Machine learning outperformed logistic regression classification even with limit sample size: A model to predict pediatric HIV mortality and clinical progression to AIDS

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naive Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression

Host-Directed Therapies for tackling Multi-Drug Resistant TB – learning from the Pasteur-Bechamp debates

Tuberculosis (TB) remains a global emergency causing an estimated 1.5 million deaths annually. For several decades the major focus of TB treatment has been on antibiotic development targeting Mycobacterium tuberculosis (M.tb). The lengthy TB treatment duration and poor treatment outcomes associated with multi-drug resistant TB (MDR-TB) are of major concern. The sparse new TB drug pipeline and widespread emergence of MDR-TB signal an urgent need for more innovative interventions to improve treatment outcomes. Building on the historical Pasteur-Bechamp debates on the role of the ‘microbe’ versus the ‘host internal milieu’ in disease causation, we make the case for parallel investments into host-directed therapies (HDTs). A range of potential HDTs are now available which require evaluation in randomized controlled clinical trials as adjunct therapies for shortening the duration of TB therapy and improving treatment outcomes for drug-susceptible TB and MDR-TB. Funder initiatives that may enable further research into HDTs are described

Towards host-directed therapies for tuberculosis

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies. Despite the availability of effective antibiotics for tuberculosis (TB) for the past half century, it remains an important global health problem; there are ~9 million active TB cases and ~1.5 million TB-induced deaths per year (see the World Health Organization (WHO) Global Tuberculosis Report in Further information). Health services around the world face major barriers to achieving optimal outcomes from current TB treatment regimens. These barriers include: the spread of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB); complex and toxic treatment regimens for MDR-TB; HIV co-infection; pharmacokinetic interactions between TB drugs and antiretroviral drugs; relapse; permanent damage to lung and other tissues; long-term functional disability; immune reconstitution inflammatory syndrome (IRIS); and co-morbidity with non-communicable diseases such as diabetes and chronic obstructive airway diseases. Another fundamental problem is the long duration of TB drug treatment (6 months for drug-sensitive TB and at least 18 months for drug-resistant TB) to achieve a cure, owing to the presence of dormant Mycobacterium tuberculosis bacilli that are phenotypically resistant to current classes of anti-TB drugs, which can only target bacterial replication. There is therefore an urgent need for new TB treatments. However, the TB drug pipeline is thin1, 2. For the past 60 years, efforts to develop new treatments have focused on compounds and regimens that target M. tuberculosis directly. Recently, however, attention has focused on investigating a range of adjunct treatment interventions known as host-directed therapies (HDTs) that instead target the host response to infection. Here, we highlight the rationale for HDTs, the current portfolio of HDTs and their mechanisms of action, and a consortium-based approach to drive forward their evaluation in clinical trials

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Caractérisation des bases moléculaires de la résistance des virus de l'immunodéficience humaine de type 1 ( VIH-1) de sous-type non-B aux antirétroviraux

Grâce aux traitements antirétroviraux le Sida est devenu une maladie chronique. Un des défis de la lutte contre le VIH/SIDA est de caractériser la résistance développée par le VIH aux ARV. Or, les connaissances portent essentiellement sur le sous-type B du VIH-1 circulant majoritairement dans les pays industrialisés. Ainsi, il est important d étudier les bases moléculaires de la résistance du VIH-1 de sous-type non-B avec l accès de plus en plus important aux ARV au Sud. Le premier travail a évalué l efficacité d une première ligne Triomune® d4T/3TC/NVP chez l adulte, lors d un échec virologique précoce. Cette étude a montré que lors d un échec précoce nous avons des profils de mutation au 3TC (M184V) et aux INNTI (K103N et Y181C). La deuxième partie a consisté en la mesure de la prévalence de la résistance primaire, ainsi qu en la caractérisation des sous-types de VIH-1 circulant au Mali et nous avons obtenu une prévalence de 11,5%. La troisième partie a étudié la barrière génétique à la résistance des inhibiteurs d integrase vis-à-vis des sous-types B et CRF02_AG et l évaluation de la prévalence des mutations associées à la résistance à l ETR chez patients infectés par des VIH-1 de sous-types non-B et naïfs d ARV. Ces deux sous-types (B et CRF02_AG) présentent une barrière génétique similaire, mais on note une barrière génétique plus élevée pour le CRF02_AG aux positions 140 et 151 de l integrase. Nous avons obtenu 10% de virus portant des mutations de résistance à l ETR chez patients infectés par des sous-types non-B et naïfs d ARV. Ces données sont importantes à prendre en compte pour l établissement des 2èmes et 3èmes lignes de traitement ARV dans les pays du Sud.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Re-engagement in care of people living with HIV lost to follow-up after initiation of antiretroviral therapy in Mali: Who returns to care?

