Establishing a national reference laboratory for antimicrobial resistance using a whole-genome sequencing framework: Nigeria's experience.

Whole-genome sequencing (WGS) is finding important applications in the surveillance of antimicrobial resistance (AMR), providing the most granular data and broadening the scope of niches and locations that can be surveilled. A common but often overlooked application of WGS is to replace or augment reference laboratory services for AMR surveillance. WGS has supplanted traditional strain subtyping in many comprehensive reference laboratories and is now the gold standard for rapidly ruling isolates into or out of suspected outbreak clusters. These and other properties give WGS the potential to serve in AMR reference functioning where a reference laboratory did not hitherto exist. In this perspective, we describe how we have employed a WGS approach, and an academic-public health system collaboration, to provide AMR reference laboratory services in Nigeria, as a model for leapfrogging to national AMR surveillance.

Serum cytokine profile of pregnant women with malaria, intestinal helminths and HIV infections in Ibadan, Nigeria.

Malaria, helminthiasis and HIV are widespread in developing countries taking a heavy toll on pregnant women. Due to similar environmental and human factors of transmission, they co-exist. The epidemiology and pathology of these diseases have been extensively studied but data on serum cytokine profile changes which is crucial in pregnancy is limited. The aim of this study was to evaluate the co-infections and their impact on peripheral blood cytokines. Blood and stool samples were collected from recruited 18-45-year-old pregnant women in different trimesters who were apparently healthy with no obvious complications in pregnancy. Pretested questionnaires were administered for personal and socio-demographic details. Malaria parasitemia in Giemsa-stained thick blood films was examined microscopically. Stool samples were screened for helminths using Kato-Katz method. Cytokine levels of TNF-α, IFN-γ, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and IL-17 in 121 serum samples were determined using ELISA. Data were analysed using descriptive statistics and Mann-Whitney U test at α0.05. Relative to the single infections, there were significant reductions in IFN-γ and IL-13 in second and third trimesters respectively in those with Plasmodium and helminth co-infection. IFN-γ and IL-17 were elevated while IL-1α and IL-12p70 were reduced in co-infection of helminths and HIV. Co-infection of Plasmodium and HIV in second and third trimesters showed significant elevations in IL-1α, IL-10 and IL-17 while TNF-α, IL-4 and IL-12p70 were significantly reduced. HIV in pregnancy and its co-infection with Plasmodium resulted in significant distortions in the cytokine profile. However, helminth and its co-infection with Plasmodium or HIV produced less changes in the cytokine profile.

Non-Malaria Causes of Fever among under-5 Children with Negative Results for Malaria Rapid Diagnostic Test in South-Western Nigeria.

BACKGROUND: Although the global malaria burden is decreasing, there are still concerns about overdiagnosis of malaria and the danger of misdiagnosis of non-malaria causes of fever. Clinicians continue to face the challenge of differentiating between these causes despite the introduction of malaria rapid diagnostic tests (mRDTs). AIM: To determine the prevalence and causes of non-malaria-caused fever in children in South-Western Nigeria. METHODS: Secondary analysis of data obtained to evaluate the effect of restricting antimalarial treatment to positive mRDT children in rural and urban areas of southwest Nigeria. Clinical examinations, laboratory tests for malaria parasites (including thick blood film and mRDT) and bacterial identification were performed on children aged 3-59 months (n = 511). The non-malaria group comprised febrile children who had both negative mRDT and microscopy results, while the malaria group included those who were positive for either mRDT or microscopy. We compared the causes of fever among children with non-malaria fever and those with malaria. RESULTS: The prevalence of non-malaria fever and bacteria-malaria co-infection was 37.2% and 2.0%, respectively. Non-malarial pathogens identified were viral (54.7%) and bacterial (32.1%) infections. The bacterial infections included bacteriaemia (2.7%), urinary tract infections (21.6%), skin infections (11.6%) and otitis media (2.6%). The leading bacterial isolates were Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae. CONCLUSION: The high prevalence and wide range of non-malarial infections reinforces the need for point-of-care tests to identify bacterial and viral infections to optimize the treatment of febrile illnesses in malaria-endemic areas.

Targeted polymerase chain reaction-based expression of putative halitogenic bacteria and volatile sulphur compound analysis among halitosis patients at a tertiary hospital in Nigeria.

