Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations.

Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies focusing on other ancestral groups. Consequently, the degree to which facial traits share a common genetic basis across diverse sets of humans remains largely unknown. We therefore investigated the genetic basis of facial morphology in an East African cohort. We applied an open-ended data-driven phenotyping approach to a sample of 2,595 3D facial images collected on Tanzanian children. This approach segments the face into hierarchically arranged, multivariate features that capture the shape variation after adjusting for age, sex, height, weight, facial size and population stratification. Genome scans of these multivariate shape phenotypes revealed significant (p < 2.5 × 10-8) signals at 20 loci, which were enriched for active chromatin elements in human cranial neural crest cells and embryonic craniofacial tissue, consistent with an early developmental origin of the facial variation. Two of these associations were in highly conserved regions showing craniofacial-specific enhancer activity during embryological development (5q31.1 and 12q21.31). Six of the 20 loci surpassed a stricter threshold accounting for multiple phenotypes with study-wide significance (p < 6.25 × 10-10). Cross-population comparisons indicated 10 association signals were shared with Europeans (seven sharing the same associated SNP), and facilitated fine-mapping of causal variants at previously reported loci. Taken together, these results may point to both shared and population-specific components to the genetic architecture of facial variation.

Maternal exposure to arsenic and mercury in small-scale gold mining areas of Northern Tanzania.

Artisanal and small-scale gold mining (ASGM) in Tanzania results in occupational exposures and environmental contamination to toxic chemical elements such as arsenic and mercury. Populations living in such areas may be exposed by various routes, and prenatal exposure to arsenic and mercury has been associated with adverse birth outcomes and developmental delays. The aim of this study was to determine if levels of arsenic and mercury differed among pregnant women living in areas with and without ASGM activities in Northern Tanzania. This cross-sectional study is part of the ongoing Mining and Health prospective longitudinal study. Spot urine samples and dried blood spots were collected at the antenatal health clinics from pregnant women (n = 1056) at 16-27 weeks gestation. Urine samples were analyzed for total arsenic (T-As) and dried blood spots were analyzed for total mercury (T-Hg). Women in the ASGM cohort had median T-As levels (9.4 µg/L; IQR: 4.9-15.1) and T-Hg levels (1.2 µg/L; IQR: 0.8-1.86) that were significantly higher than the median T-As levels (6.28 µg/L; IQR: 3.7-14.1) and T-Hg levels (0.66 µg/L; IQR: 0.3-1.2) of women in the non-ASGM cohort (Mann-Whitney U test, T-As: z = -9.881, p = 0.0005; T-Hg: z = -3.502, p < 0.0001). Among pregnant women from ASGM areas, 25% had urinary T-As and 75% had blood T-Hg above the established human biomonitoring reference values of 15 and 0.80 µg/L. In the ASGM cohort, lower maternal education and low socioeconomic status increased the odds of higher T-As levels by 20% (p < 0.05) and 10% (p < 0.05), respectively. Women involved in mining activities and those of low socioeconomic status had increased odds of higher T-Hg by 70% (p < 0.001) and 10% (p < 0.05), respectively. Arsenic and mercury concentrations among women in non-ASGM areas suggest exposure sources beyond ASGM activities that need to be identified. Arsenic and mercury levels in women in Tanzania are of public health concern and their association with adverse birth and child developmental outcomes will be examined in future studies on this cohort.

Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape.

The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics.

A variant source of arterial supply to the ascending, transverse and descending colon.

Anatomic variations involving arterial supply of the large intestines are of clinical significance. Variations range from the pattern of origin, branching and territorial supply. The colon, the part of the large intestine, usually receives its arterial blood supply from branches of the superior and inferior mesenteric arteries. However, anatomic variation in this vascular arrangement has been reported, with vascular anatomy of the right colon being described as complex and more variable compared with the left colon. During routine cadaveric dissection of the supracolic and infracolic viscera, we encountered an additional mesenteric artery originating directly from the anterior surface of the abdominal aorta between the origins of the superior and inferior mesenteric arteries. This additional "inferior mesenteric artery" ran obliquely superiorly toward the left colon giving rise to two branches supplying the distal part of the ascending colon, the transverse colon and the proximal part of the descending colon. Awareness and knowledge of this anatomic variation are important for radiologists and surgeons to improve the quality of surgery and avoid both intra- and postoperative complications during surgical procedures of the colon.

