Visceral leishmaniasis (VL) is a neglected tropical disease that is transmitted by female sandflies. VL is the most severe of the three forms of leishmaniasis and is almost always fatal without treatment. The World Health Organization (WHO) estimates there are between 50,000 to 90,000 new cases worldwide every year.

The review based on the Infectious Diseases Data Observatory (IDDO) VL library of published efficacy studies, described methodological aspect of design, conduct, analysis, and reporting from 89 studies published during 2000-2021.

The review highlighted substantial variations in definitions adopted for patient screening, disease diagnosis and therapeutic outcomes along with variability in inclusion and exclusion criteria adopted for patient enrolment.

One of the study authors Prabin Dahal said: “By studying existing literature, gaps in knowledge can be identified and research can be targeted at specific patient populations. For example, our review identified that patients with severe malnutrition or pregnant women were excluded in vast majority of the trials, highlighting limited evidence regarding treatment efficacy in this patient population.”

Prof Ahmed Musa, a globally recognised expert on Visceral Leishmaniasis clinical trials design and conduct from the University of Khartoum, Sudan, stated: “This review is timely and provides a comprehensive overview of the existing methodological practices in VL trials from the literature. This can serve as a useful source of information regarding different aspects of trial to inform future designs. This is particularly important to maximise existing resources as undertaking randomised trials for novel drug regimens in VL remains a major challenge due to financial constraints and operational difficulties.”

Read the full paper: ‘Design, conduct, analysis, and reporting of therapeutic efficacy studies in Visceral Leishmaniasis: A systematic review of published reports, 2000-2021’ 

Visceral leishmaniasis (VL) is the most severe of the three forms of leishmaniasis and is fatal without treatment. A blood transfusion is an important aspect of patient management but currently the trigger to carry out the procedure is poorly understood.

The 2010 World Health Organization (WHO) technical report on leishmaniasis suggests undertaking transfusion in patients with severe anaemia. Transfusion may also be indicated in cases of acute blood loss due to invasive procedures such as splenic aspiration. Despite the importance of transfusion in the management of VL patients, the actual practice in clinical trials is poorly reported and remains largely unclear.

Researchers used the IDDO VL clinical trials library and accessed 160 studies between 1980–2021. A total of 16 studies, with 3,459 patients, included a description of blood transfusion.  The review found the number of patients receiving a transfusion was explicitly reported in only 10 studies and of the 2,421 patients enrolled, 217 underwent transfusion. Of the 217 patients, for 58, transfusion occurred before the start of treatment for VL, in 46 it was during the treatment/follow-up phase, and for 113 patients the time was not mentioned.

Transfusion was initiated solely based on haemoglobin (Hb) measurement in nine studies, combining Hb measurement with an additional condition (epistaxis/poor health/clinical instability) in three studies, and the criteria was not mentioned in four studies. Hb threshold range for triggering transfusion was 3-8 g/dL.

One of the study authors Dr Prabin Dahal said: “We found data regarding blood transfusion in the treatment of VL remains largely unreported. In particular, the risk-benefit of transfusion practices in VL case management couldn’t be gauged from existing studies. Our research demonstrates the need for the research community to adopt a standardised methodology to generate and report transfusion related data. This type of data could help in assessing the impact of transfusion triggers on treatment outcomes.”

Prof Ahmed Musa, a globally recognised expert on visceral leishmaniasis from the University of Khartoum, Sudan said: “Patients with VL who require blood transfusion have low concentrations of cellular blood elements mainly red blood cells and plasma proteins including clotting factors. So, they commonly present with high-output heart failure or pending failure, bleeding and peripheral oedema due to low oncotic pressure of the blood and fatigue due to low oxygen tension at the tissue level leading to metabolic acidosis. Blood transfusion prevents the above-mentioned complications and can possibly accelerate the cure of visceral leishmaniasis. The selection of patients for blood transfusion is critical and should not depend on the level of haemoglobin only. This is because some patients adapt with low haemoglobin levels. This review provides an important evidence towards the need for incorporating clinical parameters as a part of transfusion trigger”.

Read the full paper Blood transfusion in the care of patients with visceral leishmaniasis: a review of practices in therapeutic efficacy studies

Find out more about accessing VL data

A new systematic scoping review of post-kala-azar dermal leishmaniasis (PKDL) studies found 56 studies published since 1973, with more than half of the studies dating from the last decade. Based on the relatively recent studies, which together include nearly 2,500 patients, the authors believe that the establishment of a PKDL data platform is feasible. The study is published in PLoS Neglected Tropical Diseases. 

PKDL is a dermatosis that can happen after successful visceral leishmaniasis (VL) treatment, manifesting in skin rashes that can be a reservoir of infection via sandfly vectors. 

PKDL is therefore a public health problem, because it means that patients otherwise successfully treated for visceral leishmaniasis can still transmit the disease. Current PKDL treatments are either expensive, need to be taken for a long time, and/or have safety concerns. 

“There are still a lot of gaps in current scientific knowledge of PKDL, including its pathophysiology and risk factors that can affect treatment outcome,” said the study’s corresponding author Dr Krishna Pandey, Director of the Indian Council of Medical Research-Rajendra memorial Research Institute of Medical Sciences (ICMR-RMRIMS). 

IDDO already hosts an established VL data platform, and Dr Pandey is also a member of the Visceral Leishmaniasis scientific advisory board at IDDO. This IDDO data platform has a critical mass of data from VL clinical trials conducted over the past 20 years. 

Dr Rishikesh Kumar, also from ICMR-RMRIMS and joint first author of the study, said, “Based on the number of studies we have identified in this review, we think that establishing a similar platform for PKDL is feasible, and will help address key knowledge gaps in PKDL.” 

“Creating such a platform will enable in-depth individual patient data analyses, enabling researchers to address new research questions from existing data,” added Dr Prabin Dahal, study author and statistics lead IDDO.

The researchers calculated that if the number of patients from non-randomised studies were pooled, an individual patient data platform would have a large set of data from studies exploring the efficacy and safety of the three main medications used for PKDL. 

“With the help of the global PKDL community and the right funding, we do think that a PKDL platform can be realised,” added IDDO’s Dr Sauman Singh, the paper’s first and corresponding author.

“This will allow a nuanced exploration of the safety and efficacy of PKDL drugs which can ultimately produce better treatments for patients,” said Professor Philippe Guerin, the review’s principal investigator and IDDO Director.

Read the review.