New infections and HIV-1 subtypes among febrile persons and blood donors in Oyo State, Nigeria.

PURPOSE: There were approximately 37.9 million persons infected with HIV in 2018 globally, resulting in 770,000 deaths annually. Over 50% of this infection and deaths occur in sub-Saharan Africa, with countries like Nigeria being seriously affected. Nigeria has one of the highest rates of new infections globally. To control HIV infection in Nigeria, there is a need to continually screen high-risk groups for early HIV infection and subtypes using very sensitive methods. In this study, new HIV-1 infection and circulating HIV-1 subtypes among febrile persons and blood donors were determined. Performance characteristics of three commercial EIA kits were also evaluated. METHODS: In total, 1028 participants were recruited for the study. New HIV-1 infection and subtypes were determined using enzyme immunoassays and molecular techniques, respectively. Sensitivity, specificity, predictive values, and agreements were compared among the EIA kits using PCR-confirmed HIV-positive and negative samples. RESULTS: The overall prevalence of HIV infection in this study was 5.35%. The rate of new HIV infection was significantly different (p < .03674) among 1028 febrile persons (Ibadan: 2.22%; Saki: 1.36%) and blood donors (5.07%) studied. Three subtypes, CRF02_AG, A, and G, were found among those with new HIV infection. Whereas the commercial ELISA kits had very high specificities (94.12%, 100%, and 100%) for HIV-1 detection, Alere Determine HIV-1 antibody rapid kit had the lowest sensitivity score (50%). CONCLUSION: Genetic diversity of HIV-1 strains among infected individuals in Oyo State, Nigeria, is still relatively high. This high level of diversity of HIV-1 strains may impact the reliability of diagnosis of the virus in Nigeria and other African countries where many of the virus strains co-circulate.

Early HIV infection is associated with reduced proportions of gamma delta T subsets as well as high creatinine and urea levels.

Renal dysfunctions are major predictors of co-morbidities and mortality in HIV-infected individuals. Unconventional T cells have been shown to regulate kidney functions. However, there is dearth of information on the effect of HIV-associated nephropathies on γδ and DN T cells. It is also not clear whether γδ T cell perturbations observed during the early stages of HIV infection occur before immune activation. In this study, we investigated the relationship between creatinine and urea on the number of unconventional T cells in HIV-infected individuals at the early and chronic stages of infection. Persons in the chronic stage of infection were divided into treatment naïve and exposed groups. Treatment exposed individuals were further subdivided into groups with undetectable and detectable HIV-1RNA in their blood. Creatinine and urea levels were significantly higher among persons in the early HIV infection compared with the other groups. Proportions of γδ T, γδ + CD8, γδ + CD16 cells were also significantly reduced in the early stage of HIV infection (P < .01). Markers of immune activation, CD4 + HLA-DR and CD8 + HLA-DR, were also significantly reduced during early HIV infection (P < .01). Taken together, our findings suggest that high levels of renal markers as well as reduced proportions of gamma delta T cells are associated with the early stages of HIV infection. This event likely occurs before systemic immune activation reaches peak levels. This study provides evidence for the need for early HIV infection diagnosis and treatment.

Early HIV infection among persons referred for malaria parasite testing in Nigeria.

Persons in the early stages of HIV infection are the major drivers of new infections. These individuals may also develop renal dysfunctions at this time. Nigeria, as other African countries, has one of the highest prevalence of newly diagnosed HIV infections. Despite this, limited information exists on early HIV detection in the continent. This may be related to difficulties in providing early HIV diagnosis and treatment. Patients referred for malaria testing may provide a unique opportunity for early HIV detection. In this study, a method for identifying early HIV-infected individuals was assessed. HIV-1 subtype and renal function biomarkers were also analyzed in these persons. To identify early HIV infection, over a period of 18 months blood samples were collected from persons referred by clinicians for malaria parasite tests in Nigeria. A total of 671 samples were collected and analyzed for HIV antigen/antibody and subtypes. 101 of these samples were categorized into one of four groups: early HIV, chronic HIV, malaria infection and control groups for renal function analysis. 29% of HIV infected individuals were at the early stages of infection. The predominant subtype detected was CRF02_AG (57.14%). The early HIV group had the highest mean serum creatinine (95 µmol/L) and urea (5.7 mmol/L) values across all groups with the difference significant at P < 0.05. There was no significant difference between the circulating subtype and the stage of HIV infection. Our results show the feasibility of screening persons referred for malaria tests for early HIV. This can be used to control new HIV infections in sub-Saharan Africa.

