quality assurance in laboratory practice: the case with rapid diagnostic tests (rdts) for malaria

UNIZIK 1

In collaboration with

GUILD OF MEDICAL LABORATORY DIRECTORS

ANAMBRA STATE BRANCH NIGERIA

QUALITY ASSURANCE IN LABORATORY PRACTICE: THE CASE WITH RAPID DIAGNOSTIC TESTS (RDTs) FOR MALARIA

O. O. Ikpeze DVM, M.Sc, PhD, MRDN, FRHD

(Public Health Parasitologist & Entomologist)

Department of Parasitology and Entomology, Faculty of Biosciences,

Nnamdi Azikiwe University (UNIZIK) Awka, Nigeria

E-mail: [email protected]

mailto:[email protected]

Ikpeze, O.O (2013). Quality Assurance in Laboratory Practice: The case with Rapid Diagnostic Tests (RDTs) for Malaria. Continuing Programme Development Workshop/Training in Quality Essentials for South East Zone, Nigeria.

MSH-USAID in collaboration with Guild of Medical Laboratory Directors, Anambra State Branch, Nigeria. October 4-5, 2013, Chike Okoli Centre for Entrepreneurial Studies, Nnamdi Azikiwe University, Awka

2

Contents

Continuing Programme Development Workshop \ Training on Quality Assurance Page

Quality assurance in laboratory practice: The case with rapid diagnostic tests for malaria 1

Contents 2

Introduction 3

Need for quality, quality control and quality assurance programme 3

Good laboratory practice (GLP) 3

Standard operating procedures (SOPs) 3

Simple rules of GLP that will protect the integrity and quality of laboratory data used to back up

a product application 4

Malaria RDTs as a case study for quality assurance in medical laboratory practice 4

WHO recommendation on diagnosis before treatment for malaria 4

Role of Malaria Rapid Diagnostic Tests (RDTs) 4

RDT common formats (Cassette. Dipstick, Card and Hybrid) 5-6

Advantages of the RDT cassette 6

Components the RDT cassette 6

Ancillary items needed when RDTs are specified as ‘point of care tests’ 6

Factors that particularly influence the quality and diagnostic performance of RDTs 7

RDTs currently on the market are designed to target 7

Antigen targets of RDTs for malaria 7

Choice of RDT according to prevalence of malaria species in malaria endemic Zones 7-8

Summary of steps in selecting an appropriate RDT for the intended area of use 9

RDT vulnerability of RDTs and Quality Assurance 9

Vulnerability of various components of malaria RDT kits that affect quality of RDTs 10

Vulnerability in procuring malaria RDT kits that affect quality of RDTs 11

Checklist on Standard operating procedures (SOPs) for malaria RDT 12

Good laboratory practice (GLP) for malaria RDT 13

Malaria RDT interpretation and reporting 14

Reading of Negative, Invalid and Positive results of a malaria RDT 15

Actions following positive and negative results RDTs results 16

Brain-storming activities on Workshop/Training on quality assurance for malaria RDTs 16-17

Summary 18

References 18



3

Introduction

This Workshop/ Training Section on Quality Assurance in Medical Laboratory Practice will focus

mainly on:

Test Facility Management

Requirements of the Test Facility

Equipment Selection, Procurement, Receipt, Handling, and Storage

Standard Operating Procedures and Good Laboratory Practice

Interpretation and Reporting of Test Results

Need for Quality, Quality Control and Quality Assurance Programme

Quality is the Capability to Systematically Produce the Same Product to meet the Same

Specifications all the Time

Quality Control is the Process, Procedures and Authority used to Accept or Reject all drug

product containers, closures, in-process materials, packaging material, labeling and drug

products and the Authority to review Production Records to Assure that no Errors have

occurred, that they have been Fully Investigated

Quality Assurance Programme is meant to be the Control of a number of Technical Features

and Specifications which are needed to ensure the Integrity of the System and the Quality of

the Data Generated. Quality Assurance Programme guarantee that studies performed comply

with Principles of Good Laboratory Practice. Purchasing and testing should be handled by a

quality assurance program (Lori et al., 2009). In order to guarantee the quality of the data,

appropriate conditions should be established and maintained for the care of biological test

system.

