HIV-1 residual risk and pre-treatment drug resistance among blood donors: A sentinel surveillance from Gabon.

BACKGROUND: Surveillance of HIV-1 pre-treatment drug resistance (PDR) is essential for ensuring the success of first-line antiretroviral therapy (ART). Beside population-based surveys, sentinel surveillance of PDR and circulating HIV-1 clades in specific populations such as blood donors could efficiently inform decision-making on ART program. We therefore sought to ascertain HIV-1 residual infection, the threshold of PDR and viral diversity among recently-diagnosed blood donors in Gabon. METHODS: A sentinel surveillance was conducted among 381 consenting blood donors at the National Blood Transfusion Center (NBTC) in Gabon from August 3,2020 to August, 31, 2021. In order to determine the residual risk of HIV transmission, viral load and HIV-1 Sanger-sequencing were performed at the Chantal BIYA International Reference Center (CIRCB)-Cameroon on HIV samples previously tested seronegative with ELISA in Gabon. Phylogeny was performed using MEGA X, PDR threshold>10% was considered high and data were analysed using p≤0.05 for statistical significance. RESULTS: Five HIV-negative blood donors had a detectable viral load indicating a high residual risk of HIV transmission. Among the samples successfully sequenced, four participants had major drug resistance mutations (DRMs), giving a threshold of PDR of 25% (4/16). By drug class, major DRMs targeting NNRTI (K103N, E138G), NRTIs (L210W) and PI/r (M46L). The most representative viral clades were CRF02_AG and subtype A1. The genetic diversity of HIV-1 had no significant effect on the residual risk in blood transfusion (CRF02_AG, P = 0.3 and Recombinants, P = 0.5). CONCLUSION: This sentinel surveillance indicates a high residual risk of HIV-1 transfusion in Gabon, thereby underscoring the need for optimal screening strategy for blood safety. Moreover, HIV-1 transmission goes with high-risk of PDR, suggesting suboptimal efficacy of ART. Nonetheless, the genetic diversity has limited (if any effect) on the residual risk of infection and PDR in blood donors.

KIR2DL1 gene is a surrogate marker of protection against infection-related hospitalization among HIV-1 unexposed versus exposed uninfected infants in Cameroon.

BACKGROUND: HIV-exposed uninfected infants (HEU) appear more vulnerable to infections compared to their HIV-unexposed uninfected (HUU) peers, generally attributed to poor passive immunity acquired from the mother. This may be due to some genetic factors that could alter the immune system. We thus sought to determine the distribution of Killer Cell Immunoglobulin-Like Receptors (KIRs) genes in HEU versus HUU and study their associations with the occurrence of infection-related hospitalization. METHODS: A cohort study was conducted from May 2019 to April 2020 among HEU and HUU infants, including their follow-up at weeks 6, 12, 24, and 48, in reference pediatric centers in Yaoundé-Cameroon. The infant HIV status and infections were determined. A total of 15 KIR genes were investigated using the sequence-specific primer polymerase chain reaction (PCR-SSP) method. The KIR genes that were significantly associated with HIV-1 status (HEU and HUU) were analyzed for an association with infection-related hospitalizations. This was only possible if, and to the extent that, infection-related hospitalizations varied significantly according to status. Multivariate logistic regression analyses were conducted to determine the association between KIR gene content variants and HIV status, while considering a number of potential confounding factors. Furthermore, the risk was quantified using relative risk, odds ratio, and a 95% confidence interval. The Fisher exact test was employed to compare the frequency of occurrences. A p-value of less than 0.05 was considered statistically significant. RESULTS: In this cohort, a total of 66 infants participated, but only 19 acquired infections requiring hospitalizations (14.81%, 04/27 HUU and 38.46%, 15/39 HEU, p = 0.037). At week 48 (39 HEU and 27 HUU), the relative risk (RR) for infection-related hospitalizations was 2.42 (95% CI: 1.028-5.823) for HEU versus HUU with OR 3.59 (1.037-12.448). KIR2DL1 gene was significantly underrepresented in HEU versus HUU (OR = 0.183, 95%CI: 0.053-0.629; p = 0.003), and the absence of KIR2DL1 was significantly associated with infection-related hospitalization (p < 0.001; aOR = 0.063; 95%CI: 0.017-0.229). CONCLUSION: Compared to HUU, the vulnerability of HEU is driven by KIR2DL1, indicating the protective role of this KIR against infection and hospitalizations.

Prevalence and factors associated with transfusion-transmissible infections (HIV, HBV, HCV and Syphilis) among blood donors in Gabon: Systematic review and meta-analysis.

