Structure-Activity Relationship Study to Develop Peptide Amphiphiles as Species-Specific Antimicrobials.

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.

3D Printed Materials for Combating Antimicrobial Resistance.

Three-dimensional (3D) printing is a rapidly growing technology with a significant capacity for translational applications in both biology and medicine. 3D-printed living and non-living materials are being widely tested as a potential replacement for conventional solutions for testing and combating antimicrobial resistance (AMR). The precise control of cells and their microenvironment, while simulating the complexity and dynamics of an in vivo environment, provides an excellent opportunity to advance the modeling and treatment of challenging infections and other health conditions. 3D-printing models the complicated niches of microbes and host-pathogen interactions, and most importantly, how microbes develop resistance to antibiotics. In addition, 3D-printed materials can be applied to testing and delivering antibiotics. Here, we provide an overview of 3D printed materials and biosystems and their biomedical applications, focusing on ever increasing AMR. Recent applications of 3D printing to alleviate the impact of AMR, including developed bioprinted systems, targeted bacterial infections, and tested antibiotics are presented.

Molecular characterization of Streptococcus pneumoniae causing disease among children in Nigeria during the introduction of PCV10 (GSK).

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (n=189) and Abuja (n=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, n=35), 6B (16 %, n=31), 1 (9 %, n=17), 5 (9 %, n=17) and 6A (9 %, n=17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance.

Polyethylene Glycol-Mediated Directional Conjugation of Biological Molecules for Enhanced Immunoassays at the Point-of-Care.

Rapid and reliable point-of-care (POC) diagnostic tests can have a significant impact on global health. One of the most common approaches for developing POC systems is the use of target-specific biomolecules. However, the conjugation of biomolecules can result in decreased activity, which may compromise the analytical performance and accuracy of the developed systems. To overcome this challenge, we present a polymer-based cross-linking protocol for controlled and directed conjugation of biological molecules. Our protocol utilizes a bifunctional thiol-polyethylene glycol (PEG)-hydrazide polymer to enable site-directed conjugation of IgG antibodies to the surface of screen-printed metal electrodes. The metal surface of the electrodes is first modified with thiolated PEG molecules, leaving the hydrazide groups available to react with the aldehyde group in the Fc fragments of the oxidized IgG antibodies. Using anti-Klebsiella pneumoniae carbapenemase-2 (KPC-2) antibody as a model antibody used for antimicrobial resistance (AMR) testing, our results demonstrate a ~10-fold increase in antibody coupling compared with the standard N-hydroxysuccinimide (NHS)-based conjugation chemistry and effective capture (>94%) of the target KPC-2 enzyme antigen on the surface of modified electrodes. This straightforward and easy-to-perform strategy of site-directed antibody conjugation can be engineered for coupling other protein- and non-protein-based biological molecules commonly used in POC testing and development, thus enhancing the potential for improved diagnostic accuracy and performance.

Fatal Primary Amebic Meningoencephalitis in Nebraska: Case Report and Environmental Investigation, August 2022.

Primary amebic meningoencephalitis (PAM) is a rare and lethal infection caused by Naegleria fowleri. We report an epidemiological and environmental investigation relating to a case of PAM in a previously healthy boy age 8 years. An interview of the patient's family was conducted to determine the likely exposure site and to assess risk factors. Data from the United States Geological Survey site at Waterloo, NE, on the Elkhorn River were used to estimate water temperature and streamflow at the time and site of exposure. Data from the National Weather Service were used to estimate precipitation and ambient air temperature at the time and site of exposure. Despite conventional treatment, the patient died 2 days after hospital admission. The patient participated in recreational water activities in the Elkhorn River in northeastern Nebraska 5 days before symptom onset. In the week before exposure, water and ambient air high temperatures reached annual highs, averaging 32.4°C and 35.8°C, respectively. The day before infection, 2.2 cm of precipitation was reported. Streamflow was low (407 ft3/s). Infections in several northern states, including Nebraska, suggest an expanding geographic range of N. fowleri transmission, which may lead to increased incidence of PAM in the United States. Similar environmental investigations at suspected exposure sites of future cases will allow data aggregation, enabling investigators to correlate environmental factors with infection risk accurately.

