Estomih Mduma - Academia.edu (original) (raw)
Papers by Estomih Mduma
Children (Basel), Sep 11, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Nutrition and dietary supplements, Aug 31, 2023
Background: Micronutrients (iron, iodine, vitamin B12 and folate) deficiency is prevalent globall... more Background: Micronutrients (iron, iodine, vitamin B12 and folate) deficiency is prevalent globally affecting more than two billion people majority being from low-and middle-income countries. Women of reproductive age are in an increased risk of iron deficiency. About 29.4% of women aged 15-49 years worldwide are estimated to be affected by iron deficiency. Food fortification with micronutrients is important in addressing micronutrients deficiency. Aim: To evaluate if the quadruple fortified with iodine, iron, vitamin B12, and folic acid (QFS), will be more effective in improving the hemoglobin level of women aged 18 to 49 years compared to the double fortified with iodine and iron (DFS) and iodized salt in rural Tanzania. Methods: A double-blinded three-arm randomized controlled trial was conducted between July 2020 and December 2021 at the Haydom Lutheran Hospital catchment area. We randomized women aged 18-49 years with haemoglobin between 8 and 12 g/dl who were neither pregnant nor lactating into three groups 55 Iodized salts (IS), 57 Double fortified salt (DFS), and 57 quadruple fortified salt (QFS). The participants used study salt for 10 months. Results: Over the ten months of use of study salts, the overall mean haemoglobin level of women was significantly higher in QFS by 0.43g/dl compared to IS. The ferritin levels were significantly higher in QFS and DFS by 9.60ng/mL and 9.09ng/mL, respectively, compared to IS. Vitamin B12 was insignificantly higher in QFS by 52.19pg/mL compared to DFS, and folate concentration were insignificantly higher in QFS by 7.57nmoL/L and 4.51nmoL/L compared to DFS and IS groups, respectively. Conclusion: Salt fortification with iron, iodine, folate, and Vitamin B12 is feasible and has the potential to increase the serum ferritin, Vitamin B12 and folate levels with subsequent improvement of haemoglobin levels of individuals with relatively low haemoglobin. ClinicalTrial.org Number: NCT04404751.
American Journal of Tropical Medicine and Hygiene, Apr 24, 2023
ABSTRACT. At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so i... more ABSTRACT. At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so in children and adolescents, which is hampering global elimination goals. Prolonged symptom duration presents a high-risk scenario for childhood TB in endemic areas, but the prolonged period of symptoms and its impact on educational attainment are rarely documented. Using a mixed method approach, we aimed to quantify the duration of respiratory symptoms and describe their impact on education among children from a rural area of Tanzania. We used data from a prospectively enrolled cohort of children and adolescents aged 4–17 years in rural Tanzania at the start of active TB treatment. We report on the cohort’s baseline characteristics and explore the correlation between duration of symptoms and other variables. In-depth qualitative interviews were designed on the basis of a grounded theory approach to explore the impact of TB on educational attainment among school-aged children. In this cohort, children and adolescents diagnosed with TB experienced symptoms for a median of 85 days (interquartile range: 30, 231 days) prior to treatment initiation. In addition, 56 participants (65%) had a TB exposure in the household. Of the 16 families with school-aged children who were interviewed, 15 (94%) reported a significant negative impact of TB on the schooling of their children. Children in this cohort experienced a long duration of TB symptoms; the extent of illness impacted absenteeism at school. Screening initiatives for households affected by TB may lead to a shortened duration of symptoms and may minimize the impact on school attendance.
PLOS ONE, Dec 20, 2023
Background Early childhood enteric infection with Shigella/EIEC, enteroaggregative E. coli (EAEC)... more Background Early childhood enteric infection with Shigella/EIEC, enteroaggregative E. coli (EAEC), Campylobacter, and Giardia has been associated with reduced child growth, yet a recent randomized trial of antimicrobial therapy to reduce these infections did not improve growth outcomes. To interrogate this discrepancy, we measured the enteric infections from this study. Methods We leveraged the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) trial, a randomized double-blind placebo-controlled trial of antimicrobial therapy with azithromycin and nitazoxanide provided quarterly to infants from 6 to 15 months of age. We tested 5,479 stool samples at time points across the study for 34 enteropathogens using quantitative PCR. Results There was substantial carriage of enteropathogens in stool. Azithromycin administration led to reductions in Campylobacter jejuni/coli, enteroaggregative E. coli, and Shigella/EIEC (absolute risk difference ranged from-0.06 to 0.24) 2 weeks after treatment however there was no effect after 3 months. There was no difference in Giardia after nitazoxanide administration (ARR 0.03 at the 12 month administration). When examining the effect of
Acta Paediatrica, Mar 22, 2018
Aim: We explored the diagnostic accuracy of the Clinical Dehydration Scale (CDS), the World Healt... more Aim: We explored the diagnostic accuracy of the Clinical Dehydration Scale (CDS), the World Health Organization (WHO) scale and the Gorelick scale for assessing dehydration in children admitted to a Tanzanian referral hospital.
