Effect of HAART on growth parameters and absolute CD4 count among HIV-infected children in a rural community of central Nigeria

Background:Monitoring response to highly active antiretroviral therapy (HAART) in HIV infected children using both laboratory and physical growth parameter is important. But monitoring laboratory parameters could sometimes be challenging in resource-poor settings as the machines used for these measurements may not always be functional or the required technical expertise be available especially in rural areas. Hence, changes in weight-for-age (WAZ), height-for -age (HAZ) and body mass indexfor age (BAZ) Z scores during clinic follow-up visits with or without changes in absolute CD4 count, could be used instead of viral load measurements as indicators of response to HAART in children.Objectives: To determine the effect in children of treatment with HAART - on changes in physical growth using WAZ, HAZ and BAZ and on changes in CD4 count using absolute CD4 count.Methods: Data on demographic/ clinical variables, viral load, absolute CD4 count, and weight and height measurements done at enrolment and at follow-up visits for 72 eligible children < 15 years who were consecutively enrolled into HAART were analysedResults: After nine months of HAART, the median absolute CD4 count increased by 28.2% and median WAZ increased by 28.6%. The reduction in the proportion of children with moderate malnutrition (WAZ < -2) from time of HAART commencement to nine months after HAART, was by 61.5% in those without severe immune suppression (SIS) and by 50% in those with SISConclusion: This study showed that WAZ and absolute CD4 count changes could be useful for monitoring response to HAART in resource –limited settings.Key words: Growth, Absolute CD4 count, Z score, HAAR

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

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

Diagnosis of paediatric TB using Xpert® MTB/RIF Ultra on fresh respiratory samples.

OBJECTIVE: To evaluate the diagnostic accuracy of Xpert® MTB/RIF Ultra (Ultra) on fresh respiratory samples for the diagnosis of pulmonary TB (PTB) in children.METHODS: Between July 2017 and December 2019, children with presumed TB were prospectively enrolled at clinical sites in three African countries. Children were assessed using history, physical examination and chest X-ray. Sputum or gastric aspirate samples were analysed using Ultra and culture. The diagnostic accuracy of Ultra was calculated against culture as the reference standard.RESULTS: In total, 547children were included. The median age was 4.7 years, 77 (14.1%) were HIV infected and 77 (14.1%) had bacteriologically confirmed TB. Ultra detected an additional 20 cases in the group of children with negative culture results. The sensitivity of Ultra was 66.3% (95% CI 47-82), and the specificity was 95.4% (95% CI 89-99) when assessed against culture as the reference standard.CONCLUSION: Despite the improved performance of Ultra as compared to Xpert as was previously reported, its sensitivity remains sub-optimal for the detection of TB in children. Ultra detected additional 20 cases which otherwise could not have been detected by culture alone, suggesting that the latter is an imperfect reference standard

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

Childhood dilated cardiomyopathy in Jos, Nigeria

Objective: to study the pattern of childhood dilated cardiomyopathy in Jos University Teaching Hospital, Nigeria.Methodology: Paediatric echocardiography records (January 2000 to June 2002 2 and ½ years) were reviewed and cases of dilated cardiomyopathy (DCM) identified. Clinical, radiologic, electro- and echocardiographic data of identified cases were reviewed.Results: childhood DCM (6 cases) was the commonest acquired heart condition diagnosed in children under the age of 5 years. Four patients presented with recurrent episodes of congestive heart failure (CHF) while 2 presented during their first episode. DCM was initially considered in only 1 child. Another child suffered a cerebro-vascular accident (CVA) before the diagnosis was made.Conclusions: DCM should be considered early in young children with long-standing or recurrent CHF. A high index of suspicion, early diagnosis and appropriate management should reduce morbidity, prevent complications and prolong survival. Sahel Medical Journal Vol. 8(4) 2005: 100-10

Trend of Antiretroviral therapy interruption in a clinic cohort of HIV-infected children in Jos, Nigeria

Background: In the early years of introducing antiretroviral therapy (ART), compromised adherence to ART in children, from treatment interruptions, was a challenge partly due to lack of trained or experienced personnel with expertise in adherence counselling. Over subsequent years with increasing expertise coupled with more patient education and public awareness it is expected that these interruptions would decline. We therefore determined the trend in ART interruptions in a clinic cohort of HIV-1 infected children attending the Jos University Teaching Hospital (JUTH).Methods: This was a retrospective analysis of data on 580 children, aged 2 months – 15 years, who were enrolled on ART between February 2006 and December 2010 at JUTH. Children who had ART interruptions were compared with those who did not. The odds of ART interruption versus no ART interruption, across the categories of year enrolled on ART were examined using the test of homogeneity of odds. The trend in ART interruptions over a period of 5 years was examined using score test for trend of odds.Results: The overall frequency of ART interruptions per child among the 580 study subjects over a period of 5 years was 20.2%, that is, 4.04% per year. The odds of ART interruptions was different across the years from 2006 to 2010 (p= &lt;0.0001). There was also evidence for a trend in the decreasing odds of ART interruptions over the years (p= &lt;0.0001).Conclusion: ART interruptions declined over the years in children attending the HIV clinic and this may have been due to enhanced ART adherence as a result of repeated health education and decreasing HIV stigmatization.Keywords: Antiretroviral therapy interruptions, Trend, HIV- 1, Adherence, Health educatio

Are congenital anomalies common in Jos-Nigeria?