Facial shape manifestations of growth faltering in Tanzanian children.

Variation in the shape of the human face and in stature is determined by complex interactions between genetic and environmental influences. One such environmental influence is malnourishment, which can result in growth faltering, usually diagnosed by means of comparing an individual's stature with a set of age-appropriate standards. These standards for stature, however, are typically ascertained in groups where people are at low risk for growth faltering. Moreover, genetic differences among populations with respect to stature are well established, further complicating the generalizability of stature-based diagnostic tools. In a large sample of children aged 5-19 years, we obtained high-resolution genomic data, anthropometric measures and 3D facial images from individuals within and around the city of Mwanza, Tanzania. With genome-wide complex trait analysis, we partitioned genetic and environmental variance for growth outcomes and facial shape. We found that children with growth faltering have faces that look like those of older and taller children, in a direction opposite to the expected allometric trajectory, and in ways predicted by the environmental portion of covariance at the community and individual levels. The environmental variance for facial shape varied subtly but significantly among communities, whereas genetic differences were minimal. These results reveal that facial shape preserves information about exposure to undernourishment, with important implications for refining assessments of nutritional status in children and the developmental-genetics of craniofacial variation alike.

Body size and allometric variation in facial shape in children.

OBJECTIVES: Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allometry for human facial shape. METHODS: Our study is based on two large cross-sectional cohorts of children, one from Tanzania and the other from the United States (N = 7,173). We employ 3D facial imaging and geometric morphometrics to relate facial shape to age and anthropometric measures. RESULTS: The two populations differ significantly in facial shape, but the magnitude of this difference is small relative to the variation within each group. Allometric variation for facial shape is similar in both populations, representing a small but significant proportion of total variation in facial shape. Different measures of size are associated with overlapping but statistically distinct aspects of shape variation. Only half of the size-related variation in facial shape can be explained by the first principal component of four size measures and age while the remainder associates distinctly with individual measures. CONCLUSIONS: Allometric variation in the human face is complex and should not be regarded as a singular effect. This finding has important implications for how size is treated in studies of human facial shape and for the developmental basis for allometric variation more generally.

Rapid automated landmarking for morphometric analysis of three-dimensional facial scans.

Automated phenotyping is essential for the creation of large, highly standardized datasets from anatomical imaging data. Such datasets can support large-scale studies of complex traits or clinical studies related to precision medicine or clinical trials. We have developed a method that generates three-dimensional landmark data that meet the requirements of standard geometric morphometric analyses. The method is robust and can be implemented without high-performance computing resources. We validated the method using both direct comparison to manual landmarking on the same individuals and also analyses of the variation patterns and outlier patterns in a large dataset of automated and manual landmark data. Direct comparison of manual and automated landmarks reveals that automated landmark data are less variable, but more highly integrated and reproducible. Automated data produce covariation structure that closely resembles that of manual landmarks. We further find that while our method does produce some landmarking errors, they tend to be readily detectable and can be fixed by adjusting parameters used in the registration and control-point steps. Data generated using the method described here have been successfully used to study the genomic architecture of facial shape in two different genome-wide association studies of facial shape.

Participatory science and innovation for improved sanitation and hygiene: process and outcome evaluation of project SHINE, a school-based intervention in Rural Tanzania.

