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.

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.

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

OBJECTIVE: To evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (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 (interquartile range) 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% confidence interval [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.

Pretreatment and Acquired Drug Resistance in Children With Human Immunodeficiency Virus Type 1 in Jos, Nigeria.

We determined pretreatment and acquired human immunodeficiency virus (HIV) drug resistance among children with HIV type 1 (HIV-1) in Jos, Nigeria. The majority (71%) of those who failed first-line antiretroviral therapy were on a nevirapine-containing regimen. The prevalence of pretreatment (48%) and acquired (76%) HIV drug resistance mutations was high in our study. Wider access to HIV drug resistance testing after treatment failure is necessary to optimize second-line treatment options among children with HIV in Nigeria.

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.

Immunization status of children 1-5 years old seen at the Emergency Pediatric Unit of a Teaching Hospital in North-Central Nigeria.

Introduction: Advocacy for immunization has been ongoing in various parts of the world to improve immunization uptake amongst children. Annually within the last decade, immunization has been reported to avert over two million deaths globally. This study determined the current immunization status of children 1-5 years of age, the factors affecting immunization uptake and recommends ways of improving immunization uptake among children presenting at an Emergency Pediatric Unit (EPU). Methods: This was a prospective cross-sectional study conducted from 1st October to 30th November 2019. All eligible children aged 1-5 years old seen within the study period whose mothers/caregivers consented to participate in the study were recruited in the EPU of Jos University Teaching Hospital (JUTH), Plateau State, Nigeria. A systematic sampling technique was employed in the selection of caregiver/mother-child pair while data were obtained using an interviewer-administered questionnaire. Results: A total of 191 (76.4%) children were fully immunized for age. Distance to the health facility, experience of vaccine side effects and health workers' attitude were significantly associated with immunization status. Distance to health facility was an independent predictor of complete immunization while short messaging service (SMS) was the most preferred 190 (76.0%) way suggested to improve immunization uptake. Conclusions: This study has brought to light a suboptimal level of full immunization status for age, which can be improved by targeting homegrown interventions at improving accessibility to the facility and addressing adverse events following immunization promptly.

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-gamma. 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.

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 latent tuberculosis infection in HIV-1-infected children on antiretroviral therapy in Jos, Nigeria.

Background: There are few studies investigating the prevalence of latent tuberculosis infection (LTBI) in HIV-1-infected children on antiretroviral therapy (ART), but no data from Nigeria. This study determined the prevalence of LTBI in HIV-1-infected children on ART in our clinic. Knowing the prevalence and thus the burden of LTBI could help improve HIV care by enabling targeted isoniazid (INH) prophylaxis. Method: This observational study was carried out from September 2016 to August 2017 at the pediatric HIV clinic of the Jos University Teaching Hospital among HIV-1-infected children on ART, aged 6 months-15 years. LTBI was diagnosed using an interferon-gamma release assay, the ELISpot test, T-SPOT®.TB assay (Oxford Immunotec, Abingdon, UK) on freshly collected whole blood samples within 2 h. Children with a positive test were treated with INH after first excluding TB by chest X-ray and clinical evaluation. Results: Of the 90 children studied, 4 (4.4%) had LTBI diagnosed by ELISpot. Their median interquartile range (IQR) age was 10.4 years (7.9-12.5), the majority were male (54.4%) and most of them had originally received Bacille Calmette-Guérin (83/89, 93.3%). They had a median CD4 count of 694 cells/µL (472-1045). The median (IQR) CD4 count was higher in LTBI compared to non-LTBI children: 1286 cells/µL (953-1375) versus 683 cells/µL (465-1040), (P = 0.044). Conclusion: Although this study showed a very low prevalence of LTBI in our setting, it was still beneficial to the few children on ART identified with LTBI as it enabled treatment with INH. A larger study will be required to ascertain the actual burden of LTBI in such children in our setting.

Improving the diagnosis of pulmonary tuberculosis using line probe assay and determining the factors associated with the disease in children in Jos, Nigeria.

