Allergen skin test reactivity and asthma are inversely associated with ratios of IgG4/IgE and total IgE/allergen-specific IgE in Ugandan communities.

BACKGROUND: Serum inhibition of allergen-specific IgE has been associated with competing IgG4 and non-specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth-associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low-income countries. METHODS: Among community residents of Ugandan rural Schistosoma mansoni (Sm)-endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non-asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)-specific, Schistosoma egg antigen (SEA)-specific and allergen (house dust mite [HDM] and German cockroach)-specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural-urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma. RESULTS: Total IgE, total IgG4 and SWA-, SEA- and allergen-specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen-specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma-specific IgG4, allergen-specific IgG4/IgE ratios and total IgE/allergen-specific IgE ratios. Asthmatic schoolchildren, compared with non-asthmatic controls, had significantly higher levels of total and allergen-specific IgE, but lower ratios of allergen-specific IgG4/IgE and total IgE/allergen-specific IgE. CONCLUSIONS AND CLINICAL RELEVANCE: Our immuno-epidemiological data support the hypothesis that the IgG4-IgE balance and the total IgE-allergen-specific IgE balance are more important than absolute total, helminth- or allergen-specific antibody levels in inhibition of allergies in the tropics.

Cross-reactive carbohydrate determinant-specific IgE obscures true atopy and exhibits ⍺-1,3-fucose epitope-specific inverse associations with asthma.

BACKGROUND: In high-income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy-related diseases (ARDs). In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross-reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti-CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD. METHODS: Using an allergen extract-based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan rural Schistosoma mansoni (Sm)-endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren. RESULTS: Overall, IgE sensitization to extracts was highly prevalent (43%-73%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%-36%); instead, over 40% of all participants recognized CCD-bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core ß-1,2-xylose, α-1,3-fucose) was positively associated with sensitization to extracts, rural environment and Sm infection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core α-1,3-fucose-carrying N-glycans was inversely associated with asthma. CONCLUSIONS: CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma.

The Impact of Intensive Versus Standard Anthelminthic Treatment on Allergy-related Outcomes, Helminth Infection Intensity, and Helminth-related Morbidity in Lake Victoria Fishing Communities, Uganda: Results From the LaVIISWA Cluster-randomized Trial.

BACKGROUND: The prevalence of allergy-related diseases is increasing in low-income countries. Parasitic helminths, common in these settings, may be protective. We hypothesized that intensive, community-wide, anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity. METHODS: In an open, cluster-randomized trial (ISRCTN47196031), we randomized 26 high-schistosomiasis-transmission fishing villages in Lake Victoria, Uganda, in a 1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel plus albendazole daily for 3 days) or standard (annual praziquantel plus 6 monthly single-dose albendazole) MDA. Primary outcomes were recent wheezing, skin prick test positivity (SPT), and allergen-specific immunoglobulin E (asIgE) after 3 years of intervention. Secondary outcomes included helminths, haemoglobin, and hepatosplenomegaly. RESULTS: The outcome survey comprised 3350 individuals. Intensive MDA had no effect on wheezing (risk ratio [RR] 1.11, 95% confidence interval [CI] 0.64-1.93), SPT (RR 1.10, 95% CI 0.85-1.42), or asIgE (RR 0.96, 95% CI 0.82-1.12). Intensive MDA reduced Schistosoma mansoni infection intensity: the prevalence from Kato Katz examinations of single stool samples from each patient was 23% versus 39% (RR 0.70, 95% CI 0.55-0.88), but the urine circulating cathodic antigen test remained positive in 85% participants in both trial arms. Hookworm prevalence was 8% versus 11% (RR 0.55, 95% CI 0.31-1.00). There were no differences in anemia or hepatospenomegaly between trial arms. CONCLUSIONS: Despite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy-related diseases, or helminth-related pathology. This could be due to sustained low-intensity infections; thus, a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has a limited impact in high-schistosomiasis-transmission fishing communities, in the absence of other interventions. CLINICAL TRIALS REGISTRATION: ISRCTN47196031.

Do helminth infections underpin urban-rural differences in risk factors for allergy-related outcomes?

