Source: tdr-scientists@who.ch
WHO/TDR Newsletter Feb.99 - Research needed
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Combinations to combat resistance
In our last issue, reference was made to an initiative to combat anti-
malarial drug resistance (TDRnews, 1998, 57: 7). Since activities under
the initiative began in July 1998, three studies have been conducted
and completed: a pharmacokinetic interaction study, a pilot clinical
study, and a double-blinded clinical study of a combination of sul-
phadoxine/pyrimethamine + artesunate. Studies with chloroquine or amo-
diaquine are about to start; and a meta-analysis is planned for late
1999 - as soon as data on the over 4000 patients to be enrolled in the
various studies become available.
Upon completion of this first 'proof-of-principle' phase, the intention
is to select combinations of drugs to be tested in large, longitudinal,
population-based studies. Centres interested in carrying out community-
based studies to test the hypothesis that antimalarial drug combina-
tions can delay or contain the emergence of resistance should contact:
Dr P. Olliaro
Manager, Working Group on Research on Drug Resistance and Policies
Tel: +41-22-791-3734
Fax: +41-22-791-4854
mailto:olliarop@who.int
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Molecular targets for filariases drug discovery
Studies on the genome and biochemistry of Onchocerca volvulus, Wucher-
eria bancrofti and Brugia malayi have led to the identification of a
myriad of enzymes, receptors, and metabolic pathways as potential tar-
gets for chemotherapy. Modern drug discovery relies more on molecular
targets such as these than it does on random screening. Molecular tar-
gets in filarial diseases were the subject of a meeting of researchers
from both public and private sectors (universities, institutes and bio-
logical laboratories) in Africa, America, Australia and Europe held in
WHO/HQ in November 1998. The challenge was to identify potential chemo-
therapeutic targets and novel strategies from among all the candidates.
There were 21 presentations that addressed, in this context, the stage
of parasite life cycle, biological processes, and the specificity and
uniqueness of possible targets as well as the availability of infra-
structures (crystallography, genomics, proteomics, etc.) that could fa-
cilitate the drug discovery process.
TDR filarial drug discovery is now becoming more targeted. It is aimed
at discovering new macrofilaricides, discovering anthelmintics, which
sterilise adult female worms, and identifying new microfilaricides to
combat any emergence of ivermectin resistance. It includes work on ex-
isting drugs such as antibiotics, anti-fungals and anti-parasitic
agents whose spectra of activity seem likely to be extendable. Calls
for grant proposals for filarial drug discovery research have already
been sent out and the first grants will be disbursed by mid-1999
through the Drug Discovery Research Steering Committee, which meets in
Geneva, April 26-30. The closing date is February 28. Anybody inter-
ested in this area should contact:
Janis Lazdin
Manager, Filariasis R&D
Tel: +41-22-791-3818/2111
Fax: +41-22-791-4854
mailto:lazdinsj@who.int
or
Rob Ridley
Manager, Steering Committee on Drug Discovery Research
Tel: +41-22-791-3884
Fax: +41-22-791-4854
mailto:ridleyr@who.int
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African Trypanosomiasis
The control of African trypanosomiasis is based on case detection,
treatment of infected persons and vector control. Medical surveillance
provides an indication of the local epidemiological situation as an
early warning of increases in incidence. It allows reduction of the
reservoir of infection in humans and early detection and treatment of
patients.
The research needed in this respect is as follows:
Studies to compare the sensitivity and specificity of the CIATT with
the CATT. Multicentre prospective cohort studies in patients over 16
years who are CATT-positive/parasite negative and those who are CATT-
negative. Multicentre clinicals trial of patients with parasitologi-
cally confirmed Human African Trypanosomiasis with normal cerebrospinal
fluid (CSF) using 3 vs. 7 injections of pentamidine. Development of a
protocol to determine the epidemiological effect of treatment of sero-
positive but apparently aparasitaemic patients. Prediction of cost-
effectiveness of control strategies based on treatment of seropositive
but apparently aparasitaemic patients.
Those interested should contact the Task Force Manager to request ap-
plication forms:
Dr Alvaro Moncayo
Manager, Task Force on Operational Research on African Trypanosomiasis
TDR,
World Health Organization
CH-1211 Geneva 27
Tel: +41-22-791-3826/3897/3794
Fax: +41-22-791-4854
mailto:moncayoa@who.ch
N.B.: The entries to list of TDR Calls for proposals, and TDR Steering
Committee Workplans, appear at TDR Homepage:
http://www.who.int/tdr
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