Efficacy and safety of pyronaridine-artesunate versus artemether-lumefantrine in the treatment of acute uncomplicated malaria in children in South-West Nigeria: an open-labelled randomized controlled trial.

BACKGROUND: In Nigeria, declining responsiveness to artemether-lumefantrine (AL), the artemisinin-based combination therapy (ACT) of choice since 2005, has been reported. Pyronaridine-artesunate (PA) is a newer fixed-dose ACT recently prequalified by the WHO for the treatment of uncomplicated falciparum malaria. However, PA data from the Nigerian pediatric population is scarce. Therefore, the efficacy and safety of PA and AL using the WHO 28-day anti-malarial therapeutic efficacy study protocol in Ibadan, southwest Nigeria, were compared. METHODS: In an open-labelled, randomized, controlled clinical trial, 172 children aged 3-144 months with a history of fever and microscopically confirmed uncomplicated Plasmodium falciparum malaria were enrolled in southwest Nigeria. Enrollees were randomly assigned to receive PA or AL at standard dosages according to body weight for 3 days. Venous blood was obtained for hematology, blood chemistry, and liver function tests on days 0, 3, 7, and 28 as part of the safety evaluation. RESULTS: 165 (95.9%) of the enrolled individuals completed the study. About half (52.3%; 90/172) of enrollees were male. Eighty-seven (50.6%) received AL, while 85 (49.4%) received PA. Day 28, adequate clinical and parasitological response for PA was 92.7% [(76/82) 95% CI 83.1, 95.9] and 71.1% [(59/83) 95% CI 60.4, 79.9] for AL (0.001). Fever and parasite clearance were similar in both groups. Two of six and eight of 24 parasite recurrences were observed among PA- and AL-treated children, respectively. PCR-corrected Day-28 cure rates for PA were 97.4% (76/78) and 88.1% (59/67) for AL (= 0.04) in the per-protocol population after new infections were censored. Hematological recovery at day 28 was significantly better among PA-treated patients (34.9% 2.8) compared to those treated with AL (33.1% 3.0) (0.002). Adverse events in both treatment arms were mild and similar to the symptoms of malaria infection. Blood chemistry and liver function tests were mostly within normal limits, with an occasional marginal rise. CONCLUSION: PA and AL were well-tolerated. PA was significantly more efficacious than AL in both the PCR-uncorrected and PCR-corrected per-protocol populations during this study. The results of this study support the inclusion of PA in the anti-malarial treatment guidelines in Nigeria. RETROSPECTIVE TRIAL REGISTRATION: Clinicaltrials.gov: NCT05192265.

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.

Transcranial Doppler screening in Nigerian children with sickle cell disease: A 10-year longitudinal study on the SPPIBA cohort.

BACKGROUND: Primary stroke prevention programmes for children with sickle cell disease (SCD) have been shown to be feasible interventions in resource-poor countries. Different hydroxyurea (HU) regimens have been utilised in ameliorating the severity of SCD. OBJECTIVE: To determine the long-term outcomes of the stroke prevention programme for children with SCD in Ibadan (SPPIBA), Nigeria. METHODS: A longitudinal study of 396 children with haemoglobin SS disease who had been on the stroke prevention programme for a minimum period of 5 years. All enrollees had nonimaging TCD performed at baseline and thereafter 3-monthly or annually. Children with TCD velocities ≥170 cm/s were treated with HU by dose-escalation regimen. RESULTS: The mean age at first TCD examination was 102 ± 46.7 months and the period of follow-up ranged from 5 to 10 years (mean = 7.2 ± 1.7). Time to significant decline in TCD velocities ranged from 5 to 35 months, (median = 10.0 months). The minimum dose of HU required to achieve significant decline in TCD velocities ranged from 15 to 31 mg/kg/day, mean 23.7 (±3.9). HU dose escalation beyond 20 mg/kg/day was required to attain significant reductions in the time-averaged mean of maximal velocities (TAMMV) in 69.1% of the cases. Two stroke events occurred giving a stroke incidence of 0.08 per 100 patient-years. CONCLUSION: The majority of Nigerian children with SCD and elevated TCD velocities achieved significant decline in TAMMV within the first year of HU therapy but on higher doses of HU. It might be important to individualise HU doses for optimal outcomes in primary stroke prevention.