European Respiratory Journal
BackgroundSuboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavo... more BackgroundSuboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.MethodsWe systematically searched MEDLINE, Embase and Web of Science (1990–2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration–time curve from 0 to 24 h post-dose (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0–24andCmaxwere assessed with linear mixed-effects models.ResultsOf 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geome...
Globally, deaths around the time of birth are unacceptably high of which there are about 2.7 mill... more Globally, deaths around the time of birth are unacceptably high of which there are about 2.7 million neonatal deaths and 2.6 million stillborn annually. Perinatal mortality accounts for deaths after 28 weeks of gestation to seven days after birth. Perinatal mortality is a public health concern with a huge impact on the health, social and economic well being affecting both family and society. The burden of perinatal mortality is obvious in the low and middle-income countries, and more on the countries south of sub-Sahara Africa. East Africa being among the sub-Sahara countries is also experiencing a high rate of perinatal mortally, with Tanzania taking the lead. Almost half of stillborns are alive at the start of labor offering an opportunity for prevention. Likewise, 44% of the neonatal deaths occur on the first day of life and are predominantly the result of intrapartum events. Events during labor, including birth asphyxia (interruption of placental blood flow) account for one-quar...
International Journal of Environmental Research and Public Health, Jan 12, 2020
Extreme floods pose multiple direct and indirect health risks. These risks include contamination ... more Extreme floods pose multiple direct and indirect health risks. These risks include contamination of water, food, and the environment, often causing outbreaks of diarrheal disease. Evidence regarding the effects of flooding on individual diarrhea-causing pathogens is limited, but is urgently needed in order to plan and implement interventions and prioritize resources before climate-related disasters strike. This study applied a causal inference approach to data from a multisite study that deployed broadly inclusive diagnostics for numerous high-burden common enteropathogens. Relative risks (RRs) of infection with each pathogen during a flooding disaster that occurred at one of the sites-Loreto, Peru-were calculated from generalized linear models using a comparative interrupted time series framework with the other sites as a comparison group and adjusting for background seasonality. During the early period of the flood, increased risk of heat-stable enterotoxigenic E. coli (ST-ETEC) was identified (RR = 1.73 [1.10, 2.71]) along with a decreased risk of enteric adenovirus (RR = 0.36 [0.23, 0.58]). During the later period of the flood, sharp increases in the risk of rotavirus (RR = 5.30 [2.70, 10.40]) and sapovirus (RR = 2.47 [1.79, 3.41]) were observed, in addition to increases in transmission of Shigella spp. (RR = 2.86 [1.81, 4.52]) and Campylobacter spp. (RR = 1.41 (1.01, 1.07). Genotype-specific exploratory analysis reveals that the rise in rotavirus transmission during the flood was likely due to the introduction of a locally atypical, non-vaccine (G2P[4]) strain of the virus. Policy-makers should target interventions towards these pathogens-including vaccines as they become available-in settings where vulnerability to flooding is high as part of disaster preparedness strategies, while investments in radical, transformative, community-wide, and locally-tailored water and sanitation interventions are also needed.
Open Forum Infectious Diseases, May 13, 2022
Background. The application of molecular diagnostics has identified enteric group adenovirus sero... more Background. The application of molecular diagnostics has identified enteric group adenovirus serotypes 40 and 41 as important causes of diarrhea in children. However, many aspects of the epidemiology of adenovirus 40/41 diarrhea have not been described. Methods. We used data from the 8-site Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project birth cohort study to describe site-and age-specific incidence, risk factors, clinical characteristics, and seasonality. Results. The incidence of adenovirus 40/41 diarrhea was substantially higher by quantitative polymerase chain reaction than enzyme immunoassay and peaked at 30 episodes per 100 child-years in children aged 7-15 months, with substantial variation in incidence between sites. A significant burden was also seen in children 0-6 months of age, higher than other viral etiologies with the exception of rotavirus. Children with adenovirus 40/41 diarrhea were more likely to have a fever than children with norovirus, sapovirus, and astrovirus (adjusted odds ratio [aOR], 1.62; 95% CI, 1.16-2.26) but less likely than children with rotavirus (aOR, 0.66; 95% CI, 0.49-0.91). Exclusive breastfeeding was strongly protective against adenovirus 40/41 diarrhea (hazard ratio, 0.64; 95% CI, 0.48-0.85), but no other risk factors were identified. The seasonality of adenovirus 40/41 diarrhea varied substantially between sites and did not have clear associations with seasonal variations in temperature or rainfall. Conclusions. This study supports the situation of adenovirus 40/41 as a pathogen of substantial importance, especially in infants. Fever was a distinguishing characteristic in comparison to other nonrotavirus viral etiologies, and promotion of exclusive breastfeeding may reduce the high observed burden in the first 6 months of life.
