Publications Library

Abstract

Childhood mortality remains a major public health challenge in low-income and middle-income countries, particularly in sub-Saharan Africa, despite major advances in universal sanitation and immunisations. Mass drug administration (MDA) of azithromycin, a broad-spectrum antibiotic, has shown promise in reducing under-5 mortality in high-risk regions, although its mechanism of protection remains largely unknown. In this Personal View, we analyse current evidence, potential effect of MDA on antimicrobial resistance, and relevant ethical principles, and propose priorities for future public health interventions. Our review of key randomised controlled trials revealed highly variable outcomes of azithromycin MDA differing by participants' age, geographical location, comorbidities, coinfections, and concurrent therapies. Intermittent use of azithromycin has been linked to rising macrolide resistance in several pathogens, spillover effects in untreated populations, and ecological disruptions. Ethical concerns, including informed consent and allocation of limited resources, require careful consideration. We propose a multifaceted approach including investments in water, sanitation, and hygiene infrastructure, vaccination programmes, and robust antimicrobial resistance surveillance. Policy makers and global health stakeholders must prioritise context-specific, evidence-based strategies that strengthen local capacity, improve community engagement, and implement robust monitoring systems to ensure that the potential benefits of MDA are sustained and do not imperil public health.

Abstract

Background: Dehydration is a prevalent and potentially serious condition, particularly affecting vulnerable populations such as children and older adults. Prompt recognition and intervention are critical for preventing associated complications. 

Methods: A systematic review and meta-analysis were conducted, registered in PROSPERO (CRD42024594780), to identify key clinical and demographic risk factors associated with dehydration. A comprehensive search of PubMed, Scopus, and the Cochrane Library was performed for studies published between 2000 and 2024. The risk of bias in included studies was assessed using the Newcastle-Ottawa Scale and the Cochrane Risk-of-Bias (RoB) tool. Ten studies met the inclusion criteria for quantitative synthesis. Based on pooled diagnostic metrics, a preliminary scoring tool was developed for dehydration risk stratification.

 Results: The pooled sensitivity and specificity of common clinical signs, such as thirst, dry mouth, and dark urine, were 85% (95% CI: 80-90%) and 70% (95% CI: 65-75%), respectively. The positive predictive value (PPV) was 75%, and the negative predictive value (NPV) was 80%. Pediatric subgroup analysis yielded the most robust data, while data for adult and elderly populations were limited. A conceptual risk scoring system was proposed based on relative diagnostic utility, though it has not yet been externally validated. 

Conclusions: Simple clinical signs demonstrate reasonable diagnostic accuracy for identifying individuals at risk of dehydration. The proposed scoring system offers a promising, evidence-informed framework for early risk assessment but requires further validation in prospective studies before integration into clinical practice.

Abstract

Background: Globally, several gaps in vaccine safety surveillance exist, particularly in low- and middle- income countries (LMICs). Establishing and maintaining vaccine surveillance platforms in resource-constrained settings poses significant challenges. These countries often rely on paper-based medical records and immunization cards, lack unique patient identifiers across the healthcare systems, have limited electronic data capture capabilities, and face a shortage of clinical reviewers for case assessments. This report highlights the establishment of two active vaccine safety surveillance studies across nine African countries: (i) Active COVID-19 vaccine safety surveillance (ACVaSS) in eight COVAX 92 Advanced Market Commitment (AMC-92) eligible African countries including Ethiopia, Ghana, Kenya, Mali, Malawi, Mozambique, Nigeria and Eswatini and (ii) the South African COVID-19 vaccine safety surveillance study (SA-CVSS).

Methods: Both ACVaSS and SA-CVSS were hospital-based sentinel active surveillance studies designed to monitor the safety of COVID-19 vaccines in the aforementioned COVAX AMC-92 countries and South Africa, a middle-income African country. Patients presenting to healthcare facilities with illnesses resembling pre-selected adverse events of special interest (AESIs), were enrolled, with informed consent, into the studies. The Brighton Collaboration Case Definitions were applied to classify AESIs.