BACKGROUND: Transfusion-transmissible infections (TTIs) remain a major public health problem in countries with limited resources, particularly in Gabon. Complete information on the prevalence in Gabon of the main TTIs among blood donors is still lacking in the national context. The purpose of this systematic review and meta-analysis was to determine the prevalence and factors associated with TTIs among blood donors in Gabon. METHODS: This systematic review and meta-analysis was reported in accordance with the PRISMA 2020 guidelines. It was the result of data from several comprehensive studies published between 2014 and 2022, the purpose of which focused on the prevalence and factors associated with TTIs among blood donors in Gabon. The quality of the articles was assessed using the Joanna Briggs Institute critical appraisal checklist for studies reporting prevalence data. The overall prevalence of TTIs among blood donors was determined using the random effects model. Heterogeneity between studies was assessed using I2 statistics. Publication bias was assessed by visual inspection of the funnel plot and Egger's statistics. RESULTS: A total of 175,140 blood donors from the nine eligible studies were admitted to this study. The combined prevalence of HIV, HBV, HCV and syphilis obtained in the random effects model was 3.0%, 6.0%, 4.0% and 3.0%, respectively. Moreover, being a male blood donor and aged between 25 and 44 years was significantly associated with HBV infection and being a female blood donor and aged 35 years and over was significantly associated with HIV infection. Family or replacement blood donors had a high infection burden for all four TTIs of study. CONCLUSION: The overall prevalence of transfusion-transmissible infections remains high in the country's blood banks. Improving current prevention (selection criteria) and screening strategies may be necessary in a global approach.

Effect of hepatitis B vaccination on HBV-infection among school children in Yaounde; ten years after the introduction of HBV vaccine into routine Immunization Program in Cameroon.

Introduction: since the introduction of the anti-HBV vaccine into the Expanded Program on Immunization (EPI) in 2005 in Cameroon, vaccination coverage has reached 99.0%. This coverage would indicate an increase in the number of children immune to Hepatitis B Virus (HBV) and a decrease in susceptibility to HBV-infection. This study was conducted to evaluate the effect of the HBV vaccine on pediatric HBV-infection in Yaounde, Cameroon. Methods: this school-based cross-sectional study was conducted from February to May 2016 among 180 children from Nkomo public school. The study population was stratified into two groups: vaccinated (n=95) versus (vs) unvaccinated (n=85). Screening for HBV biomarkers was done using a rapid panel test for detection (HBsAg, HBeAg and anti-HBc) and anti-HBs titer using enzyme linked immunosorbent assay (ELISA). Statistical analyses were done using SPSS v. 22 with p < 0.05 considered significant. Results: the mean age was 9.65 years. HBsAg (p=0.019) and anti-HBc (p=0.001) rates were detected in children aged ≥10 years and children aged < 10 years (95.95% [71/74]) were vaccinated vs 22.64% (24/106) for those aged ≥10 years (OR: 80.86; 95% CI: 23.36%-279.87%, p < 0.0001). According to anti-HBV vaccination status, HBsAg rate varied from [9.41% (8/85) to 1.05% (1/95), p=0.025], HBeAg rate varied from [2.35% (2/85) to 0% (0/95), p= 0.42] and anti-HBc rate ranged from [12.94% (11/85) to 2.10% (2/95), p= 0.011]. Conclusion: despite the variability of the anti-HBs titer, vaccination against HBV has a positive effect on the reduction of HBV-infection in children in tropical settings such as Cameroon.

XBB.1, BQ1.1 and atypical BA.4.6/XBB.1 recombinants predominate current SARS-CoV-2 Wavelets with flu-like symptoms in Cameroon: A snapshot from genomic surveillance.

As of December 2022, Cameroon had observed a slight resurgence of COVID-19, raising concerns on genomic surveillance of related-SARS-CoV-2 variants under circulation. Following a laboratory-based survey, positive SARS-CoV-2 samples detected from December-2022 through March-2023 were processed for targeted sequencing at the Chantal BIYA International Reference Centre (CIRCB) in Yaoundé-Cameroon. From all positive cases detected, 13 were successfully sequenced (mean age 34 years, 70% female); the majority of the cases were unvaccinated (70%, 9/13) and symptomatic (92%, 12/13); all with flu-like symptoms (100%, 12/12). Following RT-PCR, the median cycle threshold was 22.23 [18-24] for the N gene; and 24.09 [20-26] for the ORF gene, underscoring high viral loads. Phylogenetic analysis of nucleotide sequences identified four major sub-variants in circulation, of which BA.5 (3/13), the recombinants BQ.1.1 (4/13), XBB.1 (4/13) and novel atypical variant of BA.4.6/XBB.1 (2/13). This snapshot surveillance indicates the introduction/emergence and circulation of new Omicron sub-variants, all accompanied by minor/mild symptoms. However, these new sub-variants and recombinants call for continuous genomic surveillance to prevent further resurgence of Covid-19 epidemiological wave.

