Rapid Quantification of C. difficile Glutamate Dehydrogenase and Toxin B (TcdB) with a NanoBiT Split-Luciferase Assay.

C. difficile infection (CDI) is a leading healthcare-associated infection with a high morbidity and mortality and is a financial burden. No current standalone point-of-care test (POCT) is sufficient for the identification of true CDI over a disease-free carriage of C. difficile, so one is urgently required to ensure timely, appropriate treatment. Here, two types of binding proteins, Affimers and nanobodies, targeting two C. difficile biomarkers, glutamate dehydrogenase (GDH) and toxin B (TcdB), are combined in NanoBiT (NanoLuc Binary Technology) split-luciferase assays. The assays were optimized and their performance controlling parameters were examined. The 44 fM limit of detection (LoD), 4-5 log range and 1300-fold signal gain of the TcdB assay in buffer is the best observed for a NanoBiT assay to date. In the stool sample matrix, the GDH and TcdB assay sensitivity (LoD = 4.5 and 2 pM, respectively) and time to result (32 min) are similar to a current, commercial lateral flow POCT, but the NanoBit assay has no wash steps, detects clinically relevant TcdB over TcdA, and is quantitative. Development of the assay into a POCT may drive sensitivity further and offer an urgently needed ultrasensitive TcdB test for the rapid diagnosis of true CDI. The NanoBiTBiP (NanoBiT with Binding Proteins) system offers advantages over NanoBiT assays with antibodies as binding elements in terms of ease of production and assay performance. We expect this methodology and approach to be generally applicable to other biomarkers.

Engaging traditional barbers to identify and refer newborns for routine immunization services in Sokoto, Nigeria: a mixed methods evaluation.

OBJECTIVES: This study evaluates the effectiveness of an intervention that engaged traditional barbers to inform parents about the importance of vaccination and then refer newborns for vaccination services. METHODS: We conducted a pre-post quasi-experimental study (n = 2639) to evaluate changes in the coverage of three birth antigens among children aged 0-5 months in response to the intervention. We also conducted in-depth interviews and focus group discussions to assess the enabling factors and challenges associated with implementation. RESULTS: We found mothers who received a yellow referral card from a traditional barber were two to three times more likely to vaccinate their children with the three birth antigens. Qualitative findings indicated that the intervention influenced parent's decision to vaccinate their newborn because the barbers were considered a trusted community advisor. Challenges stemmed from the low levels of literacy among community leaders and barbers that resulted in the need for continuous training, low-literacy training materials and supervision. CONCLUSIONS: Efforts to increase vaccine coverage rates in northern Nigeria should consider expanding the role of traditional barbers to encourage parents to accept vaccines.

Community case management of pneumonia: at a tipping point?

Pneumonia is the leading cause of child mortality globally. Community case management (CCM) of pneumonia by community health workers is a feasible, effective strategy to complement facility-based management for areas that lack access to facilities. We surveyed experts in the 57 African and Asian countries with the highest levels and rates of childhood mortality to assess current policies, implementation and plans regarding CCM of pneumonia. About one-third (20/54) of countries reported policies supporting CCM for pneumonia, and another third (18/54) reported no policy against the strategy. Half (27/54) the countries reported some implementation of CCM for pneumonia, but often on a small scale. A few countries sustain a large-scale programme. Programmes, community health workers and policy parameters varied greatly among implementing countries. About half (12/26) of non-implementing countries are planning to move ahead with the strategy. Momentum is gathering for CCM for pneumonia as a strategy to address the pneumonia treatment gap and help achieve Millennium Development Goal 4. Challenges remain to: (1) introduce this strategy into policy and implement it in high pneumonia burden countries; (2) increase coverage of this strategy in countries currently implementing it; and (3) better define and monitor implementation at the country level.

Differential community response to introduction of zinc for childhood diarrhea and combination therapy for malaria in southern Mali.

