Use-case scenarios for an anti-Cryptosporidium therapeutic.

Cryptosporidium is a widely distributed enteric parasite that has an increasingly appreciated pathogenic role, particularly in pediatric diarrhea. While cryptosporidiosis has likely affected humanity for millennia, its recent "emergence" is largely the result of discoveries made through major epidemiologic studies in the past decade. There is no vaccine, and the only approved medicine, nitazoxanide, has been shown to have efficacy limitations in several patient groups known to be at elevated risk of disease. In order to help frontline health workers, policymakers, and other stakeholders translate our current understanding of cryptosporidiosis into actionable guidance to address the disease, we sought to assess salient issues relating to clinical management of cryptosporidiosis drawing from a review of the literature and our own field-based practice. This exercise is meant to help inform health system strategies for improving access to current treatments, to highlight recent achievements and outstanding knowledge and clinical practice gaps, and to help guide research activities for new anti-Cryptosporidium therapies.

Innovations in Addressing Pediatric Diarrhea in Low Resource Settings.

Diarrhea has long been recognized as an important cause of mortality during childhood. In parallel with ensuring access to proven care practices is the imperative to apply modern advances in medicine, science, and technology to accelerate progress against diarrheal disease, particularly in developing countries where the burden of avoidable harm is the greatest. In order to highlight achievements and identify outstanding areas of need, we reviewed the landscape of recent innovations that have significance for the study and clinical management of pediatric diarrhea in low resource settings.

Drug Discovery for Kinetoplastid Diseases: Future Directions.

Kinetoplastid parasites have caused human disease for millennia. Significant achievements have been made toward developing new treatments for leishmaniasis (particularly on the Indian subcontinent) and for human African trypanosomiasis (HAT). Moreover, the sustained decrease in the incidence of HAT has made the prospect of elimination a tantalizing reality. Despite the gains, no new chemical or biological entities to treat kinetoplastid diseases have been registered in more than three decades, and more work is needed to discover safe and effective therapies for patients with Chagas disease and leishmaniasis. Advances in tools for drug discovery and novel insights into the biology of the host-parasite interaction may provide opportunities for accelerated progress. Here, we summarize the output from a gathering of scientists and physicians who met to discuss the current status and future directions in drug discovery for kinetoplastid diseases.

Fundamental science behind today's important medicines.

Today's most transformative medicines exist because of fundamental discoveries that were made without regard to practical outcome and with their relevance to therapeutics only appearing decades later.

Epidemiology of pharyngitis as reported by Zambian school children and their families: implications for demand-side interventions to prevent rheumatic heart disease.

BACKGROUND: Prompt and appropriate treatment of streptococcal pharyngitis decreases the risk of acute rheumatic fever and rheumatic heart disease (RHD). Understanding public perceptions and behaviors related to sore throat is fundamental to inform health programs aimed at eliminating new cases of RHD in endemic regions. We sought to describe the epidemiology of pediatric pharyngitis and its treatment, as reported by children and their parents or guardians in Lusaka, Zambia. METHODS: This was a cross-sectional investigation using interviews and written surveys, nested in a school-based RHD prevalence study. Students and their parents were asked to report number of sore throats in the previous 12 months, treatment received, and type and place of treatment. A focused history and physical examination to detect pharyngitis was conducted and children were referred for follow-up as indicated. RESULTS: A total of 3462 students from 47 schools participated in the study, along with their parents or guardians. Six hundred and fifty eight (19%) parents/guardians reported their child had at least one sore throat in the previous year, and 835 (24%) of students reported at least one sore throat in the same time period. Girls were reported to have pharyngitis 50% more often than boys, and also made up two-thirds of the total students treated. Approximately two-thirds of children who had at least one episode of pharyngitis during the previous year were also reported to have received some form of treatment. The majority of treatments were received in government clinics (36.6%) and at home (26.3%). Half of treatments included an antibiotic. Nineteen students (0.5%) had clinically-apparent pharyngitis at screening. CONCLUSION: Pharyngitis is common among school-aged children and adolescents in Zambia, with females reporting significantly more sore throat episodes than males. Parents/guardians have variable knowledge about the frequency of sore throat in their children, and management of pharyngitis may be suboptimal for many children since more than a quarter were reported to have received treatment without skilled assessment. These results provide insight into current perceptions and practices related to sore throat in Zambia and will be used to design public awareness activities aimed at reducing RHD.