Halitosis (bad breath) can be a cause of anxiety, depression and psychosocial stress, with pathological changes in the oral microbiota playing an important role in its development. Despite its prevalence, studies on the microbiology of halitosis are rare in Nigeria. This study determines the presence of five putative periodontal pathogens viz: Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola on the tongue dorsa of halitosis and non-halitosis patients using a 16S rDNA-directed polymerase chain reaction assay. Furthermore, an association of these bacteria with oral malodour [as assessed by volatile sulphur compounds (VSC) measurements] with a portable sulphide monitor, the Halimeter (Interscan Corp, Chatsworth, California), was performed. The results showed that the prevalence of halitosis in this environment as defined by VSC level above 160 ppb is 14.9%. Halitosis is affected by gender with males having it more than the females. Males also tend to present more with self-reported complaints of halitosis than females. Age does not appear to contribute to the incidence of halitosis. Fusobacterium nucleatum, P. gingivalis, P. intermedia are responsible for increased production of VSCs in halitosis patients while A. actinomycetemcomitans and T. denticola appear to play no part in the production of VSCs. Evaluation of halitogenic bacteria and VSCs may potentially become a surrogate biomarker for monitoring halitosis. Targeted assessment of putative halitogenic bacteria may provide a rapid point-of-care diagnostic tool for halitosis.

Consequences of restricting antimalarial drugs to rapid diagnostic test-positive febrile children in south-west Nigeria.

OBJECTIVES: To investigate the consequence of restricting antimalarial treatment to febrile children that test positive to a malaria rapid diagnostic test (MRDT) only in an area of intense malaria transmission. METHODS: Febrile children aged 3-59 months were screened with an MRDT at health facilities in south-west Nigeria. MRDT-positive children received artesunate-amodiaquine (ASAQ), while MRDT-negative children were treated based on the clinical diagnosis of non-malaria febrile illness. The primary endpoint was the risk of developing microscopy-positive malaria within 28 days post-treatment. RESULTS: 309 (60.5%) of 511 children were MRDT-positive while 202 (39.5%) were MRDT-negative at enrolment. 18.5% (50/275) of MRDT-positive children and 7.6% (14/184) of MRDT-negative children developed microscopy-positive malaria by day 28 post-treatment (ρ = 0.001). The risk of developing clinical malaria by day 28 post-treatment was higher among the MRDT-positive group than the MRDT-negative group (adjusted OR 2.74; 95% CI, 1.4, 5.4). A higher proportion of children who were MRDT-positive at enrolment were anaemic on day 28 compared with the MRDT-negative group (12.6% vs. 3.1%; ρ = 0.001). Children in the MRDT-negative group made more unscheduled visits because of febrile illness than those in MRDT-positive group (23.2% vs. 12.0%; ρ = 0.001). CONCLUSION: Restricting ACT treatment to MRDT-positive febrile children only did not result in significant adverse outcomes. However, the risk of re-infection within 28 days was significantly higher among MRDT-positive children despite ASAQ treatment. A longer-acting ACT may be needed as the first-line drug of choice for treating uncomplicated malaria in high-transmission settings to prevent frequent re-infections.

