Advanced pharmaceutical care and anti microbial resistance

MODULE : APPLIED THERAPEUTICS
COMP: ADVANCED PHARMACEUTICAL CARE
ABD ANTI-MICROBIAL RESISTANCE
ADVANCED PHARMACEUTICAL CARE
 Ethical Considerations In Pharmacy Practice
 Acquiring The Knowledge You Need To Practice
 Standards Of Practice For Pharmaceutical Care
 Establishment Of A New Pharmaceutical Care Practice In Rwanda
ANTI-MICROBIAL RESISTANCE
 Viral Drug Resistances Phenomena (HIV)
 Bacterial Drug Resistances Phenomena Anti-TB Drug Resistance
 Plasmodial Resistances Phenomena
COLLEGE OF MEDICINE AND HEALTH SCIENCES
SCHOOL OF MEDICINES AND PHARMACY
DEPARTMENT OF PHARMACY

PHARMACEUTICAL CARE
ETHICAL CONSIDERATIONS IN PHARMACY PRACTICE
Advanced Pharmaceutical Care
Designed and Moderated
by Einstein ,MINANI Theobald
Student , Year 2018, PHARMACY YEAR 3, Level 4

Introduction
Pharmacy ethics is a branch of medical ethics that provides a
framework for pharmacists to use in resolving questions about
what ought to be done in pharmacy practice.
To conduct an ethical exercise requires that one ask normative
questions about what should be done, rather than that one
ask only legal questions about what must be done, or
empirical questions about why something is done.
 To address a question from an ethical perspective requires that
one reflect on the morality of a situation; that one ask what will
be the impact on others of one’s own action and whether one
can justify one’s action to a higher authority3

4
Introduction con’t ethical theories
Modern medical ethics has its roots in two classical theories
known as deontology and utilitarianism.
 It is a gross oversimplification to say that the deontological view is
idealistics, while the utilitarian view is consequentialists,
but that is an effective way of beginning to think of these two
differing approaches to ethical theory.
The deontologist is generally considered to be means and
ends oriented, while the utilitarian is usually considered to be
ends oriented only.
In other words, for the deontologist the process matters more
than the result, while for the utilitarian it is the result that matters
most.

Introduction con’t
Pharmacy as a profession has evolved to a model of
"pharmaceutical care."
Pharmaceutical care is defined as the responsible provision
of drug therapy for the purpose of achieving definite
outcomes that improve a patient quality of life.
Three major functions are involved:
 Identifying potential and actual drug-related problems
 Resolving actual drug-related problems
 Preventing potential drug-related problems.
5

Introduction con’t
 The mission of pharmacy practice is no longer just to dispense
the right drug upon the authorization by a physician prescriber
but to render pharmaceutical care.
 Ethical obligations and guidelines distinguish professions from
occupations
 Ethics: Branch of Philosophy and focuses on values, rules of
conduct, moral principles.
 The common distinction between morality and ethics is that
morality is a personal or societal pursuit of right action, while
ethics is the study of morality or moral systems.
6

Ethical Principles Applied to Pharmacy Practice
Long-established and Accepted Ethical Principles
(“Virtues”)
Beneficence: Do good
 Non-maleficence: Do no harm
Autonomy:
Self-determination, human dignity, respect for the individual.
 Utility:
The end result should be useful to patients and to society.
Justice:
Impartiality in applying beneficence and distributing resources.
Veracity: Truthfulness, candor.
Fidelity: Keeping your word. Maintaining confidentiality 7

FIP STATEMENT OF PROFESSIONAL
STANDARDS CODES OF ETHICS FOR
PHARMACISTS
 The FIP recommends that in every country the
appropriate association of pharmacists should
produce a Code of Ethics for pharmacists setting
out their professional obligations and take steps to
ensure that pharmacists comply with the
provisions of that Code
8

 The obligations of pharmacists set out in these
codes should include:
To act with fairness and equity in the allocation of
any health resources made available to them.
To ensure that their priorities are the safety, well
being and best interests of those to whom they
provide professional services and that they act at
all times with integrity in their dealings with
them.
FIP STATEMENT OF PROFESSIONAL STANDARDS
CODES OF ETHICS FOR PHARMACISTS con’t
9

FIP STATEMENT OF PROFESSIONAL STANDARDS CODES
OF ETHICS FOR PHARMACISTS con’t
 To collaborate with other health professionals to
ensure that the best possible quality of healthcare is
provided both to individuals and the community at
large.
 To respect the rights of individual patients to
participate in decisions about their treatment with
medicinal products and to encourage them to do so.
 To recognize and respect the cultural differences,
beliefs and values of patients, particularly as they may
affect a patient’s attitude to suggested treatment.
10

FIP STATEMENT OF PROFESSIONAL STANDARDS CODES OF
ETHICS FOR PHARMACISTS con’t
 To respect and protect the confidentiality of information
acquired in the course of providing professional services and
ensure that information about an individual is not disclosed to
others except with the informed consent of that individual or
in specified exceptional circumstances
 To act in accordance with professional standards and scientific
principles.
 To act with honesty and integrity in their relationships with
other health professionals, including pharmacist colleagues,
and not engage in any behavior or activity likely to bring the
profession into disrepute or undermine public confidence in
the profession.
11

 To ensure that they keep their knowledge and professional
skills up-to-date through continuing professional
development.
 To comply with legislation and accepted codes and
standards of practice in the provision of all professional
services and pharmaceutical products and ensure the
integrity of the supply chain for medicines by purchasing only
from reputable sources.
 To ensure that members of support staff to whom tasks are
delegated have the competencies necessary for the efficient
and effective undertaking of these tasks12

