Pathogens and Global Health最新文献

Toxocariasis is a zoonosis that represents a serious threat to public health particularly in tropical and subtropical areas. Currently, albendazole, the most effective drug for treating visceral toxocariasis, shows moderate efficacy against the larvae in tissues and has some adverse effects. Artemether is an antiparasitic drug mainly used in the treatment of malaria and showed effectiveness against numerous helminthic infections. Besides, it possesses potent anti-inflammatory, antiapoptotic, antifibrotic, and neuroprotective properties. Thus, the study's aim was to investigate artemether's effects in comparison with albendazole on the therapeutic outcome of experimental toxocariasis. For this aim, 140 laboratory-bred mice were divided into four main groups: uninfected control, treatment control, albendazole-treated, and artemether-treated groups. The treatment regimens were started at the 15^th dpi (early treatment), and at the 35^th dpi (late treatment). The effectiveness of treatment was determined by brain larval count, histopathological, immunohistochemical, and biochemical examination. Artemether showed more effectiveness than albendazole in reducing brain larval counts, markers of brain injury including NF-κB, GFAP, and caspase-3, the diameter and number of hepatic granulomas, hepatic oxidative stress, hepatic IL-6, and TG2 mRNA, and pulmonary inflammation and fibrosis. The efficacy of artemether was the same when administered early or late in the infection. Finally, our findings illustrated that artemether might be a promising therapy for T. canis infection and it could be a good substitution for albendazole in toxocariasis treatment.

The eradication of smallpox and the cessation of vaccination have led to the growth of the susceptible human population to poxviruses. This has led to the increasing detection of zoonotic orthopoxviruses. Among those viruses, monkeypox virus (MPV) is the most commonly detected in Western and Central African regions. Since 2022, MPV is causing local transmission in newly affected countries all over the world. While the virus causing the current outbreak remains part of clade II (historically referred to as West African clade), it has a significant number of mutations as compared to other clade II sequences and is therefore referred to as clade IIb. It remains unclear whether those mutations may have caused a change in the virus phenotype. Vaccine effectiveness data show evidence of a high cross-protection of vaccines designed to prevent smallpox against mpox. These vaccines therefore represent a great opportunity to control human-to-human transmission, provided that their availability has short time-frames and that mistakes from the recent past (vaccine inequity) will not be reiterated.

The visceral form of leishmaniasis (VL), due to infection by Leishmania infantum, is a neglected tropical disease. The accessible therapeutic options are limited. Artemisinin is an efficient antileishmanial product with poor biological availability that requires high repetition of therapeutic doses in VL. Solid lipid nanoparticles (SLNs) provide targeted delivery, increase bioavailability and reduce toxicity of the traditional therapeutic strategy. The spherical shape artemisinin-loaded SLNs were prepared in a particle diameter of 222.0 ± 14.0 nm. The SLNs showed no particular toxic effect on the parasites, whereas the native artemisinin demonstrated a significant toxicity rate of 31% in viability of the promastigotes at the 250 µg/ml concentration. The therapeutic efficacy of the artemisinin-loaded SLNs was demonstrated in the experimental VL, using the L. infantum-infected BALB/c mice, in the present study. The 10 and 20 mg/kg doses of artemisinin-loaded SLNs showed higher level of antileishmanial efficacy compared with the free artemisinin. There was a significant diminishing of the parasite burden in liver (84.7 ± 4.9%) and spleen (85.0 ± 3.1%) and hepatosplenomegaly by the artemisinin-loaded SLNs treated at 20 mg/kg compared to the free artemisinin. Therefore, the present study supports the superior efficacy of artemisinin-loaded SLNs over the free artemisinin and could be considered as a new therapeutic strategy in the treatment of leishmaniasis.

