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.

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.

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.

A pragmatic approach to the diagnosis of inborn errors of metabolism in developing countries.

Inborn errors of metabolism (IEM) are a group of genetically derived diseases that are individually rare but collectively common and can be very severe. While high-income countries usually employ modern scientific technologies like tandem mass spectrometry for IEM investigation, these disorders are, in contrast, only rarely screened for in developing countries due to misconceptions that the required facilities are beyond the reach of these countries. This paper attempts to educate scientists and clinicians in developing countries on low-technology IEM screening methods that only require moderate facilities. Although a definitive diagnosis of IEM may require specialised laboratory investigations and attendant interpretation, in most cases, the basic facilities available in the average clinical chemistry laboratory in developing countries can allow the early detection of IEM. This early detection would facilitate critical early decision making, thus leading to better management, optimised treatment, and reduced morbidity and or mortality of IEM in these resource-limited countries. With this approach, a few referral centres for confirmatory investigation, comparable to those existing in developed countries, could be established. This can be integrated into creative health education for healthcare professionals and families who have individuals with IEM. What this study adds: IEMs are important enough that every country, developed or developing, should have screening plans and basic laboratory facilities that are adequate for initial IEM diagnosis. No country should therefore give up on testing for IEMs on the excuse of a paucity of advanced facilities.

Short-term Persistence of Protective Maternally Acquired Immunity in Neonates Delivered by Primiparous Women in Ibadan, Nigeria.

BACKGROUND: Unresolved questions remain concerning the protective effect and duration of immunity acquired from mothers. This study investigated persistence of immunity against tetanus in the first two weeks of life among neonates in Nigeria. METHODS: In a longitudinal study, 244 primiparous mothers and their newborns were consecutively recruited at 16 selected Primary Healthcare Centres in Ibadan, Nigeria. All the newborns were tested for protection against tetanus using a validated rapid diagnostic, "Tetanos Quick Sticks" (TQS) on days 1, 7 and 14. Persistent immunity was defined as positive TQS result on day-14. Data were analysed using descriptive statistics, Chi-square and logistic regression at p = 0.05. RESULTS: There were 137(56.1%) male neonates; 87.7% were delivered at ≥37weeks of gestation. The prevalence of protective immunity against tetanus (PIaT) among neonates on day-1 was 63.5%; 119 out of 153 neonates remained positive to TQS test by day-14, giving a persistence rate of 77.8%. Independent predictors of persistent PIaT were residence in urban area (OR = 9.66; 95% CI = 2.42-38.45), maternal age (OR = 2.06; 95% CI = 1.49-2.85) and gestational age (OR = 1.84; 95% CI = 1.23-2.74). CONCLUSION: Protective immunity against tetanus waned in some neonates over the first two weeks of life, and this decline was inversely related to maternal and gestational ages.

Non-protective immunity against tetanus in primiparous women and newborns at birth in rural and urban settings in Ibadan, Nigeria.

INTRODUCTION: Nigeria remains among the few countries that are yet to achieve eradication of neonatal tetanus in the world despite the availability of an effective vaccine. This study investigated immunity against tetanus in primiparous mothers and neonates at birth, and identified associated factors. METHODS: This cross-sectional study involved consecutive selection of 244 primiparous mother-neonate pairs (119 from rural areas, 125 from urban areas, 137 male neonates and 107 female neonates) delivered at primary healthcare facilities in Ibadan, Nigeria. Socio-demographic characteristics, obstetric history, immunisation and birthweight were obtained from mothers by interview. A validated immunochromatographic rapid diagnostic test kit was used to test for immunity against tetanus. Positive and negative results were interpreted as protective immunity against tetanus (PIaT) and non-protective immunity against tetanus (NPIaT), respectively. Data were analysed using descriptive statistics, Chi-square and logistic regression at p = 0.05. RESULTS: The mean age of mothers was 27.9±3.4 years (range: 20-33) and median birthweight was 2700g (range: 1760-3300). Of the 244 mothers, 198 (81.1%) received at least two doses of tetanus toxoid injection during pregnancy and prevalence of NPIaT and PIaT was 28.7% and 71.3%, respectively. The prevalence of PIaT was significantly higher among mothers in urban areas (n= 96; 80.7%) than rural (n=78; 62.4%), p<0.001.The prevalence of NPIaT among neonates was 36.5% (n= 89). Predictors of NPIaT among neonates were residence in rural LGA (OR = 2.22; 95% CI = 1.23-3.99) and maternal tetanus immunisation <2 doses (OR = 11.68; 95% CI = 4.05-21.75). CONCLUSION: Lack of protective immunity against tetanus among neonates of primiparous women in Ibadan is prevalent and a more conscientious enforcement of routine tetanus prevention practices is needed.

Hypoxemia predicts death from severe falciparum malaria among children under 5 years of age in Nigeria: the need for pulse oximetry in case management.