Good Laboratory Practice (GLP) GLP is “a Quality System related with the Organizational Process and the Conditions under which

non-Clinical Health and Environmental Safety Studies are:

Planned

Performed

Monitored

Recorded

Archived

Reported

The principles of good laboratory practice (GLP) are to support the development of quality and

validity of test data used for determining the safety of chemicals and chemicals product (Clasby,

2005). Good Laboratory Practice is based on four principles:

The Management

The Quality Assurance

The Study Director

The National Compliance Monitoring Authority.

In a study for compliance with GLP, the most important aspects may be characterized as

“suitability”, “capacity” and “integrity” (OECD, 1998)

Standard Operating Procedures (SOPs)

Written procedures for a Laboratory’s Program

Approved Protocols indicating Test Objectives and Methods

SOPs are intended to Ensure the Quality and Integrity of the Data Generated by the Test

Facility

The Test Facility should have a documented Quality Assurance Programme to Guarantee that

studies performed Comply with the Principles of GLP



4

Simple Rules of GLP that will protect the Integrity and Quality of Laboratory Data used to

Back Up a Product Application (Jean Cobb, 2007)

Say what you Do with written Standard Operating Procedures, SOPs)

Do what you Say by following the SOPs

Prove what you Do with Good Record Keeping

Malaria RDTs as a case study for quality assurance in medical laboratory practice Since malaria remains an important endemic disease in sub-Saharan Africa, the selection, acquisition, and

application of an appropriate Malaria Rapid Diagnostic Test (RDT) for an intended area of use will serve as

useful illustration of the principles of Quality Assurance in Medical Laboratory Practice outlined above.

Malaria is caused by a protozoan parasite of the genus Plasmodium

The infection is transmitted to humans through the bite of infected female anopheline

mosquitoes

All malaria infections initially present as a febrile illness

Malaria is most prevalent in Africa and Asia, affecting approximately 225 million people and

causing 781 000 deaths in 2009

World Health Organization (WHO) Recommendation on Diagnosis before Treatment for

Malaria (WHO, 2010)

Prompt parasitological confirmation by Microscopy or RDTs in all suspected cases of malaria

before treatment is started

Treatment solely on the basis of clinical suspicion should be considered only when a

parasitological diagnosis is not accessible

Rapid, Accurate Diagnosis and Appropriate Treatment are crucial, as a delay of even a few

hours in the management of malaria may have lethal consequences

Role of Malaria Rapid Diagnostic Tests

RDTs are adequate to diagnose malaria in febrile patients

Demonstration of the presence of malaria parasites is advised before treatment with

antimalarial medicines

Diagnosis based solely on clinical symptoms is of poor accuracy and leads to over diagnosis of

malaria, waste of antimalarial medicines, an increased frequency of adverse side-effects and

increased drug pressure on resistant parasites

Early exclusion of malaria can enhance early diagnosis and appropriate management of other,

potentially severe causes of fever

Parasitological diagnosis improves malaria case detection and surveillance systems

RDTs, sometimes called ‘Rapid Diagnostic Devices’ Facilitate the diagnosis of malaria by

providing evidence of the presence of Plasmodium-specific proteins (antigens) in human blood

Many products are available on the market but some can detect only one species (e.g. only P.

falciparum), while others also detect further species of the parasite (i.e. P. vivax, P. malariae

and P. ovale) in different combinations

Most RDTs detect malaria species-specific antigens2 produced by parasites present in the

blood of infected individuals

Enough blood for the diagnostic test can usually be obtained from a finger-prick

The RDTs detect an Antigen of the parasite and not the Antibodies due to the Human

Immunological reaction, so result is not affected by Impaired Immunity (due to e.g., HIV

Infection or Malnutrition).



5

RDTs COMMON FORMATS

Cassette The Nitrocellulose Strip is encased in a Plastic Cassette, with Key Features:

Control Line (C)

Test Line (T)

Well (S) for Blood Sample

Buffer Solution (A)

Dipstick The Nitrocellulose Strip is placed in Wells containing Blood and Buffer

Card The Nitrocellulose Strip is mounted on a Card.