The Lancet Planetary Health, Jun 1, 2019
Background Climate change threatens to undermine recent progress in reducing global deaths from d... more Background Climate change threatens to undermine recent progress in reducing global deaths from diarrhoeal disease in children. However, the scarcity of evidence about how individual environmental factors affect transmission of specific pathogens makes prediction of trends under different climate scenarios challenging. We aimed to model associations between daily estimates of a suite of hydrometeorological variables and rotavirus infection status ascertained through community-based surveillance. Methods For this analysis of multisite cohort data, rotavirus infection status was ascertained through communitybased surveillance of infants in the eight-site MAL-ED cohort study, and matched by date with earth observation estimates of nine hydrometeorological variables from the Global Land Data Assimilation System: daily total precipitation volume (mm), daily total surface runoff (mm), surface pressure (mbar), wind speed (m/s), relative humidity (%), soil moisture (%), solar radiation (W/m²), specific humidity (kg/kg), and average daily temperatures (°C). Lag relationships, independent effects, and interactions were characterised by use of modified Poisson models and compared with and without adjustment for seasonality and between-site variation. Final models were created with stepwise selection of main effects and interactions and their validity assessed by excluding each site in turn and calculating Tjur's Coefficients of Determination. Findings All nine hydrometeorological variables were significantly associated with rotavirus infection after adjusting for seasonality and between-site variation over multiple consecutive or non-consecutive lags, showing complex, often non-linear associations that differed by symptom status and showed considerable mutual interaction. The final models explained 5•9% to 6•2% of the variability in rotavirus infection in the pooled data and their predictions explained between 0•0% and 14•1% of the variability at individual study sites. Interpretation These results suggest that the effect of climate on rotavirus transmission was mediated by four independent mechanisms: waterborne dispersal, airborne dispersal, virus survival on soil and surfaces, and host factors. Earth observation data products available at a global scale and at subdaily resolution can be combined with longitudinal surveillance data to test hypotheses about routes and drivers of transmission but showed little potential for making predictions in this setting.
Journal of Clinical Microbiology, Apr 1, 2014
Campylobacter is a common bacterial enteropathogen that can be detected in stool by culture, enzy... more Campylobacter is a common bacterial enteropathogen that can be detected in stool by culture, enzyme immunoassay (EIA), or PCR. We compared culture for C. jejuni/C. coli, EIA (ProSpecT), and duplex PCR to distinguish Campylobacter jejuni/C. coli and non-jejuni/coli Campylobacter on 432 diarrheal and matched control stool samples from infants in a multisite longitudinal study of enteric infections in Tanzania, Bangladesh, and Peru. The sensitivity and specificity of culture were 8.5% and 97.6%, respectively, compared with the results of EIA and 8.7% and 98.0%, respectively, compared with the results of PCR for C. jejuni/C. coli. Most (71.6%) EIA-positive samples were positive by PCR for C. jejuni/C. coli, but 27.6% were positive for nonjejuni/coli Campylobacter species. Sequencing of 16S rRNA from 53 of these non-jejuni/coli Campylobacter samples showed that it most closely matched the 16S rRNA of C. hyointestinalis subsp. lawsonii (56%), C. troglodytis (33%), C. upsaliensis (7.7%), and C. jejuni/C. coli (2.6%). Campylobacter-negative stool spiked with each of the above-mentioned Campylobacter species revealed reactivity with EIA. PCR detection of Campylobacter species was strongly associated with diarrhea in Peru (odds ratio [OR] ؍ 3.66, P < 0.001) but not in Tanzania (OR ؍ 1.56, P ؍ 0.24) or Bangladesh (OR ؍ 1.13, P ؍ 0.75). According to PCR, Campylobacter jejuni/C. coli infections represented less than half of all infections with Campylobacter species. In sum, in infants in developing country settings, the ProSpecT EIA and PCR for Campylobacter reveal extremely high rates of positivity. We propose the use of PCR because it retains high sensitivity, can ascertain burden, and can distinguish between Campylobacter infections at the species level.
American Journal of Tropical Medicine and Hygiene, Jun 15, 2022
We identified the determinants of positive (children who had a birth weight , 2.5 kg and/or mater... more We identified the determinants of positive (children who had a birth weight , 2.5 kg and/or maternal height , 145 cm but were nonstunted at 24 months of age) and negative (children who had a birth weight $ 2.5 kg and maternal height $ 145 cm but were stunted at 24 months of age) deviance in childhood linear growth. We found that socioeconomic status (b 5 1.54, P , 0.01), serum retinol (b 5 0.05, P , 0.01), hemoglobin (b 5 0.36, P , 0.01), length-forage Z-score (LAZ) at birth (b 5 0.47, P , 0.01), and tetanus vaccine titer (b 5 0.182, P , 0.05) were positively and maternal depressive symptom (b 5-0.05, P , 0.01), serum ferritin (b 5-0.03, P , 0.01), male sex (b 5-1.08, P , 0.01), and a1-antitrypsin (b 5-0.81, P , 0.01) were negatively associated with positive deviance. Further, diarrhea episodes (b 5 0.02, P , 0.01), male sex (b 5 0.72, P , 0.01), and a1-antitrypsin (b 5 0.67, P , 0.01) were positively and hemoglobin (b5-0.28, P , 0.01), soluble transferrin receptor level (b 5-0.15, P , 0.01), and LAZ score at birth (b 5-0.90, P , 0.01) were negatively associated with negative deviance. To summarize, enteric protein loss, micronutrient deficiency, vaccine responses and maternal depressive symptoms were associated with linear growth deviance in early childhood. In such a background, public health approaches aimed at reducing the risk of intestinal inflammation and altered gut permeability could prove fruitful in ensuring desired linear growth in children. In addition, maternal mental health issue should also be considered, especially for promoting better nutritional status in children in the context of linear growth deviance.