BACKGROUND: It is proposed that helminth exposure protects against allergy-related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses. OBJECTIVE: We aimed to assess how helminth exposure influences rural-urban differences in risk factors for allergy-related outcomes in tropical low- and middle-income countries. METHODS: In cross-sectional surveys in Ugandan rural Schistosoma mansoni (Sm)-endemic islands, and in nearby mainland urban communities with lower helminth exposure, we assessed risk factors for atopy (allergen-specific skin prick test [SPT] reactivity and IgE [asIgE] sensitization) and clinical allergy-related outcomes (wheeze, urticaria, rhinitis and visible flexural dermatitis), and effect modification by Sm exposure. RESULTS: Dermatitis and SPT reactivity were more prevalent among urban participants, urticaria and asIgE sensitization among rural participants. Pairwise associations between clinical outcomes, and between atopy and clinical outcomes, were stronger in the urban survey. In the rural survey, SPT positivity was inversely associated with bathing in lakewater, Schistosoma-specific IgG4 and Sm infection. In the urban survey, SPT positivity was positively associated with age, non-Ugandan maternal tribe, being born in a city/town, BCG scar and light Sm infection. Setting (rural vs urban) was an effect modifier for risk factors including Sm- and Schistosoma-specific IgG4. In both surveys, the dominant risk factors for asIgE sensitization were Schistosoma-specific antibody levels and helminth infections. Handwashing and recent malaria treatment reduced odds of asIgE sensitization among rural but not urban participants. Risk factors for clinical outcomes also differed by setting. Despite suggestive trends, we did not find sufficient evidence to conclude that helminth (Sm) exposure explained rural-urban differences in risk factors. CONCLUSIONS AND CLINICAL RELEVANCE: Risk factors for allergy-related outcomes differ between rural and urban communities in Uganda but helminth exposure is unlikely to be the sole mechanism of the observed effect modification between the two settings. Other environmental exposures may contribute significantly.

Prevalence and associated factors of neurodevelopmental disability among infants in eastern Uganda: a population based study.

BACKGROUND: Neurodevelopmental disability (NDD) is increasingly acknowledged as one of the important causes of disease burden in low income countries. None the less, there is a dearth of data on the burden of NDD and its determinants in these settings. We aimed to establish the prevalence and factors associated with NDD among infants in Eastern Uganda. METHODS: We assessed 487 infants aged 9-12 months within Iganga-Mayuge Health Demographic Surveillance Site in Eastern Uganda using the Malawi Developmental Assessment Tool. The tool has four domains: gross motor, fine motor, language and social domains. An infant failed a domain if she/he failed more than two parameters of the expected at his/her age. We interviewed mothers on factors that could influence the infants' neurodevelopmental outcomes. Data were analysed using STATA version 14. We used odds ratios and 95% confidence intervals to assess statistical significance of associations. RESULTS: Of the 487 infants, 62(12.7%) had an NDD in at least one of the domains. The most affected was social behaviour where 52(10.7%) infants had an NDD. Severe impairment was seen among 9(1.8%) infants with NDD in either three or four domains. Factors associated with NDD at multivariate logistic regression included: parity of more than three children (aOR = 1.8, 95% CI: 1.02-3.18); failure to cry at birth (aOR = 3.6, 95% CI: 1.46-9.17) and post-neonatal complications (aOR = 4.15, 95% CI: 1.22-14.10). Low birth weight, immediate and exclusive breast feeding were not significantly associated with NDD. CONCLUSION: We found a high NDD burden among infants particularly in the social behaviour domain. To optimise the socio-neural development of infants, programs are needed to educate and work with families on how to engage and stimulate infants. Existing immunisation clinics and community health worker strategies provide an excellent opportunity for stemming this burden.

Life-course of atopy and allergy-related disease events in tropical sub-Saharan Africa: A birth cohort study.

