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BACKGROUND: Environmental degradation facilitates the emergence of vector-borne diseases, such as malaria, through changes in the ecological landscape that increase human-vector contacts and that expand vector habitats. However, the modifying effects of environmental degradation on climate-disease relationships have not been well explored. Here, we investigate the rapid re-emergence of malaria in a transmission hotspot in southern Venezuela and explore the synergistic effects of environmental degradation, specifically gold-mining activity, and climate variation. METHODS: In this spatiotemporal modelling study of the 46 parishes of the state of Bolívar, southeast Venezuela, we used data from the Venezuelan Ministry of Health including population data and monthly cases of Plasmodium falciparum malaria and Plasmodium vivax malaria between 1996 and 2016. We estimated mean precipitation and temperature using the ERA5-Land dataset and used monthly anomalies in sea-surface temperature as an indicator of El Niño events between 1996 and 2016. The location of suspected mining sites in Bolívar in 2009, 2017, and 2018 were sourced from the Amazon Geo-Referenced Socio-Environmental Information Network. We estimated measures of cumulative forest loss and urban development by km2 using annual land cover maps from the European Space Agency Climate Change Initiative between 1996 and 2016. We modelled monthly cases of P falciparum and P vivax malaria using a Bayesian hierarchical mixed model framework. We quantified the variation explained by mining activity before exploring the modifying effects of environmental degradation on climate-malaria relationships. FINDINGS: We observed a 27% reduction in the additional unexplained spatial variation in incidence of P falciparum malaria and a 23% reduction in P vivax malaria when mining was included in our models. The effect of temperature on malaria was greater in high mining areas than low mining areas, and the P falciparum malaria effect size at temperatures of 26·5°C (2·4 cases per 1000 people [95% CI 1·78-3·06]) was twice as high as the effect in low mining areas (1 case per 1000 people [0·68-1·49]). INTERPRETATION: We show that mining activity in southern Venezuela is associated with hotspots of malaria transmission. Increased temperatures exacerbated malaria transmission in mining areas, highlighting the need to consider how environmental degradation modulates climate effect on disease risk, which is especially important in areas subjected to rapidly rising temperatures and land-use change globally. Our findings have implications for the progress towards malaria elimination in the Latin American region. Our findings are also important for effectively targeting timely treatment programmes and vector-control activities in mining areas with high rates of malaria transmission. FUNDING: Biotechnology and Biological Sciences Research Council, Royal Society, US National Institutes of Health, and Global Challenges Research Fund. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

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The coronavirus disease 2019 (COVID-19) pandemic has particularly affected countries with weakened health services in Latin America, where proper patient management could be a critical step to address the epidemic. In this study, we aimed to characterize and identify which epidemiological, clinical, and paraclinical risk factors defined COVID-19 infection from the first confirmed cases through the first epidemic wave in Venezuela. A retrospective analysis of consecutive suspected cases of COVID-19 admitted to a sentinel hospital was carried out, including 576 patient cases subsequently confirmed for severe acute respiratory syndrome coronavirus 2 infection. Of these, 162 (28.1%) patients met the definition criteria for severe/critical disease, and 414 (71.2%) were classified as mild/moderate disease. The mean age was 47 (SD 16) years, the majority of which were men (59.5%), and the most frequent comorbidity was arterial hypertension (23.3%). The most common symptoms included fever (88.7%), headache (65.6%), and dry cough (63.9%). Severe/critical disease affected mostly older males with low schooling (p < 0.001). Similarly, higher levels of glycemia, urea, aminotransferases, total bilirubin, lactate dehydrogenase, and erythrocyte sedimentation rate were observed in severe/critical disease patients compared to those with mild/moderate disease. Overall mortality was 7.6% (44/576), with 41.7% (28/68) dying in hospital. We identified risk factors related to COVID-19 infection, which could help healthcare providers take appropriate measures and prevent severe clinical outcomes. Our results suggest that the mortality registered by this disease in Venezuela during the first epidemic wave was underestimated. An increase in fatalities is expected to occur in the coming months unless measures that are more effective are implemented to mitigate the epidemic while the vaccination process is ongoing.