Developing effective, affordable, and sustainable delivery strategies for the isolated low-income populations that stand to gain the most from micronutrient interventions has proven difficult. We discuss our experience with implementation of zinc as treatment for diarrhea in children less than 5 y of age over the course of 3 operational research studies in rural Sikasso Region, Mali, West Africa. The initial formative research study highlighted how malaria affects perceptions of diarrhea and its causes and that malaria and diarrhea are not necessarily viewed as distinct conditions. The second-phase pilot introduction demonstrated that, in introducing zinc treatment in malaria-endemic regions, it is especially important that both community- and facility-level providers be trained to manage sick children presenting with multiple symptoms. The third-phase study on large-scale implementation detected that the experience with implementation of new treatments for malaria is distinct from that of diarrhea. To some extent zinc treatment is the solution to a problem that communities may not recognize at all. Interventions to improve case management of sick children must be integrated across diseases and nutritional problems at both the facility and community levels. Operational research can identify points where integration should occur and how it should be carried out. Programs targeting single diseases or single nutritional problems can have a variety of deleterious effects on health systems, no matter how well they are planned.

Effect of HIV/AIDS and malaria on the context for introduction of zinc treatment and low-osmolarity ORS for childhood diarrhoea.

Diarrhoea was estimated to account for 18% of the estimated 10.6 million deaths of children aged less than five years annually in 2003. Two--Africa and South-East Asia--of the six regions of the World Health Organization accounted for approximately 40% and 31% of these deaths respectively, or almost three-quarters of the global annual deaths of children aged less than five years attributable to diarrhoea. Much of the effort to roll out low-osmolarity oral rehydration solution (ORS) and supplementation of zinc for the management of diarrhoea accordingly is being devoted to sub-Saharan Africa and to South and South-East Asia. A number of significant differences exist in diarrhoea-treatment behaviours and challenges of the public-health systems between Africa and Asia. The differences in rates of ORS use are the most common indicator of treatment of diarrhoea and vary dramatically by and within region and may significantly influence the roll-out strategy for zinc and low-osmolarity ORS. The prevalence of HIV/AIDS and the endemicity of malaria also differ greatly between regions; both the diseases consume the attention and financial commitment of public-health programmes in regions where rates are high. This paper examined how these differences could affect the context for the introduction of zinc and low-osmolarity ORS at various levels, including the process of policy dialogue with local decision-makers, questions to be addressed in formative research, implementation approaches, and strategies for behaviour-change communication and training of health workers.

Operational issues and trends associated with the pilot introduction of zinc for childhood diarrhoea in Bougouni district, Mali.

Zinc for the treatment of childhood diarrhoea was introduced in a pilot area in southern Mali to prepare for a cluster-randomized effectiveness study and to inform policies on how to best introduce and promote zinc at the community level. Dispersible zinc tablets in 14-tablet blister packs were provided through community health centres and drug kits managed by community health workers (CHWs) in two health zones in Bougouni district, Mali. Village meetings and individual counselling provided by CHWs and head nurses at health centres were the principal channels of communication. A combination of methods were employed to (a) detect problems in communication about the benefits of zinc and its mode of administration; (b) identify and resolve obstacles to implementation of zinc through existing health services; and (c) describe household-level constraints to the adoption of appropriate home-management practices for diarrhoea, including administration of both zinc and oral rehydration solution (ORS). Population-based household surveys with caretakers of children sick in the previous two weeks were carried out before and four months after the introduction of zinc supplementation. Household follow-up visits with children receiving zinc from the health centres and CHWs were conducted on day 3 and 14 after treatment for a subsample of children. A qualitative process evaluation also was conducted to investigate operational issues. Preliminary evidence from this study suggests that the introduction of zinc does not reduce the use of ORS and may reduce inappropriate antibiotic use for childhood diarrhoea. Financial access to treatments, management of concurrent diarrhoea and fever, and high use of unauthorized drug vendors were identified as factors affecting the effectiveness of the intervention in this setting. The introduction of zinc, if not appropriately integrated with other disease-control strategies, has the potential to decrease the appropriate presumptive treatment of childhood malaria in children with diarrhoea and fever in malaria-endemic areas.

