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.

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%.

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.

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.

A Systematic Review and Meta-analysis of Sex Differences in Morbidity and Mortality of Acute Lower Respiratory Tract Infections Among African Children.

CONTEXT: Although biological sex influences Acute Lower Respiratory Tract Infections (ALRIs) morbidity and mortality patterns in children living in sub-Saharan Africa, the exact mechanism about the effect is unknown. OBJECTIVE: We assessed the quality and strength of evidence on the association of sex with incidence, etiology, and outcomes of ALRI in African children. DATA SOURCES STUDY SELECTION AND DATA EXTRACTION: We systematically searched electronic databases for publications from 1971-2016 in PubMed, African Journals Online, and Google scholar for ALRI literature in the African children. We used (pneumonia OR bronchiolitis OR "community-acquired pneumonia" OR CAP OR "hospital-acquired pneumonia" OR "nosocomial pneumonia" OR "ventilator-acquired pneumonia" OR "lung abscess" OR "pleural effusion" OR "empyema thoracis") AND (sex OR gender) AND (Africa OR Sub-Saharan) as search terms. We included the published peer-reviewed journal articles reporting on incidence, etiology, and case fatality. We summarized the findings using narrative and meta-analysis methods. RESULTS: We included 14 studies with sex-related data; the median (IQR) number of reported pneumonia cases was 148 (87-770) and 114 (56-599) for male and female patients, respectively. Only two studies reported a sex-specific incidence. The odds of sex were in favor of male sex, and the chances of identification of Respiratory Syncytia Virus (RSV) were significantly lower in males than in females (OR=0.60; 95% CI: 0.42, 0.86). Estimates from 9 studies showed that the death rate for males was significantly higher than for females (OR=1.26; 95% CI=1.20-1.33). CONCLUSIONS: Sex-disaggregated data on incidence, etiology, and case fatality of pneumonia are scarcely reported in studies published in Africa. However, males appear to die more often than females, and females more likely to have RSV infection.

Data-driven malaria prevalence prediction in large densely populated urban holoendemic sub-Saharan West Africa.

Over 200 million malaria cases globally lead to half-million deaths annually. The development of malaria prevalence prediction systems to support malaria care pathways has been hindered by lack of data, a tendency towards universal "monolithic" models (one-size-fits-all-regions) and a focus on long lead time predictions. Current systems do not provide short-term local predictions at an accuracy suitable for deployment in clinical practice. Here we show a data-driven approach that reliably produces one-month-ahead prevalence prediction within a densely populated all-year-round malaria metropolis of over 3.5 million inhabitants situated in Nigeria which has one of the largest global burdens of P. falciparum malaria. We estimate one-month-ahead prevalence in a unique 22-years prospective regional dataset of > 9 × 104 participants attending our healthcare services. Our system agrees with both magnitude and direction of the prediction on validation data achieving MAE ≤ 6 × 10-2, MSE ≤ 7 × 10-3, PCC (median 0.63, IQR 0.3) and with more than 80% of estimates within a (+ 0.1 to - 0.05) error-tolerance range which is clinically relevant for decision-support in our holoendemic setting. Our data-driven approach could facilitate healthcare systems to harness their own data to support local malaria care pathways.

Aflatoxin exposure in Nigerian children with severe acute malnutrition.

Aflatoxin exposure is an important public health concern in sub-Saharan Africa as well as parts of Latin America and Asia. In addition to hepatocellular carcinoma, chronic aflatoxin exposure is believed to play a role in childhood growth impairment. The most reliable biomarker of chronic aflatoxin exposure is the aflatoxin-albumin adduct, as measured by ELISA or isotope dilution mass spectrometry (IDMS). In this report, we have used high resolution LC-MS/MS with IDMS to quantitate AFB1-lysine in an extremely vulnerable population of Nigerian children suffering from severe acute malnutrition. To increase the sensitivity and reliability of the analyses, a labelled AFB1-13C615N2-lysine internal standard was synthesized. AFB1-lysine concentrations in this population ranged between 0.2 and 59.2 pg/mg albumin, with a median value of 2.6 pg/mg albumin. AFB1-lysine concentrations were significantly higher in stunted children (median = 4.6 pg/mg) compared to non-stunted (1.2 pg/mg), as well as in children with severe acute malnutrition (4.3 pg/mg) compared to controls (0.8 pg/mg). The median concentrations were also higher in children with kwashiorkor (6.3 pg/mg) compared to those suffering from marasmus (0.9 pg/mg). This is the first report of the use of high-resolution mass spectrometry to quantitate AFB1-lysine in humans.

