Pattern and Trends of Respiratory Disease Admissions at the Emergency Paediatrics Unit of Jos University Teaching Hospital – A Four Year Review

Aims: Respiratory diseases contributes substantially to the number of Paediatric admissions and deaths especially in low income countries. Understanding the trends will help in health planning and resource distribution. This study is to describe the pattern and trend of respiratory diseases in children in a tertiary healthcare facility in north-central Nigeria. Study Design: This study was a retrospective study including all patients admitted and managed with respiratory diseases. The relevant clinical information was extracted from the hospital records. Place and Duration of Study: The Emergency Paediatric Unit (EPU) of the Jos University Teaching Hospital (JUTH), Jos Nigeria, between January 2012 and December 2015. Methodology: A total of 2277 children aged 6 weeks-18 years were admitted into the unit within the study period. Out of these, 498 (21.9%) were diagnosed with respiratory disease. Clinical records were retrieved and reviewed. Those with inconclusive diagnosis as well as those with associated co-morbidities such as cardiac anomalies were excluded. The data collected were entered and analyzed using Epi Info version 7.2. Student t-test and chi-square test were used to analyze categorical and continuous variables respectively. Results: Pneumonia accounted for 54.4% of total respiratory diseases. Cases of Pneumonia were mostly seen at the peak of the rainy and the harmattan seasons. (March, June/July and October/November). The highest number of cases of respiratory diseases were in the under-fives. The commonest complication was congestive cardiac failure and it was commoner in the younger age group. Conclusion: The prevalence of respiratory diseases remains high and contributes significantly to hospital admissions especially in the under five children. There is need to introduce new vaccines and re-enforce existing immunization against common organisms that cause pneumonia in children. There is also need to introduce policies that would ensure appropriate treatment for children to reduce the burden of these diseases

Detection and Diagnostic Accuracy of Rapid Urine Lipoarabinomannan Lateral-Flow Assay in Pulmonary Tuberculosis patients in Nigeria

Background: Tuberculosis (TB) is a public health challenge in both developed and developing countries. Early diagnosis is essential in preventing the further spread of the disease, but the control programs are currently facing a number of constraints and fewer than 25% of all tuberculosis cases especially childhood cases are detected. We aimed to evaluate diagnostic accuracy of a commercially available qualitative immunoassay for the detection of lipoarabinomannan (LAM) antigen of Mycobacteria in human urine by comparing its sensitivity and specificity in TB patients with the AFB and GeneXpert in individuals with presumptive tuberculosis cases.Methods: A cross-sectional study that consecutively enrolled 53 eligible TB adults’ patients attending TB Centre, Mangu, Plateau State from February to March 2017. We applied the LAM test on urine collected as a spot and early morning sample. Diagnostic accuracy was analyzed for a microbiological TB reference standard based on Gene Xpert MTB/RIF results and for a composite reference standard including clinical data. Performance of sputum smear microscopy (AFB) was included for comparison. Results: The mean age of the respondents was 41.0±17.0 years.) The male proportion was 36(68.0%) and female was 17(32.0%). The patients with HIV-1 Co-infection were 9(23.8%). Of the 53 patients, the positive testing rate of TB using LAM test was 11 (20.8 %). The proportion of those who tested positive using Gene Xpert was 9(17.0%) and AFB was 33(62.2%), and the sensitivity and specificity were 33.3% and 93.2%, respectively. Negative and positive predictive values were 87.23% and 50.0%, diagnostic accuracy was 83.02%. Conclusion: The study showed great sensitivity of urine LAM test suggesting it could be useful as point of care diagnostic test for presumptive TB cases. Its high negative predictive value suggests a role in screening out uninfected patients; though GeneXpert had superior sensitivity, but the ease of the LAM test holds operational advantage as a screening method, however larger studies are needed to further determine diagnostic accuracy

Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis.

Inhibition of nitric oxide (NO) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor, and arginine, the NOS substrate. We carried out a community-based case-control study of Gambian children to determine whether ADMA and arginine homeostasis is disrupted during severe or uncomplicated malaria infections. Circulating plasma levels of ADMA and arginine were determined at initial presentation and 28 days later. Plasma ADMA/arginine ratios were elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children (p<0.0001 for each comparison). To test the hypothesis that DDAH1 is inactivated during Plasmodium infection, we examined DDAH1 in a mouse model of severe malaria. Plasmodium berghei ANKA infection inactivated hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue ADMA, elevated ADMA/arginine ratio in plasma, and decreased whole blood nitrite concentration. Loss of hepatic DDAH1 activity and disruption of ADMA/arginine homeostasis may contribute to severe malaria pathogenesis by inhibiting NO synthesi

Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis.

Inhibition of nitric oxide (NO) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor, and arginine, the NOS substrate. We carried out a community-based case-control study of Gambian children to determine whether ADMA and arginine homeostasis is disrupted during severe or uncomplicated malaria infections. Circulating plasma levels of ADMA and arginine were determined at initial presentation and 28 days later. Plasma ADMA/arginine ratios were elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children (p<0.0001 for each comparison). To test the hypothesis that DDAH1 is inactivated during Plasmodium infection, we examined DDAH1 in a mouse model of severe malaria. Plasmodium berghei ANKA infection inactivated hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue ADMA, elevated ADMA/arginine ratio in plasma, and decreased whole blood nitrite concentration. Loss of hepatic DDAH1 activity and disruption of ADMA/arginine homeostasis may contribute to severe malaria pathogenesis by inhibiting NO synthesis

Diagnostic accuracy of Xpert® MTB/RIF Ultra for childhood tuberculosis in West Africa - a multicentre pragmatic study