 To ensure that all information provided to patients,
other members of the public and other health
professionals is accurate and objective, and is given
in a manner designed to ensure that it is
understood.
 To treat all those who seek their services with
courtesy and respect.
 To ensure the continuity of provision of professional
services in the event of conflict with personal moral
beliefs or closure of a pharmacy. In the event of
labor disputes, to make every effort to ensure that
people continue to have access to pharmaceutical
services.13

REFERENCES
 David B. Brushwood, Pharmacy Law & Ethics.
 2009 fip global pharmacy workforce report.
 AE the hague, the netherlands, international pharmaceutical
federation.
 FIP statement of professional standards on he role of the pharmacist in
encouraging adherence to long-term treatments (sydney 2003).
 fip statement of policy on confidentiality of information gained in the
course of pharmacy practice (2004, new orleans).
 the code of ethics and standards for pharmacy practice in kenya.
14

ACQUIRING THE KNOWLEDGE YOU NEED TO
PRACTICE

Introduction
 Acquiring knowledge is a pharmaceutical care
practice concern and it requires three main
categories:
 knowledge about patient (The individual),
 knowledge about drug and
 knowledge about diseases (Environment).

 Acquiring the knowledge you need to
practice necessitates the following:
 Becoming Familiar With What You Need to Know
 Understanding the Important Relationships
 Knowledge You Need About the Patient
 Knowledge You Need About the Patient's Medical
Conditions
 Knowledge You Need About the Patient's Drug
Therapies.

1. BECOMING FAMILIAR WITH WHAT YOU NEED
TO KNOW
 Learning all that is required may seem like an enormous task,
but there are three basic concepts that will help to make it
manageable:
 The knowledge that you must learn, integrate, and use in
practice can be classified into three broad categories:
• knowledge about patients,
• knowledge about diseases, and
• knowledge about drugs.
 All three categories of knowledge are equally important;
however, your unique expertise will lie in drug therapies.

2. UNDERSTANDING THE IMPORTANT RELATIONSHIPS
 The Pharmacotherapy Workup serves as the conceptual framework
to gather, organize, evaluate, and learn new patient, disease,
and drug information.
 In a generalist's practice, common things are common, meaning that
the most frequently encountered medical conditions, drug products,
and drug therapy problems represent a majority of the information
needed to be mastered.
 The most valuable clinical skills you learn are those needed to be
reflective in practice—it is the best way to improve yourself as a
practitioner.
 The pharmacotherapy case presentation has a specific format that
facilitates the successful communication among practitioners who
share the responsibility for managing medications.

3. KNOWLEDGE YOU NEED ABOUT THE PATIENT
 The dimensions of the patient that become
most important include
®the personal medication experience
®living environment, and
®physiological status, including medical
conditions or illnesses that need to be
managed with drug therapy.

4. KNOWLEDGE YOU NEED ABOUT THE PATIENT'S
MEDICAL CONDITIONS
The disease information that becomes most
important includes
 the characteristics,
 prognosis, and
 natural course of the disease, and
 the goals of therapy that are achievable
with drug therapy.

5. KNOWLEDGE YOU NEED ABOUT THE PATIENT'S DRUG
THERAPIES
 Pharmacological information that is central to all
patient cases includes the
©characteristics of the drug and its pharmacology aspect,
©mechanism of action and toxicity
©pharmacokinetic and pharmacodynamic properties,
©the effectiveness and safety that can be expected for a
patient
 This is unique knowledge that focuses on pharmacology and
pharmacotherapy and is applied to resolve and prevent drug
therapy problems and optimize the patient's medication
experience.

 However, the mere accumulation of knowledge is not
sufficient; the key is applying this knowledge to help
patients.
 Caring for patients and resolving drug therapy
problems require that you integrate patient, disease,
and drug knowledge, and then apply it to a specific
patient.
 There are often other practitioners such as physicians
or nurses who will know more than you do about a
specific patient or a disease, but no other patient care
practitioner will know more about the drug therapy.

ACQUIRING KNOWLEDGE
 Pharmacy has historically acquired knowledge
through these 9 main sources:

1. TRADITION
 Tradition means the passing on of customs
or beliefs from generation to generation
 Traditions include truths on beliefs that are based
on customs and past trends.
 They can positively influence pharmacy practice be
cause they were developed from past experiences.
 They can also narrow and limit the knowledge sou
ght for pharmacy practice.

2. AUTHORITY
 Knowledge acquired from authority is
illustrated when one person credits another
person as the source of information.
 Pharmacists who publish articles and books or d
evelop theories are frequently considered
authorities.
 Though, these authorities are good sources,
they should be verified by conducting
researches.

3. EXPERIENCE
 Experience means practical involvement in an
activity, event etc. It represents a familiar and
functional source of knowledge.
 Personal experience involves gaining knowledge
by being personally involved in an event , situation or
circumstance. It is the foundation and stimulus
for learning.
 In Pharmacy, personal experience enables one to gain
skills and expertise by providing care to patients an
d families in clinical settings.

4. BORROWING
 Borrowing in pharmacy involves appropriation
and use of knowledge from other fields or
disciplines to guide pharmacy practice
 It helps pharmacists
use advances in technology to become highly
specialized and focused on the detection and
treatment of disease to the health promotion
and illness prevention.