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Testing and isolation have been crucial for controlling the COVID-19 pandemic. Venezuela has one of the weakest testing infrastructures in Latin America and the low number of reported cases in the country has been attributed to substantial underreporting. However, the Venezuelan epidemic seems to have lagged behind other countries in the region, with most cases occurring within the capital region and four border states. Here, we describe the spatial epidemiology of COVID-19 in Venezuela and its relation to the population mobility, migration patterns, non-pharmaceutical interventions and fuel availability that impact population movement. Using a metapopulation model of SARS-CoV-2 transmission dynamics, we explore how movement patterns could have driven the observed distribution of cases. Low within-country connectivity most likely delayed the onset of the epidemic in most states, except for those bordering Colombia and Brazil, where high immigration seeded outbreaks. NPIs slowed early epidemic growth and subsequent fuel shortages appeared to be responsible for limiting the spread of COVID-19 across the country.

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Malaria elimination in Latin America is becoming an elusive goal. Malaria cases reached a historical ~1 million in 2017 and 2018, with Venezuela contributing 53% and 51% of those cases, respectively. Historically, malaria incidence in southern Venezuela has accounted for most of the country's total number of cases. The efficient deployment of disease prevention measures and prediction of disease spread to new regions requires an in-depth understanding of spatial heterogeneity on malaria transmission dynamics. Herein, we characterized the spatial epidemiology of malaria in southern Venezuela from 2007 through 2017 and described the extent to which malaria distribution has changed country-wide over the recent years. We found that disease transmission was focal and more prevalent in the southeast region of southern Venezuela where two persistent hotspots of Plasmodium vivax (76%) and P. falciparum (18%) accounted for ~60% of the total number of cases. Such hotspots are linked to deforestation as a consequence of illegal gold mining activities. Incidence has increased nearly tenfold over the last decade, showing an explosive epidemic growth due to a significant lack of disease control programs. Our findings highlight the importance of spatially oriented interventions to contain the ongoing malaria epidemic in Venezuela. This work also provides baseline epidemiological data to assess cross-border malaria dynamics and advocates for innovative control efforts in the Latin American region.

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In the past 5-10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.

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Venezuela's tumbling economy and authoritarian rule have precipitated an unprecedented humanitarian crisis. Hyperinflation rates now exceed 45,000%, and Venezuela's health system is in free fall. The country is experiencing a massive exodus of biomedical scientists and qualified healthcare professionals. Reemergence of arthropod-borne and vaccine-preventable diseases has sparked serious epidemics that also affect neighboring countries. In this article, we discuss the ongoing epidemics of measles and diphtheria in Venezuela and their disproportionate impact on indigenous populations. We also discuss the potential for reemergence of poliomyelitis and conclude that action to halt the spread of vaccine-preventable diseases within Venezuela is a matter of urgency for the country and the region. We further provide specific recommendations for addressing this crisis.

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A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized quinones were tested against cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2-aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds.

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BACKGROUND: The prolonged effectiveness of antiretroviral therapy (ART) in a developing country is not well established. METHODS: An observational database was established at the HIV clinic of the Almenara Hospital in Lima, Peru in 1996. All 564 initially antiretroviral-naive HIV-infected persons (mean CD4 count of 91 cells/mm3) who received combination ART were followed over time. RESULTS: The overall survival rate was 96% at year 2, 94% at year 4, and 91% at year 5. Among persons who initiated therapy with CD4 counts <100 cells/mm3, the overall survival rate at 3 years was 95%. Opportunistic infections while on ART occurred in 20% of persons. Patients who received 2 reverse transcriptase (RT) inhibitors plus a protease inhibitor had slightly better survival rates and less opportunistic disease in the first year of therapy as compared with those receiving 2 RT inhibitors and a nonnucleoside reverse transcriptase inhibitor or 3 RT inhibitors. CONCLUSIONS: This study demonstrates the long-term effectiveness of ART in a developing country urban setting. It provides evidence of the importance of continuing global financing initiatives to provide widespread HIV therapy for countries in the developing world.

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OBJECTIVE: Few reports have described the clinical and pathologic characteristics of HIV-related systemic non-Hodgkin lymphoma (sNHL) in developing countries. We aimed to determine these characteristics from a national HIV reference center in Peru and to evaluate factors associated with survival. METHODS: A retrospective/prospective study of patients with HIV-related sNHL from the Guillermo Almenara General Hospital in Lima, Peru between 1993 and 2004. Clinical characteristics at diagnosis included age, gender, risk behavior, previous AIDS diagnosis, opportunistic diseases, previous highly active antiretroviral therapy, Karnofsky score, origin, clinical stage and B-cell symptoms of sNHL, and CD4 cell count. Cases of sNHL were classified according to the criteria of the World Health Organization. RESULTS: Thirty-three cases were identified (26 male, age range: 38 +/- 10 years). Ten patients (30%) had a prior history of AIDS, 14 (42%) had a Karnofsky score of

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