Expanding access to biotherapeutics in low-income and middle-income countries through public health non-exclusive voluntary intellectual property licensing: considerations, requirements, and opportunities.

Biotherapeutics, such as recombinant proteins and monoclonal antibodies, have become mainstays of modern medicine as shown by their increasing number in the WHO Model List of Essential Medicines. However, despite frequently offering clinical advantages over standards of care, they remain largely out of reach for populations in low-income and middle-income countries (LMICs), partly because of high costs. Accordingly, the WHO Model List of Essential Medicines Expert Committee has requested that the Medicines Patent Pool explore intellectual property licensing to address this challenge. We therefore investigated how licensing could successfully improve affordability of and timely access to biotherapeutics in LMICs, by leveraging expert consultations, literature analysis, and internal technical knowledge. The key elements identified as relevant to support access to affordable biosimilars in LMICs through licensing include: prioritising potential biotherapeutic targets according to their potential for public health impact; supporting biosimilar product and clinical development (including through technology transfer to expedite regulatory approval); and facilitating biosimilars' entry and use in LMICs (by meeting procurement, supply chain, and health system requirements).

Burden of non-communicable diseases among adolescents aged 10-24 years in the EU, 1990-2019: a systematic analysis of the Global Burden of Diseases Study 2019.

BACKGROUND: Disability and mortality burden of non-communicable diseases (NCDs) have risen worldwide; however, the NCD burden among adolescents remains poorly described in the EU. METHODS: Estimates were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Causes of NCDs were analysed at three different levels of the GBD 2019 hierarchy, for which mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were extracted. Estimates, with the 95% uncertainty intervals (UI), were retrieved for EU Member States from 1990 to 2019, three age subgroups (10-14 years, 15-19 years, and 20-24 years), and by sex. Spearman's correlation was conducted between DALY rates for NCDs and the Socio-demographic Index (SDI) of each EU Member State. FINDINGS: In 2019, NCDs accounted for 86·4% (95% uncertainty interval 83·5-88·8) of all YLDs and 38·8% (37·4-39·8) of total deaths in adolescents aged 10-24 years. For NCDs in this age group, neoplasms were the leading causes of both mortality (4·01 [95% uncertainty interval 3·62-4·25] per 100 000 population) and YLLs (281·78 [254·25-298·92] per 100 000 population), whereas mental disorders were the leading cause for YLDs (2039·36 [1432·56-2773·47] per 100 000 population) and DALYs (2040·59 [1433·96-2774·62] per 100 000 population) in all EU Member States, and in all studied age groups. In 2019, among adolescents aged 10-24 years, males had a higher mortality rate per 100 000 population due to NCDs than females (11·66 [11·04-12·28] vs 7·89 [7·53-8·23]), whereas females presented a higher DALY rate per 100 000 population due to NCDs (8003·25 [5812·78-10 701·59] vs 6083·91 [4576·63-7857·92]). From 1990 to 2019, mortality rate due to NCDs in adolescents aged 10-24 years substantially decreased (-40·41% [-43·00 to -37·61), and also the YLL rate considerably decreased (-40·56% [-43·16 to -37·74]), except for mental disorders (which increased by 32·18% [1·67 to 66·49]), whereas the YLD rate increased slightly (1·44% [0·09 to 2·79]). Positive correlations were observed between DALY rates and SDIs for substance use disorders (rs=0·58, p=0·0012) and skin and subcutaneous diseases (rs=0·45, p=0·017), whereas negative correlations were found between DALY rates and SDIs for cardiovascular diseases (rs=-0·46, p=0·015), neoplasms (rs=-0·57, p=0·0015), and sense organ diseases (rs=-0·61, p=0·0005). INTERPRETATION: NCD-related mortality has substantially declined among adolescents in the EU between 1990 and 2019, but the rising trend of YLL attributed to mental disorders and their YLD burden are concerning. Differences by sex, age group, and across EU Member States highlight the importance of preventive interventions and scaling up adolescent-responsive health-care systems, which should prioritise specific needs by sex, age, and location. FUNDING: Bill & Melinda Gates Foundation.

Effectiveness of integrated nutrition interventions on childhood stunting: a quasi-experimental evaluation design.

