Visceral Leishmaniasis (VL) baseline clinical presentations and

association with initial treatment outcome among East African patientsThaddeus Egondi1, Monique Wasunna1, Robert Kimutai1, Raymond Omollo1, Lillian Were1, Menza Peninah1, Gabriel Omwalo1, Jane Mbui2, Fabiana

Alves F3, Séverine Blesson3, Alexandra Solomos3, Jorge Alvar3, Ahmed Musa4, Eltahir Khalil4, Asrat Hailu5, Joseph Olobo6

1Drugs for Neglected Diseases initiative, Nairobi, Kenya; 2Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; 3Drugs for Neglected Diseases initiative, Geneva, Switzerland; 4Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan; 5Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia; 6Faculty of

Medicine, Makerere University, Kampala, Uganda

Background:Visceral Leishmaniasis (VL) is among the most neglected of the tropical diseases,afflicting the poorest of the poor. It is characterized by irregular bouts of fever,weight loss, enlargement of the spleen and liver, and anaemia. It is highly endemicin the Indian subcontinent and in Eastern Africa. An estimated 200,000 to 400,000new cases of VL occur worldwide each year.

Clinical presentation of VL is dependent on many factors but mainly age, severity,and geographical location. Presence of concomitant secondary infections such asmalaria, tuberculosis, and pneumonia complicate the disease presentation. Inchildren, malnutrition, anaemia and subsequent impaired immunity increase thelikelihood of disease progression.

The assessment of VL cure is done at day 28-30 as initial cure or at 6 months asdefinitive cure. Therefore, understanding of baseline clinical symptoms isimportant in monitoring treatment response, and in identifying and reporting ofadverse events in VL trials.

Objectives: The objective of the data review is to identify the prevalent symptoms and clinicalsigns among VL patients enrolled in LEAP clinical trials, describe baseline clinicalpresentation of VL patients by country and region, and assess the change ofclinical symptoms and clinical signs from baseline to initial cure at 28-30 days.

WorldLeish Congress

16th – 20th May 2017, Toledo, Spain

Poster Number: C1671

Method:We reviewed data from five open-label randomized clinical trials conductedin the region by Drugs for Neglected Diseases initiative (DNDi) between 2004and 2015. The trials included non-HIV primary VL patients who presented fortreatment. The studies were conducted in Ethiopia, Kenya, Sudan, andUganda. Data were analyzed to estimate the proportion of different clinicalsymptoms at baseline and the association with initial treatment outcome.The analysis also included the distribution of multiple symptoms. Logisticregression was used to assess the likelihood of initial treatment failure fordifferent baseline symptoms and clinical signs.

Results:

Conclusion:Majority of participants in the LEAP clinical trials were male, children (4-14 years) and from Sudan. There is variation in clinical presentation of symptoms among VLpatients in the four countries. The most common baseline symptoms in addition to fever were abdominal swelling, weight loss, inguinal lymphadenopathy and mucosalpallor. These symptoms were however not significantly associated with initial treatment failure. The findings also point to fever clearance as a better indicator of initialtreatment success.

Study Recruitment period Sample size

Study drug (s)

LEAP 0104 2004-2009 1,107 • Paromomycin (PM)• Sodium stibogluconate (SSG) • PM+SSG combination

Ambi 0106 2008-2010 124 • AmBisome® single • multiple dose

LEAP 0208 2010-2012 151 • combination AmBisome® + SSG• combination AmBisome® + miltefosine • Miltefosine

Fexi VL001 2013-2014 14 • FexinidazoleLEAP 0714 2015 30 • Miltefosine allometric dosingTotal 2004-2015 1,426

List of LEAP clinical trials reviewed

40328.3% 288

20.2%

70249.2%

332.3%

79255.5%

38426.9%

23016.1%

201.4%

1,017, 71.3%

40928.7%

Ethiopia Kenya Sudan Uganda 4-14 15-24 25-44 45-60 Male Female

Country Age group (Years) Sex

63%

57%

56%

56%

79%

75%

80%

80%

68%

Muscle wasting

Inguinal lymphadinopathy

Petchial haemorrhages

Jaundice

Abdominal swelling

Mucosal pallor

Inguinal lymphadinopathy

Weight loss

Mucosal pallor

Eth

iop

iaK

en

ya/U

gan

da

Sud

an

46%

46%

38%

16%

15%

14%

22%

20%

19%

Weight loss

Abdominal swelling

Mucosal pallor

Petchial haemorrhages

Diarrhoea

Jaundice

Jaundice

Petchial haemorrhages

Skin lesions

Eth

iop

iaK

en

ya/U

gan

da

Sud

an

The research leading to these results has received funding from the European Union Seventh Framework Programme under grant agreement no. 305178; French Development Agency (AFD), France; Department for International Development (DFID), UK; Dutch Ministry of Foreign Affairs (DGIS), The Netherlands; Federal ministry of Education and Research (BMBF) through KFW, Germany; Ministry of Foreign Affairs and International Development, France; Medicor Foundation, Liechtenstein; Spanish Agency for International Development Cooperation (AECID), Spain; Médecins Sans Frontières; Swiss Agency for International Development and Cooperation (SDC), Switzerland; Other Private donors

Proportion with different symptoms by regionPatient Demographics

Baseline symptoms associated with initial treatment failure (D28-D30)

Multiple occurrence of symptoms by treatment outcome

Symptoms evolution from baseline to initial cure Day 28-30

Distribution of recruited patients by region, age and sex Most common symptoms Least common symptoms

Initial Cure Initial failure

0.4%

25.7%