Middle-income Countries Research Articles

Using digital health technologies to optimise antimicrobial use globally.

Digital health technology (DHT) describes tools and devices that generate or process health data. The application of DHTs could improve the diagnosis, treatment, and surveillance of bacterial infection and the prevention of antimicrobial resistance (AMR). DHTs to optimise antimicrobial use are rapidly being developed. To support the global adoption of DHTs and the opportunities offered to optimise antimicrobial use consensus is needed on what data are required to support antimicrobial decision making. This Series paper will explore bacterial AMR in humans and the need to optimise antimicrobial use in response to this global threat. It will also describe state-of-the-art DHTs to optimise antimicrobial prescribing in high-income and low-income and middle-income countries, and consider what fundamental data are ideally required for and from such technologies to support optimised antimicrobial use.

Anaemia during pregnancy: could riboflavin deficiency be implicated?

Anaemia affects more than 36% of all pregnancies globally and is associated with significant maternal and neonatal morbidity and mortality. Iron deficiency is widely recognised as the most common nutritional cause of anaemia but other nutrient deficiencies are also implicated, including the B vitamin riboflavin, albeit its role is largely under-investigated and thus typically overlooked. Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), is required for numerous oxidation-reduction reactions, antioxidant function, and in the metabolism of other B vitamins and iron. While clinical deficiency of riboflavin is largely confined to low-income countries, sub-clinical (functional) deficiency is much more widespread, including in high-income countries, and is particularly common among women of reproductive age and during pregnancy. Limited observational evidence from high-income populations suggests that suboptimal riboflavin status contributes to an increased risk of anaemia. Furthermore, randomised controlled trials in pregnant women from low- and middle-income countries have demonstrated beneficial effects of riboflavin on haematological status and anaemia. Various mechanisms have been proposed to explain the contribution of riboflavin deficiency to anaemia, with the strongest evidence pointing to an adverse effect on iron metabolism, given that riboflavin co-factors are required for the release of iron from storage ferritin in the production of red blood cells. Overall, this review investigates riboflavin intakes and status during pregnancy in different populations and evaluates the available evidence for the under-recognised role of riboflavin in the maintenance of haemoglobin concentrations together with its potential to protect against the development of anaemia during pregnancy.

Autosomal recessive polycystic kidney disease: late-onset renal enlargement and proteinuria with rare PKHD1 mutation—a case report

Abstract Background Autosomal recessive polycystic kidney disease (ARPKD) is a genetically inherited pediatric disorder. It is caused by a mutation in the PKHD1 gene located on chromosome 6. The predominant phenotype is characterized by early-onset bilateral enlarged kidneys, as well as fibrocystic changes in the kidney and liver. Fetuses or infants usually present with Potter syndrome, and they are more likely to develop severe renal insufficiency. Generally, patients die perinatally or in infancy. Liver involvement has been reported in adults with ARPKD who have survived the neonatal period and childhood. However, renal involvement is rarely expected in adulthood. The case is being presented for its clinical rarity, in addition to emphasize the critical role of NGS approaches in diagnosis. Case presentation We hereby describe a 33-year-old female with adult-onset proteinuria and nephromegaly. She had a rare homozygous missense mutation of the PKHD1 gene with autosomal recessive inheritance. The proband has consanguineous heterozygote parents. The mutation was identified by whole-exome sequencing, and the results were confirmed by segregation analysis. Conclusion Here, we reported a thorough literature review of late-onset autosomal recessive polycystic kidney disease. Furthermore, we explored the importance of genetic work-up in families with genetic disorders and consanguineous marriages, particularly in underdeveloped countries.