Dynamics of CD4 cell count among HIV-infected individuals in Lagos, Nigeria.

Human immunodeficiency virus (HIV) infection leads to progressive loss of CD4 T cells. Antiretroviral therapy has been able to inhibit this process, resulting in significant level of immune recovery and function. Our aim is to investigate the dynamics of CD4 recovery among HIV patients in Lagos, Nigeria. A total of 213 HIV-positive individuals were enrolled between October 2007 and May 2008, and followed up for 9 months based on CD4 count. CD4 analysis was done by flow cytometry at enrollment and after every 3 months. Data were grouped according to age range, antiretroviral treatment (ART), and time between infection and diagnosis. Kaplan-Meier survival analysis was used for data analysis. There was a significant difference in CD4 count between antiretroviral (ART) naïve and ART experienced subjects (P < 0.001). About 50% of the ART experienced population was identified to show poor CD4 reconstitution unable to achieve a CD4 of 500 cells/µl after 9 months of therapy. Time interval between infection and therapy was also identified to contribute to poor CD4 restoration. Further studies need to be done to classify immunological nonresponders among HIV patients in Nigeria. We also recommend introduction of programs that will facilitate early detection of HIV infection.

CD4 Decay Rate as an Indicator of the Time Interval between Initial Infection and First Diagnosis among Drug-Naïve Human Immunodeficiency Virus Seropositive Individuals in Lagos, Nigeria.

OBJECTIVE: The aim of this study was to determine the time interval between human immunodeficiency virus (HIV) infection and the first diagnosis among drug-naïve individuals in Badagry, Nigeria. SUBJECTS AND METHODS: A sample of 213 subjects who tested HIV positive for the first time were enrolled in this study. The HIV diagnosis was performed using Startpak® and Determine® kits, and a CD4 count was carried out using a FACS Count® flow cytometer. The mean CD4 values were determined by gender and age groups. The time interval between initial HIV infection and first testing was calculated based on the average CD4 decay rate per calendar year, and data analysis was performed using SPSS software. RESULTS: At diagnosis, the mean CD4 values showed that females recorded 270 cells/µl and males 244 cells/µl. By age range, individuals <25 years recorded 437 cells/µl, those between 25 and 40 years of age had 237 cells/µl, and those aged ≥41 years had 192 cells/µl. There was a significant difference between CD4 cell categorization and age range (p < 0.001). Subjects aged between 25 and 40 years recorded the highest distribution of all CD4 cell counts. The time interval between infection and testing for females was 8.1 years and for males 6.7 years. Within the age group <25 years the interval was 5.1 years, whilst it was 8.1 years for those aged ≥41 years. CONCLUSION: Most of the population presented for testing during the advanced stages of infection. We suggest an upscaling of HIV voluntary counseling and testing to encourage early detection and better treatment outcomes.

Epidemiological Evaluation of Rubella Virus Infection among Pregnant Women in Ibadan, Nigeria.