Malaria parasite density and plasma apolipoprotein A1 in symptomatic and asymptomatic infections in Nigerian children.

BACKGROUND & OBJECTIVES: Alterations in plasma apolipoproteins in individuals with malaria infection and their potential roles in the pathogenesis are known but the link between the malaria parasite density and apolipoprotein A1 (apo-A1) level is insufficiently understood. This study was conducted to determine whether the plasma apo-A1 level is influenced by the degree of parasitaemia in malaria infections. METHODS: In a case-control study, a convenient sample of children aged 2-10 years with uncomplicated malaria cases (UMC), asymptomatic parasitaemia cases (APC) and healthy children without parasitaemia (HCP) was recruited. The cases consisted of 61 UMC and 21 APC, while the controls consisted of 24 HCP. Levels of apo-A1 was determined using immunoturbidimetric assay and compared among the different degrees of parasite density. RESULTS: Of the 82 participants with parasitaemia, density was ≤1000/µL in 12, 1001-10000/µL in 21 and >10000/µL in 49 children. There was significant difference among the mean values of apolipoprotein A1 of the three groups, viz: UMC [91.4 (95% CI: 81.3, 101.5) mg/dL], APC [67.0 (95% CI: 48.9, 84.9) mg/dL] and HCP [99.0 (95% CI: 76.6, 121.3) mg/dL], p=0.029. Post-hoc analysis revealed that the mean plasma level of apo-A1 in HCP was significantly higher than APC by 32.0±12.4 mg/dL and UMC by 7.5±4.2 mg/dL. However, there were no differences in the mean apolipoprotein A1 levels among the three groups of parasite density. INTERPRETATION & CONCLUSION: The presence of parasitaemia causes a remarkable reduction in apolipoprotein A1 level that was not influenced by the degree of parasitaemia.

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.

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria.

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

Circulatory hepcidin is associated with the anti-inflammatory response but not with iron or anemic status in childhood malaria.

Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore, it is important to understand the pathology underlying the development of CM and SMA as opposed to uncomplicated malaria (UM). Increased levels of hepcidin have been associated with UM, but its level and role in severe malarial disease remains to be investigated. Plasma and clinical data were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, Nigeria. Here, we report that hepcidin levels are lower in children with SMA or CM than in those with milder outcome (UM). While different profiles of pro- and anti-inflammatory cytokines were observed between the malaria syndromes, circulatory hepcidin levels remained associated with the levels of its regulatory cytokine interleukin-6 and of the anti-inflammatory cytokine inerleukin-10, irrespective of iron status, anemic status, and general acute-phase response. We propose a role for hepcidin in anti-inflammatory processes in childhood malaria.

Serum Apolipoprotein-A1 and Cholesterol Levels in Nigerian Children with Plasmodium falciparum Infection.

OBJECTIVE: This study was carried out to determine whether or not Plasmodium falciparum malaria infection significantly affected apolipoprotein-A1 and cholesterol levels and if apolipoprotein-A1 correlated with the malaria severity in children younger than 5 years old. SUBJECTS AND METHODS: Two hundred and fifty-five children, 170 of whom had microscopically confirmed P. falciparum infection, i.e. 85 cases of uncomplicated malaria (UM) and 85 of complicated malaria (CM), and 85 healthy controls were enrolled in this study. Serum levels of apolipoprotein-A1, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides were determined. These levels were compared among the malaria and control groups, using ANOVA and post hoc analyses at p = 0.05. RESULTS: There were significant differences in the mean serum levels of apolipoprotein-A1 (UM: 104.5 ± 38.1 mg/dl, CM: 90.9 ± 33.3 mg/dl and controls: 129.7 ± 48.3 mg/dl; p < 0.001), total cholesterol (UM: 138.8 ± 62.9 mg/dl, CM: 121.2 ± 55.2 mg/dl and controls: 155.1 ± 69.8 mg/dl; p = 0.002) and LDL (UM: 98.2 ± 55.5 mg/dl, CM: 84.3 ± 47.4 mg/dl and controls: 122.7 ± 69.4 mg/dl; p < 0.001). Post hoc analyses revealed that children with UM and CM had significantly lower levels of apolipoprotein-A1, cholesterol, HDL and LDL than controls but that there was no difference between the 2 malaria groups. Reductions in levels of lipids and apolipoprotein-A1 were worse in CM than in UM. CONCLUSION: Altered levels of serum lipids with CM were associated with a reduction in apolipoprotein-A1. These findings have potential diagnostic utility for the management of malaria.

