RESUMO
Stunting affects almost one-quarter of children globally, leading to reduced human capacity and increased long-term risk of chronic disease. Despite intensive infant and young child feeding (IYCF) interventions, many children do not meet their requirements for essential nutrients. This study aimed to assess the feasibility of implementing an IYCF intervention utilizing nutrient-dense powders from egg, biofortified sugar beans and Moringa oleifera leaf in rural Zimbabwe. A mixed-methods formative study was conducted comprising the following: (i) a recipe formulation trial, (ii) trials of improved practices to assess acceptability of the intervention, and (iii) a participatory message formulation process to develop counselling modules for the IYCF-plus intervention. Twenty-seven mother-baby pairs were recruited between November 2019 and April 2020. Key domains affecting IYCF practices that emerged were time, emotional and physical space, cultural and religious beliefs, indigenous knowledge systems and gender dynamics. Household observations and sensory evaluation indicated high acceptability of the new ingredients. Recipe formulation and participatory message formulation by participants instilled community ownership and served to demystify existing misconceptions about the new food products. Families noted the potential for intervention sustainability because the foods could be grown locally. Supplementing complementary foods with nutrient-dense local food ingredients as powders has the potential to sustainably address nutrient-gaps in the diets of young children living in rural lower- and middle-income countries. Comprehensive IYCF counselling utilizing a gender-lens approach, family support and indigenous knowledge systems or resources are key elements to support positive behaviour change in complementary feeding interventions.
Assuntos
Saúde da Criança , Estado Nutricional , Pré-Escolar , Feminino , Humanos , Lactente , Agricultura/métodos , Aleitamento Materno , Dieta , Fenômenos Fisiológicos da Nutrição do Lactente , Nutrientes , Zimbábue , MasculinoRESUMO
INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.
Assuntos
Mortalidade Infantil , Morte Perinatal , Lactente , Recém-Nascido , Criança , Humanos , Feminino , Gravidez , América Latina/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , África Subsaariana , Ásia/epidemiologiaRESUMO
BACKGROUND: Despite achieving relatively high rates of antenatal care, institutional delivery, and HIV antiretroviral therapy for women during pregnancy, neonatal mortality has remained stubbornly high in Zimbabwe. Clearer understanding of causal pathways is required to inform effective interventions. METHODS: This study was a secondary analysis of data from the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial, a cluster-randomized community-based trial among pregnant women and their infants, to examine care during institutional and non-institutional deliveries in rural Zimbabwe and associated birth outcomes. RESULTS: Among 4423 pregnant women, 529 (11.9%) delivered outside a health institution; hygiene practices were poorer and interventions to minimise neonatal hypothermia less commonly utilised for these deliveries compared to institutional deliveries. Among 3441 infants born in institutions, 592 (17.2%) were preterm (< 37 weeks gestation), while 175/462 (37.9%) infants born outside health institutions were preterm (RR: 2.20 (1.92, 2.53). Similarly, rates of stillbirth [1.2% compared to 3.0% (RR:2.38, 1.36, 4.15)] and neonatal mortality [2.4% compared to 4.8% (RR: 2.01 1.31, 3.10)] were higher among infants born outside institutions. Among mothers delivering at home who reported their reason for having a home delivery, 221/293 (75%) reported that precipitous labor was the primary reason for not having an institutional delivery while 32 (11%), 34 (12%), and 9 (3%), respectively, reported distance to the clinic, financial constraints, and religious/personal preference. CONCLUSIONS: Preterm birth is common among all infants in rural Zimbabwe, and extremely high among infants born outside health institutions. Our findings indicate that premature onset of labor, rather than maternal choice, may be the reason for many non-institutional deliveries in low-resource settings, initiating a cascade of events resulting in a two-fold higher risk of stillbirth and neonatal mortality amongst children born outside health institutions. Interventions for primary prevention of preterm delivery will be crucial in reducing neonatal mortality in Zimbabwe. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, number NCT01824940.