Home management of childhood diarrhoea in southern Mali--implications for the introduction of zinc treatment.

Diarrhoea remains one of the leading killers of young children. A recent meta-analysis demonstrated that a two-week course of zinc tablets once daily significantly reduces the severity and duration of diarrhoea and mortality in young children (Bhutta et al., 2000. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: Pooled analysis of randomized controlled trials. American Journal of Clinical Nutrition, 72(6), 1516-1522). Formative research is being conducted in a number of countries to prepare for the large-scale promotion of this new treatment. In-depth and semi-structured interviews with parents, community health workers, and traditional healers were conducted to examine the household management of diarrhoea in the Sikasso region of southern Mali in preparation for the introduction of a short-course of daily zinc for childhood diarrhoea at the community level. Supporting data from a subsequent household survey are also presented. Although nearly all parents knew oral rehydration solution (ORS) could replace lost fluids, its inability to stop diarrhoea caused parents to seek antibiotics from local markets, traditional medicines or anti-malarials to cure the illness. The notion of combining multiple treatments to ensure the greatest therapeutic benefit was prevalent, and modern medicines were often administered simultaneously with traditional therapies. As parents often deem ORS insufficient and judge that an additional treatment should be combined with ORS to cure diarrhoea, the concept of joint therapy of zinc and ORS should be well accepted in the community. Mothers-in-law and fathers, who play a significant role in decisions to seek treatment for sick children, as well as traditional healers, should also be considered when designing new programs to promote zinc. Similarities with formative research conducted for a previous generation of diarrhoea control programmes are discussed.

How the introduction of a human resources information system helped the Democratic Republic of Congo to mobilise domestic resources for an improved health workforce.

The Democratic Republic of Congo has flagged health workforce management and compensation as issues requiring attention, including the problem of ghost workers (individuals on payroll who do not exist and/or show up at work). Recognising the need for reliable health workforce information, the government has worked to implement iHRIS, an open source human resources information system that facilitates health workforce management. In Kasaï Central and Kasaï Provinces, health workers brought relevant documentation to data collection points, where trained teams interviewed them and entered contact information, identification, photo, current job, and employment and education history into iHRIS on laptops. After uploading the data, the Ministry of Public Health used the database of over 11 500 verified health worker records to analyse health worker characteristics, density, compensation, and payroll. Both provinces had less than one physician per 10 000 population and a higher urban versus rural health worker density. Most iHRIS-registered health workers (57% in Kasaï Central and 73% in Kasaï) reported receiving no regular government pay of any kind (salaries or risk allowances). Payroll analysis showed that 27% of the health workers listed as salary recipients in the electronic payroll system were ghost workers, as were 42% of risk allowance recipients. As a result, the Ministries of Public Health, Public Service, and Finance reallocated funds away from ghost workers to cover salaries (n = 781) and risk allowances (n = 2613) for thousands of health workers who were previously under- or uncompensated due to lack of funds. The reallocation prioritised previously under- or uncompensated mid-level health workers, with 49% of those receiving salaries and 68% of those receiving risk allowances representing cadres such as nurses, laboratory technicians, and midwifery cadres. Assembling accurate health worker records can help governments understand health workforce characteristics and use data to direct scarce domestic resources to where they are most needed.

Prescription and administration of a 14-day regimen of zinc treatment for childhood diarrhea in Mali.

We evaluated prescription and correct dosing of a 14-day course of dispersible zinc tablets prescribed to young children with diarrhea by community and facility workers in rural, southern Mali, West Africa. One hundred twenty-three children were followed at home on days 3 and 14 after being prescribed zinc. The age-appropriate dose of zinc was dispensed in 94% of cases. Ninety-five percent of mothers dissolved the tablet in a small amount of water and gave it with a spoon. Only eight caretakers reported problems with zinc administration: either vomiting or refusal to take the tablets. Sixty-four percent of children received the full 14-day course of treatment, and more than 89% of children were given at least a 10-day course of zinc treatment. The levels of correct administration were very good but might be lower under non-research conditions.