Open Forum Infectious Diseases, Nov 1, 2018
at bedside for patients admitted with sepsis. A future prospective interventional study is needed... more at bedside for patients admitted with sepsis. A future prospective interventional study is needed in order to validate the score, captured at bedside electronically, in terms of improving patients' outcomes. Disclosures. All authors: No reported disclosures.
The American Journal of Clinical Nutrition, 2019
ABSTRACTBackgroundEnvironmental enteric dysfunction (EED) is thought to increase the risk of micr... more ABSTRACTBackgroundEnvironmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation.ObjectiveWe tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status.MethodsUsing data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods ...
Science Advances, Apr 10, 2020
Malnutrition continues to affect the growth and development of millions of children worldwide, an... more Malnutrition continues to affect the growth and development of millions of children worldwide, and chronic undernutrition has proven to be largely refractory to interventions. Improved understanding of metabolic development in infancy and how it differs in growth-constrained children may provide insights to inform more timely, targeted, and effective interventions. Here, the metabolome of healthy infants was compared to that of growthconstrained infants from three continents over the first 2 years of life to identify metabolic signatures of aging. Predictive models demonstrated that growth-constrained children lag in their metabolic maturity relative to their healthier peers and that metabolic maturity can predict growth 6 months into the future. Our results provide a metabolic framework from which future nutritional programs may be more precisely constructed and evaluated.
Biomedical Signal Processing and Control
Healthcare
Background: SaferBirths Bundle of Care (SBBC) is a package of innovative clinical and training to... more Background: SaferBirths Bundle of Care (SBBC) is a package of innovative clinical and training tools coupled with low-dose high-frequency simulation-based on-job training guided by local data. This bundle of care is a new initiative being implemented in 30 health facilities from five regions of Tanzania aiming at improving birth outcomes. Objective: To assess the perception of healthcare workers and facility leaders on the “SaferBirths Bundle of Care” towards saving women’s and newborns’ lives at birth. Method: We used a qualitative approach using focused group discussion (FGD) and individual interviews. A total of 21 FGD and 43 individual interviews were conducted between August and November 2022. In total, 94 midwives and 12 doctors were involved, some of whom were in leadership roles. The framework method for the analysis of qualitative data was used for analysis. Results: Healthcare workers and facility leaders received the bundle well and regarded it as effective in saving live...
Nature Communications
Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and m... more Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and middle-income countries (LMICs). Although Giardia associates with early-life linear growth restriction, mechanistic explanations for Giardia-associated growth impairments remain elusive. Unlike other intestinal pathogens associated with constrained linear growth that cause intestinal or systemic inflammation or both, Giardia seldom associates with chronic inflammation in these children. Here we leverage the MAL-ED longitudinal birth cohort and a model of Giardia mono-association in gnotobiotic and immunodeficient mice to propose an alternative pathogenesis of this parasite. In children, Giardia results in linear growth deficits and gut permeability that are dose-dependent and independent of intestinal markers of inflammation. The estimates of these findings vary between children in different MAL-ED sites. In a representative site, where Giardia associates with growth restriction, infected...
The American Journal of Tropical Medicine and Hygiene
At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so in children... more At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so in children and adolescents, which is hampering global elimination goals. Prolonged symptom duration presents a high-risk scenario for childhood TB in endemic areas, but the prolonged period of symptoms and its impact on educational attainment are rarely documented. Using a mixed method approach, we aimed to quantify the duration of respiratory symptoms and describe their impact on education among children from a rural area of Tanzania. We used data from a prospectively enrolled cohort of children and adolescents aged 4–17 years in rural Tanzania at the start of active TB treatment. We report on the cohort’s baseline characteristics and explore the correlation between duration of symptoms and other variables. In-depth qualitative interviews were designed on the basis of a grounded theory approach to explore the impact of TB on educational attainment among school-aged children. In this cohort, child...