Assuntos
Nascimento Prematuro , Natimorto , Lactente , Criança , Recém-Nascido , Feminino , Gravidez , Humanos , Natimorto/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Zimbábue/epidemiologia , Mortalidade Infantil , Instituições de Assistência AmbulatorialRESUMO
BACKGROUND: Schistosoma haematobium is a parasitic helminth that causes urogenital pathology. The impact of urogenital schistosomiasis during pregnancy on birth outcomes and child growth is poorly understood. METHODS: Risk factors for urogenital schistosomiasis were characterized among 4437 pregnant women enrolled in a cluster-randomized community-based trial in rural Zimbabwe. Infection was defined via urine microscopy (≥1 S. haematobium egg) and urinalysis (hematuria). Associations between infection and pregnancy outcomes were assessed in case-control analyses using conditional logistic regression. The association of maternal infection with birthweight and length-for-age Z scores (LAZ) at 1 and 18 months of age were assessed using generalized estimating equations. RESULTS: Urogenital schistosomiasis (egg positive and/or hematuria positive) was detected in 26.8% of pregnant women. Risk factors significantly associated with infection were maternal age, education, marital status, and religion; household drinking water source and latrine; study region; and season. Urogenital schistosomiasis was not significantly associated with adverse pregnancy outcomes (miscarriage, stillbirth, preterm, and small-for-gestational age), birthweight, neonatal death, or LAZ. CONCLUSIONS: Including pregnant women in antihelminthic treatment programs would benefit a large number of women in rural Zimbabwe. However, clearance of the low-intensity infections that predominate in this context is unlikely to have additive benefits for pregnancy outcomes or child growth. CLINICAL TRIALS REGISTRATION: NCT01824940.
Assuntos
Morte Perinatal , Complicações Parasitárias na Gravidez/epidemiologia , Resultado da Gravidez , Esquistossomose Urinária , Animais , Peso ao Nascer , Desenvolvimento Infantil , Feminino , Hematúria , Humanos , Lactente , Recém-Nascido , Microscopia , Gravidez , Gestantes , Schistosoma haematobium , Esquistossomose Urinária/complicações , Esquistossomose Urinária/epidemiologia , UrináliseRESUMO
BACKGROUND: Clinical outcomes of children who are human immunodeficiency virus (HIV)-exposed in sub-Saharan Africa remain uncertain. METHODS: The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial evaluated improved infant and young child feeding (IYCF) and/or improved water, sanitation, and hygiene in 2 rural Zimbabwean districts with 15% antenatal HIV prevalence and > 80% prevention of mother-to-child transmission (PMTCT) coverage. Children born between February 2013 and December 2015 had longitudinal HIV testing and anthropometry. We compared mortality and growth between children who were HIV-exposed and HIV-unexposed through 18 months. Children receiving IYCF were excluded from growth analyses. RESULTS: Fifty-one of 738 (7%) children who were HIV-exposed and 198 of 3989 (5%) children who were HIV-unexposed (CHU) died (hazard ratio, 1.41 [95% confidence interval {CI}, 1.02-1.93]). Twenty-five (3%) children who were HIV-exposed tested HIV positive, 596 (81%) were HIV-exposed uninfected (CHEU), and 117 (16%) had unknown HIV status by 18 months; overall transmission estimates were 4.3%-7.7%. Mean length-for-age z score at 18 months was 0.38 (95% CI, .24-.51) standard deviations lower among CHEU compared to CHU. Among 367 children exposed to HIV in non-IYCF arms, 147 (40%) were alive, HIV-free, and nonstunted at 18 months, compared to 1169 of 1956 (60%) CHU (absolute difference, 20% [95% CI, 15%-26%]). CONCLUSIONS: In rural Zimbabwe, mortality remains 40% higher among children exposed to HIV, vertical transmission exceeds elimination targets, and half of CHEU are stunted. We propose the composite outcome of "alive, HIV free, and thriving" as the long-term goal of PMTCT programs. CLINICAL TRIALS REGISTRATION: NCT01824940.
