Neutralizing monoclonal antibodies to human immunodeficiency virus type 1 do not inhibit viral transcytosis through mucosal epithelial cells

AbstractHIV-1 transcytosis has been proposed as a potential mechanism allowing the virus to cross the epithelium during mucosal transmission. Epitopes of the HIV-1 envelope involved in this process have not been identified yet. Here, we assessed a large panel of HIV neutralizing antibodies recognizing well-characterized epitopes of the HIV-1 envelope for their ability to block HIV-1 transcytosis across a confluent epithelial monolayer.We found that all of the 13 HIV-1-specific monoclonal antibodies tested in the present study, including the three broadly neutralizing antibodies 2F5, 2G12 and IgG1b12, lacked the ability to inhibit transcytosis of cell-free and cell-associated R5- as X4-tropic HIV-1 across a tight and polarized monolayer of HEC-1 epithelial cells. In contrast, anti-gp160 polyclonal antibodies purified from serum or breast milk of HIV-1-infected individuals potently inhibited HIV-1 transcytosis. Furthermore, polymeric S-IgA exhibited similar ability to inhibit transcytosis compared to IgG despite their lower anti-gp160 specific activity. Together, these results demonstrate that the major neutralizing envelope epitopes of HIV-1 are not involved in HIV-1 transcytosis, and suggest that surface agglutination of virus particles may participate to the blocking effect observed with both polyclonal and polymeric anti-gp160 immunoglobulins

First introduction of pandemic influenza A/H1N1 and detection of respiratory viruses in pediatric patients in Central African Republic

BACKGROUND: Acute viral respiratory illnesses in children in sub-Saharan Africa have received relatively little attention, although they are much more frequent causes of morbidity and mortality than in developed countries. Active surveillance is essential to identify the causative agents and to improve clinical management, especially in the context of possible circulation of pandemic viruses. FINDINGS: A prospective study was conducted in the Central African Republic (CAR) between January and December 2010 among infants and children aged 0–15 years attending sentinel sites for influenza-like illness or acute respiratory illness. Nasopharyngeal swabs were collected, and one-step real-time and multiplex reverse transcription-polymerase chain reaction were used to detect respiratory viruses. Respiratory viruses were detected in 49 of the 329 (14.9%) nasopharyngeal samples: 29 (8.8%) contained influenza viruses (5 (1.5%) had pandemic influenza A/H1N1 virus and 24 (7.3%) had influenza B viruses), 11 (3.3%) contained parainfluenza viruses types 1 and 3 and 9 (2.7%) contained human respiratory syncytial virus. Most cases were detected during the rainy season in the CAR. Analysis of the amplicon sequences confirmed the identity of each detected virus. CONCLUSIONS: The influenza surveillance system in the CAR has provided valuable data on the seasonality of influenza and the circulation of other respiratory viruses. Our network could therefore play a valuable role in the prevention and control of influenza epidemics in the CAR

Infection tuberculeuse latente chez l’enfant à Bangui: à propos de 524 cas exposés à domicile aux cas index de tuberculose pulmonaire à microscopie positive

Introduction: malgré la vaccination par le BCG, le risque de développer la tuberculose chez les jeunes enfants dans les régions endémiques reste plus élevé après exposition au cas de tuberculose chez l´adulte. Le but de cette étude était de réduire le risque de tuberculose active chez les enfants contacts des cas index adultes à domicile. Méthodes: une étude transversale multisite (avril 2016-janvier 2019) a été réalisée sur des enfants de 0 à 59 mois, contacts des cas index à domicile, dépistés et suivis au centre pédiatrique de Bangui. Résultats: cinq cent vingt- quatre (524) enfants ont été enregistrés. La moyenne d´âge était de 2 ans et 1 mois et le sex ratio garçon/fille de 1,02. Environ quatre-vingt-huit pourcent (88,5%) des contacts étaient vaccinés avec le BCG contre 11,5% non vaccinés. Dans plus de la moitié des cas (52%), les contacts et les cas index ont partagé la même chambre et le temps de contact journalier était supérieur à 12h dans 56% des ménages. Un peu plus de neuf pourcent (9,35%) des contacts avaient une IDR positive. Tous les enfants ont été mis sous chimioprophylaxie à base de Rifampicine + Isoniazide selon les directives nationales et malgré cela, 14 soit 2,67% ont développé une tuberculose active dont 13 formes pulmonaires et une forme ganglionnaire. Conclusion: la chimio prophylaxie tuberculeuse a sans doute permis de réduire considérablement le risque de survenue de la tuberculose chez des enfants ayant été en contact avec les cas index à domicile

Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated with First-Line Stavudine-Containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine

Background The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. Methods We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. Results Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. Conclusions Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therap

First case of Elizabethkingia anophelis meningitis in the Central African Republic.