BACKGROUND: Diarrheal disease is a major cause of mortality and morbidity in low and middle income countries with children being disproportionately affected. Project SHINE (Sanitation & Hygiene INnovation in Education) is a grassroots participatory science education and social entrepreneurship model to engage youth and the wider community in the development of sustainable strategies to improve sanitation and hygiene. METHODS: Based in rural and remote Tanzania, this pilot study engaged pastoralist high-school students and communities in the development and evaluation of culturally and contextually relevant strategies to improve sanitation and hygiene. Using a train-the-trainer approach, key activities included teacher workshops, school-based lessons, extra-curricular activities, community events and a One Health sanitation science fair which showcased projects related to water, sanitation and hygiene in relation to human and animal health. The process and outcome of the study were evaluated through qualitative interviews and focus group discussions with diverse project participants, as well as pre- and post- questionnaires completed by students on knowledge, attitudes and practices concerning sanitation and hygiene. RESULTS: The questionnaire results at baseline and follow-up showed statistically significant improvements on key measures including a decrease in unhygienic behaviors, an increase in the perceived importance of handwashing and intention to use the toilet, and increased communication in the social network about the importance of clean water and improved sanitation and hygiene practices, however there were no significant changes in sanitation related knowledge. Qualitative data highlighted strong leadership emerging from youth and enthusiasm from teachers and students concerning the overall approach in the project, including the use of participatory methods. There was a high degree of community engagement with hundreds of community members participating in school-based events. Sanitation science fair projects addressed a range of pastoralist questions and concerns regarding the relationship between water, sanitation and hygiene. Several projects, such as making soap from local materials, demonstrate potential as a sustainable strategy to improve health and livelihoods in the long-term. CONCLUSIONS: The Project SHINE model shows promise as an innovative capacity building approach and as an engagement and empowerment strategy for youth and communities to develop locally sustainable strategies to improve sanitation and hygiene.

Household-level predictors of maternal mental health and systemic inflammation among infants in Mwanza, Tanzania.

OBJECTIVES: Household conditions and culturally/socially variable childcare practices influence priming of the inflammatory response during infancy. Maternal mental health may partially mediate that effect. Among mother-infant dyads in Mwanza, Tanzania, we hypothesized that poorer maternal mental health would be associated with adverse household ecology, lower social capital, and greater inflammation among infants under the age of one; and that mental health would mediate any effects of household ecology/social capital on inflammation. METHODS: We collected dried blood spots from mother-infant dyads (N = 88) at health centers near Mwanza, Tanzania. To assess household ecology and social capital, we conducted interviews with mothers using the Household Food Insecurity Access Scale, the MacArthur Subjective Social Status Scale, and a household wealth inventory. We employed the Hopkins Symptom Checklist to assess maternal mental health. A high-sensitivity C-reactive protein (CRP) assay was used to quantify inflammation. RESULTS: Severe food insecurity (OR: 5.16), lower subjective social status (r = -0.32), and lower household wealth (r = -0.26) were associated with high symptoms of maternal depression. Lower household wealth (r = -0.21) and severe food insecurity (OR: 2.52) were associated with high anxiety. High depression symptoms (OR: 2.56) and severe food insecurity (OR: 2.77) each were associated with greater-than-median infant CRP. However, mediation was not supported. CONCLUSIONS: Maternal mental health should be considered alongside nutritional status, pathogen exposure, and education as a potential driver of very early innate immune system development. Proximal mechanisms warrant further investigation. Am. J. Hum. Biol. 28:461-470, 2016. © 2015 Wiley Periodicals, Inc.

'WE CAN'T GET WORMS FROM COW DUNG': REPORTED KNOWLEDGE OF PARASITISM AMONG PASTORALIST YOUTH ATTENDING SECONDARY SCHOOL IN THE NGORONGORO CONSERVATION AREA, TANZANIA.