5. TRIAL AND ERROR
 In this approach, alternatives are tried successively
until a solution to a problem is found.
 Trial and error is an approach with unknown outcome
usedinsituation of uncertainty, when other source of
knowledge are unavailable.
 Example: May patients dislike the taste of potassium
chloride solution. pharmacists try to disguise the taste
of the medication in various ways until one method
meets with the approval of the patient.

6. ROLE MODELING AND MENTORSHIP
 Modeling is learning by imitating the behaviour of an
exemplar.
 An exemplar or role model is viewed as knowing the
appropriate and rewarded roles for a profession and
the roles reflect the attitudes and include the
standards and name of behaviour for that profession.
 It enables novice pharmacists to learn through intera
ction with or to follow examples set by expert
pharmacists.

 Intuition means acquiring knowledge by
ourselves.
 It is a type of knowledge that cannot be
explained on the basis of reasoning or prior
instruction.
 Thus, intuition is the result of
deep knowledge.
7. INTUITION

8. REASONING
 Reasoning is the processing and
organizing of ideas in order to reach
conclusions.
 Through reasoning people are able
to “make sense” of both their
thoughts and experiences.

CONCLUSION
 Acquiring knowledge through
 tradition, authority, borrowing, trial
and error, personnel experience, role-
modeling, intuition and reasoning
 is important in pharmacy practice as they help
achieving the patients related needs and drug
therapy problem management needed in
pharmaceutical care.

REFERENCES
 Pharmaceutical care book by Robert J. Cipolle; Linda M.
Strand; Peter C. Morley
 Denise. F.Polit, Cheryl Tatano Beck, Nursing Research –
Principles and methods, 7th ed.
 Pharmaceutical Care Practice: The Clinician's Guide:
Cipolle, Robert J. PharmD ISBN-13: 9780071362597 .
 White Paper on Pharmacy Student Professionalism,
Wendell T. Hill, Jr.1 Journal of the American
Pharmaceutical Association.
 Pharmaceutical Care by Sherif Kamal DPS Director

STANDARDS OF PRACTICE FOR PHARMACEUTICAL CARE

 Standards of practice for pharmaceutical care
include standards of care and professional
standards.
 Standards of Care:
A set of expectations of the
performance of an individual
practitioner.
 Professional Standards:
A set of expectations for a community
of practitioners.

There are seven standards of
care which are grouped into
three categories:
A.STANDARDS OF CARE FOR
PHARMACEUTICAL CARE PR
ACTITIONERS

 Standard 1.
o Relevant patient‐specific information is collected by the
practitioner so as to be used in decision ‐ making concern
all drug therapies.
 Standard 2.
The practitioner analyzes the assessment data to determine
if the patient’s drug ‐ related needs are being met that all
the patient’s medications are appropriately indicated, the
most effective available, the safest possible, and the patient
is able and willing to take the medication as intended.
CATEGORY I. ASSESSMENT

 Standard 3.
Identification of drug therapy problems:
The practitioner analyzes the assessm
ent data to determine if any drug thera
py problems are present.
CATEGORY I. ASSESSMENT

CATEGORY II. CARE PLAN DEVELOPMENT
 Standard 4.
o The practitioner identifies goals of therapy that are indivi
dualized to the patient.
 Standard 5.
o The practitioner develops a care plan that includes
interventions to: resolve drug therapy problems, achieve
goals of therapy, and prevent drug therapy problems.
 Standard 6.
o The practitioners develop a schedule to follow-
up and evaluate the effectiveness of
o drug therapies and assess any adverse events experience
d by the patient.

CATEGORY III. FOLLOW‐UP
EVALUATION
Standard7.
The practitioner evaluates the patient’s actual
outcomes and determines the patient’s
progress toward the achievement of the goals of
therapy, determines if any safety or compliance
issues are present, and assesses whether any
new drug therapy problems have developed .

FULL EXPLANATIONS OF SEVEN STANDARDS OF CARE
 Standard of Care 1: Collection of Patient‐specific
Information The practitioner collects relevant
patient‐specific information to use in decision
making concerning all drug therapies.
Measurement criteria
 1.Appropriate interview techniques are used to
collect pertinent data.
 2.The patient, family and care‐givers, and health
care providers are involved in data collection when
appropriate.

 3.The medication experience is elicited by the
practitioner and incorporated as the context for
decision‐making.
 4.The data are used to develop a pharmacologically
relevant description of the patient and the patient’s
drug‐related needs.
 5.The patient’s present conditions, illnesses, wants and
needs determine the relevance and significance of the
data collected
 6.The medication history is complete and accurate.

 7.The current medication record is complete and
accurate.
 8.The data collection process is systematic and
ongoing.
 9.Only data that are required and used by the
practitioner are elicited from the patient.
 10. Relevant data are documented in a retrievable
form.
 11. All data elicitation and documentation is
conducted in a manner that ensures patient
 Confidentiality

Standard of Care 2: Assessment of
Drug‐related Needs.
The practitioner analyzes the assessment data
to determine if the patient’s drug‐related needs
are being met, that all the patient’s medications
are appropriately indicated, the
most effective available, the safest possible, and
the patient is able and willing to take the
medication as intended.

 1.The patient‐specific data collected in the assessment are
used to decide if all of the patient’s medications are
appropriately indicated.
 2.The data collected are used to decide if the patient
needs additional medications that are not presently being
taken.
 3.The data collected are used to decide if all of the
patient’s medications are the most effective products
available for the conditions.
 4.The data collected are used to decide if all of the
patient’s medications are dosed appropriately to achieve
the goals of therapy.