Treatment of prehypertension among adults with HIV: a randomized clinical trial

Objective: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti. Design: An unblinded randomized clinical trial (enrolled April 2021–March 2022) with 12-month follow-up. Setting: GHESKIO Centres, Port-au-Prince, Haiti. Participants: Two hundred fifty adults with HIV with prehypertension (SBP 120–138 or DBP 80–89) not on medication, aged 18–65 years, virally suppressed, and without pregnancy, diabetes, or kidney disease. Intervention: Participants were randomized to treatment (amlodipine 5 mg) or control (no amlodipine unless two BP ≥140/90 mmHg). Main outcome measure: Primary outcome was mean change in SBP between intervention versus control groups from enrollment to 12 months. Results: Among 250 adults, median age was 49 years, 40.8% were women. Baseline median BP was 129/78 mmHg intervention versus 128/77 mmHg control. After 12 months, the difference in mean change between study groups for SBP was -5.9 mmHg [95% confidence interval (95% CI) -8.8 to -3.0] and for DBP was -5.5 mmHg (95% CI -7.9 to -3.2). At 12 months, 5.6% intervention and 23.0% control participants developed incident hypertension (hazard ratio 0.18; 95% CI 0.07–0.47). There were no differences in viral load suppression at 12 months or drug-related serious adverse events. Intervention acceptability was high among providers and participants in qualitative interviews. Conclusion: In PWH in a resource-poor setting, prehypertension treatment was feasible, acceptable, and effective in reducing mean SBP and incident hypertension. Registration: Clinicaltrials.gov NCT04692467

Effectiveness and equity of mHealth apps for preeclampsia management in LMICs: A rapid review protocol.

Preeclampsia remains a formidable public health challenge, particularly in low- and middle-income countries (LMICs), where it significantly contributes to the high rates of maternal and neonatal morbidity and mortality. The advent of mobile health (mHealth) applications presents a promising avenue for enhancing the management of preeclampsia. This review protocol is designed to systematically assess the effectiveness and equity of mHealth apps in managing preeclampsia within LMICs, with a focus on clinical outcomes and the broader implications for accessibility, affordability, and cultural relevance. To achieve the objectives of this review, a rapid review methodology will be employed, encompassing a structured search strategy to identify pertinent studies from databases such as PubMed, Cochrane Library, and Google Scholar, as well as grey literature. The inclusion criteria are set to encompass randomized controlled trials (RCTs), controlled clinical trials (CCTs), observational studies, and qualitative studies that offer insights into the effectiveness and user experience of mHealth apps for preeclampsia management. Participants in these studies will include pregnant women at risk for or diagnosed with preeclampsia, healthcare providers, and app developers. The quality of the included studies will be critically appraised using standardized tools, and data extraction will focus on study characteristics, interventions, outcomes, and equity considerations. The implications of this review are far-reaching, offering the potential to inform stakeholders including policymakers, healthcare providers, and app developers about the deployment and development of mHealth solutions for preeclampsia management in LMICs. Ultimately, the anticipated findings of this review are expected to contribute significantly to the understanding of mHealth apps' role in improving preeclampsia management and addressing healthcare disparities, thereby guiding future strategies to enhance maternal and neonatal health outcomes in LMICs.

Comparative life cycle assessment of on-site sanitation systems using lagoons or drying beds for fecal sludge treatment in low-income tropical countries

ABSTRACT Environmental challenges in low-income countries, such as Haiti, persist due to inadequate sanitation infrastructure. This study assesses the environmental impacts of nine on-site sanitation systems to identify those with the least environmental impacts and explore improvement options. Nine scenarios were developed, each representing different systems for managing 1 ton of fecal sludge over 1 year. The ‘Impact World + ’ and ‘IPCC 2013 GWP 100a’ methods evaluated impacts on ecosystems, human health, and climate change. Data sources included interviews, weighing records, and scientific publications. Results show that Scenario 8 (Flush Toilet – Evacuation – Planted Drying Beds) is most impactful on health (1.17 × 10−2 DALY), while Scenario 1 (Composting Toilet – Evacuation – Unplanted Drying Beds) is least impactful (1.77 × 10−3 DALY). For ecosystem impacts, Scenario 2 (Container-based Toilet – Evacuation – Planted Drying Beds) is most impactful (3.81 × 103 PDF·m2·year), while Scenario 6 (VIP latrine – Evacuation – Lagoons) is least impactful (3.52 × 103 PDF·m2·year). Key hotspots include toilet paper, wood shavings, GHG emissions, and water use. The study recommends an integrated approach combining environmental life cycle assessment (LCA) with life cycle cost assessment and social LCA for sustainable decision-making on sanitation systems in low-income countries.

Post-Asphyxial Aftercare and Management of Neonates in Low- and Middle-Income Countries: A Systematic Evidence Synthesis

Introduction: Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs). Methods: Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews. Results: Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities. Conclusion: The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care.

Approaches, enablers and barriers to govern the private sector in health in low- and middle-income countries: a scoping review

IntroductionThe private sector plays a substantial role in delivering and financing healthcare in low- and middle-income countries (LMICs). Supporting governments to govern the private sector effectively, and so improve outcomes...