Primary health workers' knowledge and practices relating to neonatal jaundice in Ibadan, Nigeria.

BACKGROUND: Over half of births and newborn care occur in primary healthcare facilities in Nigeria, but information on activities of personnel working there is scarce. AIM: To assess the knowledge and practices relating to neonatal jaundice (NNJ) among community health workers (CHWs) and community birth attendants (CBAs) in Nigeria. SETTING: We conducted a cross-sectional survey of all 227 CHWs and 193 registered CBAs in Ibadan, Nigeria. METHODS: Knowledge and practices regarding NNJ were measured using a pretested questionnaire. Knowledge and practices were assessed on a 33-point scale and a 13-point scale, respectively. Scores ≤  17 and ≤  9 was regarded as poor knowledge and as wrong practice, respectively. RESULTS: Many (64.5%) of the respondents could not correctly describe examination for NNJ (CHWs: 49.4%; CBAs: 50.6%). Of the 200 (47.6%) who treated NNJ 3 months prior to the study, 62.5% (CHWs: 66.9% and CBAs: 53.7%) treated NNJ with orthodox drugs. Drugs prescribed included: antibiotics (93.3%), antimalarials (5.3%), multivitamins (28.0%), paracetamol (6.2%) and phenobarbitone (7.1%). Significantly more CHWs than CBAs practiced exposure to sunlight (33.1% versus 16.4%) and administration of glucose water (28.6% versus 14.9%), while 58.0% of all respondents referred cases to secondary health facilities. Overall, 80.2% had poor knowledge (CHWs: 78.9%; CBAs: 81.9%) and 46.4% engaged in wrong practices (CHWs: 57.3%; CBAs: 33.7%). CHWs were more likely to indulge in wrong practices than CBAs (OR = 2.22, 95% CI = 1.03, 4.79). CONCLUSION: Primary Health Workers in Ibadan had poor knowledge and engaged in wrong practices about NNJ. The needs to organise regular training programmes were emphasised.

Self-reported sleep pattern, quality, and problems among schooling adolescents in southwestern Nigeria.

OBJECTIVE: Understanding sleep patterns and related factors is vital to development in adolescence, but there is a dearth of this information among adolescents in developing countries such as Nigeria. Therefore, this study describes the sleep patterns, problems, and predictors of poor sleep quality among schooling adolescents. METHODS: In a cross-sectional study design, 450 adolescents were selected and interviewed about their sleep experience and problems over the preceding one-month period using a validated form with components adapted from the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Data were analyzed using descriptive statistics, χ2, and logistic regression model with p set at 0.05. RESULTS: The mean age of respondents was 13.4 ± 1.2 years. Only half (50.2%) had a global PSQI score of <6, suggesting little or no difficulty with sleep. Significantly, a higher proportion of respondents spent a short time in bed before sleep, ≤15 min among those who had good sleep quality (81.4%) compared with those who had poor sleep quality (65.2%) (p < 0.001). The odds of having poor sleep quality was significantly higher in the subgroup who had ≤8.5 h sleep than those who had 8.5 h sleep or more (adjusted odds ratio = 4.62; 95% confidence interval = 2.61, 8.17, p < 0.001). CONCLUSION: Remarkably poor sleep quality exists among schooling adolescents in Ibadan, Nigeria, and sleep problems are prevalent, especially among those with short sleep duration.

Primary health workers' knowledge and practices relating to neonatal jaundice in Ibadan, Nigeria