Assuntos
Infecções por HIV , Complicações Infecciosas na Gravidez , Criança , Feminino , HIV , Infecções por HIV/epidemiologia , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Gravidez , Saneamento , Zimbábue/epidemiologiaRESUMO
BACKGROUND: Young children require high-quality care for healthy growth and development. We defined "maternal capabilities" as factors that influence mothers' caregiving ability (physical and mental health, social support, time, decision-making autonomy, gender norm attitudes, and mothering self-efficacy), and developed survey tools to assess them. OBJECTIVES: We hypothesized that mothers with stronger capabilities during pregnancy would be more likely to practice improved care behaviors after their child was born. METHODS: We assessed maternal capabilities among 4667 pregnant women newly enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial. Several improved child-care practices were promoted until 18 mo postpartum, the trial endpoint. Care practices were assessed by survey, direct observation, or transcription from health records during postpartum research visits. We used logistic regression to determine the predictive association between maternal capabilities during pregnancy and child-care practices. RESULTS: Mothers with more egalitarian gender norm attitudes were more likely to have an institutional delivery [adjusted OR (AOR), 2.06; 95% CI, 1.57-2.69], initiate breastfeeding within 1 h of delivery (AOR, 1.38; 95% CI, 1.03-1.84), exclusively breastfeed (EBF) from birth to 3 mo (AOR, 2.55; 95% CI, 1.95-3.35) and 3-6 mo (AOR, 1.75; 95% CI, 1.36-2.25), and, among households randomized to receive extra modules on sanitation and hygiene, have soap and water at a handwashing station (AOR, 1.76; 95% CI, 1.29-2.39). Mothers experiencing time stress were less likely to EBF from birth to 3 mo (AOR, 0.79; 95% CI, 0.66-0.93). Greater social support was associated with institutional delivery (AOR, 1.53; 95% CI, 1.37-1.98) and, among mothers randomized to receive extra complementary feeding modules, feeding children a minimally diverse diet (AOR, 1.18; 95% CI, 1.01-1.37). Depressed mothers were 37% and 33%, respectively, less likely to have an institutional delivery (AOR, 0.63; 95% CI, 0.44-0.88) and a fully immunized child (AOR, 0.67; 95% CI, 0.50-0.90). CONCLUSIONS: Interventions to reduce maternal depression, time stress, inadequate social support, and inequitable gender norms may improve maternal child caregiving.
Assuntos
Cuidadores , Comportamento Materno , População Rural , Adolescente , Adulto , Comportamento Infantil , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Lactente , Mães/psicologia , Gravidez , Fatores Socioeconômicos , Adulto Jovem , ZimbábueRESUMO
Between birth and 2 years, children's well-being depends on the quality of care they receive from caregivers, primarily their mothers. We developed a quantitative survey instrument to assess seven psychosocial characteristics of women that determine their caregiving ability ('maternal capabilities': physical health, mental health, decision-making autonomy, social support, mothering self-efficacy, workload and time stress, and gender norm attitudes). We measured maternal capabilities in 4,025 mothers and growth in their 4,073 children participating in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. We used generalized estimating equation models with exchangeable correlation structure to test the association between each maternal capability during pregnancy, and infant length-for-age Z (LAZ) at 18 months, accounting only for within-cluster correlation and intervention arms in unadjusted analyses and for potential confounders in adjusted analyses to examine the association between each capability, assessed during pregnancy, with child LAZ at 18 months of age. In adjusted models, each unit increase in gender norm attitudes score (reflecting more equitable gender norm attitudes) was associated with +0.09 LAZ (95% CI: 0.02, 0.16) and a decreased odds of stunting (adjusted odds ratio [AOR]: 0.86; 95% CI: 0.74, 1.01); each unit increase in social support score was associated with +0.11 LAZ (95% CI: 0.05, 0.17, p < 0.010) and decreased odds of stunting (AOR: 0.83; 95% CI: 0.73, 0.96). Each unit increase in decision-making autonomy was associated with a 6% reduced odds of stunting (AOR: 0.94; 95% CI: 0.89, 0.996, p = 0.04). Interventions and social programming that strengthen these maternal capabilities may improve child nutritional status.