 5The data collected are used to decide if any of
the patient’s medications are causing adverse
effects.
 6.The data collected are used to decide if any of
the patient’s medications are dosed excessively
and causing toxicities.
 7.The patient’s behavior is assessed to determine
if all of his/her medications are being taken
appropriately in order to achieve the goals of
therapy.

STANDARD OF CARE 3: IDENTIFICATION OF
DRUG THERAPY PROBLEMS
The practitioner analyzes the assessment data to
determine if any drug therapy problems are present.
Measurement Criteria:
 1.Drug therapy problems are identified from the
assessment findings.
 2.Drug therapy problems are validated with the
patient, his/her family, caregivers, and/or health care
providers, when necessary.

3.Drug therapy problems are expressed so that the
medical condition and the drug therapy involved are
explicitly stated and the relationship or cause of the
problem is described.
4.Drug therapy problems are prioritized, and those
that will be resolved first are selected.
5.Drug therapy problems are documented in a
manner that facilitates the determination of goals of
therapy within the care plan.

STANDARD OF CARE 4: DEVELOPMENT OF GOALS OF
THERAPY
 The practitioner identifies goals of therapy that are
individualized to the patient.
Measurement Criteria
 1.Goals of therapy are established for each indication for
drug therapy.
 2.Desired goals of therapy are described in terms of the
observable or measurable clinical and/or laboratory
parameters to be used, to evaluate effectiveness of drug
therapy.
 3.Goals of therapy are mutually negotiated with the
patient and health care providers when appropriate.

STANDARD OF CARE 5: STATEMENT OF INTERVENTIONS
The practitioner develops a plan of care that involves
interventions to resolve drug therapy problems and
interventions to achieve goals of therapy.
Measurement criteria:
 1.Each intervention is individualized to the patient’s
condition, needs, and drug therapy problems.
STD OF CARE 4, MEASURING CRITERIA
 4.Goals of therapy are realistic in relation to the patient’s
present and potential capabilities.
 5.Goals of therapy are attainable in relation to resources
available to the patient.
 6.Goals of therapy include a timeframe for achievement.

 Measurement criteria:
 2.All appropriate therapeutic alternatives to resolve
the drug therapy problems are considered, and the
best are selected.
 3.The plan is developed in collaboration with the
patient, his/her family and/or care‐givers, and health
care providers, when appropriate.
 4.All interventions are documented.
 5.The plan provides for continuity of care by
including a schedule for continuous follow‐up
evaluation.

STANDARD OF CARE 6: ESTABLISHING A
SCHEDULE FOR FOLLOW‐UP EVALUATIONS
The practitioner develops a schedule to follow‐up and
evaluate the effectiveness of the outcomes from drug
therapies and assess any adverse events experienced by
the patient.
 1.The clinical and laboratory parameters to evaluate
effectiveness are established, and a timeframe for
collecting the relevant information is selected.

 2.The clinical and laboratory parameters that
reflect the safety of the patient’s medications are
selected, and a timeframe for collecting the
relevant information is determined.
 3.A schedule for the follow‐up evaluation is
established with the patient.
 4.The plan for follow‐up evaluation is documented

STANDARD OF CARE 7: FOLLOW‐UP EVALUATION
The practitioner evaluates the patient’s actual
outcomes and determines the patient’s progress
toward the achievement of the goals of therapy,
determines if any safety or compliance issues are
present, and assesses whether any new drug therapy
problems have developed.
1.The patient’s actual outcomes from drug therapies
and other interventions are
documented.

 2.The effectiveness of drug therapies is evaluated,
and the patient’s status is determined by
comparing the outcomes within the expected
timeframe to achieve the goals of therapy.
 3.The safety of the drug therapy is evaluated.
 4.Patient compliance is evaluated.
 5.The care plan is revised, as needed.

 Measurement Criteria:
 6Revisions in the care plan are documented.
 7.Evaluation is systematic and ongoing until all
goals of therapy are achieved.
 8.The patient, family and/or care‐givers, and health
care providers are involved in the evaluation
process, when appropriate.

There are seven standards for professional
behavior and they are explained below.
Standard I. Quality of Care
The practitioner evaluates his/her own
practice in relation to professional practice
standards and relevant statutes and
regulations.
B.THE STANDARDS FOR PROFESSIONAL
BEHAVIOR

 Measurement criteria
 1.The pharmaceutical care practitioner uses
data from the literature to evaluate his/her
performance in practice.
 2.The pharmaceutical care practitioner seeks
peer review on a continual and frequent basis.
 3.The pharmaceutical care practitioner
utilizes data generated from his/her practice
to critically self‐evaluate performance

Standard II. Ethics
 The practitioner’s decisions and actions on
behalf of patients are determined in an ethical
manner
 1.The practitioner maintains patient
confidentiality.
 2.The practitioner acts as a patient advocate.

 3.The practitioner delivers care in a nonjudgmental
and nondiscriminatory manner that is sensitive to
patient diversity.
 4.The practitioner delivers care in a manner that
preserves/protects patient autonomy, dignity, and
rights.
 5. The practitioner seeks available resources to help
formulate ethical decisions.

STANDARD III. COLLEGIALITY
The pharmaceutical care practitioner contributes to
the professional development of peers, colleagues,
students, and others.
 1.The practitioner offers assistance to other
practitioners whenever asked.
 2.The practitioner promotes relationships with
patients, physicians, nurses, and other health care
providers.

STANDARD IV. COLLABORATION
 The practitioner collaborates with the patient, family
and/or care‐givers, and health care providers in
providing patient care.
 1.The patient is seen as the ultimate decision maker
and the practitioner collaborates accordingly.
 2.The practitioner collaborates with the patient’s
health care providers whenever it is in the best
interest of the patient.