Records at the Endulen Hospital in the Ngorongoro Conservation Area (NCA), Tanzania, reveal that soil-transmitted helminth infections and protozoa are consistently in the top ten diagnoses for Maasai pastoralists, indicating a significant public health concern. Nevertheless, Maasai pastoralist adaptations to life in close proximity to livestock and to unreliable access to water raise important questions about experiences of, and resiliency to, parasitic infections. Though these infections are particularly prevalent among youth in low- and middle-income countries (LMIC), a focus on resiliency highlights local capacity to recover from and prevent illness. For instance, how is human parasitism perceived and experienced among communities displaying behaviours that studies have associated with transmission of diarrhoeal diseases, such as open defecation? Among these communities, how is parasitism seen to impact the health and development of children? And, what resources are available to endure or mitigate this heavy disease burden among affected communities? This study draws on formative research carried out in May 2014 in anticipation of an innovative school-based and youth-driven water, sanitation and hygiene education intervention rolled out in two boarding schools in the NCA in subsequent months. The initiative is grounded in a One Health approach to health promotion, drawing on partnerships in medicine, public health and veterinary medicine to appreciate the unique interactions between humans, animals and the environment that shape well-being among pastoralist communities. Qualitative data generated through group discussions with secondary school youth (n=60), Maasai teachers (n=6) and a women's group (n=8) in the NCA convey existing knowledge of the prevalence, prevention and treatment of human parasitism. An underlying principle of the larger initiative is to engage youth as creative agents of change in developing and sustaining locally relevant health promotion strategies. Findings highlight practical knowledge around certain 'neglected tropical diseases', namely helminths, among pastoralist communities in the NCA, in turn feeding into the development of the science fair and related interventions.

Improving gross anatomy learning using reciprocal peer teaching.

BACKGROUND: The use of cadavers in human anatomy teaching requires adequate number of anatomy instructors who can provide close supervision of the students. Most medical schools are facing challenges of lack of trained individuals to teach anatomy. Innovative techniques are therefore needed to impart adequate and relevant anatomical knowledge and skills. This study was conducted in order to evaluate the traditional teaching method and reciprocal peer teaching (RPT) method during anatomy dissection. METHODS: Debriefing surveys were administered to the 227 first year medical students regarding merits, demerits and impact of both RPT and Traditional teaching experiences on student's preparedness prior to dissection, professionalism and communication skills. Out of this, 159 (70 %) completed the survey on traditional method while 148 (65.2 %) completed survey on RPT method. An observation tool for anatomy faculty was used to assess collaboration, professionalism and teaching skills among students. Student's scores on examinations done before introduction of RPT were compared with examinations scores after introduction of RPT. RESULTS: Our results show that the mean performance of students on objective examinations was significantly higher after introduction of RPT compared to the performance before introduction of RPT [63.7 ± 11.4 versus 58.6 ± 10, mean difference 5.1; 95 % CI = 4.0-6.3; p-value < 0.0001]. Students with low performance prior to RPT benefited more in terms of examination performance compared to those who had higher performance [Mean difference 7.6; p-value < 0.0001]. Regarding student's opinions on traditional method versus RPT, 83 % of students either agreed or strongly agreed that they were more likely to read the dissection manual before the RPT dissection session compared to 35 % for the traditional method. Over 85 % of respondents reported that RPT improved their confidence and ability to present information to peers and faculty compared to 38 % for the tradition method. The majority of faculty reported that the learning environment of the dissection groups was very active learning during RPT sessions and that professionalism was observed by most students during discussions. CONCLUSIONS: Introduction of RPT in our anatomy dissection laboratory was generally beneficial to both students and faculty. Both objective (student performance) and subjective data indicate that RPT improved student's performance and had a positive learning experience impact. Our future plan is to continue RPT practice and continually evaluate the RPT protocol.

Facial morphometrics of children with non-syndromic orofacial clefts in Tanzania.