Blood Sample and Buffer Solution are placed on Absorptive Pads

The Card is closed for Reading

Open Card Closed Card



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Hybrid formats (which combine different elements of them) Combines elements of Cassettes and Dipsticks

The Strip is dipped into the Wells

Then placed into the Cassette for Reading

Blood Sample and Buffer Solution Wells

RDTs for malaria respond to testing needs at different levels of the health care system. They can be

used to confirm a diagnosis of malaria at a peripheral health facility where microscopy is not

available, or in facilities with laboratory services, to reduce the workload of malaria microscopy or to

confirm a diagnosis at times when microscopy services are not available.

Advantages of the RDT Cassette

Although Cassettes and Cards tend to be more expensive

They are Simpler to use

Require less training (particularly of minimally trained, non-laboratory users in remote

locations)

Are Cleaner and Safer

And may require fewer Ancillary Materials (e.g., Tubes)

The Components of the Cassette

A plastic case

A test strip, comprising the nitrocellulose strip and the materials bound to it (inside the

cartridge)

A sample well (into which blood is transferred)

A buffer well (into which drops of buffer solution are placed)

A ‘results window’ (in which test and control lines appear).

In some RDTs, one well is used for both the sample and the buffer

Ancillary Items needed when RDTs are specified as ‘Point of Care Tests’ A sterile Lancet (in the box)

A blood collection device (in the box or pouch)

A buffer bottle and dropper (in the box or pouch)

An alcohol swab (in the box)

Appropriate desiccants (if specified). Absence of desiccant from a Manufacturer’s

Specification and Product is not a deficiency, as specific RDTs may not require a desiccant

Gloves and safe disposal kits (e.g. sharps boxes) are bought and provided separately

Clocks (watches, mobile phones) are generally already available in health facilities

Minimum–maximum thermometers may be required for monitoring storage temperature

The Dipstick Format requires a Well or Tube for mixing Blood and Buffer, into which the

Immuno-Chromatographic Nitrocellulose Test Strip is dipped. This Facility is in-built in the

Card and Cassette.



7

Factors that particularly influence the Quality & Diagnostic Performance of RDTS

Quality of the manufacturing process

Antigen threshold the RDT is designed to detect,

Species of parasite,

Density and strain of parasites present,

Concentration of target antigen,

Exposure of the test to extreme temperatures and relative humidity,

Technique used in performing the test, and

Correct interpretation of the results.

RDTs currently on the market are designed to target

P. Falciparum (Pf)

P. vivax (Pv)

P. malariae (Pm)

P. ovale (Po)

all of them (pan)

or only the non-falciparum Malaria species (Pvom) in the following combinations

Pf only

Pf/pan

Pf/Pv

Pf/Pvom

Pf/pan/Pv

Pv only

pan only

Antigen targets of rapid diagnostic tests for malaria Parasite species HRP2 Aldolase

pLDH pLDH-pf pLDH-pan pLDH-Pvom pLDH-pv

P. falciparum x x x x

P. vivax x x x x

P. malariae x x x

P. ovale x x x

Histidine rich protein-2 (HRP2)

Plasmodium lactate dehydrogenase specific for P. falciparum (pLDH-Pf)

Plasmodium lactate dehydrogenase common to all species (pLDH-pan)

Plasmodium lactate dehydrogenase specific for P. vivax (pLDH-Pv)

Plasmodium lactate dehydrogenase specific for P. vivax, P. ovale and P. malariae (pLDH-Pvom)

Aldolase

Choice of Rapid Diagnostic Test according to Prevalence of Malaria species in Malaria Endemic Zones

(WHO 2011)

Zone 1 Prevalent parasites Recommended RDT Rationale

Most areas of

sub-Saharan

Africa and

lowland Papua

New Guinea

Prevalent parasites: predominantly for P. falciparum

with rare non falciparum

RDTs that detect only

P. falciparum are

generally preferable.

Generally better thermal

stability

Malaria infections: majority of

non-falciparum infections occur as

mixed P. falciparum infections,

rarely as single-species infections

RDT target antigens:

• HRP2

• pLDH-pf

HRP2-detecting RDTs in

general are likely to be more

sensitive than pLDH- and

aldolase-detecting RDTs for

P. falciparum infections in

most environments



8


Most endemic areas

of Asia and the

Americas and

isolated areas in the

Horn of Africa

Prevalent parasites:

P. falciparum and non-

falciparum

Combination RDTs that

detect all species and

distinguish P. falciparum

from non-falciparum

infections

HRP2-detecting tests in

general are more

sensitive than pLDH

and aldolase-detecting

tests for P. falciparum

infection in most areas.