STANDARD V.EDUCATION
 The practitioner acquires and maintains current
knowledge in pharmacology, pharmacotherapy, and
pharmaceutical care practice.
 1. The practitioner uses the skills of reflectivity to
identify areas where knowledge needs to be
supplemented.
 2. The practitioner continually updates knowledge with
publications, professional journal subscriptions, current
texts, practitioner interactions, and continuing
education programs.

STANDARD VI. RESEARCH
 The practitioner routinely uses research findings in
practice and contributes to research findings when
appropriate.
 1.The practitioner uses research as the basis for practice.
 2.The pharmaceutical care practitioner systematically
reviews the literature to identify knowledge, skills,
techniques, and products that are helpful in practice and
implements them in a timely manner.
 3.The practitioner approaches his/her practice with a
perspective to conduct applied research when appropriate.

STANDARD VII.RESOURCE ALLOCATION
 The practitioner considers factors related to effectiveness,
safety, and cost in planning and delivering patient care
 1.The pharmaceutical care practitioner is sensitive to the
financial needs and resource limitations of the patient,
the health care providers, and the institutions with which
he/she interacts.
 2.Decisions are made by the pharmaceutical care
practitioner to conserve resources and maximize the
value of those resources consumed in practice.

CONCLUSION
In conclusion, standards of practice in
pharmaceutical care are needed to
increase therapeutic outcomes of
patients and minimize side effects.
Each country should follow those
standards in order to professionally
provide good health care to patients
and improve health care systems.

 REFERENCES
 www.pharmacy.umn.edu
 www.psa.or.au/supporting-
practice/professional-practice-
standards
 www.who.int/medicine

ESTABLISHMENT OF A NEW PHARMACEUTICAL CARE
PRACTICE IN RWANDA

INTRODUCTION
 Whether pharmacists are reviewing a prescription or a
patient medication record, talking to a patient or
responding to symptoms, they are automatically assessing
needs, prioritizing and creating a plan to meet those
needs.
 What they often fail to do is to accept responsibility for
this care. Consequently they may not adequately
document, monitor and review the care given.
 Accepting such responsibility is essential to the practice of
pharmaceutical care and should be referred to relevant
sections of national or local evidence-based guidelines.

INTRODUCTION CONT'D
 The practice of pharmaceutical care makes explicit
the pharmacist’s responsibility to the patient for the
prevention of medicine-related illness.
 In this practice, the pharmacist evaluates a patient’s
medicine-related needs, then determines whether
one or more drug therapy problems exist, and, if so,
works with the patient and other health care
professionals to design, implement and monitor a
care plan.
 This plan should be kept as simple as possible.

INTRODUCTION CONT'D
 A drug therapy problem is defined as:
 “An undesirable event, a patient experience that
involves, or is suspected to involve drug therapy, and
that actually or potentially, interferes with a desired
patient outcome”.(Cipolle et al., 1998)
 Pharmaceutical care is the responsible provision of
drug therapy for the purpose of achieving definite
outcomes that improve or maintain a patient's quality
of life. Hepler and Strand (1990).

These outcomes are
 cure of a disease;
 elimination or reduction of a patient's
symptomatology
 arresting or slowing of a disease process
 Preventing a disease or symptomatology.
 Pharmaceutical care is delivered at the individual
patient level.

THE PHARMACEUTICAL CARE PROCESS
 The delivery of effective pharmaceutical care
to patients requires pharmacists to practice in
a way that uses their time effectively and
reflects their responsibility and
accountability.
 Ideally all patients who receive
pharmaceutical products or services should
also receive pharmaceutical care.

 Pharmacists should assume that all patients require pharmaceutical
care until they have been assessed to exclude drug therapy problems
(Step 1).
 However, due to limited resources, this step is not always possible
and a systematic approach (see Figure 1 below) may need to be
adopted to facilitate the targeting of care.
 Prioritization is used routinely in health care, especially in resource-
constrained environments, to ensure that services are targeted
particularly to those patient groups and individual patients who
need them most.
 Targeting may occur prior to Step 1 or as part of Step 1 depending on
available resources.
THE PHARMACEUTICAL CARE PROCESS CONT'D

This involves the following four steps:
 Step 1: Assess the patient’s drug therapy needs and identify
actual and potential drug therapy problems
 Step 2: Develop a care plan to resolve and/or prevent the drug
therapy problems
 Step 3: Implement the care plan
 Step 4:Follow up Evaluation and review the care plan
Pharmaceutical care as a new practice to be adopted in Rwanda
should be implemented following these 4 steps.
A SYSTEMATIC APPROACH TO THE DELIVERY OF
PHARMACEUTICAL CARE

Step 1: Assess The Patient’s Drug Therapy Needs And
Identify Actual And Potential Drug Therapy Problems
 Good communication needs to be established with
othe patient, carer and
oother members of the health care team at the outset
 This is done in order for pharmacists to
ocollect, synthesize and
o interpret the relevant information.
 When pharmacists assess patients, they must take full account
of all patient and medication factors that may predispose
patients to the risk of drug therapy problems.