BACKGROUND: In high-income countries, allergy-related diseases (ARDs) follow a typical sequence, the 'Atopic March'. Little is known about the life-course of ARDs in the markedly different, low-income, tropical environment. We describe ARDs in a tropical, African birth cohort. METHODS: Ugandan children were followed from birth to 9 years. ISAAC questionnaires were completed at intervals; doctor-diagnosed ARDs were recorded throughout follow-up. Skin prick tests (SPTs) were performed at 3 and 9 years. Atopy was defined as ≥1 positive SPT. RESULTS: Of the 2345 live-born children, 1214 (52%) were seen at 9 years. Wheeze and eczema were common in infancy, but by 9 years, only 4% reported recent wheeze, 5% eczema and 5% rhinitis. Between 3 and 9 years, atopy prevalence increased from 19% to 25%. Atopy at 3 or 9 years was associated with reported ARD events at 9 years, for example OR = 5.2 (95% CI 2.9-10.7) for atopy and recent wheeze at 9 years. Reported or doctor-diagnosed ARD events in early childhood were associated with the same events in later childhood, for example OR = 4.4 (2.3-8.4) for the association between reported wheeze before 3 years with reported recent wheeze at 9 years, but progression from early eczema to later rhinitis or asthma was not observed. CONCLUSION: Allergen sensitization started early in childhood and increased with age. Eczema and wheeze were common in infancy and declined with age. Atopy was strongly associated with ARD among the few affected children. The typical Atopic March did not occur. Environmental exposures during childhood may dissociate atopy and ARD.

Schistosoma mansoni and HIV infection in a Ugandan population with high HIV and helminth prevalence.

OBJECTIVES: Recent reports suggest that Schistosoma infection may increase the risk of acquiring human immunodeficiency virus (HIV). We used data from a large cross-sectional study to investigate whether Schistosoma mansoni infection is associated with increased HIV prevalence. METHODS: We conducted a household survey of residents in island fishing communities in Mukono district, Uganda, between October 2012 and July 2013. HIV status was assessed using rapid test kits. Kato-Katz (KK) stool tests and urine-circulating cathodic antigen (CCA) were used to test for Schistosoma infection. Multivariable logistic regression, allowing for the survey design, was used to investigate the association between S. mansoni infection and HIV infection. RESULTS: Data from 1412 participants aged 13 years and older were analysed (mean age 30.3 years, 45% female). The prevalence of HIV was 17.3%. Using the stool Kato-Katz technique on a single sample, S. mansoni infection was detected in 57.2% (719/1257) of participants; urine CCA was positive in 73.8% (478/650) of those tested. S. mansoni infection was not associated with HIV infection. [KK (aOR = 1.04; 95% CI: 0.74-1.47, P = 0.81), CCA (aOR = 1.53; 95% CI: 0.78-3.00, P = 0.19)]. The median S. mansoni egg count per gram was lower in the HIV-positive participants (P = 0.005). CONCLUSIONS: These results add to the evidence that S. mansoni has little effect on HIV transmission, but may influence egg excretion.

Maternal hookworm modifies risk factors for childhood eczema: results from a birth cohort in Uganda.

BACKGROUND: Worms may protect against allergy. Early-life worm exposure may be critical, but this has not been fully investigated. OBJECTIVES: To investigate whether worms in pregnancy and in early childhood are associated with childhood eczema incidence. METHODS: The Entebbe Mother and Baby Study, an anthelminthic treatment trial, enrolled pregnant women between 2003 and 2005 in Uganda. Mothers were investigated for worms during pregnancy and children annually. Eczema was doctor-diagnosed from birth to age five years. A planned observational analysis was conducted within the trial cohort to investigate associations between worms and eczema. RESULTS: Data for 2345 live-born children were analysed. Hookworm was the most prevalent maternal worm (45%). Childhood worms were less prevalent. Eczema incidence was 4.68/100 person-years. Maternal hookworm was associated with reduced eczema incidence [adjusted hazard ratio (95% confidence interval), p-value: 0.71(0.51-0.99), 0.04] and modified effects of known risk factors for eczema: Dermatophagoides-specific IgE in children was positively associated with eczema incidence if the mother had no hookworm [2.72(1.11-6.63), 0.03], but not if the mother had hookworm [0.41(0.10-1.69), 0.22], interaction p-value = 0.03. Similar interactions were seen for maternal history of eczema {[2.87(1.31-6.27, 0.008) vs. [0.73(0.23-2.30), 0.60], interaction p-value = 0.05}, female gender {[1.82(1.22-2.73), 0.004 vs. [0.96(0.60-1.53), 0.87], interaction p-value = 0.04} and allergen-specific IgE. Childhood Trichuris trichiura and hookworm were inversely associated with eczema. CONCLUSIONS: Maternal hookworm modifies effects of known risk factors for eczema. Mechanisms by which early-life worm exposures influence allergy need investigation. Worms or worm products, and intervention during pregnancy have potential for primary prevention of allergy.

