Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis

Despite the fact that eflornithine was considered as the safer drug to treat human African trypanosomiasis (HAT) and has been freely available since 2001, the difficulties in logistics and cost burden associated with this drug meant that the toxic melarsoprol remained the drug of choice. The World Health Organization responded to the situation by designing a medical kit containing all the materials needed to use eflornithine, and by implementing a training and drugs distribution programme which has allowed a transition to this much safer treatment. The introduction of the combination of nifurtimox and eflornithine (NECT) has accelerated the shift from melarsoprol to the best treatment available, due to reduced dosage and treatment time for eflornithine that has significantly lessened the cost and improved the burden of logistics encountered during treatment and distribution. The decrease in the use of more dangerous but cheaper melarsoprol has meant a rise in the per patient cost of treating HAT. Although NECT is cheaper than eflornithine monotherapy, an unexpected consequence has been a continuing rise in the per patient cost of treating HAT. The ethical decision of shifting to the best available treatment imposes a financial burden on HAT control programmes that might render long-term application unsustainable. These factors call for continuing research to provide new safer and more effective drugs that are simple to administer and cheaper when compared to current drug

The journey towards elimination of gambiense human African trypanosomiasis: not far, nor easy

Considering the epidemic situation of gambiense human African trypanosomiasis (HAT) at the end of the twentieth century, the World Health Organization (WHO) and partners strengthened disease control and surveillance. Over the last 15 years, the activities implemented through the National Control Programmes have brought gambiense HAT under control and now its elimination is deemed as an achievable goal. In 2012, WHO targeted gambiense HAT for elimination as a public health problem by 2020. The final goal will be the sustainable disease elimination by 2030, defined as the interruption of the transmission of gambiense HAT. The elimination is considered feasible, because of the epidemiological vulnerability of the disease, the current state of control, the availability of strategies and tools and international commitment and political will. Integration of activities in the health system is needed to ensure the sustainability of the elimination. The development of user-friendly diagnostic and treatment tools will facilitate the integration process. Adequate funding is needed to implement activities, but also to support research that will make the elimination sustainable. A long-term commitment by donors is needed and ownership of the process by endemic countries is critica

Feasibility of eliminating visceral leishmaniasis from the Indian subcontinent: explorations with a set of deterministic age-structured transmission models

textabstractBackground: Visceral leishmaniasis (VL) is a neglected tropical disease transmitted by sandflies. On the Indian subcontinent (ISC), VL is targeted for elimination as a public health problem by 2017. In the context of VL, the elimination target is defined as an annual VL incidence of <1 per 10,000 capita at (sub-)district level. Interventions focus on vector control, surveillance and on diagnosing and treating VL cases. Many endemic areas have not yet achieved optimal control due to logistical, biological as well as technical challenges. We used mathematical modelling to quantify VL transmission dynamics and predict the feasibility of achieving the VL elimination target with current control strategies under varying assumptions about the reservoir of infection in humans. Methods: We developed three deterministic age-structured transmission models with different main reservoirs of infection in humans: asymptomatic infections (model 1), reactivation of infection after initial infection (model 2), and post kala-azar dermal leishmaniasis (PKDL; model 3). For each model, we defined four sub-variants based on different assumptions about the duration of immunity and age-patterns in exposure to sandflies. All 12 model sub-variants were fitted to data from the KalaNet study in Bihar (India) and Nepal, and the best sub-variant was selected per model. Predictions were made for optimal and sub-optimal indoor residual spraying (IRS) effectiveness for three different levels of VL endemicity. Results: Structurally different models explained the KalaNet data equally well. However, the predicted impact of IRS varied substantially between models, such that a conclusion about reaching the VL elimination targets for the ISC heavily depends on assumptions about the main reservoir of infection in humans: asymptomatic cases, recovered (immune) individuals that reactivate, or PKDL cases. Conclusions: Available data on the impact of IRS so far suggest one model is probably closest to reality (model 1). According to this model, elimination of VL (incidence of <1 per 10,000) by 2017 is only feasible in low and medium endemic settings with optimal IRS. In highly endemic settings and settings with sub-optimal IRS, additional interventions will be required

Revealing the Jet Structure of GRB 030329 with High Resolution Multicolor Photometry

We present multicolor optical observations of the nearby (z=0.1685) GRB 030329 obtained with the same instrumentation over a time period of 6 hours for a total of an unprecedented 475 quasi-simultaneous BVR observations. The achromatic steepening in the optical, which occurs at t~0.7 days, provides evidence for a dynamic transition of the source, and can be most readily explained by models in which the GRB ejecta are collimated into a jet. Since the current state-of-the-art modeling of GRB jets is still flawed with uncertainties, we use these data to critically assess some classes of models that have been proposed in the literature. The data, especially the smooth decline rate seen in the optical afterglow, are consistent with a model in which GRB 030329 was a homogeneous, sharp-edged jet, viewed near its edge interacting with a uniform external medium, or viewed near its symmetry axis with a stratified wind-like external environment. The lack of short timescale fluctuations in the optical afterglow flux down to the 0.5 per cent level puts stringent constraints on possible small scale angular inhomogeneities within the jet or fluctuations in the external density

On the Afterglow of the X-ray Flash of 2003 July 23: Photometric evdence for an Off-Axis Gamma-Ray burst with an Associated Supernova