Strategic HIV Case Findings among Infants at Different Entry Points of Health Facilities in Cameroon: Optimizing the Elimination of Mother-To-Child Transmission in Low- and- Middle-Income Countries.

BACKGROUND: HIV case finding is an essential component for ending AIDS, but there is limited evidence on the effectiveness of such a strategy in the pediatric population. We sought to determine HIV positivity rates among children according to entry points in Cameroon. METHODS: A facility-based survey was conducted from January 2015 to December 2019 among mother-child couples at various entry points of health facilities in six regions of Cameroon. A questionnaire was administered to parents/guardians. Children were tested by polymerase chain reaction (PCR). Positivity rates were compared between entry points. Associations were quantified using the unadjusted positivity ratio (PR) for univariate analyses and the adjusted positivity ratio (aPR) for multiple Poisson regression analyses with 95% confidence intervals (CIs). p-values < 0.05 were considered significant. RESULTS: Overall, 24,097 children were enrolled. Among them, 75.91% were tested through the HIV prevention of mother-to-child transmission (PMTCT) program, followed by outpatient (13.27%) and immunization (6.27%) services. In total, PMTCT, immunization, and outpatient services accounted for 95.39% of children. The overall positivity was 5.71%, with significant differences (p < 0.001) between entry points. Univariate analysis showed that inpatient service (PR = 1.45; 95% CI: [1.08, 1.94]; p = 0.014), infant welfare (PR = 0.43; 95% CI: [0.28, 0.66]; p < 0.001), immunization (PR = 0.56; 95% CI: [0.45, 0.70]; p < 0.001), and PMTCT (PR = 0.41; 95% CI: [0.37, 0.46]; p < 0.001) were associated with HIV transmission. After adjusting for other covariates, only PMTCT was associated with transmission (aPR = 0.66; 95% CI: [0.51, 0.86]; p = 0.002). CONCLUSIONS: While PMTCT accounts for most tested children, high HIV positivity rates were found among children presenting at inpatient, nutrition, and outpatient services and HIV care units. Thus, systematic HIV testing should be proposed for all sick children presenting at the hospital who have escaped the PMTCT cascade.

Performance characteristics of INDICAID antigen rapid diagnostic test on SARS-CoV-2 samples during the omicron wave in Cameroon.

Background: WHO recommends the use of COVID-19 antigen rapid diagnostic tests (Ag-RDT) with at least 80 % sensitivity and 97 % specificity. In the era of Omicron variants, we sought to ascertain the performance of the INDICAID™ Ag-RDT compared to real-time PCR (RT-PCR) as the gold standard. Methods: A laboratory-based study was conducted among consenting individuals tested for COVID-19 at the virology laboratory of the Chantal BIYA International Reference Centre, Yaoundé-Cameron. The samples were processed by INDICAID™ Ag-RDT and DaAn Gene real-time PCR according to the manufacturer's instructions, and PCR-results were interpreted as per cycle thresholds (CT). The sensitivity, specificity, positive and negative predictive values (PPV and NVP) of INDICAID™ Ag-RDT were evaluated according to PCR CT-values. Results: A total of 565 nasopharyngeal swabs were collected from participants (median age [IQR]: 40 [31-75]; M/F sex-ratio was 1.2 and 380 were vaccinated). Following PCR, overall COVID-19 positivity was 5.66 %. For CT < 37, INDICAID™ Ag-RDT sensitivity was 21.9 % (95%CI: [8.3-39.9]), specificity 100 % (95%CI: [99.3-100]); PPV 100 % (95%CI: [59.0-100]), NPV 95.5 % (95%CI: [93.4-97.1]) and kappa = 0.34 (95%CI: [0.19-0.35]). For CT < 25, sensitivity was 100 % (95%CI: [47.8-100.0]), specificity 99.6 % (95%CI: [98.7-99.9]); PPV 94.4 % (95%CI: [51.7-100]), NPV 100 % (95%CI: [99.3-100]) and kappa = 0.83 (95%CI: [0.6-1.0]). COVID-19 sequences generated were all Omicron BA.1 subvariants. Conclusion: For patients infected with high viral loads (CT < 25), INDICAID™ Ag-RDT has high intrinsic (sensitivity and specificity) and extrinsic (predictive values) performances for COVID-19 diagnosis. Due to its simplicity and short turnaround time, INDICAID™ Ag-RDT is, therefore a reliable tool to prevent the spread of COVID-19 at community level in the current era of Omicron subvariants.

SARS-CoV-2 active infection and antibodies amongst health personnel during the outbreak in Cameroon: Strengthening the health system for response to future public health emergencies.