Background: Over half of births and newborn care occur in primary healthcare facilities in Nigeria, but information on activities of personnel working there is scarce. Aim: To assess the knowledge and practices relating to neonatal jaundice (NNJ) among community health workers (CHWs) and community birth attendants (CBAs) in Nigeria. Setting: We conducted a cross-sectional survey of all 227 CHWs and 193 registered CBAs in Ibadan, Nigeria.Methods: Knowledge and practices regarding NNJ were measured using a pretested questionnaire. Knowledge and practices were assessed on a 33-point scale and a 13-point scale, respectively. Scores ≤ 17 and ≤ 9 was regarded as poor knowledge and as wrong practice, respectively. Results: Many (64.5%) of the respondents could not correctly describe examination for NNJ (CHWs: 49.4%; CBAs: 50.6%). Of the 200 (47.6%) who treated NNJ 3 months prior to the study, 62.5% (CHWs: 66.9% and CBAs: 53.7%) treated NNJ with orthodox drugs. Drugs prescribed included: antibiotics (93.3%), antimalarials (5.3%), multivitamins (28.0%), paracetamol (6.2%) and phenobarbitone (7.1%). Significantly more CHWs than CBAs practiced exposure to sunlight (33.1% versus 16.4%) and administration of glucose water (28.6% versus 14.9%), while 58.0% of all respondents referred cases to secondary health facilities. Overall, 80.2% had poor knowledge (CHWs: 78.9%; CBAs: 81.9%) and 46.4% engaged in wrong practices (CHWs: 57.3%; CBAs: 33.7%). CHWs were more likely to indulge in wrong practices than CBAs (OR = 2.22, 95% CI = 1.03, 4.79). Conclusion: Primary Health Workers in Ibadan had poor knowledge and engaged in wrong practices about NNJ. The needs to organise regular training programmes were emphasised

Intestinal Bacterial Colonization in the First 2 Weeks of Life of Nigerian Neonates Using Standard Culture Methods.

OBJECTIVE: The pattern and timing of development of intestinal microflora in Nigerian infants have been scarcely researched. This study was carried out to investigate the bacteria flora in the rectum of healthy neonates in Ibadan, Nigeria. PATIENTS AND METHODS: In this hospital-based longitudinal study, rectal swabs of 70 neonates were taken within 6-12 h of birth (day 1) and subsequently on days 3, 9, and 14. Information collected included maternal sociodemographic characteristics, antibiotic use for the neonates, and type of feeding during the first 14 days of life. Identification and speciation of gram-negative isolates were done using the Analytical Profile Index 20E® and 20NE® as appropriate. Gram-positive bacteria were identified biochemically using the catalase and coagulase tests. Data were analyzed using descriptive statistics and Chi-square at p = 0.05. RESULTS: Majority (92.9%) of the neonates were delivered vaginally with a median gestational age of 38 weeks (range = 34-42). On the first day of life, Escherichia coli was isolated more frequently from the rectal swabs of preterm (50.0%) than term (23.1%) neonates (p = 0.031). On day 3 of life, coagulase-negative staphylococcus was the most frequently isolated bacteria from the rectal swabs of nonasphyxiated (64.4%) compared with asphyxiated (27.3%) neonates' rectal swabs (p = 0.042). Staphylococcus aureus was the most frequently isolated bacteria from the rectal swabs of nonexclusively breastfed (66.7%) than exclusively breastfed (21.3%) neonates on day 14 (p = 0.004). CONCLUSION: Staphylococcus aureus and Escherichia coli were the predominant isolates from the rectum of Nigerian neonates, and these isolates were influenced by breastfeeding and mild-moderate asphyxia. In all, bacterial diversity in the rectum increased as the neonates got older.

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.

Prevalence and socio-demographic factors associated with non-protective immunity against tetanus among high school adolescents girls in Nigeria.

BACKGROUND: The low uptake of tetanus vaccine and its resultant high burden of tetanus in Nigeria suggest the need to improve routine and booster vaccination in children and adolescents. However, epidemiological evidence for vaccination in the adolescent age group needed for effective strategy and policy formulation is lacking. This study was carried out to determine the prevalence of protective immunity against tetanus and to identify risk factors for non-protective immunity among schooling adolescents. METHODS: Using a three-stage sampling technique, 851 female adolescents were randomly selected from secondary schools in Ibadan, Nigeria. A pre-tested questionnaire was used to obtain data on demographic and socio-economic characteristics and history of tetanus vaccination. An immuno-chromatographic rapid test kit, "Tetanos Quick Stick" was used to test specific anti-tetanus antibody protective level in venous blood samples. Descriptive statistics, Chi-square and logistic regression analyses were done with level of significance set at p = 0.05. RESULTS: Mean age of participants was 14.3 ± 1.9 years. Seroprevalence of protective immunity against tetanus was 38.1% and it significantly decreased with increasing age. More adolescents in public (65.4%) than private (44.7%) schools had non-protective level of immunity. A significantly increasing trend in the risk of non-protective immunity was observed with decreasing level of mothers' education. Also, the Odds of non-protective level of immunity was significantly higher in public than private schools (OR = 2.14; 95% CI =1.39, 3.20) but lower among adolescents who had history of recent tetanus toxoid injection than those who did not (OR = 0.11 95% CI = 0.09, 0.22). However, no significant association was found between protective immunity against tetanus and parents' marital status as well as family size. CONCLUSION: Protective immunity against tetanus among female adolescents was poor, more so in public schools and those who had not received vaccination a year prior to the study. Policy-makers need to consider the inclusion of immunization against tetanus in the school health programme.