Features and outcomes of malaria infection in glucose-6-phosphatedehydrogenase normal and deficient Nigerian children.

BACKGROUND & OBJECTIVES: Malaria and G6PD deficiency-related haemolyses are known causes of hospital admissions in Nigeria and pose great danger to child survival but data on interactions of these two pathologies are scarce. This study was carried out to determine the association between features of Plasmodium falciparum infection and G6PD status. METHODS: G6PD and haemoglobin were typed by fluorescent spot test and electrophoresis respectively, in 1120 children with microscopically-proven falciparum malaria. Clinical features of malaria were compared between G6PD normal and deficient children. RESULTS: There were 558 males and 562 females with median age of 35 months (range, 6 months-12 yr). In males, prevalence of G6PD-deficiency in patients with uncomplicated malaria (UM), severe malarial anaemia (SMA) and cerebral malaria (CM) was 23.4, 7 and 16.7%, respectively compared with 11.1, 7.3 and 4.4%, respectively among females. In both males and females, convulsion and rectal temperature above 38°C were less likely presentations among G6PD-deficient compared with G6PD-normal children (p <0.05). The proportions of children with pallor, convulsion and impaired consciousness were significantly lower among G6PD-deficient than normal males (p <0.05) but these features were not different between deficient and normal females (p >0.05). INTERPRETATION & CONCLUSION: Convulsions, pallor and elevated temperature were more frequent features of malaria in G6PD normal than deficient children. G6PD-deficient male children are protected against impaired consciousness. These differences may offer useful hints in malaria treatment and researches in endemic regions.

Ultrasonographic renal sizes, cortical thickness and volume in Nigerian children with acute falciparum malaria.

BACKGROUND: Utility of sonographic assessments of renal changes during malaria illness are rarely reported in African children in spite of the high burden of malarial-related kidney damage. METHODS: In this case-control study, renal sizes, cortical thickness and volume of the kidneys of 131 healthy children and 170 with acute falciparum malaria comprising 85 uncomplicated malaria (UM) and 85 complicated malaria (CM) cases, measured within 24 hours of presenting in the hospital were compared. RESULTS: The mean age of children with UM, CM and control groups was 49.7 ± 26.2 months, 50.7 ± 29.3 months and 73.4 ± 25.5 months, respectively (p < 0.001). The mean right kidney length of CM group was higher than control by 0.41cm (95% CI = 0.16, 0.65; p < 0.001) and UM by 0.32 cm (95% CI = 0.02, 0.62; p = 0.030). Similarly, mean left kidney length of CM was higher than control and UM by 0.34 cm (95% CI = 0.09, 0.60; p = 0.005) and 0.41cm (95% CI = 0.09, 0.72; p = 0.006), respectively. Estimated mean renal volume of the CM group was significantly higher than control group by 7.82 cm(3) for right and by 5.79 cm(3) for left kidneys respectively; in the UM group by 9.31cm(3) for right and 8.87 cm(3) for left kidneys respectively. CONCLUSION: There was a marginal increase in renal size of children with Plasmodium falciparum infection, which worsened with increasing severity of malaria morbidity. Ultrasonography provides important information for detecting renal changes in children with acute malaria.

Trends of infant vaccination timeliness and completion in selected urban slum communities in Ibadan, Southwestern Nigeria: A four-year review.