BACKGROUND: Although malnutrition particularly stunting is recognized as multi-causal, there has been limited integrated nutrition interventions to reduce its burden in children under-fives and those existing are not well evaluated. This study tested the effectiveness of provision of health and nutrition education and promotion of home gardening in child stunting. METHODS: The study used a quasi-experimental evaluation design. Two rounds of household surveys were done to assess changes in behaviors (uptake of Antenatal Care services and child feeding practices) and stunting among children under-5 years. The sample size was calculated to detect a 10% percent absolute baseline-to-end-line change in stunting. A two-stage stratified sampling process was used to sample 896 and 1736 households at each round of data collection in the intervention and control districts respectively. Mothers delivered in the past 24 months preceding the survey and all children under-5 years residing in selected households were eligible. The difference in difference (DID) analysis was used to estimate effect of the interventions. All ethical clearances were obtained from relevant authorities prior to data collection. RESULTS: A total of 3467 and 4145 children under 5 years were recruited at baseline and endline respectively. The proportional of stunted children decreases from 35.9 to 34.2% in intervention and from 29.3 to 26.8% in the control sites. Overall, no statistically significant stunting reduction was observed between intervention and control sites. However, a significant effect was observed in intermediate outcomes; Uptake of iron folic acid (DID: 5.2%, (95% CI: 1.7-8.7), p = 0.003), health facility delivery (DID: 6.5%, (95% CI: 1.8-11.2), p = 0.006), pre-lacteal feeding (DID: - 5.9%, (95%CI: - 9.2, - 2.5), p = 0.001), breast feeding within 1 h after birth (DID: 7.8%, (95%CI: 2.2-13.4), p = 0.006) and exclusive breast feeding in children under 6 months (DID:20.3%, (95% CI: 10.5-30.1), p = 0.001). CONCLUSION: The 3 years program did not result in significant evidence of stunting reduction, but the observed effect on health and nutrition behavioural indicators are at the causal pathways to improved child nutritional outcomes in the long run. Implementation of these integrated packages over a longer duration is needed to witness significant reduction in the prevalence of stunting.

Effectiveness of screening and treatment of children with severe acute malnutrition by community health workers in Simiyu region, Tanzania: a quasi-experimental pilot study.

Health system constraints hamper treatment of children with severe acute malnutrition (SAM) in Tanzania. This non-inferiority quasi-experimental study in Bariadi (intervention) and Maswa (control) districts assessed the effectiveness, coverage, and cost-effectiveness of SAM treatment by community health workers (CHWs) compared with outpatient therapeutic care (OTC). We included 154 and 210 children aged 6-59 months with SAM [mid-upper arm circumference (MUAC) < 11.5 cm] without medical complications in the control and intervention districts, respectively. The primary treatment outcome was cure (MUAC ≥ 12.5 cm). We performed costing analysis from the provider's perspective. The probability of cure was higher in the intervention group (90.5%) than in the control group (75.3%); risk ratio (RR) 1.17; 95% CI 1.05, 1.31 and risk difference (RD) 0.13; 95% CI 0.04, 0.23. SAM treatment coverage was higher in the intervention area (80.9%) than in the control area (41.7%). The cost per child treated was US$146.50 in the intervention group and US$161.62 in the control group and that per child cured was US$161.77 and US$215.49 in the intervention and control groups, respectively. The additional costs per an additional child treated and cured were US$134.40 and US$130.92, respectively. Compared with OTC, treatment of children with uncomplicated SAM by CHWs was effective, increased treatment coverage and was cost-effective.

A simplified diagnostic work-up for the detection of gestational diabetes mellitus in low resources settings: achievements and challenges.

PURPOSE: Modern strategies for the screening and diagnosis of Gestational Diabetes Mellitus (GDM) rely on universal Oral Glucose Tolerance Test (OGTT). However, they are unsustainable in low-income countries. In this study, we aimed at assessing the feasibility of a simplified diagnostic policy. METHODS: The study took place in an urban referral hospital in Freetown, Sierra Leone. During an 11-month period, pregnant women were offered capillary blood test for glucose assessment. They could be screened at any time during pregnancy. GDM was diagnosed if fasting glucose was ≥ 92 mg/dl or if the OGTT was positive. The latter was prescribed only to women presenting after 24 weeks' gestation with at least one risk factor for GDM and fasting capillary glucose between 85 and 91 mg/dl. A definitive diagnosis required confirmation to this aim, women with values above the thresholds were invited to refer the next working day for repeating the test after fasting overnight. RESULTS: Overall, 7827 women were referred for screening, of whom 6872 (87%) underwent at least one capillary glucose assessment. However, 895 of those who had a positive test did not return for confirmation. Overall, a definite assessment could be done in 5799 subjects corresponding to 76% (95% CI 75-77%) of those eligible. GDM was diagnosed in 128 women (1.9%, 95% CI 1.6-2.2%). Based on an expected confirmation rate of 22% (calculated from those who referred for confirmation) in the 895 women who did not come back, one could infer that GDM would have been diagnosed in additional 197 women, raising the prevalence to 4.7% (95% CI 4.2-5.3%). CONCLUSION: Three quarters of subjects could be assessed with our approach. Data also suggest that GDM is not rare even if identification of affected cases remains challenging.

Diabetes and pre-diabetes among adults reaching health centers in Luanda, Angola: prevalence and associated factors.

With the lack of surveys, surveillance program and/or statistical data, epidemiologic studies can provide a better understanding of diabetes in Sub-Saharan Africa. This was a cross-sectional survey to determine prevalence of diabetes and impaired fasting glucose (IFG) among adults attending six health centres in six different districts of Luanda (Angola) during August-November 2018, followed by a case-control study to assess the risk factors for IFG and diabetes in a subgroup of subjects not receiving treatment for diabetes. Factors associated with diabetes/IFG were assessed using a generalized ordered logit model and the effects were expressed as odds ratios (OR1 for IFG/diabetes vs. no IFG/diabetes; OR2 for diabetes vs. no diabetes) with 95% CI (confidence interval). Some 1,803 participants were included in the survey. Prevalence of diabetes was 12.0% (95%CI 10.5% to 13.5%) and prevalence of IFG was 9.0% (95%CI 7.7% to 10.4%). Older age (OR1 = OR2 1.03, 95%CI 1.02 to 1.04), higher weight (OR1 = OR2 1.01, 95%CI 1.01 to 1.03), having measured glycaemia before (OR2 2.07, 95%CI 1.29 to 3.31), feeling polyuria (OR1 1.93, 95%CI 1.13 to 3.28; OR2 2.18, 95%CI 1.32 to 3.59), feeling polydipsia (OR1 1.92, 95%CI 1.16 to 3.18), feeling weakness (OR1 = OR2 2.22, 95%CI 1.39 to 3.55), consumption of free-sugars food/beverages (OR1 = OR2 2.34, 95%CI 1.44 to 3.81) and time spent seated (OR1 1.80, 95%CI 1.17 to 2.76) were associated with increased likelihood of diabetes and/or IFG, while eating vegetables was associated with decreased likelihood of IFG or diabetes (OR1 = OR2 0.69, 95%CI 0.47 to 0.99). In conclusion, the high prevalence of diabetes and IFG, with common unawareness of the disease, calls for appropriate interventions in Angolan urban settings. Further research may evaluate the impact of context-specific factors to enhance intervention strategies and feed the results into local health policies. In addition, such information may be useful for selecting high-risk subjects to test.

Supportive supervision to improve the quality and outcome of outpatient care among malnourished children: a cluster randomised trial in Arua district, Uganda.

INTRODUCTION: Suboptimal quality of paediatric care has been reported in resource-limited settings, but little evidence exists on interventions to improve it in such settings. This study aimed at testing supportive supervision (SS) for improving health status of malnourished children, quality of case management, overall quality of care, and the absolute number of children enrolled in the nutritional services. METHODS: This was a cluster randomised trial conducted in Arua district. Six health centres (HCs) with the highest volume of work were randomised to either SS or no intervention. SS was delivered by to HCs staff (phase 1), and later extended to community health workers (CHWs) (phase 2). The primary outcome was the cure rate, measured at children level. Quality of case management was assessed by six pre-defined indicators. Quality of care was assessed using the national Nutrition Service Delivery Assessment (NSDA) tool. Access to care was estimated with the number of children accessing HC nutritional services. RESULTS: Overall, 737 children were enrolled. In the intervention arm, the cure rate (83.8% vs 44.9%, risk ratio (RR)=1.91, 95% CI: 1.56-2.34, p=0.001), quality of care as scored by NSDA (RR=1.57, 95% CI: 1.01-2.44, p=0.035) and correctness in complementary treatment (RR=1.52, 95% CI: 1.40-1.67, p=0.001) were significantly higher compared with control. With the extension of SS to CHWs (phase 2), there was a significant 38.6% more children accessing care in the intervention HCs (RR=1.26, 95% CI: 1.11-1.44, p=0.001) compared with control. CONCLUSION: SS significantly improved the cure rate of malnourished children, and the overall quality of care, SS to CHWs significantly increased the crude number of children enrolled in the nutritional services. More studies should confirm these results, and evaluate the cost-effectiveness of SS.

