying, or ready-to-use therapeutic foods. For newborn care, very few promote kangaroo care, and they do not provide antibiotics or resuscitation. Even if CHWs are as varied as the health systems in which they work, more work must be done in terms of the design and implementation of the CHW programs for them to realize their potential.

Cost-effectiveness analysis of cataract surgery: a global and regional analysis.

OBJECTIVE: To estimate the population health effects, costs and cost effectiveness of selected cataract surgery interventions in areas of the world with different epidemiological profiles. METHODS: Effectiveness estimates are based on a review of the literature taking into account factors such as operative failure, complications and patient non-compliance. A population model was applied to follow the lifelong impact on individuals having cataract surgery. Costing estimates are based on primary data collected in 14 epidemiological subregions by regional costing teams and on a literature review. Costings were estimated for different geographical coverage levels using non-linear cost functions. FINDINGS: Intra- and extra-capsular cataract surgeries are cost-effective ways to reduce the impact of cataract-blindness. Extra-capsular cataract surgery is more cost-effective than intra-capsular surgery in all regions considered. Providing extra-capsular cataract surgery to 95% of those who need it (95% coverage level) would avert over 3.5 million disability-adjusted life years (DALYs) per year globally. The cost-effectiveness ranges from 57 International dollars (1 dollar) per DALY in the WHO South-East Asia Region where there is high overall child and adult mortality to 1 dollar 2307 per DALY in the WHO Western Pacific Region where there is low overall child and adult mortality. CONCLUSION: Extra-capsular surgery for cataracts at a high level of coverage is the most cost-effective way of restoring sight in all epidemiological subregions considered. Analysts from countries within a region are encouraged to further contextualize the results based on their own country's specific parameters.