Effectiveness of the WHO Safe Childbirth Checklist program in reducing severe maternal, fetal, and newborn harm in Uttar Pradesh, India: study protocol for a matched-pair, cluster-randomized controlled trial.

BACKGROUND: Effective, scalable strategies to improve maternal, fetal, and newborn health and reduce preventable morbidity and mortality are urgently needed in low- and middle-income countries. Building on the successes of previous checklist-based programs, the World Health Organization (WHO) and partners led the development of the Safe Childbirth Checklist (SCC), a 28-item list of evidence-based practices linked with improved maternal and newborn outcomes. Pilot-testing of the Checklist in Southern India demonstrated dramatic improvements in adherence by health workers to essential childbirth-related practices (EBPs). The BetterBirth Trial seeks to measure the effectiveness of SCC impact on EBPs, deaths, and complications at a larger scale. METHODS/DESIGN: This matched-pair, cluster-randomized controlled, adaptive trial will be conducted in 120 facilities across 24 districts in Uttar Pradesh, India. Study sites, identified according to predefined eligibility criteria, were matched by measured covariates before randomization. The intervention, the SCC embedded in a quality improvement program, consists of leadership engagement, a 2-day educational launch of the SCC, and support through placement of a trained peer "coach" to provide supportive supervision and real-time data feedback over an 8-month period with decreasing intensity. A facility-based childbirth quality coordinator is trained and supported to drive sustained behavior change after the BetterBirth team leaves the facility. Study participants are birth attendants and women and their newborns who present to the study facilities for childbirth at 60 intervention and 60 control sites. The primary outcome is a composite measure including maternal death, maternal severe morbidity, stillbirth, and newborn death, occurring within 7 days after birth. The sample size (n = 171,964) was calculated to detect a 15% reduction in the primary outcome. Adherence by health workers to EBPs will be measured in a subset of births (n = 6000). The trial will be conducted in close collaboration with key partners including the Governments of India and Uttar Pradesh, the World Health Organization, an expert Scientific Advisory Committee, an experienced local implementing organization (Population Services International, PSI), and frontline facility leaders and workers. DISCUSSION: If effective, the WHO Safe Childbirth Checklist program could be a powerful health facility-strengthening intervention to improve quality of care and reduce preventable harm to women and newborns, with millions of potential beneficiaries. TRIAL REGISTRATION: BetterBirth Study Protocol dated: 13 February 2014; ClinicalTrials.gov: NCT02148952 ; Universal Trial Number: U1111-1131-5647.

Rates of motorcycle helmet use and reasons for non-use among adults and children in Luang Prabang, Lao People's Democratic Republic.

BACKGROUND: Motorcycles make up 81 % of the total vehicle population and 74 % of road traffic deaths in Lao PDR. Helmets reduce the risk and severity of injuries resulting from motorcycle accidents by 72 %. Although Lao law mandates motorcycle helmet use among drivers and passengers, the prevalence of helmet use in Luang Prabang, Lao PDR is unknown. This project aimed to measure the prevalence of motorcycle helmet use among riders (i.e., drivers and passengers) in Luang Prabang. METHODS: An observational survey in Luang Prabang was conducted in February 2015 to measure the prevalence of motorcycle helmet use among drivers and passengers. Additionally, non-helmet wearing riders were surveyed to identify the reasons for helmet non-use. RESULTS: Of 1632 motorcycle riders observed, only 16.2 % wore helmets. Approximately 29 % of adults wore helmets while less than 1 % of all children wore helmets. When surveyed about attitudes towards helmet use, the majority of adult drivers indicated that they did not like how adult helmets feel or made them look. Additionally, almost half of motorcyclists who did not own child helmets reported that their child was too young to wear a helmet. CONCLUSIONS: Our finding that children wear helmets at significantly lower rates compared to adults is consistent with findings from neighboring countries in Southeast Asia. Results of this study have implications for public health campaigns targeting helmet use, especially among children.

Anti-malarial prescribing practices in Sudan eight years after introduction of artemisinin-based combination therapies and implications for development of drug resistance.