CONSÉQUENCES DE LA RESTRICTION DES ANTIPALUDIQUES AUX ENFANTS FÉBRILES POSITIFS AU TEST DE DIAGNOSTIC RAPIDE DANS LE SUD-OUEST DU NIGÉRIA: OBJECTIFS: Investiguer la conséquence de restreindre le traitement antipaludéen uniquement à des enfants fébriles avec un résultat positif à un test de diagnostic rapide (TDR) du paludisme dans une zone de forte transmission du paludisme. MÉTHODES: Les enfants fébriles âgés de 3 à 59 mois ont été dépistés avec un TDR du paludisme dans des établissements de santé du sud-ouest du Nigéria. Les enfants avec un TDR positif ont reçu de l'artésunate-amodiaquine (ASAQ), tandis que ceux avec un TDR négatif ont été traités sur la base du diagnostic clinique de maladie fébrile non liée au paludisme. Le critère d'évaluation principal était le risque de développer un paludisme positif au microscope dans les 28 jours suivant le traitement. RÉSULTATS: 309 (60,5%) des 511 enfants étaient positifs au TDR du paludisme tandis que 202 (39,5%) étaient négatifs au moment de leur inscription. 18,5% (50/275) des enfants TDR-positifs et 7,6% (14/184) des enfants TDR-négatifs ont développé un paludisme positif au microscope endéans le jour 28 après le traitement (ρ = 0,001). Le risque de développer un paludisme clinique endéans le 28è jour après le traitement était plus élevé dans le groupe TDR-positif que dans le groupe TDR-négatif (OR ajusté = 2,74; IC95%: 1,4 - 5,4). Une proportion plus élevée d'enfants TDR-positifs au moment de l'inscription étaient anémiques au 28è jour par rapport au groupe TDR-négatif (12,6% contre 3,1%; ρ = 0,001). Les enfants du groupe TDR-négatif ont effectué plus de visites non planifiées en raison d'une maladie fébrile que ceux du groupe TDR-positif (23,2% contre 12,0%; ρ = 0,001). CONCLUSION: Le fait de limiter le traitement de combinaison à l'artémisinine (TCA) aux seuls enfants fébriles présentant un résultat positif au TDR n'a pas eu d'effet indésirable significatif. Cependant, le risque de réinfection dans les 28 jours était significativement plus élevé chez les enfants TDR-positifs malgré le traitement par ASAQ. Un TCA à action prolongée pourrait être nécessaire en tant que médicament de choix en première ligne pour traiter le paludisme sans complications dans les régions à forte transmission afin de prévenir les réinfections fréquentes.

Plant antibacterials: The challenges and opportunities.

Nature possesses an inexhaustible reservoir of agents that could serve as alternatives to combat the growing threat of antimicrobial resistance (AMR). While some of the most effective drugs for treating bacterial infections originate from natural sources, they have predominantly been derived from fungal and bacterial species. However, a substantial body of literature is available on the promising antibacterial properties of plant-derived compounds. In this comprehensive review, we address the major challenges associated with the discovery and development of plant-derived antimicrobial compounds, which have acted as obstacles preventing their clinical use. These challenges encompass limited sourcing, the risk of agent rediscovery, suboptimal drug metabolism, and pharmacokinetics (DMPK) properties, as well as a lack of knowledge regarding molecular targets and mechanisms of action, among other pertinent issues. Our review underscores the significance of these challenges and their implications in the quest for the discovery and development of effective plant-derived antimicrobial agents. Through a critical examination of the current state of research, we give valuable insights that will advance our understanding of these classes of compounds, offering potential solutions to the global crisis of AMR. © 2017 Elsevier Inc. All rights reserved.

SD-Bioline malaria rapid diagnostic test performance and time to become negative after treatment of malaria infection in Southwest Nigerian Children.

Context and Aim: Given the challenges of microscopy, we compared its performance with SD-Bioline malaria rapid diagnostic test (MRDT) and polymerase chain reaction (PCR) and evaluated the time it took for positive results to become negative after treatment of children with acute uncomplicated malaria. Subjects and Methods: We present the report of 485 participants with complete MRDT, microscopy, and PCR data out of 511 febrile children aged 3-59 months who participated in a cohort study over a 12-month period in rural and urban areas of Ibadan, Nigeria. MRDT-positive children received antimalaria and tested at every visit over 28 days. Speciation was also carried out by PCR. Results: With microscopy as the gold standard, SD-Bioline™ had 95.2% sensitivity, 66.4% specificity, 67.5% positive predictive value (PPV), and 94.9 negative predictive value (NPV), while with PCR the findings were 84.3% sensitivity, 66.5% specificity, 72.7% PPV, and 80.1% NPV. PCR speciation of malaria parasites revealed 91.6% Plasmodium falciparum, 18.9% Plasmodium malariae, and 4.4% Plasmodium ovale. Among the 47 children with P. malariae infections, 66.0% were coinfected with P. falciparum, while 54.6% cases of P. ovale occurred as coinfections with P. falciparum. The median time to a negative MRDT was 23.2 days, while the median time to a negative malaria microscopy was 3.8 days. The two survival curves were significantly different. Conclusions: The SD-BiolineTM MRDT performed well, with remarkable persistence of rapid test-positive for an average of 23 days post treatment. The prevalence of P. malaria is somewhat greater than expected.