BACKGROUND: Orofacial clefts (cleft lip/palate; CL/P) are among the most common congenital anomalies, with prevalence that varies among different ethnic groups. Craniofacial shape differences between individuals with CL/P and healthy controls have been widely reported in non-African populations. Knowledge of craniofacial shape among individuals with non-syndromic CL/P in African populations will provide further understanding of the ethnic and phenotypic variation present in non-syndromic orofacial clefts. METHODS: A descriptive cross-sectional study was carried out at Bugando Medical Centre, Tanzania, comparing individuals with unrepaired non-syndromic CL/P and normal individuals without orofacial clefts. Three-dimensional (3D) facial surfaces were captured using a non-invasive 3D camera. The corresponding 3D coordinates for 26 soft tissue landmarks were used to characterize facial shape. Facial shape variation within and between groups, based on Procrustes superimposed data, was studied using geometric morphometric methods. RESULTS: Facial shape of children with cleft lip differed significantly from the control group, beyond the cleft itself. The CL/P group exhibited increased nasal and mouth width, increased interorbital distance, and more prognathic premaxillary region. Within the CL/P group, PCA showed that facial shape variation is associated with facial height, nasal cavity width, interorbital distance and midfacial prognathism. The isolated cleft lip (CL) and combined cleft lip and palate (CLP) groups did not differ significantly from one another (Procrustes distance = 0.0416, p = 0.50). Procrustes distance permutation tests within the CL/P group showed a significant shape difference between unilateral clefts and bilateral clefts (Procrustes distance = 0.0728, p = 0.0001). Our findings indicate the morphological variation is similar to those of studies of CL/P patients and their unaffected close relatives in non-African populations. CONCLUSION: The mean facial shape in African children with non-syndromic CL/P differs significantly from children without orofacial clefts. The main differences involve interorbital width, facial width and midface prognathism. The axes of facial shape differences we observed are similar to the patterns seen in Caucasian populations, despite apparent differences in cleft prevalence and cleft type distribution. Similar facial morphology in individuals with CL/P in African and Caucasian populations suggests a similar aetiology.

Emotional preparedness for human body donor dissection in premedical education: A pilot program evaluation.

Dissection of bodies provided by donors continues to be utilized as a critical part of medical education. It also represents a rite of passage that socializes students to prepare them for the stress that comes with working in a clinical environment as a medical professional. Just as proper guidance in acquiring technical skills is critical in anatomy education, there is an important need for proper emotional guidance throughout the human dissection process. A pilot curriculum was developed by an interdisciplinary faculty team to emotionally prepare students for their first visit to the anatomy laboratory. Students were first-year foundation premedical students who had expressed an interest in visiting the laboratory. Pre- and post-visit surveys were conducted to explore students' emotional responses to a first visit to the anatomy laboratory and their utilization of coping strategies. The survey findings show an overwhelming favorable feeling in anticipation of the human gross anatomy laboratory visit. About 20% of the students experienced anxiety at the anticipation of the laboratory visit, but only 5.3% experienced anxiety during the visit. The decrease in the number of students experiencing anxiety may be attributed to the interventions introduced before and during the visit. Talking with a close friend was the main coping strategy utilized by 63% of students experiencing fear or anxiety during and after the laboratory visit. The findings from this program evaluation provide a better understanding of student emotional preparedness and utilization of coping strategies, which may help prepare and guide future students for the dissection experience.

Orofacial clefts at Bugando Medical Centre: associated factors and postsurgical complications.

OBJECTIVE: To determine factors associated with orofacial clefts and postsurgical complications of cleft lip and palate repair surgeries in northwestern Tanzania. METHODS: This was a cohort study involving patients with orofacial clefts. Associated factors (family history of orofacial clefts, maternal use of alcohol and cigarette smoking during pregnancy) were obtained through interviews with accompanying parents. Antenatal cards were used to obtain maternal age at birth and birth weight. RESULTS: Ninety-four patients with different orofacial clefts were seen. Among them, 46.8% (44/94), 13.8% (13/94), and 39.4% (37/94) had cleft lip, cleft palate, and cleft lip and palate, respectively. About 15% of orofacial cleft cases had a positive family history of orofacial clefts. Among these, 7.4% had an affected relative on the maternal side, 4.3% had an affected relative on the paternal side, and 3.2% had an affected sibling. This difference was statistically significant (chi-square  =  27.7, p < .001). Orofacial cleft was significantly associated with order of birth (chi-square  =  21.0, p < .001). Postoperative complications observed included palatal fistula and philtrum dehiscence. CONCLUSION: Family history of orofacial clefts and order of birth were significantly associated with orofacial clefts in northwestern Tanzania. These factors have been associated with risk of orofacial clefts elsewhere and suggest a hereditary role in the etiology of orofacial cleft. Palatal fistula and philtrum dehiscence were postsurgical complications observed in orofacial clefts patients who had primary surgery past the recommended age. These complications could have resulted from delayed surgery and absence of presurgical procedures.