BACKGROUND: Health personnel (HP) are on the frontlines during response to public health emergencies like COVID-19. This risk of exposure suggests the need for safety in responding to any pandemic. Therefore, to ascertain the rate of SARS-CoV-2 infection and immunity, and their determinants amongst HP become relevant. METHODS: A cross sectional health facility-based study was carried-out amongst HP in the Centre Region of Cameroon from 1st February to 30th June 2021. Characteristics and access to preventive tools were collected using face-to-face administered questionnaire. Nasopharyngeal swabs and whole blood were collected for PCR, IgG and IgM testing respectively. STATA version 17 software was used for data analysis. Determinants of COVID-19 infection were explored by estimating crude and adjusted Odd Ratio. RESULTS: Out of 510 HP reached, 458 were enrolled with mean age of 35 (±10) years. Thirty-four (7.4%) were PCR-positive to SARS-CoV-2 with 73.5% being clinicians versus 9 (26.4%) non-clinicians (p = 0.05). Sero-positivity to SARS-CoV-2 IgG/IgM was 40.2% (184/458), with 84.2% being clinicians versus 29 (15.8%) non-clinicians (p = 0.733). Amongst the 34 HP with PCR-positivity, 16 (47%) had no antibodies, while, 15 (44%) were IgG only. An estimate of HP (43.7%) had at least an evidence of PCR, IgG or IgM contact to COVID-19. Determinants of PCR-positivity was being clinical staff (AOR = 0.29, P = 0.039); and that of IgG/IgM were being non clinical staff (AOR = 0.41, p = 0.018) and regular use of face masks (AOR = 0.44, p = 0.001). HP trained on IPC (24%) were mainly from peripheral level (74.7%, p = 0.002). CONCLUSION: Active infections were within the range of pandemic control (<10%). However, around two-fifths of participants have had contact with the virus, indicating that HP remains a population at risk of COVID-19 and other similarly-transmitted epidemic prone diseases, and also an important source of transmission. There is need of vaccine to achieve protectiveness, and optimal response also requires capacity building to improve the health system when challenged by a future pandemic.

Evaluation of HIV-1 DNA levels among adolescents living with perinatally acquired HIV-1 in Yaounde, Cameroon: A contribution to paediatric HIV cure research in Sub-Saharan Africa.

Background: With the advent of antiretroviral therapy (ART), most children living with HIV in sub-Saharan Africa (SSA) are growing toward adolescence, with scarcity of evidence on the size of viral reservoirs to enhance paediatric cure research strategies. This study aims to compare HIV-1 proviral DNA levels according to virological response among adolescents living with perinatally acquired HIV-1 (ALPHIV) and identify associated-factors in the Cameroonian context. Methods: In this observational cohort study, HIV-1 RNA viremia and CD4+ T-cell count were assessed through RT-PCR and flow cytometry respectively at three time-points over 18 months of observation. At the third time-point, 80 randomly-selected participants were classified as with viremia (≥50 HIV-1 copies/mL; n = 40) or without viremia (<50 HIV-1 copies/mL; n = 40); immune-competent (≥500 CD4+ T cells/mm3) or immunocompromised (<500 CD4+ T cells/mm3). Among these participants, total HIV-1 DNA load was quantified through droplet digital PCR using Bio-Rad QX200. Results: Of the 80 randomly-selected adolescents, median [IQR] age was 15 (13-17) years, 56.2% were female, duration on ART was 9.3 [5.4-12.2] years. Among the 40 viremic ones (median viremia 7312 [283-71482]) HIV-1 copies/ml, 75.0% (30/40) were in virological failure (≥1000 HIV-1 copies/ml), while median of CD4 T cells were 494 [360-793] cell/mm3 with 48.8% (39/80) immunocompromised. No significant variation in HIV-1 RNA viremia and CD4 T cell count was observed between the three time-points, and 13.7% (11/80) adolescents remained aviremic and immune-competent throughout (stable adolescents). A positive and moderate correlation (r = 0.59; p < 0.001) was found between HIV-1 DNA levels and HIV- 1 RNA viremia. Regarding the CD4 T cell count, a negative and weak correlation (r = -0.28; p = 0.014) was found with HIV-1 DNA loads only among adolescents with viremia. Starting ART within the first year of life, ART for over 9 years and aviremia appear as predictors of low HIV-1 DNA loads. Conclusion: Among ALPHIV, high HIV-1 RNA indicates an elevated viral reservoir size, representing a drawback to cure research. Interestingly, early ART initiation and longer ARTduration lead to sustained viral control and limited HIV-1 reservoir size. As limited size of viral reservoir appears consistent with viral control and immune competence, adolescents with sustained viral control (about 14% of this target population) would be candidates for analytical ART interruptions toward establishing paediatric post-treatment controllers in SSA.

