Cost-effectiveness of SARS-CoV-2 self-testing at routine gatherings to minimize community-level infections in lower-middle income countries: A mathematical modeling study.

Places of worship serve as a venue for both mass and routine gathering around the world, and therefore are associated with risk of large-scale SARS-CoV-2 transmission. However, such routine gatherings also offer an opportunity to distribute self-tests to members of the community to potentially help mitigate transmission and reduce broader community spread of SARS-CoV-2. Over the past four years, self-testing strategies have been an impactful tool for countries' response to the COVID-19 pandemic, especially early on to mitigate the spread when vaccination and treatment options were limited. We used an agent-based mathematical model to estimate the impact of various strategies of symptomatic and asymptomatic self-testing for a fixed percentage of weekly routine gatherings at places of worship on community transmission of SARS-CoV-2 in Brazil, Georgia, and Zambia. Testing strategies assessed included weekly and bi-weekly self-testing across varying levels of vaccine effectiveness, vaccine coverage, and reproductive numbers to simulate developing stages of the COVID-19 pandemic. Self-testing symptomatic people attending routine gatherings can cost-effectively reduce the spread of SARS-CoV-2 within places of worship and the community, resulting in incremental cost-effectiveness ratios of $69-$303 USD. This trend is especially true in contexts where population level attendance at such gatherings is high, demonstrating that a distribution approach is more impactful when a greater proportion of the population is reached. Asymptomatic self-testing of attendees at 100% of places of worship in a country results in the greatest percent of infections averted and is consistently cost-effective but remains costly. Budgetary needs for asymptomatic testing are expensive and likely unaffordable for lower-middle income countries (520-1550x greater than that of symptomatic testing alone), promoting that strategies to strengthen symptomatic testing should remain a higher priority.

Association of SNPs in HLA-C and ZNRD1 Genes With HIV-1 Mother-to-Child Transmission in Zambia Population.

BACKGROUND: Human leukocyte antigen C (HLA-C) and Zinc ribbon domain containing 1 (ZNRD1) are considered HIV-1 restriction factors and are expressed in the placenta. Variations in HLA-C and ZNRD1 genes are known to influence HIV-1 infection, including viral replication and progression to AIDS. Little is known about the role of variants in these genes in HIV-1 mother-to-child transmission. METHODS: We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321, rs3869068) variants in a Zambian population composed of 333 children born to HIV-1+ mothers (248 HIV-1 noninfected/85 HIV-1 infected) and 97 HIV-1+ mothers. RESULTS: Genotypic distribution of HLA-C and ZNRD1 were in Hardy-Weinberg equilibrium, except for HLA-C rs10484554 in both groups. In mothers, no significant differences were observed in their allele and genotypic distributions for both genes. The T and TT variants (rs10484554-HLA-C) were significantly more frequent among HIV-1+ children, specifically those who acquired the infection in utero (IU) and intrapartum (IP). For ZNRD1, the T allele (rs3869068) was more frequent in HIV-1- children, showing significant differences in relation to those infected via IP and postpartum (PP). The CT and TT genotypes were significantly more frequent in HIV-1- children. CONCLUSIONS: Variations in HLA-C (T and TT-rs10484554) and ZNRD1 (T and CT/TT-rs3869068) can increase and decrease the susceptibility to HIV-1 infection via mother-to-child transmission, respectively. Further studies are encouraged focusing on a greater number of variants and sample size, with functional validation and in other populations.

Stillbirth 2010-2018: a prospective, population-based, multi-country study from the Global Network.