Assuntos
Fenômenos Fisiológicos da Nutrição do Lactente , População Rural , Criança , Feminino , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/prevenção & controle , Humanos , Lactente , Mães , Estado Nutricional , Gravidez , Saneamento , Zimbábue/epidemiologiaRESUMO
BACKGROUND: We assessed the impact of water, sanitation, and hygiene (WASH) and infant and young child feeding (IYCF) interventions on enteric infections in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. METHODS: We tested stool samples collected at 1, 3, 6, and 12 months of age and during diarrhea using quantitative molecular diagnostics for 29 pathogens. We estimated the effects of the WASH, IYCF, and combined WASH + IYCF interventions on individual enteropathogen prevalence and quantity, total numbers of pathogens detected, and incidence of pathogen-attributable diarrhea. RESULTS: WASH interventions decreased the number of parasites detected (difference in number compared to non-WASH arms, -0.07 [95% confidence interval, -.14 to -.02]), but had no statistically significant effects on bacteria, viruses, or the prevalence and quantity of individual enteropathogens after accounting for multiple comparisons. IYCF interventions had no significant effects on individual or total enteropathogens. Neither intervention had significant effects on pathogen-attributable diarrhea. CONCLUSIONS: The WASH interventions implemented in SHINE (improved pit latrine, hand-washing stations, liquid soap, point-of-use water chlorination, and clean play space) did not prevent enteric infections. Transformative WASH interventions are needed that are more efficacious in interrupting fecal-oral microbial transmission in children living in highly contaminated environments.
Assuntos
Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/virologia , Infecções/etiologia , Estado Nutricional/fisiologia , Diarreia/etiologia , Feminino , Desinfecção das Mãos , Humanos , Higiene , Lactente , Recém-Nascido , Masculino , População Rural , Saneamento , Água , Qualidade da Água , ZimbábueRESUMO
BACKGROUND: Oral vaccines have lower efficacy in developing compared to developed countries. Poor water, sanitation, and hygiene (WASH) may contribute to reduced oral vaccine immunogenicity. METHODS: We conducted a cluster-randomized 2 × 2 factorial trial in rural Zimbabwe. Pregnant women and their infants were eligible if they lived in clusters randomized to (1) standard of care (52 clusters); (2) improved infant feeding (53 clusters); (3) WASH: ventilated improved pit latrine, 2 hand-washing stations, liquid soap, chlorine, infant play space, and hygiene counseling (53 clusters); or (4) feeding plus WASH (53 clusters). This substudy compared oral rotavirus vaccine (RVV) seroconversion (primary outcome), and seropositivity and geometric mean titer (GMT) (secondary outcomes), in WASH vs non-WASH infants by intention-to-treat analysis. RESULTS: We included 801 infants with documented RVV receipt and postvaccine titer measurements (329 from 84 WASH clusters; 472 from 102 non-WASH clusters); 328 infants with prevaccination titers were included in the primary outcome. Thirty-three of 109 (30.3%) infants in the WASH group seroconverted following rotavirus vaccination, compared to 43 of 219 (19.6%) in the non-WASH group (absolute difference, 10.6% [95% confidence interval {CI}, .54%-20.7%]; P = .031). In the WASH vs non-WASH groups, 90 of 329 (27.4%) vs 107 of 472 (22.7%) were seropositive postvaccination (absolute difference, 4.7% [95% CI, -1.4% to 10.8%]; P = .130), and antirotavirus GMT was 18.4 (95% CI, 15.6-21.7) U/mL vs 14.9 (95% CI, 13.2-16.8) U/mL (P = .072). CONCLUSIONS: Improvements in household WASH led to modest but significant increases in seroconversion to RVV in rural Zimbabwean infants. CLINICAL TRIALS REGISTRATION: NCT01824940.