BACKGROUND: Suboptimal infant vaccination is common in Nigeria and multiple interventions have been deployed to address the situation. Child health indicators are reported to be worse in urban slums compared with other urban areas, but urban data are usually not disaggregated to show these disparities. Examining the timeliness and completion of infant vaccination in urban slums is important to determine the effectiveness of existing interventions in improving infant vaccination among this vulnerable population. This study explored the trends of infant vaccination in selected urban slum communities in Ibadan, Southwest Nigeria between November 2014 and October 2018. METHODS: This was a cross sectional study where infant vaccination data were extracted from the immunization clinic records of six primary health care centers that were providing infant vaccination services for seven urban slum communities. Data was analyzed using descriptive statistics and Chi square test at α = 05. RESULTS: A total of 5,934 infants vaccination records were reviewed, 2,895 (48.8%) were for female infants and 3,002(50.6%) were from Muslim families. Overall, only 0.6% infants had both timely and complete vaccination during the four years under study. The highest number of infants with timely and complete vaccination were seen in 2015(12.2%) and least in 2018(2.9%). Regarding timeliness of the vaccines, BCG, was the least timely among the vaccines given at birth and the pentavalent and oral polio vaccines' timeliness reduced as the age of the infants increased. Both yellow fever and measles vaccines were timelier than the pentavalent vaccines. Vaccines were most timely in 2016(31.3%) and least timely in 2018(12.1%). Those from Muslim families significantly had delayed and incomplete vaccinations compared with those from Chrisitan families (p = 0.026). CONCLUSION: Infant vaccinations were significantly delayed and incomplete in the study communities during the years reviewed. More focused interventions are required to ensure optimal vaccination of the infants.

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.

Haemoglobinuria among children with severe malaria attending tertiary care in Ibadan, Nigeria.

BACKGROUND: Haemoglobinuria is one of the manifestations of severe malaria and results from severe intravascular haemolysis. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been implicated in its aetiology. Haemoglobinuria may be associated with severe anaemia and, less frequently, acute renal failure. METHODS: A prospective case-control study was carried out to determine the incidence of haemoglobinuria as confirmed by dipstick urinalysis, microscopy and spectrophotometric measurement, among children with severe malaria. A total of 251 children presenting at the Children's Emergency Ward with severe malaria were recruited over a period of 21 months. The G6PD status and the outcomes of severe malaria in children with and without haemoglobinuria was studied with respect to renal failure, the recurrence of haemoglobinuria and blood pressure changes over a three-month follow-up period. RESULTS: It was found that the incidence of haemoglobinuria among children with severe malaria is 19.1%. Children <5 years constituted 76.8% of all the study patients. Patients with haemoglobinuria had median age of 52.5 months, which was significantly higher than 35 months in patients without haemoglobinuria (p=0.001). Although, haemaglobinuria was commoner among boys (54.2%) than girls (45.8%), the difference was not statistically significant. There were no significant differences between children with and without haemoglobinuria regarding their nutritional status or parasite densities. Among the clinical features of the study patients, only jaundice was significantly associated with haemoglobinuria (p=0.0001). Renal failure occurred in three out of 48 children with haemoglobinuria and in none of the 203 without. There was not recurrence of haemoglobinuria in the follow-up period. At discharge, blood pressure was elevated in six children (one previously haemoglobinuric), but all returned to normal within the follow-up period. CONCLUSIONS: Haemoglobinuria was a prominent feature of severe malaria and it was significantly associated with jaundice at presentation. Haemoglobinuria was commoner in older children than younger children but not related to sex. G6PD deficiency was not an independent predictor of the occurrence or outcome of haemoglobinuria. Blood pressure was not affected by haemoglobinuria on admission nor during follow-up.

A comparison of tympanic and rectal temperatures in term Nigerian neonates.