Integrating TB and non-communicable diseases services: Pilot experience of screening for diabetes and hypertension in patients with Tuberculosis in Luanda, Angola.

BACKGROUND: In the face of the rising burden of non-communicable diseases like diabetes mellitus (DM) and hypertension in sub-Saharan Africa, where infectious diseases like Tuberculosis (TB) are still endemic, the double burden of communicable and non-communicable diseases appears to be increasing rapidly. However, the size of the problem and what is the proper health system approach to deal with the double burden is still unclear. The aim of this project was to estimate the double burden of DM hypertension and TB and to pilot the integration of the screening for DM and hypertension in the TB national programs in six TB centers in Luanda, Angola. METHODS: All newly diagnosed pulmonary TB (PTB) patients accessing six directly observed treatment (DOT) centers in Luanda were screened for diabetes and hypertension. TB diagnosis was made clinically and/or with sputum microscopy DM diagnosis was made through estimation of either fasting plasma glucose (FPG) (considered positive if ≥ 7∙0mmol/l) or random plasma glucose (considered positive if ≥ 11∙1mmol/l). Uncontrolled hypertension was defined as systolic blood pressure (SBP) of ≥ 140 mm of Hg and/or diastolic blood pressure (DBP) of ≥ 90 mm of Hg, irrespective of use of antihypertensive drug. RESULTS: Between January 2015 and December 2016, a total of 7,205 newly diagnosed patients with PTB were included in the analysis; 3,598 (49∙9%) were males and 3,607 females. Among 7,205 PTB patients enrolled, blood pressure was measured in 6,954 and 1,352 (19∙4%) were found to have uncontrolled hypertension, more frequently in females (23%) compared to males (16%). In multivariate logistic regression analysis uncontrolled hypertension was associated with increasing age and BMI and ethnic group. The crude prevalence of DM among TB patients was close to 6%, slightly higher in males (6∙3%) compared to females (5∙7%). Age adjusted prevalence was 8%. Impaired fasting glucose (>6∙1 to <7∙0 mmol/L) was detected in 414 patients (7%). In multivariate logistic regression analysis DM prevalence was higher in males and increased with increasing age and BMI. INTERPRETATION: TB patients have a considerable hypertension and diabetes co-morbidity. It is possible to screen for these conditions within the DOTs centres. Integration of health services for both communicable and non-communicable diseases is desirable and recommended.

Neonatal resuscitation using a supraglottic airway device for improved mortality and morbidity outcomes in a low-income country: study protocol for a randomized trial.

BACKGROUND: Intrapartum-related death is the third leading cause of under-5 mortality. Effective ventilation during neonatal resuscitation has the potential to reduce 40% of these deaths. Face-mask ventilation performed by midwives is globally the most common method of resuscitating neonates. It requires considerable operator skills and continuous training because of its complexity. The i-gel® is a cuffless supraglottic airway which is easy to insert and provides an efficient seal that prevents air leakage; it has the potential to enhance performance in neonatal resuscitation. A pilot study in Uganda demonstrated that midwives could safely resuscitate newborns with the i-gel® after a short training session. The aim of the present trial is to investigate whether the use of a cuffless supraglottic airway device compared with face-mask ventilation during neonatal resuscitation can reduce mortality and morbidity in asphyxiated neonates. METHODS: A randomized phase III open-label superiority controlled clinical trial will be conducted at Mulago Hospital, Kampala, Uganda, in asphyxiated neonates in the delivery units. Prior to the intervention, health staff performing resuscitation will receive training in accordance with the Helping Babies Breathe curriculum with a special module for training on supraglottic airway insertion. A total of 1150 to 1240 babies (depending on cluster size) that need positive pressure ventilation and that have an expected gestational age of more than 34 weeks and an expected birth weight of more than 2000 g will be ventilated by daily unmasked randomization with a supraglottic airway device (i-gel®) (intervention group) or with a face mask (control group). The primary outcome will be a composite outcome of 7-day mortality and admission to neonatal intensive care unit (NICU) with neonatal encephalopathy. DISCUSSION: Although indications for the beneficial effect of a supraglottic airway device in the context of neonatal resuscitation exist, so far no large studies powered to assess mortality and morbidity have been carried out. We hypothesize that effective ventilation will be easier to achieve with a supraglottic airway device than with a face mask, decreasing early neonatal mortality and brain injury from neonatal encephalopathy. The findings of this trial will be important for low and middle-resource settings where the majority of intrapartum-related events occur. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT03133572 . Registered April 28, 2017.