Assuntos
Higiene , Imunogenicidade da Vacina , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Saneamento , Qualidade da Água , Feminino , Humanos , Masculino , Gravidez , Vacinas contra Rotavirus/administração & dosagem , Vacinação , Zimbábue/epidemiologiaRESUMO
BACKGROUND: Globally, nearly 250 million children (43% of all children under 5 years of age) are at risk of compromised neurodevelopment due to poverty, stunting, and lack of stimulation. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH) and improved infant and young child feeding (IYCF) on early child development (ECD) among children enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. METHODS AND FINDINGS: SHINE was a cluster-randomized community-based 2×2 factorial trial. A total of 5,280 pregnant women were enrolled from 211 clusters (defined as the catchment area of 1-4 village health workers [VHWs] employed by the Zimbabwean Ministry of Health and Child Care). Clusters were randomly allocated to standard of care, IYCF (20 g of small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counseling), WASH (ventilated improved pit latrine, handwashing stations, chlorine, liquid soap, and play yard), and WASH + IYCF. Primary outcomes were child length-for-age Z-score and hemoglobin concentration at 18 months of age. Children who completed the 18-month visit and turned 2 years (102-112 weeks) between March 1, 2016, and April 30, 2017, were eligible for the ECD substudy. We prespecified that primary inferences would be drawn from findings of children born to HIV-negative mothers; these results are presented in this paper. A total of 1,655 HIV-unexposed children (64% of those eligible) were recruited into the ECD substudy from 206 clusters and evaluated for ECD at 2 years of age using the Malawi Developmental Assessment Tool (MDAT) to assess gross motor, fine motor, language, and social skills; the MacArthur-Bates Communicative Development Inventories (CDI) to assess vocabulary and grammar; the A-not-B test to assess object permanence; and a self-control task. Outcomes were analyzed in the intention-to-treat population. For all ECD outcomes, there was not a statistical interaction between the IYCF and WASH interventions, so we estimated the effects of the interventions by comparing the 2 IYCF groups with the 2 non-IYCF groups and the 2 WASH groups with the 2 non-WASH groups. The mean (95% CI) total MDAT score was modestly higher in the IYCF groups compared to the non-IYCF groups in unadjusted analysis: 1.35 (0.24, 2.46; p = 0.017); this difference did not persist in adjusted analysis: 0.79 (-0.22, 1.68; p = 0.057). There was no evidence of impact of the IYCF intervention on the CDI, A-not-B, or self-control tests. Among children in the WASH groups compared to those in the non-WASH groups, mean scores were not different for the MDAT, A-not-B, or self-control tests; mean CDI score was not different in unadjusted analysis (0.99 [95% CI -1.18, 3.17]) but was higher in children in the WASH groups in adjusted analysis (1.81 [0.01, 3.61]). The main limitation of the study was the specific time window for substudy recruitment, meaning not all children from the main trial were enrolled. CONCLUSIONS: We found little evidence that the IYCF and WASH interventions implemented in SHINE caused clinically important improvements in child development at 2 years of age. Interventions that directly target neurodevelopment (e.g., early stimulation) or that more comprehensively address the multifactorial nature of neurodevelopment may be required to support healthy development of vulnerable children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01824940.
Assuntos
Desenvolvimento Infantil/fisiologia , Higiene/normas , Fenômenos Fisiológicos da Nutrição do Lactente/fisiologia , População Rural , Saneamento/normas , Qualidade da Água/normas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise por Conglomerados , Água Potável/normas , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Lactente , Pessoa de Meia-Idade , Saneamento/métodos , Adulto Jovem , Zimbábue/epidemiologiaRESUMO
BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden.
Assuntos
Diarreia/etiologia , Transtornos do Crescimento/etiologia , Higiene , Saneamento , Água/efeitos adversos , Criança , Saúde da Criança , Humanos , Pobreza , Saúde Pública/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , População RuralRESUMO
Cytomegalovirus (CMV) acquisition and inflammation were evaluated in 231 human immunodeficiency virus (HIV)-exposed uninfected (HEU) and 100 HIV-unexposed Zimbabwean infants aged 6 weeks. The HEU and HIV-unexposed infants had a similarly high prevalence of CMV (81.4% vs 74.0%, respectively; P = .14), but HEU infants had higher CMV loads (P = .005) and >2-fold higher C-reactive protein (CRP) concentrations (P < .0001). The CMV-positive HEU infants had higher CRP than the CMV-negative HEU infants; this association disappeared after adjusting for maternal HIV load. Overall, CMV acquisition is high in early life, but HEU infants have higher CMV loads and a proinflammatory milieu, which may be driven partly by maternal HIV viremia.
