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

Distinct roles for FOXP3(+) and FOXP3(-) CD4(+) T cells in regulating cellular immunity to uncomplicated and severe plasmodium falciparum Malaria

Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to pathogenesis of severe malaria. To determine whether this balance is maintained by classical regulatory T cells (CD4+ FOXP3+ CD127−/low; Tregs) we compared cellular responses between Gambian children (n = 124) with severe Plasmodium falciparum malaria or uncomplicated malaria infections. Although no significant differences in Treg numbers or function were observed between the groups, Treg activity during acute disease was inversely correlated with malaria-specific memory responses detectable 28 days later. Thus, while Tregs may not regulate acute malarial inflammation, they may limit memory responses to levels that subsequently facilitate parasite clearance without causing immunopathology. Importantly, we identified a population of FOXP3−, CD45RO+ CD4+ T cells which coproduce IL-10 and IFN-γ. These cells are more prevalent in children with uncomplicated malaria than in those with severe disease, suggesting that they may be the regulators of acute malarial inflammation

Factors Associated With Pulmonary Tuberculosis-HIV Co-Infection in Treatment-Naive Adults in Jos, North Central Nigeria

Background: Co-infection with tuberculosis and human immunodeficiency virus (TB-HIV) remains a major global health problem, with about 1.1 million new cases of TB in HIV-positive persons reported in 2011; 79% of the reported cases were amongst patients living in Africa. Advanced immune suppression remains the most important risk factor for tuberculosis in those with HIV, but epidemiological and clinical factors have also been identified. We sought to determine the prevalence and factors associated with pulmonary tuberculosis (PTB) in antiretroviral therapy (ART)- naive HIV-infected patients seeking HIV care services at a tertiary health facility in North Central Nigeria. Methods: We compared clinical and laboratory data for 218 HIV-1 positive adults with and without a diagnosis of pulmonary tuberculosis. Results from univariate analyses informed the selection of predictors to conduct multivariate analysis to determine which factors were associated with presence of PTB-HIV co-infection. Results: The prevalence of PTB-HIV co-infection in the evaluated cohort was 9.6%. Lower CD4+ cell count and the presence of oropharyngeal candidiasis were independently associated with PTB-HIV co-infection. CD4+ cell count was strongly associated with PTB-HIV co-infection (p=0.002) with the odds of co-infection reduced by 85% in those with a CD4+ cell count >100 cells/mm3 compared to those with <100 cells/ mm3. There was a strong association between oropharyngeal candidiasis and PTB-HIV co-infection, where the odds of co-infection are about 4.5 times higher in those with oropharyngeal candidiasis than those without candidiasis (p=0.008). Conclusion: PTB was prevalent among HIV patients seeking care in our setting. Severe immune suppression and oropharyngeal candidiasis were associated with PTB-HIV co-infection in our patients at presentation. Potential implications for severe immune suppression and advanced HIV disease are a poor clinical outcome and further spread of PTB. Strategies to encourage the early diagnosis of both HIV and TB should be considere

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

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

Antituberculosis drugs and hepatotoxicity among hospitalized patients in Jos, Nigeria

Background: Tuberculosis (TB) could be fatal if left untreated, however, adverse effects of anti-TB medications (anti-TBs) themselves may limit treatment. We determined the incidence and clinical characteristics of hepatotoxicity in hospitalized patients receiving first-line anti-TB treatment. Methods: A retrospective cohort study of patients aged ≥18 years seen at the medical wards of the Jos University Teaching Hospital from January 2013 to June 2013 was carried out. Data were retrieved for 110 patients who were prescribed anti-TBs. Their demographic and clinical characteristics were described, and the incidence of symptomatic hepatotoxicity determined. The incidence of hepatotoxicity by strict American Thoracic Society criteria (symptomatic hepatotoxicity plus alanine transaminase in IU/L levels >3×upper limit of normal) was also determined. Results: Twenty patients developed symptomatic hepatotoxicity, giving an incidence of 18.2%. Furthermore, 18 (16.4%) patients had hepatotoxicity according to the American Thoracic Society criteria. Those with symptomatic hepatotoxicity unexpectedly had lower baseline alanine transaminase interquartile range (IQR) (35 [16–63] vs. 67 [4–226]; p =.04) and bilirubin (μmol/L): total IQR (15.3 [10.2–74.8] vs. 20.4 [20.4–20.4]; p =.01) and conjugated IQR (7.6 [5.1–34.8] vs. 10.2 [10.2–10.2]; p =.004). However, there were no significant differences in age, sex, body mass index, and duration of anti-TB treatment, human immunodeficiency virus infection status, antiretroviral therapy status, alcohol consumption, and the presence of hepatitis B surface antigen or hepatitis C virus antibody. Conclusion: Hepatotoxicity due to first-line anti-TBs, whether based on clinical features alone or backed by liver chemistry, is common among hospitalized patients in our environment. Studies to determine the predictors of hepatotoxicity to guide clinical interventions aimed at the prevention or timely identification of cases are needed

Predictors of hyperlactataemia among children presenting with malaria in a low transmission area in The Gambia.