Some RDTs are highly

sensitive for detecting

both P. falciparum and

P. vivax. Sensitivity for

the detection of P. ovale

and P. malariae is

generally lower.

(Inappropriate to use

RDTs that detect only P.

falciparum, as this would

require that RDT

Negative patients are

treated with chloroquine

for possible P. vivax

infection, instead of

being recognized as non-

malaria cases)

First-line treatment for

P. falciparum and for

non- falciparum is

different; therefore it is

important to choose a

test that distinguishes

them.


• HRP2, aldolase

• HRP2, pLDH-pan

• HRP2, pLDH-pv

• HRP2, pLDH-pvom

• HRP2, pLDH-pan,

pLDH-pv

• pLDH-pf, pLDH-pan

• pLDH-pf, pLDH-pv

• pLDH-pf, pLDH-pvom

Low-density non-

falciparum

infections may be

missed.


Mainly vivax

Only areas of East

Asia, central Asia and

South America, and

some highland areas

elsewhere

Prevalent parasites:

non-falciparum malaria

only

RDTs that detect non-

falciparum species alone

are appropriate

(panspecific, or

P. vivax-specific if only

species).

In several countries,

falciparum malaria is not

present, and treatment of

all

non-falciparum

malaria infections is

similar. In these areas, use

of pan-specific RDT s is

appropriate.

Malaria infections:

generally P. vivax malaria

only


• aldolase

• pLD H-pan

• pLD H-Pv

• pLD H-Pvom



9

Summary of Steps in Selecting an Appropriate RDT for the Intended Area of Use

Step 1

Target Parasite Species and

Antigens

Prevalence of Malaria species

Zone 1

• HRP 2

• pLD H-Pf

Zone 2

• HRP 2, Aldolase

• HRP 2, pLD H-pan

• HRP 2, pLD H-Pv

• HRP 2, pLD H-Pvom

• HRP 2, pLD H-pan, pLD H-Pv

• pLD H-Pf, pLD H-pan

• pLD H-Pf, pLD H-Pv

• pLD H-Pf, pLD H-Pvom

Zone 3

• Aldolase

• pLD H-pan

• pLD H-Pv

• pLD H-Pvom

Step2

Performance of RDTs WHO RDT Product Testing Programme

• Panel Detection Score

• False-Positive Rate

• Invalid Rate

• Ease of Use

• Heat Stability

Sensitivity and Specificity

Step 3

WHO Recommendations

and National Treatment

Guidelines

WHO Recommended Selection Criteria

• Based on WHO RDT Product Testing Programme

• Price

• Lot Testing

National Treatment Guidelines

Step 4

Experience in use of RDTs

and Availability

In-Country Experience

Step 5

Additional Considerations Additional Considerations

• Supplier’s Production Capacity and Lead Times

• Storage Conditions, Delivery Schedules and Shelf Life

• Registration Requirements

• Budget Requirements

Vulnerability of RDT and Quality Assurance Several components of RDTs that are essential to good diagnostic performance are subject to

Vulnerability, which, depending on the situation, requires Risk Management.

If, for instance, the RDT is vulnerable to High Temperatures, it should be used only in areas

with a Temperate Climate and be Shiped under Controlled Temperature.

Depending on the level of risk, systems such as Product and Lot Testing can minimize the

Intrinsic Vulnerability of the RDT and the Risks related to Procurement.



10

Vulnerability of Various Components of Malaria RDT Kits affects Quality of RDTs

Component Characteristics that can make a Product Vulnerable

1 Nitrocellulose Membrane Variation in pore size (can affect flow of antibody–antigen

complex and clearance of blood)

2 Signal Antibody Stability of conjugation to label (e.g. colloidal gold).

Amount of antibody on strip (affects test line intensity).

Purity.

Innate ability of selected antibody to bind specific target of

interest and not others

Antibody stability.

Consistency and variability in manufacture

3 Capture Antibody Ability to adhere to membrane.

Amount of antibody on strip (affects test line intensity).

Affinity of the selected antibody for the target antigen.

Specificity of the antibody for the target antigen.

Antibody stability.