Assuntos
Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/isolamento & purificação , Infecções por HIV/epidemiologia , Inflamação/epidemiologia , Inflamação/virologia , Adulto , Proteína C-Reativa/metabolismo , DNA Viral/isolamento & purificação , Feminino , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Modelos Lineares , Masculino , Gravidez , Complicações Infecciosas na Gravidez/virologia , Prevalência , Estudos Retrospectivos , Fatores Socioeconômicos , Carga Viral , Adulto Jovem , ZimbábueRESUMO
Background: Disease progression is rapid in human immunodeficiency virus (HIV)-infected infants. Whether intestinal damage and inflammation underlie mortality is unknown. Methods: We measured plasma intestinal fatty acid binding protein (I-FABP), soluble CD14 (sCD14), interleukin 6 (IL-6), and C-reactive protein (CRP) at 6 weeks and 6 months of age in 272 HIV-infected infants who either died (cases) or survived (controls), and in 194 HIV-exposed uninfected (HEU) and 197 HIV-unexposed infants. We estimated multivariable odds ratios for mortality and postnatal HIV transmission for each biomarker using logistic regression. Results: At 6 weeks, HIV-infected infants had higher sCD14 and IL-6 but lower I-FABP than HIV-exposed and HIV-unexposed infants (P < .001). CRP was higher in HIV-exposed than HIV-unexposed infants (P = .02). At 6 months, HIV-infected infants had highest sCD14, IL-6, and CRP concentrations (P < .001) and marginally higher I-FABP than other groups (P = .07). CRP remained higher in HIV-exposed vs HIV-unexposed infants (P = .04). No biomarker was associated with mortality in HIV-infected infants, or with odds of breast-milk HIV transmission in HIV-exposed infants. Conclusions: HIV-infected infants have elevated inflammatory markers by 6 weeks of age, which increase over time. In contrast to adults and older children, inflammatory biomarkers were not associated with mortality. HEU infants have higher inflammation than HIV-unexposed infants until at least 6 months, which may contribute to poor health outcomes.
Assuntos
Biomarcadores/sangue , Infecções por HIV/sangue , Intestinos/patologia , Intestinos/virologia , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , HIV/isolamento & purificação , HIV/metabolismo , Infecções por HIV/diagnóstico , Humanos , Lactente , Inflamação/sangue , Inflamação/virologia , Interleucina-6/sangue , Receptores de Lipopolissacarídeos/sangue , Masculino , Análise Multivariada , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra , Zimbábue/epidemiologiaRESUMO
In 2011, one in every four (26%) children under 5 years of age worldwide was stunted. The realization that most stunting cannot be explained by poor diet or by diarrhoea, nor completely reversed by optimized diet and reduced diarrhoea has led to the hypothesis that a primary underlying cause of stunting is subclinical gut disease. Essentially, ingested microbes set in motion two overlapping and interacting pathways that result in linear growth impairment. Firstly, partial villous atrophy results in a reduced absorptive surface area and loss of digestive enzymes. This in turn results in maldigestion and malabsorption of much needed nutrients. Secondly, microbes and their products make the gut leaky, allowing luminal contents to translocate into systemic circulation. This creates a condition of chronic immune activation, which (i) diverts nutrient resources towards the metabolically expensive business of infection fighting rather than growth; (ii) suppresses the growth hormone-IGF axis and inhibits bone growth, leading to growth impairment; and (iii) causes further damage to the intestinal mucosa thereby exacerbating the problem. As such, the unhygienic environments in which infants and young children live and grow must contribute to, if not be the overriding cause of, this environmental enteric dysfunction. We suggest that a package of baby-WASH interventions (sanitation and water improvement, handwashing with soap, ensuring a clean play and infant feeding environment and food hygiene) that interrupt specific pathways through which feco-oral transmission occurs in the first two years of a child's life may be central to global stunting reduction efforts.