Objective: The study was prospectively conducted in the Special Care Baby Unit of the Jos University Taeching Hospital, Jos over a 28-month period to assess the pattern of congenital anomalies (CA). Method:A register of all newborn infants seen with congenital anomalies was kept in the special care baby unit. Result:A total of 104 babies with CA were seen accounting for 6.1% of all admissions into the unit, with an inborn incidence of CA being 5.3 per 1000 live-births during the period. Gastrointestinal lesions accounted for majority, 33.7% (35/104), of the lesions but myelomeningocoele was the single most common lesion seen accounting for 19.2% (20/104) of all CA. The different lesions seen were found to have affected most of the systems and a few lesions 5.8% (6/104) could not be readily classified. Mortality rate was 33.7 % (35/104) among the patients with CA, being worse in outborns. Mortality was 100 % (9/9) among patients with chromosomal anomalies followed by patients with gastrointestinal lesions with 45.7% (16/35). Conclusion:CA are common in this center. The lesions involve most of the organ systems. Prompt action is required to decrease mortality especially in case of correctible lesions and it is recommended that careful examination of all newborn prior to discharge would help in early detection of congenital anomalies

Comparative Haematologic Parameters of Paediatric Uncomplicated Plasmodium falciparum Malaria in Children Treated with Artemether-Lumefantrine and Artesunate-amodiaquine in Jos, North-Central Nigeria.

Background: Malaria is still threatening the lives of millions of children particularly the under five years living in malaria endemic countries of the world. Acute malarial episodes cause many pathophysiological changes in the haematological system of man including alterations in erythrocytes, leucocytes and thromobocytes in the peripheral blood. These changes occur before and after treatment with antimalarial drugs and could also be influenced by the type of antimalarial drugs used.Aim: To determine and compare the changes in haematologic parameters before and after treatment of uncomplicated P. falciparum malaria with artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) in under-five children using 28 day study protocol.Method: Data on 111 children aged 6 to 60 months who were enrolled into a drug therapeutic efficacy testing (DTET) comparing the efficacy, safety and tolerability of AL (20/120mg) with AA (25mg/67.5mg or 50/135mg) in the treatment of uncomplicated falciparum malaria, were analyzed. This study was over a period of 10 weeks (27/06/2010 - 16/11/2010) at the General Hospital Brakin Ladi,Plateau State, Nigeria. Inclusion criteria were: history of fever in the last 24hrs and /or measured axillary temeperature 37.5 °C, P. falciparum infection with parasitaemia ≥ 1000 to ≤ 250,000 parasites/μL, HIV seronegative status, and a written informed consent from parents/guardians including readiness to comply with the follow-up visits by the parents. The children who met the inclusion criteria were randomized into the two treatment arms and their haematological parameters (haemoglobin(HB)) levels, platelet, neutrophil, lymphocyte counts, and total white cell count (WBC) measured.Results: Of 649 subjects screened for parasitaemia in the study, 282 (43.5%) were febrile (temperature 37.5°C). Out of 649 subjects, 252 (38.8%) had parasitaemia. Only P.falciparum was identified. Parasite count varied from 1000-200,000 asexual forms/μL. The mean age (months) of study population in the AL and AA arms were 38.9 16.90 and 37.7 16.76 respectively, (p=0.72). Thirty one (55.4%) and 25 (44.6%) were males and females in the AL study arm respectively while 32 (58.2%) and 23 (41.8%) were males and females respectively in the AA study arm, (p=0.77). The mean Packed cell volume (PCV) % pre-treatment (D0) rose from 32.14.7 to 35.7 7 in AL treatment arm and from 32. 5.5 to 35.14.4 in AA treatment levels of 9.83.5 and 10.04.7 to 7.82.2 and 7.72.4, in the AL and AA treatment arms D28 post-treatment (D0) levels of 36.912.5 to 32.88 in the AL treatment arm and from 37.517.0 to 35.0 10.6 in the AA treatment arm respectively, p=0.356. The mean monocytes counts (%) similarly dropped from pre-treatment levels of 11.14.8 to 8.63.4 in the AL treatment arm and from 10.7 4.2 to 8.2 3.7 in the AA treatment arm respectively, p=0.0404. Mean platelete counts also showed a decreasing trends from 545.3215.4 and 280.2151.8 to 268.2106.3 and 258.898.7 in the AL and AA treatment arms respectively at D28, post-treatment, p=0.394. Compared to the PCV, WBC, neutrophil, monocytes and platelete subpopulations of cells, the mean lymphocyte counts demonstrated a progressive increasefrom nadir of 51.415.7 to 58.711.6 in the AL treatment arm and 52.016.6 to 56.611.4 in the AA treatment arm at D28 post-treatment respectively, p=0.630.Conclusion: Uncomplicated paediatric Plasmodium falciparum malaria induces transient alterations in haematologic parameters before and after antimalarial treatment in Jos, North Central Nigeria. Therefore, malaria infection should be considered as a differential diagnosis in febrile children with alterations in haemologic parameters

COmparative heamatologic parameters of paediatric uncomplicated plasmodium falciparum malaria in children treated with artemether-lumerantrine and artesunate-amodiaguine in Jos, North-Central Nigeria

No Abstract