BACKGROUND: Tympanic thermometry has come as a suitable alternative to traditional thermometry because of its safety and ease of use. However, it is still yet to gain wide acceptance in African settings due to conflicting results on its accuracy, thus rectal thermometry remains the gold standard in the newborn. The aim of this study was to compare tympanic and rectal temperatures in term Nigerian neonates. METHODS: Rectal and tympanic temperatures were measured simultaneously in 300 consecutive term neonates between the ages of 37 and 42 weeks gestation using mercury-in-glass and the Infrared tympanic thermometers respectively. Paired t test, Pearson correlation coefficient and the Bland-Altman plot were used to compute data. Using rectal thermometry as gold standard, the sensitivity, specificity and predictive values of tympanic thermometry at various rectal temperature cut-offs were determined. Receiver Operating Curves (ROC) were constructed and the Areas Under the Curves (AUC) were compared. RESULTS: The mean rectal temperature (37.34±0.55°C) was significantly higher than the mean tympanic temperature (37.25 ± 0.56°C) (p<0.001) with a mean difference of 0.09 °C±0.24 °C (95% CI: 0.06, 0.12). There was a strong positive correlation between the two measurements (r=0.9; p<0.001). Tympanic thermometry showed sensitivities ranging from 65% to 86% and specificities of 95% to 99% at rectal temperature cut-offs of 37.5°C to 38°C. The positive and negative predictive values of the tympanic temperatures at the various temperature cut-offs ranged from 82% to 93% and 80% to 98% respectively. Accuracy was noted to increase with higher temperatures as shown by the Receiver Operating Curves with the highest accuracy at the temperature cut-off of 38°C and AUC of 0.91. CONCLUSIONS: The sensitivity of tympanic thermometry was relatively low in detecting rectal temperatures despite the good correlation and agreement between them. The specificities and predictive values of tympanic temperatures in detecting rectal temperatures were high and accuracy increased with higher temperatures. Though using the tympanic route for measuring temperature in the newborn is relatively safe and non-invasive, its low sensitivity limits its use. Further studies would be required to further assess the accuracy of tympanic temperature measurements in the newborn.

Comparison of point-of-care glucometers and laboratory based glucose oxidase test in determining blood glucose levels.

Introduction: Alterations in blood glucose levels are common and an important determinant of a patient's admission outcomes, point-of-care glucometers, which are affected by a variety of factors, are increasingly used in clinical care. In this study we compared blood glucose levels determined by two commonly used glucometers (One Touch® and Accu-check®) with those of a standard laboratory method and determined the effect of haematocrit on glucose readings. Methods: Blood glucose levels were measured with One Touch® and Accu-Check® glucometers and the glucose oxidase method at the same time in 295 children aged 0 to 15 years over a 6-month period. Bland-Altman and correlation analysis were used to explore biases among the three methods. For all statistical tests, a p-value of less than 0.05 was considered statistically significant. Results: Most were males (51.2%) and the median (range) age was 1 year (1 day, 12 years). There was a significant correlation between each of the glucometer methods and laboratory blood sugar, and the correlation between the two glucometers was strong and significant. This correlation remained statistically significant even after controlling for haematocrit values. There was an acceptable level of bias (3.9 mg/dL) between the One Touch® and Accu-check® glucometers, but each had a remarkably large bias compared with the glucose oxidase method. Conclusion: The use of a tested glucometer in clinical settings can aid in rapid decision-making, but there is a need to periodically cross-check with the glucose oxidase method in the laboratory to optimise treatment outcomes for children with dysglycaemia.

High prevalence of Plasmodium malariae and Plasmodium ovale in co-infections with Plasmodium falciparum in asymptomatic malaria parasite carriers in southwestern Nigeria.