OBJECTIVE: To evaluate the performance of Xpert MTB/RIF Ultra ('Ultra') for diagnosis of childhood tuberculosis (TB) within public health systems. METHODS: In this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra. RESULTS: Overall, 193 children were included in the analyses with a median (IQR) age of 4.0 (1.1 - 9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% CI: 28.0 - 79.0%) and 95.0% (95% CI: 88.0 - 98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6 - 83.3%) and 70.9% (95% CI: 51.9 - 85.8%), respectively. CONCLUSION: Ultra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countries

HMOX1 Gene Promoter Alleles and High HO-1 Levels Are Associated with Severe Malaria in Gambian Children

Heme oxygenase 1 (HO-1) is an essential enzyme induced by heme and multiple stimuli associated with critical illness. In humans, polymorphisms in the HMOX1 gene promoter may influence the magnitude of HO-1 expression. In many diseases including murine malaria, HO-1 induction produces protective anti-inflammatory effects, but observations from patients suggest these may be limited to a narrow range of HO-1 induction, prompting us to investigate the role of HO-1 in malaria infection. In 307 Gambian children with either severe or uncomplicated P. falciparum malaria, we characterized the associations of HMOX1 promoter polymorphisms, HMOX1 mRNA inducibility, HO-1 protein levels in leucocytes (flow cytometry), and plasma (ELISA) with disease severity. The (GT)n repeat polymorphism in the HMOX1 promoter was associated with HMOX1 mRNA expression in white blood cells in vitro, and with severe disease and death, while high HO-1 levels were associated with severe disease. Neutrophils were the main HO-1-expressing cells in peripheral blood, and HMOX1 mRNA expression was upregulated by heme-moieties of lysed erythrocytes. We provide mechanistic evidence that induction of HMOX1 expression in neutrophils potentiates the respiratory burst, and propose this may be part of the causal pathway explaining the association between short (GT)n repeats and increased disease severity in malaria and other critical illnesses. Our findings suggest a genetic predisposition to higher levels of HO-1 is associated with severe illness, and enhances the neutrophil burst leading to oxidative damage of endothelial cells. These add important information to the discussion about possible therapeutic manipulation of HO-1 in critically ill patients

Erythrocyte invasion and merozoite ligand gene expression in severe and mild Plasmodium falciparum malaria.

Erythrocyte invasion is central to malaria parasite replication and virulence. Plasmodium falciparum parasites use different alternative erythrocyte receptors and vary in expression of erythrocyte-binding antigenic (EBA) proteins and reticulocyte-binding protein homologues (Rh). Parasite invasion phenotypes and schizont-stage transcript expression profiles of the 8 eba and Rh protein-coding genes without internal stop codons were determined for 163 clinical isolates cultured ex vivo in The Gambia. There was extensive diversity in ability to invade erythrocytes treated with neuraminidase, trypsin, or chymotrypsin, and severe malaria isolates were less restricted by trypsin treatment than were mild malaria isolates (P = .015). Expression profiles of the eba and Rh genes showed distinct clusters indicating coordinated alternative transcription. The most divergent of 5 major clusters was dominated by Rh2b, with virtually no expression of eba175 or eba140 genes (which were dominant in the other 4 clusters). Particular transcripts were significantly correlated with parasitemia (Rh5 was positively correlated and eba140 negatively correlated; P < .01 for both) and age of patients (eba181 was positively correlated and eba175 negatively correlated; P < .001 for both) but not with invasion phenotypes or severity of malaria. Severe and mild malaria isolates were also evenly represented across the different expression clusters

Prevalence of Helicobacter pylori in children by noninvasive stool Antigen Enzyme Immunoassay

Background: Helicobacter pylori (H. pylori) infection is contracted in childhood, and it is considered as an important risk factor for acid-pectic disorders and neoplasms later in life. A noninvasive H. pylori stool antigen test was used to determine the prevalence of H. pylori infection in children and the sociodemographic and clinical characteristic of children with H. pylori infection described.Methods: A total of 102, symptomatic and asymptomatic, children aged 1-15 years, were consecutively recruited at the outpatient department of Plateau State Specialist Hospital in Jos, Nigeria. Eighty-seven (87/102, 85.3%) stool samples were analyzed using H. pylori stool antigen kit (HpSATM GeneFronts elisaVUE TM, 2950 Scott Blvd, Santa Clara, CA 95054, USA) to detect H. pylori antigen. Prevalence of H. pylori infection, socio-demographic and clinical characteristics of children with H. pylori infection, and the association of these factors with H. pylori infection were determined.Results: Of 87 stool samples tested, 32 were positive for H. pylori giving a H. pylori prevalence of 36.8%. Majority of the children were males (51.2%) and their median age (IQR) 10 (6- 12) years. Majority of those with H. pylori infection resided in urban areas compared to rural areas (15, 51.7% versus 14, 48.3%); p = 0.354), lived in room type accommodation compared to flat apartment accommodation (17, 53.1% versus 15, 46.9%; p = 0.235) and fewer were HIV-positive compared to those who were negative (5, 15.6% versus 27, 84.4; p = 0.330). No significant associations were observed between any of the socio demographic or clinical variables and H. pylori infection.Conclusion: In this study, the prevalence of H. pylori infection among the children tested was low. Stool antigen testing has the potential advantage of being relatively simple to perform and is also a non-invasive technique, therefore it could be a useful tool for mass screening for H. pylori infection in children.Keywords: Helicobacter pylori, Stool antigen, Enzyme immunoassay, Prevalence, Children, Nigeri