To study the SARS-CoV-2 transmission potential in Rhode Island (RI) and its association with policy changes and mobility changes, the time-varying reproduction number, R_t, was estimated. The daily incident case counts (16 March 2020, through 30 November 2021) were bootstrapped within a 15-day sliding window and multiplied by Poisson-distributed multipliers (λ = 4, sensitivity analysis: 11) to generate 1000 estimated infection counts, to which EpiEstim was applied to generate R_t time series. The median R_t percentage change when policies changed was estimated. The time lag correlations were assessed between the 7-day moving average of the relative changes in Google mobility data in the first 90 days, and R_t and estimated infection count, respectively. There were three major pandemic waves in RI in 2020-2021: spring 2020, winter 2020-2021 and fall-winter 2021. The median R_t fluctuated within the range of 0.5-2 from April 2020 to November 2021. Mask mandate (18 April 2020) was associated with a decrease in R_t (-25.99%, 95% CrI: -37.42%, -14.30%). Termination of mask mandates on 6 July 2021 was associated with an increase in R_t (36.74%, 95% CrI: 27.20%, 49.13%). Positive correlations were found between changes in grocery and pharmacy, R_t retail and recreation, transit, and workplace visits, for both R_t and estimated infection count, respectively. Negative correlations were found between changes in residential area visits for both Rt and estimated infection count, respectively. Public health policies enacted in RI were associated with changes in the pandemic trajectory. This ecological study provides further evidence of how non-pharmaceutical interventions and vaccination slowed COVID-19 transmission in RI.

In 2022, the Mpox viral outbreak signaled a global public health emergency. Infectious disease management and prevention are crucial tasks for healthcare workers. In their line of work, orthopedic surgeons could come across cases of the Mpox virus. The aim of the present study was to explore orthopedic surgeons' knowledge of the Mpox virus, their conspiracy beliefs regarding emerging viral infections, and their self-confidence in managing the Mpox virus. In this cross-sectional survey, 137 orthopedic surgeons completed an online questionnaire. The participants had low knowledge of the Mpox virus, providing on average 11.5 correct answers (SD = 2.68) of a possible 21. In addition, the participants tended to express moderate conspiracy beliefs and to have low self-confidence in managing the Mpox virus. Age 30 or older, a higher knowledge level, and lower conspiracy beliefs predicted greater self-confidence in managing the Mpox virus. In addition, a negative association was found between knowledge of the Mpox virus and conspiracy beliefs. Arab and younger orthopedic surgeons expressed stronger conspiracy beliefs. Interventions should include introduction of material regarding emerging tropical infections in medical curricula and in-service training programs. In addition, special attention should be paid to younger and Arab orthopedic surgeons, as these subgroups may endorse higher conspiracy beliefs.

Neglected tropical diseases (NTDs) have become important public health threats that require multi-faceted control interventions. As late treatment and management of NTDs contribute significantly to the associated burdens, early diagnosis becomes an important component for surveillance and planning effective interventions. This review identifies common NTDs and highlights the progress in the development of diagnostics for these NTDs. Leveraging existing technologies to improve NTD diagnosis and improving current operational approaches for deployment of developed diagnostics are crucial to achieving the 2030 NTD elimination target. Point-of-care NTD (POC-NTD) diagnostic tools are recommended preferred diagnostic options in resource-constrained areas for mapping risk zones and monitoring treatment efficacy. However, few are currently available commercially. Technical training of remote health care workers on the use of POC-NTD diagnostics, and training of health workers on the psychosocial consequences of these diagnostics are critical in harnessing POC-NTD diagnostic potential. While the COVID-19 pandemic has challenged the possibility of achieving NTD elimination in 2030 due to the disruption of healthcare services and dwindling financial support for NTDs, the possible contribution of NTDs in exacerbating COVID-19 pandemic should motivate NTD health system strengthening.