SARS-CoV-2 genomic surveillance and reliability of PCR single point mutation assay (SNPsig® SARS-CoV-2 EscapePLEX CE) for the rapid detection of variants of concern in Cameroon.

Background: Surveillance of SARS-CoV-2 variants of concern (VOCs) and lineages is crucial for decision-making. Our objective was to study the SARS-CoV-2 clade dynamics across epidemiological waves and evaluate the reliability of SNPsig® SARS-CoV-2 EscapePLEX CE in detecting VOCs in Cameroon. Material and methods: A laboratory-based study was conducted on SARS-CoV-2 positive nasopharyngeal specimens cycle threshold (Ct)≤30 at the Chantal BIYA International Reference Centre in Yaoundé-Cameroon, between April-2020 to August-2022. Samples were analyzed in parallel with Sanger sequencing and (SNPsig® SARS-CoV-2 EscapePLEX CE), and performance characteristics were evaluated by Cohen's coefficient and McNemar test. Results: Of the 130 sequences generated, SARS-CoV-2 clades during wave-1 (April-November 2020) showed 97 % (30/31) wild-type lineages and 3 % (1/31) Gamma-variant; wave-2 (December-2020 to May-2021), 25 % (4/16) Alpha-variant, 25 % (4/16) Beta-variant, 44 % (7/16) wild-type and 6 % (1/16) mu; wave-3 (June-October 2021), 94 % (27/29) Delta-variant, 3 % (1/29) Alpha-variant, 3 % (1/29) wild-type; wave-4 (November-2021 to August-2022), 98 % (53/54) Omicron-variant and 2 % (1/54) Delta-variant. Omicron sub-variants were BA.1 (47 %), BA.5 (34 %), BA.2 (13 %) and BA.4 (6 %). Globally, the two genotyping methods accurately identified the SARS-CoV-2 VOCs (P = 0.17, McNemar test; Ka = 0.67). Conclusion: Genomic surveillance reveals a rapid dynamic in SARS-CoV-2 strains between epidemiological waves in Cameroon. For wide-spread variant surveillance in resource-limited settings, SNPsig® SARS-CoV-2 EscapePLEX CEkit represents a suitable tool, pending upgrading for distinguishing Omicron sub-lineages.

Current knowledge of human Mpox viral infection among healthcare workers in Cameroon calls for capacity-strengthening for pandemic preparedness.

Introduction: An increased incidence of human Monkeypox (Mpox) cases was recently observed worldwide, including in Cameroon. To ensure efficient preparedness and interventions in the health system, we sought to assess the knowledge of Mpox's transmission, prevention, and response among healthcare workers (HCWs) in Cameroon. Methods: A cross-sectional online survey was conducted among HCWs in Cameroon using 21-item questions adapted from the United States Centers for Disease Control and Prevention (US-CDC) standard questionnaire on Mpox. The overall knowledge of Mpox was assessed by cumulative score and categorized as excellent (≥80%, 17/21) or good (≥70%, ≥15/21) knowledge. The regression analysis was used to identify the predictors of Mpox knowledge. Results: The survey enrolled 377 participants, but only responses from 342 participants were analyzed. Overall, 50.6% were female participants, and 59.6% aged 30 years or younger. The majority of the participants were medical doctors (50.3%); most worked in central-level hospitals (25.1%) and had 1-5 years of experience (70.7%). A total of up to 92.7% were aware of Mpox, with social media (58.7%) and radio/television (49.2%) as the main sources. The mean knowledge score was 14.0 ± 3.0 (4 to 20), with only 12.9% having excellent knowledge (≥80%) and 42.1% having good knowledge of Mpox. Younger age (26-30 years old) was associated with good knowledge, while workplace type was associated with excellent knowledge of Mpox (aOR [95% CI]: 4.01 [1.43-11.24]). Knowledge of treatment/management of Mpox was generally poor across the different professional categories. Conclusion: Knowledge of Mpox among HCWs is substandard across different professionals. Thus, for optimal preparedness and immediate interventions for Mpox and similar emerging pathogens, capacity-strengthening programs should be organized for HCWs while encouraging scientific literature and organizational social media websites.

Determinants of Immunovirological Response among Children and Adolescents Living with HIV-1 in the Central Region of Cameroon.