Rubella is a vaccine-preventable, mild rash-inducing viral disease with complications that include a spectrum of birth defects in the developing fetus, especially if the infection is acquired in the early months of pregnancy. Consequently, the primary objective of global rubella control programs is prevention of congenital rubella infection and associated birth defects. Despite the availability of safe and effective vaccines, and the elimination of the rubella virus in many developed countries, substantial commitment to rubella control has not been demonstrated in developing countries. This study appraises immunity to rubella, and consequently makes appropriate recommendations aimed at facilitating effective control. A cross-sectional sero-surveillance study was carried out among defined 272 consenting ante-natal clinic attendees in south-western, Nigeria. Prevalence rates of 91.54% and 1.84% were recorded for the anti-rubella virus (anti-RV) IgG and IgM, respectively. Also, 90.7% and 92.3% of the women aged ≤30 years and >30 years, respectively, had detectable anti-RV IgG. No significant association (p = 0.94) was recorded between anti-RV IgG detection and age of the women. Previous exposure and susceptibility of significant fraction of the population to rubella infection were confirmed. Considerable political commitment and promotion of free rubella immunization specifically for women with childbearing potential were recommended.

Surveillance of Pretreatment Drug Resistance Among HIV-Infected Children in Ibadan, Nigeria.

There are about 2.1 million children infected with HIV globally and about 120,000 deaths annually. Nigeria has one of the highest rates of pediatric HIV infection globally. Pretreatment HIV drug resistance data inform the choice of first- and second-line antiretroviral therapy (ART) regimens. This study investigated the prevalence of HIV drug-resistant strains among ART-naive children in Ibadan, Nigeria. A total of 20 children aged <15 years were enrolled. Demographic, clinical, and laboratory data were documented. Total nucleic acid was extracted from blood samples after which amplification of HIV-1 pol gene was done using polymerase chain reaction. Amplified gene was sequenced using big dye sequencing method. The sequenced HIV-1 pol gene was typed and analyzed for identification of mutations indicative of drug resistance across the different classes of ART. HIV-1 RNA pol gene was successfully amplified in 12/20 (60%) children. All were identified as HIV-1 and the subtypes were G and CRF 02AG, recombinant of 02_AG/G and recombinant of 02_AG/A1. Drug-resistant mutations (DRMs) were identified in 4/12 (33%). Three out of the four mutations were identified as non-nucleoside reverse transcriptase inhibitors DRM (K103N), whereas the fourth had nucleoside reverse transcriptase inhibitors DRM (M184V). Results from this preliminary study show that drug resistance among ART-naive children is a problem in Ibadan. Pretreatment drug resistance testing is desirable in children before initiation of ART to guide effective treatment.

Microglial Implications in SARS-CoV-2 Infection and COVID-19: Lessons From Viral RNA Neurotropism and Possible Relevance to Parkinson's Disease.

Since December 2019, humankind has been experiencing a ravaging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, the second coronavirus pandemic in a decade after the Middle East respiratory syndrome coronavirus (MERS-CoV) disease in 2012. Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19), which is responsible for over 3.1 million deaths worldwide. With the emergence of a second and a third wave of infection across the globe, and the rising record of multiple reinfections and relapses, SARS-CoV-2 infection shows no sign of abating. In addition, it is now evident that SARS-CoV-2 infection presents with neurological symptoms that include early hyposmia, ischemic stroke, meningitis, delirium and falls, even after viral clearance. This may suggest chronic or permanent changes to the neurons, glial cells, and/or brain vasculature in response to SARS-CoV-2 infection or COVID-19. Within the central nervous system (CNS), microglia act as the central housekeepers against altered homeostatic states, including during viral neurotropic infections. In this review, we highlight microglial responses to viral neuroinfections, especially those with a similar genetic composition and route of entry as SARS-CoV-2. As the primary sensor of viral infection in the CNS, we describe the pathogenic and neuroinvasive mechanisms of RNA viruses and SARS-CoV-2 vis-à-vis the microglial means of viral recognition. Responses of microglia which may culminate in viral clearance or immunopathology are also covered. Lastly, we further discuss the implication of SARS-CoV-2 CNS invasion on microglial plasticity and associated long-term neurodegeneration. As such, this review provides insight into some of the mechanisms by which microglia could contribute to the pathophysiology of post-COVID-19 neurological sequelae and disorders, including Parkinson's disease, which could be pervasive in the coming years given the growing numbers of infected and re-infected individuals globally.

Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E.

Introduction. Hepatitis B virus (HBV) infection is the leading cause of hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HBV genotype E (HBV/E) is the predominant genotype in West Africa and has been linked epidemiologically with chronic and occult HBV infections as well as development of HCC. Mutations in the surface and polymerase genes of HBV have been associated with occult infection, drug resistance, vaccine escape, as well as HCC.Hypothesis/Gap Statement. There is limited data on the occurrence and patterns of mutations associated with occult infection, drug resistance, vaccine escape and HCC for HBV/E.Aim. This study characterized amino acid (aa) substitutions in the major hydrophilic (MHR) and reverse transcriptase (RT) regions of the surface and polymerase genes respectively of HBV sequences from a group of Nigerians with genotype E infection. The CpG islands of the PreC/C and PreS/S regions of these sequences were also described.Methodology. HBV surface and polymerase genes were detected using PCR techniques. Occurrence of new and previously described mutations in these genes were analysed using phylogenetic techniques.Results. Overall 13 HBV isolates were each sequenced for polymerase and surface genes mutations. Thirteen and nine PreS/S and PreC/C HBV genes respectively were analysed for CpG islands. Mutations in the MHR and a-determinants region of the S protein were discovered in eleven and nine of the 13 tested isolates respectively. These mutations were concomitant with aa changes in the RT functional domains of the isolates. Mutations associated with vaccine escape, occult infection and poor HCC prognosis were identified in HBV/E isolated in this study. Furthermore, all the isolates had at least one putative nucleotide analogue resistance mutations. Drug resistance mutations had the highest association with CpG islands.Conclusion. The results of this study contribute to further understanding of HBV variability in Nigeria and the West African region. This will aid the planning of adequate HBV immunization and treatment programmes for the countries in the region.

Non-synonymous Substitutions in HIV-1 GAG Are Frequent in Epitopes Outside the Functionally Conserved Regions and Associated With Subtype Differences.

In 2019, 38 million people lived with HIV-1 infection resulting in 690,000 deaths. Over 50% of this infection and its associated deaths occurred in Sub-Saharan Africa. The West African region is a known hotspot of the HIV-1 epidemic. There is a need to develop an HIV-1 vaccine if the HIV epidemic would be effectively controlled. Few protective cytotoxic T Lymphocytes (CTL) epitopes within the HIV-1 GAG (HIV_gagconsv) have been previously identified to be functionally conserved among the HIV-1 M group. These epitopes are currently the focus of universal HIV-1 T cell-based vaccine studies. However, these epitopes' phenotypic and genetic properties have not been observed in natural settings for HIV-1 strains circulating in the West African region. This information is critical as the usefulness of universal HIV-1 vaccines in the West African region depends on these epitopes' occurrence in strains circulating in the area. This study describes non-synonymous substitutions within and without HIV_gagconsv genes isolated from 10 infected Nigerians at the early stages of HIV-1 infection. Furthermore, we analyzed these substitutions longitudinally in five infected individuals from the early stages of infection till after seroconversion. We identified three non-synonymous substitutions within HIV_gagconsv genes isolated from early HIV infected individuals. Fourteen and nineteen mutations outside the HIV_gagconsv were observed before and after seroconversion, respectively, while we found four mutations within the HIV_gagconsv. These substitutions include previously mapped CTL epitope immune escape mutants. CTL immune pressure likely leaves different footprints on HIV-1 GAG epitopes within and outside the HIV_gagconsv. This information is crucial for universal HIV-1 vaccine designs for use in the West African region.

Virus genes and host correlates of pathology are markedly reduced during respiratory syncytial and influenza virus co-infection in BALB/c mice.