Reducing malaria misdiagnosis: the importance of correctly interpreting Paracheck Pf® "faint test bands" in a low transmission area of Tanzania.

BACKGROUND: Although malaria rapid diagnostic tests (RDTs) have been extensively evaluated since their introduction in the early 1990's, sensitivity and specificity vary widely limiting successful integration into clinical practice. This paper reviews specific issues surrounding RDT use in field settings and presents results of research investigating how to interpret "faint test bands" on ParaCheck Pf® in areas of low transmission in order to reduce malaria misdiagnosis. METHODS: A multi-phase cross-sectional study was conducted at a remote hospital in the northern Tanzanian highlands. Capillary blood samples were taken from consenting participants (n = 319) for blood smear and ParaCheck Pf® testing. Primary outcome variables were sensitivity, specificity and proportion misdiagnosed by ParaCheck Pf® and local microscopy. ParaCheck Pf® "faint bands" were classified as both true positives or true negatives during evaluation to determine appropriate clinical interpretation. Multivariate logistic regression adjusted for age and gender was conducted to determine odds of misdiagnosis for local microscopy and ParaCheck Pf®. RESULTS: Overall, 23.71% of all ParaCheck Pf® tests resulted in a "faint band" and 94.20% corresponded with true negatives. When ParaCheck Pf® "faint bands" were classified as positive, specificity was 75.5% (95% CI = 70.3%-80.6%) as compared to 98.9% (95% CI = 97.0%-99.8%) when classified as negative. The odds of misdiagnosis by local microscopy for those > 5 years as compared to those ≤ 5 years are 0.370 (95% CI = 0.1733-0.7915, p = 0.010). In contrast, even when ParaCheck Pf® faint bands are considered positive, the odds of misdiagnosis by ParaCheck Pf® for those > 5 years as compared to those ≤ 5 years are 0.837 (95% CI = 0.459-1.547, p = 0.5383). CONCLUSIONS: We provide compelling evidence that in areas of low transmission, "faint bands" should be considered a negative test when used to inform clinical decision-making. Correct interpretation of RDT test bands in a clinical setting plays a central role in successful malaria surveillance, appropriate patient management and most importantly reducing misdiagnosis.

An assessment of orofacial clefts in Tanzania.

BACKGROUND: Clefts of the lip (CL), the palate (CP), or both (CLP) are the most common orofacial congenital malformations found among live births, accounting for 65% of all head and neck anomalies. The frequency and pattern of orofacial clefts in different parts of the world and among different human groups varies widely. Generally, populations of Asian or Native American origin have the highest prevalence, while Caucasian populations show intermediate prevalence and African populations the lowest. To date, little is known regarding the epidemiology and pattern of orofacial clefts in Tanzania. METHODS: A retrospective descriptive study was conducted at Bugando Medical Centre to identify all children with orofacial clefts that attended or were treated during a period of five years. Cleft lip and/or palate records were obtained from patient files in the Hospital's Departments of Surgery, Paediatrics and medical records. Age at presentation, sex, region of origin, type and laterality of the cleft were recorded. In addition, presence of associated congenital anomalies or syndromes was recorded. RESULTS: A total of 240 orofacial cleft cases were seen during this period. Isolated cleft lip was the most common cleft type followed closely by cleft lip and palate (CLP). This is a departure from the pattern of clefting reported for Caucasian and Asian populations, where CLP or isolated cleft palate is the most common type. The distribution of clefts by side showed a statistically significant preponderance of the left side (43.7%) (χ2 = 92.4, p < 0.001), followed by the right (28.8%) and bilateral sides (18.3%). Patients with isolated cleft palate presented at very early age (mean age 1.00 years, SE 0.56). Associated congenital anomalies were observed in 2.8% of all patients with orofacial clefts, and included neural tube defects, Talipes and persistent ductus arteriosus. CONCLUSIONS: Unilateral orofacial clefts were significantly more common than bilateral clefts; with the left side being the most common affected side. Most of the other findings did not show marked differences with orofacial cleft distributions in other African populations.