<p>Performance of TaqMan array card (TAC) compared with 384 well PCR plate for AMR detectio... more <p>Performance of TaqMan array card (TAC) compared with 384 well PCR plate for AMR detection in direct stool and cultured isolates (N = 122).</p
Children (Basel), Sep 11, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Nutrition and dietary supplements, Aug 31, 2023
Background: Micronutrients (iron, iodine, vitamin B12 and folate) deficiency is prevalent globall... more Background: Micronutrients (iron, iodine, vitamin B12 and folate) deficiency is prevalent globally affecting more than two billion people majority being from low-and middle-income countries. Women of reproductive age are in an increased risk of iron deficiency. About 29.4% of women aged 15-49 years worldwide are estimated to be affected by iron deficiency. Food fortification with micronutrients is important in addressing micronutrients deficiency. Aim: To evaluate if the quadruple fortified with iodine, iron, vitamin B12, and folic acid (QFS), will be more effective in improving the hemoglobin level of women aged 18 to 49 years compared to the double fortified with iodine and iron (DFS) and iodized salt in rural Tanzania. Methods: A double-blinded three-arm randomized controlled trial was conducted between July 2020 and December 2021 at the Haydom Lutheran Hospital catchment area. We randomized women aged 18-49 years with haemoglobin between 8 and 12 g/dl who were neither pregnant nor lactating into three groups 55 Iodized salts (IS), 57 Double fortified salt (DFS), and 57 quadruple fortified salt (QFS). The participants used study salt for 10 months. Results: Over the ten months of use of study salts, the overall mean haemoglobin level of women was significantly higher in QFS by 0.43g/dl compared to IS. The ferritin levels were significantly higher in QFS and DFS by 9.60ng/mL and 9.09ng/mL, respectively, compared to IS. Vitamin B12 was insignificantly higher in QFS by 52.19pg/mL compared to DFS, and folate concentration were insignificantly higher in QFS by 7.57nmoL/L and 4.51nmoL/L compared to DFS and IS groups, respectively. Conclusion: Salt fortification with iron, iodine, folate, and Vitamin B12 is feasible and has the potential to increase the serum ferritin, Vitamin B12 and folate levels with subsequent improvement of haemoglobin levels of individuals with relatively low haemoglobin. ClinicalTrial.org Number: NCT04404751.
American Journal of Tropical Medicine and Hygiene, Apr 24, 2023
ABSTRACT. At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so i... more ABSTRACT. At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so in children and adolescents, which is hampering global elimination goals. Prolonged symptom duration presents a high-risk scenario for childhood TB in endemic areas, but the prolonged period of symptoms and its impact on educational attainment are rarely documented. Using a mixed method approach, we aimed to quantify the duration of respiratory symptoms and describe their impact on education among children from a rural area of Tanzania. We used data from a prospectively enrolled cohort of children and adolescents aged 4–17 years in rural Tanzania at the start of active TB treatment. We report on the cohort’s baseline characteristics and explore the correlation between duration of symptoms and other variables. In-depth qualitative interviews were designed on the basis of a grounded theory approach to explore the impact of TB on educational attainment among school-aged children. In this cohort, children and adolescents diagnosed with TB experienced symptoms for a median of 85 days (interquartile range: 30, 231 days) prior to treatment initiation. In addition, 56 participants (65%) had a TB exposure in the household. Of the 16 families with school-aged children who were interviewed, 15 (94%) reported a significant negative impact of TB on the schooling of their children. Children in this cohort experienced a long duration of TB symptoms; the extent of illness impacted absenteeism at school. Screening initiatives for households affected by TB may lead to a shortened duration of symptoms and may minimize the impact on school attendance.
PLOS ONE, Dec 20, 2023
Background Early childhood enteric infection with Shigella/EIEC, enteroaggregative E. coli (EAEC)... more Background Early childhood enteric infection with Shigella/EIEC, enteroaggregative E. coli (EAEC), Campylobacter, and Giardia has been associated with reduced child growth, yet a recent randomized trial of antimicrobial therapy to reduce these infections did not improve growth outcomes. To interrogate this discrepancy, we measured the enteric infections from this study. Methods We leveraged the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) trial, a randomized double-blind placebo-controlled trial of antimicrobial therapy with azithromycin and nitazoxanide provided quarterly to infants from 6 to 15 months of age. We tested 5,479 stool samples at time points across the study for 34 enteropathogens using quantitative PCR. Results There was substantial carriage of enteropathogens in stool. Azithromycin administration led to reductions in Campylobacter jejuni/coli, enteroaggregative E. coli, and Shigella/EIEC (absolute risk difference ranged from-0.06 to 0.24) 2 weeks after treatment however there was no effect after 3 months. There was no difference in Giardia after nitazoxanide administration (ARR 0.03 at the 12 month administration). When examining the effect of
Acta Paediatrica, Mar 22, 2018
Aim: We explored the diagnostic accuracy of the Clinical Dehydration Scale (CDS), the World Healt... more Aim: We explored the diagnostic accuracy of the Clinical Dehydration Scale (CDS), the World Health Organization (WHO) scale and the Gorelick scale for assessing dehydration in children admitted to a Tanzanian referral hospital.