INTRODUCTION: Diagnosing tuberculosis (TB), including pulmonary tuberculosis (PTB), in children remains a challenge, partly due to its paucibacillary nature in young children. Data on the use of line probe assay (LPA), on gastric and sputum samples, for diagnosing PTB in children are scarce. We determined the proportion of samples positive for Mycobacterium tuberculosis (MTB) by smear microscopy (SM) and LPA in presumptive PTB cases as well as the factors associated with PTB confirmed by LPA, in children in Jos, Nigeria. METHODS: An observational study in children aged 6 months-16 years. Gastric and sputum samples were examined by SM and by LPA for MTB using GenoType MTBDRplus Ver 2.0 (Hain Lifescience). Multivariate logistic regression was performed to determine the factors associated with PTB. RESULTS: Out of 103 children with presumptive PTB, 47 had confirmed PTB, 26 unconfirmed PTB and 30 unlikely PTB by LPA. In 67 gastric samples, MTB was identified by SM in 2 (3.0%) compared to 28 (41.8%) by LPA while in 31 sputum samples, MTB was identified by SM in 5 (16.1%) compared to 18 (58.1%) by LPA. The factors associated with pulmonary tuberculosis were an abnormal chest X-ray (adjusted odds ratio (AOR))=12.39 [3.75-40.90], p<0.001), sleeping in the same room with more than three persons (AOR=3.30 [1.23-8.85], p=0.018) and sleeping in a room with none or one window (AOR=2.86 [1.03-7.95], p=0.044). CONCLUSIONS: Line probe assay improves the diagnosis of pulmonary TB in children, especially with gastric samples, while an abnormal chest X-ray is a useful adjunct in PTB diagnosis. Avoiding overcrowding and having windows in sleeping rooms are a necessary part of TB prevention.

Meeting oxygen needs in Africa: an options analysis from the Gambia.

OBJECTIVE: To compare oxygen supply options for health facilities in the Gambia and develop a decision-making algorithm for choosing oxygen delivery systems in Africa and the rest of the developing world. METHODS: Oxygen cylinders and concentrators were compared in terms of functionality and cost. Interviews with key informants using locally developed and adapted WHO instruments, operational assessments, cost-modelling and cost measurements were undertaken to determine whether oxygen cylinders or concentrators were the better choice. An algorithm and a software tool to guide the choice of oxygen delivery system were constructed. FINDINGS: In the Gambia, oxygen concentrators have significant advantages compared to cylinders where power is reliable; in other settings, cylinders are preferable as long as transporting them is feasible. Cylinder costs are greatly influenced by leakage, which is common, whereas concentrator costs are affected by the cost of power far more than by capital costs. Only two of 12 facilities in the Gambia were found suitable for concentrators; at the remaining 10 facilities, cylinders were the better option. CONCLUSION: Neither concentrators nor cylinders are well suited to every situation, but a simple options assessment can determine which is better in each setting. Nationally this would result in improved supply and lower costs by comparison with conventional cylinders alone, although ensuring a reliable supply would remain a challenge. The decision algorithm and software tool designed for the Gambia could be applied in other developing countries.

Long Term Exposure to Tenofovir Disoproxil Fumarate-Containing Antiretroviral Therapy Is Associated with Renal Impairment in an African Cohort of HIV-Infected Adults.

OBJECTIVES AND METHOD: There are growing concerns of tenofovir disoproxil fumarate (TDF)-associated renal toxicity. We evaluated the effect of long-term TDF exposure on renal function in a cohort of HIV-1-infected Nigerians between 2006 and 2015. Multivariate logistic regression was used to identify predictors of renal impairment at different time over 144 weeks of antiretroviral therapy (ART). RESULTS: Data of 4897 patients, median age 42 years (interquartile range: 36-49), and 61% females were analyzed. The prevalence of renal impairment increased from 10% at week 24 to 45% at 144 weeks in TDF-exposed participants compared to an increase from 8% at 24 weeks to 14% at 144 weeks in TDF-unexposed participants. Tenofovir disoproxil fumarate exposure predicted the risk of renal impairment at 144 weeks of ART (odds ratio: 2.36; 95% confidence interval: 1.28-4.34). CONCLUSION: Long-term exposure to TDF-based ART significantly increases the likelihood of renal impairment. The continued use of TDF-based regimen in our setting should be reviewed. We recommend the urgent introduction of tenofovir alafenamide-based regimen in the HIV treatment guidelines of Nigeria and other resource-limited countries.

Serum lipid and glucose profiles in HIV-positive Nigerian children.

OBJECTIVES: To describe the fasting serum lipid and glucose profiles of HIV-positive Nigerian children and determine the prevalence and risk factors for dyslipidaemia and hyperglycaemia, which are risk factors for cardiovascular diseases. METHODS: This was a comparative cross-sectional study carried out at the Paediatric Infectious Disease Clinic (PIDC) of the Jos University Teaching Hospital (JUTH) for HIV-positive children and at two primary schools in Jos for HIV-negative children as controls. One hundred and forty-two HIV-positive children aged 6-18 years and an equal number of controls were studied by determining their fasting serum lipid and glucose levels. The prevalence of dyslipidaemia and hyperglycaemia was determined and their risk factors obtained using multivariate logistic regression. P values of less than 0.05 were considered statistically significant. RESULTS: Mean triglyceride levels were significantly higher in HIV-positive children compared with controls at 87.2 mg/dL (95% confidence interval [CI] 79.4-95.0) and 68.1 mg/dL (95% CI 62.5-72.7), respectively (P<0.001). There were no significant differences in mean glucose levels. Dyslipidaemia was significantly higher in HIV-positive children (21.8%) compared with controls (12.7%; P=0.04). Total serum cholesterol was elevated in 17 (12.0%) HIV-positive participants compared with seven (4.9%) of controls (P=0.02). Children on lopinavir/ritonavir (LPV/r) and those with no significant or mild disease had a significantly higher prevalence of hypercholesterolaemia (33.3% vs 4.8% and 14.5% vs 0.0%, respectively; P<0.001). CONCLUSION: HIV-positive children on antiretroviral (ARV) drugs, especially LPV/r, should have their lipids regularly monitored as those with dyslipidaemia stand the risk of subsequently developing cardiovascular diseases.