The role of Vitamin B12 and genetic risk factors in the etiology of neural tube defects: A systematic review.

Neural tube defects (NTDs) are birth defects that arise during embryogenesis when normal neural tube closure fails to occur. According to the World Health Organization, NTDs are detected annually in approximately 300,000 neonates worldwide. The exact etiology of NTDs remains complex and poorly understood. It is generally agreed that most NTD cases are of multifactorial origin, having a combination of multiple genes and a number of environmental risk factors. The role of folic acid, vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs, has also been extensively studied. This knowledge synthesis brings together different types of evidence to update the role of vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs. Following a PubMed search and screening for relevant articles, we included 40 studies in our review (30 case-control studies, 3 cross-sectional studies, 5 cohort studies, and 2 case reports). The available data showed that vitamin B12 levels were decreased in mothers and infants in NTD groups compared with control groups. Holo-transcobalamin, the active form of vitamin B12, was also found in lower levels in mothers with NTD-affected infants. Several studies reported elevated homocysteine levels in mothers and infants in NTD groups. Additionally, numerous studies reported links between genetic variants and increased NTD risk. These genes include GIF, LRP2, CUBN, TCb1R, MTHFR, and others. Several maternal factors have also been linked with significant NTD risk such as BMI, maternal diet, air pollutants, low maternal age, and many others. The majority of studies on NTDs have focused on the role of folic acid, hence there is a need for well-designed studies on the role of other risk factors like vitamin B12 deficiency in the etiology of NTDs.

Effects of prenatal exposure and co-exposure to metallic or metalloid elements on early infant neurodevelopmental outcomes in areas with small-scale gold mining activities in Northern Tanzania.

BACKGROUND: Artisanal and small-scale gold mining (ASGM) is associated with release of neurotoxic metallic or metalloid chemical elements including lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As). OBJECTIVE: To examine associations between prenatal exposure and co-exposure to total lead (T-Pb), total mercury (T-Hg), total cadmium (T-Cd) and total arsenic (T-As) and infant neurodevelopment at 6 to 12 months of age in areas with ASGM activities in Tanzania. METHODS: Women in their second trimester of pregnancy who resided in ASGM areas were enrolled from 2015 to 2017 (n = 883). At 6 to 12 months of age, children were assessed with the Malawi Developmental Assessment Tool (MDAT) (n = 439). We measured T-Pb, T-Hg, and T-Cd in maternal dried blood spots and T-As in maternal urines. Poisson regression was used to examine associations between prenatal concentrations of these elements and neurodevelopmental outcomes. RESULTS: Prenatal T-Hg concentration was associated with global neurodevelopment status (aPR 1.03, CI:1.01-1.04; p < 0.001) and language impairment (aPR 1.05, CI:1.03-1.07; p < 0.001) on the MDAT. When prenatal T-Hg and T-As values were at or above the human biomonitoring reference values (≥95%) of the German Environmental Survey for Human Biomonitoring, that is 0.80 µg/L and 15 µg/L, respectively, the prevalence ratio of global neurodevelopmental impairment was two times higher (aPR 2.1, CI:1.0-4.3; p = 0.034). There was a 40% increase in the prevalence ratio of global neurodevelopmental impairment (aPR 1.4, CI:0.90-2.10, p = 0.027), when prenatal T-Hg was at or above the reference value of 0.80 µg/L and T-Pb was at or above the reference value of 35 µg/L. When prenatal T-Hg was at or above the reference value of 0.80 µg/L and T-As was at or above the reference value of 15 µg/L, the prevalence ratio of global neurodevelopmental impairment was two times higher (aPR 2.1, CI:1.0-4.3; p < 0.034). DISCUSSION: Infants born to women in areas with ASGM activities are at significant risk for neurodevelopmental impairment and this is associated with exposure to higher concentrations of Hg prenatally. Co-exposure to high concentrations of Hg and Pb, or Hg and As appeared to have negative potentiated effects on infants' neurodevelopment.