Consistency and variability in manufacture

4 Buffer, Lysing Agent and

Additives

Composition (can affect the stability of antibodies, neutralize

agents that cause false- positive reactions and control red cell

lysis to release antigens).

Viscosity (can affect assay reaction rate).

Variation in composition can affect RDT performance

(antigen–antibody binding

Required volumes, packaging and unit dose of buffers can

vary among RDT s.

The shelf life of the buffer may be different from that of the

RDT

5 Cassette Housing Placing of sample well controls blood contact with the signal

antibody and varies by device.

Compression of nitrocellulose membrane (can inhibit flow).

Presence, absence and placement of evaporation holes (can

affect flow and reduce late back flow) varies by device

6 Packaging Packaging (must exclude humidity to avoid degradation of

RDT )

7 Buffer Volume Number of drops of buffer solution (controls flow and

sometimes lysis but does not control the speed of

development of the results)

8 Blood Volume Amount of blood transferred to the RDT can

Affect the availability of the target antigens if low volume,

Reduce the clearance of blood, reducing clarity of results, if

excess volume



11

Vulnerability in Procuring Malaria RDT Kits affects Quality of RDTS

Steps Procurement Vulnerability

1 Selecting an

Appropriate

RDT

Selecting HPR 2-detecting RDTs for Areas of Prevalent.

falciparum and non-falciparum malaria.

Selecting combination RDT s for areas with predominantly

falciparum malaria

2 Quantification Overestimating requirements.

Underestimating requirements

3 Budgeting Underestimating costs of transport, storage and distribution.

Poor compliance with procedural requirements of funding

agencies

4 Technical

Specifications

Lack of specifications on Diagnostic Performance requirements.

Missing information on RDT Format.

Missing Thermal Stability requirements.

Missing requirements for completeness of Kit

5 Procurement

Method

Open tender, leading to multiple offers not relevant to conditions

of use and extended bid evaluation timelines.

Direct procurement from limited suppliers, leading to limited

choices and risks for high prices and delays

6 Inviting Tenders Limited use of the assessment made by the WHO product testing

programme

7 Contracts Missing specifications on manufacturer’s liability for replacement

of delivery of defective products.

No reference to lot testing and its performance requirements.

No specification of temperature requirements for transport and

storage.

No staggering of deliveries.

Wrong timing of deliveries in relation to malaria transmission

season or training of health workers

8 Evaluating Bid

Response

Assessment of diagnostic performance based on insufficient

documentation submitted by the manufacturer.

No involvement of malaria RDT experts in assessing compliance

of the product to technical specifications set in the tender.

No submission or evaluation of RDT samples submitted by

manufacturers.

Poor evaluation of production capacity and financial viability of

the supplier

9 Lot testing Post-shipment lot testing performed after arrival in the country of

use without specification of liability for replacement in

contractual agreements with manufacturer

10 Transport and Port

clearance

No specifications to forwarding agent for temperature

requirements during transport by air or sea.

No specifications to clearing agent for temperature requirements

during port clearance and customs procedures.

Delays and demurrage costs due to insufficient preparation of port

clearance procedures



12

Checklist on Standard Operating Procedures (SOPs) for Malaria RDTs

Check the expiry date on the package.

Put on gloves before beginning. Use a new pair of gloves for each patient.

Open the RDT package and remove the contents. The blood-transfer device — it could be a

capillary tube, straw, loop, pipette or other device — is used to collect blood and transfer it to

the test cassette. (Once the packet is opened, the ‘desiccant’ sachet which absorbs moisture

from the atmosphere in the package should be discarded.) The test cassette is used to conduct

the test. The square hole labeled ‘A’ is where you add the blood. The round hole labeled ‘B’ is

where you add the buffer.

Write the patient’s name on the cassette

Open the alcohol swab and clean the patient’s third or fourth finger with alcohol

After cleaning the finger with the alcohol swab, the finger must be allowed to air dry. After

using the alcohol swab, place it on its wrapper and set it aside on the table. You will use it

again to stop the bleeding after you collect the patient’s blood

Once the patient’s finger is dry, open the lancet. Prick the patient’s finger, preferably towards

the side of the pulp (ball) of the finger. Discard the lancet in a sharps-only container

immediately after using it

Turn the ‘patient’s’ arm so their palm is facing downward. Squeeze the pricked finger and

allow a drop to well up below the finger tip. Use the loop or capillary tube or straw or the

pipette to collect the drop from underneath.