Résumé Contexte et objectif: Compte tenu des défis de la microscopie, nous avons comparé le test de diagnostic rapide du paludisme SD-Bioline (MRDT) avec la réaction en chaîne par polymérase (PCR) et évalué le temps qu'il a fallu pour que des résultats positifs deviennent négatifs après le traitement d'enfants atteints de paludisme aigu non compliqué. Sujets et méthodes: Nous présentons le rapport de 485 participants avec des données complètes de MRDT, de microscopie et de PCR sur 511 enfants fébriles âgés de 3 à 59 mois qui ont participé à une étude de cohorte sur une période de 12 mois dans les zones rurales et urbaines d'Ibadan, Nigeria. Les enfants positifs au MRDT ont reçu un antipaludique et ont été testés à chaque visite pendant 28 jours. La spéciation a également été réalisée par PCR. Résultats: Avec la microscopie comme référence, SD-Bioline TM avait une sensibilité de 95,2 %, une spécificité de 66,4 %, une valeur prédictive positive (VPP) de 67,5 % et une valeur prédictive négative (VPN) de 94,9 %, tandis qu'avec la PCR, les résultats étaient de 84,3 % de sensibilité, 66,5 % de spécificité, 72,7 % de VPP et 80,1 % de VPN. La spéciation par PCR des parasites du paludisme a révélé 91,6 % de Plasmodium falciparum, 18,9 % de Plasmodium malariae et 4,4 % de Plasmodium ovale. Parmi les 47 enfants atteints d'infections à P. malariae, 66,0 % étaient co-infectés par P. falciparum, tandis que 54,6 % des cas de P. ovale se sont produits sous forme de co-infections par P. falciparum. Le délai médian jusqu'à un MRDT négatif était de 23,2 jours, tandis que le délai médian jusqu'à une microscopie négative du paludisme était de 3,8 jours. Les deux courbes de survie étaient significativement différentes. Conclusions: Le SD-BiolineTM MRDT a donné de bons résultats, avec une infection à P. malariae un peu plus élevée que attendu dans la population et persistance remarquable des résultats positifs aux tests de diagnostic rapide pendant une moyenne de plus de 23. Mots-clés: Paludisme, microscopie, Nigéria, réaction en chaîne par polymérase, test de diagnostic rapide, spéciationjours après le traitement.

Baseline study for improving diagnostic stewardship at secondary health care facilities in Nigeria.

BACKGROUND: Blood culture diagnostics are critical tools for sepsis management and antimicrobial resistance (AMR) surveillance. A baseline study was conducted to assess reported sepsis case finding, blood culture diagnostics, antimicrobial susceptibility testing (AST) and antimicrobial use at secondary health care facilities to inform the development of diagnostic stewardship improvement strategies in Nigeria. METHODS: A cross-sectional online survey was conducted among 25 public secondary health care facilities in Abuja, Federal Capital Territory (FCT) and Lagos State in Nigeria to evaluate the capacity for pathogen identification and AST. Data were then prospectively extracted on all patients with reported suspected sepsis from electronic medical records from selected departments at two facilities in the Federal Capital Territory from October 2020 to May 2021 to further assess practices concerning sepsis case-finding, clinical examination findings, samples requested, and laboratory test results. Data were descriptively analysed, and a multivariate logistic regression analysis was conducted to determine factors associated with blood culture requests. RESULTS: In the online survey, 32% (8/25) of facilities reported performing blood cultures. Only one had access to a clinical microbiologist, and 28% (7/25) and 4% (1/25) used standard bacterial organisms for quality control of media and quality control strains for AST, respectively. At the two facilities where data abstraction was performed, the incidence of suspected sepsis cases reported was 7.1% (2924/41066). A majority of these patients came from the paediatrics department and were outpatients, and the median age was two years. Most did not have vital signs and major foci of infection documented. Blood cultures were only requested for 2.7% (80/2924) of patients, of which twelve were positive for bacteria, mainly Staphylococcus aureus. No clinical breakpoints were used for AST. Inpatients (adjusted odds ratio [aOR]: 7.5, 95% CI: 4.6-12.3) and patients from the urban health care facility (aOR:16.9, 95% CI: 8.1-41.4) were significantly more likely to have a blood culture requested. CONCLUSION: Low blood culture utilisation remains a key challenge in Nigeria. This has implications for patient care, AMR surveillance and antibiotic use. Diagnostic stewardship strategies should focus on improving access to clinical microbiology expertise, practical guidance on sepsis case finding and improving blood culture utilisation and diagnostics.