BACKGROUND: Stillbirth rates are high and represent a substantial proportion of the under-5 mortality in low and middle-income countries (LMIC). In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented cause of stillbirths or the trends in rate of stillbirth over time. METHODS: We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, Democratic Republic of Congo, India, Pakistan, and Guatemala). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Cause of stillbirth was assigned by algorithm. RESULTS: From 2010 through 2018, 573,148 women were enrolled with delivery data obtained. Of the 552,547 births that reached 500 g or 20 weeks gestation, 15,604 were stillbirths; a rate of 28.2 stillbirths per 1000 births. The stillbirth rates were 19.3 in the Guatemala site, 23.8 in the African sites, and 33.3 in the Asian sites. Specifically, stillbirth rates were highest in the Pakistan site, which also documented a substantial decrease in stillbirth rates over the study period, from 56.0 per 1000 (95% CI 51.0, 61.0) in 2010 to 44.4 per 1000 (95% CI 39.1, 49.7) in 2018. The Nagpur, India site also documented a substantial decrease in stillbirths from 32.5 (95% CI 29.0, 36.1) to 16.9 (95% CI 13.9, 19.9) per 1000 in 2018; however, other sites had only small declines in stillbirth over the same period. Women who were less educated and older as well as those with less access to antenatal care and with vaginal assisted delivery were at increased risk of stillbirth. The major fetal causes of stillbirth were birth asphyxia (44.0% of stillbirths) and infectious causes (22.2%). The maternal conditions that were observed among those with stillbirth were obstructed or prolonged labor, antepartum hemorrhage and maternal infections. CONCLUSIONS: Over the study period, stillbirth rates have remained relatively high across all sites. With the exceptions of the Pakistan and Nagpur sites, Global Network sites did not observe substantial changes in their stillbirth rates. Women who were less educated and had less access to antenatal and obstetric care remained at the highest burden of stillbirth. STUDY REGISTRATION: Clinicaltrials.gov (ID# NCT01073475).

Predictive Modeling for Perinatal Mortality in Resource-Limited Settings.

Importance: The overwhelming majority of fetal and neonatal deaths occur in low- and middle-income countries. Fetal and neonatal risk assessment tools may be useful to predict the risk of death. Objective: To develop risk prediction models for intrapartum stillbirth and neonatal death. Design, Setting, and Participants: This cohort study used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research population-based vital registry, including clinical sites in South Asia (India and Pakistan), Africa (Democratic Republic of Congo, Zambia, and Kenya), and Latin America (Guatemala). A total of 502 648 pregnancies were prospectively enrolled in the registry. Exposures: Risk factors were added sequentially into the data set in 4 scenarios: (1) prenatal, (2) predelivery, (3) delivery and day 1, and (4) postdelivery through day 2. Main Outcomes and Measures: Data sets were randomly divided into 10 groups of 3 analysis data sets including training (60%), test (20%), and validation (20%). Conventional and advanced machine learning modeling techniques were applied to assess predictive abilities using area under the curve (AUC) for intrapartum stillbirth and neonatal mortality. Results: All prenatal and predelivery models had predictive accuracy for both intrapartum stillbirth and neonatal mortality with AUC values 0.71 or less. Five of 6 models for neonatal mortality based on delivery/day 1 and postdelivery/day 2 had increased predictive accuracy with AUC values greater than 0.80. Birth weight was the most important predictor for neonatal death in both postdelivery scenarios with independent predictive ability with AUC values of 0.78 and 0.76, respectively. The addition of 4 other top predictors increased AUC to 0.83 and 0.87 for the postdelivery scenarios, respectively. Conclusions and Relevance: Models based on prenatal or predelivery data had predictive accuracy for intrapartum stillbirths and neonatal mortality of AUC values 0.71 or less. Models that incorporated delivery data had good predictive accuracy for risk of neonatal mortality. Birth weight was the most important predictor for neonatal mortality.

Oligohydramnios: a prospective study of fetal, neonatal and maternal outcomes in low-middle income countries.