Phenotypic and molecular characterization of beta-lactam resistant Multidrug-resistant Enterobacterales isolated from patients attending six hospitals in Northern Nigeria.

Infections caused by multi-drug resistant Enterobacterales (MDR-E) are difficult to treat and cause significant mortality, especially in developing countries. This study characterized the phenotypic and genotypic profiles of 49 randomly selected beta-lactam resistant MDR-E previously isolated from patients being managed in hospitals in Nigeria using whole genome sequencing. The study isolates exhibited 85.5% resistance to 3rd generation cephalosporins and 65.3% resistance to carbapenems. The blaTEM-1B (29, 59.2%), blaCTX-M-15 (38, 77.6%), and blaNDM-1 (17, 51.5%) were the most common penicillinase, ESBL, and carbapenem resistant genes across isolates, respectively. Seventeen (45%) of blaCTX-M-15 was carried on the insertion sequence ISEc9 while blaNDM-1 (11, 64.7%) were associated with ISEc33. None of the 21 plasmids detected were associated with ß-lactamase genes. Higher resistance rates were found in E. coli ST-88 (n = 2) and the high-risk ST-692 (n = 2). For Klebsiella species, the high-risk clones ST-476 (n = 8) and ST-147 (n = 3) predominated and had higher phenotypic resistance rates and higher number of AMR genes. The mechanisms and pattern of antibiotic resistance differ from patterns previously described with isolates harbouring a wide range of AMRGs. The detection of several chromosomally mediated carbapenemases in our study also represents a significant finding that warrants further investigation to better understand its' implications for clinical practice and public health. The selected MDR-Es were found to be pan-susceptible to tigecycline and had very low resistance to fosfomycin, suggesting a potential for these as empiric treatments. A surveillance approach incorporating both conventional laboratory techniques and modern molecular techniques is essential for the comprehensive characterization of the emergence and dissemination of antimicrobial resistance in Enterobacterales infections within Nigeria.

Antimicrobial resistance and virulence genes of invasive Salmonella enterica from children with bacteremia in north-central Nigeria.

Objectives: Bacteremia due to invasive Salmonella enterica has been reported earlier in children in Nigeria. This study aimed to detect the virulence and antibiotic resistance genes of invasive Salmonella enterica from children with bacteremia in north-central Nigeria. Method: From June 2015 to June 2018, 4163 blood cultures yielded 83 Salmonella isolates. This is a secondary cross-sectional analysis of the Salmonella isolates. The Salmonella enterica were isolated and identified using standard bacteriology protocol. Biochemical identifications of the Salmonella enterica were made by Phoenix MD 50 identification system. Further identification and confirmation were done with polyvalent antisera O and invA gene. Antimicrobial susceptibility testing was done following clinical and laboratory standard institute guidelines. Resistant genes and virulence genes were determined using a real-time polymerase chain reaction. Result: Salmonella typhi 51 (61.4%) was the most prevalent serovar, followed by Salmonella species 13 (15.7%), choleraesuis 8 (9.6%), enteritidis 6 (7.2%), and typhimurium 5 (6.1%). Fifty-one (61.4%) of 83 Salmonella enterica were typhoidal, while 32 (38.6%) were not. Sixty-five (78.3%) of the 83 Salmonella enterica isolates were resistant to ampicillin and trimethoprim-sulfamethoxazole, followed by chloramphenicol 39 (46.7%), tetracycline 41 (41.4%), piperacillin 33 (33.9%), amoxicillin-clavulanate, and streptomycin 21 (25.3%), while cephalothin was 19 (22.9%). Thirty-nine (46.9%) of the 83 Salmonella enterica isolates were multi-drug resistant, and none were extensive drug resistant or pan-drug resistant. A blaTEM 42 (50.6%), floR 32 (38.6%), qnrA 24 (28.9%), tetB 20 (20.1%), tetA 10 (10.0%), and tetG 5 (6.0%) were the antibiotic resistance genes detected. There were perfect agreement between phenotypic and genotypic detection of antimicrobial resistance in tetracycline, ciprofloxacin, and chloramphenicol, while beta-lactam showed κ = 0.60 agreement. All of the Salmonella enterica isolates had the virulence genes invA, sopB, mgtC, and sip4D, while 33 (39.8%), 45 (51.8%), and 2 (2.4%) had ssaQ, spvC, and ljsGI-1, respectively. Conclusion: Our findings showed multi-drug resistant Salmonella enterica in children with bacteremia in northern Nigeria. In addition, significant virulence and antimicrobial resistance genes were found in invasive Salmonella enterica in northern Nigeria. Thus, our study emphasizes the need to monitor antimicrobial resistance in Salmonella enterica from invasive sources in Nigeria and supports antibiotic prudence.

Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study.

BACKGROUND: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context. METHODS: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590). FINDINGS: Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3-5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain. INTERPRETATION: Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases. FUNDING: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.

Antimicrobial resistance and virulence genes in Salmonella enterica serovars isolated from droppings of layer chicken in two farms in Nigeria.

AIM: This study aimed to investigate the isolation rate, antibiotic resistance and virulence genes of Salmonella enterica serovar from two commercial farms in Nigeria. METHODS AND RESULTS: Salmonella isolation was performed according to the United States Food and Drug Agency (USFDA) method. Serotyping, antimicrobial susceptibility testing, detection of resistance and virulence genes were done using the Kauffman-White Scheme, disc diffusion, minimum inhibitory concentration and real-time polymerase chain reaction techniques. Salmonella serovars were isolated from only farm A at 22/50 (44.0%) while none were isolated from farm B. Salmonella Typhi, 9 (40.9%); Salmonella Typhimurium, 2 (9.1%), Salmonella Enteritidis, 2 (9.1%), Salmonella Pullorum, 1 (4.5%), Salmonella Kentucky, 4 (18.2%) were identified while 4 (18.2%) were untypable. Sixteen isolates (72.7%) showed multiple drug resistance and 17 different resistance profile types with AMP-CHL-TRM-SXT as the most prevalent pattern. Resistance genes (blaTEM, 12/22 (54.5%) and virulence genes (InvA, sopB, mgtC and spi4D, 22/22 (100.0%), ssaQ, 16/22 (72.7%) and spvC, 13/22 (59.1%) were found, while blaSHV, blaCTX-M, floR, tetA, tetB, tetG and LJSGI-1 genes were absent. CONCLUSION: Pathogenic Salmonella were isolated from the chicken droppings in this study. Most of these strains were resistant to antibiotics and possessed characteristics of virulence. SIGNIFICANCE AND IMPACT OF THE STUDY: Chicken droppings from this study area contained pathogenic strains of Salmonella and a rare occurrence of Salmonella Typhi. The study revealed that the environment and the food chain could be at risk of contamination of highly virulent and antimicrobial-resistant strains of Salmonella. These could affect the profitability of the poultry industry and food consumption. There is a need for caution in indiscriminate disposal of poultry waste and the use of uncomposted chicken droppings in soil amendment.

A Prospective Cohort Study of the Clinical Predictors of Bacteremia in Under-Five Children With Acute Undifferentiated Fever Attending a Secondary Health Facility in Northwestern Nigeria.