Successful mLearning Pilot in Senegal: Delivering Family Planning Refresher Training Using Interactive Voice Response and SMS.

BACKGROUND: In-service training of health workers plays a pivotal role in improving service quality. However, it is often expensive and requires providers to leave their posts. We developed and assessed a prototype mLearning system that used interactive voice response (IVR) and text messaging on simple mobile phones to provide in-service training without interrupting health services. IVR allows trainees to respond to audio recordings using their telephone keypad. METHODS: In 2013, the CapacityPlus project tested the mobile delivery of an 8-week refresher training course on management of contraceptive side effects and misconceptions to 20 public-sector nurses and midwives working in Mékhé and Tivaouane districts in the Thiès region of Senegal. The course used a spaced-education approach in which questions and detailed explanations are spaced and repeated over time. We assessed the feasibility through the system's administrative data, examined participants' experiences using an endline survey, and employed a pre- and post-test survey to assess changes in provider knowledge. RESULTS: All participants completed the course within 9 weeks. The majority of participant prompts to interact with the mobile course were made outside normal working hours (median time, 5:16 pm); average call duration was about 13 minutes. Participants reported positive experiences: 60% liked the ability to determine the pace of the course and 55% liked the convenience. The largest criticism (35% of participants) was poor network reception, and 30% reported dropped IVR calls. Most (90%) participants thought they learned the same or more compared with a conventional course. Knowledge of contraceptive side effects increased significantly, from an average of 12.6/20 questions correct before training to 16.0/20 after, and remained significantly higher 10 months after the end of training than at baseline, at 14.8/20, without any further reinforcement. CONCLUSIONS: The mLearning system proved appropriate, feasible, and acceptable to trainees, and it was associated with sustained knowledge gains. IVR mLearning has potential to improve quality of care without disrupting routine service delivery. Monitoring and evaluation of larger-scale implementation could provide evidence of system effectiveness at scale.

Quality of sick child care delivered by Health Surveillance Assistants in Malawi.

OBJECTIVE: To assess the quality of care provided by Health Surveillance Assistants (HSAs)-a cadre of community-based health workers-as part of a national scale-up of community case management of childhood illness (CCM) in Malawi. METHODS: Trained research teams visited a random sample of HSAs (n = 131) trained in CCM and provided with initial essential drug stocks in six districts, and observed the provision of sick child care. Trained clinicians conducted 'gold-standard' reassessments of the child. Members of the survey team also interviewed caregivers and HSAs and inspected drug stocks and patient registers. FINDINGS: HSAs provided correct treatment with antimalarials to 79% of the 241 children presenting with uncomplicated fever, with oral rehydration salts to 69% of the 93 children presenting with uncomplicated diarrhoea and with antibiotics to 52% of 58 children presenting with suspected pneumonia (cough with fast breathing). About one in five children (18%) presented with danger signs. HSAs correctly assessed 37% of children for four danger signs by conducting a physical exam, and correctly referred 55% of children with danger signs. CONCLUSION: Malawi's CCM programme is a promising strategy for increasing coverage of sick child treatment, although there is much room for improvement, especially in the correct assessment and treatment of suspected pneumonia and the identification and referral of sick children with danger signs. However, HSAs provided sick child care at levels of quality similar to those provided in first-level health facilities in Malawi, and quality should improve if the Ministry of Health and partners act on the results of this assessment.

Comparison of methods for assessing quality of care for community case management of sick children: an application with community health workers in Malawi.