Findings: Over 60,000 admitted patients were screened and over 12,700 eligible patients were enrolled in 18 months. Despite challenges in accessing and abstracting data from predominantly paper-based medical and vaccination records, the identification of specific AESIs and estimating association with vaccination status was feasible in LMIC healthcare facilities.

Conclusions: The establishment of active vaccine safety surveillance sentinel sites is achievable in LMICs, though the lack of digital medical records hindered data accessibility and availability. Regulatory authorities, health departments and organizations supporting immunization programs must prioritize the development, maintenance and funding of active vaccine safety surveillance systems. Such surveillance is crucial to ensuring that new vaccines are properly monitored and assessed for safety following their introduction and use in these populations.

Funding: The SA-CVSS study was funded by a US CDC Grant to the GVDN (grant reference: CDC Funder Award Number: 1 NU38CK000485-01-00), the South African Medical Research Council (SAMRC) and the Task Force for Global Health (RVD_CDC-COV). Gavi, The Vaccine Alliance, funded the ACVaSS study (Agreement reference: MEL10500921).

Abstract

Background: The World Health Organization (WHO) clinical case definitions for pneumonia were designed to prioritize sensitivity over specificity. In sub-Saharan Africa, the disease that is most likely to be misclassified as pneumonia is Plasmodium falciparum malaria.

Methods: By using chest X-ray positivity as an indicator for pneumonia, we estimated the extent of pneumonia misclassification due to malaria in the Pneumonia Etiology Research for Child Health (PERCH) study. Additionally, we developed a simple model to predict the proportion of pneumonia cases as defined by the WHO that could be attributed to malaria in settings with varying levels of malaria parasitaemia prevalence.

Results: In the PERCH study, the prevalence of malaria parasitaemia was low (4.7% among WHO pneumonia cases and 1.4% among controls) and we estimate that only 2.5% of WHO pneumonia cases were misclassified. However, when assuming a prevalence of malaria parasitaemia of 24%, corresponding to the average for malaria-endemic areas in Africa, we estimate that 28% of WHO pneumonia cases are misclassified. Among malaria-slide-positive WHO pneumonia cases in PERCH, lower chest wall indrawing [adjusted odds ratio (aOR) =18.1, 95% confidence interval (95% CI): 1.9, 175.8, P = 0.012], crackles on chest auscultation (aOR = 13.1, 95% CI: 1.4, 127.4, P = 0.027), and nasal flaring (aOR = 5.9, 95% CI: 1.1, 32.8, P = 0.041) were associated with chest X-ray positivity.

Conclusion: In settings that are typical of sub-Saharan Africa, we predict that one-quarter of WHO-defined pneumonia cases are malaria rather than pneumonia. Among children with WHO pneumonia who also test positive for malaria parasitaemia, clinical features that favour pneumonia include lower chest wall indrawing, nasal flaring, and crackles on chest auscultation.

Abstract

Low levels of vitamin D in maternal and cord blood have been associated with neonatal sepsis. This study assessed the association of vitamin D metabolites (25(OH)D, 3-epi-25(OH)D₃, and 24,25(OH)₂D₃) levels in maternal and cord blood with newborn sepsis evaluation in Nigerian mother-infant dyads. Maternal and cord blood from 534 mothers and 536 newborns were processed using liquid chromatography-tandem mass spectrometry. Spearman correlation was used to compare continuous variables, Mann-Whitney for dichotomous variables, and Kruskal-Wallis for two or more groups. High cord percent 3-epi-25(OH)D₃ levels were positively associated with newborn evaluation for sepsis (p = 0.036), while maternal and cord 25(OH)D and 24,25(OH)₂D₃ levels were not. Being employed was positively associated with maternal and newborn 3-epi-25(OH)D₃ concentrations (p = 0.007 and p = 0.005, respectively). The maternal 3-epi-25(OH)D₃ and percent 3-epi-25(OH)D₃ were positively associated with vaginal delivery (p = 0.013 and p = 0.012, respectively). Having a weight-for-age Z-score ≤ -2 was positively associated with newborn percent 3-epi-25(OH)D₃ levels (p = 0.004), while a weight-for-length Z-score ≤ -3 was positively associated with maternal and newborn percent 3-epi-25(OH)D₃ levels (p = 0.044 and p = 0.022, respectively). Our study highlights the need to further investigate the biological role of 3-epi-25(OH)D₃ and its clinical significance in fetal growth and newborn outcome.