Once you have collected a sufficient amount of blood, you may hand the alcohol swab back to

the patient and show him or her how to use it to stop the bleeding.

Use the device (capillary tube, straw, loop, pipette or other) to add the drop of blood to the

sample window (square hole labeled with the letter A). The blood needs to reach and be

absorbed by the pad at the base of the square hole. If the blood is mostly deposited on the

plastic edges of the well, but does not reach the pad, the test will not work correctly. Deposit

the blood in the correct place using the capillary tube, straw, loop, pipette or other. Adding too

much or too little blood can cause the test to give an invalid result or be difficult to read

Add the buffer solution to the round hole labeled B. Hold the bottle vertically when adding the

buffer solution, This ensures the correct drop size

Wait for the correct duration of time (15 or 20 minutes) after adding buffer before reading the

test results

Discard the blood-collection device (e.g. capillary tube) safely after use

Remove and discard your gloves at this time. To avoid possible contamination, the used gloves

should be discarded in the non-sharps container before you do anything else.



13

Good Laboratory Practice (GLP) for Malaria RDTs

Put on new gloves before starting each RDT

Write the patient’s name on the cassette

Clean the patient’s finger with alcohol

The lancet used must be put in a ‘sharps only’

safety box

Drawing Blood with a Capillary Tube

Adding Blood to the RDT Cassette

Adding the Buffer Solution



14

Malaria RDT Interpretation and Reporting

Results Control

Line ‘C’

Test Lines

T1

P. falciparum

T2

P. vivax

Negative

Positive : P. falciparum only

Positive : P. falciparum only or mixed with other species

Positive : non-P. falciparum (P. vivax)

Invalid

Invalid

Invalid



15

Reading of Negative, Invalid and Positive Results of a Malaria RDT

Negative: No line in T1 or T2 but a line in C

Invalid: No line in T1 or T2 and no line in C means Test is damaged

Invalid: Line in T1 or T2 and no line in C

Pf +: Line in T1 and C

Pf +: Line in T1 very faint and Line in C

Non-Pf +: Line in T2 and a line in C

(P. vivax, P. ovale, P. malariae or mixed infection of these)

Pf + or Mixed infection: Line in T1 and T2 and a line in C



16

Actions following Positive and Negative RDTs Results

Before using the RDT, ask the patient if he or she has recently taken anti-malaria

medication

If the patient has taken a complete course of anti-malaria medication in the last 5–14 days, a

positive RDT result may be misleading

It may be necessary to refer the patient to a health centre with a laboratory for further

testing using a microscope

If fever persists a few days after a negative RDT result and other appropriate management has

been applied

Re-test the patient with another RDT, as RDTs can sometimes miss early malaria

infections

If the patient has not recently taken anti-malarial medication and the test result is positive

Treat the person for malaria according to national guidelines

If a patient has fever and the second test result is still negative

Refer them to a higher level health centre

Brain-storming activities Workshop/Training on Quality Assurance for Malaria RDTs

If a package has been open for some time before the RDT is used, the RDT may be damaged

and can give an invalid (false) result

Why should this invalid result not be trusted?

What should you do if the RDT Result is Invalid?

You are confronted with more than 20 fever cases in the community around your health post at

the same time, and you will test all patients with RDTs for malaria

How do you avoid any mix-up of results?

RDTs cannot test how many malaria parasites there are in the blood

RDTs do not detect actual parasites

What do they do?

They can only test whether parasites are present or absent

They detect parasite antigens, and some parasite antigens can remain in the blood for at least

two weeks after the parasites have been killed by drugs

An RDT used within two weeks of drug treatment may still detect parasite antigens and so give

a positive result for malaria infection, even if the person no longer has parasites, because the

parasites have been killed by the drugs

Why should this positive result not be trusted?

A five-year-old child with fever tested positive for falciparum malaria with an RDT. Before

treatment, you have to check for signs of severe malaria in case he needs a referral

What are the signs and symptoms you would look for?

You treated the five-year-old child positive for falciparum malaria according to the national

guideline. The child comes back after three days with fever, and tested positive for falciparum

malaria again with an RDT

What will be your next action?

