Innovative approaches to neonatal jaundice diagnosis and management in low-resourced settings.

Persistent challenges in addressing severe neonatal hyperbilirubinaemia in resource-constrained settings have led to ongoing and often unacceptable rates of morbidity, disability and mortality. These challenges stem from limitations such as inadequate, inefficient or financially inaccessible diagnostic and therapeutic options. However, over the past decade, noteworthy innovations have emerged to address some of these hurdles, and these innovations are increasingly poised for broader implementation. This review provides a concise summary of these novel, economically viable diagnostic solutions, encompassing point-of-care assays and smartphone applications, as well as treatment modalities, notably more effective phototherapy and filtered sunlight. These advancements hold promise and have the potential to meaningfully reduce the burden of neonatal hyperbilirubinaemia, signifying a promising shift in the landscape of neonatal healthcare.

Maximizing Access and Minimizing Barriers to Research in Low- and Middle-Income Countries: Open Access and Health Equity.

Access to published research has always been difficult for researchers and clinicians in low- and middle-income countries, because of the cost of and lack of access to the relevant publications. The dramatic recent increase in electronic research publications has resulted in a marked improvement in reader access to these publications through their mainly Open Access policies, however the costs of processing of submissions and publication have now become the burden of the researchers wishing to publish, rather than the readers. For many researchers working in LMIC, the Article Processing Charges (APC) are prohibitive, hampering the publication of research being conducted in and relevant to these countries. A number of grant funding agencies and international not-for-profit organizations are trying to address these issues by including funding for article publications in their grants, or by supporting publishing entities by subsiding the cost of publication, but more needs to be done by major journal publishers through markedly reducing the APC being charged to researchers in LMIC for open access facilities.

Clinical and growth outcomes of severely malnourished children following hospital discharge in a South African setting.

BACKGROUND: Data on outcomes of children with severe acute malnutrition (SAM) following treatment are scarce with none described from any upper-middle-income country. This study established mortality, clinical outcomes and anthropometric recovery of children with SAM six months following hospital discharge. METHODS: A prospective cohort study was conducted in children aged 3-59 months enrolled on discharge from two hospitals in the Tshwane district of South Africa between April 2019 and January 2020. The primary outcome was mortality at six months. Secondary outcomes included relapse rates, type(s) and frequency of morbidities experienced and the anthropometric changes in children with SAM following hospital discharge. Standard programmatic support included nutritional supplements. RESULTS: Forty-three children were enrolled with 86% of participants followed up to six months. Only a third of the participants had normal anthropometry at hospital discharge-a quarter still had ongoing SAM. There were no deaths, although four children (9%) were re-hospitalised including two for complicated SAM. Mean weight-for-length z-scores (WLZ) and wasting rates improved at one month but deteriorated by three months. At three months, six children (14%) either had ongoing or relapsed SAM-a SAM incidence rate of 20 per 1000 person-months despite more than half of the participants still receiving nutritional supplements at the time. Risk factors associated with persistent malnutrition at three months included a low WLZ on admission (relative risk [RR] 3.3, 95% confidence interval [95%CI] 1.2-9.2), being discharged from hospital before meeting WHO SAM treatment discharge criteria (RR 5.3, 95%CI 1.3-14.8) or having any illness by three months (RR 8.6, 95%CI 1.3-55.7). CONCLUSION: Post-discharge mortality and morbidity was lower than in other less resourced settings. However, anthropometric recovery was poorer than expected. Modifying discharge criteria, optimising the use of available nutritional supplements and better integration with community-based health and social services may improve outcomes for children with SAM post-hospitalisation.

Epidemiology of SARS-CoV-2 infection and SARS-CoV-2 positive hospital admissions among children in South Africa.

INTRODUCTION: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and positive admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. METHODS: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and whose death was judged SARS-CoV-2 related by attending physician. FINDINGS: 315 570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3 548 738 tests and 1.6% of all children in the country. Of children tested, 46 137 (14.6%) were positive. Children made up 2.9% (n = 2007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals [CI] 1.08-4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28-18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01-12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none. CONCLUSIONS: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years, those in certain provinces and those with underlying conditions should be considered for increased testing and vaccination.

Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation.

BACKGROUND: We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former. METHODS: In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials. RESULTS: We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74). CONCLUSIONS: Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done.

Health system factors affecting implementation of integrated management of childhood illness (IMCI): qualitative insights from a South African province.

The Integrated Management of Childhood Illness (IMCI) strategy has been adopted by 102 countries including South Africa, as the preferred primary health care (PHC) delivery strategy for sick children under 5 years. Despite substantial investment to support IMCI in South Africa, its delivery remains sub-optimal, with varied implementation in different settings. There is scarce research globally, and in the local context, examining the effects of health system characteristics on IMCI implementation. This study explored key determinants of IMCI delivery in a South African province, with a specific focus on health system building blocks using a health system dynamics framework. In-depth interviews were conducted with 38 districts, provincial and national respondents involved with IMCI co-ordination and delivery, exploring their involvement in, and perceptions of, IMCI strategy implementation. Identified barriers included poor definition of elements of a service package for children and how IMCI aligned with this, incompetence of trained nurses exacerbated by inappropriate rotation practices, use of inappropriate indicators to track progress, multiple cadres coordinating similar activities with poor role delineation, and fragmented, vertical governance of programmes included within IMCI, such as immunization. Enabling practices in one district included the use of standardized child health records incorporating IMCI activities and stringent practice monitoring through record audits. Using IMCI as a case study, our work highlights critical health system deficiencies affecting service delivery for young children which need to be resolved to reposition IMCI within the broader child 'survive, thrive and transform' agenda. Recommendations for appropriate health system strengthening include the need for redefining IMCI within a broader PHC service package for children, prioritizing post-training supervision and mentoring of practitioners through appropriate duty allocation and rotation policies, strengthening IMCI monitoring with a specific focus on quality of care and building stronger clinical governance through workforce allocation, role delineation and improved accountability.

Child Sexual Abuse in Zimbabwe.

Although child sexual abuse is a significant public health problem globally, its incidence, prevention, and management is less well described in resource-poor settings. In poorer settings prevention initiatives assume even more importance since resources for managing abused children are severely limited. This article examines the current status of policy and practice related to the prevention of child sexual abuse in Zimbabwe. It identifies implementation challenges and highlights opportunities that could be embraced to reduce CSA in Zimbabwe, based on evidence synthesized from recent work. Although Zimbabwe has a well-established legal and regulatory framework to protect children from child sexual abuse, implementation of existing policies is weak. Financial, human, and material resource constraints are frequently cited to explain limited prevention activity. Effective strategies for the prevention of child sexual abuse should focus on implementing existing legislation, targeting schoolchildren, and getting community involvement. A dedicated budget would help entrench these strategies, but gains can be achieved even in the absence of this.

Maternal risk exposure during pregnancy and infant birth weight.

BACKGROUND: Birth weight is an important determinant of an infant's immediate and future health. AIM: This study examined associations between selected maternal psychosocial and environmental risk factors during pregnancy and subsequent infant birth weight, utilising data from the South African Birth to Twenty Plus (Bt20+) birth cohort study. SUBJECTS: Exposure to nine maternal risks were assessed in 1228 women who completed an antenatal questionnaire and whose infants were delivered within a seven-week period. OUTCOME MEASURES: The outcome of interest was infant birth weight. Birth weight z-scores (BWZ) were calculated using the World Health Organization Child Growth Standards. Bivariate analyses and multiple regression models were used to identify significant risk factors. RESULTS: The mean infant birth weight was 3139g (SD 486g), with a significant advantage in mean birth weight for male infants of 73g (p=0.008). Being unsure or not wanting the pregnancy was associated with a ~156g reduction in infant birth weight (ß=-0.32; 95% CI -0.51; -0.14). Tobacco use during pregnancy was also negatively associated with BWZ (ß=-0.32; 95% CI -0.59; -0.05). Exposure to both significant risk factors (tobacco use and pregnancy wantedness) was associated with cumulative reductions in birth weight, particularly among boys. CONCLUSIONS: This study reinforces the importance of risks related to maternal attitudes and behaviours during pregnancy, namely unwanted pregnancy and tobacco use, which significantly lowered birth weight. Both identified risks are amenable to public health policy and programme intervention.

Anti-inflammatory treatment for carditis in acute rheumatic fever.