Nurturing care practices for children with developmental disabilities in sub-Saharan Africa: A scoping review protocol.

BACKGROUND: The majority of children with neurodevelopmental disorders (NDDs) reside in low- and middle-income countries (LMICs). NDDs are a public health concern in countries in sub-Saharan Africa (SSA). Nurturing care has been recommended as a pathway for addressing the developmental needs and unlocking the full potential of children, including those with NDDs. However, little information exists on the strategies to support children with NDDs using the Nurturing Care Framework in many countries in SSA. This review aims to synthesize information on nurturing care practices for children with NDDs in SSA. The review will also determine gaps in the provision of nurturing care for children with NDDs. Further, the review will highlight the drivers of care as well as the experiences of the caregivers. METHODS: The review will be implemented in six steps: specification of the research question, identification of relevant studies, selection of studies to be included, extracting, mapping, and charting the data, collating, summarizing, and reporting the results, and stakeholder consultation. We propose a database search followed by a manual search for the literature synthesis. We will search the following electronic databases: PubMed, ScienceDirect, Scopus, Open Grey and African Journals Online (AJOL). All studies published after May 2018 to May 2023 that include relevant terms will be identified and included. The research team will develop a data extraction form for use in capturing relevant information from each of the included studies. A patterning chart that will summarize and analyze the key findings of each article will be created. DISCUSSION: We anticipate that the study will provide evidence on the existing nurturing care practices and unearth gaps in the provision of nurturing care for children with NDDs. Key determinants of care and the experiences of the parents/caregivers of children will also be identified. The study will provide key recommendations on interventions to improve the quality of care for children with NDDs. Through this study, awareness of the unmet nurturing care needs of these children will be increased. The evidence generated may assist policymakers and stakeholders in addressing the needs of children with NDDs.

Parental stress and child stimulation practices: examining associations with child developmental outcomes over time in Kenya and Zambia.

BACKGROUND: Parental stress often arises when parenting demands exceed the expected and actual resources available for parents to succeed in the parenting role. Parental stress is an important contributor to parent-child relationships. This, in turn, affects opportunities to engage their children in stimulating activities which could improve their development outcomes. However, limited evidence exists from sub-Saharan Africa (SSA) on the association between parental stress, caregiving practices, and child developmental outcomes. METHODS: The findings reported in this paper were derived from data collected through previous longitudinal work on nurturing care evaluation studies in Kisumu and Nairobi Counties in Kenya, and Chisamba District in Zambia. A total of 341 caregivers and their children who participated in the three rounds of data collection were included in this study. The children's mean age was 9.3 (SD = 8.2) months pre-intervention, 25.5 (SD = 8.6) months in mid-intervention, and 36 (SD = 10.0) months post-intervention. The Ages and Stages Questionnaire (ASQ), Parental Stress Scale (PSS), and caregiving tools were used to assess children's developmental outcomes, parental stress, and stimulation practices, respectively. A Random Intercept Cross-Lagged Panel model (RI-CLPM) was used to determine the association between caregivers' parenting stress, child stimulation practices, and child developmental outcomes. RESULTS: The findings showed that caregiver stimulation practices were positively associated with developmental outcomes. Findings on the associations between parental stress and caregivers' stimulation practices and children's developmental outcomes were not universally supported. CONCLUSION: The findings show that improved caregiver stimulation practices are likely to improve children's developmental outcomes. The policy implications of the findings from this study focus on improving parenting practices by addressing the predictors of parental stress. This includes subsidising childcare services to reduce costs. TRIAL REGISTRATION: Pan African Clinical Trials Registry ( https://pactr.samrc.ac.za/ ) database (ID number: PACTR20180774832663 Date: 26/July/2018.

Mentorship in health research institutions in Africa: A systematic review of approaches, benefits, successes, gaps and challenges.