Corrigendum: Therapeutic Potentials of Antiviral Plants Used in Traditional African Medicine With COVID-19 in Focus: A Nigerian Perspective.

[This corrects the article DOI: 10.3389/fphar.2021.596855.].

Therapeutic Potentials of Antiviral Plants Used in Traditional African Medicine With COVID-19 in Focus: A Nigerian Perspective.

The coronavirus disease 2019 (COVID-19) pandemic is caused by an infectious novel strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which was earlier referred to as 2019-nCoV. The respiratory disease is the most consequential global public health crisis of the 21st century whose level of negative impact increasingly experienced globally has not been recorded since World War II. Up till now, there has been no specific globally authorized antiviral drug, vaccines, supplement or herbal remedy available for the treatment of this lethal disease except preventive measures, supportive care and non-specific treatment options adopted in different countries via divergent approaches to halt the pandemic. However, many of these interventions have been documented to show some level of success particularly the Traditional Chinese Medicine while there is paucity of well reported studies on the impact of the widely embraced Traditional African Medicines (TAM) adopted so far for the prevention, management and treatment of COVID-19. We carried out a detailed review of publicly available data, information and claims on the potentials of indigenous plants used in Sub-Saharan Africa as antiviral remedies with potentials for the prevention and management of COVID-19. In this review, we have provided a holistic report on evidence-based antiviral and promising anti-SARS-CoV-2 properties of African medicinal plants based on in silico evidence, in vitro assays and in vivo experiments alongside the available data on their mechanistic pharmacology. In addition, we have unveiled knowledge gaps, provided an update on the effort of African Scientific community toward demystifying the dreadful SARS-CoV-2 micro-enemy of man and have documented popular anti-COVID-19 herbal claims emanating from the continent for the management of COVID-19 while the risk potentials of herb-drug interaction of antiviral phytomedicines when used in combination with orthodox drugs have also been highlighted. This review exercise may lend enough credence to the potential value of African medicinal plants as possible leads in anti-COVID-19 drug discovery through research and development.

Malaria, Helminth Infections and Clinical Status Among HIV-Infected Pregnant Women.

BACKGROUND OR OBJECTIVES: Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is widespread in sub-Saharan Africa with similarity in geographical distribution of major pathogens of public health interest. The aim of this study was to assess the effect of malaria and helminths on CD4 count, hematocrit values and viral load among HIV-infected pregnant women. METHODS: One hundred and ninety-seven HIV-infected pregnant women aged 18-45 years were recruited from a registered HIV clinic and questionnaires were administered for socio-demographic details. Screening for malaria parasites in blood was through microscopy while helminths were identified in stool using Kato-Katz method. Hematocrit levels were determined through centrifugation of blood collected in capillary tubes. At the time of recruitment, most recent CD4 count and viral load was obtained from the patients' case notes. RESULTS: About three-quarters (73.6%) of the women had above primary school level of education while more than half (60.2%) were petty traders. The prevalence of malaria parasites in the blood samples was 24.9%, while 3% were infected with helminths. There was only a single case of malaria, helminths and HIV co-infection in the study group. Prevalence of anemia was 75.6% with eight cases (4.1%) of severe anemia. About 86.6% of the women with anemia had low CD4 count (χ2= 8.801, p=0.032). The mean CD4 count was significantly lower among those with co-infection of malaria and HIV. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Malaria or helminth infection among HIV-infected women lowers the CD4 count and increases the viral load with little changes in hematocrit values. Routine screening of HIV-infected women for probable multiple infections will aid in improving their overall health and well-being.

Contributions of malaria, helminths, HIV and iron deficiency to anaemia in pregnant women attending ante-natal clinic in SouthWest Nigeria.