BACKGROUND: Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although prevention of rheumatic fever and management of recurrences have been well established, optimal management of active rheumatic carditis remains unclear. This is an update of a review published in 2003, and previously updated in 2009 and 2012. OBJECTIVES: To assess the effects, both harmful and beneficial, of anti-inflammatory agents such as aspirin, corticosteroids and other drugs in preventing or reducing further valvular damage in patients with acute rheumatic fever. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2013, Issue 9 of 12), MEDLINE (Ovid, 1948 to 2013 October Week 1), EMBASE (Ovid, 1980 to 2013 Week 41) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 17 October 2013). We last searched Index Medicus (1950 to April 2001) in 2001. We checked reference lists of identified studies and applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) versus placebo or controls, or comparing any of the anti-inflammatory agents versus one another, in adults and children with acute rheumatic fever diagnosed according to Jones, or modified Jones, criteria. The presence of cardiac disease one year after treatment was the major outcome criterion selected. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and assessed risk of bias using the methodology outlined in the Cochrane Handbook of Systematic Reviews of Interventions. Standard methodological procedures as expected by The Cochrane Collaboration were used. MAIN RESULTS: No new studies were included in this update. Eight randomised controlled trials involving 996 people were selected for inclusion in the review. Researchers compared several steroidal agents such as corticotrophin, cortisone, hydrocortisone, dexamethasone, prednisone and intravenous immunoglobulin versus aspirin, placebo or no treatment. Six trials were conducted between 1950 and 1965; one was done in 1990 and the final study was published in 2001. Overall there were no observed significant differences in risk of cardiac disease at one year between corticosteroid-treated and aspirin-treated groups (six studies, 907 participants, risk ratio 0.87, 95% confidence interval 0.66 to 1.15). Similarly, use of prednisone (two studies, 212 participants, risk ratio 1.13, 95% confidence interval 0.52 to 2.45) compared with aspirin did not reduce the risk of heart disease after one year. Investigators in five studies did not report adverse events. The three studies reporting on adverse events reported substantial adverse events. However, all results should be interpreted with caution because of the age of the studies and the substantial risk of bias. AUTHORS' CONCLUSIONS: Little evidence of benefit was found when corticosteroids or intravenous immunoglobulins were used to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. In addition, risk of bias was substantial, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever are warranted to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone and the effects of other new anti-inflammatory agents. Advances in echocardiography will allow more objective and precise assessments of cardiac outcomes.

The prevention and management of congenital syphilis: an overview and recommendations

The continued occurrence of congenital syphilis is an indictment of the inadequate antenatal care services and poor quality of programmes to control sexually transmitted infections...

Noncommunicable diseases in HIV infection in low- and middle-income countries: gastrointestinal, hepatic, and nutritional aspects.

The purpose of this review was to outline the interaction between HIV and noncommunicable diseases affecting the gastrointestinal (GI) tract, liver, and nutritional disorders in low- and middle-income countries (LMICs), and to identify research priorities. Noncommunicable GI tract disorders are only moderately influenced by HIV, and peptic ulceration is actually less common. However, the impact of HIV on GI cancers needs further investigation. HIV interacts strongly with environmental enteropathy, exacerbating malabsorption of nutrients and drugs. HIV has 2 major effects on noncommunicable liver disease: drug-induced liver injury and nonalcoholic fatty liver disease (particularly in persons of African genetic descent). The effect of HIV on nutrition was one of the first markers of the epidemic in the 1980s, and HIV continues to have major nutritional consequences. Childhood malnutrition and HIV frequently coexist in some regions, for example, southern Africa, resulting in powerful negative interactions with poorer responses to standard nutritional rehabilitation. HIV and nutritional care need to be better integrated, but many questions on how best to do this remain unanswered. Across the spectrum of GI, hepatic, and nutritional disorders in HIV infection, there is increasing evidence that the microbiome may play an important role in disease pathogenesis, but work in this area, especially in low- and middle-income countries, is in its infancy.

Ensuring quality in AFRINEST and SATT: clinical standardization and monitoring.

BACKGROUND: Three randomized open-label clinical trials [Simplified Antibiotic Therapy Trial (SATT) Bangladesh, SATT Pakistan and African Neonatal Sepsis Trial (AFRINEST)] were developed to test the equivalence of simplified antibiotic regimens compared with the standard regimen of 7 days of parenteral antibiotics. These trials were originally conceived and designed separately; subsequently, significant efforts were made to develop and implement a common protocol and approach. Previous articles in this supplement briefly describe the specific quality control methods used in the individual trials; this article presents additional information about the systematic approaches used to minimize threats to validity and ensure quality across the trials. METHODS: A critical component of quality control for AFRINEST and SATT was striving to eliminate variation in clinical assessments and decisions regarding eligibility, enrollment and treatment outcomes. Ensuring appropriate and consistent clinical judgment was accomplished through standardized approaches applied across the trials, including training, assessment of clinical skills and refresher training. Standardized monitoring procedures were also applied across the trials, including routine (day-to-day) internal monitoring of performance and adherence to protocols, systematic external monitoring by funding agencies and external monitoring by experienced, independent trial monitors. A group of independent experts (Technical Steering Committee/Technical Advisory Group) provided regular monitoring and technical oversight for the trials. CONCLUSIONS: Harmonization of AFRINEST and SATT have helped to ensure consistency and quality of implementation, both internally and across the trials as a whole, thereby minimizing potential threats to the validity of the trials' results.