Asymptomatic malaria parasite carriers do not seek anti-malarial treatment and may constitute a silent infectious reservoir. In order to assess the level of asymptomatic and symptomatic carriage amongst adolescents in a highly endemic area, and to identify the risk factors associated with such carriage, we conducted a cross-sectional survey of 1032 adolescents (ages 10-19 years) from eight schools located in Ibadan, southwestern Nigeria in 2016. Blood films and blood spot filter paper samples were prepared for microscopy and DNA analysis. The prevalence of asymptomatic malaria was determined using microscopy, rapid diagnostic tests and PCR for 658 randomly selected samples. Of these, we found that 80% of asymptomatic schoolchildren were positive for malaria parasites by PCR, compared with 47% and 9%, determined by rapid diagnostic tests and microscopy, respectively. Malaria parasite species typing was performed using PCR targeting the mitochondrial CoxIII gene, and revealed high rates of carriage of Plasmodium malariae (53%) and Plasmodium ovale (24%). Most asymptomatic infections were co-infections of two or more species (62%), with Plasmodium falciparum + P. malariae the most common (35%), followed by P. falciparum + P. malariae + P. ovale (21%) and P. falciparum + P. ovale (6%). Single infections of P. falciparum, P. malariae and P. ovale accounted for 24%, 10% and 4% of all asymptomatic infections, respectively. To compare the species composition of asymptomatic and symptomatic infections, further sample collection was carried out in 2017 at one of the previously sampled schools, and at a nearby hospital. Whilst the species composition of the asymptomatic infections was similar to that observed in 2016, the symptomatic infections were markedly different, with single infections of P. falciparum observed in 91% of patients, P. falciparum + P. malariae in 5% and P. falciparum + P. ovale in 4%.

Utilisation of malaria preventive measures during pregnancy and birth outcomes in Ibadan, Nigeria.

BACKGROUND: Malaria remains a major public health problem in sub Saharan Africa and the extent of utilisation of malaria preventive measures may impact on the burden of malaria in pregnancy. This study sought to determine the association between malaria preventive measures utilized during pregnancy and the birth outcomes of birth weight and preterm delivery. METHODS: This cross sectional survey involved 800 mothers who delivered at the University College Hospital, and Adeoyo Maternity Hospital, Ibadan. Data obtained included obstetric information, gestational age, birth weight and self reported use of malaria prevention strategies in index pregnancy. RESULTS: Most (95.6%) mothers used one or more malaria control measures. The most commonly used vector control measures were window net (84.0%), insecticide spray (71.5%) and insecticide treated bed nets (20.1%), while chemoprophylactic agents were pyrimethamine (23.5%), Intermittent Preventive Treatments with Sulphadoxine-Pyrimethamine (IPTsp) (18.5%) and intermittent chloroquine (9.5%) and 21.7% used herbal medications. The mean ± SD birthweight and gestational age of the babies were 3.02 kg ± 0.56 and 37.9 weeks ± 2.5 respectively. Preterm delivery rate was 19.4% and 9% had low birth weight. Comparing babies whose mothers had IPTsp with those who did not, mean birth weight was 3.13 kg ± 0.52 versus 3.0 kg ± 0.56 (p = 0.016) and mean gestational age was 38.5 weeks ± 2.1 versus 37.8 weeks ± 2.5 (p = 0.002). The non-use of IPTsp was associated with increased risk of having low birth weight babies (AOR: 2.27, 95% CI: 0.98; 5.28) and preterm birth (AOR: 1.93, 95% CI: 1.08, 3.44). The non use of herbal preparations (AOR: 0.55, 95% CI: 0.36, 0.85) was associated with reduced risk of preterm birth. The mean ± SD birth weight and gestational ages of babies born to mothers who slept under ITNs were not significantly different from those who did not (p = 0.07 and 0.09 respectively). CONCLUSIONS: There is a need for improved utilisation of IPTsp as well as discouraging the use of herbal medications in pregnancy in order to reduce pregnancy outcome measures of low birth weight and preterm deliveries in this environment.

Esophageal, tympanic, rectal, and skin temperatures in children undergoing surgery with general anesthesia.