STEP 2: DEVELOP A CARE PLAN TO RESOLVE
AND/OR PREVENT DRUG THERAPY PROBLEMS
 Not all patients may progress to Step 2. For example, no
problems may have been identified at Step 1 or you may not be
able to meet the needs of a particular patient due to severe
resource limitations.
 If the latter is the reason the drug therapy problems identified
should be documented and brought to the attention of the
patient and the health care team and advice provided for
reasons of ethical, clinical and professional responsibility,
even if the patient cannot be followed up.
 Whether there is no resource limitations, a care plan should
be developed following 3 important steps :

Step 2 cont'd
 Identify desired therapeutic objectives and proposed actions
 A statement should be made of what the pharmacist intends to
achieve for a patient in relation to each drug therapy problem.
 The statements should be agreed with the patient and the
health care team. These therapeutic objectives should be
expressed as measurable outcomes to be achieved within a
defined time scale.
 In deciding on the most appropriate actions it is vital that the
pharmacist confirms the acceptability of these actions with the
patient.
 If a number of options exist, the patient must be given
sufficient information to select the most appropriate option.

Step 2 cont'd
 DEVELOP A MONITORING STRATEGY
 A monitoring strategy should be identified to
measure progress towards achievement of the
therapeutic objectives.
 This strategy should be agreed with the patient
and other members of the health care team
and should be undertaken at specified
intervals and for a defined period prior to
further review.

Step 2 cont'd
Document the care plan
 The pharmacist’s record of drug therapy problems
and
 therapeutic objectives, together with the
proposed actions,
 form a documented pharmaceutical care plan.
 Good documentation
 facilitates continuity of care and clinical audit.

STEP 3: IMPLEMENT THE CARE PLAN
The pharmaceutical care plan is
implemented with the agreement of
the patient and, where possible,
within the context of the overall care
of the patient, in cooperation with
other members of the health care
team.

ILLUSTRATIVE CASE STUDY 1
 Mrs. J, aged 45 years, has recently been diagnosed with
asthma, following reversibility testing with a short-acting
bronchodilator.
 Her relevant medical history includes osteoarthritis and
hypertension. Her blood pressure was recently measured
as 170/ 110 mmHg. Mrs. J smokes 30 cigarettes a day, is a
moderate to heavy drinker and does no physical exercise.
 Previous drug therapy of bendroflumethiazide 2.5 mg in
the morning was ineffective for hypertension.

 Her current drug therapy is as follows:
 Paracetamol.....500 mg 2 as required up to 8 in 24 hrs
 Propranolol......40 mg three times daily
 Salbutamol metered dose inhaler (MDI)... 2 puffs as
required
 Budesonide turbo (dry powder inhaler).... 200 mcg
twice daily

Development of pharmaceutical care plan

STEP 4: EVALUATE AND REVIEW THE CARE PLAN
 Actual outcomes are evaluated in relation to the therapeutic
objectives to determine whether drug therapy problems have
been resolved.
 If outcomes are not achieved, the care plan should be
reviewed.
 The actual outcomes may then be accepted as being the best
achievable for the patient, or an alternative plan may be
necessary.
 The plan should develop as original drug therapy problems
resolve and new drug therapy problems appear, which require
resolution.

Pharmaceutical services
 Strand et al (1992) used the term pharmaceutical services to represent all
the services that pharmacists require to resolve a patient’s drug therapy
problems.
 These services range from the provision of medicines information to
patient counselling to medicines distribution.
 Clearly, medicines information pharmacists who provide comprehensive,
current
 and accurate information based on best evidence are supporting the
delivery of pharmaceutical care, although they themselves are not actually
delivering it.
 Patient counselling services should be incorporated into standard daily
interaction with patients in the community pharmacy setting.
 Similarly, timely and accurate drug distribution is required to ensure the
delivery of pharmaceutical care.

REFERRAL
 In providing pharmaceutical care the pharmacist has to
facilitate the continuity of care.
 As part of providing pharmaceutical care it may be necessary
for a pharmacist to refer patients to other health care
providers.
 In doing so it is essential to guarantee continuity of care for
the patient. Health care needs could range from obtaining a
prescription at a more convenient place to seeking additional
treatment.
 For this purpose, the pharmacist may need to refer a patient
to other members of the health care team or to other health
care institutions.

REFERRAL CONT'DD
 While formal referral by pharmacists is
uncommon practice in many parts of the world,
 in many countries as well as in Rwanda,
pharmacists are the first contact for advice on
health-related issues and have a good
relationship with the community.
 This relationship places a pharmacist in an ideal
position to identify and refer social and health-
related issues.

REFERRAL CONT'DD
 A formal referral system involving different health care
providers will strengthen the pharmacist’s professional
position with other care providers.
 Referring the patient to a health care provider or health
care institution for more specialized
 care than is available in the current health care setting
is referred to as up-referral
 e.g., from a primary health care facility or community
pharmacy to a medical doctor or hospital.

REFERRAL CONT'DD
 Down-referral is where it may be appropriate to
refer a patient to a less specialized care facility e.g.,
from a hospital to a primary health care clinic or
community pharmacy.
 In providing pharmaceutical care it is necessary to
address the patient’s medicine-related needs
through a holistic approach, which may require
referring a patient for social counselling to a social
worker, religious leader, traditional healer,
complementary practitioner or counsellor.

REFERRAL CONT'DD
 Social referral e.g., Substance abuse and social habits
could influence the patient’s well-being and drug therapy.
 As part of the pharmaceutical care plan it may be necessary
to refer the patient to a counsellor or institution.
 This communication may be written or verbal and should
contain the following information:
o a short summary of the patient’s medical history
o a short description of the current medical problem
o description of the need for referral
o description of the patient’s current therapy
o the pharmaceutical care plan if necessary.