BACKGROUND: The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs) as first-line treatment for uncomplicated malaria. Sudan revised its malaria treatment policy accordingly in 2004. However, eight years after ACTs were introduced in Sudan the patterns of ACT prescribing practices among health care providers remain unclear. We systematically analyzed use of ACTs in a large number of primary health facilities and we discuss the public health implications of our findings. METHODS: This cross-sectional study was based on WHO's guidance for investigating drug use in health facilities. Data were collected from 40 randomly selected primary health centers in five localities in Gezira State, Sudan. The primary outcome of the study was the proportion of patients who were adequately managed according to Sudan's recommended malaria treatment guidelines. Twelve drug-use indicators were used to assess key ACT prescribing practices. RESULTS: One thousand and two hundred patients diagnosed with uncomplicated malaria were recruited into the study. ACT was prescribed for 88.6%patients and artemether injections were (incorrectly) prescribed in 9.5% of cases. Only 40.9% of patients in the study were correctly diagnosed and 26.9% were adequately managed according to the nationally recommended treatment guidelines. Incorrect prescribing activities included failure to use generic medicine names (88.2%), incorrect dosage (27.7%), and unexplained antibiotic co-prescription (24.2%). Dispensing practices were also poor, with labeling practices inadequate (97.1%) and insufficient information given to patients about their prescribed treatment (50.5%). CONCLUSION: Irrational malaria treatment practices are common in Sudan. This has important public health implications since failure to adhere to nationally recommended guidelines could play a role in the future development of drug resistance. As such, identifying ways to improve the anti-malarial prescribing practices of heath workers in Sudan may be a priority.

Do frontline health care providers know enough about artemisinin-based combination therapy to rationally treat malaria? A cross-sectional survey in Gezira State, Sudan.

BACKGROUND: In 2004, artemisinin-based combination therapy (ACT) was introduced in Sudan for the treatment of malaria. The role of health care providers working in first-level health care facilities is central for the effective implementation of this revised malaria treatment policy. However, information about their level of ACT knowledge is inadequate. This study sought to describe frontline health care providers' knowledge about the formulations and dose regimens of nationally recommended ACT in Sudan. METHODS: This cross-sectional study took place in Gezira State, Sudan. Data were gathered from five localities comprising forty primary health care facilities. A total of 119 health care providers participated in the study (72 prescribers and 47 dispensers). The primary outcome was the proportion of health care providers who were ACT knowledgeable, a composite indicator of health care providers' ability to (1) define what combination therapy is; (2) identify the recommended first- and second-line treatments; and (3) correctly state the dose regimens for each. RESULTS: All prescribers and 95.7% (46/47) of dispensers were aware of the new national malaria treatment policy. However, 93.1% (67/72) of prescribers compared to 87.2% (41/47) of dispensers recognized artesunate-sulphadoxine/pyrimethamine as the recommended first-line treatment in Sudan. Only a small number of prescribers and dispensers (9.4% and 13.6%, respectively) were able to correctly define the meaning of a combination therapy. Overall, only 22% (26/119, 95% CI 14.6-29.4) of health care providers were found to be ACT knowledgeable with no statistically significant difference between prescribers and dispensers. CONCLUSION: Overall, ACT knowledge among frontline health care providers is very poor. This finding suggests that efforts are needed to improve knowledge of prescribers and dispensers working in first-level health care facilities, perhaps through implementing focused, provider-oriented training programmes. Additionally, a system for regularly monitoring and evaluating the quality of in-service training may be beneficial to ensure its responsiveness to the needs of the target health care providers.

Prospective Audit of Avoidable Factors in Institutional Stillbirths and Early Neonatal Deaths at Tikur Anbessa Hospital in Addis Ababa, Ethiopia.

Mortality audits are being used with increasing frequency to improve health outcomes by pinpointing precisely where deficiencies in clinical care exist. We conducted a prospective audit of stillbirths and early neonatal deaths at Tikur Anbessa Hospital in Addis Ababa, Ethiopia, as part of a broader initiative to reduce perinatal mortality in the labor room and neonatal intensive care unit. Out of 1,225 deliveries that took place during the six-month study period, there were 30 stillbirths and 31 early neonatal deaths (PMR 50/1,000). A multi-disciplinary Audit Team was established and convened monthly to review standardized data collection forms that were completed for each death. It was determined that avoidable factors were present in 70% of perinatal deaths. Health worker-related factors were the most common avoidable factors identified (accounting for 84% of avoidable factors identified), followed by patient-related factors (11%) and administrative-related factors (5%). Based on the study findings, quality improvement programs that target gaps in care are being implemented on the hospital's labor room and in the neonatal intensive care unit.

Designing the WHO Safe Childbirth Checklist program to improve quality of care at childbirth.

