Artesunate+Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Falciparum Malaria (ASPF)

Efficacy and Safety of Artesunate+Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Malaria Control Centers in Nangarhar, Kunar, Thakhar and Faryab Provinces of Afghanistan

In Afghanistan, studies over the past 15 years have shown a high degree of Plasmodium falciparum resistance to chloroquine (80%) and more recently an increasing degree of resistance to sulfadoxine-pyrimethamine monotherapy (12%). In 2003 the high failure rate of chloroquine against falciparum malaria led the national malaria treatment programme to switch its recommended first line drug treatment for uncomplicated Plasmodium falciparum malaria to artemisinin-based combination therapy (ACT) in the form of Artesunate/Sulfadoxine-Pyrimethamine (AS+SP). Second line drug treatment is oral quinine (7 days). The aim of this study is to conduct ongoing monitoring of the efficacy of the new combination against P. falciparum in a group of sentinel sites in Afghanistan.

Study Overview

• Status: Completed
• Conditions: Falciparum Malaria
• Intervention / Treatment: Drug: artesunate plus sulfadoxine-pyrimethamine (AS+SP)

Detailed Description

The objective of the study is to assess the efficacy and safety of Artesunate/Sulfadoxine-Pyrimethamine (AS+SP) for the treatment of uncomplicated P. falciparum infections in Nangarhar, Kunar, Thakhar, Faryab malaria control centers in Afghanistan.

This is an observational study. Patients will receive the recommended treatment for P. falciparum malaria in Afghanistan (Nangarhar, Kunar, Thakhar, Faryab malaria control centers). The participants will be febrile children above six months of age and non-pregnant adults with confirmed uncomplicated P. falciparum infection. Patients will be treated with AS+SP according to standard dosing regimens. Clinical and parasitological parameters will be monitored over a 42-day follow-up period to evaluate drug efficacy. The study will be conducted during the transmission season of falciparum malaria, i.e. October 2009 to January 2010 and September-December, 2010. Patients will be assessed clinically and via laboratory tests, particularly focussing on whether recurrences are recrudescences of the original infection or reinfections. All bio-medical findings will be recorded in specific patient case record forms and the electronic form of analyzed data as well as a final report will be sent to WHO-Afghanistan and National malaria control program offices for further actions. The patients will receive reasonable transportation costs for follow-up visits as well as one insecticide treated bed-net at the end of enrolment. The results of this study will be used to assist the Ministry of Health of Afghanistan in assessing the current national treatment guidelines for uncomplicated P. falciparum malaria.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Afghanistan
  • Taloqan, Afghanistan
    • Provincial Malaria Control Centers (MRC)
  • Faryab
    • Maimana, Faryab, Afghanistan
      • Provincial Malaria Control Centers (MRC)
  • Kunar
    • Asadabad, Kunar, Afghanistan
      • Provincial Malaria Control Centers (MRC)
  • Nangarhar
    • Jalalabad, Nangarhar, Afghanistan
      • Provincial Malaria Control Centers (MRC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Febrile children (above six months of age) and non-pregnant adults with confirmed uncomplicated P. falciparum infection

Description

Inclusion:

• Age over six months.
• Mono-infection with P. falciparum detected by microscopy at a level of 500-150,000/µL asexual forms
• Presence of axillary or tympanic temperature ≥ 37.5 °C or oral or rectal temperature of ≥ 38 °C or history of fever during the past 24 h;
• ability to swallow oral medication;
• ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
• Informed consent from the patient or from a parent or guardian in the case of children under 18 years of age.

Exclusion criteria:

• Presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of the World Health Organization (WHO)
• Mixed or mono-infection with another Plasmodium species detected by microscopy
• Presence of severe malnutrition (defined as a child whose growth standard is below -3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm)
• Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
• Regular medication, which may interfere with antimalarial pharmacokinetics;
• History of hypersensitivity reactions or contraindications to any of the study medications;
• Female over 12 years of age

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
falciparum malaria; Febrile children (above six months of age) and non-pregnant adults with confirmed uncomplicated P. falciparum infection	Drug: artesunate plus sulfadoxine-pyrimethamine (AS+SP); artesunate plus sulfadoxine-pyrimethamine (AS+SP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients experiencing therapeutic failure	Proportion of patients experiencing therapeutic failure	42 days

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: World Health Organization; National Malaria and Leishmaniasis Control Program, Afghanistan

Publications and helpful links

General Publications

• Awab GR, Imwong M, Pukrittayakamee S, Alim F, Hanpithakpong W, Tarning J, Dondorp AM, Day NP, White NJ, Woodrow CJ. Clinical trials of artesunate plus sulfadoxine-pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction. Malar J. 2016 Feb 25;15:121. doi: 10.1186/s12936-016-1167-z.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: March 29, 2010
• First Submitted That Met QC Criteria: April 30, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): July 12, 2012
• Last Update Submitted That Met QC Criteria: July 11, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: falciparum malaria; artemisinin combination treatments
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Folic Acid Antagonists; Schistosomicides; Antiplatyhelmintic Agents; Anti-Infective Agents, Urinary; Renal Agents; Pyrimethamine; Artesunate; Sulfadoxine; Fanasil, pyrimethamine drug combination
• Other Study ID Numbers: BAKMAL1002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No