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.

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.

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.

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.

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.

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.

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.

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.

Assessment of cardiovascular risk factors among HIV-infected patients aged 50 years and older in Cameroon.

Background: Increasing the longevity of people living with HIV (PLHIV) around the world has been accompanied by an increase in the prevalence of cardiovascular disease (CVD) risk factors and morbidity. The impact of these trends on the epidemiology of CVD among PLHIV is less clear. The aim of this study was to assess the risk factors for CVD, and to estimate these risks at 10 years in PLHIV aged 50 and above. Methods: This was a descriptive and analytical study carried out at Mvog Ada District Hospital in Yaounde, Cameroon from January 2020 to January 2021. Descriptive bivariate analyses were used to present the data. The data are presented as frequencies and percentages for categorical variables, and in terms of means and standard deviations for continuous variables where appropriate. The 10-year CVD risk score was calculated using two tools: the validated Framingham risk score (FRS) (low < 10%, moderate 10-20% and high ≥ 20%) and SCORE score (SSC) (low < 3%, moderate 3-4% and high ≥ 5%). Multiple logistic regression models were constructed to examine the respective relationships between the binary dependent variable high CVD risk (FRS ≥ 20%) and the population group, alcohol consumption (more than 10 glasses of beer per week, or more than 35.7 cl/day) and hypertriglyceridemia (independent variables). A p-value less than or equal to 0.05 was considered statistically significant. Results: A total of 112 people aged 50 and above were enrolled in the study out of 180 people registered at the HIV care unit, that is a participation rate of 62.22%. The average age of the participants was 57.3 ± 6.4 years, and the female/male ratio was 1.6. The majority of participants (53.57%) had normal glycaemia levels (<1.10 g/L), 4.46% were diabetic and 46.40% had high blood pressure. The adherence rate for ARV treatment was 98.20%; most participants (77.20%) were alcohol consumers, and 28.10% of participants had hypertriglyceridemia. The estimates of overall cardiovascular risk in 10 years presented 50.90% of participants with low risk, 33% with moderate risk and 16.10% with high risk. Conclusions: Our study indicated an overall risk of cardiovascular events in 10 years is 16.10%, with the main conditional risk factor being hypertriglyceridemia and alcohol consumption, which appeared to triple the risk of CVD among PLHIV.

Enhanced passive surveillance dengue infection among febrile children: Prevalence, co-infections and associated factors in Cameroon.

Dengue virus (DENV) causes a spectrum of diseases ranging from asymptomatic, mild febrile to a life-threatening illness: dengue hemorrhagic fever. The main clinical symptom of dengue is fever, similar to that of malaria. The prevalence of dengue virus infection, alone or in association with other endemic infectious diseases in children in Cameroon is unknown. The aim of this study was to determine the prevalence of dengue, malaria and HIV in children presenting with fever and associated risk factors. Dengue overall prevalence was 20.2%, Malaria cases were 52.7% and HIV cases represented 12.6%. The prevalence of dengue-HIV co-infection was 6.0% and that of Malaria-dengue co-infection was 19.5%. Triple infection prevalence was 4.3%. Dengue virus infection is present in children and HIV-Dengue or Dengue- Malaria co-infections are common. Dengue peak prevalence was between August and October. Sex and age were not associated with dengue and dengue co-infections. However, malaria as well as HIV were significantly associated with dengue (P = 0.001 and 0.028 respectively). The diagnosis of dengue and Malaria should be carried out routinely for better management of fever.

Alteration of the gut fecal microbiome in children living with HIV on antiretroviral therapy in Yaounde, Cameroon.

Multiple factors, such as immune disruption, prophylactic co-trimoxazole, and antiretroviral therapy, may influence the structure and function of the gut microbiome of children infected with HIV from birth. In order to understand whether HIV infection altered gut microbiome and to relate changes in microbiome structure and function to immune status, virological response and pediatric ART regimens, we characterized the gut microbiome of 87 HIV-infected and 82 non-exposed HIV-negative children from Yaounde, a cosmopolitan city in Cameroon. We found that children living with HIV had significantly lower alpha diversity in their gut microbiome and altered beta diversity that may not be related to CD4+ T cell count or viral load. There was an increased level of Akkermansia and Faecalibacterium genera and decreased level of Escherichia and other Gamma proteobacteria in children infected with HIV, among other differences. We noted an effect of ethnicity/geography on observed gut microbiome composition and that children on ritonavir-boosted protease inhibitor (PI/r)-based ART had gut microbiome composition that diverged more from HIV-negative controls compared to those on non-nucleoside reverse-transcriptase inhibitors-based ART. Further studies investigating the role of this altered gut microbiome in increased disease susceptibility are warranted for individuals who acquired HIV via mother-to-child transmission.

USAGE OF A RAPID DIAGNOSTIC TEST FOR MALARIA IN CHILDREN.

BACKGROUND: Malaria is still the primary cause of pediatric deaths. The efficient management of pediatric malaria requires its rapid and accurate diagnosis. To fulfill this requirement, rapid diagnostic tests have been developed, but their evaluation before commercialization is never exhaustive. The aim of this study was to evaluate the performance of a rapid diagnostic test (SD Bioline Malaria Antigen P.f/Pan) to diagnose malaria in children. MATERIALS AND METHODS: Testing was conducted on children aged between 6 months and 15 years who were examined at the "Centre Mère Enfant (CME) of the "Chantal Biya" Foundation (FCB). as a result of fever. Enrollment took place from April to October 2014. All children presenting with fever were sampled (3ml of blood). These blood samples were tested for malaria using microscopy on a thick blood smear and by a rapid diagnostic test (RDT) SD Bioline Malariae Antigen P.f/Pan. RESULTS: A total of 249 children were enrolled in this study. Malaria presence as determined by microscopy and by RDT was 30.9% and 58.2% respectively. The sensitivity, specificity, positive and negative predictive values compared to microscopy were: 75; 48.8; 39, and 81.6%. With these performances, the malaria SD Bioline rapid test presents lower values compared to WHO recommendations for rapid tests (sensitivity > 95%) in children. CONCLUSION: SD Bioline Malaria Antigen P.f/Pan test should only be used in peripheral health structures that lack resources, and should be aided by clinical diagnosis.