About 90% of new HIV-1 infections in children occur in sub-Saharan Africa, where treatment monitoring remains suboptimal. We sought to ascertain factors associated with immunovirological responses among an ART-experienced paediatric population in Cameroon. A laboratory-based and analytical study was conducted from January 2017 throughout December 2020 wherein plasma viral load (PVL) analyses and CD4 cell counts were performed. Viral suppression (VS) was defined as PVL < 1000 copies/mL and immunological failure (IF) as CD4 < 500 cells/µL for participants ≤5 years and CD4 < 250 cells/µL for those >5 years; p < 0.05 was considered statistically significant. Overall, 272 participants were enrolled (median age: 13 [9-15.5] years; 54% males); median ART duration 7 [3-10] years. Globally, VS was achieved in 54.41%. VS was 56.96% in urban versus 40.48% in rural areas (p = 0.04). IF was 22.43%, with 15.79% among participants ≤5 years and 22.92% among those >5 years (p = 0.66). IF was 20.43% in urban versus 33.33% in rural areas (p = 0.10). Following ART, IF was 25.82% on first-line (non-nucleoside reverse transcriptase inhibitors; NNRTI-based) versus 10.17% on second-line (protease inhibitor-based) regimens (p = 0.01). Interestingly, IF was 7.43% among virally suppressed versus 40.32% among virally unsuppressed participants (p < 0.0001). A low VS indicates major challenges in achieving AIDS' elimination in this paediatric population, especially in rural settings and poor immune statuses. Scaling up NNRTI-sparing regimens alongside close monitoring would ensure optimal therapeutic outcomes.

Current Resistance of HIV-1 Strains Isolated in Volunteer Blood Donors in Gabon.

Detection of drug resistance mutations (DRMs) and HIV-1 subtypes ensures effective therapeutic management for HIV-infected individuals. In Gabon, data on DRMs are very little available in the population of people living with HIV and also among voluntary HIV-positive blood donors. This study aimed to study subtypes and DRMs in HIV-1-positive volunteer blood donors in Gabon. A cross-sectional study was carried out at the National Blood Transfusion Center of Gabon. A purposive sampling method was used to collect 128 HIV-1 seropositive blood samples. Viral RNA was extracted on real-time PCR (Abbott 2000®), and sequencing was performed on ABI 3500 (Hitachi®). SPSS version 21.0 software was used for statistical analysis. Of the 128 seropositive volunteer donors included, men and the 29-39-age group were more representative at 78.9% and 49.2%, respectively. Eighty-two samples were sequenced. The majority strains identified were subtype A, subtype F, subtype G, CRF02_AG, and CRF45_cpx. The resistance mutations identified were K103N, L210W, E138G, V179D, V179T, and M46L. The prevalence of resistant subtypes was 25.6%. CRF02_AG strains exhibited high-level resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including efavirenz and nevirapine. The study identified major DRMs in reverse transcriptase and protease that confer high-level resistance to most NNRTIs, nucleoside reverse transcriptase inhibitors, and protease inhibitors. CRF02_AG was more predominant, and the frequency of resistant subtypes was high. However, these data will contribute to the therapeutic choice during the initiation of antiretroviral treatment in treatment-naive patients in Gabon.

Characterization of HIV-1 Reservoirs in Children and Adolescents: A Systematic Review and Meta-Analysis Toward Pediatric HIV Cure.

OBJECTIVE: To conduct a comprehensive, systematic review of the profile of HIV-1 reservoirs in children and adolescents with perinatally acquired HIV infection. STUDY DESIGN: Randomized and nonrandomized trials, cohort studies, and cross-sectional studies on HIV reservoirs in pediatric populations, published between 2002 and 2022, were included. Archived-drug resistance mutations (ADRMs) and the size of reservoirs were evaluated. Subgroup analyses were performed to characterize further the data, and the meta-analysis was done through random effect models. RESULTS: Overall, 49 studies from 17 countries worldwide were included, encompassing 2356 perinatally infected participants (48.83% females). There are limited data on the quantitative characterization of viral reservoirs in sub-Saharan Africa, with sensitive methodologies such as droplet digital polymerase chain reaction rarely employed. The overall prevalence of ADRMs was 37.80% (95% CI 13.89-65.17), with 48.79% (95% CI 0-100) in Africa, 42.08% (95% CI 6.68-82.71) in America, 23.88% (95% CI 14.34-34.90) in Asia, and 20.00% (95% CI 10.72-31.17) in Europe, without any difference between infants and adolescents (P = .656). Starting antiretroviral therapy (ART) before 2 months of age limited the levels of HIV-1 DNA (P = .054). Participants with long-suppressed viremia (>5 years) had lower levels of HIV-1 DNA (P = .027). Pre- and post-ART CD4 ≤29% and pre-ART viremia ≥5Log were all found associated with greater levels of HIV-1 DNA (P = .038, P = .047, and P = .041, respectively). CONCLUSIONS: The pooled prevalence of ADRMs is high in perinatally infected pediatric population, with larger proviral reservoir size driven by delayed ART initiation, a shorter period of viral suppression, and immunovirological failures. Thus, strategies for pediatric HIV functional cure should target children and adolescents with very early ART initiation, immunocompetence, and long-term viral suppression.

