Understanding key drivers and barriers to implementation of the WHO recommendations for the case management of childhood pneumonia and possible serious bacterial infection with amoxicillin dispersible tablets (DT) in Bangladesh: a qualitative study.

BACKGROUND: Pneumonia and possible serious bacterial infection (PSBI) are leading causes of death among under-five children. The World Health Organization (WHO) issued global recommendations for the case management of childhood pneumonia and PSBI when referral is not feasible with oral amoxicillin. However, few governments to date have incorporated child-friendly amoxicillin dispersible tablets (DT) into their national treatment guidelines and policies. We aimed to understand the key drivers to the implementation of WHO recommendations for childhood pneumonia and PSBI using amoxicillin DT in Bangladesh. METHODS: A qualitative study was conducted from October 2017 to March 2018 in two districts of Bangladesh. Interviews were completed with 67 participants consisting of government officials and key stakeholders, international development agencies, health service providers (HSPs), and caregivers of young children diagnosed and treated with amoxicillin for pneumonia or PSBI. Data were analyzed thematically. RESULTS: Policies and operational planning emerged as paramount to ensuring access to essential medicines for childhood pneumonia and PSBI. Though amoxicillin DT is included for National Newborn Health Programme and Integrated Management of Childhood Illnesses in the Operational Plan of the Directorate General of Health Services, inclusion in Community-Based Healthcare Project and Directorate General of Family Planning policies is imperative to securing national supply, access, and uptake. At the sub-national level, training on the use of amoxicillin DT as a first line intervention is lacking, resulting in inadequate management of childhood pneumonia by HSPs. Advocacy activities are needed to create community-wide demand among key stakeholders, HSPs, and caregivers not yet convinced that amoxicillin DT is the preferred formulation for the management of childhood pneumonia and PSBI. CONCLUSION: Challenges in policy and supply at the national level and HSP preparedness at the sub-national levels contribute to the slow adoption of WHO recommendations for amoxicillin DT in Bangladesh. A consultation meeting to disseminate study findings was instrumental in driving the development of recommendations by key stakeholders to address these challenges. A comprehensive and inclusive evidence-based strategy involving all divisions of the Ministry of Health and Family Welfare will be required to achieve national adoption of WHO recommendations and country-wide introduction of amoxicillin DT in Bangladesh.

Qualitative development of the 'Questionnaire on Pain caused by Spasticity (QPS),' a pediatric patient-reported outcome for spasticity-related pain in cerebral palsy.

PURPOSE: To develop a patient-reported outcome measure for spasticity-related pain in children/adolescents (age 2-17 years) with cerebral palsy (CP), the 'Questionnaire on Pain caused by Spasticity (QPS).' METHODS: Using a semi-structured interview guide, concept elicitation interviews on spasticity-related pain in upper and lower limbs were conducted in 21 children and caregiver pairs. Data were used to modify initial QPS modules and develop six draft modules, which were subsequently refined and finalized in four consecutive cognitive interview waves (12 children and caregiver pairs). RESULTS: To accommodate the broad range in the children's communication skills, QPS child/adolescent modules were developed in both interviewer-administered and self-administered formats. With the additional parent modules, three QPS modules were developed for each of the upper and lower limb applications. Information gained from the parent/caregiver modules complements the child/adolescent assessment. Parents report observed signs and frequency of pain in the same situations used to capture the child/adolescent reports of pain severity (e.g., rest, usual daily activities, active mobilization, and physically difficult activities). Participating children/adolescents and parents/caregivers reported that the final QPS instruments were comprehensive, relevant to the child's spasticity-related experience, and easy to understand and complete. CONCLUSIONS: The QPS is a novel instrument for the assessment of spasticity-related pain in children/adolescents with CP that was developed with direct patient input. Its modules allow the use of this instrument in children/adolescents with varied levels of impairment and communication skills.

Effect of rotavirus vaccination on death from childhood diarrhea in Mexico.

