Antimalarial and antitubercular C-glycosylated benz[α]anthraquinones from the marine-derived Streptomyces sp. BCC45596

Three naturally new C-glycosylated benz[α]anthraquinone derivatives, urdamycinone E (1), urdamycinone G (2), dehydroxyaquayamycin (3) have been isolated from the marine Streptomycetes sp. BCC45596. Urdamycin E (4), the possible biosynthetic precursor of 1–3, has also been identified after a re-cultivation of the strain. These compounds (1–4) exhibited potent anti-Plasmodium palcifarum K1 strain with IC₅₀ values in a range of 0.0534–2.93 μg/mL and anti-Mycobacterium tuberculosis with minimum inhibition concentrations (MICs) in a range of 3.13–12.50 μg/mL. Cytotoxicity against KB, MCF-7, NCI-H187, and Vero cells was also evaluated.     

Evalution of the “Iceberg Phenomenon” in Johne's Disease through Mathematical Modelling

Johne''s disease (JD) is a chronic, enteric disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Disease progression follows four distinct stages: silent, subclinical, clinical and advanced. Available diagnostic tests have poor sensitivity and cannot detect early stages of the infection; as a result, only animals in the clinical and advanced stages, which represent the tip of the ‘iceberg’, are identified through testing. The Iceberg Phenomenon is then applied to provide estimates for JD prevalence. For one animal in the advanced stage, it is assumed that there are one to two in the clinical stage, four to eight in the subclinical stage, and ten to fourteen in the silent stage. These ratios, however, are based on little evidence. To evaluate the ratios, we developed a deterministic ordinary differential equation model of JD transmission and disease progression dynamics. When duration periods associated with the natural course of the disease progression are used, the above ratios do not hold. The ratios used to estimate JD prevalence need to be further investigated.     

Poverty,Disease, and the Ecology of Complex Systems

Understanding why some human populations remain persistently poor remains a significant challenge for both the social and natural sciences. The extremely poor are generally reliant on their immediate natural resource base for subsistence and suffer high rates of mortality due to parasitic and infectious diseases. Economists have developed a range of models to explain persistent poverty, often characterized as poverty traps, but these rarely account for complex biophysical processes. In this Essay, we argue that by coupling insights from ecology and economics, we can begin to model and understand the complex dynamics that underlie the generation and maintenance of poverty traps, which can then be used to inform analyses and possible intervention policies. To illustrate the utility of this approach, we present a simple coupled model of infectious diseases and economic growth, where poverty traps emerge from nonlinear relationships determined by the number of pathogens in the system. These nonlinearities are comparable to those often incorporated into poverty trap models in the economics literature, but, importantly, here the mechanism is anchored in core ecological principles. Coupled models of this sort could be usefully developed in many economically important biophysical systems—such as agriculture, fisheries, nutrition, and land use change—to serve as foundations for deeper explorations of how fundamental ecological processes influence structural poverty and economic development.     

Economic inequality caused by feedbacks between poverty and the dynamics of a rare tropical disease: the case of Buruli ulcer in sub-Saharan Africa

Neglected tropical diseases (NTDs) have received increasing attention in recent years by the global heath community, as they cumulatively constitute substantial burdens of disease as well as barriers for economic development. A number of common tropical diseases such as malaria, hookworm or schistosomiasis have well-documented economic impacts. However, much less is known about the population-level impacts of diseases that are rare but associated with high disability burden, which represent a great number of tropical diseases. Using an individual-based model of Buruli ulcer (BU), we demonstrate that, through feedbacks between health and economic status, such NTDs can have a significant impact on the economic structure of human populations even at low incidence levels. While average wealth is only marginally affected by BU, the economic conditions of certain subpopulations are impacted sufficiently to create changes in measurable population-level inequality. A reduction of the disability burden caused by BU can thus maximize the economic growth of the poorest subpopulations and reduce significantly the economic inequalities introduced by the disease in endemic regions.     

Assessing Coverage,Equity and Quality Gaps in Maternal and Neonatal Care in Sub-Saharan Africa: An Integrated Approach