BACKGROUND: Iron deficiency is a dominant source of anaemia in many settings. To evaluate the key cause of anaemia in the study area, the prevalence of anaemia due to major public health diseases was compared with anaemia due to iron deficiency. METHODS: Pregnant women were recruited from ante-natal (n=490) and HIV clinics (n=217) with their personal data documented using a questionnaire. Microscopy of Giemsa-stained thick smears was used for detection of malaria parasites while helminths in stools were detected using direct smear method. Haematocrit values were determined by capillary method. Serum ferritin levels were determined using enzyme-linked immunosorbent assay. Data was analysed using SPSS version 22.0. RESULTS: The mean age of the recruited women was 28.6±5.4 years old. There were 68.1% cases of anaemia of which 35.5% was due to infections only predominantly HIV and malaria, 14.9% from unknown sources while anaemia due to iron deficiency only was 7.1%. CONCLUSION: It can safely be inferred that malaria and HIV predispose to anaemia than iron deficiency in the study area. Although pregnant women are dewormed and given IPTp for helminths and malaria treatment respectively, there should be complementary routine malaria screening at ANC visits for those with HCT values <33% and those infected with HIV.

Malaria at parturition in Nigeria: current status and delivery outcome.

BACKGROUND: To evaluate the current status of malaria at parturition and its impact on delivery outcome in Nigeria. METHODS: A total of 2500 mother-neonate pairs were enrolled at 4 sites over a 12-month period. Maternal and placental blood smears for malaria parasitaemia and haematocrit were determined. RESULTS: Of the 2500 subjects enrolled, 625 were excluded from analysis because of breach in study protocol. The mean age of the remaining 1875 mothers was 29.0 +/- 5.1 years. The prevalence of parasitaemia was 17% and 14% in the peripheral blood and placenta of the parturient women, respectively. Peripheral blood parasitaemia was negatively associated with increasing parity (P < .0001). Maternal age <20 years was significantly associated with both peripheral blood and placental parasitaemia. After adjusting for covariates only age <20 years was associated with placental parasitaemia. Peripheral blood parasitaemia in the women was associated with anaemia (PCV < or =30%) lower mean hematocrit (P < .0001). lower mean birth weight (P < .001) and a higher proportion of low birth weight babies (LBW), (P = .025). CONCLUSION: In Nigeria, maternal age < 20 years was the most important predisposing factor to malaria at parturition. The main impacts on pregnancy outcome were a twofold increase in rate of maternal anaemia and higher prevalence of LBW.

Evaluation of the efficacy and safety of artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in Nigerian infants and children.

BACKGROUND: The six-dose regimen of artemether-lumefantrine (AL) is now considered the gold standard for the treatment of uncomplicated Plasmodium falciparum malaria. There are few reports evaluating co-artemether in very young Nigerian infants and children. Results of the evaluation of the six-dose regimen in very young infants and children in Nigeria are presented in this report. METHODS: As part of a larger African study, this open label, non-comparative trial, assessed the efficacy and safety of six-dose regimen of AL tablets in 103 Nigerian infants and children weighing between five and 25 kg suffering from acute uncomplicated malaria. Treatment was administered under supervision over three days with children as in-patients. 12-lead ECG tracings were taken pre-treatment and at day 3. RESULTS: Ninety-three infants and children completed the study as stipulated by the protocol. Mean fever and parasite clearance times for the intent to treat population (ITT) were 24.9 h +/- (1.28) and 26 h +/- (4.14) and the corresponding figures for the per-protocol population (PP) were 19.24 h +/- 13.9 and 25.62 h +/- 11.25 respectively. Day 14 cure rates for the ITT and PP were 95.1% and 100% respectively while day 28 cure rates were 91.3% and 95.7% respectively. The overall PCR corrected day 28 cure rate was 95.1% for the ITT. The six-dose regimen of AL was well tolerated with no drug-related serious adverse events. Although six patients recorded a QTc prolongation of > 60 ms on D3 over D0 recording, no patient recorded a QTc interval > 500 ms. CONCLUSION: The six-dose regimen of AL tablets is safe and effective for the treatment of acute uncomplicated malaria in Nigerian infants and children weighing between five and 25 kg. TRIAL REGISTRATION: NCT00709969.

Molecular epidemiology of pneumococci obtained from Gambian children aged 2-29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine.

BACKGROUND: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children METHODS: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. RESULTS: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618. CONCLUSION: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia.

Performance of malaria rapid diagnostic test in febrile under-five children at Oni Memorial Children's Hospital in Ibadan, Nigeria, 2016.