The hidden burden of measles in Ethiopia: how distance to hospital shapes the disease mortality rate.

BACKGROUND: A sequence of annual measles epidemics has been observed from January 2013 to April 2017 in the South West Shoa Zone of the Oromia Region, Ethiopia. We aimed at estimating the burden of disease in the affected area, taking into account inequalities in access to health care due to travel distances from the nearest hospital. METHODS: We developed a dynamic transmission model calibrated on the time series of hospitalized measles cases. The model provided estimates of disease transmissibility and incidence at a population level. Model estimates were combined with a spatial analysis to quantify the hidden burden of disease and to identify spatial heterogeneities characterizing the effectiveness of the public health system in detecting severe measles infections and preventing deaths. RESULTS: A total of 1819 case patients and 36 deaths were recorded at the hospital. The mean age was 6.0 years (range, 0-65). The estimated reproduction number was 16.5 (95% credible interval (CI) 14.5-18.3) with a cumulative disease incidence of 2.34% (95% CI 2.06-2.66). Three thousand eight hundred twenty-one (95% CI 1969-5671) severe cases, including 2337 (95% CI 716-4009) measles-related deaths, were estimated in the Woliso hospital's catchment area (521,771 inhabitants). The case fatality rate was found to remarkably increase with travel distance from the nearest hospital: ranging from 0.6% to more than 19% at 20 km. Accordingly, hospital treatment prevented 1049 (95% CI 757-1342) deaths in the area. CONCLUSIONS: Spatial heterogeneity in the access to health care can dramatically affect the burden of measles disease in low-income settings. In sub-Saharan Africa, passive surveillance based on hospital admitted cases might miss up to 60% of severe cases and 98% of related deaths.

Quality of care for children with acute malnutrition at health center level in Uganda: a cross sectional study in West Nile region during the refugee crisis.

BACKGROUND: Arua district, in Uganda, hosts some of the largest refugee camps in the country. The estimated prevalence of moderate and severe acute malnutrition in children is higher than the national estimates (10.4 and 5.6% respectively, compared to 3.6 and 1.3%). This study aimed at assessing the quality of care provided to children with acute malnutrition at out-patient level in such a setting. METHODS: Six facilities with the highest number of children with malnutrition were selected. The main tool used was the National Nutrition Service Delivery Assessment Tool, assessing 10 key areas of service delivery and assigned a score as either poor, fair, good or excellent. Health outcomes, quality of case management and data quality were assessed from the health management information system and from the official nutrition registers. RESULTS: All facilities except two scored either poor or fair under all the 10 assessment areas. Overall, 33/60 (55%) areas scored as poor, 25/60 (41%) as fair, 2/60 (3.3%) as good, and none as excellent. Main gaps identified included: lack of trained staff; disorganised patient flow; poor case management; stock out of essential supplies including ready-to-use therapeutic foods; weak community linkage. A sample coverage of 45.4% (1020/2248) of total children admitted in the district during the 2016 financial year were included. The overall mean cure rate was 52.9% while the default rate was 38.3%. There was great heterogeneity across health facilities in health outcomes, quality of case management, and data quality. CONCLUSION: This study suggests that quality of care provided to children with malnutrition at health center level is substandard with unacceptable low cure rates. It is essential to identify effective approaches to enhance adherence to national guidelines, provision of essential nutritional commodities, regular monitoring of services and better linkage with the community through village health teams.

Effect of a Low-Dose/High-Frequency Training on Real-Life Neonatal Resuscitation in a Low-Resource Setting.

