Transcript Gametocyte carriage following SP treatment in

Drug Management for Malaria within LSDI region
Barnes K1, Kishuna A, Camba T, Streat EA, Lee C, Wilkins J, Durrheim DN
1 University
of Cape Town Division of Pharmacology
Abstract
Problem Statement: Early effective case management is a cornerstone of malaria control in the tropics.
This depends on effective management, reliable supply, and rational use of antimalarials. Stock-outs
of vital antimalarials result in disease progression to severe malaria and increased malaria
transmission. Irrational antimalarial use results in treatment failure and increased drug resistance
while fueling malaria transmission.
Objectives: To identify and address weaknesses in antimalarial drug management, supply, and use in
four LSDI areas in South Africa and southern Mozambique, where the public sector is in the process
of phasing in the implementation of artemisinin-based combination therapy.
Design: Before/after study with no control group.
Setting: Health care facilities in Mpumalanga and KwaZulu-Natal provinces, South Africa (low-intensity
malaria transmission), and in Namaacha and Matatuine districts, Mozambique (moderate-intensity
malaria transmission, following effective vector management).
Study Population: A sample of central-, provincial-, and district-level health care facilities
(Mpumalanga, 31; KwaZulu-Natal, 21; Namaacha, 7; Matatuine, 12).
Outcome Measures and Intervention: The Drug Management for Malaria (DMM) Manual was used as an
indicator-based approach to assess antimalarial management systems. Interventions were then
developed to address those problems that could be resolved by study participants in partnership
with ministries of health. The success of these interventions was then assessed by repeating
appropriate components of the DMM Manual.
Results: Problems identified in South Africa included the high purchase price paid for antimalarials when
compared with international median prices, and the fact that 40% of facilities in Mpumalanga did
not have inventory control systems. In KwaZulu-Natal, there were 164 health care facility days
without artemether-lumefantrine, resulting in 36.2% of patients being treated with ineffective
therapy, although this proportion decreased to 8% within three months of AL implementation. In
Mozambique, there were 258 health care facility days without vital antimalarials in Namaacha, but
few stockouts in Matatuine.[2] Inadequate patient information had been provided at all sites,
although the majority of patients and caregivers in Mozambique could accurately describe how to
take chloroquine. The effect of interventions to reduce antimalarial prices in South Africa, to
prevent stock-outs, and to improve patient education and adherence will be presented.
Conclusions: The DMM Manual is generally a useful tool for assessing antimalarial management, supply,
and use, although a few modifications were required for the study sites. It has been possible to
develop successful interventions to address some of the limitations identified.
Benefits of ACT depend on widespread coverage and rational use
1st line Rx with
Artemisinin-based
Combination
Therapy (ACT)
?
Treatment Coverage
Rational Use
?
Improve clinical cure rates
Delay emergence of
resistance
Reduce transmission
Objectives and study design
Objective
To optimise the implementation of artemisinin-based combination therapy,
by identifying and addressing weaknesses in drug management, availability
and use.
Study Sites:
Mozambique: Namaacha and Matatuine districts
South Africa: KwaZulu Natal and Mpumalanga Provinces
Study design: Cross-sectional; Before-after; No control group.
Based on Drug Management for Malaria Manual1
Pharmaceutical Management Review at National and Provincial levels
Health Care Facility Review

Public sector facilities (MPU = 16; KZN = 15; NAM = 7; MAT = 12)

Private sector facilities (MPU = 15; KZN = 6)