INTRODUCTION: The World Health Organization (WHO) recommends testing of suspected malaria cases before treatment. Malaria rapid diagnostic test (mRDT) has been recommended for this purpose in endemic countries where microscopy is not accessible. However, its diagnostic performance remains a concern in clinical settings. We assessed diagnostic performance of RDT among febrile under-five children (U5) presenting at Oni Memorial Children's Hospital, Ibadan (OMCH). METHODS: A cross-sectional study was conducted among 370 febrile U5 attending OMCH February to May, 2016. We examined their finger prick blood samples for malaria parasitaemia using CareStartTM histidine rich protein II (HRP-2) RDT and microscopy. The sensitivity, specificity, positive and negative predictive values (PPV, NPV), false positive (FP), invalid rates (IR), likelihood ratio of positive and negative tests (LRP and LRN), were calculated. RESULTS: Mean age of the children was 28.17 ± 15.59 months. Malaria prevalence was 21.6% and 15.1% by mRDT and microscopy, respectively. Sensitivity of CareStartTM HRP-2 RDT was 94.6% (95% confidence interval (CI): 84.2-98.6), specificity: 91.4% (CI: 87.6-94.2), PPV: 66.3% (CI: 54.7-76.2), NPV: 98.9% (CI: 96.8-99.7), FPR 6.5%, IR 8.1%, LRP:10.6 and LRN:0.1. CONCLUSION: Diagnostic performance of CareStartTM used in the study met the ≥ 95% sensitivity at 100 parasites/µL recommended by WHO. This finding provides clinical evidence that testing before anti-malarial treatment as recommended by WHO will identify cases of malaria infection and reduce unnecessary use of drugs. Healthcare workers should be educated on diagnostic accuracy of mRDT and adhere to the WHO's test-treat strategy for anti-malaria therapy.

Long-lasting insecticidal net use and asymptomatic malaria parasitaemia among household members of laboratory-confirmed malaria patients attending selected health facilities in Abuja, Nigeria, 2016: A cross-sectional survey.

INTRODUCTION: In Nigeria, malaria remains a major burden. There is the presupposition that household members could have common exposure to malaria parasite and use of long-lasting insecticidal net (LLIN) could reduce transmission. This study was conducted to identify factors associated with asymptomatic malaria parasitaemia and LLIN use among households of confirmed malaria patients in Abuja, Nigeria. METHODS: A cross-sectional survey was conducted from March to August 2016 in twelve health facilities selected from three area councils in Abuja, Nigeria. Participants were selected using multi-stage sampling technique. Overall, we recruited 602 participants from 107 households linked to 107 malaria patients attending the health facilities. Data on LLIN ownership, utilization, and house characteristics were collected using a semi-structured questionnaire. Blood samples of household members were examined for malaria parasitaemia using microscopy. Data were analyzed using descriptive statistics, Chi-square, and logistic regression (α = 0.05). RESULTS: Median age of respondents was 16.5 years (Interquartile range: 23 years); 55.0% were females. Proportions of households that owned and used at least one LLIN were 44.8% and 33.6%, respectively. Parasitaemia was detected in at least one family member of 102 (95.3%) index malaria patients. Prevalence of asymptomatic malaria parasitaemia among study participants was 421/602 (69.9%). No association was found between individual LLIN use and malaria parasitaemia (odds ratio: 0.9, 95% confidence interval (95%CI): 0.6-1.3) among study participants. Having bushes around the homes was associated with having malaria parasitaemia (adjusted OR (aOR): 2.7, 95%CI: 1.7-4.2) and less use of LLIN (aOR: 0.4, 95%CI: 0.2-0.9). Living in Kwali (aOR: 0.1, 95% CI: 0.0-0.2) was associated with less use of LLIN. CONCLUSION: High prevalence of asymptomatic malaria and low use of LLIN among household members of malaria patients portend the risk of intra-household common source of malaria transmission. We recommend household health education on LLIN use and environmental management. Study to explore the role of preventive treatment of household members of confirmed malaria patient in curbing transmission is suggested. Strategies promoting LLIN use need to be intensified in Kwali.

Dihydroartemisinin suppository in moderately severe malaria: comparative efficacy of dihydroartemisinin suppository versus intramuscular artemeter followed by oral sulfadoxine-pyrimethamine in the management of moderately severe malaria in Nigerian children.