How can you perform RDTs for malaria safely and effectively?

How can you avoid contaminating yourself and your patients with another person’s

blood?

How can you record the results accurately?

The most important symptom of malaria is fever (or a history of fever within the last two to

three days)

An attack often begins with shivering (body shaking)

This is followed by a period of fever, and finally there is profuse sweating



17

During an attack the patient often complains of headache and pains in the back, joints, and all

over the body

There may also be loss of appetite, vomiting, and diarrhoea

The patient may feel better the next day, but may have another attack the day after that, and so

on

What may happen if untreated or inadequately treated?

Malaria can result in weeks of poor health, anaemia and general weakness

Some patients rapidly become very ill and may die within a few days

• A four-year-old patient is presented to you with fever of 38°C. The child also has poor

appetite, is weak and has yellowish eyes.

What other questions should you ask his mother or guardian to try and find out if the

child is suffering from malaria?

What are the reasons for your answer?

You should try to find out how long the child has had fever Whether the fever has alternated with a stage of sweating, followed by a cold, shivering stage

A child with a fever could have malaria, but fever can also be a symptom of other diseases

However, a child who has gone through stages of fever, sweating and shivering is much more

likely to be suffering from malaria, as this is the typical pattern of malarial fever attacks

Why do you think children are at higher risk of getting severely ill or dying of malaria

than adults? Children have a much weaker immunity against malaria

Immunity develops after repeated exposures to the malaria parasite and this takes time

How do RDTs work? Malaria parasites produce proteins called antigens. RDTs detect malaria antigens, so if they

are present, the person will test positive. If malaria antigens are not present, the person will test

negative.

• What are the reasons for using RDTs? RDTs enable you to find out if a fever is really caused by malaria rather than by other illnesses.

The information provided by RDTs is able to tell quickly whether a patient with fever has

malaria or not ensures that the patient can receive the correct treatment.

In this way provide a more accurate diagnosis than a clinical or presumptive diagnosis.

If a patient does have malaria, knowing which parasite may be involved is important, as some

malaria parasites are more dangerous than others and require more urgent treatment.

RDTs give results in about 15–20 minutes, so a patient with malaria can begin treatment right

away.

RDTs do not require any expensive or complicated equipment and can be used by you in the

patient’s home.

You should be able to learn to use RDTs in just a few hours in your practical training

programme.



18

Summary

The concerns of this Workshop/Training may be summarized as follows:

Test Facility Management

Requirements of the Test Facility

Equipment Selection, Procurement, Receipt, Handling, and Storage

Standard Operating Procedures and Good Laboratory Practice

Interpretation and Reporting of Test Results

However, sequence of Steps for Procuring Quality-Assured RDTs requires that all the responsible

bodies are well coordinated and that there is prompt, transparent information flow so that all the steps

are executed in harmony.

Steps Description Responsible Bodies

1 Requirements for selecting RDTs National malaria control Programme

2 Estimating needs National malaria control programme, quantification

and forecasting team, laboratory department,

procurement department

3 Budgeting and budget components National malaria control Programme

4 Defining technical specifications National malaria control Programme

5 Procurement method and tender

documents

Procurement unit team members, with input on

technical and quality aspects from national malaria

control programme

6 Inviting tenders Procurement management unit in consultation with

regulatory authority

7 Evaluating bids and awarding

contracts

Procurement management unit and national malaria

control programme

8 Quality assurance in procurement and

use

Procurement management unit and national malaria

control programme

9 Quality control by lot testing Procurement management unit, quality assurance

officer

10 Transport, port clearance and receipt Procurement management unit, supply chain

manager

11 Monitoring Procurement management unit and national malaria

control programme

12 Continuous improvement Procurement management unit and national malaria

control programme

References

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http://www.docstoc.com/docs/18191459/Good-Laboratory-Practices.

Lori Gladney, Osakwe Izabella, Ford Endia (2009). Good Laboratory Practices. Available at:

http://science.kennesaw.edu/~jhendrix/regs/GLP.

OECD (1998). OECD series on Principles of Good Laboratory Practice and Compliance Monitoring.

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http://www.oecd.org/officialdocuments/displaydocumentpdf/

quality assurance in laboratory practice: the case with rapid diagnostic tests (rdts) for malaria

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