Epidemiology of International Patients with Lower-Limb Deficiencies Treated at a United States–Based Pediatric Prosthesis Clinic

ABSTRACT Introduction Limited epidemiological or clinical research exists describing pediatric lower-limb deficiency (LLD) patients born outside the United States (US). Objectives The purpose of this study was to characterize a cohort of international patients treated at a single tertiary care orthopedic hospital. We set out to quantify the prevalence of international patients within a broader cohort of pediatric limb deficiency patients. In addition, we evaluated similarities and differences between adopted and nonadopted internationally born patients as well as their US-born counterparts. Study Design Retrospective chart review was performed on patients born outside the US between 1995 and 2020. Methods Patients were divided into groups based on place of birth, country of residence, and adoption status. Statistical analysis was performed using χ2 and t-test. Results A total of 111/579 (19.2%) patients seen in our limb difference clinic were born outside the US, with 39.6% adopted. Geographically, patients represented 32 countries, and 96.4% were born in low- or middle-income countries (LMICs). The most common causes of LLD were congenital malformations (72.1%), trauma (17.1%), and tumor (5.4%). Syme was the most common amputation level (26.6%), followed by knee disarticulation (23.7%) and transtibial (18.7%). Congenital diagnoses were more frequent in adoptees (93.1% vs. 58.2%), whereas nonadoptees often had trauma (25.4%) or tumor (8.9%) diagnoses leading to amputation (P = 0.0003). A total of 23/60 (38.3%) international patients with preexisting lower-limb amputations had never worn a prosthesis at the time of initial presentation. Conclusions Many pediatric patients with prosthetic needs presenting for care in the US were born in LMIC. Adopted and nonadopted internationally born patients had significant differences in clinical etiologies of their LLD. Clinical Relevance Statement Internationally born patients may constitute a substantial percentage of US-based specialty clinics treating children with lower-limb differences, particularly from low- or middle-income countries where access to orthopedic and prosthetic care may be limited. This study highlights the importance of multidisciplinary health care providers addressing these children’s distinct clinical needs for improved patient-centered care.

Private sector engagement for immunisation programmes: a pragmatic scoping review of 25 years of evidence on good practice in low-income and middle-income countries

IntroductionMany National Immunisation Programmes attempt to leverage the private sector ; however, there is limited consolidated and synthesised documentation on good practices, gaps and lessons learnt. A 2017 WHO guidance...

The effect of interhospital transfer on pediatric burn injury mortality in a resource-limited setting.

The World Health Organization's burn mortality estimate is 180,000 annually. Ninety-five percent of all mortality caused by fire-related burns worldwide occurs in low- and middle-income countries (LMICs). Prior studies have shown that transfer status (direct transfer from an injury scene to a trauma center vs. indirect transfer from another health facility) affects patient outcomes. We evaluated the effect of interhospital transfer on burn mortality. We analyzed a burn database of pediatric patients admitted to the Kamuzu Central Hospital (KCH) burn unit in Lilongwe, Malawi. We performed a bivariate analysis based on their transfer status and mortality and a logistic regression analysis to determine the effect of transfer status on mortality after burn injury. A total of 2301 patients were analyzed, with 1095 (47.6%) being in the transfer cohort from referring hospitals. The median age was 3years (IQR 1-4). The transfer cohort had more patients presenting to the hospital more than 48h after injury. Upon multivariate logistic regression, controlling for pertinent variables, including time to presentation, burn-injured patients in the transfer cohort had increased odds of mortality (OR 2.26, 95% CI 1.22-4.19, and p=0.01) compared to patients who were not transferred. The predictive probabilities of burn mortality by TBSA showed significant differences in mortality based on transfer status at TBSA between 20% and 80%. Ensuring district hospitals and other primary health care centers in resource-limited settings are sufficiently equipped to provide initial burn resuscitation and care may decrease mortality rates associated with transferred patients.