Cost-effectiveness analysis of infant feeding strategies to prevent mother-to-child transmission of HIV in South Africa.

Despite increasing availability of perinatal interventions to prevent mother-to-child transmission (MTCT) of HIV in South Africa, MTCT remains high due to breastfeeding. To inform policy decisions in the country, cost-effectiveness of alternative infant-feeding interventions was conducted. Mathematical modelling was used to simulate post-natal transmission and mortality due to infant feeding in a hypothetical cohort of 1 000 HIV-exposed infants. Lifetime costs to the health system were calculated for each strategy. Interventions compared with current practice were: increasing coverage of extended nevirapine prophylaxis (ENP) to infants from 30% (base case) to 60% without changing current feeding practices; actively supporting breastfeeding with ENP to infants for 12 months; and actively supporting exclusive formula (replacement) feeding for 6 months. HIV-free survival at 24 months and disability-adjusted life years (DALYs) averted were estimated for typical rural and certain urban settings. Base-case analysis revealed that expanding coverage of nevirapine prophylaxis with breastfeeding is cost-saving and improves HIV-free survival. Changing feeding practices is beneficial, depending on context. Breastfeeding is dominant (less costly, more effective) in rural settings, whilst formula feeding is a dominant strategy in urban settings. Cost-effectiveness was most sensitive to proportion of women on lifelong antiretroviral therapy (ART) and infant mortality rate (IMR). When >55% of women are on ART, breastfeeding dominates in the urban settings modelled, whilst formula feeding is cost-effective in rural settings when IMR ≤ 45/1000. The study concludes that strategies to support breastfeeding are essential. Strengthening health systems is critical to ensure optimal nevirapine delivery during breastfeeding. A case can be made for formula feeding or breastfeeding in HIV-infected women in specific contexts.

Can a new paediatric sub-specialty improve child health in South Africa?

Compared with other middle-income countries, child health in South Africa is in a poor state, and should be addressed by focusing on the health care needs of all children across a system or region. Paediatricians have had little effect on this situation, partly because their training is not aligned with South African needs. The proposed re-engineering of primary health care will be limited by the skewed distribution of staff and the lack of suitable skills. A 'community' placement during specialist training, and the creation of a sub-specialty in Community Paediatrics and Child Health, could address the skills shortage and possibly attract health personnel to under-served areas through creating an appropriate career path. This proposal would also support the Department of Health's encouraging plans to re-engineer primary health care.

Anti-inflammatory treatment for carditis in acute rheumatic fever.

BACKGROUND: Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although the prevention of rheumatic fever and the management of recurrences is well established, the optimal management of active rheumatic carditis is still unclear. This is an update of a review published in 2003 and previously updated in 2009. OBJECTIVES: To assess the effects of anti-inflammatory agents such as aspirin, corticosteroids, immunoglobulin and pentoxifylline for preventing or reducing further heart valve damage in patients with acute rheumatic fever. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2011), MEDLINE (1966 to Aug 2011), EMBASE (1998 to Sept 2011), LILACS (1982 to Sept 2011), Index Medicus (1950 to April 2001) and references lists of identified studies. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) with placebo or controls, or comparing any of the anti-inflammatory agents with one another, in adults and children with acute rheumatic fever diagnosed according to the Jones, or modified Jones criteria. The presence of cardiac disease one year after treatment was the major outcome criteria selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data. Risk of bias was assessed using methodology outlined in the Cochrane handbook. MAIN RESULTS: No new studies were included in this update. Eight randomised controlled trials involving 996 people were included. Several steroidal agents corticotrophin, cortisone, hydrocortisone, dexamethasone and prednisone, and intravenous immunoglobulin were compared to aspirin, placebo or no treatment in the various studies. Six of the trials were conducted between 1950 and 1965, one study was done in 1990, and the final study was published in 2001. Overall there was no significant difference in the risk of cardiac disease at one year between the corticosteroid-treated and aspirin-treated groups (six studies, 907 participants, relative risk 0.87, 95% confidence interval 0.66 to 1.15). Similarly, use of prednisone (two studies, 212 participants, relative risk 1.13, 95% confidence interval 0.52 to 2.45) compared to aspirin did not reduce the risk of developing heart disease after one year. Adverse events were not reported in five studies. The three studies reporting on adverse events all reported substantial adverse events. However, all results should be interpreted with caution due to the age of the studies and to substantial risk of bias. AUTHORS' CONCLUSIONS: There is little evidence of benefit from using corticosteroids or intravenous immunoglobulins to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. Additionally there was substantial risk of bias, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone, and other new anti-inflammatory agents are warranted. Advances in echocardiography will allow for more objective and precise assessments of cardiac outcomes.