BACKGROUND: Oxygen saturation is a good marker for disease severity in emergency care. However, studies have not considered its use in identifying individuals infected with Plasmodium falciparum at risk of deaths. OBJECTIVE: To investigate the prevalence and predictive value of hypoxaemia for deaths in under-5s with severe falciparum malaria infection. METHODS: Oxygen saturation was prospectively measured alongside other indicators of disease severity in 369 under-5s admitted to a tertiary hospital in Nigeria. Participants were children in whom falciparum malaria parasitaemia was confirmed with blood film microscopy in the presence of any of the World Health Organization-defined life-threatening features for malaria. RESULTS: Overall mortality rate was 8.1%. Of the 16 indicators of the disease severity assessed, hypoxaemia (OR=7.54; 95% CI=2.80, 20.29), co-morbidity with pneumonia (OR=19.27; 95% CI=2.87, 29.59), metabolic acidosis (OR=6.21; 95% CI=2.21, 17.47) and hypoglycaemia (OR=19.71; 95% CI=2.61, 25.47) were independent predictors of death. Cerebral malaria, male gender, wasting, hypokalaemia, hyponatriaemia, azotaemia and renal impairment were significantly associated with death in univariate analysis but not logistic regression model. CONCLUSIONS: Hypoxaemia predicts deaths in Nigerian children with severe malaria, irrespective of other features. Efforts should always be made to measure oxygen saturation as part of the treatments for severe malaria in children.

Plasma homocysteine and B vitamins levels in Nigerian children with nephrotic syndrome.

INTRODUCTION: Available data on plasma homocysteine level in patients with nephrotic syndrome (NS) are controversial with increased, decreased and unchanged values reported. Therefore, plasma homocysteine and serum B vitamins in Nigerian children with NS were assessed in this study. METHODS: Fasting blood samples were analysed for plasma homocysteine, serum folate and B vitamins in 42 children with NS and 42 age and sex-matched healthy controls in this case control study. Data were compared between NS and control using t test and Chi square. Relationships were tested with regression analysis with p set at 0.05. RESULTS: Prevalence of hyperhomocysteinaemia, low folate and cyanocobalamin in NS was 57.1%, 14.3% and 9.5% respectively. The mean homocysteine level was significantly higher in NS than control (11.3±2.6 µmol/L versus 5.5±2.3 µmol/L). Also, NS had lower folate and cyanocobalamin than control: 9.1±3.9 ng/mL versus 11.2±3.1 ng/dL and 268.5±95.7 pg/mL versus 316±117.2 pg/mL respectively. Weak but significant correlation between homocysteine and serum albumin (r = 0.347), folate (r = -0.607) and vitamin B12 (r = -0.185) were found in the NS group. Significant relationship was also found between homocysteine and vitamin B12 (ß = -0.64, 95% CI = -1.20, -0.08) after controlling for folate and vitamin B6 levels. CONCLUSION: Clinically important hyperhomocysteinaemia and low B vitamins occur in Nigerian children with nephrotic syndrome. This data suggest that potential usefulness of folate and vitamin B supplementation for reducing high homocysteine levels in nephrotic syndrome need to be further investigated.

Immunity Against Tetanus Infection, Risk Factors for Non-Protection, and Validation of a Rapid Immunotest Kit among Hospitalized Children in Nigeria.

Seroepidemiological studies of tetanus in Africans have focused mainly on adults especially pregnant women and data on children are scarcely reported. We investigated the seroprevalence of protective immunity level, determined risk factors for non-protection against tetanus, and evaluated the performance of Tetanos Quick Stick(®) (TQS) among hospitalized children aged 1-9 years in Nigeria. Blood IgG antibody levels to tetanus was determined using enzyme-linked immunosorbent assay (ELISA) in the laboratory and TQS (an immunochromatographic test) at the bedside for 304 children admitted into emergency unit of a tertiary hospital in Ibadan, Nigeria. Demographic information and vaccination history were also collected. TQS results were compared with anti-tetanus antibody measured by ELISA using seroprotection cut-off of 0.1 IU/ml. Seroprevalence of protective level of immunity against tetanus using ELISA and TQS methods was 44.7 and 45.4% respectively. Protective level of immunity increased as age increases. Of the seven potential factors assessed, male gender and being second or more position among mother's children were independent predictors of non-protective level of immunity. Absence of history of recent tetanus toxoid injection was significantly associated with non-protective level of immunity in univariate analysis but not logistic regression model. The agreement between the ELISA and the TQS results was good with a k coefficient of 0.931. TQS sensitivity was 95.7%, specificity 97.6%, positive predictive value 98.0%, and negative predictive values 96.0%. This study showed that lack of protective immunity against tetanus is common; few demographic characteristics correctly predict non-protection and IgG antibody levels to tetanus was accurately detected by TQS.