Salmonella Typhi Haplotype 58 biofilm formation and genetic variation in isolates from typhoid fever patients with gallstones in an endemic setting in Kenya

Although typhoid fever has largely been eliminated in high-income countries, it remains a major global public health concern especially among low- and middle-income countries. The causative agent, Salmonella enterica serovar Typhi (S. Typhi), is a human restricted pathogen with a limited capacity to replicate outside the human host. Human carriers, 90% of whom have gallstones in their gallbladder, continue to shed the pathogen for an ill-defined period of time after treatment. The genetic mechanisms involved in establishing the carrier state are poorly understood, but S. Typhi is thought to undergo specific genetic changes within the gallbladder as an adaptive mechanism. In the current study, we aimed to identify the genetic differences in longitudinal clinical S. Typhi isolates from asymptomatic carriers with gallstones in a typhoid endemic setting in Nairobi, Kenya. Whole-genome sequences were analyzed from 22 S. Typhi isolates, 20 from stool samples, and 2 from blood samples, all genotype 4.3.1 (H58). Out of this, 19 strains were from four patients also diagnosed with gallstones, of whom three had typhoid symptoms and continued to shed S. Typhi after treatment. All isolates had point mutations in the quinolone resistance-determining region (QRDR), and only sub-lineage 4.3.1.2.EA3 encoded multidrug resistance genes. There was no variation in antimicrobial resistance patterns among strains from the same patient/household. Non-multidrug resistant (MDR) isolates formed significantly stronger biofilms in vitro than the MDR isolates, p<0.001. A point mutation within the treB gene (treB A383T) was observed in strains isolated after clinical resolution from patients living in 75% of the households. For missense mutations in Vi capsular polysaccharide genes, tviE P263S was also observed in 18% of the isolates. This study provides insights into the role of typhoid carriage, biofilm formation, AMR genes, and genetic variations in S. Typhi during asymptomatic carriage.

Coping strategies for household water insecurity in rural Gambia, mediating factors in the relationship between weather, water and health.

Rural communities in low- and middle-income countries, such as The Gambia, often experience water insecurity periodically due to climate drivers such as heavy rainfall and reduced rainfall, as well as non-climate drivers such as infrastructural issues and seasonal workloads. When facing these challenges households use a variety of coping mechanisms that could pose a risk to health. We aimed to understand the drivers of water insecurity (climate and non-climate), the behavioural responses to water insecurity and the risks these responses pose to the health of communities in rural Gambia and map these findings onto a conceptual framework. We interviewed 46 participants using multiple qualitative methods. This included in-depth interviews and transect walks. A subset of 27 participants took part in three participatory pile-sorting activities. In these activities participants were asked to rank water-related activities, intrahousehold prioritisation of water, and the coping strategies utilised when facing water insecurity. Multiple strategies were identified that people used to cope with water shortages, including: reductions in hygiene, changes to food consumption, and storing water for long periods. Many of these could inadvertently introduce risks for health. For example, limiting handwashing increases the risk of water-washed diseases. Deprioritising cooking foods such as millet, which is a nutrient-dense staple food, due to the high water requirements during preparation, could impact nutritional status. Additionally, storing water for long periods could erode water quality. Social factors appeared to play an important role in the prioritisation of domestic water-use when faced with water shortages. For example, face-washing was often maintained for social reasons. Health and religion were also key influencing factors. People often tried to protect children from the effects of water insecurity, particularly school-aged children, but given the communal nature of many activities this was not always possible. Many people associated water insecurity with poor health. To reduce the risks to health, interventions need to address the drivers of water insecurity to reduce the need for these risky coping behaviours. In the short term, the promotion of behavioural adaptations that can help buffer health risks, such as water treatment, may be beneficial.

Risk Factors for Non-Communicable Diseases in Refugees, Asylum Seekers, and Subsidiary Protection Beneficiaries Resettled or Relocated in Portugal Between 2015 and 2020

Non-communicable diseases, previously thought of as a problem of high-income countries, now coexist in low- and middle-income countries, including the countries of origin for many refugees traveling to Europe. We aimed to describe the prevalence of risk factors for non-communicable diseases among refugees, asylum seekers, and subsidiary protection beneficiaries resettled or relocated in Portugal between 2015 and 2020 and compare these to the prevalence of risk factors in the 12 months before they left their country of origin. A cross-sectional study was conducted between 2019 and 2020 of all refugees, asylum seekers, and subsidiary protection beneficiaries attending a Lisbon, Portugal refugee center. Behavioral and biological risk factors were assessed using the WHO STEPwise modified questionnaire. A descriptive statistical analysis was conducted, which included 80 respondents, mainly men, with an average age of of 30.3 ± 9.8 years. The prevalence of several behavioral risk factors for non-communicable diseases among refugees, asylum seekers, and subsidiary protection beneficiaries was higher at the time of the study than in the 12 months before leaving the country of origin. Differences between men and women were noted in tobacco (49.1% vs. 25.9%) and alcohol use (43.4% vs. 18.5%) in the receiving country. Overweight and obesity also showed differences by gender (7.5% vs. 11.1% and 39.6% vs. 48.1%). The prevalence of suicidal ideation and suicidalplanning was high, and varied from 6.3% and 20% in the country of origin to 16.3% and 38.5% respectively in the receiving country, however the prevalence of suicide attempts was lower in the receiving country (66.7%) compared to the country of origin (100.0%). Information on health and social determinants is critical to identify priorities and increase access to access to gender-specific health and community level interventions, including mental health, to reduce risk factors associated with refugee relocation and resettlement.