SUMMARY
 Pharmaceutical care is a prospective patient-centred practice with
a focus on identifying, resolving and preventing drug therapy
problems.
 This objective is achieved by a patient care process comprising
four steps: assess the patient’s drug therapy needs; develop a care
plan to meet those needs; implement the care plan; and evaluate
and review the care plan.
 Pharmacists require a high level of knowledge and skills to deliver
pharmaceutical care and an organizational structure to facilitate
its delivery.
 This structure must provide for the referral of patients who
cannot be managed at a particular level of care to a different level,
where optimal pharmaceutical care can be provided. Ultimately,
as patients benefit from appropriate drug therapy, this will also
have a beneficial impact on their families and the communities in
which they live and work.

CONCLUSION
 Pharmaceutical care is a necessary element of health care and
should be integrated with other elements.
 Pharmaceutical care is, however, provided for the direct
benefit of the patient, and the pharmacist is responsible
directly to the patient for the quality of that care.
 The fundamental relationship in pharmaceutical care is a
mutually beneficial exchange in which the patient grants
authority to the provider, and the provider gives competence
and commitment (accept responsibility) to the patient.
 The fundamental goals, processes, and relationships of
pharmaceutical care exist regardless of practice setting.

Viral drug resistances phenomena (HIV)
Anti-Microbial Resistances

CONTENT
CONCEPT OF HIV DRUG RESISTANCE
DEVELOPED FROM THE INITIAL INFECTION
CAUSES OF HIV DRUG RESISTANCE
MECHANISMS OF HIV DRUG RESISTANCE
STRATEGIES FOR PREVENTION OF
ANTIRETROVIRAL RESISTANCE
TREATMENT OPTIONS OF HIV IN RWANDA

HIV DRUG RESISTANCE CONCEPT
At the time of infection, a single virus may be
introduced and goes on to replicate with the help of a
single CD4+ cell.
A number of new virions are produced, each for
which goes on to use other to CD4+ cells to replicate
further.
During this process different strains of the virus are
produced which differ from one another by random
mutations in their genetic structures.
Some of these mutations are minor and are called
base substitutions or amino acid substitutions.

Concept continue
Other mutations are significant as they involve
combinations of amino acids substitutions, deletions, or
insertions.
Some of these mutations are good for the virus, as they
can help the virus to escape the pressure of the immune
system, providing it with a survival advantage.
Other mutations are harmful to the virus.
With the start of a single antiretroviral agent, it is
likely that treatment will be initially effective in
reducing the dominant, usually wild types strain of
HIV.

Concept of HIV drug resistance
However among the diverse population of virus, there
will likely be at least one strain harboring a
particular mutation that confers a small survival
advantage in the presence of a particular
antiretroviral drug.
If this variant strain is permitted to continue
replicating, it will continue to diversify, with some
progeny accumulating additional mutations that
confer greater resistance to the antiretroviral
agent being used.

Causes of HIV resistance
The Common cause of HIV resistance is
mutation.
HIV replicates very rapidly and makes many
mistakes (mutations) in the process
HIV replicates very rapidly and makes many
mistakes (mutations) in the process
This results in mutant viruses that can be
resistant to one or more of the drugs used
in HIV therapy.

MECHANISMS OF HIV RESISTANCE
A variety of mutations through which HIV
acquire resistance have been identified and
the mechanism by which they confer
resistance: Mutations Involved in Resistance
of HIV
 to Nucleoside Analogues,
to Nonnucleoside Reverse-Transcriptase
Inhibitors (NNRTIs),
to Protease Inhibitors.

Resistance to Nucleoside and Nucleotide
Analogues
Nucleoside analogues and nucleotide analogues
arrest the synthesis of viral DNA by reverse
transcriptase.
After phosphorylation by cellular kinases, these
compounds are incorporated by reverse
transcriptase into the nascent chain of viral DNA
Because these drugs lack a 3' hydroxyl group, no
additional nucleotides can be attached to them,
and the synthesis of viral DNA is arrested.

Mechanism cont’d
Two distinct mechanisms are involved in
HIV resistance to these drugs:
impairment of the incorporation of
the analogue into DNA
 removal of the analogue from the
prematurely terminated DNA chain.

Impairment of Analogue Incorporation
Several mutations or groups of mutations in reverse
transcriptase can promote resistance by selectively
impairing the ability of reverse transcriptase to
incorporate an analogue into DNA.
They essentially include the M184V mutation, the
Q151M complex of mutations, and the K65R
mutation.
The M184V mutation involves the replacement of
methionine by valine at position 184 of the reverse
transcriptase and is the main mutation that confers
resistance to lamivudine.

Impairement cont’d
Methionine 184 is located at the heart of the
catalytic site of reverse transcriptase, and its
replacement by a valine, which has a different side
chain, interferes with the proper positioning of
lamivudine triphosphate within the catalytic site
The M184V mutation induces very high levels of
resistance to lamivudine.
 The group of mutations referred to as the Q151M complex is
most often selected for the cause of the failure of regimens
containing stavudine and didanosine.

 This pathway always starts with the Q151M substitution,
 a residue located in the immediate vicinity of the nucleotide-
binding site of reverse transcriptase,
 followed by the gradual accumulation of secondary
mutations that enhance resistance and increase the activity of
the enzyme.
 Q151M confer high-level resistance to most — but not all (e.g.,
lamivudine and tenofovir) — analogues
 Q151M complex is markedly more frequent in HIV-2 than in
HIV-1.

The K65R mutation is seen with
increasing frequency in patients in whom
therapy with nucleoside or nucleotide
analogues fails
especially when the regimen includes
tenofovir or abacavir.
This mutation appears to confer
resistance to most analogues, with the
exception of zidovudine.