BACKGROUND: As intrapartum-related events represent a quarter of all neonatal deaths, education on neonatal resuscitation is a critical priority. OBJECTIVE: To assess the impact of a low-dose/high-frequency neonatal resuscitation training on clinical practice of midwives in a low-resource setting. METHODS: Eight months after a modified Neonatal Resuscitation Program (NRP) course, we implemented a low-dose/high-frequency training for midwives at Beira Central Hospital, Mozambique. The training lasted 6 months and included weekly practice sessions. Fifty consecutive resuscitations after the low-dose/high-frequency training were compared with those registered before (n = 50) and after (n = 50) participation in the adapted NRP course using video recording. RESULTS: All 150 neonates received the initial steps; 103 required bag-mask ventilation and 41 required chest compressions. The scores for initial steps, bag-mask ventilation and chest compressions improved after the course (p < 0.0001, p = 0.005 and p = 0.03) and did not change after the low-dose/high-frequency training (p = 0.34, p = 0.99 and p = 0.30). The low-dose/high-frequency training decreased the total time of the procedure (p < 0.0001) and anticipated start time of airway suctioning and tactile stimulation (p = 0.003 and p < 0.0001), but had no effect on the time of initiation of bag-mask ventilation (p = 0.30). CONCLUSIONS: In a low- income setting, a low-dose/high-frequency training after participation in an adapted NRP course contributed to improving the initiation and times of some procedures. However, many aspects of neonatal resuscitation remained poor. Low-dose/high-frequency training should focus on improving the prevention of thermal loss, face mask ventilation and heart rate assessment.

Thermal Effect of a Woolen Cap in Low Birth Weight Infants During Kangaroo Care.

BACKGROUND AND OBJECTIVES: World Health Organization guidelines recommend covering the head during kangaroo mother care (KMC), but the effect of a cap on neonatal thermal control during KMC remains to be defined. Our objective was to assess the effectiveness and safety of a woolen cap in maintaining low birth weight infants (LBWIs) in normal thermal range during KMC. METHODS: Three hundred LBWI candidates for KMC in 3 African hospitals were randomly assigned to KMC with (CAP group) or without (NOCAP group) a woolen cap in a 1:1 ratio during the first week after birth. Axillary temperature was measured every 6 hours. Maternal and room temperature and adherence to skin-to-skin contact were registered at the same time points. RESULTS: A total number of 5064 measurements were recorded (median 19 measurements per subject; interquartile range: 10-25). Mean time spent in normal temperature range was 55% (SD 24) in CAP and 56% (SD 24) in NOCAP groups. Multivariable analysis estimated a rate ratio of 0.92 (95% confidence interval: 0.84 to 1.00; P = .06) for the effect of the cap versus no cap on time spent in the normal temperature range. CONCLUSIONS: In these 3 African, low-resource settings and so many days post birth, the use of a woolen cap was safe but provided no advantages in maintaining LBWI in the normal thermal range while being in a KMC ward. LBWIs spent only half of the time in the normal temperature range despite warm rooms and skin-to-skin contact. Maintaining normothermia in LBWIs remains an unfinished challenge in low-resource settings.

Changing the role of traditional birth attendants in Yirol West County, South Sudan.

Effective from May 2014, community-based traditional birth attendants (TBAs) in Yirol West County, South Sudan, were directed to start referring all women in labour to health facilities for childbirth instead of assisting them in the villages. This study aimed to understand the degree of integration of TBAs in the health system, to reveal the factors influencing the integration, and to explore the perceived solutions to the challenges faced by TBAs. A qualitative study utilising 11 focus group discussions with TBAs, 6 focus group discussions with women, and 18 key informant interviews with members of village health committees, staff of health facilities, and staff of the County Health Department was conducted. Data were analysed using qualitative content analysis. The study found that many TBAs were referring women to health facilities for delivery, but some were still attending to deliveries at home. Facilitators of the adoption of the new role by TBAs were: acceptance of the new TBAs' role by the community, women and TBAs, perceptions about institutional childbirth and risks of home childbirth, personal commitment and motivation by some TBAs, a good working relationship between community-based TBAs and health facility staff, availability of incentives for women at health facilities, and training of TBAs. Challenges of integrating TBAs in the health system included, among others, communication problems between TBAs and health care facilities, delays in seeking care by women, insecurity, lack of materials and supplies for TBAs, health system constraints, insufficient incentives for TBAs, long distances to health facilities and transportation problems. This study has revealed encouraging developments in TBAs' integration in the formal health system in Yirol West. However, there is need to address the challenges faced by TBAs in assuming their new role in order to sustain the integration.

Barriers to utilisation of antenatal care services in South Sudan: a qualitative study in Rumbek North County.