TRIM5α 136Q, CCR5 Promoter 59029G And CCR264I Alleles Impact The Progression Of HIV In Children And Adolescents.

BACKGROUND: Children show various degrees of vulnerability regarding HIV infection and disease progression. This disparity presents challenges for the follow-up of infected children. Here we investigated reasons behind this variability focusing on some host-related HIV genes. METHODS: We screened 570 Cameroonian children and adolescents, aged 1 to 19 years old. Among them, 137 were followed over 4 years, from 2010 to 2015. Upon signing a proxy consent, children and adolescents were classified according to their age, CD4 count, viral load and clinical symptoms as long-term non-progressors (LTNP), slow progressors (SP) and rapid progressors (RP). Their blood was collected every 6 months and used for biological and host genetic polymorphism analyses. Five genes were genotyped: Trim5α (R136Q), CCR5 promoter 59029G, CCR2-64I, SDF 3'A and CCR5-Δ32. Exposed non-infected (HEU) and unexposed HIV negative children (HNEU) were recruited as control groups. RESULTS: Among the 5 genes studied, the protective allele of Trim5α (R136Q) was present in all LTNP and in 72.34% and 2.56% of SP and RP, respectively (p<0.0001). The CCR5 promoter 59029G/G was also more present in LTNP and SP than in RP (p=0.02; p=0.04). The protective CCR2-64I homozygous genotype was almost absent in all groups, only the heterozygous genotype was present with a significant difference between RP vs SP (p=0.0001), and SP vs LTNP (p=0.0002). The CCR2-∆32 was completely absent either as homozygous or heterozygous genotype. It was a monomorphic allele. SDF 3'A was almost present as homozygous wild-type genotype in our study population and was associated neither to disease acquisition nor to disease progression. CONCLUSION: Among the 5 genes described in the study, Trim 5α (R136Q), CCR5 promoter 59029G and CCR2V64I alleles were associated to the progression of HIV infection in children and adolescents.

MicroRNA hsa-miR-29a-3p is a plasma biomarker for the differential diagnosis and monitoring of tuberculosis.

The diagnosis of tuberculosis (TB) continues to pose substantial public health problems. The quest for diagnostic biomarkers for TB is therefore primordial. This study aimed to evaluate the diagnostic and anti-TB treatment monitoring potentials of some selected miRNAs. Quantitative real time polymerase chain reaction and Receiver operating characteristics were used to estimate the ability of miRNAs to discriminate between healthy controls (HEC), latent (LTB) and active TB (ATB). The study showed that: hsa-miR-29a-3p, hsa-miR-155-5p and hsa-miR-361-5p were significantly upregulated in ATB compared to HEC while hsa-miR-29a-3p, and hsa-miR-361-5p were also significantly up-regulated in ATB compared to LTB (all P ≤ 0.05). MiR-29a-3p showed a good (81.37%) distinguishing performance in discriminating ATB from HEC and a good (84.35%) diagnostic performance in discriminating ATB from LTB. The performance of miR-29a-3p present in the blood in discriminating active TB from latent TB and healthy controls indicates it may be a useful biomarker for diagnosis of TB. Because this miRNA is found in blood (plasma) which is easy to collect compared to sputum it could be used in pediatric and extra-pulmonary TB cases.

IMPLICATION OF FIVE AIDS RELATED GENES IN MOTHER-TO-CHILD TRANSMISSION AND ACQUISITION OF HUMAN IMMUNODEFICIENCY VIRUS 1 IN CAMEROON.

BACKGROUND: Genetic variants in the mother and/or infant have been described with evidence to be associated with mother-to-child transmission of HIV, but somehow with contradictory results depending on ethnic or geographic populations. We aimed at looking at the association between the allelic frequency of some genes with vertical transmission or acquisition of HIV in Cameroon. METHODOLOGY: A total of 262 mothers (212 HIV-infected and 50 HIV non-infected) with their babies (270 in total, 42 HIV exposed-infected, 178 HIV exposed non-infected and 50 HIV non-exposed) were recruited in Yaounde-Cameroon. Their genotypes for CCR5-Delta32, CCR5 promoter59029A/G, CCR2-64I, SDF1-3'A and TRIM5α-136Q were analyzed using polymerase chain reaction and restriction fragment length polymorphisms. RESULTS: Allelic frequencies were 14.7%, 41.9%, 9.5% and 14.7% for CCR2-64I, CCR5-59029-A/G, TRIM5α-136Q, SDF1-3'A respectively in the mothers and 18.8%, 35.9%, 11.3% and 20.5% in the babies. No delta 32 mutation in the CCR5 gene was found. The mutant genotype was most significantly frequent in the non-transmitter than in the transmitter (p= 0.005) for the SDF-1 3'A. SDF1-3'A [Odd ratio = 1.69; 95% confidence interval: 0.1158 to 0.7277); was associated to MTCT, P = 0.008.The homozygote mutants for the CCR5-59029-G were significantly higher in the infected than in the exposed uninfected babies (p=0.04). The mutations in the other genes were neither implicated in the acquisition nor in the transmission. CONCLUSION: SDF1-3'A was associated to the reduction of MTCT. The CCR5-59029-A/G favored acquisition of HIV by babies. Our study showed that polymorphisms in chemokine ligand may be involved in MTCT.