BACKGROUND: Poor-quality care during institutional births in low- and middle-income countries is a major contributing factor to preventable maternal and newborn harm, but progress has been slow in identifying effective methods to address these deficiencies at scale. Based on the success of checklist programs in other disciplines, WHO led the design and field testing of the WHO Safe Childbirth Checklist-a 29-item tool that targets the major causes of maternal and newborn mortality globally. METHODS: The development process consisted of comprehensive evidence and guideline review, in-person consultation with content experts and other key stakeholders, iterative refinement through ongoing discussions with a wide collaborator network, and field evaluation for usability in 9 countries, primarily in Africa and Asia. Pilot testing in South India demonstrated major improvement in health workers' delivery of essential safety practices after introduction of the program. RESULTS: WHO has launched a global effort to support further evaluation of the program in a range of contexts, and a randomized trial is underway in North India to measure the effectiveness of the program in reducing severe maternal, fetal, and newborn harm. CONCLUSION: A novel checklist program has been developed to support health workers in low-resource settings to prevent avoidable childbirth-related deaths.

Access to essential technologies for safe childbirth: a survey of health workers in Africa and Asia.

BACKGROUND: The reliable availability of health technologies, defined as equipment, medicines, and consumable supplies, is essential to ensure successful childbirth practices proven to prevent avoidable maternal and newborn mortality. The majority of global maternal and newborn deaths take place in Africa and Asia, yet few data exist that describe the availability of childbirth-related health technologies in these regions. We conducted a cross-sectional survey of health workers in Africa and Asia in order to profile the availability of health technologies considered to be essential to providing safe childbirth care. METHODS: Health workers in Africa and Asia were surveyed using a web-based questionnaire. A list of essential childbirth-related health technologies was drawn from World Health Organization guidelines for preventing and managing complications associated with the major causes of maternal and newborn mortality globally. Demographic data describing each birth center were obtained and health workers reported on the availability of essential childbirth-related health technologies at their centers. Comparison analyses were conducted using Rao-Scott chi-square test statistics. RESULTS: Health workers from 124 birth centers in 26 African and 15 Asian countries participated. All facilities exhibited gaps in the availability of essential childbirth-related health technologies. Availability was significantly reduced in birth centers that had lower birth volumes and those from lower income countries. On average across all centers, health workers reported the availability of 18 of 23 essential childbirth-related health technologies (79%; 95% CI, 74%, 84%). Low-volume facilities suffered severe shortages; on average, these centers reported reliable availability of 13 of 23 technologies (55%; 95% CI, 39%, 71%). CONCLUSIONS: Substantial gaps exist in the availability of essential childbirth-related health technologies across health sector levels in Africa and Asia. Strategies that facilitate reliable access to vital health technologies in these regions are an urgent priority.

'Helping babies breathe' training in sub-saharan Africa: educational impact and learner impressions.

BACKGROUND: Poor resuscitation contributes significantly to neonatal deaths globally. Helping Babies Breathe (HBB) is a new evidence-based neonatal resuscitation curriculum for low-resource settings. OBJECTIVE: We sought to characterize knowledge changes after national-level HBB training in Ethiopia, factors correlated with successful training, resuscitation skills and trainees' perceptions. METHODS: Trainees completed multiple-choice questionnaires (MCQ) before and after a 2-day course. After training, bag-mask ventilation (BMV) skills were assessed and feedback questionnaires completed. RESULTS: Resuscitation knowledge improved from 8.7/10 (SD 1.4) to 9.4/10 (SD 1.1; p = 0.003). Correct MCQ responses relating to essential aspects of resuscitation increased 68-79%. Pre-training knowledge differences between physicians and non-physicians disappeared. MCQ scores increased as trainer:trainee ratio decreased (p = 0.004). Mean post-HBB BMV scores [5.7/7 (SD 1.6)] were not impacted by trainer:trainee ratio. CONCLUSIONS: Ethiopian HBB training improved neonatal resuscitation knowledge and was well received. Lower trainer:trainee ratio was associated with increased MCQ scores. HBB eliminated baseline knowledge differences between Ethiopian healthworker cadres.

Improving quality of care for maternal and newborn health: prospective pilot study of the WHO safe childbirth checklist program.