International audienceAn 8-day-old girl of indigenous origin delivered by caesarean section to an HIV-negative mother with an uneventful pregnancy presented to the Complexe Pédiatrique in Bangui, Central African Republic, in March 2011 with a 3-day history of fever at 38.5 °C. The newborn had a history of intubation and mechanical ventilation at birth due to asphyxia, followed by 2 days of hospitalization. At admission, she was irritable, feeding poorly, had a seizure and had lost 1500 g (32%) of her birth weight. She showed ..

Molecular assessment of kelch13 non-synonymous mutations in Plasmodium falciparum isolates from Central African Republic (2017–2019)

International audienceBackground:Over the last decade, artemisinin‑based combination therapy (ACT ) has contributed substantially to the decrease in malaria‑related morbidity and mortality. The emergence of Plasmodium falciparum parasites resistant to artemisinin derivatives in Southeast Asia and the risk of their spread or of local emergence in sub‑Saharan Africa are a major threat to public health. This study thus set out to estimate the proportion of P. falciparum isolates, with Pfkelch13 gene mutations associated with artemisinin resistance previously detected in Southeast Asia.Methods:Blood samples were collected in two sites of Bangui, the capital of the Central African Republic (CAR) from 2017 to 2019. DNA was extracted and nested PCR were carried out to detect Plasmodium species and mutations in the propeller domain of the Pfkelch13 gene for P. falciparum samples.Results:A total of 255 P. falciparum samples were analysed. Plasmodium ovale DNA was found in four samples (1.57%, 4/255). Among the 187 samples with interpretable Pfkelch13 sequences, four samples presented a mutation (2.1%, 4/187), including one non‑synonymous mutation (Y653N) (0.5%, 1/187). This mutation has never been described as associated with artemisinin resistance in Southeast Asia and its in vitro phenotype is unknown.Conclusion:This preliminary study indicates the absence of Pfkelch13 mutant associated with artemisinin resistance in Bangui. However, this limited study needs to be extended by collecting samples across the whole country along with the evaluation of in vitro and in vivo phenotype profiles of Pfkelch13 mutant parasites to estimate the risk of artemisinin resistance in the CAR

Main characteristics of study mother-child couples, including 8 couples of HIV-1-infected mothers and their breastfed non HIV-infected babies (group I), and 6 couples of HIV-1-infected mothers and their breastfed HIV-1-infected babies (group II).

£<p>World Health Organization (WHO) clinical staging of HIV/AIDS for adults and adolescent with established HIV infection according to the 2010-revised WHO recommendations for HIV care in in babies and children for resource-limited settings <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063408#pone.0063408-WHO2" target="_blank">[31]</a>;</p>$<p>WHO clinical staging of HIV/AIDS for children with established HIV infection according to the 2010-revised WHO recommendations for HIV care in babies and children for resource-limited settings <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063408#pone.0063408-WHO1" target="_blank">[30]</a>; CD4 T cell count in infants were not available because the national AIDS programme has focused on universal treatment for infants less than 12 months, independently of their clinical or immunological status;</p>*<p>Plasma HIV-1 RNA load was measuredby the Generic HIV-1 RNA quantification assay (Biocentric, Bandol, France), which threshold of detectability is 300 copies/ml <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063408#pone.0063408-Rouet2" target="_blank">[35]</a>.The molecular diagnosis of HIV infection was carried out at time of sampling; the timing of HIV infection in study children could not be assessed.</p><p>NA: Not applicable.</p

Relative ratios of excretion (RRE) by reference to lactoferrin of total IgA, IgG and IgM (A) and anti-gp160 antibodies of the IgA, IgG and IgM classes (B) in stool samples from8 HIV-1-infected mothers and their breast milk exposed non HIV-infected babies (group I) (grey bars) and from 6 couples of HIV-1-infected mothers and their breastfed HIV-1-infected babies (group II) (hatched grey bars).

<p>RRE is expressed as mean±standard error. The stars indicate the significant differences between the mean RRE of IgA, IgG and IgM, and those of HIV-specific IgA, IgG and IgM in the whole 14 study babies breastfed by their HIV-infected mothers (groups I and II) (* P<0.01).</p

Levels of total IgA, IgG and IgM in breast milk (white bars in left) and children’s stools (black bars in right) samples from 8 HIV-1-infected mothers and their breast milk exposed non HIV-infected babies (group I), 6 couples of HIV-1-infected mothers and their breastfed HIV-infected babies (group II), and 10 healthy HIV-negative breast-feeding women and their breastfed non HIV-infected babies as negative controls.

<p>The mean concentrations of milk IgA were higher than those of IgG or IgM in HIV-infected mothers as in HIV-negative mothers. The levels of milk IgG was 5.5 higher in HIV-infected mothers than in HIV-negative mothers. The levels of stool IgA and IgG in babies born from HIV-infected mothers were higher than those of HIV-negative control babies. Immunoglobulins levels are expressed in µg/ml ± standard error. The stars indicate the significant differences by comparison to HIV-negative control samples (* P<0.01).</p