The purpose of this study was to determine the degrees of agreement between various sites of temperature measurement and examine the trend of body temperature in children during surgery under general anaesthesia. Thirty-six consecutive children who underwent surgery with general anaesthesia, had temperatures measured at the oesophagus, skin, ear canal and rectum at baseline, every 15 minutes for the first hour and every 30 minutes thereafter. Spearman correlation and Bland-Altman analyses were used to compare data and trends of mean differences assessed by line graphs. The median age of the sample was 48 months. There were 575 temperature measurements taken. The inter-method correlation coefficients was highest for the oesophageal vs rectal (r = 0.96) temperature and lowest for rectal vs skin (r = -0.11) temperature. The lowest mean difference (95% CI) in temperature at commencement of surgery was between the oesophageal and rectal sites, -0.03°C (-0.08, -0.01) while the highest mean difference (95% CI) temperature was between oesophageal and skin sites, 3.24°C (2.65, 3.85). The trend in differential temperatures between sites remained throughout the duration of surgery. Bland-Altman plots showed that the least difference (bias) at baseline (0.3°C) was between the oesophageal and tympanic temperatures while at 1 hour (0.13°C ) was between the oesophageal and rectal temperatures. The oesophageal site was the closest to rectal for monitoring core temperature while the skin was the least reliable site in the study population. In the situation where oesophageal probe is not routine or functioning, rectal or tympanic temperatures may be used.

Edwardsiella ictaluri, an unusual cause of bacteraemia in a Nigerian child with acute bloody diarrhoea.

Enteric septicaemia of catfish was first detected in 1976 as an economically significant disease associated with commercial catfish production. Initially, Edwardsiella ictaluri was a host specific pathogen of catfish species but has also been reported from other hosts other than the catfish such as the zebrafish. E. ictaluri has not been isolated in humans hence it is not a zoonotic infection. There has been no previous report of isolation of this organism in humans. This was a case report of a 5 year old boy who presented with fever, vomiting, passage of bloody stool of 6 days and abdominal pain of a day duration. In the case of this 5 year old boy who presented with features of dysentery, blood culture using BACTEC™ grew E. ictaluri. E. ictaluri may be a pathogen which can infect humans just like another closely related species, Edwardsiella tarda. Although, E. ictaluri has not been reported in humans, could this be the first case? Non availability of diagnostic technique appropriate for its diagnosis may explain the rare incidence of the organism in humans, hence many cases would have been treated without isolating the organism.

Efficacy and safety of dual intravenous artesunate plus quinine compared to intravenous artesunate for cerebral malaria in a triple blinded parallel multisite randomized controlled trial in Nigerian children: DUAL PAQ TRIAL Protocol.

BACKGROUND: Evidence exists as to the criticality of the first 24 h in the management of cerebral malaria. The morbidity and the mortality rate (35%) with the current intravenous monotherapy for the initial treatment of cerebral malaria are unacceptably high. Combination therapy and a shorter course of effective medication have been shown to improve outcomes in human participants in the treatment of other diseases. This study outlines a protocol to conduct a triple blinded parallel randomized controlled trial on cerebral malaria using dual intravenous medications compared to the current standard of monotherapy. METHODS: This is a parallel multi-site randomized controlled superiority triple blinded trial consisting of intravenous artesunate plus quinine and a control arm of intravenous artesunate only. Eligible and assenting children aged 6 months to 17 years will be recruited from 4 tertiary hospitals by random selection from the list of tertiary hospitals in Nigeria. Participants will be randomized and assigned in parallel into two arms using random numbers generated from GraphPad Prism (version 9) by a clinical pharmacologist who has no link with the investigators, the patients, or the statistician. The primary measurable outcome is survival at 12, 24, and 48 h post-randomization. A composite secondary outcome consists of the number of children that regained consciousness, parasitaemia and defervescence at 12 and 24 h post-randomization and haematological and inflammatory markers at 24 and 48 h post-randomization. Adverse events both solicited and unsolicited are recorded all through the study post-randomization. The study is approved by the State Research Ethics Review Committee. Data analysis will be performed in GraphPad Prism version 9. DISCUSSION: The outcome of this analysis will give insight into the efficacy and safety of dual intravenous antimalaria in the treatment of cerebral malaria among Nigerian children compared with the standard of care. The safety profile of this intervention will also be highlighted. This may help inform physicians on the optimal treatment for cerebral malaria to improve outcomes and reduce recrudescence and treatment failure. TRIAL REGISTRATION: Pan Africa Clinical Trial Registry PACTR202102893629864 . 23/02/2021.