BACKGROUND: Most maternal deaths, intrapartum-related stillbirths, and newborn deaths in low income countries are preventable but simple, effective methods for improving safety in institutional births have not been devised. Checklist-based interventions aid management of complex or neglected tasks and have been shown to reduce harm in healthcare. We hypothesized that implementation of the WHO Safe Childbirth Checklist program, a novel childbirth safety program for institutional births incorporating a 29-item checklist, would increase delivery of essential childbirth practices linked with improved maternal and perinatal health outcomes. METHODS AND FINDINGS: A pilot, pre-post-intervention study was conducted in a sub-district level birth center in Karnataka, India between July and December 2010. We prospectively observed health workers that attended to women and newborns during 499 consecutively enrolled birth events and compared these with observed practices during 795 consecutively enrolled birth events after the introduction of the WHO Safe Childbirth Checklist program. Twenty-nine essential practices that target the major causes of childbirth-related mortality, such as hand hygiene and uterotonic administration, were evaluated. The primary end point was the average rate of successful delivery of essential childbirth practices by health workers. Delivery of essential childbirth-related care practices at each birth event increased from an average of 10 of 29 practices at baseline (95%CI 9.4, 10.1) to an average of 25 of 29 practices afterwards (95%CI 24.6, 25.3; p<0.001). There was significant improvement in the delivery of 28 out of 29 individual practices. No adverse outcomes relating to the intervention occurred. Study limitations are the pre-post design, potential Hawthorne effect, and focus on processes of care versus health outcomes. CONCLUSIONS: Introduction of the WHO Safe Childbirth Checklist program markedly improved delivery of essential safety practices by health workers. Future study will determine if this program can be implemented at scale and improve health outcomes.

Neonatal resuscitation capacity in Nepal.

AIM: Perinatal asphyxia is a major contributor to the nearly 4 million neonatal deaths worldwide each year in resource-limited settings. Neonatal resuscitation, a proven method for preventing newborn deaths, is effective only when local caregivers have proper training and access to essential supplies. There are few published data describing neonatal resuscitation capacity in Nepal, where neonatal mortality rates are high. The goal of this study was to quantify neonatal resuscitation capacity at birthing sites in urban and rural Nepal. METHODS: Seventeen birth centres ranging from tertiary care hospitals to rural health posts were evaluated. Assessments included standardised interviews of health-care workers and evaluation of newborn resuscitation areas. The availability of essential resuscitation tools was recorded. RESULTS: Eleven of the 17 health centres conducted deliveries on-site. Of those, 45% had posted and visible resuscitation algorithms; 72% had infant warmers; 91% had mechanical suction machines; 36% had bulb suctions and 82% had bag-mask ventilation devices available. Tertiary hospitals were much better equipped compared with smaller health centres. None of the health-care workers who attended home deliveries had access to algorithms, warming devices, suction or bag-mask ventilation devices. CONCLUSIONS: Availability of appropriate resuscitation supplies was variable in health centres providing delivery services on-site and was severely deficient among health staff attending to home deliveries. Limited availability of resuscitation equipment may contribute to the high neonatal mortality rates seen in Nepal. Sustainable training programmes and distribution of neonatal resuscitation equipment are critical priorities in this region.

Mississippi's infectious disease hotline: a surveillance and education model for future disasters.

INTRODUCTION: The potential for outbreaks of epidemic disease among displaced residents was a significant public health concern in the aftermath of Hurricane Katrina. In response, the Mississippi Department of Health (MDH) and the American Red Cross (ARC) implemented a novel infectious disease surveillance system, in the form of a telephone "hotline", to detect and rapidly respond to health threats in shelters. METHODS: All ARC-managed shelters in Mississippi were included in the surveillance system. A symptom-based, case reporting method was developed and distributed to shelter staff, who were linked with MDH and ARC professionals by a toll-free telephone service. Hotline staff investigated potential infectious disease outbreaks, provided assistance to shelter staff regarding optimal patient care, and helped facilitate the evaluation of ill evacuees by local medical personnel. RESULTS: Forty-three shelters sheltering 3,520 evacuees participated in the program. Seventeen shelters made 29 calls notifying the hotline of the following cases: (1) fever (6 cases); (2) respiratory infections (37 cases); (3) bloody diarrhea (2 cases); (4) watery diarrhea (15 cases); and (5) other, including rashes (33 cases). Thirty-four of these patients were referred to a local physician or hospital for further diagnosis and disease management. Three cases of chickenpox were identified. No significant infectious disease outbreaks occurred and no deaths were reported. CONCLUSIONS: The surveillance system used direct verbal communication between shelter staff and hotline managers to enable more rapid reporting, mapping, investigation, and intervention, far beyond the capabilities of a more passive or paper-based system. It also allowed for immediate feedback and education for staff unfamiliar with the diseases and reporting process. Replication of this program should be considered during future disasters when health surveillance of a large, disseminated shelter population is necessary.