The New Era of mRNA Vaccines: The Success of the Covid-19 Vaccines and the Safety Concerns in Adolescents

Abstract A remarkable scientific achievement during the Covid pandemic is the rapid development and deployment of the mRNA vaccines which played a crucial role in reducing the Covid-related morbidity and mortality. The first-time safe use of the mRNA vaccine platform in humans opened up a new era in vaccinology. In the near future, the mRNA vaccine platform is likely to be used for other diseases as well. Though the Covid mRNA vaccine has been found to be safe in children, a matter of concern is the rare adverse event myocarditis, which was mostly observed among male adolescents. In this setting, we briefly discuss mRNA vaccine-related myocarditis and suggest that the safety concerns need to be alleviated by larger studies with long-term follow-up. We also stress the need for the generation of safety data from children in lower- and middle-income countries as there is limited experience with mRNA vaccines in such settings. The underlying mechanisms need to be understood well as the mRNA vaccine platform holds enormous promise for the future development of vaccines for several diseases.

Climate legislation and green agricultural production: impacts, transmission mechanisms and heterogeneities

PurposeThis study examines the impact of climate legislation on green agricultural production and tests the heterogeneous impact of different types of climate legislation on agricultural green production.Design/methodology/approachIn this study, the super-slacks-based measure (super-SBM) model is used to calculate agricultural green total factor productivity (AGTFP). The impact of climate legislation (including legislative acts and executive orders) on AGTFP is examined through regression analysis. The transmission mechanism of climate legislation affecting agricultural green production is further investigated.FindingsThis study shows that climate legislation has a positive long-term effect on AGTFP. It stimulates innovation in agricultural green technology but has a negative impact on resource allocation efficiency. Executive orders have a more significant effect on AGTFP than climate legislative acts. The effectiveness of climate legislation is more significant in countries with stronger legislation. Moreover, climate legislation reduces AGTFP in low-income countries while enhancing AGTFP in high-income countries. This effect is most prominent in upper-middle-income countries.Originality/valueThis study examines the different effects of various types of climate legislation, considering the level of economic development and the strength of the legal system on AGTFP. The findings can offer a global perspective and insights for China’s policymaking.

Economic growth and food insecurity: evidence via panel estimation

ABSTRACT This study investigates the effect of income changes on the prevalence of undernourishment as a proxy for food insecurity using a balanced panel of 145 economies. Additionally, it examines whether there are heterogeneous effects on undernourishment based on country income strata. Utilizing a panel local projections (LP) model, this study demonstrates that higher-income growth alleviates food insecurity, particularly in lower-income countries. These results underscore the significance of food insecurity within the framework of economic development and offer policymakers vital information on the degree to which economic progress can alleviate it.

Relationship between justice and economic growth: the effects of rule of law and democracy

ABSTRACT This study analyses the effects of justice on economic growth. In this context, the study investigates the impact of justice on per capita income in 43 middle-income countries between 2005–2021 with Parks-Kmenta, Beck-Katz estimators and the extended mean group estimator (AMG). Rule of law and democracy variables are used as justice indicators. National income per capita is used as an indicator of economic growth, and national income, fixed capital investments, fertility rates, public expenditures, education expenditures, life expectancy and openness to internationalization are used as control variables. The findings show that the rule of law has a positive effect on per capita GDP in Albania, Armenia, Ecuador, Jordan, Malaysia, North Macedonia, South Africa, Thailand and El Salvador. Democracy only has a positive effect on GDP per capita in Turkey. The study contributes to the limited literature on the relationship justice and economic grow. It differs from the literature by analysing the effects of the rule of law and democracy both on a country group basis and country-specific effects.

Thibang Diphatlha: a sequential multiple assignment randomized trial designed to increase timely adoption of cervical cancer treatment in Botswana.

