Background: In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.

A total of 2,570 apparently healthy human immunodeficiency virus-negative adults from the six geopolitical zones in the country were enrolled in our study in 2006. The samples were assayed using the Cyflow technique. Data were analyzed using the Statistical Package for Social Scientists (SPSS). The majority (64%) of the participants had CD4 counts within the range of 501 to 1,000 cells/l. The reference range for CD4 was 365 to 1,571 cells/l, while the reference range for CD8 was 145 to 884 cells/l.In Nigeria, although country-specific reference ranges for some hematological measures have been determined (3,5,6), national data for CD4 reference values are still not available. Prior to a few recent monocenter studies carried out among defined populations of healthy Nigerians (2, 13), CD4 reference range values from literature based on studies in western countries were largely employed for clinical decision making.However, as the access to treatment increased in Nigeria, it became critically necessary to determine on a national level the reference values for CD4 cell counts and the factors that may affect it. This was necessary to inform the clinicians of the required minimal range for the initiation of antiretroviral therapy, and also for accurate monitoring of responses to therapy and other treatment outcomes.The national study reported in this document was a multicenter study conducted among healthy human immunodeficiency virus (HIV)-negative adult Nigerians, in eight sites across the six geopolitical zones of the country. Therefore, the objective of this study was to establish the normal reference values of CD4 and CD8, as well as CD4/CD8 lymphocyte ratios, indigenous to Nigeria.This project was carried out as a cross-sectional study among apparently healthy Nigerians aged 18 years and older who tested HIV negative at voluntary counseling and testing site sites. Exclusion criteria included pregnancy, sickle cell anemia, or clinical illness.A 5-ml sample of blood was collected from each participant by venipuncture into a Vacutainer EDTA bottle. These samples were retested using the Genie II kit (Bio-Rad), which is a rapid HIV serology test kit. Only samples that were confirmed negative were assayed for CD4 and CD8 cell counts concurrently using the Cyflow technique, with an instrument known as the Cyflow counter (Partec). This instrument is for counting and analyzing particles and cells. The first step in the measurement of cells is staining with a fluorescent dye. The fluorescent molecules are taken up by the cells. The cells are individually illuminated by light of a defined wavelength. The light activates the fluorescent molecules so that they emit light of a characteristic color (wavelength). This fluorescent light is filtered out, and its intensity is measured by a ploidy analyzer for each single cell. The fluorescence light intensity emitted by a labeled cell is proportional to its CD4 or CD8 content. For cell counting or concentration determination, the sample volume detector measures exactly 0.2 ml of th...

ObjectivesOur objectives were to assess trends in late presentation and advanced HIV disease (AHD) and determine associated risk factors. MethodsWe conducted a retrospective cohort analysis of patients who had received care and treatment at the AIDS Prevention Initiative Nigeria Plus (APIN)/Harvard School of Public Health− President's Emergency Plan for AIDS Relief (PEPFAR) programme at the Jos University Teaching Hospital, Jos, Nigeria from 2005 to 2010. We used the European Consensus Definition to assess trends in late presentation (CD4 count < 350 cells/μL or AIDS-defining illness) and AHD (CD4 count < 200 cells/μL or AIDS-defining illness) and evaluated associated risk factors using logistic regression methods. ResultsAmong 14 487 eligible patients, 12 401 (85.6%) were late presenters and 9127 (63.0%) presented with AHD. Late presentation decreased from 88.9% in 2005 to 80.1% in 2010 (P < 0.001). Similarly, AHD decreased from 67.8% in 2005 to 53.6% in 2010 (P < 0.001). In logistic regression models adjusting for sociodemographic and biological variables, male sex [adjusted odds ratio (aOR) = 1.80; 95% confidence interval (CI) 1.60-2.04], older age (aOR = 1.37; 95% CI 1.22-1.54), civil service employment (aOR = 1.48; 95% CI 1.00-2.21), referral from out-patient (aOR = 2.18; 95% CI 1.53-3.08) and in-patient (aOR = 1.55; 95% CI 1.11-2.17) services, and hepatitis B virus (aOR = 1.43; 95% CI 1.26-1.63) and hepatitis C virus (aOR = 1.18; 95% CI 1.02-1.37) coinfections were associated with late presentation. Predictors of AHD were male sex (aOR = 1.67; 95% CI 1.54-1.82), older age (aOR = 1.26; 95% CI 1.16-1.36), unemployment (aOR = 1.34; 95% CI 1.00-1.79), referral from out-patient (aOR = 2.40; 95% CI 1.84-3.14) and in-patient (aOR = 1.97; 95% CI 1.51-2.57) services and hepatitis B virus coinfection (aOR = 1.30; 95% CI 1.19-1.42). ConclusionsEfforts to reduce the proportion of patients who first seek care at late stages of disease are needed. The identified risk factors should be utilized in formulating targeted public health interventions to improve early diagnosis and presentation for HIV care.

BackgroundTo date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.Methods and FindingsFrom 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0–5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0–6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir.ConclusionsThis is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.