BACKGROUND: In Africa, where the burden of diseases is disproportionately high, significant challenges arise from a shortage of skilled researchers, lack of research funding, and limited mentorship opportunities. The continent faces a substantial gap in research output largely attributed to the dearth of mentorship opportunities for early career researchers. OBJECTIVE: To explore existing mentorship approaches, identify challenges, gaps, successes, and benefits, and provide insights for strengthening mentorship programs in African health research institutions. METHODS: We registered the review protocol on the International Prospective Register of Systematic Reviews [CRD42021285018] and searched six electronic databases-EMBASE, AJOL, Web of Science, PubMed, DOAJ, and JSTOR from inception to 10 November 2023, for studies published in English reporting on approaches of mentorship in health research in African countries. We also searched grey literature repositories, institutional websites, and reference lists of included studies for additional literature. Two independent reviewers conducted screening of titles and abstracts of identified studies, full-text screening, assessment of methodological quality, and data extraction. We assessed study quality against the Mixed Methods Appraisal Tool (MMAT). We resolved any disagreements through discussion and consensus. We employed a narrative approach to synthesize the findings. RESULTS: We retrieved 1799 articles and after screening, included 21 studies in the review. The reviewers identified 20 mentorship programs for health researchers (N = 1198) in 12 African countries mostly focusing on early-career researchers and junior faculty members. A few included mid-career and senior researchers. We categorized the programs under three key mentoring approaches: international collaborative programs, regional and in-country collaborations, and specialized capacity-building initiatives. Our review highlighted the following successes and benefits of health research mentorship programs: the establishment of collaborations and partnerships, development of research programs and capacities, improvement of individual skills and confidence, increased publications, and successful grant applications. The gaps identified were limited funding, lack of a mentorship culture, negative attitudes towards research careers, and lack of prioritization of research mentorship. CONCLUSION: Our review highlights a diverse landscape of health research mentorship aspects predominantly targeting early career researchers and heavily driven by the North. There is a need for locally driven mentorship initiatives in Africa to strengthen mentorship to advance health research in the region. TRIAL REGISTRATION: PROSPERO registration number: CRD42021285018.

Maternal HIV infection and other factors associated with growth outcomes of HIV-uninfected infants in Entebbe, Uganda.

OBJECTIVE: To assess the associations between maternal HIV infection and growth outcomes of HIV-exposed but uninfected infants and to identify other predictors for poor growth among this population. DESIGN: Within a trial of de-worming during pregnancy, the cohort of offspring was followed from birth. HIV status of the mothers and their children was investigated and growth data for children were obtained at age 1 year. Length-for-age, weight-for-age and weight-for-length Z-scores were calculated for each child; Z-scores ,22 were defined as stunting, underweight and wasting, respectively. SETTING: The study was conducted in Entebbe municipality and Katabi subcounty, Uganda. SUBJECTS: The sample consisted of 1502 children aged 1 year: HIV-unexposed (n 1380) and HIV-exposed not infected (n 122). RESULTS: Prevalence of stunting, underweight and wasting was 14.2%, 8.0% and 3.9%, respectively. There was evidence for an association between maternal HIV infection and odds of being underweight (adjusted OR52.32; 95% CI 1.32, 4.09; P=0.006) but no evidence for an association with stunting or with wasting. Young maternal age, low maternal education, low birth weight, early weaning and experiencing a higher number of episodes of malaria during infancy were independent predictors for stunting and underweight. A higher number of living children in the family was associated with wasting. CONCLUSIONS: Maternal HIV infection was associated with being underweight in HIV-exposed uninfected infants. The success of programmes for prevention of mother-to-child HIV transmission means that an increasing number of infants will be born to HIV-infected women without acquiring HIV. Therefore, viable nutritional interventions need to be identified for this population.

Developing an intervention to improve the quality of childcare centers in resource-poor urban settings: a mixed methods study in Nairobi, Kenya.