European Respiratory Journal
BackgroundSuboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavo... more BackgroundSuboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.MethodsWe systematically searched MEDLINE, Embase and Web of Science (1990–2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration–time curve from 0 to 24 h post-dose (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0–24andCmaxwere assessed with linear mixed-effects models.ResultsOf 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geome...
Globally, deaths around the time of birth are unacceptably high of which there are about 2.7 mill... more Globally, deaths around the time of birth are unacceptably high of which there are about 2.7 million neonatal deaths and 2.6 million stillborn annually. Perinatal mortality accounts for deaths after 28 weeks of gestation to seven days after birth. Perinatal mortality is a public health concern with a huge impact on the health, social and economic well being affecting both family and society. The burden of perinatal mortality is obvious in the low and middle-income countries, and more on the countries south of sub-Sahara Africa. East Africa being among the sub-Sahara countries is also experiencing a high rate of perinatal mortally, with Tanzania taking the lead. Almost half of stillborns are alive at the start of labor offering an opportunity for prevention. Likewise, 44% of the neonatal deaths occur on the first day of life and are predominantly the result of intrapartum events. Events during labor, including birth asphyxia (interruption of placental blood flow) account for one-quar...
International Journal of Environmental Research and Public Health, Jan 12, 2020
Extreme floods pose multiple direct and indirect health risks. These risks include contamination ... more Extreme floods pose multiple direct and indirect health risks. These risks include contamination of water, food, and the environment, often causing outbreaks of diarrheal disease. Evidence regarding the effects of flooding on individual diarrhea-causing pathogens is limited, but is urgently needed in order to plan and implement interventions and prioritize resources before climate-related disasters strike. This study applied a causal inference approach to data from a multisite study that deployed broadly inclusive diagnostics for numerous high-burden common enteropathogens. Relative risks (RRs) of infection with each pathogen during a flooding disaster that occurred at one of the sites-Loreto, Peru-were calculated from generalized linear models using a comparative interrupted time series framework with the other sites as a comparison group and adjusting for background seasonality. During the early period of the flood, increased risk of heat-stable enterotoxigenic E. coli (ST-ETEC) was identified (RR = 1.73 [1.10, 2.71]) along with a decreased risk of enteric adenovirus (RR = 0.36 [0.23, 0.58]). During the later period of the flood, sharp increases in the risk of rotavirus (RR = 5.30 [2.70, 10.40]) and sapovirus (RR = 2.47 [1.79, 3.41]) were observed, in addition to increases in transmission of Shigella spp. (RR = 2.86 [1.81, 4.52]) and Campylobacter spp. (RR = 1.41 (1.01, 1.07). Genotype-specific exploratory analysis reveals that the rise in rotavirus transmission during the flood was likely due to the introduction of a locally atypical, non-vaccine (G2P[4]) strain of the virus. Policy-makers should target interventions towards these pathogens-including vaccines as they become available-in settings where vulnerability to flooding is high as part of disaster preparedness strategies, while investments in radical, transformative, community-wide, and locally-tailored water and sanitation interventions are also needed.
Open Forum Infectious Diseases, May 13, 2022
Background. The application of molecular diagnostics has identified enteric group adenovirus sero... more Background. The application of molecular diagnostics has identified enteric group adenovirus serotypes 40 and 41 as important causes of diarrhea in children. However, many aspects of the epidemiology of adenovirus 40/41 diarrhea have not been described. Methods. We used data from the 8-site Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project birth cohort study to describe site-and age-specific incidence, risk factors, clinical characteristics, and seasonality. Results. The incidence of adenovirus 40/41 diarrhea was substantially higher by quantitative polymerase chain reaction than enzyme immunoassay and peaked at 30 episodes per 100 child-years in children aged 7-15 months, with substantial variation in incidence between sites. A significant burden was also seen in children 0-6 months of age, higher than other viral etiologies with the exception of rotavirus. Children with adenovirus 40/41 diarrhea were more likely to have a fever than children with norovirus, sapovirus, and astrovirus (adjusted odds ratio [aOR], 1.62; 95% CI, 1.16-2.26) but less likely than children with rotavirus (aOR, 0.66; 95% CI, 0.49-0.91). Exclusive breastfeeding was strongly protective against adenovirus 40/41 diarrhea (hazard ratio, 0.64; 95% CI, 0.48-0.85), but no other risk factors were identified. The seasonality of adenovirus 40/41 diarrhea varied substantially between sites and did not have clear associations with seasonal variations in temperature or rainfall. Conclusions. This study supports the situation of adenovirus 40/41 as a pathogen of substantial importance, especially in infants. Fever was a distinguishing characteristic in comparison to other nonrotavirus viral etiologies, and promotion of exclusive breastfeeding may reduce the high observed burden in the first 6 months of life.