Structured Interviews, document review, physical inventory checks, case
record reviews, simulated purchases, direct observation, exit interviews
1Clark
M. Drug Management for Malaria Manual (Draft Version 2000). Published for USAID by the Rational Pharmaceutical
Management Project. Arlington, VA. Management Sciences for Health
Procurement…… SA vs. International median price
Mpumalanga
Chloroquine
KwaZulu Natal
3 times higher
2.5 times higher
Sulfadoxinepyrimethamine
7 times higher
13.5 times higher
Quinine
6 times higher
7.5 times higher
Primaquine
82 times higher
96 times higher
Co-artemether
Not available
1.5 times higher
Drug Availability
Mpumalanga KwaZulu
Natal
Matatuine
Namaacha
Average
availability of
unexpired
antimalarials
Public: 96%
(33-100%)
Public: 93%
(50-100%)
Public: 57%
(50-100%)
Level of
Stockouts
Depots (2)
Regional
hospital (1)
Health post
(1)
Health posts
(6)
Average Time
out of stock
1st line
0.6%
(37 days)
3.3%
(164 days)
0.18%
(4 days)
11.8
(258 days)
Public: 99%
(83-100%)
Private: 37% Private: 38%
(0-71%)
(29-57%)
Drug Use
Mpumalanga
KwaZulu Natal
Matatuine /
Namacha
Compliance with STGs
81.4%
(495/608)
60.8%
(162/267)
96%
357/415
% Treated with
ineffective therapy
2.5%
(15/608)
36.2%
(96/267)
NA
HCPs provided some
patient information
93.5%
(87/93)
62%
(31/50)
18%
(16/89)
Patients advised when
to return
57%
(53/93)
14%
(7/50)
0%
Patients advised on
potential adverse
events
29%
(27/93)
8%
(4/50)
0%
Patients correctly
describe how to take
treatment
69.5%
(57/82)
63.9%
(39/61)
78.7%
(70/89)
Interim Assessment of Interventions
Price Negotiations:

Artemether-lumefantrine
 ZAR 44.46/adult course = USD 6.39 i.e. 2.5X International Median price

Artesunate-SP: NA
Drug management

KZN MCP informed HCF that they covered initial Artemether-lumefantrine
costs so that SP stocks could be replaced by AL at no cost to HCF.
 By May 2001 93.4% of patients treated with artemether-lumefantrine.

Mpumalanga: Malaria Control Programme facilitating AS/SP management
and distribution while improved provincial systems being developed.

Southern Mozambique: Strengthened drug management system, focusing
on antimalarials, introduced in March 2004.
Training and education material

Specific treatment guidelines, training material, wallcharts, patient
education material developed for public and private sector healthcare
providers at each site, based on weaknesses identified in DMM .
 High compliance reported in patients followed up:
 Mpumalanga: 99% (636/638)
 KwaZulu Natal 94% (66/70)
Public Health Impact 1:
>85% decrease in malaria notifications in KwaZulu Natal
7000
6000
B: IRS southern Mozambique
5000
4000
3000
C: Artemether-lumefantrine
implemented
2000
1000
0
Ja
n9
M 7
ay
-9
Se 7
p9
Ja 7
n9
M 8
ay
-9
Se 8
p9
Ja 8
n9
M 9
ay
-9
Se 9
p9
Ja 9
n0
M 0
ay
-0
Se 0
p0
Ja 0
n0
M 1
ay
-0
Se 1
p01
Ja
n0
M 2
ay
-0
Se 2
p0
Ja 2
n0
M 3
ay
-0
Se 3
p03
Notified malaria cases
A: DDT reintroduced (traditional homesteads)
Public health impact 2:
47% decrease in Malaria Notifications in Mpumalanga
Month
Jan-04
Oct-03
Jul-03
Apr-03
Oct-02
Jul-02
Apr-02
Jan-02
Oct-01
Jul-01
Apr-01
Jan-01
Oct-00
Jul-00
Apr-00
2000
1500
1000
500
0
Jan-03
AS/SP implemented
3000
2500
Jan-00
Malaria cases
IRS southern Mozambique
Limitations of this study
Follow-up assessments to quantify the effectiveness of
interventions not completed.
Stock records not always adequate for quantifying stockouts.
Ethical concerns precluded conducting “simulation patient”
component of DMM in private sector.
Sample size limited for exit interviews and patient encounter
observations.
Treatment seeking and compliance not assessed through DMM
(but were assessed separately through household surveys and
focus group discussions).
Future Research Agenda
Quantitative evaluation of the effectiveness and sustainability
of each intervention to improve drug management, availability
and use, in both public and private sectors.
Qualitative evaluation of drug use patterns by healthcare
providers and patients.
Process and impact of integrating vertical drug supply
management of antimalarials into routine pharmaceutical
services.
Acknowledgements
The authors gratefully acknowledge the data collectors and the key informants, staff and
patients participating at each of the study sites. Financial support for piloting the DMM
Manual was kindly provided by Management Sciences for Health, and the UNDP / World
Bank / WHO Special Programme for Research and Training in tropical Diseases (TDR)
provides core funding for the SEACAT evaluation within which this study was nested.