Assuntos
Países em Desenvolvimento/estatística & dados numéricos , Transtornos do Crescimento/prevenção & controle , Higiene , Enteropatias/complicações , Enteropatias/prevenção & controle , Abastecimento de Água , Pré-Escolar , Diarreia/complicações , Dieta , Meio Ambiente , Comportamento Alimentar , Transtornos do Crescimento/etiologia , Desinfecção das Mãos , Humanos , Lactente , Recém-Nascido , Enteropatias/fisiopatologia , SaneamentoRESUMO
Environmental enteric dysfunction (EED) is a virtually ubiquitous, but poorly defined, disorder of the small intestine among people living in conditions of poverty, which begins early in infancy and persists. EED is characterized by altered gut structure and function, leading to reduced absorptive surface area and impaired intestinal barrier function. It is hypothesized that recurrent exposure to fecal pathogens and changes in the composition of the intestinal microbiota initiate this process, which leads to a self-perpetuating cycle of pathology. We view EED as a primary gut disorder that drives chronic systemic inflammation, leading to growth hormone resistance and impaired linear growth. There is currently no accepted case definition or gold-standard biomarker of EED, making field studies challenging. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in Zimbabwe is evaluating the independent and combined effects of a package of infant feeding and/or water, sanitation, and hygiene interventions on stunting and anemia. SHINE therefore provides an opportunity to longitudinally evaluate EED in a well-characterized cohort of infants, using a panel of biomarkers along the hypothesized causal pathway. Our aims are to describe the evolution of EED during infancy, ascertain its contribution to stunting, and investigate the impact of the randomized interventions on the EED pathway. In this article, we describe current concepts of EED, challenges in defining the condition, and our approach to evaluating EED in the SHINE trial.
Assuntos
Fezes/microbiologia , Intestinos/fisiopatologia , Anemia , Biomarcadores , Ingestão de Alimentos , Feminino , Microbioma Gastrointestinal , Transtornos do Crescimento/fisiopatologia , Humanos , Higiene , Lactente , Inflamação , Intestinos/imunologia , Intestinos/microbiologia , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , População Rural , Saneamento , ZimbábueRESUMO
Two reasons for the lack of success of programs or interventions are poor alignment of interventions with the causes of the problem targeted by the intervention, leading to poor efficacy (theory failure), and failure to implement interventions as designed (program failure). These failures are important for both public health programs and randomized trials. In the Sanitation Hygiene and Infant Nutrition Efficacy (SHINE) Trial, we utilize the program impact pathway (PIP) approach to track intervention implementation and behavior uptake. In this article, we present the SHINE PIP including definitions and measurements of key mediating domains, and discuss the implications of this approach for randomized trials. Operationally, the PIP can be used for monitoring and strengthening intervention delivery, facilitating course-correction at various stages of implementation. Analytically, the PIP can facilitate a richer understanding of the mediating and modifying determinants of intervention impact than would be possible from an intention-to-treat analysis alone.
Assuntos
Saúde da Criança , Higiene , Avaliação de Programas e Projetos de Saúde , Feminino , Humanos , Lactente , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , População Rural , Saneamento , ZimbábueRESUMO
The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial is designed to measure the independent and combined effects of improved water, sanitation, and hygiene and improved infant feeding on child stunting and anemia in Zimbabwe. We developed and pilot-tested the infant feeding intervention delivered by 9 village health workers to 19 mothers of infants aged 7-12 months. Between September 2010 and January 2011, maternal knowledge was assessed using mixed methods, and infant nutrient intakes were assessed by 24-hour recall. We observed positive shifts in mothers' knowledge. At baseline, 63% of infants met their energy requirement and most did not receive enough folate, zinc, or calcium; none met their iron requirement. Postintervention, all infants received sufficient fat and vitamin A, and most consumed enough daily energy (79%), protein (95%), calcium (89%), zinc (89%), folate (68%), and iron (68%). The SHINE trial infant feeding intervention led to significant short-term improvements in maternal learning and infant nutrient intakes.