BACKGROUND: Children with acute febrile illness with no localizing signs often receive antibiotics empirically in most resource-poor settings. However, little is known about the burden of bacteremia in this category of patients, and an appraisal is thus warranted. This will guide clinical practice and promote rational antibiotics use. METHODS: We prospectively followed up 140 under-five children who presented with acute undifferentiated fever at the emergency/outpatient pediatric unit of a secondary healthcare facility. Baseline clinical and laboratory information was obtained and documented in a structured questionnaire. We compared baseline characteristics between participants with bacteremia and those without bacteremia. We further fitted a multivariable logistic regression model to identify factors predictive of bacteremia among the cohort. RESULT: The prevalence of bacteremia was 17.1%, and Salmonella Typhi was the most frequently (40.9%) isolated pathogen. The majority (78.6%) of the study participants were managed as outpatients. The participants who required admission were four times more likely to have bacteremia when compared to those managed as outpatients (AOR 4.08, 95% CI 1.19 to 14.00). There is a four times likelihood of bacteremia (AOR 4.75, 95% CI 1.48 to 15.29) with a fever duration of beyond 7 days. Similarly, participants who were admitted with lethargy were six times more likely to have bacteremia (AOR 6.20, 95% CI 1.15 to 33.44). Other significant predictors were tachypnea and lymphopenia. CONCLUSION: Among under-five children with acute undifferentiated fever, longer duration of fever, lethargy, inpatient care, tachypnea, and lymphopenia were the significant predictors of bacteremia.

Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism.

Hyper-virulent Streptococcus pneumoniae serotype 1 strains are endemic in Sub-Saharan Africa and frequently cause lethal meningitis outbreaks. It remains unknown whether genetic variation in serotype 1 strains modulates tropism into cerebrospinal fluid to cause central nervous system (CNS) infections, particularly meningitis. Here, we address this question through a large-scale linear mixed model genome-wide association study of 909 African pneumococcal serotype 1 isolates collected from CNS and non-CNS human samples. By controlling for host age, geography, and strain population structure, we identify genome-wide statistically significant genotype-phenotype associations in surface-exposed choline-binding (P = 5.00 × 10-08) and helicase proteins (P = 1.32 × 10-06) important for invasion, immune evasion and pneumococcal tropism to CNS. The small effect sizes and negligible heritability indicated that causation of CNS infection requires multiple genetic and other factors reflecting a complex and polygenic aetiology. Our findings suggest that certain pathogen genetic variation modulate pneumococcal survival and tropism to CNS tissue, and therefore, virulence for meningitis.

Paper-based microchip electrophoresis for point-of-care hemoglobin testing.

Nearly 7% of the world's population live with a hemoglobin variant. Hemoglobins S, C, and E are the most common and significant hemoglobin variants worldwide. Sickle cell disease, caused by hemoglobin S, is highly prevalent in sub-Saharan Africa and in tribal populations of Central India. Hemoglobin C is common in West Africa, and hemoglobin E is common in Southeast Asia. Screening for significant hemoglobin disorders is not currently feasible in many low-income countries with the high disease burden. Lack of early diagnosis leads to preventable high morbidity and mortality in children born with hemoglobin variants in low-resource settings. Here, we describe HemeChip, the first miniaturized, paper-based, microchip electrophoresis platform for identifying the most common hemoglobin variants easily and affordably at the point-of-care in low-resource settings. HemeChip test works with a drop of blood. HemeChip system guides the user step-by-step through the test procedure with animated on-screen instructions. Hemoglobin identification and quantification is automatically performed, and hemoglobin types and percentages are displayed in an easily understandable, objective way. We show the feasibility and high accuracy of HemeChip via testing 768 subjects by clinical sites in the United States, Central India, sub-Saharan Africa, and Southeast Asia. Validation studies include hemoglobin E testing in Bangkok, Thailand, and hemoglobin S testing in Chhattisgarh, India, and in Kano, Nigeria, where the sickle cell disease burden is the highest in the world. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. Study design, methods, and results are presented according to the Standards for Reporting Diagnostic Accuracy (STARD). HemeChip correctly identified all subjects with hemoglobin S, C, and E variants with 100% sensitivity, and displayed an overall diagnostic accuracy of 98.4% in comparison to reference standard methods. HemeChip is a versatile, mass-producible microchip electrophoresis platform that addresses a major unmet need of decentralized hemoglobin analysis in resource-limited settings.

Pulmonary hypertension and right ventricular function in Nigerian children with sickle cell anaemia.

