Artículos de revista (Inst. Salud Tropical)
Permanent URI for this collectionhttps://hdl.handle.net/10171/52056
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- BOHEMIA: Broad One Health Endectocide-based Malaria Intervention in Africa -a phase III cluster-randomized, open-label, clinical trial to study the safety and efficacy of ivermectin mass drug administration to reduce malaria transmission in two African settings(2023) Schürch, R. (Roger); Mrema, S. (Sigilbert); Xia, K. (Kang); Montaña-López, J. (Julia); Hammann, F. (Felix); Selvaraj, P. (Prashant); Sacoor, C. (Charfudin); Lyimo, I. (Issa); Marathe, A. (Achla); Rabinovich, N.R. (N. Regina); Elobolobo, E. (Eldo); Jones, C. (Caroline); Chaccour, C.J. (Carlos J.); Nicolas, P. (Paula); Maia, M. (Marta); Ruiz-Castillo, P. (Paula); Duthaler, U. (Urs); Casellas, A. (Aina); Mael, M. (Mary); Kakolwa, M. (Mwaka); Rist, C. (Cassidy); Okumu, F. (Fredros); Saute, F. (Francisco)Background Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission.Methods A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (> 15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTsDiscussion The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission.
- Current and historic HIV‑1 molecular epidemiology in paediatric and adult population from Kinshasa in the Democratic Republic of Congo(2020) Carlos-Chillerón, S. (Silvia); Holguín, Á. (África); Galán, J.C.; Rubio-Garrido, M. (Marina); González‑Alba, J.M. (José María); Barquín, D. (David); Reina, G. (Gabriel); Ndarabu, A. (Adolphe)HIV-1 diversity may impact monitoring and vaccine development. We describe the most recent data of HIV-1 variants and their temporal trends in the Democratic Republic of Congo (DRC) from 1976 to 2018 and in Kinshasa from 1983–2018. HIV-1 pol sequencing from dried blood collected in Kinshasa during 2016–2018 was done in 340 HIV-infected children/adolescents/adults to identify HIV-1 variants by phylogenetic reconstructions. Recombination events and transmission clusters were also analyzed. Variant distribution and genetic diversity were compared to historical available pol sequences from the DRC in Los Alamos Database (LANL). We characterized 165 HIV-1 pol variants circulating in Kinshasa (2016–2018) and compared them with 2641 LANL sequences from the DRC (1976–2012) and Kinshasa (1983–2008). During 2016–2018 the main subtypes were A (26.7%), G (9.7%) and C (7.3%). Recombinants accounted for a third of infections (12.7%/23.6% Circulant/Unique Recombinant Forms). We identifed the frst CRF47_BF reported in Africa and four transmission clusters. A signifcant increase of subtype A and sub-subtype F1 and a signifcant reduction of sub-subtype A1 and subtype D were observed in Kinshasa during 2016–2018 compared to variants circulating in the city from 1983 to 2008. We provide unique and updated information related to HIV-1 variants currently circulating in Kinshasa, reporting the temporal trends of subtypes/CRF/URF during 43 years in the DRC, and providing the most extensive data on children/adolescents.
- HIV-1 diagnosis using dried blood spots from patients in Kinshasa, DRC: a tool to detect misdiagnosis and achieve World Health Organization 2030 targets(Elsevier, 2021) Carlos-Chillerón, S. (Silvia); Makonda, B. (Benit); Holguín, Á. (África); Fernández-Alonso, M. (Miriam); Rubio-Garrido, M. (Marina); Barquín, D. (David); Reina, G. (Gabriel); Ndarabu, A. (Adolphe)Introduction: Currently, only 54% of the population of the Democratic Republic of the Congo (DRC) know their HIV status. The aim of this study was to detect HIV misdiagnosis from rapid diagnostic tests (RDT) and to evaluate serological immunoassays using dried blood spots (DBS) from patients in Kinshasa, DRC. Methods: Between 2016 and 2018, 365 DBS samples were collected from 363 individuals and shipped to Spain. The samples were from people with a new HIV positive (n = 123) or indeterminate (n = 23) result, known HIV-positive patients (n = 157), and a negative control group (n = 62). HIV serology was performed using Elecsys HIV combi PT (Roche), VIDAS HIV Duo Quick (BioMérieux), and Geenius (Bio- Rad). In addition, HIV RNA detection was performed in all samples using the COBAS AmpliPrep/COBAS Taqman HIV-1 Test 2.0 (Roche). Results: Overall, 272 samples were found to be positive and 93 to be negative for HIV serology. The sensitivity was 100% for both Elecsys and VIDAS techniques, but specificity was slightly higher for the VIDAS test: 100% (96.1–100%) vs 98.9% (94.1–99.9%). Of the 23 indeterminate cases using RDT, only three cases were true-positives with a detectable viral load. Eleven samples out of the 280 classified as positive by RDT corresponded to nine patients who had received a false diagnosis of HIV through RDT (3.9%); six of them had been on antiretroviral therapy for at least 2 years. Conclusions: Elecsys HIV combi PT and VIDAS HIV Duo Quick immunoassays showed high sensitivity and specificity when using DBS. RDT-based serological diagnosis can lead to HIV misdiagnosis with personal and social consequences in sub-Saharan Africa.