Background: Globally, 350 million under-5s do not have adequate childcare. This may damage their health and development and undermine societal and economic development. Rapid urbanization is changing patterns of work, social structures, and gender norms. Parents, mainly mothers, work long hours for insecure daily wages. To respond to increasing demand, childcare centers have sprung up in informal settlements. However, there is currently little or no support to ensure they provide safe, nurturing care accessible to low-income families. Here, we present the process of co-designing an intervention, delivered by local government community health teams to improve the quality of childcare centers and ultimately the health and development of under-5 children in informal settlements in Kenya. Methods: This mixed methods study started with a rapid mapping of the location and basic characteristics of all childcare centers in two informal settlements in Nairobi. Qualitative interviews were conducted with parents and grandparents (n = 44), childcare providers, and community health teams (n = 44). A series of 7 co-design workshops with representatives from government and non-governmental organizations (NGOs), community health teams, and childcare providers were held to design the intervention. Questionnaires to assess the knowledge, attitudes, and practices of community health volunteers (n = 22) and childcare center providers (n = 66) were conducted. Results: In total, 129 childcare centers were identified -55 in Korogocho and 77 in Viwandani. School-based providers dominated in Korogocho (73%) while home-based centers were prevalent in Viwandani (53%). All centers reported minimal support from any organization (19% supported) and this was particularly low among home-based (9%) and center-based (14%) providers. Home-based center providers were the least likely to be trained in early childhood development (20%), hence the co-designed intervention focused on supporting these centers. All co-design stakeholders agreed that with further training, community health volunteers were well placed to support these informal centers. Findings showed that given the context of informal settlements, support for strengthening management within the centers in addition to the core domains of WHO's Nurturing Care Framework was required as a key component of the intervention. Conclusion: Implementing a co-design process embedded within existing community health systems and drawing on the lived experiences of childcare providers and parents in informal settlements facilitated the development of an intervention with the potential for scalability and sustainability. Such interventions are urgently needed as the number of home-based and small center-based informal childcare centers is growing rapidly to meet the demand; yet, they receive little support to improve quality and are largely unregulated. Childcare providers, and government and community health teams were able to co-design an intervention delivered within current public community health structures to support centers in improving nurturing care. Further research on the effectiveness and sustainability of support to private and informal childcare centers in the context of low-income urban neighborhoods is needed.

The economic burden incurred by families caring for a young child with developmental disability in Uganda.

Each year, nearly 30 million children globally are at risk of developmental difficulties and disability as a result of newborn health conditions, with the majority living in resource-constrained countries. This study estimates the annual cost to families related to caring for a young child with developmental disability in Uganda. Nested within a feasibility trial of early care and support for young children with developmental disabilities, this sub-study estimated the cost of illness, the cost of paternal abandonment of the caregiver and the affordability of care by household. Seventy-three caregivers took part in this sub-study. The average annual cost of illness to families was USD 949. The main cost drivers were the cost of seeking care and income lost due to loss of employment. Households caring for a child with a disability spent more than the national average household expenditure, and the annual cost of illness for all households was more than 100% of the national GDP per capita. In addition, 84% of caregivers faced economic consequences and resorted to wealth-reducing coping strategies. Families caring for a child with severe impairment incurred USD 358 more on average than those with mild or moderate impairment. Paternal abandonment was common (31%) with affected mothers losing an average of USD 430 in financial support. Caring for a young child with developmental disability was unaffordable to all the study households. Programmes of early care and support have the potential to reduce these financial impacts. National efforts to curb this catastrophic health expenditure are necessary.

Perceptions of the influence of a mobile phone-based messaging platform on caregiver ECD knowledge, attitudes and practices: a qualitative exploration in an informal settlement in Nairobi.

BACKGROUND: Programs supporting initiatives for children younger than three years are inadequate and not accessible to many families, particularly in resource-limited settings. Many primary caregivers have little knowledge on how to monitor the development of their children or the importance of engaging children in stimulative activities during the course of early development. Health system limitations make it difficult for health workers to educate and demonstrate stimulative engagement to caregivers. The massive use of technology can be used to facilitate access to growth and development programs for children. We developed and implemented a mobile phone technology to help caregivers monitor and stimulate their children's development in real-time. This study explored the influence that this intervention had on the caregivers' early child development (ECD) knowledge, attitudes and practices. METHODS: In this qualitative cross-sectional study, we conducted interviews through eight (8) focus group discussions, three (3) key informant interviews and 9 indepth interviews among a total of 111 participants including primary caregivers (n = 87), community health volunteers (CHVs) (n = 21) health managers and workers (n = 3) to determine their attitudes and experience with the intervention with regards to improving their KAP. Interviews were audio-recorded, transcribed, and analyzed thematically. RESULTS: Caregivers and CHVs reported that the intervention had provided them with new knowledge that positively influenced their ECD caregiving attitudes and practices. CHVs and health workers and managers reported that the intervention had provided caregivers with confidence in caring for their children while increasing their knowledge on how to monitor and stimulate their children's development. CONCLUSION: Mobile phone technology can be effectively used to enhance caregivers' knowledge of ECD and enable them to monitor and support their children's development in real-time. TRIAL REGISTRATION: The trial was registered with the Pan African Clinical Trial Registry ( www.pactr.org ) database (ID number: PACTR201905787868050 Date: 6/05/2019.