We compared two dose forms of artemisinin derivatives, dihydroartemisinin suppository (DHA) and intramuscular artemether (ART), in children 6 months to 10 years of age with moderately severe malaria for which oral therapy was not appropriate. Children were randomly allocated to receive three daily doses of DHA or ART followed by a single oral dose of sulfadoxine-pyrimethamine on the third day of both treatment regimens and were monitored for parasitologic and clinical response for 14 days. At enrollment, parasite density was 1,640-523,333/microL (geometric mean parasite density [GMPD] = 58,129/microL) in patients treated with DHA, whereas that for children who received ART was 1,440-559,400/microL (GMPD = 60,387/microL). Mean parasite and fever clearance times were similar in both groups. Days 14 and 28 parasitologic cure rates were 100% (34 of 34) and 96.2% (25 of 26) versus 96.2% (25 of 26) and 91.7% (22 of 24) for children treated with DHA and ART, respectively. In conclusion, both treatment regimens were efficacious and well tolerated.

Prevalence and Etiology of Bacteremia in Febrile Children with Sickle Cell Disease at a Nigeria Tertiary Hospital.

BACKGROUND & OBJECTIVES: As a result of immune defects in Sickle cell disease (SCD), affected individuals are prone to infection from encapsulated bacterial pathogens like Streptococcus Pneumoniae. Studies on the etiological agents of bacteremia in children with SCD in Nigeria are few and have revealed a spectrum of organisms that is different from those recorded in other parts of the world. AIM AND OBJECTIVES: The objectives of this study were to determine the prevalence of bacteremia, etiological agents and antibiotic susceptibility pattern in febrile children with SCD attending the University College Hospital (UCH), Ibadan, Nigeria. METHODS: The study was cross-sectional and took place at the Department of Pediatrics of the UCH, Ibadan. Children with SCD, ages 0-17 years presenting with axillary temperature ≥ 38°C were enrolled after obtaining informed consent. History was obtained and complete physical examination performed after which blood was collected for culture and antibacterial susceptibility tests. RESULTS: A total of 116 children were studied of which 69 (59.5%) were males, 111 (95.7%) were of the Hemoglobin SS phenotype and 5 (4.3%) of the Hemoglobin SC phenotype. Bacteremia was present in 16 (13.8%) of the 116 children. Gram negative bacteria constituted 10 (62.5%) of all isolates, while the predominant isolates were Klebsiella pneumoniae 4, (25%) and Staphylococcus aureus, 4 (25%). Over 80% of the isolates were susceptible to Ceftriaxone, Amikacin and Meropenem. CONCLUSIONS: Klebsiella pneumoniae and Staphylococcus aureus are the predominant causes of bacteremia in children with SCD in Ibadan, contrary to findings in western countries.

Etiology of early onset septicemia among neonates at the University College Hospital, Ibadan, Nigeria.

INTRODUCTION: Neonatal septicemia remains a major cause of newborn deaths in developing countries. Its burden is further compounded by the emergence of multidrug-resistant pathogens, which is related to a lack of antibiotic protocols resulting in unrestricted use of antibiotics. The absence of reliable antibiotic sensitivity testing makes the formulation of antibiotic guidelines and judicious use of antibiotics difficult. This study sought to identify the current bacterial agents associated with early onset septicemia (EOS; age <72 hours) and their antibiotic susceptibility patterns among neonates at the University College Hospital, Ibadan, Nigeria. METHODOLOGY: A total of 202 inborn and outborn neonates with risk factors for or clinical features of septicemia in the first 72 hours of life had samples for blood cultures and antibiotic sensitivity patterns taken prior to treatment. RESULTS: Of the subjects, 95 (47.0%) were inborn and 107 (53.0%) outborn, with a M:F ratio of 1.3:1; 12.5% were culture positive, and the prevalence of EOS was 8.8/1,000 live births. The isolates were Staphylococcus aureus (52%), 30.7% of which were methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae (12%), Enterobacter aerogenes (8%), Enterococcus spp. (8%), Eschericia coli (4%), and other Gram-negatives (12%). All the isolates except Staphylococcus aureus were susceptible to ampicillin, ampicillin/sulbactam, amikacin, gentamicin, and third-generation cephalosporins. All MRSA were sensitive to amikacin, ciprofloxacin, and chloramphenicol, while all methicillin-sensitive Staphylococcus aureus were sensitive to ampicillin/sulbactam. CONCLUSIONS: Staphylococcus aureus was the commonest cause of EOS in our setting, with 30.7% of the Staphylococcus aureus isolates being MRSA. Only MRSA demonstrated multidrug resistance.