Changes in the haematological parameters of HIV-1 infected children at 6 and 12 months of antiretroviral therapy in a large clinic cohort, North-Central Nigeria.

BACKGROUND: Prior to commencing antiretroviral therapy (ART), haematological abnormalities are a common occurrence in individuals diagnosed with human immunodeficiency virus (HIV). In the course of receiving ART, these abnormalities usually improve. We determined the prevalence of haematological abnormalities in children diagnosed with HIV-1 and the changes in haematological parameters that occur after 6 and 12 months of being on ART. METHODS: A cross-sectional study of HIV-1 infected children aged 2 months to 15 years, between July 2005 and March 2013, at the paediatric HIV clinic of the Jos University Teaching Hospital, Jos. Median values of repeated measures were compared using the Wilcoxon signed-rank sum test. RESULTS: The prevalence of anaemia, thrombocytopenia and leukopenia among the 941 children studied, prior to ART was 6.4%, 7.0% and 8.6%. Median (IQR) haemoglobin (Hb) levels increased from 10 g/dL (9-11 g/dL) at baseline to 11 g/dL (10-12 g/dL) and 11 g/dL (10-12 g/dL) at 6 and 12 months of ART (P<0.001 and P<0.001), respectively, a 10% increase in both cases. Also, platelet count increased from a median of 327×103/µL (243-426×103/µL) at baseline to 333×103/µL (266-408×103/µL) at 6 months and 339×103/µL (267-420×103/µL) at 12 months, representing a 1.8% and 3.7% increase, respectively. The median total white blood cell count decreased from 7.4×103/µL (5.3-9.9×103/µL) at baseline to 5.9×103/µL (4.6-8.0×103/µL) and 5.8×103/µL (4.5-7.5×103/µL) at 6 and 12 months of ART (P<0.001 and P<0.001), a 20.3% and 21.6% decrease, respectively. CONCLUSION: During the 12 months of ART, children in our cohort had significant improvements in haematological parameters such as haemoglobin levels and platelet counts, which would suggest an early positive response to ART.

Demographic and clinical correlates of HIV-1 RNA levels in antiretroviral therapy-naive adults attending a tertiary hospital in Jos, Nigeria.

BACKGROUND: Plasma HIV-RNA viral load (VL) of HIV-infected persons is an important prognostic factor in HIV management. We determined the VL among antiretroviral therapy (ART)-naive patients to identify the association between patients' demographic, clinical and laboratory characteristics with VL. METHOD: A cross-sectional study of 224 ART-naive HIV-1-infected patients (≥15 years of age) accessing care at the Jos University Teaching Hospital AIDS Prevention Initiative in Nigeria ART treatment centre, from October 2010 to April 2011. A log-linear model was used to determine if VL was related to demographic and clinical variables. RESULTS: The patients had a median (interquartile range) age of 34 (28-41) years with females in the majority (59%). Females compared to males and pulmonary tuberculosis (PTB) co-infected compared to not co-infected patients had a significantly higher VL (14.9 loge versus 11.5 loge, P=0.003 and 11.31 loge versus 11.89 loge, P=0.047, respectively). VL tended to decrease with increasing CD4+ cell count levels in females, but remained relatively unchanged in males across all values of CD4+ cell counts. The difference (ß) in the mean change in VL between males and females was loge 0.64 copies/mL, P=0.005. CONCLUSION: In ART-naive HIV-1-infected patients in our setting, females had significantly higher VL and lower CD4+ cell count, at the same VL threshold, compared to males, and hence were more likely to be at a higher risk of rapid progression to AIDS. Therefore, gender-based strategies for early identification and engaging females into care are required in this setting to mitigate against rapid progression to AIDS.

Mortality among pulmonary tuberculosis and HIV-1 co-infected Nigerian children being treated for pulmonary tuberculosis and on antiretroviral therapy: a retrospective cohort study.