Delays and missed opportunities for timely treatment contribute significantly to stark inequities in cervical cancer mortality in low- and middle-income countries (LMICs) compared to high-income countries. The vast majority (approximately 90%) of new cases and deaths occur in LMICs, particularly those with high rates of HIV such as Botswana. To date, most of the implementation and cancer control research in Botswana and other LMICs has focused on cancer prevention and screening, with limited focus on cancer treatment. As such, there is a critical need to identify effective strategies to ensure timely care, and to understand contextual factors that shape the response to strategies. Without this fundamental knowledge, cervical cancer will remain a public health crisis in Botswana and other LMICs. To help fill this known gap, this study tests the effectiveness of adaptive strategies on timely treatment adoption using a hybrid (type III) Sequential Multiple Assignment Randomized Trial (SMART) design and evaluate contextual mechanisms contributing to the success or failure of each adaptive strategy. The adaptive strategies are designed to target contextual determinants identified in our prior work, including delayed communication of results to patients, individual and structural barriers to accessing treatment, and suboptimal care coordination between referring and cancer treatment clinics, and are supported by systematic evidence of the effectiveness of nudge strategies in clinical care. The primary implementation outcome is adoption, defined as the initiation of treatment within 90days. Secondary outcomes include fidelity, reach, acceptability, implementation costs, and cancer and HIV-related clinical outcomes. The rationale for the study is that enhancing coordination, communication, and navigation through centralized outreach will both increase timely treatment adoption and be scalable and sustainable after the project is completed. This innovative study seeks to decrease cervical cancer mortality in LMICs by developing and implementing effective and sustainable strategies that can be sustained and adapted to other contexts. Additionally, this study seeks to advance the long-term impact of global implementation science through strong and sustained partnerships in Botswana and other LMICs. ClinicalTrials.govNCT05952141. Registered on July 11, 2023. https://clinicaltrials.gov/study/NCT05952141 PROTOCOL VERSION AND DATE: Version 1 (September 28, 2024).

Prevention and Treatment of Neonatal Infections in Facility and Community Settings of Low- and Middle-Income Countries: A Descriptive Review

Introduction: We present a robust and up-to-date synthesis of evidence on the effectiveness of interventions to prevent and treat newborn infections in low- and middle-income countries (LMICs). Newborn infection prevention interventions included strategies to reduce antimicrobial resistance (AMR), prevention of healthcare-associated infections (HAIs), clean birth kits (CBKs), chlorhexidine cleansing, topical emollients, and probiotic and synbiotic supplementation. Interventions to treat suspected neonatal infections included prophylactic systemic antifungal agents and community-based antibiotic delivery for possible serious bacterial infections (PSBIs). Methods: A descriptive review combining different methodological approaches was conducted. To provide the most suitable recommendations for real-world implementation, our analyses considered the impact of these interventions within three distinct health settings: facility, mixed, and community. Results: In facility settings, the strongest evidence supported the implementation of multimodal stewardship interventions for AMR reduction and device-associated infection prevention bundles for HAI prevention. Emollients in preterm newborns reduced the risk of invasive infection compared to routine skin care. Probiotics in preterm newborns reduced neonatal mortality, invasive infection, and necrotizing enterocolitis (NEC) risks compared to standard care or placebo. There was insufficient evidence for synbiotics and prophylactic systemic antifungals in LMICs. In mixed settings, CBKs reduced neonatal mortality risk compared to standard care. In community settings, chlorhexidine umbilical cord cleansing reduced omphalitis risk compared to dry cord care. For the treatment of PSBIs, purely domiciliary-based antibiotic delivery reduced the risk of all-cause neonatal mortality when compared to the standard hospital referral. Conclusion: Strategies for preventing HAIs and reducing AMR in healthcare facilities should be multimodal, and strategy selection should consider the feasibility of integration within existing newborn care programs. Probiotics are effective for facility-based use in preterm newborns; however, the establishment of high-quality, cost-effective mass production of standardized formulations is needed. Chlorhexidine cord cleansing is effective in community settings to prevent omphalitis in contexts where unhygienic cord applications are prevalent. Community-based antibiotic delivery of simplified regimens for PSBIs is a safe alternative when hospital-based care in LMICs is not possible or is declined by parents. More randomized trial evidence is needed to establish the effectiveness of CBKs, emollients, synbiotics, and prophylactic systemic antifungals in LMICs.