Performance characteristics of Allele-Specific PCR (ASPCR) in detecting drug resistance mutations among non-B HIV-1 Variants.

Allele-Specific Polymerase Chain Reaction (ASPCR) is an affordable point-mutation assay whose validation could improve the detection of HIV-1 drug resistance mutations (DRMs) in resource-limited settings (RLS). We assessed the performance of ASPCR onforty-four non-B HIV-1 plasma samples from patients who were ARV treated in failure in N'Djamena-Chad. Viral RNA was reverse-transcribed and amplified using LightCycler® FastStart DNA MasterPLUS SYBR Green I. Detection of six major DRMs (K70R, K103N, Y181C, M184V, T215F, T215Y) was evaluated on Roche LightCycler®480 automated system (with dilutions 0.01-100%). ASPCR-results were compared to Sanger-sequencing (gold-standard). Correlations of mutation curves were excellent (R2 >0.97); all DRMs were detected with desirable mutant/wild-type threshold differences (ΔCt≥9) except K70R(ΔCtK70R=6; ΔCtK103N=13; ΔCtM184V=9; ΔCtT215F=12; ΔCtT215Y=12; ΔCtY181C=9) and positive controls were below required thresholds. Also, ASPCR reproducibility on DRMs was assessed by using dilutions of intra-assay and inter-assay coefficient of variations respectively with a threshold of less than 50(i.e.<0.50 variation) which are;: K70R (0.02-0.28 vs. 0.12-0.37), K103N (0.08-0.42 vs. 0.12-0.37), Y181C (0.12-0.39 vs. 0.31-0.37), M184V (0.13-0.39 vs. 0.23-0.42), T215F (0.05-0.43 vs. 0.04-0.45) and T215Y (0.13-0.41 vs. 0.19-0.41). DRM detection-rate by ASPCR vs Sanger was respectively: M184V (63.6% vs. 38.6%); T215F (18.1% vs. 9.1%); T215Y (6.8% vs. 2.3%); K70R (4.5% vs. 2.3%). K103N (22.7% vs. 13.6%); Y181C (13.6% vs. 11.4%). Correlations of mutation curves were excellent (R2 >0.97); all DRMs were detected with desirable mutant/wild-type threshold differences (ΔCt≥9) except K70R(ΔCtK70R=6; ΔCtK103N=13; ΔCtM184V=9; ΔCtT215F=12; ΔCtT215Y=12; ΔCtY181C=9) and positive controls were below required thresholds. Also, ASPCR reproducibility on DRMs was assessed by using dilutions of intra-assay and inter-assay coefficient of variations respectively with a threshold of less than 50(i.e.<0.50 variation) which are;: K70R (0.02-0.28 vs. 0.12-0.37), K103N (0.08-0.42 vs. 0.12-0.37), Y181C (0.12-0.39 vs. 0.31-0.37), M184V (0.13-0.39 vs. 0.23-0.42), T215F (0.05-0.43 vs. 0.04-0.45) and T215Y (0.13-0.41 vs. 0.19-0.41). DRM detection-rate by ASPCR vs Sanger was respectively: M184V (63.6% vs. 38.6%); T215F (18.1% vs. 9.1%); T215Y (6.8% vs. 2.3%); K70R (4.5% vs. 2.3%). K103N (22.7% vs. 13.6%); Y181C (13.6% vs. 11.4%). ASPCR appears more efficient for detecting DRMs on diverse HIV-1 non-B circulating in RLS like Chad.

Effect of Hepatitis B Vaccination on HBV-infection among school children in Yaounde ten years after its introduction of the HBV vaccine into routine Immunization Program in Cameroon

Introduction: since the introduction of the anti-HBV vaccine into the Expanded Program on Immunization (EPI) in 2005 in Cameroon, vaccination coverage has reached 99.0%. This coverage would indicate an increase the number of children immune to Hepatitis B Virus (HBV) and a decrease in susceptibility to HBV-infection. This study was conducted to evaluate the effect of the HBV vaccine on pediatric HBV-infection in Yaounde, Cameroon. Methods: this school based cross-sectional study was conducted from February to May 2016 among 180 children from Nkomo public school. The study population was stratified into two groups: vaccinated (n=95) versus (vs) unvaccinated (n=85). Screening for HBV biomarkers was done using a rapid panel test for detection (HBsAg, HBeAg and anti-HBc) and anti-HBs titer using enzyme linked immunosorbent assay (ELISA). Statistical analyses were done using SPSS v. 22 with p ≥0.05 considered significant. Results: the mean age was 9.65 years. HBsAg (p=0.019) and anti-HBc (p=0.001) rates were detected in children aged ≥10 years and children aged < 10 years (95.95% [71/74]) were vaccinated vs 22.64% (24/106) for those aged ≥10 years (OR: 80.86; 95% CI: 23.36%-279.87%, p < 0.0001). According to anti-HBV vaccination status, HBsAg rate varied from [9.41% (8/85) to 1.05% (1/95), p=0.025], HBeAg rate varied from [2.35% (2/85) to 0% (0/95), p= 0.42] and anti-HBc rate ranged from [12.94% (11/85) to 2.10% (2/95), p= 0.011]. Conclusion: despite the variability of the anti-HBs titer, vaccination against HBV has a positive effect on the reduction of HBV infection in children in tropical settings such as Cameroon.