BACKGROUND: Access to adequate antenatal care (ANC) is critical in ensuring a good maternal health and in preventing maternal and neonatal morbidity and mortality. South Sudan has one of the world's poorest health indicators due to a fragile health system and a combination of socio-cultural, economic, and political factors. This study was conducted to identify barriers to utilisation of ANC services in Rumbek North County. METHODS: Using a qualitative design, data were collected through 14 focus group discussions with 169 women and 45 men and 12 key informant interviews with community leaders, staff working in health facilities, and the staff of the County Health Department. Data were analysed using inductive content analysis. RESULTS: The perceived barriers to ANC utilisation were categorised as follows: 1) Issues related to access to health facilities and lack of resources. These included long distance to health facilities, lack of means of transportation to the health facilities, floods and poor roads, and demand for payment for health care at some health facilities; 2) The influence of the socio-cultural context and conflict including heavy burden of domestic chores, the negative influence of husbands who were reluctant to allow their wives to attend ANC, and insecurity; 3) Perceptions about pregnancy including misperceptions about the benefits of ANC and low perceived risk of pregnancy-related complications; and 4) Perceptions about the quality of care and the efficacy of medical treatment. CONCLUSIONS: This study identified a myriad of factors deeply entrenched in the society, which prevent women from utilising ANC services. It also elicits broad aspects of interconnectedness among the barriers. To ensure effectiveness, strategies to improve utilisation of ANC in the study area and in similar contexts need to take into account the barriers identified by this study.

Social determinants of therapy failure and multi drug resistance among people with tuberculosis: A review.

BACKGROUND: Social determinants influence health and the development of tuberculosis (TB). However, a paucity of data is available considering the relationship of social determinants influencing therapy failure and multi drug resistance (MDR). We conducted a review investigating the relationship of common social determinants on therapy failure and MDR in people with TB. METHODS: PubMed and SCOPUS were searched without language restrictions until February 02, 2016 for studies reporting the association between socioeconomic factors (income, education and alcohol abuse) and therapy failure or MDR-TB. The association between social determinants and outcomes was explored by pooling data with a random effects model and calculating crude and adjusted odds ratios (ORs) ±95% confidence intervals (CIs). RESULTS: Fifty studies with 407,555 participants with TB were included. Analysis demonstrated that low income (unadjusted OR = 2.00 (95% CI: 1.69-2.38; I2 = 88%; 33 studies, adjusted OR 1.77, p < 0.0001), low education (unadjusted OR 2.11, 95% CI 1.55-2.86, 26 studies, adjusted OR 1.69, p < 0.0001) and alcohol abuse (unadjusted OR = 2.43 (95% CI: 1.56-3.80, 16 studies, adjusted OR 2.13, p < 0.0001) were associated with therapy failure. Similarly, low income (unadjusted OR = 1.67; 95% CI: 1.12-2.41, p = 0.006; 14 studies, adjusted OR 2.16, p < 0.0001) and alcohol abuse (unadjusted OR = 1.88; 95% CI: 1.18-3.00, 7 studies, adjusted OR 1.43, p = 0.06) were associated with MDR-TB. Increasing age of the population was able to explain a consistent part of the heterogeneity found.

Barriers to Institutional Childbirth in Rumbek North County, South Sudan: A Qualitative Study.

BACKGROUND: South Sudan has one of the world's poorest health indicators due to a fragile health system and a combination of socio-cultural, economic and political factors. This study was conducted to identify barriers to utilisation of institutional childbirth services in Rumbek North County. METHODS: Data were collected through 14 focus group discussions with 169 women and 45 men, and 18 key informant interviews with community leaders, staff working in health facilities, traditional birth attendants, and the staff of the County Health Department. Data were analysed using inductive content analysis. RESULTS: The barriers to institutional childbirth were categorised under four main themes: 1) Issues related to access and lack of resources: long distance to health facilities, lack of transportation means, referral problems, flooding and poor roads, and payments in health facilities; 2) Issues related to the socio-cultural context and conflict: insecurity, influence of the husband, lack of birth preparedness, domestic chores of women, influence of culture; 3) Perceptions about pregnancy and childbirth: perceived benefit of institutional childbirth, low childbirth risk perception, and medicalisation of childbirth including birth being perceived to be natural, undesirable birth practices, privacy concerns, and fear of caesarean section; and 4) Perceptions about the quality of care: inadequate health facility infrastructure and perceived neglect during admission. CONCLUSIONS: Multiple factors hinder institutional childbirth in Rumbek North. Some of the factors such as insecurity and poor roads are outside the scope of the health sector and will require a multi-sectoral approach if childbirth services are to be made accessible to women. Detailed recommendations to increase utilisation of childbirth services in the county have been suggested.