Prevalence and predictors of hypoxaemia in respiratory and non-respiratory primary diagnoses among emergently ill children at a tertiary hospital in south western Nigeria.

BACKGROUND: Hypoxaemia is a potentially harmful complication of both acute lower respiratory tract infections (ALRI) and non-ALRI in children but its contribution to burden and outcomes of hospital admissions in Africa is unclear. We investigated prevalence and predictors of hypoxaemia in ALRI and non-ALRI according to age and primary diagnoses in emergently ill children in south western Nigeria. METHODS: In 1726 emergently ill children admitted to a tertiary hospital in Ibadan, south western Nigeria, oxygen saturation was measured shortly after admission. Hypoxaemia was defined as oxygen saturation <90%. Clinical features and the primary admission diagnoses were recorded. Prevalence of hypoxaemia according to age and diagnoses was calculated. Symptoms and signs associated with hypoxaemia were compared between children with ALRI and those with non-ALRI. RESULTS: Hypoxaemia was detected in 28.6% (494/1726) of admissions. Prevalence of hypoxaemia varied in different conditions: it was 49.2% (154/313) in ALRI, 41.1% (188/454) in neonates, 27.2% (6/22) in post-neonatal tetanus, 23.3% (14/60) in sickle cell anaemia, 22.6% (38/168) in septicaemia and 14.4% (76/527) of malaria cases. Nasal flaring (OR 3.86; 95% CI 1.70 to 8.74) and chest retraction (OR 4.77; 95% CI 1.91 to 11.92) predicted hypoxaemia in ALRI but not in non-ALRI. CONCLUSIONS: Hypoxaemia is common among Nigerian children admitted to an emergency unit and is associated with a poor outcome irrespective of primary admission diagnosis. Provision of equipment to measure oxygen saturation and facilities for effective oxygen delivery might substantially reduce mortality.

Static skinfold thickness in African newborns as an index of fetal nutritional assessment.

BACKGROUND: Fetal malnutrition (FM) has grave implications for the neonate and is reliably assessed by the CANSCORE which is time-consuming. Static skinfold thickness, a measure of adiposity, is a validated method of assessing malnutrition in older children. AIM: To establish if static skinfold measurements in neonates can serve as a reliable measure of FM. OBJECTIVE: To compare static skinfold thickness measurements in neonates using the CANSCORE for the identification of FM. METHOD: 252 consecutive term neonates delivered at University College Hospital, Ibadan, Nigeria had their CANSCOREs and static skinfold thickness measured within 24 hours of delivery. Using correlation and linear regression analysis, static skinfold thickness cut-off points for FM were determined using a reference CANSCORE of <25. RESULTS: Prevalence of FM was 20.2% and 26.2% using the CANSCORE and the sum of five skinfold thickness measurements, respectively. The mean (SD) skinfold thicknesses were triceps 3.91 mm (0.74), biceps 2.84 mm (0.55), subscapular 3.79 mm (0.91), supra-iliac 2.64 mm (0.62), quadriceps 4.43 mm (1) and the sum of all measurements 17.61 mm (3.16). All the skinfold thickness measurements correlated significantly with the CANSCORE, but the sum of the five had the best correlation. The quadriceps had the highest specificity of 85.6% and lowest sensitivity of 54.9%, while the sum of all had a sensitivity of 66.7% and specificity of 84.0%. CONCLUSION: The sum of all five skinfold measurements might be a useful screening tool for FM in view of its objectivity, convenience and simplicity, but it is not sufficiently sensitive or specific to replace the CANSCORE in the identification of FM in neonates.

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.

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.

Severe childhood malaria syndromes defined by plasma proteome profiles.

BACKGROUND: 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). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. METHODS AND FINDINGS: Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. CONCLUSIONS: We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes.