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.

Polyoxygenated Stigmastane-Type Steroids from Vernonia kotschyana Sch. Bip. ex Walp. and Their Chemophenetic Significance.

Four polyoxygenated stigmastanes (1-4) alongside known analogues (7-8) and flavonoids (5-6) were isolated from a dichloromethane/methanol (1:1, v/v) extract of the whole plant of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae). Their structures were determined by means of spectroscopic and spectrometric analysis. The relative stereochemistry of the new compounds was established and confirmed via biosynthesis evidence and cyclization of 1 under acidic conditions. A plausible biosynthetic pathway to the new compounds and the chemophenetic significance of the isolated constituents were also discussed. The crude extract, fractions, and compounds (1-3) were assessed for their antibacterial activity against five highly prevalent bacterial strains. The fractions and compounds showed low to moderate activity with minimal inhibitory concentrations (MICs) > 125 µg/mL.

Constituents of the Stem Bark of Symphonia globulifera Linn. f. with Antileishmanial and Antibacterial Activities.

The chemical investigation of the n-hexane fraction from the methanol extract of the stem bark of Symphonia globulifera Linn f., which displayed good in vitro activity against Leishmania donovani NR-48822 promastigotes (IC50 43.11 µg/mL), led to the isolation of three previously unreported polyprenylated benzophenones, guttiferone U (1), V (2)/W (3), and a new tocotrienol derivative named globuliferanol (4), along with 11 known compounds (5-15). Their structures were elucidated based on their NMR and MS data. Some isolated compounds were assessed for both their antileishmanial and cytotoxic activities against L. donovani and Vero cells, respectively. Guttiferone K (5) exhibited the best potency (IC50 3.30 µg/mL), but with low selectivity to Vero cells. The n-hexane fraction and some compounds were also assessed in vitro for their antibacterial activity against seven bacterial strains. All the samples exhibited moderate to potent antibacterial activity (MICs ≤ 15.6 µg/mL) against at least one of the tested strains.

Bioactive Arylnaphthalide Lignans from Justicia depauperata.

Eleven previously undescribed arylnaphthalide lignans (1-11) together with seven known compounds were isolated from the whole plant of Justicia depauperata. The structures of 1-11 were elucidated by spectroscopic analysis and mass spectrometry. Compounds 6 (IC50 = 4.1 µM) and 9 (IC50 = 9.5 µM) displayed cytotoxic activity against the KB-3-1 cervical carcinoma cell line. This report provides an insight into the conformational equilibria occurring in the arylnaphthalide lignan constituents of this plant.

Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease.

BACKGROUND: Previous studies have shown that tuberculosis (TB) is a risk factor for chronic airflow limitation. Chronic obstructive pulmonary disease (COPD) is recognized as the result of chronic inflammation, usually related to noxious particles. Post-TB airflow obstruction and tobacco-related COPD have the same functional pathway characterized by persistent airflow limitation. We sought to compare the profile of 29 cytokines in the sputum of subjects with post-TB airflow obstruction and those with COPD related to tobacco. RESULTS: The forced expiratory volume in the first second (FEV1) and forced expiratory volume/forced vital capacity (FEV/FVC) ratio were lower in the COPD patients with the history of smoking compared to the post-TB airflow obstruction subgroup. The stages of the disease were more advanced in COPD / tobacco patients. Among the cytokines, IL-1α, IL-1ß, MIP-1ß, sCD40L and VEGF levels were higher in COPD patients, compared to the controls with p values ​​of 0.003, 0.0001, 0.03, 0.0001 and 0.02 respectively. When the two COPD subgroups were compared, IL-1α, IL-6, TNF-α and IL-8 levels were higher in the COPD patients with the history of tobacco compared to the COPD patients with the history of TB with p-values ​​of 0.031, 0.05, 0.021 and 0.016, respectively. CONCLUSION: COPD related to tobacco is more severe than post-TB airflow obstruction. The pathogenesis of post-TB airflow obstruction appears to involve the cytokines IL-1RA, IL-1α, IL-1ß, IL-17, GRO and sCD40L, while COPD related to tobacco involves more cytokines.

Intestinal Parasites Infections among HIV Infected Children Under Antiretrovirals Treatment in Yaounde, Cameroon.

BACKGROUND: Intestinal parasitic infections are among the most common communicable diseases worldwide, particularly in developing countries. Human immunodeficiency virus (HIV) causes dysregulation of the immune system through the depletion of CD4+ T lymphocytes which gives rise to opportunistic infections. METHODOLOGY: A cross-sectional study was conducted from January to October 2018. Stool and blood samples were collected from participants aged 1 to 19. Stool samples were analyzed for intestinal parasites. Blood samples were analyzed for HIV and CD4 + T cell counts. RESULTS: Out of 214 children enrolled, 119 (55.6%) were HIV infected and 95 (44.4%) were HIV non-infected. All infected children were on antiretroviral treatment (ART). The prevalence of intestinal parasites was 20.2% in HIV infected and 15.8% in non-infected children. Among the 119 HIV infected children, 33 (27.7%) of them had a CD4+ T cell count less than 500 cells/mm3, and amongst them 5.9% had CD4+ T cell count less than 200 cells/mm3. Among HIV infected children, Cryptosporidium spp. was frequently detected, 7/119 (5.9%), followed by Giardia lamblia 5/119 (4.2%) then Blastocystis hominis 3/119 (2.5%) and Entamoeba coli 3/119 (2.5%). Participants on ART and prophylactic co-trimoxazole for >10 years had little or no parasite infestation. CONCLUSIONS: Although ART treatment in combination with prophylactic co-trimoxazole reduces the risk of parasitic infection, 20.2% of HIV infected children harbored intestinal parasites including Cryptosporidium spp. Stool analysis may be routinely carried out in order to treat detected cases of opportunistic parasites and such improve more on the life quality of HIV infected children.

HLA A*32 is associated to HIV acquisition while B*44 and B*53 are associated with protection against HIV acquisition in perinatally exposed infants.

BACKGROUND: Human leukocyte antigen (HLA) molecules play a key role in the cellular immune system. They may be determinants of mother-to-child transmission which is the driving force in pediatric HIV infection. We intended to look at the impact of the distribution of these polymorphic HLA genes in the mother-to-child transmission (MTCT) of HIV in Cameroon. METHODS: A total of 156 mother-baby pairs were enrolled in three hospitals of Yaounde, capital of Cameroon. After the extraction of the DNA from blood samples using the Qiagen Kit as per manufacturer' instructions, the polymorphism of the HLA class 1 ABC was determined using the PCR- sequence specific primers assay. RESULTS: The distribution of HLA class 1 revealed that none of the allele studied was associated with transmitters or non-transmitters, so was not implicated in transmission. The regression analysis showed that HLA A*32 [OR 0.062 (CI; 0.0075 to 0.51)] is associated with HIV acquisition while HLA B*44 [OR 0.47 (CI; 0.21 to 1.14)] and HLA B*53 [OR; 0.14 (CI; 0.018 to 1.22)] were implicated in reducing the acquisition of HIV by infants. The homozygosity of locus C [OR 6.99 (CI; 1.81 to 26.88), p = 0.0027] was found as a risk factor for the acquisition, while the A*32-B*44 haplotype [OR 10.1 (CI 1.17 to 87.87), p = 0.03] was a risk factor for the transmission. CONCLUSION: This study has found that HLA A*32, B*44 and B*53 have an impact in MTCT outcomes. The homozygosity of locus C and the A*32-B*44 haplotype were risk factors for acquisition and transmission respectively.

Maternal age, infant age, feeding options, single/multiple pregnancy, type of twin sets and mother-to-child transmission of HIV.

BACKGROUND: Some risk factors for mother-to-child transmission (MTCT) of HIV have been identified. To further reduce MTCT, other risk factors were evaluated. MATERIALS AND METHODS: A retrospective study on early infant diagnosis was conducted. Two-sided chi-square test was used to assess associations with infant HIV status. RESULTS: A total of 15 233 HIV-infected mothers and 15 404 infants were recruited. MTCT rate was 9.34%. Only 3.8% of infants born to mothers on antiretroviral treatment were infected. Under nevirapine, 4.1% of infants were infected. MTCT increased with infant' age at testing. Younger mothers tend to transmit more HIV (P = 0.003). More children were infected in single pregnancies compared with multiple pregnancies, P < 0.001. There were more infections in male-female twins' sets (P = 0.037). CONCLUSIONS: Maternal age, type of pregnancy and twins' sets are new MTCT risk factors. Strategies to further decrease transmission through family planning, pre/post natal consultations and clinical practices are needed.

An assessment of antiretroviral drug initiation to pregnant women of unknown HIV status during labour and delivery in Cameroon.

BACKGROUND: Evidence from previous research has shown that antiretroviral (ARV) drug initiation to seropositive pregnant women could significantly contribute to eliminating new paediatric infections even when started during labour and delivery. This study therefore seeks to assess missed opportunities for ARV initiation during this critical period of pregnancy to improve outcomes of the prevention of mother-to-child transmission (PMTCT) programmes in Cameroon. METHODS: A retrospective study was conducted on the 2014 PMTCT data for labour and delivery among pregnant women of unknown HIV status within health facilities in six regions of Cameroon (428 eligible facilities). Outcomes were summarised using (relative) frequencies. ARV initiations for eligible facilities were stratified per region and per facility type (public and private facilities). Initiation to ARV was reported using odds ratios and 95% confidence intervals. RESULTS: An average of 14.6% of the 9 170 pregnant women presenting with unknown HIV status at labour and delivery, were diagnosed HIV-positive. A cumulative average from the six regions revealed that only half (51.4%) of these seropositive women received an ARV regimen. The findings from the North-West region depict 100% initiation to ARV among the study population. The odds of ARV initiation in the study population was more likely in the public health facilities than the private facilities for five regions, excluding the North-West (odds ratio of 1.35 [1.07, 170]). CONCLUSION: A significant portion of women do not receive the care required, especially in private health facilities. Evidence from the results in the North West region suggest that processes to address health system barriers to improve PMTCT uptake are feasible in Cameroon.

Estimating mother-to-child HIV transmission rates in Cameroon in 2011: a computer simulation approach.

BACKGROUND: Despite the progress in the Prevention of the Mother-to-Child Transmission of HIV (PMTCT), the paediatric HIV epidemic remains worrying in Cameroon. HIV prevalence rate for the population of pregnant women was 7.6% in 2010 in Cameroon. The extent of the paediatric HIV epidemic is needed to inform policymakers. We developed a stochastic simulation model to estimate the number of new paediatric HIV infections through MTCT based on the observed uptake of services during the different steps of the PMTCT cascade in Cameroon in 2011. Different levels of PMTCT uptake was also assessed. METHODS: A discrete events computer simulation-based approach with stochastic structure was proposed to generate a cohort of pregnant women followed-up until 6 weeks post-partum, and optionally until complete breastfeeding cessation in both prevalent and incident lactating HIV-infected women. The different parameters of the simulation model were fixed using data sources available from the 2011 national registry surveys, and from external cohorts in Cameroon. Different PMTCT coverages were simulated to assess their impact on MTCT. Available data show a low coverage of PMTCT services in Cameroon in 2011. RESULTS: Based on a simulation approach on a population of 995, 533 pregnant women, the overall residual MTCT rate in 2011 was estimated to be 22.1% (95 % CI: 18.6%-25.2%), the 6-week perinatal MTCT rate among prevalent HIV-infected mothers at delivery is estimated at 12.1% (95% CI: 8.1%-15.1%), with an additional postnatal MTCT rate estimated at 13.3% (95% CI: 9.3%-17.8%). The MTCT rate among children whose mothers seroconverted during breastfeeding was estimated at 20.8% (95% CI: 14.1%-26.9%). Overall, we estimated the number of new HIV infections in children in Cameroon to be 10, 403 (95% CI: 9, 054-13, 345) in 2011. When PMTCT uptake have been fixed at 100%, 90% and 80%, global MTCT rate failed to 0.9% (9% CI: 0.5%-1.7%), 2.0% (95% CI: 0.9%-3.2%) and 4.3% (95% CI: 2.4%-6.7%) respectively. CONCLUSIONS: This model is helpful to provide MTCT estimates to guide the national HIV policy in Cameroon. Increasing supply and uptake of PMTCT services among prevalent HIV infected pregnant women, as well as HIV-prevention interventions including the offer and acceptance of HIV testing and counselling in lactating women could reduce significantly the residual HIV MTCT in Cameroon. A public health effort should be made to encourage health care workers and pregnant women to use PMTCT services until complete breastfeeding cessation.

The shifts in intergenerational relations in Cameroon and their potential impact on the health of older adults.

INTRODUCTION: Africa is experiencing a gradual demographic shift due to rising life expectancy and increasing urbanisation. In sub-Saharan Africa, elderly individuals typically reside with their children. The rise in life expectancy by almost a decade and the prevalence of precarious living conditions raise concerns about the sustainability of the healthcare system, which has traditionally relied on intergenerational solidarity. METHODS: The research aims to analyse the evolving role of older adults in Cameroonian society and to examine the potential impact of this change on intergenerational relationships and the health of older adults. A qualitative methodology was employed, using intergenerational focus groups in Cameroon. RESULTS: Traditionally, older adults held a central role in knowledge transmission through discourse. However, the modernisation of society is challenging this position.The emergence of new technologies, particularly communication tools, is leading to a questioning of older adults' experiential knowledge. Societal changes are contributing to a decline in respect for older adults in discourse. Older adults deplore these societal changes and fear for their place in society while young people are questioning the central role of older people in society. DISCUSSION: These changes could reduce the sense of usefulness of older people, with negative consequences for their health. Several studies have highlighted the impacts of ageism on the health of older adults in industrialised countries. However, there are little data on the impact of the marginalisation of older adults on their health in industrialising societies. Further research is needed to study the impact on the health of older adults.

Low prevalence of HIV in the northern Cameroon: contribution of some AIDS restriction genes and potential implications for gene therapy.

Background: HIV infection and its progression to AIDS depend on several factors including host genetic factors. The immunological mechanisms of host resistance to HIV infection greatly influence the prevalence of HIV in a given region. Worldwide, Cameroon not exempted, the frequency of AIDS-associated genes varies and may influence this prevalence. The North and Far North Regions of Cameroon have had the lowest HIV prevalence in the country for many years despite risky behaviors associated with their customs and habits. In this work, we seek to explore the contribution of host genes to the HIV low prevalence in these regions. Methodology: Five genes variants previously described as HIV AIDS related were studied. These genes are: CCR5Δ32, CCR5promoter59029G, CCR2-64I, SDF1-3'A and Trim5α(R136Q). A total of 384 consented participants were included in this study. The HIV serological status was confirmed using national algorithm. Genomic DNA was extracted from the buffy coats and used for genotyping. The results obtained were compiled in Excel 2016, Epi Info 7.1 and snpStats software and Chi two tests allowed us to compare the frequencies of the AIDS related alleles in the North with those in other Regions of Cameroon and to measure the impact of these ARGs on protection against HIV. Results: The frequency of protective alleles CCR5Δ32, CCR5promoter59029G, CCR2-64I, SDF1-3'A and Trim5α(R136Q) was the allelic frequencies should be expressed as percentages i.e. 0.52%; 37.56%; 36.46%; 25.19% and 69.33%. These allelic frequencies exhibited a significant difference when compared to those obtained in other regions of Cameroon (p < 0.01). Protective alleles were predominant in the Northern region compared to others and were associated with resistance to HIV [(p < 0.0001); OR = 2.02 CI, 95%]. Conclusion: The higher frequency of HIV-protective alleles in the northern regions may be a contributing factor to the lower prevalence of HIV. Nevertheless, this should be reinforced by other preventive and surveillance methods to guarantee the sustained low prevalence. HIV can develop resistance through the process of mutation, but the host targets themselves are genetically stable. The study of these host genetic restriction factors is of great value in the design of a practical cure for HIV infection or an effective vaccine.

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.

Protection level of anti-hepatitis B vaccine and immunoglobulin in a pediatric Cameroonian population.

Despite the availability for nearly twenty years of an effective vaccine, hepatitis B remains one of the most frequent viral diseases throughout the world. Mother-to-child transmission is one of the primary routes of transmission in children. To assess the vaccine response in children born to HBV infected mothers. HBsAg-positive consenting mothers registered in the antenatal care (ANC) service database of Centre Hospitalier Dominicain St-Martin de Porres, Yaounde were enrolled with their children. Socio-demographic characteristics were collected using a tested questionnaire. The 5 markers of hepatitis B were tested and the quantification of anti-HBsAg antibodies was done by indirect ELISA method. The data collected was analyzed using Microsoft excel and Epi-info softwares. Out of 5,996 women registered, 143 were identified as HBsAg positive (2.38% prevalence) and none was HBeAg positive. Of these 143 HBsAg positive women, 50 were enrolled in the study. Of the 50 positive mothers, 78 children were included with a mean age ± standard deviation of 2.33±2.86 years. No child was infected with HBV, but all have been exposed to the virus (HBeAb-positive). Overall 64 (82.05%) received at birth both anti-HBs immunoglobulin (HBIG) and a dose of vaccine, while 14 (17.95%) received only the birth dose of vaccine. 72 (92.31%) children received all three recommended doses of vaccine. Vaccine responders were 62.82% (above 10 IU/ml), while 37.18% of children were non-responders; representing a higher risk group if not boosted. The coverage of the anti-HBV vaccine in children in this study was 92.31%. The protection level of 62.82% is below the 95% recommended rate by WHO. The factors sustaining this suboptimal protection should be investigated.

Maternal Socio-Demographic Factors and Mother-to-Child Transmission of HIV in the North Region of Cameroon.

Background and Objective: Socio-demographic factors are important risk factors for HIV infection. Maternal socio-demographic factors associated with HIV transmission from mother to child are not well elucidated to our knowledge. This study aimed to assess the maternal socio-demographic factors associated with HIV vertical transmission. Methods: A matched case-control study was conducted among children under 15 years of age born to HIV-infected mothers; using a structured questionnaire. The study was conducted in four health facilities in the North Region of Cameroon from July 2015 to October 2016. HIV- infected children were the cases, and HIV-uninfected children were the controls. One case was matched to nearly 4 controls according to age and sex. A total of 113 HIV-infected mothers of children under 15 years of age were purposively enrolled in the study. A questionnaire was administered to mothers and socio-demographic characteristics were collected. Blood samples were collected from the mother and her child for the determination or confirmation of HIV status. Univariate and multiple logistic regressions were used to assess associations between socio-demographic variables and HIV transmission from mother to child. Results: A total of 113 HIV-infected mothers and 113 children under 15 years of age were enrolled in this study. The majority of the mothers were between the age ranges of 25 years to 34 years. Of the 113 HIV-infected mothers, 69 (61%) were Muslims, 33 (32.1%) were not educated, 88 (77.8%) were unemployed, 80 (70.9%) were married, out of which 49 (61.6%) were engaged in a monogamous union. Of the 113 children (49.6%) were female, 25 (22.1%) were HIV-infected and 88 (77.9%) were HIV-exposed uninfected. At the univariate level, mothers who achieved a primary level of education were less likely to transmit HIV to infants compared to uneducated mothers [OR=0.28; CI (0.08-0.95); p=0.04]; and widows had a higher likelihood of HIV transmission to infants compared to married mothers [OR=4.65; CI (1.26-17.20); p=0.02]. Using multiple logistic regression, the maternal primary education level [aOR=0.32; CI (0.08-0.90); p=0.03] and widowerhood [aOR=7.05; CI (1.49-33.24); p=0.01] remained highly associated with the likelihood of HIV transmission to infants. Conclusion and Global Health Implications: Uneducated mothers and widows had a higher likelihood of mother-to-child transmission of HIV. Our findings should prompt reinforcement of prevention strategies targeting uneducated women and widows.

Antibacterial constituents of Rumex nepalensis spreng and its emodin derivatives.

The CH2Cl2-MeOH (1:1) extract of roots of Rumex nepalensis (Polygonaceae) displayed significant antibacterial activity against five bacterial strains with MICs (62.5-31.2 µg.mL-1). The EtOAc soluble fraction displayed a significant activity against the same strains with MICs (31.2-3.9 µg.mL-1). The purification of the EtOAc fraction yielded one new phenylisobenzofuranone derivative, berquaertiide (1), along with 19 known compounds (2-20). Their structures were elucidated based on the analysis of their NMR and MS data. All the isolated compounds were assessed for their antibacterial activity. Compound 2 was the most active against all the tested strains (15.7 to 1.9 µg.mL-1), while compounds 3-7 displayed good activities on at least one of the tested strains. In addition, seven analogues (21-27) of compound 2 were prepared and further assessed for their antibacterial activity. Compounds 26 and 27 were most active than 2 against Salmonella enterica and Klebsiella pneumoniae with MIC (125 and 15.6 µg.mL-1, respectively).

Constituents of the Stem Bark of Trichilia monadelpha (Thonn.) J. J. De Wilde (Meliaceae) and Their Antibacterial and Antiplasmodial Activities.

The chemical investigation of the EtOH extract from the stem bark of Trichilia monadelpha (Thonn.) J. J. De Wilde afforded two new limonoids (1 and 2): 24-acetoxy-21,25-dihydroxy-21,23-epoxytirucall-7-en-3-one (1) and (6R)-1-O-deacetylkhayanolide E (2), together with eleven known compounds (3-13), including additional limonoids, flavonoids, triterpenoids, steroids, and fatty acid. Their structures were determined using 1D- and 2D-NMR experiments, ESI mass spectrometry, and single crystal X-ray diffraction analysis. The antibacterial and antiplasmodial activities of the extracts, sub-extracts, fractions, and some of the isolated compounds were evaluated in known pathogenic strains, including Staphylococcus aureus and Plasmodium falciparum. Fraction E (n-Hex/EtOAc 30:70, v/v) showed significant activity against S. aureus ATCC 25923 with a MIC value of 3.90 µg/mL, while one of its constituents (epicatechin (9)) exhibited significant activity with MIC values of 7.80 µg/mL. Interestingly, grandifotane A (6) (IC50 = 1.37 µM) and khayanolide D (5) (IC50 = 1.68 µM) were highly active against the chloroquine-sensitive/sulfadoxine-resistant plasmodium falciparum 3D7 strain, unlike their corresponding plant extract and fractions.

The mother-to-child transmission of HIV-1 and profile of viral reservoirs in pediatric population: A systematic review with meta-analysis of the Cameroonian studies.

BACKGROUND: The mother-to-child transmission of HIV-1 (MTCT) remains on the major route of HIV-transmission among pediatric populations in Africa. Though a prevention of MTCT (PMTCT) high-priority country, data on the MTCT burdens in Cameroon remains fragmented. OBJECTIVE: We sought to assess the pooled MTCT rate, its risk-factors, and to characterize viral reservoirs of infected-children in Cameroon. METHODS: All relevant observational cohort and cross-sectional studies conducted in Cameroon were searched from PubMed, African Journals Online, Google scholar, ScienceDirect and academic medical education databases. Heterogeneity and publication bias were respectively assessed by the I2 statistic and the Egger/funnel plot test. Meta-analysis was performed using the random effects model. MTCT rate >5% was considered as "high". This review was registered in the Prospero database, CRD42021224497. RESULTS: We included a total of 29 studies and analyzed 46 684 children born from HIV-positive mothers. The overall rate of MTCT was 7.00% (95% CI = 6.07-8.51). According to regions, the highest burden was in Adamaoua-region (17.51% [95% CI:14.21-21.07]) with only one study found. PMTCT option-B+ resulted in about 25% reduction of MTCT (8.97% [95% CI: 8.71-9.24] without option-B+ versus 2.88% [95% CI: 5.03-9.34] with option-B+). Regarding risk-factors, MTCT was significantly associated with the absence of PMTCT-interventions both in children (OR:5.40 [95% CI: 2.58-11.27]) and mothers (OR: 3.59 [95% CI: 2.15-5.99]). Regarding viral reservoirs, a pro-viral DNA mean of 3.34±1.05 log10/mL was observed among 5/57 children and archived HIV drug resistance mutations were identified in pro-viral DNA marker among 21/79 infected-children. CONCLUSION: In spite of the dropdown in MTCT following option-B+ implementation, MTCT remains high in Cameroon, with substantial disparities across regions. Thus, in this era of option-B+, achieving MTCT elimination requires interventions in northern-Cameroon. The variation in pro-viral load in infected-children underlines the relevance of characterizing viral reservoirs for possible infection control in tropical settings.

Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: a contribution toward optimal pediatric HIV control strategies.

Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm3. As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p<0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1ß) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p<0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm3) vs. immunocompromised (CD4<500 cell/mm3), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p<0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1ß, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response.

Expression profiles of miR3181 and miR199a in plasma and placenta of virally suppressed HIV-1 infected Cameroonian pregnant women at delivery.

Human immunodeficiency virus (HIV)-1 infection during pregnancy reduces the transplacental transfer of protective maternal antibodies needed to confer immunity during early postnatal life. However, the mediation of MicroRNA in this dysregulation is not well understood MicroRNAs 3181 and 199a have been shown to mediate neonatal Fc receptor (FcRn)-like transmembrane antibody transfer and endocytosis respectively but their expression levels in the placenta and plasma in women living with HIV have not been extensively investigated. The objective of this study was to determine how the expression levels of miR-3181 and miR-199a in the placenta and plasma are affected in women chronically infected with HIV who are on antiretroviral therapy (ART) and are virally suppressed at delivery. In this pilot case-control study, plasma and placenta biopsies were obtained from 36 (18 HIV+ and 18 HIV-) Cameroonian women at delivery. MicroRNAs 3181 and 199a expression levels were measured using RT-qPCR, data was analyzed using SPSS22.0 and R 3.60, and p values below 0.05 were considered statistically significant. All the HIV-infected women were on known ART regimens and were virally suppressed. There was no significant difference in the levels of miR-3181 (p>0.05) in the placenta and plasma amongst HIV-infected and HIV uninfected women. The expression levels of miR-199a were significantly greater in the plasma compared to the placenta of HIV+ (p = 0.00005) and HIV- (p = 0.027) women. Moreover, there was a significantly higher (p = 0.02) level of miR-199a in the plasma of women with HIV and their uninfected counterparts. Linear regression models adjusted for systolic pressure showed no significant difference (p>0.05) in the levels of miR-199a and miR-3181 in both the placenta and plasma due to HIV infection. Our findings suggest that even though ART uptake and viral suppression might help in maintaining miR3181 and miR199a levels in the placenta of women with HIV at comparative levels to those of their HIV negative counterparts, the significantly higher levels of miR-199a in the plasma of women with HIV compared to the placenta might highlight lurking systemic dangers and requires further investigation.