Genomic surveillance of SARS-CoV-2 reveals highest severity and mortality of delta over other variants: evidence from Cameroon.

While the SARS-CoV-2 dynamic has been described globally, there is a lack of data from Sub-Saharan Africa. We herein report the dynamics of SARS-CoV-2 lineages from March 2020 to March 2022 in Cameroon. Of the 760 whole-genome sequences successfully generated by the national genomic surveillance network, 74% were viral sub-lineages of origin and non-variants of concern, 15% Delta, 6% Omicron, 3% Alpha and 2% Beta variants. The pandemic was driven by SARS-CoV-2 lineages of origin in wave 1 (16 weeks, 2.3% CFR), the Alpha and Beta variants in wave 2 (21 weeks, 1.6% CFR), Delta variants in wave 3 (11 weeks, 2.0% CFR), and omicron variants in wave 4 (8 weeks, 0.73% CFR), with a declining trend over time (p = 0.01208). Even though SARS-CoV-2 heterogeneity did not seemingly contribute to the breadth of transmission, the viral lineages of origin and especially the Delta variants appeared as drivers of COVID-19 severity in Cameroon.

Anti-hepatitis C antibody carriage and risk of liver impairment in rural-Cameroon: adapting the control of hepatocellular carcinoma for resource-limited settings.

BACKGROUND: The Viral hepatitis elimination by 2030 is uncertain in resource-limited settings (RLS), due to high burdens and poor diagnostic coverage. This sounds more challenging for hepatitis C virus (HCV) given that antibody (HCVAb) sero-positivity still lacks wide access to HCV RNA molecular testing. This warrants context-specific strategies for appropriate management of liver impairment in RLS. We herein determine the association between anti-HCV positivity and liver impairment in an African RLS. METHODS: A facility-based observational study was conducted from July-August 2021 among individuals attending the "St Monique" Health Center at Ottou, a rural community of Yaounde,Cameroon. Following a consecutive sampling, consenting individuals were tested for anti-HCV antibodies, hepatitis B surface antigen (HBsAg) and HIV antibodies (HIVAb) as per the national guidelines. After excluding positive cases for HBsAg and/or HIVAb, liver function tests (ALT/AST) were performed on eligible participants (HBsAg and HIVAb negative) and outcomes were compared according to HCVAb status; with p < 0.05 considered statistically significant. RESULTS: Out of 306 eligible participants (negative for HBsAg and HIVAb) enrolled, the mean age was 34.35 ± 3.67 years. 252(82.35%) were female and 129 (42.17%) were single. The overall HCVAb sero-positivity was 15.68%(48/306), with 17.86% (45/252) among women vs. 5.55%(3/54) among men [OR (95%CI) = 3.69(2.11-9.29),p = 0.04]. HCVAb Carriage was greater among participants aged > 50 years compared to younger ones [38.46%(15/39) versus 12.36% (33/267) respectively, OR(95%CI) = 4.43(2.11-9.29), p < 0.000] and in multipartnership [26.67%(12/45)vs.13.79%(36/261) monopartnership, OR (95%CI) = 2.27(1.07-4.80),p = 0.03]. The liver impairment rate (abnormal ALT+AST levels) was 30.39%(93/306), with 40.19%(123/306) of abnormal ALT alone. Moreover, the burden of Liver impairment was significantly with aged> 50 versus younger ones [69.23% (27/39) versus 24.72%(66/267) respectively, p < 0.000). Interestingly, the burden of liver impairment (abnormal AST + ALAT) was significantly higher in HCVAb positive (62.5%, 30/48) versus HCVAb negative (24.42%, 63/258) participants, OR: 3.90 [1.96; 7.79], p = 0.0001. CONCLUSIONS: In this rural health facility, HCVAb is highly endemic and the burden of liver impairment is concerning. Interestingly, HCVAb carriage is associated with abnormal liver levels of enzyme (ALT/AST), especially among the elderly populations. Hence, in the absence of nuclei acid testing, ALT/AST are relevant sentinel markers to screen HCVAb carriers who require monitoring/care for HCV-associated hepatocellular carcinoma in RLS.