BACKGROUND: Hyperlactataemia and metabolic acidosis are important risk factors for malaria death, but measuring lactate at the point of care is not financially viable in many resource-poor settings. This study aimed to identify combinations of routinely available parameters that could identify children at high risk of hyperlactataemia. METHODS: Using data from a study of Gambian children aged six months to 16 years with severe or uncomplicated malaria, logistic regression modelling with a forward stepwise model selection process was used to develop a predictive model for hyperlactataemia from routinely available demographic, clinical and laboratory parameters. Potential predictors of hyperlactataemia considered for the modelling process were patient characteristics (age, sex, prior use of anti-malarials, and weight percentile for age), respiratory symptoms (deep breathing, irregular respiration, use of accessory muscles of respiration, lung crepitations, grunting respiration, cough, and age-specific respiratory rate), other clinical parameters recorded at presentation (duration of symptoms, Blantyre coma score, number of convulsions prior to admission, axillary temperature, dehydration, severe prostration, splenomegaly) and laboratory measures from blood tests (percentage parasitaemia, white cell count, lymphocyte count, neutrophil count, monocyte count, platelet count, haemoglobin level, blood glucose level). RESULTS: 495 children were included, and 68 (14%) had laboratory-confirmed hyperlactataemia (lactate > 7 mmol/L). Four features were independently associated with increased hyperlactataemia risk in a multivariable age- and sex-adjusted model: lower Blantyre score (odds ratio (OR) compared to score 5 = 2.68 (95% CI, 1.03-6.96) for score 3-4 and 6.18 (95% CI, 2.24-17.07) for score 0-2, p = 0.001), higher percentage parasitaemia (OR = 1.07 (1.03-1.11) per 0031% increase, p < 0.001), high respiratory rate for age (OR = 3.09 (1.50-6.38) per unit increase, p = 0.002), and deep breathing (OR = 2.81 (1.20-6.60), p = 0.02). Cross-validated predictions from the final model achieved area under the receiver operating characteristic curve of 0.83. CONCLUSIONS: This study identified predictors of hyperlactataemia requiring only simple bedside clinical examination and blood film examination that can be carried out in resource-limited settings to quickly identify children at risk of dangerously raised lactate. A simple spreadsheet tool implementing the final model is supplied as supplementary material

Prevalence of and risk factors for pulmonary tuberculosis among newly diagnosed HIV-1 infected Nigerian children

Introduction: Studies on the prevalence of and risk factors for tuberculosis (TB) among newly diagnosed human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa are scarce and in Nigeria there is paucity of reported data. We determined the prevalence of and risk factors for pulmonary TB (PTB) in newly diagnosed (treatment-naïve) HIV-1 infected children at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Nigeria. Methods: We performed a retrospective analysis of 876 children, aged 2 months – 13 years, diagnosed with HIV-1 infection between July 2005 and December 2012, of which 286 were diagnosed with PTB at presentation after TB screening. The study site was the AIDS Prevention Initiative in Nigeria (APIN)-supported Pediatric HIV clinic at JUTH, Jos. A multivariate forward logistic regression modelling was used to identify risk factors for PTB-HIV co-infection. Results: The prevalence of PTB-HIV co-infection was 32% (286/876). Severe immunosuppression (SI) and World Health Organization (WHO) HIV clinical stage 3/4 were identified as independent risk factors for PTB-HIV co-infection in HIV infected children. The odds of PTB-HIV co-infection was increased two-fold in HIV-infected children with WHO clinical stage 3/4 compared to those with stage 1/2 (adjusted odds ratio (AOR) 1.76 [1.31-2.37], p<0.001) and 1.5-fold in children with SI compared to those without SI (AOR 1.52 [1.12-2.06], p=0.007). Conclusion: In our setting, the burden of PTB was high among newly diagnosed HIV-infected children, and late WHO HIV clinical stage and severe immunosuppression were associated with PTB-HIV co-infection. Therefore there is a clear need to improve strategies for early diagnosis of both HIV and PTB to optimize clinical outcomes