BACKGROUND: Oligohydramnios is a condition of abnormally low amniotic fluid volume that has been associated with poor pregnancy outcomes. To date, the prevalence of this condition and its outcomes has not been well described in low and low-middle income countries (LMIC) where ultrasound use to diagnose this condition in pregnancy is limited. As part of a prospective trial of ultrasound at antenatal care in LMICs, we sought to evaluate the incidence of and the adverse maternal, fetal and neonatal outcomes associated with oligohydramnios. METHODS: We included data in this report from all pregnant women in community settings in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo (DRC) who received a third trimester ultrasound as part of the First Look Study, a randomized trial to assess the value of ultrasound at antenatal care. Using these data, we conducted a planned secondary analysis to compare pregnancy outcomes of women with to those without oligohydramnios. Oligohydramnios was defined as measurement of an Amniotic Fluid Index less than 5 cm in at least one ultrasound in the third trimester. The outcomes assessed included maternal morbidity and fetal and neonatal mortality, preterm birth and low-birthweight. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models using general estimating equations to account for the correlation of outcomes within cluster. RESULTS: Of 12,940 women enrolled in the clusters in Guatemala, Pakistan, Zambia and the DRC in the First Look Study who had a third trimester ultrasound examination, 87 women were diagnosed with oligohydramnios, equivalent to 0.7% of those studied. Prevalence of detected oligohydramnios varied among study sites; from the lowest of 0.2% in Zambia and the DRC to the highest of 1.5% in Pakistan. Women diagnosed with oligohydramnios had higher rates of hemorrhage, fetal malposition, and cesarean delivery than women without oligohydramnios. We also found unfavorable fetal and neonatal outcomes associated with oligohydramnios including stillbirths (OR 5.16, 95%CI 2.07, 12.85), neonatal deaths < 28 days (OR 3.18, 95% CI 1.18, 8.57), low birth weight (OR 2.10, 95% CI 1.44, 3.07) and preterm births (OR 2.73, 95%CI 1.76, 4.23). The mean birth weight was 162 g less (95% CI -288.6, - 35.9) with oligohydramnios. CONCLUSIONS: Oligohydramnos was associated with worse neonatal, fetal and maternal outcomes in LMIC. Further research is needed to assess effective interventions to diagnose and ultimately to reduce poor outcomes in these settings. TRIAL REGISTRATION: NCT01990625.

Association of mother's handwashing practices and pediatric diarrhea: evidence from a multi-country study on community oriented interventions.

INTRODUCTION: Improved hand hygiene in contexts with high levels of diarrheal diseases has shown to reduce diarrheal episodes in children under five years. A quasi-experimental multi-country study with matched comparisons was conducted in four rural districts/sub districts in Cambodia, Guatemala, Kenya and Zambia. METHODS: Community oriented interventions including health promotion for appropriate hand washing was implemented in the intervention sites, through community health workers (CHW) and social accountability mechanisms. Community councils were strengthened/established in all study sites. Using household surveys, information on mother's handwashing practices and diarrhea incidence of children 2 weeks preceding the study was obtained. RESULTS AND CONCLUSION: Access to safe drinking water was reportedly higher for communities in Guatemala and Zambia (> 80%), than those in Cambodia and Kenya (< 63%), with significantly higher levels in intervention sites for Guatemala and Kenya. Improved sanitation was low (< 10%), for Kenya and Zambia, compared to Cambodia and Guatemala (> 40%); intervention sites reporting significantly higher levels, except for Zambia. Hand washing index; hand washing before food preparation, after defecation, attending to a child after defecation, and before feeding children was significantly higher for intervention sites in Cambodia, Guatemala and Kenya (Cambodia, 2.4 vs 2.2, p < 0.001, Guatemala, 3.0 vs 2.5, p < 0.001, Kenya, 2.6 vs 2.3, p < 0.001). Factors significantly associated with lower odds of diarrhea were; mother's marital status, higher educational status, one or more handwashing practices, wealthier quintiles, older (> 24 m), and female children. The findings suggest that caretaker handwashing with soap or ash has a protective effect on prevalence of diarrhea in children.

Development and validation of a prediction model for active tuberculosis case finding among HIV-negative/unknown populations.

A prediction model of prevalent pulmonary tuberculosis (TB) in HIV negative/unknown individuals was developed to assist systematic screening. Data from a large TB screening trial were used. A multivariable logistic regression model was developed in the South African (SA) training dataset, using TB symptoms and risk factors as predictors. The model was converted into a scoring system for risk stratification and was evaluated in separate SA and Zambian validation datasets. The number of TB cases were 355, 176, and 107 in the SA training, SA validation, and Zambian validation datasets respectively. The area under curve (AUC) of the scoring system was 0·68 (95% CI 0·64-0·72) in the SA validation set, compared to prolonged cough (0·58, 95% CI 0·54-0·62) and any TB symptoms (0·6, 95% CI 0·56-0·64). In the Zambian dataset the AUC of the scoring system was 0·66 (95% CI 0·60-0·72). In the cost-effectiveness analysis, the scoring system dominated the conventional strategies. The cost per TB case detected ranged from 429 to 1,848 USD in the SA validation set and from 171 to 10,518 USD in the Zambian dataset. The scoring system may help targeted TB case finding under budget constraints.

The Longitudinal Effects of Non-injection Substance Use on Sustained HIV Viral Load Undetectability Among MSM and Heterosexual Men in Brazil and Thailand: The Role of ART Adherence and Depressive Symptoms (HPTN 063).

The effect of non-injection substance use on HIV viral load (VL) is understudied in international settings. Data are from HPTN063, a longitudinal observational study of HIV-infected individuals in Brazil, Thailand, and Zambia, with focus on men with VL data (Brazil = 146; Thailand = 159). Generalized linear mixed models (GLMM) assessed whether non-injection substance use (stimulants, cannabis, alcohol, polysubstance) was associated with VL undetectability. ART adherence and depressive symptoms were examined as mediators of the association. In Thailand, substance use was not significantly associated with VL undetectability or ART adherence, but alcohol misuse among MSM was associated with increased odds of depression (AOR = 2.75; 95% CI 1.20, 6.32, p = 0.02). In Brazil, alcohol misuse by MSM was associated with decreased odds of undetectable VL (AOR = 0.34; 95% CI 0.13, 0.92, p = 0.03). Polysubstance use by heterosexual men in Brazil was associated with decreased odds of ART adherence (AOR = 0.25; 95% CI 0.08, 0.78, p = 0.02). VL suppression appears attainable among non-injection substance users. Substance use interventions among HIV-positive men should address depression, adherence, and VL undetectability.

Prevalence of awareness, ever-use and current use of nicotine vaping products (NVPs) among adult current smokers and ex-smokers in 14 countries with differing regulations on sales and marketing of NVPs: cross-sectional findings from the ITC Project.

AIMS: This paper presents updated prevalence estimates of awareness, ever-use, and current use of nicotine vaping products (NVPs) from 14 International Tobacco Control Policy Evaluation Project (ITC Project) countries that have varying regulations governing NVP sales and marketing. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A cross-sectional analysis of adult (≥ 18 years) current smokers and ex-smokers from 14 countries participating in the ITC Project. Data from the most recent survey questionnaire for each country were included, which spanned the period 2013-17. Countries were categorized into four groups based on regulations governing NVP sales and marketing (allowable or not), and level of enforcement (strict or weak where NVPs are not permitted to be sold): (1) most restrictive policies (MRPs), not legal to be sold or marketed with strict enforcement: Australia, Brazil, Uruguay; (2) restrictive policies (RPs), not approved for sale or marketing with weak enforcement: Canada, Malaysia, Mexico, New Zealand; (3) less restrictive policies (LRPs), legal to be sold and marketed with regulations: England, the Netherlands, Republic of Korea, United States; and (4) no regulatory policies (NRPs), Bangladesh, China, Zambia. Countries were also grouped by World Bank Income Classifications. Country-specific weighted logistic regression models estimated adjusted NVP prevalence estimates for: awareness, ever/current use, and frequency of use (daily versus non-daily). FINDINGS: NVP awareness and use were lowest in NRP countries. Generally, ever- and current use of NVPs were lower in MRP countries (ever-use = 7.1-48.9%; current use = 0.3-3.5%) relative to LRP countries (ever-use = 38.9-66.6%; current use = 5.5-17.2%) and RP countries (ever-use = 10.0-62.4%; current use = 1.4-15.5%). NVP use was highest among high-income countries, followed by upper-middle-income countries, and then by lower-middle-income countries. CONCLUSIONS: With a few exceptions, awareness and use of nicotine vaping products varied by the strength of national regulations governing nicotine vaping product sales/marketing, and by country income. In countries with no regulatory policies, use rates were very low, suggesting that there was little availability, marketing and/or interest in nicotine vaping products in these countries where smoking populations are predominantly poorer. The higher awareness and use of nicotine vaping products in high income countries with moderately (e.g. Canada, New Zealand) and less (e.g. England, United States) restrictive policies, is likely due to the greater availability and affordability of nicotine vaping products.

Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis.

BACKGROUND: Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF. METHODS: We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394. FINDINGS: Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68-1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65-1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60-0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2<20% for the primary outcome). INTERPRETATION: Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact. FUNDING: US National Institutes of Health.

Overlapping vitamin A interventions in the United States, Guatemala, Zambia, and South Africa: case studies.

Vitamin A (VA) deficiency is a serious public health problem, especially in preschool children who are at risk of increased mortality. In order to address this problem, the World Health Organization recommends periodic high-dose supplementation to children 6-59 months of age in areas of highest risk. Originally, supplementation was meant as a short-term solution until more sustainable interventions could be adopted. Currently, many countries are fortifying commercialized common staple and snack foods with retinyl palmitate. However, in some countries, overlapping programs may lead to excessive intakes. Our review uses case studies in the United States, Guatemala, Zambia, and South Africa to illustrate the potential for excessive intakes in some groups. For example, direct liver analysis from 27 U.S. adult cadavers revealed 33% prevalence of hypervitaminosis A (defined as ≥1 µmol/g liver). In 133 Zambian children, 59% were diagnosed with hypervitaminosis A using a retinol isotope dilution, and 16% had ≥5% total serum VA as retinyl esters, a measure of intoxication. In 40 South African children who frequently consumed liver, 72.5% had ≥5% total serum VA as retinyl esters. All four countries have mandatory fortified foods and a high percentage of supplement users or targeted supplementation to preschool children.

The Role of Religious Service Attendance, Psychosocial and Behavioral Determinants of Antiretroviral Therapy (ART) Adherence: Results from HPTN 063 Cohort Study.

Early and sustained antiretroviral therapy (ART) adherence can suppress the HIV virus in individuals and reduce onward transmission of HIV in the population. Religiosity has been associated with better HIV clinical outcomes. Data are from a longitudinal, observational study of 749 HIV-infected individuals from Brazil, Zambia, and Thailand (HPTN 063). Ordered logistic regression assessed whether religious service attendance was associated with ART adherence (self-reported and plasma HIV-RNA) and moderated the association between alcohol problems and ART adherence. In each country, > 80% of participants reported high self-reported ART adherence (good/very good/excellent). Religious service attendance exceeded 85% but was statistically unrelated to adherence. In combined-country models, (p = 0.03) as alcohol problems increased, the probability of high self-reported ART adherence, as well as viral-load, became weaker at higher compared to low service attendance frequency. Future studies should evaluate spirituality variables and replicate the moderation analyses between religious attendance and alcohol problems.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Dietary Protein Intake in Young Children in Selected Low-Income Countries Is Generally Adequate in Relation to Estimated Requirements for Healthy Children, Except When Complementary Food Intake Is Low.

Background: Previous research indicates that young children in low-income countries (LICs) generally consume greater amounts of protein than published estimates of protein requirements, but this research did not account for protein quality based on the mix of amino acids and the digestibility of ingested protein.Objective: Our objective was to estimate the prevalence of inadequate protein and amino acid intake by young children in LICs, accounting for protein quality.Methods: Seven data sets with information on dietary intake for children (6-35 mo of age) from 6 LICs (Peru, Guatemala, Ecuador, Bangladesh, Uganda, and Zambia) were reanalyzed to estimate protein and amino acid intake and assess adequacy. The protein digestibility-corrected amino acid score of each child's diet was calculated and multiplied by the original (crude) protein intake to obtain an estimate of available protein intake. Distributions of usual intake were obtained to estimate the prevalence of inadequate protein and amino acid intake for each cohort according to Estimated Average Requirements.Results: The prevalence of inadequate protein intake was highest in breastfeeding children aged 6-8 mo: 24% of Bangladeshi and 16% of Peruvian children. With the exception of Bangladesh, the prevalence of inadequate available protein intake decreased by age 9-12 mo and was very low in all sites (0-2%) after 12 mo of age. Inadequate protein intake in children <12 mo of age was due primarily to low energy intake from complementary foods, not inadequate protein density.Conclusions: Overall, most children consumed protein amounts greater than requirements, except for the younger breastfeeding children, who were consuming low amounts of complementary foods. These findings reinforce previous evidence that dietary protein is not generally limiting for children in LICs compared with estimated requirements for healthy children, even after accounting for protein quality. However, unmeasured effects of infection and intestinal dysfunction on the children's protein requirements could modify this conclusion.