Globally, influenza A virus (IAV) and respiratory syncytial virus (RSV) infection remain very high. There is also a high burden of IAV and RSV co-infection in developing countries. To develop universally protective vaccines against these infections, it is imperative that viral genes and immune correlates of pathology are elucidated. As such, we profiled virus genes expressions, histopathology and immunological responses of BALB/c mice infected with RSV and/or IAV in this study. RSV A2 and/or influenza A/H3N2/Perth/16/09 (Pr/H3N2) were induced over a seven-day period in BALB/c mice. Anaesthetized BALB/c mice (12-14 g) were divided into six groups (15-20 mice per group), inoculated with 32 µl each of 3LD50 Pr/H3N2 and/or 100 TCID50 RSV. Two groups (R or I) received RSV or Pr/H3N2 intranasally. Prior infection with either RSV or Pr/H3N2 was followed with a second challenge of the other virus 24 hours post inoculation in RI and IR groups. Another set was exposed to the two viruses simultaneously (I + R group) while the last group served as healthy controls. Five to seven mice per group were euthanized at days 2, 4 and 7. Lung and spleen organs were harvested for virus genes quantitation and immune cells phenotyping respectively. I + R group showed progressive downregulation of RSV F, G, NS1 and NS2 genes. IAV PB2 and M genes had high fold increase on day 2 and 4 post infections. However, by day 7 post infection, M and PB2 fold increase was lower. Also, increased proportions of NKT and T cell subsets were observed throughout the period in I + R group. Conversely, I group was characterized by reduced NKT cell counts and enhanced CD8 T cells levels while R group only showed an increased proportion of CD8 T cells towards the peak of infection. This study shows that RSV and IAV co-infection lead to reduced virulence and pathology compared to single infections. This information is very useful in combinatorial RSV/IAV vaccine design and development.

Proportions of circulating follicular helper T cells are reduced and correlate with memory B cells in HIV-infected children.

INTRODUCTION: HIV causes defects in memory B cells in children, but the mechanisms of those defects have not been fully elucidated. One possible mechanism is the lack of T-cell help to B cells during immune reactions. However, few studies have assessed the effect of HIV on follicular helper T cells (TFH cells) in children. METHODS: In this study, follicular-homing CD4 T cells and memory B cells were assessed in HIV-infected children and compared with children from the community. CXCR5 and CD45RO were used as markers of follicular-homing T cells and memory T cells, respectively. Memory TFH cells were identified as CD3+CD8-CD4+CXCR5+CD45RO+PD1+. Central memory T cells were identified based on CCR7 expression. Relationship between the proportions of follicular-homing CD4 T cells and memory B cells were determined in multivariable regression models. RESULTS: Highly viremic HIV-infected children had lower proportions of memory TFH cells when compared with community control children. In multivariable analyses, high proportions of memory TFH cells were associated with increased percentages of resting memory B cells after adjusting for other covariates. CONCLUSION: The impact of HIV on follicular helper T cells could influence the accumulation of memory B cells in HIV-infected children.

Measles Virus Infection Among Vaccinated and Unvaccinated Children in Nigeria.

This study investigated measles infection in vaccinated and unvaccinated children presenting with fever and maculopapular rash during measles outbreaks in the southern and western states of Nigeria. Measles, an acute viral illness caused by a virus in the family Paramyxoviridae, is a vaccine-preventable disease. Measles outbreak is common in Nigeria, despite the national immunization program. Children presenting with symptoms of measles infection in general hospitals and health centers in the states of southern and western Nigeria were recruited for this study. Vaccination history, clinical details, and 5 mL of blood were obtained from the children. Their sera samples were screened for specific immunoglobulin M antibodies to measles virus. Of 234 children tested (124 [53.2%] female), 133 (56.8%) had previously been vaccinated against measles virus, while 93 (39.7%) had not been vaccinated. Vaccination information for eight children could not be retrieved. One hundred and forty-three (62.4%) had measles IgM antibodies. Of these, 79 (55.3%) had been vaccinated for measles, while 65 (44.7%) had not. Despite the ongoing vaccination program in Nigeria, a high number of children are still being infected with measles, despite their vaccination status. Therefore, there is need to identify the reason for the low level of vaccine protection.