Direct observation (DO) with re-examination (RE) by a skilled clinician is a rigorous method for assessing health worker performance, but is not always feasible. We assessed the performance of 131 community health workers in Malawi in community case management of sick children with cough and fast breathing, fever, and diarrhea. We compared estimates of correct treatment measured through DO with RE (n = 382 cases) to DO only (n = 382 cases), register review (n = 1,219 cases), and case scenarios (n = 917 cases). Estimates of correct treatment of uncomplicated fever and diarrhea measured through DO only, register review, and case scenarios were within 9 percentage points of DO with RE estimates, while estimates for uncomplicated cough and fast breathing, and severe illness were substantially higher than DO with RE (12-51 percentage points above the estimate). Those planning for community health worker assessments in community case management can use these results to make an informed choice of methods on the basis of their objectives and the local context.

Health workers' and managers' perceptions of the integrated community case management program for childhood illness in Malawi: the importance of expanding access to child health services.

Community case management (CCM) is a promising task-shifting strategy for expanding treatment of childhood illness that is increasingly adopted by low-income countries. Its success depends in part on how the strategy is perceived by those responsible for its implementation. This study uses qualitative methods to explore health workers' and managers' perceptions about CCM provided by health surveillance assistants (HSAs) during the program's first year in Malawi. Managers and HSAs agreed that CCM contributed beneficially by expanding access to the underserved and reducing caseloads at health facilities. Managers differed among themselves in their endorsements of CCM, most offered constrained endorsement, and a few had stronger justifications for CCM. In addition, HSAs uniformly wanted continued expansion of their clinical role, while managers preferred to view CCM as a limited mandate. The HSAs also reported motivating factors and frustrations related to system constraints and community pressures related to CCM. The impact of CCM on motivation and workload of HSAs is noted and deserves further attention.

Local terminology for medicines to treat fever in Bougouni District, Mali: implications for the introduction and evaluation of malaria treatment policies.

OBJECTIVE: To explore Bambara language terminology and classification for locally available antimicrobial medicines in order to better target promotional messages and improve evaluation measures in Bougouni District, Mali. METHODS: Mothers (n = 20) and drug vendors (n = 15) were asked to freelist medicines used to treat childhood illnesses, and to identify all medicines that corresponded to each of the listed terms from an array of medicines displayed with their packaging. RESULTS: Each Bambara language medicine term can refer to numerous modern medicines, and each modern medicine has several Bambara names. The term nivakini (Nivaquine), often translated as 'chloroquine', refers to a wide range of medicines commonly used to treat malaria, many with no antimalarial effect. Antibiotics were also identified as common treatments for malaria. Mothers and vendors used slightly different terminology when discussing treatments for malaria, and sometimes employed the same term to refer to different medicines. Neither mothers nor vendors clearly differentiated between antimalarial medicines. Colour, shape and packaging play a large role in their recognition, classification and use. CONCLUSIONS: Current household survey methods are likely to provide inaccurate estimates of appropriate treatment of febrile illness, and thus alternative approaches are recommended. In introducing new malaria treatments, malaria control programmes should differentiate recommended treatments from other medications through distinctive packaging, drug appearance and appropriate Bambara language terms.

Intervention models for the management of children with signs of pneumonia or malaria by community health workers.

A systematic review was conducted to categorize and describe Intervention Models involving community health workers (CHWs) that aim to improve case management of sick children at the household and community levels. The review focused on management of children with signs of malaria or pneumonia. Seven Intervention Models were identified, and classified according to: (1) the role of CHWs and families in assessment and treatment of children, (2) system of referral to the nearest health facility (verbal or facilitated), and (3) the location in the community of the drug stock. Standardization of terminology for Intervention Models using this or a similar classification could facilitate comparison and selection of models, including deciding how to modify programmes when policies change concerning first-line drugs, and setting priorities for further research. Of the seven models, that of CHW pneumonia case management (Model 6) has the strongest evidence for an impact on mortality. Pneumonia case management by CHWs is a child health intervention that warrants considerably more attention, particularly in Africa and South Asia.