The feasibility, acceptability, cost and benefits of a "communities of practice" model for improving the quality of childcare centres: a mixed-methods study in the informal settlements in Nairobi.

Background: Informal childcare centres have mushroomed in the informal settlements of Nairobi, Kenya to meet the increasing demand. However, centre providers are untrained and the facilities are below standard putting children at risk of poor health and development. We aimed to co-design and test the feasibility, acceptability, cost and potential benefits of a communities of practice (CoP) model where trained community health volunteers (CHVs) provide group training sessions to build skills and improve practices in informal childcare centres. Methods: A CoP model was co-designed with sub-county health teams, centre providers and parents with inputs from Kidogo, government nutritionists and ECD experts and implemented in 68 childcare centres by trained CHVs. Its feasibility and potential benefits were measured quantitatively and qualitatively. Centre provider (n = 68) and CHV (n = 20) knowledge and practice scores before and after the intervention were assessed and compared. Intervention benefits were examined using linear regressions adjusting for potential confounding factors. We conducted in-depth interviews with 10 parents, 10 CHVs, 10 centre providers and 20 local government officials, and two focus groups with CHVs and centre providers. Qualitative data were analysed, focusing on feasibility, acceptability, potential benefits, challenges and ideas for improvement. Cost for delivering and accessing the intervention were examined. Results: The intervention was acceptable and feasible to deliver within existing government community health systems; 16 CHVs successfully facilitated CoP sessions to 58 centre providers grouped into 13 groups each with 5-6 centre providers, each group receiving four sessions representing the four modules. There were significant improvements in provider knowledge and practice (effect size = 0.40; p < 0.05) and quality of centre environment (effect size = 0.56; p < 0.01) following the intervention. CHVs' scores showed no significant changes due to pre-existing high knowledge levels. Qualitative interviews also reported improvements in knowledge and practices and the desire among the different participants for the support to be continued. The total explicit costs were USD 22,598 and the total opportunity costs were USD 3,632 (IQR; USD 3,570, USD 4,049). Conclusion: A simple model delivered by CHVs was feasible and has potential to improve the quality of informal childcare centres. Leveraging these teams and integration of the intervention into the health system is likely to enable scale-up and sustainability in Kenya and similar contexts.

Predictors of quality of childcare centers in low-income settings: findings from a cross-sectional study in two Nairobi slums.

Background: Rapid urbanization and increased women's involvement in paid work have contributed to the upsurge of informal childcare centers, especially in low-income settings where quality is a major issue. However, there are limited data on the factors associated with the quality of childcare centers in informal settlements in Africa. Methods: We conducted a quantitative observation and questionnaire survey of 66 childcare centers to identify the factors associated with the quality of childcare services in two informal settlements (Korogocho and Viwandani) in Nairobi. The quality of the centers (outcome variable) was assessed using a locally developed tool. Data on center characteristics including type, size, location, length of operation, charges, and number of staff were collected. Center providers' knowledge, attitude, and practices (KAP) in childcare were assessed through a questionnaire, focusing on nurturing care and business management. Data were described using means and standard deviation or frequencies and percentages. Associations between quality center score (outcome variable) and other variables were examined using multivariable linear regression to identify potential predictors of the quality of the center environment. Findings: A total of 129 childcare centers were identified and categorized as home-based (n = 45), center-based (n = 14), school-based (n = 61), and church-based (n = 9). The number of home-based centers was particularly high in Viwandani (n = 40; 52%). Only 9% of home-based centers reported any external support and 20% had any training on early childhood development. Of the 129 centers, 66 had complete detailed assessment of predictors of quality reported here. Unadjusted linear regressions revealed associations between quality of childcare center and center providers' education level, type of center, support received, caregiver-child ratio, number of children in the center, and center providers' KAP score (p < 0.05). However, in the multivariable regression, only higher levels of center provider KAP (ß = 0.51; 95% CI: 0.18, 0.84; p = 0.003) and center type (ß = 8.68; 95% CI: 2.32, 15.04; p = 0.008) were significantly associated with center quality score. Implication: Our results show that center providers' knowledge and practices are a major driver of the quality of childcare centers in informal settlements in Nairobi. Interventions for improving the quality of childcare services in such settings should invest in equipping center providers with the necessary knowledge and skills through training and supportive supervision.

Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections. METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447. FINDINGS: Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30-0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34-0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3-43·7), of diarrhoea was 134·1 (129·2-139·2), and of pneumonia was 22·3 (20·4-24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79-1.14], diarrhoea [1·06, 0·96-1·16], pneumonia [1·11, 0·90-1·38]) or praziquantel treatment (malaria [1·00, 0·84-1·20], diarrhoea [1·07, 0·98-1·18], pneumonia [1·00, 0·80-1·24]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35-1·42) or praziquantel (0·60, 0·29-1·23) treatment. INTERPRETATION: These results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed. FUNDING: Wellcome Trust.

Maternal recall of birthweight and birth size in Entebbe, Uganda.

OBJECTIVES: To assess the reliability of maternally recalled birthweight and size in Entebbe, Uganda. METHODS: The study population comprised 404 mothers, who were participants in the Entebbe Mother and Baby Study (EMaBS). Mothers were recruited to EMaBS during antenatal care, maternal characteristics were recorded during pregnancy, and birthweight was recorded at delivery. Four to seven years after delivery, mothers were asked to recall the child's birthweight and size. Their responses were compared with the birthweight recorded in the EMaBS database. RESULTS: Of 404 interviewed mothers, 303 (75%) were able to give an estimate of birthweight and for 265 of these EMaBS data on recorded birthweights were available. Women who were educated and whose children had low birth order were more likely to be able to give an estimate: 37 (14%) recalled the exact recorded birthweight; a further 52 (20%) were accurate to within 0.1 kg of the recorded weight. On average, mothers overestimated birthweight by 0.06 kg (95% CI: 0.00-0.13 kg, P = 0.04). Recalled and recorded birthweights showed moderate agreement with an intraclass correlation coefficient of 0.64. Four hundered mothers gave an estimate of birth size: the sensitivity and specificity of recalled birth size for classifying low birthweight were 76% (95% CI: 50-93%) and 70% (95% CI: 65-75%), respectively. CONCLUSIONS: Mothers' recall of birthweight was not precise but in absence of other data, recall of birthweight and size may have some value in epidemiological studies in these settings.

Effects of maternal worm infections and anthelminthic treatment during pregnancy on infant motor and neurocognitive functioning.

We tested the hypothesis that maternal worm infections in pregnancy affect infant motor and neurocognitive development, and that anthelminthic treatment during pregnancy can reverse these effects. We used measures which examine infant motor, cognitive and executive function, including inhibition. We assessed 983 Ugandan infants aged 15 months, using locally appropriate measures within the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy. Key exposures were maternal worm infections and anthelminthic treatment during pregnancy. Effects of other health and social factors were controlled for statistically. Of the five major worm species found in the pregnant women, two had influences on the developmental measures: Maternal Mansonella perstans and Strongyloides stercoralis infections showed negative associations with the A-not B-task, and Language, respectively. Performance on other psychomotor and cognitive measures was associated with illnesses during infancy and infants' behavior during assessment, but not with maternal worm infections. There were no positive effects of maternal anthelminthic treatment on infant abilities. Mansonella perstans and Strongyloides stercoralis infection during pregnancy seem associated with impaired early executive function and language, respectively, but single-dose anthelminthic treatment during pregnancy was not beneficial. The biological mechanisms that could underlie these neurocognitive effects are discussed.