The Lancet Planetary Health, Jun 1, 2019
Background Climate change threatens to undermine recent progress in reducing global deaths from d... more Background Climate change threatens to undermine recent progress in reducing global deaths from diarrhoeal disease in children. However, the scarcity of evidence about how individual environmental factors affect transmission of specific pathogens makes prediction of trends under different climate scenarios challenging. We aimed to model associations between daily estimates of a suite of hydrometeorological variables and rotavirus infection status ascertained through community-based surveillance. Methods For this analysis of multisite cohort data, rotavirus infection status was ascertained through communitybased surveillance of infants in the eight-site MAL-ED cohort study, and matched by date with earth observation estimates of nine hydrometeorological variables from the Global Land Data Assimilation System: daily total precipitation volume (mm), daily total surface runoff (mm), surface pressure (mbar), wind speed (m/s), relative humidity (%), soil moisture (%), solar radiation (W/m²), specific humidity (kg/kg), and average daily temperatures (°C). Lag relationships, independent effects, and interactions were characterised by use of modified Poisson models and compared with and without adjustment for seasonality and between-site variation. Final models were created with stepwise selection of main effects and interactions and their validity assessed by excluding each site in turn and calculating Tjur's Coefficients of Determination. Findings All nine hydrometeorological variables were significantly associated with rotavirus infection after adjusting for seasonality and between-site variation over multiple consecutive or non-consecutive lags, showing complex, often non-linear associations that differed by symptom status and showed considerable mutual interaction. The final models explained 5•9% to 6•2% of the variability in rotavirus infection in the pooled data and their predictions explained between 0•0% and 14•1% of the variability at individual study sites. Interpretation These results suggest that the effect of climate on rotavirus transmission was mediated by four independent mechanisms: waterborne dispersal, airborne dispersal, virus survival on soil and surfaces, and host factors. Earth observation data products available at a global scale and at subdaily resolution can be combined with longitudinal surveillance data to test hypotheses about routes and drivers of transmission but showed little potential for making predictions in this setting.
Journal of Clinical Microbiology, Apr 1, 2014
Campylobacter is a common bacterial enteropathogen that can be detected in stool by culture, enzy... more Campylobacter is a common bacterial enteropathogen that can be detected in stool by culture, enzyme immunoassay (EIA), or PCR. We compared culture for C. jejuni/C. coli, EIA (ProSpecT), and duplex PCR to distinguish Campylobacter jejuni/C. coli and non-jejuni/coli Campylobacter on 432 diarrheal and matched control stool samples from infants in a multisite longitudinal study of enteric infections in Tanzania, Bangladesh, and Peru. The sensitivity and specificity of culture were 8.5% and 97.6%, respectively, compared with the results of EIA and 8.7% and 98.0%, respectively, compared with the results of PCR for C. jejuni/C. coli. Most (71.6%) EIA-positive samples were positive by PCR for C. jejuni/C. coli, but 27.6% were positive for nonjejuni/coli Campylobacter species. Sequencing of 16S rRNA from 53 of these non-jejuni/coli Campylobacter samples showed that it most closely matched the 16S rRNA of C. hyointestinalis subsp. lawsonii (56%), C. troglodytis (33%), C. upsaliensis (7.7%), and C. jejuni/C. coli (2.6%). Campylobacter-negative stool spiked with each of the above-mentioned Campylobacter species revealed reactivity with EIA. PCR detection of Campylobacter species was strongly associated with diarrhea in Peru (odds ratio [OR] ؍ 3.66, P < 0.001) but not in Tanzania (OR ؍ 1.56, P ؍ 0.24) or Bangladesh (OR ؍ 1.13, P ؍ 0.75). According to PCR, Campylobacter jejuni/C. coli infections represented less than half of all infections with Campylobacter species. In sum, in infants in developing country settings, the ProSpecT EIA and PCR for Campylobacter reveal extremely high rates of positivity. We propose the use of PCR because it retains high sensitivity, can ascertain burden, and can distinguish between Campylobacter infections at the species level.
American Journal of Tropical Medicine and Hygiene, Jun 15, 2022
We identified the determinants of positive (children who had a birth weight , 2.5 kg and/or mater... more We identified the determinants of positive (children who had a birth weight , 2.5 kg and/or maternal height , 145 cm but were nonstunted at 24 months of age) and negative (children who had a birth weight $ 2.5 kg and maternal height $ 145 cm but were stunted at 24 months of age) deviance in childhood linear growth. We found that socioeconomic status (b 5 1.54, P , 0.01), serum retinol (b 5 0.05, P , 0.01), hemoglobin (b 5 0.36, P , 0.01), length-forage Z-score (LAZ) at birth (b 5 0.47, P , 0.01), and tetanus vaccine titer (b 5 0.182, P , 0.05) were positively and maternal depressive symptom (b 5-0.05, P , 0.01), serum ferritin (b 5-0.03, P , 0.01), male sex (b 5-1.08, P , 0.01), and a1-antitrypsin (b 5-0.81, P , 0.01) were negatively associated with positive deviance. Further, diarrhea episodes (b 5 0.02, P , 0.01), male sex (b 5 0.72, P , 0.01), and a1-antitrypsin (b 5 0.67, P , 0.01) were positively and hemoglobin (b5-0.28, P , 0.01), soluble transferrin receptor level (b 5-0.15, P , 0.01), and LAZ score at birth (b 5-0.90, P , 0.01) were negatively associated with negative deviance. To summarize, enteric protein loss, micronutrient deficiency, vaccine responses and maternal depressive symptoms were associated with linear growth deviance in early childhood. In such a background, public health approaches aimed at reducing the risk of intestinal inflammation and altered gut permeability could prove fruitful in ensuring desired linear growth in children. In addition, maternal mental health issue should also be considered, especially for promoting better nutritional status in children in the context of linear growth deviance.
