Developing countries and neglected diseases: challenges and perspectives

It is now commonly admitted that the so-called (most) neglected tropical diseases have been given little attention. According to World Health Organization, neglected diseases are hidden diseases as they affect almost exclusively extremely poor populations living in remote areas beyond the reach of health service. The European Parliament recognised that, to our shame, Neglected Diseases have not received the attention they deserve from EU actions. In the Millennium Development Goals they were given very little attention and mentioned just as other disease. Investing in drugs for these diseases is thought to be not marketable or profitable. However, despite their low mortality, neglected diseases are causing severe and permanent disabilities and deformities affecting approximately 1 billion people in the world, yielding more than 20 millions of Disability Adjusted Life Years (56.6 million according to Lancet's revised estimates) and important socio-economic losses. Urgent pragmatic and efficient measures are needed both at international and national levels

Dependence of the Star Formation Efficiency on the Parameters of Molecular Cloud Formation Simulations

We investigate the response of the star formation efficiency (SFE) to the main parameters of simulations of molecular cloud formation by the collision of warm diffuse medium (WNM) cylindrical streams, neglecting stellar feedback and magnetic fields. The parameters we vary are the Mach number of the inflow velocity of the streams, Msinf, the rms Mach number of the initial background turbulence in the WNM, and the total mass contained in the colliding gas streams, Minf. Because the SFE is a function of time, we define two estimators for it, the "absolute" SFE, measured at t = 25 Myr into the simulation's evolution (sfeabs), and the "relative" SFE, measured 5 Myr after the onset of star formation in each simulation (sferel). The latter is close to the "star formation rate per free-fall time" for gas at n = 100 cm^-3. We find that both estimators decrease with increasing Minf, although by no more than a factor of 2 as Msinf increases from 1.25 to 3.5. Increasing levels of background turbulence similarly reduce the SFE, because the turbulence disrupts the coherence of the colliding streams, fragmenting the cloud, and producing small-scale clumps scattered through the numerical box, which have low SFEs. Finally, the SFE is very sensitive to the mass of the inflows, with sferel decreasing from ~0.4 to ~0.04 as the the virial parameter in the colliding streams increases from ~0.15 to ~1.5. This trend is in partial agreement with the prediction by Krumholz & McKee (2005), since the latter lies within the same range as the observed efficiencies, but with a significantly shallower slope. We conclude that the observed variability of the SFE is a highly sensitive function of the parameters of the cloud formation process, and may be the cause of significant scatter in observational determinations.Comment: 19 pages, submitted to MNRA

T. brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes

Aims: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response. Methods and results: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release (Ca2+ waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10–15% increase of SERCA activity but reduced SR Ca2+ content, suggesting a concomitant increased SR-mediated Ca2+ leak. This conclusion was supported by data demonstrating that TbCatL increased Ca2+ wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events. Conclusion: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function

Chagas disease: an impediment in achieving the Millennium Development Goals in Latin America

<p>Abstract</p> <p>Background</p> <p>Achieving sustainable economic and social growth through advances in health is crucial in Latin America within the framework of the United Nations Millennium Development Goals.</p> <p>Discussion</p> <p>Health-related Millennium Development Goals need to incorporate a multidimensional approach addressing the specific epidemiologic profile for each region of the globe. In this regard, addressing the cycle of destitution and suffering associated with infection with <it>Trypanosoma cruzi</it>, the causal agent of Chagas disease of American trypanosomiasis, will play a key role to enable the most impoverished populations in Latin America the opportunity to achieve their full potential. Most cases of Chagas disease occur among forgotten populations because these diseases persist exclusively in the poorest and the most marginalized communities in Latin America.</p> <p>Summary</p> <p>Addressing the cycle of destitution and suffering associated with <it>T. cruzi </it>infection will contribute to improve the health of the most impoverished populations in Latin America and will ultimately grant them with the opportunity to achieve their full economic potential.</p

The Neglected Tropical Diseases of Latin America and the Caribbean: A Review of Disease Burden and Distribution and a Roadmap for Control and Elimination

The neglected tropical diseases (NTDs) represent some of the most common infections of the poorest people living in the Latin American and Caribbean region (LAC). Because they primarily afflict the disenfranchised poor as well as selected indigenous populations and people of African descent, the NTDs in LAC are largely forgotten diseases even though their collective disease burden may exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria. Based on their prevalence and healthy life years lost from disability, hookworm infection, other soil-transmitted helminth infections, and Chagas disease are the most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis, trachoma, leprosy, and lymphatic filariasis. On the other hand, for some important NTDs, such as leptospirosis and cysticercosis, complete disease burden estimates are not available. The NTDs in LAC geographically concentrate in 11 different sub-regions, each with a distinctive human and environmental ecology. In the coming years, schistosomiasis could be eliminated in the Caribbean and transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America. However, the highest disease burden NTDs, such as Chagas disease, soil-transmitted helminth infections, and hookworm and schistosomiasis co-infections, may first require scale-up of existing resources or the development of new control tools in order to achieve control or elimination. Ultimately, the roadmap for the control and elimination of the more widespread NTDs will require an inter-sectoral approach that bridges public health, social services, and environmental interventions

Risk Factors for Death in Children with Visceral Leishmaniasis

Visceral leishmaniasis (VL) is a deadly disease caused by a protozoan called Leishmania. It is transmitted to humans from infected animals by a sandfly bite. Most people actually manage to control the infection and do not get sick, while others develop a range of symptoms. VL impairs the production of blood components and causes the immune system to malfunction, thus anemia, bleeding, and bacterial infections often complicate the disease and can lead to death. To identify risk factors for death from VL, the authors studied 546 children in a referral center in Recife, Brazil. They looked at clinical history, physical examination and full blood counts on the assumption these could be easily assessed in peripheral health facilities. They found that the presence of fast breathing, jaundice, mucosal (e.g. gum) bleeding and bacterial infections would each increase the risk of death in three to four-fold. The presence of very low counts of neutrophils and platelets would increase the risk of death in three and 12-fold respectively. This knowledge can help clinicians to anticipate the use of antibiotics or transfusion of blood products in high risk patients, who would potentially benefit from transfer to centers with advanced life support facilities