Proactive familial cancer risk assessment: a service development study in UK primary care.

BACKGROUND: Family history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention, and Early Detection (SPED). Family History Questionnaire Service (FHQS) is a resource-efficient patient-facing online tool to facilitate this. In the UK, cancer risk assessment is usually only offered to concerned individuals proactively self-presenting to their GP, leading to inequity in accessing SPED in the community. AIM: To improve access to community cancer genetic risk assessment and explore barriers to uptake. DESIGN & SETTING: Service development project of a digital pathway using the FHQS for cancer risk assessment across four general practices within the clinical remit of the South West Thames Centre for Genomics (SWTCG). METHOD: 3100 individuals aged 38-50 years were invited to complete the FHQS through either text message or email. A random selection of 100 non-responders were contacted to determine barriers to uptake. RESULTS: In total, n = 304/3100 (10%) registered for the FHQS. Responders were more likely to be British (63% vs 47%, P<0.001), speak English as their main language (92% vs 76%, P<0.001), and not require an interpreter (99.6% vs 94.9%, P = 0.001). Of 304 responders, 158 (52%) were automatically identified as at population-risk without full family history review. Of the remaining 146 responders, 52 (36%) required either additional screening referral (n = 23), genetics referral (n = 15), and/or advice to relatives (n = 18). Of 100 non-responders contacted, eight had incorrect contact details and 53 were contactable. Reasons for not responding included not receiving invitation details (n = 26), losing the invitation (n = 5), or forgetting (n = 4). CONCLUSION: The FHQS can be used as part of a low-resource primary care pathway to identify individuals in the community above population-risk for cancer requiring action. This study highlighted barriers to uptake requiring consideration to maximise impact and minimise inequity.

Direct and indirect costs of acute diarrhea in children under five years of age in Indonesia: Health facilities and community survey.

BACKGROUND: Diarrhea remains a major cause of child morbidity and mortality in low- and middle-income countries. Reliable data on the economic burden of diarrhea is required to support the selection of appropriate health intervention programs. This study aimed to estimate the costs of acute diarrhea in children under five years of age in Indonesia, a large middle-income country with a substantial diarrheal burden. METHODS: Direct medical cost data were extracted retrospectively for 1050 children under five years of age with acute diarrhea receiving inpatient care across 45 health facilities in seven Indonesian provinces during 2017-2020. Direct medical costs for children treated in outpatient settings were estimated by collecting unit costs associated with standard diarrhea case management in children. A structured interview of 240 caregivers of inpatients was also conducted retrospectively to estimate direct non-medical costs as well as indirect costs from caregiver income loss. RESULTS: The weighted average direct medical cost for treatment of acute diarrhea as an inpatient and outpatient across health facility types was US$99.8 (SD±$56.8)(35% room costs, 29% professional fees, 26% medication costs, 10% diagnostic costs) and US$7.6 (SD±$4.3) (34% diagnostic costs, 28% medication costs, 27% professional fees, 10% registration fees), respectively. The average direct non-medical household cost for an acute diarrheal admission was US$4.90 and the indirect cost was US$9.90. CONCLUSION: There is a significant economic burden associated with acute diarrhea in children in Indonesia. This study, based on a wide variety of health care settings and geographical regions, provides data to inform the economic evaluation of rotavirus vaccines and other diarrheal prevention programs. FUNDING: This work was supported by a research grant from the Murdoch Children's Research Institute (MCRI) and PATH; and the Indonesian Technical Advisory Group on Immunization (ITAGI).

Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Indonesian children: A cross-sectional study.

Streptococcus pneumoniae is an important cause of infection and commonly colonizes the nasopharynx of young children, along with other potentially pathogenic bacteria. The objectives of this study were to estimate the carriage prevalence of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in young children in Indonesia, and to examine interactions between these bacterial species. 302 healthy children aged 12-24 months were enrolled in community health centers in the Bandung, Central Lombok, and Padang regions. Nasopharyngeal swabs were collected and stored according to World Health Organization recommendations, and bacterial species detected by qPCR. Pneumococcal serotyping was conducted by microarray and latex agglutination/Quellung. Overall carriage prevalence was 49.5% for S. pneumoniae, 27.5% for H. influenzae, 42.7% for M. catarrhalis, and 7.3% for S. aureus. Prevalence of M. catarrhalis and S. pneumoniae, as well as pneumococcal serotype distribution, varied by region. Positive associations were observed for S. pneumoniae and M. catarrhalis (OR 3.07 [95%CI 1.91-4.94]), and H. influenzae and M. catarrhalis (OR 2.34 [95%CI 1.40-3.91]), and a negative association was found between M. catarrhalis and S. aureus (OR 0.06 [95%CI 0.01-0.43]). Densities of S. pneumoniae, H. influenzae, and M. catarrhalis were positively correlated when two of these species were present. Prior to pneumococcal vaccine introduction, pneumococcal carriage prevalence and serotype distribution varies among children living in different regions of Indonesia. Positive associations in both carriage and density identified among S. pneumoniae, H. influenzae, and M. catarrhalis suggest a synergistic relationship among these species with potential clinical implications.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

BACKGROUND: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. METHODS: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. RESULTS: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). CONCLUSIONS: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.