Open Forum Infectious Diseases, Nov 1, 2018
at bedside for patients admitted with sepsis. A future prospective interventional study is needed... more at bedside for patients admitted with sepsis. A future prospective interventional study is needed in order to validate the score, captured at bedside electronically, in terms of improving patients' outcomes. Disclosures. All authors: No reported disclosures.
The American Journal of Clinical Nutrition, 2019
ABSTRACTBackgroundEnvironmental enteric dysfunction (EED) is thought to increase the risk of micr... more ABSTRACTBackgroundEnvironmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation.ObjectiveWe tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status.MethodsUsing data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods ...
Science Advances, Apr 10, 2020
Malnutrition continues to affect the growth and development of millions of children worldwide, an... more Malnutrition continues to affect the growth and development of millions of children worldwide, and chronic undernutrition has proven to be largely refractory to interventions. Improved understanding of metabolic development in infancy and how it differs in growth-constrained children may provide insights to inform more timely, targeted, and effective interventions. Here, the metabolome of healthy infants was compared to that of growthconstrained infants from three continents over the first 2 years of life to identify metabolic signatures of aging. Predictive models demonstrated that growth-constrained children lag in their metabolic maturity relative to their healthier peers and that metabolic maturity can predict growth 6 months into the future. Our results provide a metabolic framework from which future nutritional programs may be more precisely constructed and evaluated.
Biomedical Signal Processing and Control
Healthcare
Background: SaferBirths Bundle of Care (SBBC) is a package of innovative clinical and training to... more Background: SaferBirths Bundle of Care (SBBC) is a package of innovative clinical and training tools coupled with low-dose high-frequency simulation-based on-job training guided by local data. This bundle of care is a new initiative being implemented in 30 health facilities from five regions of Tanzania aiming at improving birth outcomes. Objective: To assess the perception of healthcare workers and facility leaders on the “SaferBirths Bundle of Care” towards saving women’s and newborns’ lives at birth. Method: We used a qualitative approach using focused group discussion (FGD) and individual interviews. A total of 21 FGD and 43 individual interviews were conducted between August and November 2022. In total, 94 midwives and 12 doctors were involved, some of whom were in leadership roles. The framework method for the analysis of qualitative data was used for analysis. Results: Healthcare workers and facility leaders received the bundle well and regarded it as effective in saving live...
Nature Communications
Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and m... more Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and middle-income countries (LMICs). Although Giardia associates with early-life linear growth restriction, mechanistic explanations for Giardia-associated growth impairments remain elusive. Unlike other intestinal pathogens associated with constrained linear growth that cause intestinal or systemic inflammation or both, Giardia seldom associates with chronic inflammation in these children. Here we leverage the MAL-ED longitudinal birth cohort and a model of Giardia mono-association in gnotobiotic and immunodeficient mice to propose an alternative pathogenesis of this parasite. In children, Giardia results in linear growth deficits and gut permeability that are dose-dependent and independent of intestinal markers of inflammation. The estimates of these findings vary between children in different MAL-ED sites. In a representative site, where Giardia associates with growth restriction, infected...
The American Journal of Tropical Medicine and Hygiene
At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so in children... more At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so in children and adolescents, which is hampering global elimination goals. Prolonged symptom duration presents a high-risk scenario for childhood TB in endemic areas, but the prolonged period of symptoms and its impact on educational attainment are rarely documented. Using a mixed method approach, we aimed to quantify the duration of respiratory symptoms and describe their impact on education among children from a rural area of Tanzania. We used data from a prospectively enrolled cohort of children and adolescents aged 4–17 years in rural Tanzania at the start of active TB treatment. We report on the cohort’s baseline characteristics and explore the correlation between duration of symptoms and other variables. In-depth qualitative interviews were designed on the basis of a grounded theory approach to explore the impact of TB on educational attainment among school-aged children. In this cohort, child...
<p>Performance of TaqMan array card (TAC) compared with 384 well PCR plate for AMR detectio... more <p>Performance of TaqMan array card (TAC) compared with 384 well PCR plate for AMR detection in direct stool and cultured isolates (N = 122).</p