Assuntos
Educação em Saúde , Fenômenos Fisiológicos da Nutrição do Lactente/normas , Mães/educação , Dieta/normas , Feminino , Humanos , Lactente , Masculino , Micronutrientes , Projetos Piloto , População Rural , ZimbábueRESUMO
We sought to develop a water, sanitation, and hygiene (WASH) intervention to minimize fecal-oral transmission among children aged 0-18 months in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial. We undertook 4 phases of formative research, comprising in-depth interviews, focus group discussions, behavior trials, and a combination of observations and microbiological sampling methods. The resulting WASH intervention comprises material inputs and behavior change communication to promote stool disposal, handwashing with soap, water treatment, protected exploratory play, and hygienic infant feeding. Nurture and disgust were found to be key motivators, and are used as emotional triggers. The concept of a safe play space for young children was particularly novel, and families were eager to implement this after learning about the risks of unprotected exploratory play. An iterative process of formative research was essential to create a sequenced and integrated longitudinal intervention for a SHINE household as it expects (during pregnancy) and then cares for a new child.
Assuntos
Fezes/microbiologia , Higiene , Intestinos/fisiopatologia , Saneamento , Ensaios Clínicos como Assunto/métodos , Ingestão de Alimentos , Feminino , Desinfecção das Mãos , Comportamentos Relacionados com a Saúde , Hemoglobinas/análise , Humanos , Lactente , Recém-Nascido , Masculino , Projetos de Pesquisa , População Rural , Abastecimento de Água , ZimbábueRESUMO
Access to water and sanitation are important determinants of behavioral responses to hygiene and sanitation interventions. We estimated cluster-specific water access and sanitation coverage to inform a constrained randomization technique in the SHINE trial. Technicians and engineers inspected all public access water sources to ascertain seasonality, function, and geospatial coordinates. Households and water sources were mapped using open-source geospatial software. The distance from each household to the nearest perennial, functional, protected water source was calculated, and for each cluster, the median distance and the proportion of households within <500 m and >1500 m of such a water source. Cluster-specific sanitation coverage was ascertained using a random sample of 13 households per cluster. These parameters were included as covariates in randomization to optimize balance in water and sanitation access across treatment arms at the start of the trial. The observed high variability between clusters in both parameters suggests that constraining on these factors was needed to reduce risk of bias.
Assuntos
Sistemas de Informação Geográfica , Saneamento , Análise Espacial , Abastecimento de Água , Características da Família , Feminino , Humanos , Lactente , Masculino , População Rural , ZimbábueRESUMO
UNLABELLED: Child stunting and anemia are intractable public health problems in developing countries and have profound short- and long-term consequences. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial is motivated by the premise that environmental enteric dysfunction (EED) is a major underlying cause of both stunting and anemia, that chronic inflammation is the central characteristic of EED mediating these adverse effects, and that EED is primarily caused by high fecal ingestion due to living in conditions of poor water, sanitation, and hygiene (WASH). SHINE is a proof-of-concept, 2 × 2 factorial, cluster-randomized, community-based trial in 2 rural districts of Zimbabwe that will test the independent and combined effects of protecting babies from fecal ingestion (factor 1, operationalized through a WASH intervention) and optimizing nutritional adequacy of infant diet (factor 2, operationalized through an infant and young child feeding [IYCF] intervention) on length and hemoglobin at 18 months of age. Within SHINE we will measure 2 causal pathways. The program impact pathway comprises the series of processes and behaviors linking implementation of the interventions with the 2 child health primary outcomes; it will be modeled using measures of fidelity of intervention delivery and household uptake of promoted behaviors and practices. We will also measure a range of household and individual characteristics, social interactions, and maternal capabilities for childcare, which we hypothesize will explain heterogeneity along these pathways. The biomedical pathway comprises the infant biologic responses to the WASH and IYCF interventions that ultimately result in attained stature and hemoglobin concentration at 18 months of age; it will be elucidated by measuring biomarkers of intestinal structure and function (inflammation, regeneration, absorption, and permeability); microbial translocation; systemic inflammation; and hormonal determinants of growth and anemia among a subgroup of infants enrolled in an EED substudy. This article describes the rationale, design, and methods underlying the SHINE trial. CLINICAL TRIALS REGISTRATION: NCT01824940.