BACKGROUND: Pulmonary hypertension (PH), a complication of sickle cell anaemia (SCA), results in considerable morbidity. This study aims to determine the prevalence and associations of echocardiography-suggested PH in children with SCA. METHODS: We performed a cross-sectional comparative study involving 100 systematically sampled SCA subjects 3-14 y of age in their steady state with matched haemoglobin AA phenotype controls. Clinical, laboratory and echocardiography data (including tricuspid regurgitation velocity [TRV], mean pulmonary arterial pressure [mPAP] and tricuspid annular plane systolic excursion [TAPSE]) were obtained from all patients. Statistical analyses were performed using SPSS version 22 (IBM, Armonk, NY, USA). A p-value <0.05 was considered statistically significant. RESULTS: Of the 100 SCA subjects studied, 22 (22%) had echocardiographic findings suggestive of PH compared with none in the controls. The median TAPSE was significantly lower in the PH group (2.55 cm [interquartile range {IQR} 2.2-2.8]) compared with the no PH group (2.77 cm [IQR 2.4-3.2]) (p=0.03). No significant correlation existed between mPAP and age, nor any laboratory parameters studied. The odds ratio (OR) suggested PH significantly increased with an increase in the frequency of hospitalizations for vaso-occlusive crises within a 12-month period (OR 15.15 [95% CI 1.57 to 146.35], p=0.02) and a lifetime history of blood transfusion (OR 5.44 [95% CI 1.09 to 27.24], p=0.04). CONCLUSIONS: Echocardiography-suggested PH is common in children with SCA and is associated with poorer right ventricular function, frequent vaso-occlusive crises and blood transfusions.

Emergence of New Delhi Metallo-ß-Lactamase (NDM-5) in Klebsiella quasipneumoniae from Neonates in a Nigerian Hospital.

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-ß-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 blaNDM-5-bearing IncX3-type plasmids from other members of the EnterobacteriaceaeIMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is of global health importance, yet there is a paucity of genome-based studies in Africa. Here we report fatal blood-borne NDM-5-producing K. quasipneumoniae subsp. similipneumoniae infections from Nigeria, Africa. New Delhi metallo-ß-lactamase (NDM)-producing Klebsiella spp. are responsible for high mortality and morbidity, with the NDM-5 variant showing elevated carbapenem resistance. The prevalence of NDM-5 in Klebsiella has been limited primarily to K. pneumoniae, with only one isolate being collected from Africa. During an outbreak of sepsis in a teaching hospital in Nigeria, five NDM-5-producing K. quasipneumoniae subsp. similipneumoniae sequence type 476 isolates were identified. Given the increased resistance profile of these strains, this study highlights the emerging threat of blaNDM-5 dissemination in hospital environments. The observation of these NDM-5-producing isolates in Africa stresses the urgency to improve monitoring and clinical practices to reduce or prevent the further spread of resistance.

Dry Gangrene in Children with Typhoid Intestinal Perforation: A Report of Two Cases.

Intestinal perforation is a life-threatening complication of typhoid fever commonly seen in developing countries, but extraintestinal complications are infrequently reported. We report herein two cases of gangrene seen in children managed for typhoid intestinal perforation, highlighting the challenges faced in their management.

Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link?

Non-typhoidal Salmonella usually induces self-limiting gastroenteritis. However, in many parts of Africa, especially in individuals who are malnourished, infected with malaria, or have sickle cell disease, the organism causes serious and potentially fatal systemic infections. Since the portal of entry of non-typhoidal Salmonella into the systemic circulation is by way of the intestine, we argue that an increased gut permeability plays a vital role in the initiation of invasive non-typhoidal Salmonella in these patients. Here, we will appraise the evidence supporting a breach in the intestinal barrier and propose the mechanisms for the increased risks for invasive non-typhoidal Salmonella infections in these individuals.

Detection of Streptococcus pneumoniae from culture-negative dried blood spots by real-time PCR in Nigerian children with acute febrile illness.