Soil transmitted helminth infection in primary school children varies with ecozone in the Ngorongoro Conservation Area, Tanzania.

BACKGROUND: Soil-transmitted helminthiasis is a neglected tropical disease, thriving in environments of poverty and disadvantage. Our objective was to determine the prevalence and intensity of four soil transmitted helminths (STH) among primary school children in the Ngorongoro Conservation Area (NCA), Tanzania. METHODS: A cross-sectional study was performed between May 15th and June 2nd, 2014. Six of 20 primary schools were chosen, based on elevation, designated low elevation ecozone (LEE) or high elevation ecozone (HEE). A total of 340 children from standards one to four were recruited. Height and weight of each child was determined and body mass index (BMI) was calculated. Stool samples were analyzed using the Kato-Katz, Wisconsin, and Baermann techniques to detect STH eggs and larvae. An interviewer-administered questionnaire on socio-demographic variables was used to capture information from the school's headmaster and a checklist was used to assess sanitation facilities. RESULTS: STHs identified included Ascaris (presumably lumbricoides), Trichuris (presumably trichiura), hookworms (presumably Ancylostoma duodenale and/or Necator americanus), and Strongyloides (presumably stercoralis). The overall prevalence of STH infection was 29.0% in LEE and 34.0% in HEE. Prevalence was 34.3% and 28.2% in males versus females, respectively. Ascaris sp. were only identified in HEE, prevalence of Trichuris sp. and hookworms were significantly higher in HEE compared to LEE, and Strongyloides spp. prevalence was lower in HEE. Intensity of Trichuris sp. was significantly higher in HEE and lower for hookworms. We did not detect a significant relationship between BMI and helminth intensity; however, BMI was lower in lower elevations and in males vs. females. Sanitation practices are taught at the schools, but challenges were identified when implementing. Latrine facilities were available and latrine-cleaning routines were practiced; however, hand washing practices were challenging due to restricted water availability. CONCLUSIONS: Significant differences in prevalence in HEE and LEE exist, and STH infections are still very common among school children suggesting that anthelminthic intervention and education may be necessary in this region. Based on this outcome, the study area in the NCA would be classified as a medium risk area, where periodic treatment recommendations should be based on prevalence estimations in the different ecozones. TRIAL REGISTRATION: Ethics approval was obtained from the Catholic University of Health and Allied Sciences (CUHAS; Lake Zone Institutional Review Board MR/53/100/307)); the Conjoint Health Research Ethics Board (CHREB) at the University of Calgary in Canada (Study ID REB14-0127); the National Institute of Medical Research (NIMR) of Tanzania; and the Tanzania Commission for Science and Technology (COSTEC).

Genome-wide copy number variations in a large cohort of bantu African children.

BACKGROUND: Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent. METHODS: We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania. Signal intensity data from high density (> 2.5 million probes) genotyping arrays were used for CNV calling with three algorithms including PennCNV, DNAcopy and VanillaICE. Stringent quality metrics and filtering criteria were applied to obtain high confidence CNVs. RESULTS: We identified over 400,000 CNVs larger than 1 kilobase (kb), for an average of 120 CNVs (SE = 2.57) per individual. We detected 866 large CNVs (≥ 300 kb), some of which overlapped genomic regions previously associated with multiple congenital anomaly syndromes, including Prader-Willi/Angelman syndrome (Type1) and 22q11.2 deletion syndrome. Furthermore, several of the common CNVs seen in our cohort (≥ 5%) overlap genes previously associated with developmental disorders. CONCLUSIONS: These findings may help refine the phenotypic outcomes and penetrance of variations affecting genes and genomic regions previously implicated in diseases. Our study provides one of the largest datasets of CNVs from individuals of African ancestry, enabling improved clinical evaluation and disease association of CNVs observed in research and clinical studies in African populations.