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1.
Sci One Health ; 3: 100074, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262844

RESUMO

In sub-Saharan Africa, limited studies have investigated zoonotic pathogens that may be harboured by ticks infesting reptiles such as tortoises. Here, we report the presence of pathogenic Rickettsia in ticks (Amblyomma marmoreum) collected from the leopard tortoise (Geochelone pardalis) in rural Zambia. Using polymerase chain reaction, 56% (49/87) of ticks were positive for the Rickettsia outer membrane protein (ompB) gene. Multi-locus sequence and phylogenetic analysis based on the ompB, ompA, and citrate synthase (gltA) genes showed that the ticks carried R. africae, and other Rickettsia spp. closely related to R . raoultii, R . massiliae, R . tamurae and R . monacensis. Given the proximity between humans, livestock, and wildlife in these habitats, there exists a considerable risk of transmission of zoonotic Rickettsia to human populations in this rural setting. These results call for heightened awareness and further research into the dynamics of tick-borne diseases in regions where humans and animals coexist, particularly in the context of tortoise-associated ticks as vectors. Understanding and addressing these potential disease vectors is crucial for effective public health measures and the prevention of Rickettsia zoonoses.

2.
Clin Cancer Res ; 30(17): 3768-3778, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38869830

RESUMO

PURPOSE: In this single-institution phase II investigator-initiated study, we assessed the ability of MAPK and VEGF pathway blockade to overcome resistance to immunotherapy in microsatellite-stable metastatic colorectal cancer (MSS mCRC). PATIENTS AND METHODS: Patients with MSS, BRAF wild-type mCRC who progressed on ≥2 prior lines of therapy received pembrolizumab, binimetinib, and bevacizumab until disease progression or unacceptable toxicity. After a safety run-in, patients were randomized to a 7-day run-in of binimetinib or simultaneous initiation of all study drugs, to explore whether MEK inhibition may increase tumor immunogenicity. The primary endpoint was objective response rate (ORR) in all patients combined (by Response Evaluation Criteria in Solid Tumors v1.1). RESULTS: Fifty patients received study drug treatment; 54% were male with a median age of 55 years (range, 31-79). The primary endpoint, ORR, was 12.0% [95% confidence interval (CI) 4.5%-24.3%], which was not statistically different than the historical control data of 5% (P = 0.038, exceeding prespecified threshold of 0.025). The disease control rate was 70.0% (95% CI, 55.4%-82.1%), the median progression-free survival 5.9 months (95% CI, 4.2-8.7 months), and the median overall survival 9.3 months (95% CI, 6.7-12.2 months). No difference in efficacy was observed between the randomized cohorts. Grade 3 and 4 adverse events were observed in 56% and 8% of patients, respectively; the most common were rash (12%) and increased aspartate aminotransferase (12%). CONCLUSIONS: Pembrolizumab, binimetinib, and bevacizumab failed to meet its primary endpoint of higher ORR compared with historical control data, demonstrated a high disease control rate, and demonstrated acceptable tolerability in refractory MSS mCRC.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Benzimidazóis , Bevacizumab , Neoplasias Colorretais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Bevacizumab/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/genética , Repetições de Microssatélites , Resultado do Tratamento
3.
Malar J ; 19(1): 326, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887619

RESUMO

BACKGROUND: Indoor residual spraying (IRS) is an effective method to control malaria-transmitting Anopheles mosquitoes and often complements insecticide-treated mosquito nets, the predominant malaria vector control intervention. With insufficient funds to cover every household, malaria control programs must balance the malaria risk to a particular human community against the financial cost of spraying that community. This study creates a framework for modelling the distance to households for targeting IRS implementation, and applies it to potential risk prioritization strategies in four provinces (Luapula, Muchinga, Eastern, and Northern) in Zambia. METHODS: Optimal network models were used to assess the travel distance of routes between operations bases and human communities identified through remote sensing. Network travel distances were compared to Euclidean distances, to demonstrate the importance of accounting for road routes. The distance to reaching communities for different risk prioritization strategies were then compared assuming sufficient funds to spray 50% of households, using four underlying malarial risk maps: (a) predicted Plasmodium falciparum parasite rate in 2-10 years olds (PfPR), or (b) predicted probability of the presence of each of three main malaria transmitting anopheline vectors (Anopheles arabiensis, Anopheles funestus, Anopheles gambiae). RESULTS: The estimated one-way network route distance to reach communities to deliver IRS ranged from 0.05 to 115.69 km. Euclidean distance over and under-estimated these routes by - 101.21 to 41.79 km per trip, as compared to the network route method. There was little overlap between risk map prioritization strategies, both at a district-by-district scale, and across all four provinces. At both scales, agreement for inclusion or exclusion from IRS across all four prioritization strategies occurred in less than 10% of houses. The distances to reaching prioritized communities were either lower, or not statistically different from non-prioritized communities, at both scales of strategy. CONCLUSION: Variation in distance to targeted communities differed depending on risk prioritization strategy used, and higher risk prioritization did not necessarily translate into greater distances in reaching a human community. These findings from Zambia suggest that areas with higher malaria burden may not necessarily be more remote than areas with lower malaria burden.


Assuntos
Anopheles , Habitação , Inseticidas/administração & dosagem , Malária/prevenção & controle , Mosquitos Vetores , Animais , Modelos Teóricos , Medição de Risco/estatística & dados numéricos , Zâmbia
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