OBJECTIVES: Acute febrile illness is a common cause of hospital admission, and its associated infectious causes, of which a key bacterial causative agent is Streptococcus pneumoniae, contribute to substantial morbidity and mortality. We sought to evaluate the utility of real-time (rt)-PCR on dried blood spots (DBS) for diagnosis of S. pneumoniae in acute febrile illness among children presenting to hospitals in Nigeria. We previously described preliminary results in a sample of 537 patients. Here we present data from a larger collection of 1038 patients. RESULTS: Using rt-PCR for Streptococcus pneumoniae on 1038 dried blood spots from children prospectively enrolled with acute febrile illness, including 79 healthy controls, we detected pneumococcal DNA in nine of 15 blood culture-positive specimens, one culture-negative specimen from a high-risk group, a culture-confirmed non-pneumococcal specimen and a healthy control. Six culture-positive isolates (40%) were negative. Sensitivity was 60%, specificity 99.7%, positive predictive value 75% and negative predictive value 99.4%. Rt-PCR of DBS has limited sensitivity in blood specimens from acute febrile illness in children.

Typhoid Fever: Tracking the Trend in Nigeria.

Typhoid fever continues to pose a serious health challenge in developing countries. A reliable database on positive blood cultures is essential for prompt interventions. To generate reliable data on Salmonella enterica serovar Typhi (S. Typhi)-positive blood culture trends in typhoidal Salmonella in Nigeria alongside changing contextual factors and antimicrobial resistance patterns, a retrospective cohort study was conducted in two hospitals in Lagos between 1993 and 2015. Medical records of typhoid patients were reviewed for positive culture and antibiogram, using standard procedures and analyzed. Additional data were retrieved from a previous study in seven facilities in Abuja and three hospitals in Kano from 2008 to 2017 and 2013 to 2017, respectively. A declining trend in percent positivity of S. Typhi was observed in Abuja with more erratic trends in Lagos and Kano. In Lagos, more than 80% of the isolates from the entire study period exhibited multiple drug resistance with a generally increasing trend. Of the chosen contextual factors, improvements were recorded in female literacy, access to improved water supply, diarrheal mortality in children younger than 5 years, gross domestic product, and poverty while access to improved sanitation facilities decreased over time nationally. Typhoid fever still poses a serious health challenge in Nigeria and in antibiotic resistance, and is a major health security issue. A combined approach that includes the use of typhoid vaccines, improvements in sanitation, and safe water supply is essential.

A meta-analysis of antimicrobial susceptibility profiles for pneumococcal pneumonia in sub-Saharan Africa.

BACKGROUND: Pneumonia causes an enormous burden of childhood disease globally, particularly in low- and middle-income countries. Pneumococcus is the most common bacterial aetiology of pneumonia; however, antimicrobials are limited and may not adequately address the local epidemiology of the region. AIM: To undertake a review and meta-analysis of pneumonia studies in sub-Saharan Africa to evaluate antimicrobial susceptibility patterns in childhood pneumonia. METHODS: Articles published in PubMed and Google between 2006 and 2016 which evaluated antimicrobial susceptibility profiles of pneumococcal pneumonia in children in sub-Saharan Africa were identified. The source of specimens, pathogens and antimicrobial susceptibility data were extracted. Pooled analysis of susceptible isolates was conducted using random effects models. RESULTS: Children from 15 studies and 1634 isolates were included in the meta-analysis. In cases of childhood pneumonia, the mean overall proportion of penicillin susceptibility from invasive specimens of Streptococcus pneumoniae was 85.7% (95% CI 80.1-91.3), and of trimethoprim-sulfamethoxazole was 21.0% (95% CI 5.1-36.9). Compared with all S. pneumoniae specimens, penicillin susceptibility was 68.6% (95% CI 59.6-77.5) and that of trimethoprim-sulfamethoxazole was 26.3% (95% CI 14.1-38.6). CONCLUSIONS: A high level of heterogeneity was detected, reflecting the paucity of data available. The establishment of national and regional diagnostic platforms to monitor antimicrobial susceptibility profiles for pneumonia as well as other invasive diseases will provide data with which to assess the relevance and adaptation of antimicrobial prescribing recommendations.