BackgroundGaps in coverage, equity and quality of health services hinder the achievement of the Millennium Development Goals 4 and 5 in most countries of sub-Saharan Africa as well as in other high-burden countries, yet few studies attempt to assess all these dimensions as part of the situation analysis. We present the base-line data of a project aimed at simultaneously addressing coverage, equity and quality issues in maternal and neonatal health care in five districts belonging to three African countries.MethodsData were collected in cross-sectional studies with three types of tools. Coverage was assessed in three hospitals and 19 health centres (HCs) utilising emergency obstetric and newborn care needs assessment tools developed by the Averting Maternal Death and Disability program. Emergency obstetrics care (EmOC) indicators were calculated. Equity was assessed in three hospitals and 13 HCs by means of proxy wealth indices and women delivering in health facilities were compared with those in the general population to identify inequities. Quality was assessed in three hospitals using the World Health Organization’s maternal and neonatal quality of hospital care assessment tool which evaluates the whole range of aspects of obstetric and neonatal care and produces an average score for each main area of care.ResultsAll the three hospitals qualified as comprehensive EmOC facilities but none of the HCs qualified for basic EmOC. None of the districts met the minimum requisites for EmOC indicators. In two out of three hospitals, there were major quality gaps which were generally greater in neonatal care, management of emergency and complicated cases and monitoring. Higher access to care was coupled by low quality and good quality by very low access. Stark inequities in utilisation of institutional delivery care were present in all districts and across all health facilities, especially at hospital level.ConclusionOur findings confirm the existence of serious issues regarding coverage, equity and quality of health care for mothers and newborns in all study districts. Gaps in one dimension hinder the potential gains in health outcomes deriving from good performances in other dimensions, thus confirm the need for a three-dimensional profiling of health care provision as a basis for data-driven planning.     

Periodic oscillations and backward bifurcation in a model for the dynamics of malaria transmission

A deterministic ordinary differential equation model for the dynamics of malaria transmission that explicitly integrates the demography and life style of the malaria vector and its interaction with the human population is developed and analyzed. The model is different from standard malaria transmission models in that the vectors involved in disease transmission are those that are questing for human blood. Model results indicate the existence of nontrivial disease free and endemic steady states, which can be driven to instability via a Hopf bifurcation as a parameter is varied in parameter space. Our model therefore captures oscillations that are known to exist in the dynamics of malaria transmission without recourse to external seasonal forcing. Additionally, our model exhibits the phenomenon of backward bifurcation. Two threshold parameters that can be used for purposes of control are identified and studied, and possible reasons why it has been difficult to eradicate malaria are advanced.     

Isariotins G–J from cultures of the Lepidoptera pathogenic fungus Isaria tenuipes

Four new alkaloids isariotins G–J (1–4), together with the known isariotins, were isolated from cultures of the Lepidoptera pathogenic fungus Isaria tenuipes. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. Compounds 1–4 exhibited antimalarial and cytotoxic activities.     

Warming temperatures could expose more than 1.3 billion new people to Zika virus risk by 2050

In the aftermath of the 2015 pandemic of Zika virus (ZIKV), concerns over links between climate change and emerging arboviruses have become more pressing. Given the potential that much of the world might remain at risk from the virus, we used a previously established temperature‐dependent transmission model for ZIKV to project climate change impacts on transmission suitability risk by mid‐century (a generation into the future). Based on these model predictions, in the worst‐case scenario, over 1.3 billion new people could face suitable transmission temperatures for ZIKV by 2050. The next generation will face substantially increased ZIKV transmission temperature suitability in North America and Europe, where naïve populations might be particularly vulnerable. Mitigating climate change even to moderate emissions scenarios could significantly reduce global expansion of climates suitable for ZIKV transmission, potentially protecting around 200 million people. Given these suitability risk projections, we suggest an increased priority on research establishing the immune history of vulnerable populations, modeling when and where the next ZIKV outbreak might occur, evaluating the efficacy of conventional and novel intervention measures, and increasing surveillance efforts to prevent further expansion of ZIKV.     

Observance of period-doubling bifurcation and chaos in an autonomous ODE model for malaria with vector demography

We illustrate that an autonomous ordinary differential equation model for malaria transmission can exhibit period-doubling bifurcations leading to chaos when ecological aspects of malaria transmission are incorporated into the model. In particular, when demography, feeding, and reproductive patterns of the mosquitoes that transmit the malaria-causing parasite are explicitly accounted for, the resulting model exhibits subcritical bifurcations, period-doubling bifurcations, and chaos. Vectorial and disease reproduction numbers that regulate the size of the vector population at equilibrium and the endemicity of the malaria disease, respectively, are identified and used to simulate the model to show the different bifurcations and chaotic dynamics. A subcritical bifurcation is observed when the disease reproduction number is less than unity. This highlights the fact that malaria control efforts need to be long lasting and sustained to drive the infectious populations to levels below the associated saddle-node bifurcation point at which control is feasible. As the disease reproduction number increases beyond unity, period-doubling cascades that develop into chaos closely followed by period-halving sequences are observed. The appearance of chaos suggests that characterization of the physiological status of disease vectors can provide a pathway toward understanding the complex phenomena that are known to characterize the dynamics of malaria and other indirectly transmitted infections of humans. To the best of our knowledge, there is no known unforced continuous time deterministic host-vector transmission malaria model that has been shown to exhibit chaotic dynamics. Our results suggest that malaria data may need to be critically examined for complex dynamics.