BACKGROUND: A phased introduction of a monovalent rotavirus vaccine occurred in Mexico from February 2006 through May 2007. We assessed the effect of vaccination on deaths from diarrhea in Mexican children in 2008 and 2009. METHODS: We obtained data on deaths from diarrhea, regardless of cause, from January 2003 through May 2009 in Mexican children under 5 years of age. We compared diarrhea-related mortality in 2008 and during the 2008 and 2009 rotavirus seasons with the mortality at baseline (2003-2006), before the introduction of the rotavirus vaccine. Vaccine coverage was estimated from administrative data. RESULTS: By December 2007, an estimated 74% of children who were 11 months of age or younger had received one dose of rotavirus vaccine. In 2008, there were 1118 diarrhea-related deaths among children younger than 5 years of age, a reduction of 675 from the annual median of 1793 deaths during the 2003-2006 period. Diarrhea-related mortality fell from an annual median of 18.1 deaths per 100,000 children at baseline to 11.8 per 100,000 children in 2008 (rate reduction, 35%; 95% confidence interval [CI], 29 to 39; P<0.001). Among infants who were 11 months of age or younger, diarrhea-related mortality fell from 61.5 deaths per 100,000 children at baseline to 36.0 per 100,000 children in 2008 (rate reduction, 41%; 95% CI, 36 to 47; P<0.001). As compared with baseline, diarrhea-related mortality was 29% lower for children between the ages of 12 and 23 months, few of whom were age-eligible for vaccination. Mortality among unvaccinated children between the ages of 24 and 59 months was not significantly reduced. The reduction in the number of diarrhea-related deaths persisted through two full rotavirus seasons (2008 and 2009). CONCLUSIONS: After the introduction of a rotavirus vaccine, a significant decline in diarrhea-related deaths among Mexican children was observed, suggesting a potential benefit from rotavirus vaccination.

Feasibility Study for the Rectal Route of Administration for Gentamicin Evaluated in the Neonatal Minipig Model.

Neonatal infections are a major cause of newborn mortality in low- and middle-income countries, particularly in areas without access to inpatient care. To address this, the World Health Organization developed guidelines for delivering simplified antibiotic regimens (oral amoxicillin and intramuscular gentamicin) in outpatient settings to young infants with suspected serious bacterial infection when referral is not feasible. However, there are still limitations to access, as the regimen requires a health care provider trained in giving intramuscular injections to infants. To provide a needle-free, simplified alternate to intramuscular delivery, PATH investigated the feasibility of the rectal administration of gentamicin. Potential formulations were screened by in vitro testing, and 2 liquid enema formulations and a cocoa butter suppository were developed and evaluated in a preclinical study of the rectal uptake of gentamicin in a neonatal minipig model. Sera samples from the control group, dosed by intramuscular injection, resulted in expected sera concentrations of gentamicin, but no gentamicin was detected in the sera of groups rectally dosed with the test formulations. The results of this study did not provide evidence to support the therapeutic feasibility of rectally absorbed gentamicin.

Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis.

Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19×19 needles and 500µm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378µm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5µg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo.

Impact of rotavirus vaccination on diarrhea-related hospitalizations among children < 5 years of age in Mexico.

BACKGROUND: Single-strain rotavirus vaccine was added to the national immunization program in Mexico in May 2007. We assessed the impact of vaccination on the number of diarrhea-related hospitalizations in Mexican children in 2008 and 2009. METHODS: We obtained data on all-cause diarrhea-related hospitalizations from January 2003 to June 2009 in Mexican children <5 years of age. We compared diarrhea-related hospitalizations during the 2008 and 2009 rotavirus seasons with the median number of diarrhea-related hospitalizations at baseline (2003-2006), before rotavirus vaccine introduction, at 306 Ministry of Health hospitals. We estimated vaccine coverage using administrative data. RESULTS: A median number of 10,993 diarrhea-related hospitalizations (range: 9877-11958) occurred each prevaccine rotavirus season from 2003 to 2006 among children < 5 years of age. Diarrhea-related hospitalizations decreased by 11% (N = 9836) in 2008 and by 40% (N = 6597) in 2009. The greatest declines occurred in infants < 12 months of age during 2008 (25%) and 2009 (52%), with 1-dose rotavirus vaccination coverage of 74% and 89% during these years, respectively. A 43% decline was also noted among children 12 to 23 months of age during the 2009 season. No declines were noted during either 2008 or 2009 among unvaccinated children >24 months of age during the study period. CONCLUSIONS: Marked declines in diarrhea-related hospitalizations among vaccine-eligible Mexican children < 24 months of age have occurred during the first 2 complete rotavirus seasons following rotavirus vaccination. Rotavirus-specific surveillance and epidemiologic studies are necessary for a better understanding of the changes in disease epidemiology and public health impact from rotavirus vaccination.