Malaria is a parasitic disease distributed in tropical areas but with a high number of imported cases in non-endemic countries. The most specific and sensitive malaria diagnostic methods are PCR and LAMP. However, both require specific equipment, extraction procedures and a cold chain. This study aims to solve some limitations of LAMP method with the optimization and validation of six LAMP assays, genus and species-specific, using an easy and fast extraction method, the incorporation of a reaction control assay, two ways (Dual) of result reading and reagent lyophilization. The Dual-LAMP assays were validated against the Nested-Multiplex Malaria PCR. A conventional column and saline extraction methods, and the use of lyophilized reaction tubes were also assessed. A new reaction control Dual-LAMP-RC assay was designed. Dual-LAMP-Pspp assay showed no cross-reactivity with other parasites, repeatability and reproducibility of 100%, a significant correlation between parasite concentration and time to amplification and a LoD of 1.22 parasites/µl and 5.82 parasites/µl using column and saline extraction methods, respectively. Sensitivity and specificity of the six Dual-LAMP assays reach values of 100% or close to this, being lower for the Dual-LAMP-Pm. The Dual-LAMP-RC assay worked as expected. Lyophilized Dual-LAMP results were concordant with the reference method. Dual-LAMP malaria assays with the addition of a new reaction control LAMP assay and the use of a fast and easy saline extraction method, provided low limit of detection, no cross-reactivity, and good sensitivity and specificity. Furthermore, the reagent lyophilization and the dual result reading allow their use in most settings.

During the 2022 monkeypox (mpox) epidemic's first 100 days, 99 non-endemic countries, including 25 Latin American and Caribbean (LAC) countries, reported >64,000 cases. We aim to assess the cases' introduction, epidemiological profile, initial response, transmission dynamics, and main challenges ahead among LAC countries during the first 100 days of the mpox 2022 epidemic. We used mixed methods, including desktop research and open data analysis. The 2022 mpox epidemic has progressed consistently through LAC, with Brazil and Peru combining for over 80% of the confirmed LAC cases. Although Brazil reports the highest mpox case counts (n = 4472), Peru reports the highest incidence (41 confirmed cases per 1 million inhabitants). Initially, LAC missed the opportunity to focus on the high-risk population, including the people living with HIV (PLHIV) and gay, bisexual, and men who have sex with men (GBMSM). Moreover, the main challenges ahead include stigmatization, vaccine inequity, barriers to accessing diagnostics, and complete isolation. Furthermore, we estimated that Colombia, Brazil, the United States, and Peru are the world frontrunners in mpox duplication time (estimated between 6.4 and 8.8) and effective reproductive number (estimated between 2.7 and 3.8). In addition, Brazil reported its first case of inverse zoonosis in a dog and Peru its first autochthonous MPXV lineage, B.1.6. LAC has become the epicenter of the 2022 mpox epidemic, with Brazil and Peru emerging as the new mpox hot zones. Therefore, LAC countries must join efforts to control this epidemic and overcome the challenges of vaccine inequity and stigmatization.

Diagnostic biomarkers for childhood pneumonia could guide management and improve antibiotic stewardship in low-resource settings where chest x-ray (CXR) is not always available. In this cross-sectional study, we measured chitinase 3-like protein 1 (CHI3L1), surfactant protein D (SP-D), lipocalin-2 (LCN2), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in Ugandan children under the age of five hospitalized with acute lower respiratory tract infection. We determined the association between biomarker levels and primary end-point pneumonia, indicated by CXR consolidation. We included 89 children (median age 11 months, 39% female). Primary endpoint pneumonia was present in 22 (25%). Clinical signs were similar in children with and without CXR consolidation. Broad-spectrum antibiotics (ceftriaxone) were administered in 83 (93%). Levels of CHI3L1, SP-D, LCN2 and TIMP-1 were higher in patients with primary end-point pneumonia compared to patients with normal CXR or other infiltrates. All markers were moderately accurate predictors of primary end-point pneumonia, with area under receiver operator characteristic curves of 0.66-0.70 (p<0.05 for all markers). The probability of CXR consolidation increased monotonically with the number of markers above cut-off. Among 28 patients (31%) in whom all four markers were below the cut-off, the likelihood ratio of CXR consolidation was 0.11 (95%CI 0.015 to 0.73). CHI3L1, SP-D, LCN2 and TIMP-1 were associated with CXR consolidation in children with clinical pneumonia in a low-resource setting. Combinations of quantitative biomarkers may be useful to safely withhold antibiotics in children with a low probability of bacterial infection.