International audienc

Risk factors for loss to follow-up, transfer or death among people living with HIV on their first antiretroviral therapy regimen in Mali

International audienceOBJECTIVES: Risk factors for loss to follow-up (LTFU) were assessed for people living with HIV (PLHIV) at various reference out-patient clinics (expertise level II) and hospitals (expertise level III) in Mali.METHODS: HIV-1-positive adults starting antiretroviral therapy (ART) in 2006-2013 were eligible for inclusion. Risk factors for LTFU, defined as no visit in the 6 months preceding the last database update, were assessed with the Cox model, taking into account the competing risks of transfer and death. Potential risk factors at the start of ART were demographic and socioeconomic variables, World Health Organization (WHO) stage, CD4 count, period of ART initiation, type of ART, region of care, expertise level and distance from home.RESULTS: We included 9821 PLHIV, 33% of whom were male, starting ART at nine out-patient clinics and seven hospitals [five and two in the capital Bamako and four and five in the 'regions' (i.e. districts outside the capital), respectively] with a median (interquartile range) CD4 count of 153 (56-270) cells/μL. Five-year cumulative incidences of LTFU, transfer and death were 35.2, 9.7 and 6.7%, respectively. People followed at Bamako hospitals > 5 km from home, at regional hospitals or at regional out-patient clinics < 5 km from home were at higher risk of LTFU than people followed at Bamako out-patient clinics, whereas people followed at regional out-patient clinics 5-50 km away from home were at lower risk for LTFU. Deaths were less frequent at hospitals, whether in Bamako or in the regions, than at Bamako out-patient clinics, and more frequent at regional out-patient clinics.CONCLUSIONS: Expertise level and distance to care were associated with LTFU. Stigmatization may play a role for PLHIV living close to the centres in the regions

High Prevalence of Anal Oncogenic Human Papillomavirus Infection in Young Men Who Have Sex with Men Living in Bamako, Mali

International audienceBackground: High-risk human papillomavirus (HR-HPV) anal infection is a major problem among men who have sex with men (MSM) living in sub-Saharan Africa. The prevalence of anal HR-HPV infection and associated risk factors were estimated in a cross-sectional study in MSM living in Bamako, Mali.Methods: MSM consulting at sexual health center of the National NGO Soutoura, Bamako, were prospectively included. Sociodemographic and clinical-biological data were collected. HPV detection and genotyping were performed from anal swabs using multiplex real-time PCR. Risk factors associated with anal HPV infection were assessed by logistic regression analysis.Results: Fifty MSM (mean age, 24.2 years; range, 18-35) of which 32.0% were infected with HIV-1, were prospectively included. The overall prevalence of anal HPV infection of any genotypes was 70.0% (35/50) with 80.0% (28/35) of swabs positive for HR-HPV. HR-HPV-58 was the most detected genotype [13/35 (37.1%)], followed by HR-HPV-16 and low-risk (LR)-HPV-6 [12/35 (34.2%)], LR-HPV-40 [10/35 (28.6%)], LR-HPV-11 [9/35 (25.7%)], HR-HPV-51 [8/35 (22.8%)], HR-HPV types 18 and 39 [7/35 (20.0%)] and LR-HPV-43 [6/35 (17.1%)]. HR-HPV-52 and LR-HPV-44 were detected in lower proportions [5/35 (14.3%) and 4/35 (11.4%), respectively]. LR-HPV-42, LR-HPV-54, HR-HPV-31 and HR-HPV-35 were detected in very low proportions [3/35 (8.5%)]. Multiple HR-HPV infections were diagnosed in one-third of anal samples [16/50 (32.0%)], including around half of HR-HPV-positive anal swabs [16/35 (45.7%)]. More than half [27/50 (54.0%)] swabs were infected by at least one of HPV genotypes targeted by Gardasil-9® vaccine, including a majority of vaccine HR-HPV [22/50 (44.0%)]. In multivariate analysis, participation to sex in group was associated with anal infection by multiple HPV (aOR: 4.5, 95% CI: 1.1-18.1%; P = 0.032), and HIV-1 infection was associated with anal shedding of multiple HR-HPV (aOR: 5.5, 95% CI: 1.3-24.5%; P = 0.024).Conclusions: These observations indicate that the MSM community living in Bamako is at high-risk for HR-HPV anal infections, with a unique epidemiological HPV genotypes profile and high prevalence of anal HPV covered by the Gardasil-9® vaccine. Scaling up prevention strategies against HPV infection and related cancers adapted to this highly vulnerable MSM community should be urgently prioritized with innovative interventions