Is a woolen cap effective in maintaining normothermia in low-birth-weight infants during kangaroo mother care? Study protocol for a randomized controlled trial.

BACKGROUND: Neonatal hypothermia is an important challenge associated with morbidity and mortality. Preventing neonatal hypothermia is important in high-resource countries, but is of fundamental importance in low-resource settings where supportive care is limited. Kangaroo mother care (KMC) is a low-cost intervention that, whenever possible, is strongly recommended for temperature maintenance. During KMC, the World Health Organization (WHO) guidelines recommend the use of a cap/hat, but its effect on temperature control during KMC remains to be established. In the hospitals participating in the projects of the non-governmental organization CUAMM, KMC represents a standard of care, but the heads of the babies often remain uncovered due to local habits or to the unavailability of a cap. The aim of the present study will be to assess the effectiveness and safety of using a woolen cap in maintaining normothermia in low-birth-weight infants (LBWI) during KMC. METHODS/DESIGN: This is a multicenter (three hospitals), multicountry (three countries), prospective, unblinded, randomized controlled trial of KMC treatment with and without a woolen cap in LBWI. After obtaining parental consent, all infants with a birth weight below 2500 g and who are candidates for KMC, based on the clinical decision of the attending physician, will be assigned to the KMC with a woolen cap group or to the KMC without a woolen cap group in a 1:1 ratio according to a computer-generated, randomized sequence. The duration of the study will be until the patient's discharge, with a maximum treatment duration of 7 days. The primary outcome measure will be whether the infants' temperatures remain within the normal range (36.5-37.5 °C) in the course of KMC during the intervention. In all participants, axillary temperature will be measured with a digital thermometer four times per day. In addition, maternal and room temperature will be recorded. Secondary outcome measures will be: episodes of apnea; sepsis; mortality before hospital discharge; in-hospital growth; and age at discharge. DISCUSSION: The findings of this study will be important for other units/settings in high- as well low-resource countries where KMC is routinely performed. Based on the results of the present study, we could speculate whether the use of a woolen cap may help to maintain the neonate within the normal thermal range. Furthermore, potential complications such as hyperthermia will be strictly monitored and collected. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02645526 (registered on 31 December 2015).

Availability, utilisation and quality of maternal and neonatal health care services in Karamoja region, Uganda: a health facility-based survey.

BACKGROUND: Maternal mortality is persistently high in Uganda. Access to quality emergency obstetrics care (EmOC) is fundamental to reducing maternal and newborn deaths and is a possible way of achieving the target of the fifth millennium development goal. Karamoja region in north-eastern Uganda has consistently demonstrated the nation's lowest scores on key development and health indicators and presents a substantial challenge to Uganda's stability and poverty eradication ambitions. The objectives of this study were: to establish the availability of maternal and neonatal healthcare services at different levels of health units; to assess their utilisation; and to determine the quality of services provided. METHODS: A cross sectional study of all health facilities in Napak and Moroto districts was conducted in 2010. Data were collected by reviewing clinical records and registers, interviewing staff and women attending antenatal and postnatal clinics, and by observation. Data were summarized using frequencies and percentages and EmOC indicators were calculated. RESULTS: There were gaps in the availability of essential infrastructure, equipment, supplies, drugs and staff for maternal and neonatal care particularly at health centres (HCs). Utilisation of the available antenatal, intrapartum, and postnatal care services was low. In addition, there were gaps in the quality of care received across these services. Two hospitals, each located in the study districts, qualified as comprehensive EmOC facilities. The number of EmOC facilities per 500,000 population was 3.7. None of the HCs met the criteria for basic EmOC. Assisted vaginal delivery and removal of retained products were the most frequently missing signal functions. Direct obstetric case fatality rate was 3%, the met need for EmOC was 9.9%, and 1.7% of expected deliveries were carried out by caesarean section. CONCLUSIONS: To reduce maternal and newborn morbidity and mortality in Karamoja region, there is a need to increase the availability and the accessibility of skilled birth care, address the low utilisation of maternity services and improve the quality of care rendered. There is also a need to improve the availability and accessibility of EmOC services, with particular attention to basic EmOC.