BACKGROUND: Mortality data, including the risk factors for mortality in HIV-infected children with pulmonary TB (PTB) being treated for PTB and who are on antiretroviral therapy (ART), are scarce in Nigeria. We determined the mortality rate and risk factors for mortality among such children, at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Jos, Nigeria. METHODS: We performed a retrospective cohort study on 260 PTB-HIV-1 co-infected children, aged 2 months to 13 years, being treated for PTB and on ART from July 2005 to March 2013. The mortality rate and associated risk factors were determined using multivariate Cox proportional hazards modelling. RESULTS: The mortality rate for the study cohort was 1.4 per 100 child-years of follow-up. Median follow-up time was 5.2 years (IQR, 3.5-6.0 years) with total study time being 1159 child-years. The median age of those who died was lower than that of survivors, 1.9 years (IQR, 0.6-3.6 years) versus 3.8 years (IQR, 1.8-6.0 years), p=0.005). The majority of the deaths occurred in males (13, 81.2%), those <5 years of age (14, 87.4%) and those who had severe immunosuppression (11, 68.8%). Risk factors for death were age (with the risk of dying decreasing by 25% for every 1 year increase in age, adjusted hazard ratio (AHR)=0.75 [0.58-0.98], p=0.032), male gender (AHR=3.80 [1.07-13.5], p=0.039) and severe immunosuppression (AHR=3.35 [1.16-9.66], p=0.025). CONCLUSION: In our clinic setting, mortality among our PTB-HIV co-infected children being treated for PTB and on ART was low. However, those presenting with severe immunosuppression and who are males and very young, should be monitored more closely during follow-up in order to further reduce mortality.

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 ⩾18years 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.

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.

Molecular characterization of cryptosporidium in children aged 0- 5 years with diarrhea in Jos, Nigeria.

INTRODUCTION: Cryptosporidium is an important cause of diarrhea in children and immune-compromised individuals. Recent advances in molecular diagnostics have led to the discovery of subtype families that are thought to be more commonly associated with diarrhea. We aimed to isolate and characterize Cryptosporidium spp among children with diarrhea in Jos, Nigeria. METHODS: Stool samples were collected from165 children aged 0-5 years with diarrhea. Cryptosporidium oocysts were examined by wet mount preparation, using formalin ether and a modified acid fast staining method. DNA was extracted from positive samples using QIAamp DNA stool mini kit and PCR-RFLP assay was carried out after quantification. Genotyping and phylogenetic analysis were done to determine the subtype families and their relatedness. RESULTS: From the 165 children studied, 8 (4.8%) were infected with Cryptosporidium. PCR-RFLP assay and genotype characterization found the following Cryptosporidium species: C. hominis 6 (75%) and C. parvum 2 (25.0%), with family subtypes Id-5, Ie-1 and IIa-1, IId-1 respectively.The most common species was C. hominis and the frequent subtype was C. hominis-Id 5 (62.5%). CONCLUSION: Cryptosporidium is not an uncommon cause of diarrhea in children, with C. hominis being the dominant species. Also C. hominis Id is the commonest sub-family subtype. Put together, zoonotic species may be an important cause of diarrhea in children aged 0-5 years in Jos, Nigeria.

Factors associated with antiretroviral treatment interruption in human immunodeficiency virus (HIV)-1-infected children attending the Jos University Teaching Hospital, Jos, Nigeria.

BACKGROUND: Interrupting anti-retroviral therapy (ART) for any number of reasons is an indication of a compromised adherence to ART. Several factors, including the pill burden from other drugs used in treating co-infections in children with human immunodeficiency virus (HIV), may influence ART adherence. The aim of this study was to identify the factors associated with ART interruption in HIV-1-infected children. MATERIALS AND METHODS: A retrospective cohort study analysing data on 580 children consecutively enrolled on ART between February 2006 and December 2010 at the paediatric HIV clinic of Jos University Teaching Hospital (JUTH), Jos. Subjects were children aged 2 months - 15 years diagnosed with HIV-1 infection and on first-line ART. Cotrimoxazole prophylaxis was usually commenced at diagnosis while awaiting ART commencement. Children diagnosed with tuberculosis (TB) were also placed on multiple individual anti-TB drugs. STATISTICAL ANALYSIS USED: A comparison of the data on children with and without ART interruption was made. Variables associated with ART interruption in a univariate analysis were fit in a multivariate logistic model to determine the factors that were associated with ART interruption. RESULTS: Children on anti-TB drugs were twice more likely to interrupt ART compared to those who were not, (adjusted odds ratio, AOR = 1.84 (1.03-3.28); P = 0.04). But children on cotrimoxazole prophylaxis had a 57% reduction in the odds of interrupting ART compared to those who were not, (AOR = 0.43 (0.20-0.93); P = 0.03). CONCLUSION: Children on ART and also taking multiple individual anti-TB drugs should be monitored closely for ART adherence. Cotrimoxazole prophylaxis should be encouraged in children diagnosed with HIV while awaiting ART commencement as this may prime them for a better ART adherence.