Assessing the Safety of Vitamin A Delivered Through Large-Scale Intervention Programs: Workshop Report on Setting the Research Agenda.

BACKGROUND: Vitamin A (VA) deficiency (VAD) is still a concern in many parts of the world, and multiple intervention strategies are being implemented to reduce the prevalence of VAD and associated morbidity and mortality. Because some individuals within a population may be exposed to multiple VA interventions, concerns have been raised about the possible risk of hypervitaminosis A. OBJECTIVES: A consultative meeting was held in Vienna, Austria, in March 2014 to (1) review current knowledge concerning the safety and effectiveness of large-scale programs to control VAD, (2) develop a related research agenda, and (3) review current available methods to assess VA status and risk of hypervitaminosis A. METHODS: Multiple countries were represented and shared their experiences using a variety of assessment methods, including retinol isotope dilution (RID) techniques. Discussion included next steps to refine assessment methodology, investigate RID limitations under different conditions, and review programmatic approaches to ensure VA adequacy and avoid excessive intakes. RESULTS: Fortification programs have resulted in adequate VA status in Guatemala, Zambia, and parts of Cameroon. Dietary patterns in several countries revealed that some people may consume excessive preformed VA from fortified foods. CONCLUSION: Additional studies are needed to compare biomarkers of tissue damage to RID methods during hypervitaminosis A and to determine what other biomarkers can be used to assess excessive preformed VA intake.

Intimacy versus isolation: a qualitative study of sexual practices among sexually active HIV-infected patients in HIV care in Brazil, Thailand, and Zambia.

The success of global treatment as prevention (TasP) efforts for individuals living with HIV/AIDS (PLWHA) is dependent on successful implementation, and therefore the appropriate contribution of social and behavioral science to these efforts. Understanding the psychosocial context of condomless sex among PLWHA could shed light on effective points of intervention. HPTN 063 was an observational mixed-methods study of sexually active, in-care PLWHA in Thailand, Zambia, and Brazil as a foundation for integrating secondary HIV prevention into HIV treatment. From 2010-2012, 80 qualitative interviews were conducted with PLWHA receiving HIV care and reported recent sexual risk. Thirty men who have sex with women (MSW) and 30 women who have sex with men (WSM) participated in equal numbers across the sites. Thailand and Brazil also enrolled 20 biologically-born men who have sex with men (MSM). Part of the interview focused on the impact of HIV on sexual practices and relationships. Interviews were recorded, transcribed, translated into English and examined using qualitative descriptive analysis. The mean age was 25 (SD = 3.2). There were numerous similarities in experiences and attitudes between MSM, MSW and WSM across the three settings. Participants had a high degree of HIV transmission risk awareness and practiced some protective sexual behaviors such as reduced sexual activity, increased use of condoms, and external ejaculation. Themes related to risk behavior can be categorized according to struggles for intimacy and fears of isolation, including: fear of infecting a sex partner, guilt about sex, sexual communication difficulty, HIV-stigma, and worry about sexual partnerships. Emphasizing sexual health, intimacy and protective practices as components of nonjudgmental sex-positive secondary HIV prevention interventions is recommended. For in-care PLWHA, this approach has the potential to support TasP. The overlap of themes across groups and countries indicates that similar intervention content may be effective for a range of settings.

Comparison of therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis

OBJECTIVE: To compare the therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis to provide a basis for clinical practice. METHODS: Data from 83 patients with rheumatoid arthritis undergoing total knee arthroplasty were retrospectively analyzed. The 83 patients were divided into a drainage blood reinfusion group (DR group, n = 45) and a temporary clamping drainage group (CD group, n = 38). In the DR group, postoperative drainage blood was used for autotransfusion. In the CD group, closed drainage was adopted, and the drainage tube was clamped for 2 h postoperatively followed by patency. The postoperative drainage amount, hemoglobin level, rate and average volume of allogeneic blood transfusion, swelling and ecchymosis of the affected knee joint, time to straight-leg raising and range of active knee flexion were compared between the two groups. RESULTS: The total drainage volume was higher in the DR group than in the CD group (P = 0.000). The average volume of postoperative allogeneic blood transfusion (P = 0.000) and the decrease in the hemoglobin level 24 h after total knee arthroplasty (P = 0.012) were lower in the DR group than in the CD group. Swelling and ecchymosis of the affected knee joint, time to straight-leg raising and the range of active knee flexion were improved in the DR group compared with the CD group (all P<0.05). CONCLUSION: Compared with temporary clamping drainage, drainage blood reinfusion after total knee arthroplasty can reduce the allogeneic blood transfusion volume and is conducive to early rehabilitation in patients with rheumatoid arthritis. .