- High drug resistance levels could compromise the control of HIV infection in paediatric and adolescent population in Kinshasa, the Democratic Republic of Congo.(2021) Carlos-Chillerón, S. (Silvia); Holguín, Á. (África); Rubio-Garrido, M. (Marina); Rodríguez-Galet, A. (Ana); Barquín, D. (David); Reina, G. (Gabriel); Ndarabu, A. (Adolphe); Valadés-Alcaraz, A. (Ana)Background The inadequacy of HIV viraemia and resistance monitoring in Africa leads to uncontrolled circulation of HIV strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART) effectiveness. This study describes the DRM prevalence and its therapeutic impact in HIV-infected pediatric patients from Kinshasa (Democratic Republic of Congo, DRC). Methods From 2016-2018, dried blood were collected from 71 HIV-infected children and adolescents under ART in two hospitals in Kinshasa for HIV-1 DRM pol analysis, predicted ARV-susceptibility by Stanford and phylogenetic characterization. Results HIV-1 sequences were recovered from 55 children/adolescents with 14 years of median-age. All had received nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI), 9.1% protease inhibitors (PI) and only one integrase inhibitor (INI). Despite the use of ART, 89.1% showed virological failure and 67.3% carried viruses with major-DRM to one (12.7%), two (47.3%), or three (5.5%) ARV-families. Most children/adolescents harbored DRM to NNRTI (73.5%) or NRTI (61.2%). Major-DRM to PI was present in 8.3% and minor-DRM to INI in 15%. Dual-class-NRTI+NNRTI resistance appeared in 53.1% of patients. Viruses presented high/intermediate resistance to nevirapine (72.9% patients), efavirenz (70.9%), emtricitabine/lamivudine (47.9%), rilpivirine (41.7%), etravirine (39.6%), doravidine (33.3%), zidovudine (22.9%), among others. Most participants were susceptible to INI and PI. Great diversity of variants was found, with a high rate (40%) of unique recombinants. Conclusion The high DRM prevalence observed among HIV-infected children and adolescents in Kinshasa could compromise the 95-95-95-UNAIDS targets in the DRC. It also reinforces the need for routine resistance monitoring for optimal rescue therapy election in this vulnerable population to control the spread of resistant HIV in the country.
- Utility Of POC Xpert HIV-1 Tests For Detection-Quantifcation Of Complex HIV Recombinants Using Dried Blood Spots From Kinshasa, D. R. Congo(Springer Science and Business Media LLC, 2019) Carlos-Chillerón, S. (Silvia); Holguín, Á. (África); Fernández-Alonso, M. (Miriam); Rubio-Garrido, M. (Marina); Barquín, D. (David); Reina, G. (Gabriel); Ndarabu, A. (Adolphe)Point-of-Care (POC) molecular assays improve HIV infant diagnosis and viral load (VL) quantification in resource-limited settings. We evaluated POC performance in Kinshasa (Democratic Republic of Congo), with high diversity of HIV-1 recombinants. In 2016, 160 dried blood samples (DBS) were collected from 85 children (60 HIV-, 18 HIV+, 7 HIV-exposed) and 75 HIV+ adults (65 treated, 10 naive) at Monkole Hospital (Kinshasa). We compared viraemia with Cepheid-POC-Xpert-HIV-1VL and the non-POC-COBAS®AmpliPrep/COBAS®TaqMan®HIV-1-Testv2 in all HIV+, carrying 72.4%/7.2% HIV-1 unique/complex recombinant forms (URF/CRF). HIV-1 infection was confirmed in 14 HIV+ children by Cepheid-POC-Xpert-HIV-1Qual and in 70 HIV+ adults by both Xpert-VL and Roche-VL, identifying 8 false HIV+ diagnosis performed in DRC (4 adults, 4 children). HIV-1 was detected in 95.2% and 97.6% of 84 HIV+ samples by Xpert-VL and Roche-VL, respectively. Most (92.9%) HIV+ children presented detectable viraemia by both VL assays and 74.3% or 72.8% of 70 HIV+ adults by Xpert or Roche, respectively. Both VL assays presented high correlation (R2 = 0.89), but showing clinical relevant ≥0.5 log VL differences in 15.4% of 78 cases with VL within quantification range by both assays. This is the first study confirming the utility of Xpert HIV-1 tests for detection-quantification of complex recombinants currently circulating in Kinshasa.
- Dissolving microneedles for intradermal vaccination against shigellosis(2019) Peñuelas-Sanchez, I. (Ivan); Quincoces, G. (Gemma); Donnelly, R. (Ryan); Gamazo, C. (Carlos); Pastor, Y. (Yadira); Larrañeta, E. (Eneko); Erhard, Á. (Álvaro); Irache, J.M. (Juan Manuel)Intradermal (ID) immunization is of increasing interest due to the easy accessibility and excellent immunogenic properties of the skin. Among ID immunization methods, dissolving microneedles (MNs) have appeared as an alternative to traditional hypodermic immunization, offering many advantages, such as being an easily administered method, with no need for health personnel, painless, and avoiding the use of needles and sharp wastage. In this study, an affordable and easy-to-produce MNs method was developed based on aqueous blends of 30% w/w poly (methyl vinyl ether-co-maleic anhydride). As an antigen model, a subunit vaccine candidate based on outer membrane vesicles from Shigella flexneri was used. Both unloaded and antigen-loaded MNs were synthetized and characterized. The MNs were successfully validated in an in vitro Parafilm M skin model and in a pig skin ex vivo model. Biodistribution studies were performed in BALB/c mice using 99mTcO4- radiolabeled samples. Results indicated that the vesicle vaccine was successfully released from the MNs and targeted gastrointestinal tract after 6 h post-administration. In vivo immunization and protection studies were performed in BALB/c mice. Mice were intradermally immunized through ear skin with one single dose of 200 g antigenic complex, eliciting the production of specific systemic IgG and mucosal IgA.