Peer reviewe

Pre-ALMA observations of GRBs in the mm/submm range

GRBs generate an afterglow emission that can be detected from radio to X-rays during days, or even weeks after the initial explosion. The peak of this emission crosses the mm/submm range during the first hours to days, making their study in this range crucial for constraining the models. Observations have been limited until now due to the low sensitivity of the observatories in this range. We present observations of 10 GRB afterglows obtained from APEX and SMA, as well as the first detection of a GRB with ALMA, and put them into context with all the observations that have been published until now in the spectral range that will be covered by ALMA. The catalogue of mm/submm observations collected here is the largest to date and is composed of 102 GRBs, of which 88 had afterglow observations, whereas the rest are host galaxy searches. With our programmes, we contributed with data of 11 GRBs and the discovery of 2 submm counterparts. In total, the full sample, including data from the literature, has 22 afterglow detections with redshift ranging from 0.168 to 8.2. GRBs have been detected in mm/submm wavelengths with peak luminosities spanning 2.5 orders of magnitude, the most luminous reaching 10^33erg s^-1 Hz^-1. We observe a correlation between the X-ray brightness at 0.5 days and the mm/submm peak brightness. Finally we give a rough estimate of the distribution of peak flux densities of GRB afterglows, based on the current mm/submm sample. Observations in the mm/submm bands have been shown to be crucial for our understanding of the physics of GRBs, but have until now been limited by the sensitivity of the observatories. With the start of the operations at ALMA, the sensitivity will be increased by more than an order of magnitude. Our estimates predict that, once completed, ALMA will detect up to 98% of the afterglows if observed during the passage of the peak synchrotron emission.Comment: 23 pages, 14 figures, 5 tables (one big one!), Accepted for publication in A&A. Includes the first observation of a GRB afterglow with ALM

Policy Recommendations From Transmission Modeling for the Elimination of Visceral Leishmaniasis in the Indian Subcontinent.

Background: Visceral leishmaniasis (VL) has been targeted by the World Health Organization (WHO) and 5 countries in the Indian subcontinent for elimination as a public health problem. To achieve this target, the WHO has developed guidelines consisting of 4 phases of different levels of interventions, based on vector control through indoor residual spraying of insecticide (IRS) and active case detection (ACD). Mathematical transmission models of VL are increasingly used for planning and assessing the efficacy of interventions and evaluating the intensity and timescale required to achieve the elimination target. Methods: This paper draws together the key policy-relevant conclusions from recent transmission modeling of VL, and presents new predictions for VL incidence under the interventions recommended by the WHO using the latest transmission models. Results: The model predictions suggest that the current WHO guidelines should be sufficient to reach the elimination target in areas that had medium VL endemicities (up to 5 VL cases per 10000 population per year) prior to the start of interventions. However, additional interventions, such as extending the WHO attack phase (intensive IRS and ACD), may be required to bring forward elimination in regions with high precontrol endemicities, depending on the relative infectiousness of different disease stages. Conclusions: The potential hurdle that asymptomatic and, in particular, post-kala-azar dermal leishmaniasis cases may pose to reaching and sustaining the target needs to be addressed. As VL incidence decreases, the pool of immunologically naive individuals will grow, creating the potential for new outbreaks

Policy Recommendations From Transmission Modeling for the Elimination of Visceral Leishmaniasis in the Indian Subcontinent.

Background: Visceral leishmaniasis (VL) has been targeted by the World Health Organization (WHO) and 5 countries in the Indian subcontinent for elimination as a public health problem. To achieve this target, the WHO has developed guidelines consisting of 4 phases of different levels of interventions, based on vector control through indoor residual spraying of insecticide (IRS) and active case detection (ACD). Mathematical transmission models of VL are increasingly used for planning and assessing the efficacy of interventions and evaluating the intensity and timescale required to achieve the elimination target. Methods: This paper draws together the key policy-relevant conclusions from recent transmission modeling of VL, and presents new predictions for VL incidence under the interventions recommended by the WHO using the latest transmission models. Results: The model predictions suggest that the current WHO guidelines should be sufficient to reach the elimination target in areas that had medium VL endemicities (up to 5 VL cases per 10000 population per year) prior to the start of interventions. However, additional interventions, such as extending the WHO attack phase (intensive IRS and ACD), may be required to bring forward elimination in regions with high precontrol endemicities, depending on the relative infectiousness of different disease stages. Conclusions: The potential hurdle that asymptomatic and, in particular, post-kala-azar dermal leishmaniasis cases may pose to reaching and sustaining the target needs to be addressed. As VL incidence decreases, the pool of immunologically naive individuals will grow, creating the potential for new outbreaks

Broadband Monitoring Tracing the Evolution of the Jet and Disk in the Black Hole Candidate X-ray Binary MAXI J1659-152

MAXI J1659−152 was discovered on 2010 September 25 as a new X-ray transient, initially identified as a gamma-ray burst, but was later shown to be a new X-ray binary with a blackhole as the most likely compact object. Dips in the X-ray light curves have revealed that MAXI J1659−152 is the shortest period black hole candidate identified to date. Here we present the results of a large observing campaign at radio, submillimetre, near-infrared (nIR), optical and ultraviolet (UV) wavelengths. We have combined this very rich data set with the available X-ray observations to compile a broad-band picture of the evolution of this outburst. We have performed broad-band spectral modelling, demonstrating the presence of a spectral break at radio frequencies and a relationship between the radio spectrum and X-ray states. Also, we have determined physical parameters of the accretion disc and put them into context with respect to the other parameters of the binary system. Finally, we have investigated the radio–X-ray and nIR/optical/UV–X-ray correlations up to ∼3 yr after the outburst onset to examine the link between the jet and the accretion disc, and found that there is no significant jet contribution to the nIR emission when the source is in the soft or intermediate X-ray spectral state, consistent with our detection of the jet break at radio frequencies during these states