Abstract

Antimicrobial peptide amphiphiles (PAs) are a promising class of molecules that can disrupt the bacterial membrane or act as drug nanocarriers. In this study, we prepared 33 PAs to establish supramolecular structure-activity relationships. We studied the morphology and activity of the nanostructures against different Gram-positive and Gram-negative bacterial strains (such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii). Next, we used principal component analysis (PCA) to determine the key contributors to activity. We found that for S. aureus, the zeta potential was the major contributor to the activity while Gram-negative bacteria were more influenced by the partition coefficient (LogP) with the following order P. aeruginosa>E. coli>A. baumannii. We also performed a study of the mechanism of action of selected PAs on the bacterial membrane assessing the membrane permeability and depolarization, changes in zeta potential and overall integrity. We studied the toxicity of the nanostructures against mammalian cells. Finally, we performed an in vivo study using the wax moth larvae to determine the therapeutic efficacy of the active PAs. This study shows cationic PA nanostructures can be an intriguing platform for the development of nanoantibacterials.

Abstract

The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to a free HPV vaccine is a public health concern. HPV is one of the most common sexually transmitted infections (STIs) in Nigeria, while the most known types of HPV genotypes being transmitted are the high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) University located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on Google Forms and it was distributed to the university community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, and knowledge about HPV infection and genotypes, as well as the sexual health of the participants. All variables were described using frequencies and percentage distribution; chi-squared test statistics were used to explore the association between HPV infection (medical records of HPV infection) and the participants' profile, and a logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26-40 years (81.3%) and those currently not in a sexually active relationship-single/divorced (26.4%)-who have self-reported having the HPV-16 and -18 genotypes. Moreover, participants between 26-40 years of age (OR: 0.45, 95%CI: 0.22-0.89) reported themselves to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university.

Abstract

It is known that the quantity, makeup, and distribution of bodily fluids have a significant impact on the cognitive health, physiological health, and cell activity of human beings. This narrative could be influenced by the level of knowledge about hydration, dehydration, and the practice of Adequate Water Intake (AWI) of an individual based on the recommended daily Total Water Intake (TWI) by either the World Health Organization (WHO) or the European Food Safety Authority (EFSA). In this study, we have developed and validated a scale to adequately measure knowledge of the recommended daily Total Water Intake (TWI) practices among foreign students at Óbuda University, Hungary. Hence, we implemented an 11-item scale to measure the Knowledge of Hydration (KH-11) and evaluate its psychometric properties among students. This study is an online cross-sectional study assessing water intake knowledge with the use of the KH-11 tool among 323 students with ages ranging from 18 to 35 years, who have enrolled for at least two semesters at the University. The statistical analysis performed was reliability (using Cronbach alpha ≥ 70%) and factor analysis. Knowledge levels were categorized as poor (<50%), intermediate (50-70%), or adequate (71-100%). The intraclass correlation, chi-square, and rotated component matrix were also estimated and reported. Data were analyzed using SPSS version 25. Cronbach's alpha analysis revealed that the KH-11 had an overall good reliability with a value of 0.80, where the survey items had an acceptable level of consistency ranging from 0.75 to 0.81 and demonstrated sufficient independence from each other as Pearson's R within factors was positive and ranged from 0.02 to 0.74. In evaluating the participants' knowledge of hydration, the total possible score for the scale is 72, while the mean score for the KH-11 was 55.2 ± 11.61 SD, and the factor analysis model yielded an acceptable fit (χ² = 3259.4, p = 0.000). We recorded a high-level positive concordance of 0.770 with an average intraclass correlation of 0.80 at a 95% CI, where p-value = 0.000. Our findings show that the majority (66.3%) of the students have a good knowledge of hydration. However, the skewed distribution of the knowledge scores suggests that some may have lower levels of knowledge, which may warrant further study to improve knowledge in those students.