A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries.

OBJECTIVE: To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths. METHODS: A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum. FINDINGS: Between 2010 and 2012, 214,070 of 220,235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100,000 live births, ranging from 69 per 100,000 in Argentina to 316 per 100,000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97-11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26-5.67) and 7-day (RR: 3.94; 95% CI: 2.74-5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54-9.77). CONCLUSION: Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality.

First look: a cluster-randomized trial of ultrasound to improve pregnancy outcomes in low income country settings.

BACKGROUND: In high-resource settings, obstetric ultrasound is a standard component of prenatal care used to identify pregnancy complications and to establish an accurate gestational age in order to improve obstetric care. Whether or not ultrasound use will improve care and ultimately pregnancy outcomes in low-resource settings is unknown. METHODS/DESIGN: This multi-country cluster randomized trial will assess the impact of antenatal ultrasound screening performed by health care staff on a composite outcome consisting of maternal mortality and maternal near-miss, stillbirth and neonatal mortality in low-resource community settings. The trial will utilize an existing research infrastructure, the Global Network for Women's and Children's Health Research with sites in Pakistan, Kenya, Zambia, Democratic Republic of Congo and Guatemala. A maternal and newborn health registry in defined geographic areas which documents all pregnancies and their outcomes to 6 weeks post-delivery will provide population-based rates of maternal mortality and morbidity, stillbirth, neonatal mortality and morbidity, and health care utilization for study clusters. A total of 58 study clusters each with a health center and about 500 births per year will be randomized (29 intervention and 29 control). The intervention includes training of health workers (e.g., nurses, midwives, clinical officers) to perform ultrasound examinations during antenatal care, generally at 18-22 and at 32-36 weeks for each subject. Women who are identified as having a complication of pregnancy will be referred to a hospital for appropriate care. Finally, the intervention includes community sensitization activities to inform women and their families of the availability of ultrasound at the antenatal care clinic and training in emergency obstetric and neonatal care at referral facilities. DISCUSSION: In summary, our trial will evaluate whether introduction of ultrasound during antenatal care improves pregnancy outcomes in rural, low-resource settings. The intervention includes training for ultrasound-naïve providers in basic obstetric ultrasonography and then enabling these trainees to use ultrasound to screen for pregnancy complications in primary antenatal care clinics and to refer appropriately. TRIAL REGISTRATION: Clinicaltrials.gov (NCT # 01990625).

Strong association between the prevalence of bacterial vaginosis and male point-concurrency.

OBJECTIVE: The prevalence of bacterial vaginosis (BV) differs considerably between different populations, and individual-level risk factors such as number of sex partners seem unable to explain these differences. The effect of network-level factors, such as the prevalence of partner concurrency (the proportion of sexual partnerships that overlap in time as opposed to running sequentially) on BV prevalence has not hitherto been investigated. STUDY DESIGN: We performed linear regression to assess the relationship between the prevalence of male concurrency and prevalence of BV in each of 11 countries for which we could obtain comparable data. The data for concurrency prevalence were taken from the WHO/Global Programme on AIDS (GPA) sexual behavioural surveys. BV prevalence rates were obtained from a systematic review of the global patterning of BV. RESULTS: We found a strong relationship between the prevalence of male concurrency and BV prevalence (Pearson's R(2)=0.57; P=0.007). CONCLUSIONS: The findings of a strong ecological-level association between BV and partner concurrency need to be replicated and augmented with different types of studies such as multilevel prospective studies tracking the incidence of BV and associated individual, partner and network level risk factors.