Abstract

Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa's most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures.

Abstract

Introduction: Antimicrobial resistance (AMR) is a concern as this increases morbidity, mortality, and costs, with sub-Saharan Africa having the highest rates globally. Concerns with rising AMR have resulted in international, Pan-African, and country activities including the development of national action plans (NAPs). However, there is variable implementation across Africa with key challenges persisting.

Areas covered: Consequently, there is an urgent need to document current NAP activities and challenges across sub-Saharan Africa to provide future guidance. This builds on a narrative review of the literature.

Expert opinion: All surveyed sub-Saharan African countries have developed their NAPs; however, there is variable implementation. Countries including Botswana and Namibia are yet to officially launch their NAPs with Eswatini only recently launching its NAP. Cameroon is further ahead with its NAP than these countries; though there are concerns with implementation. South Africa appears to have made the greatest strides with implementing its NAP including regular monitoring of activities and instigation of antimicrobial stewardship programs. Key challenges remain across Africa. These include available personnel, expertise, capacity, and resources to undertake agreed NAP activities including active surveillance, lack of focal points to drive NAPs, and competing demands and priorities including among donors. These challenges are being addressed, with further co-ordinated efforts needed to reduce AMR.

Abstract

Objectives: The understanding of antimicrobial utilization patterns is pertinent to successful implementation of the National Action Plans on Antimicrobial Resistance (AMR). There is, however, limited information on antibiotics utilization in Nigeria. This study was undertaken to build on existing information and provide direction for appropriate interventions including Antibiotics Stewardship Programs (ASP).

Method: A Point Prevalence Study (PPS) was conducted in two public urban health facilities in Lagos, Nigeria using a design adapted from the European Center for Disease Prevention and Control (ECDC) and Global-PPS surveys.

Results: The prevalence of antibiotics use was 80.6% administered mostly parenterally (83.1% of total prescriptions) with concerns with extended surgical antibiotics prophylaxis. The mostly used antibiotics in the secondary hospital were parenteral metronidazole (32.4%), ceftriaxone (27.5%), and amoxicillin + clavulanate (8.2%) while the mostly used in the tertiary hospital were ceftriaxone (25.3%), parenteral metronidazole (19.1%), and amoxicillin + clavulanate (9.3%). There was an appreciable lack of specific functional capacities, policies, and processes to promote appropriate antimicrobial use in both hospitals.

Conclusions: There is high rate of antibiotics utilization in these facilities with lack of institutional frameworks and processes for ensuring appropriate antibiotic use. The study provides the information needed to improve future antimicrobial use in hospitals and reduce AMR.

ABSTRACT

Outbreaks of infection occur more often than they are reported in most developing countries, largely due to poor diagnostic services. A Klebsiella species bacteremia outbreak in a newborn unit with high mortality was recently encountered at a location being surveilled for childhood bacteremia. These surveillance efforts offered the opportunity to determine the cause of this neonatal outbreak. In this report, we present the whole-genome sequences of New Delhi metallo-β-lactamase (NDM-5)-containing Klebsiella quasipneumoniae subsp. similipneumoniae bloodstream isolates from a neonatal bacteremia outbreak at a tertiary hospital in Nigeria and as part of the largest collection of K. pneumoniae bloodstream isolates from children in Africa. Comparative analysis of the genetic environment surrounding the NDM-5 genes revealed nearly perfect sequence identity to bla_NDM-5-bearing IncX3-type plasmids from other members of the Enterobacteriaceae.

Abstract

Background: Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt-PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture.

Methods: Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples.

Results: A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4-90.1%) and 62.5% (95% CI 24.5-91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture.

Conclusions: Rt-PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as S. pneumoniae by rt-PCR despite growth of a non-S. pneumoniae pathogen on culture. A precise definition of what constitutes a positive result is required to avoid falsely over-identifying specimens.