Removal of the Analogue from the Terminated DNA Chain
Removal of the nucleoside analogue from the terminated
DNA chain is associated with a group of mutations
commonly termed “thymidine analogue mutations”.
Mutations from this group are most frequently selected
for after the failure of drug combinations that
include thymidine analogues, such as zidovudine
and stavudine
Thymidine analogue mutations promote resistance
by fostering ATP- or pyrophosphate-mediated
removal of nucleoside analogues from the 3' end of
the terminated DNA strand.

Removal of the Analogue from the Terminated DNA Chain
ATP and pyrophosphate, which are abundant in
normal lymphocytes, do not participate in the
DNA-polymerization reaction
But the structure of a reverse transcriptase
expressing thymidine analogue mutations facilitates
ATP and PYROPHOSPHATE entry into a site
adjacent to the incorporated analogue.
 In this position, ATP or pyrophosphate can attack
the phosphodiester bond that links the
analogue to DNA, resulting in removal of the
analogue.

RESISTANCE TO NONNUCLEOSIDES
REVERSE TRANSCRIPTASE INHIBITORS
Nonnucleoside reverse-transcriptase inhibitors
are small molecules that have a strong affinity
for a hydrophobic pocket located close to
the catalytic domain of the reverse
transcriptase
The binding of the inhibitors affects the
flexibility of the enzyme, thereby blocking its
ability to synthesize DNA.

RESISTANCE TO NONNUCLEOSIDES REVERSE
TRANSCRIPTASE INHIBITORS
The mutations that are selected for after the failure of
treatment with nonnucleoside reverse-transcriptase
inhibitors are all located in the pocket targeted by these
compounds, and they reduce the affinity of the drug.
the mutations that emerge most frequently are drug-
dependent .
Resistance to nevirapine is often associated with the
Y181C mutation
Initial resistance to efavirenz is generally characterized
by the K103N mutation, but the Y188L mutation is also
seen.

RESISTANCE TO PROTEASE INHIBITORS
The HIV protease cleaves large polyprotein precursors
at specific sites, releasing the structural proteins and
enzymes necessary for the assembly of infectious viral
particles.
The HIV protease cleaves large polyprotein precursors at
specific sites, releasing the structural proteins and enzymes
necessary for the assembly of infectious viral particles.
Resistance to protease inhibitors is the consequence of
amino acid substitutions that emerge either inside
the substrate-binding domain of the enzyme or at
distant sites.

RESISTANCE TO PROTEASE INHIBITORS
Directly or indirectly, these
amino acid changes modify
the number and the nature of
the points of contact between
the inhibitors and the
protease, thereby reducing
their affinity for the enzyme.

RESISTANCE TO FUSION INHIBITORS
HIV enters target cells through an intricate sequence of
interactions between the HIV envelope
glycoprotein (gp) complex (gp120–gp41) and
specific cell-surface receptors.
The early steps in this process allow gp41, the
fusogenic component of the complex, to interact with
the cell membrane, thereby tethering the virus to its
target.
 The membranes of the virus and target cell are then
brought into close proximity, fostering their fusion, by
further rearrangement of gp41.

RESISTANCE TO FUSION INHIBITORS
oEnfuvirtide, a 36-amino-acid peptide derived from HR2,
destabilizes this process by binding to HR1 and blocks
the infectivity of HIV-1.
oViral resistance to Enfuvirtide usually results from
mutations located in a stretch of 10 amino acids within
HR1.
ochanges in amino acids in gp41 outside HR1 — and even
changes in gp120 — appear to be associated with
significant differences in the susceptibility of the virus to
Enfuvirtide

CROSS RESISTANCE
Cross-resistance, defined as resistance to drugs to
which a virus has never been exposed, results from
mutations that have been selected for by the use of
another drug.
Cross-resistance is always restricted to drugs within a
given class of antiretroviral agents but all three classes
of antiretroviral drugs are affected.
in patients infected with strains that have low levels of
cross-resistance, the switch to apparently active
alternative drugs can be accompanied by rapid
selection for highly resistant variants, at the expense of
minimal evolutionary changes.

STRATEGIES FOR PREVENTION RESISTANCE TO
ANTIRETROVIRAL TREATMENT
To develop standardized tools that support a public
health approach to HIV-DR surveillance and
monitoring
To collect information from WHO-supported studies
and other researches to inform HIV care and prevention
guideline policies globally.
To support research and initiatives that will limit HIV-
DR
Development and promulgation of cheaper, more
feasible HIV associated laboratory test
Standardization of basic minimum database for HIV
care and harmonization of international indicators

STRATEGIES FOR PREVENTION RESISTANCE TO
ANTIRETROVIRAL TREATMENT
Strengthening ART programs to support
adherence and remove barriers to ART continuity.
Implementation of pharmacovigilance and
strategies to minimize adverse ART associated
events.
 Recommendations to guide the public health
approach to HIV care and prevention, to prioritize
the development of ARV drug formulation and
support wider availability and lower prices of ARV
drugs

HIV AIDS IN RWANDA
The current prevalence of HIV and AIDS in
Rwanda in adult population aged from 15-19
years has stabilized at 3%, in the last fie years,
estimated at 206,000.
HIV -prevalence among children is about 1000.
But-HIV being a mixed epidemic, the
prevalence is high in some groups for example
among the female sex workers (FSWs) the
prevalence is 51%

PROPHYLAXISIS FOR OPPORTUNISTIC INFECTIONS
The national protocol recommends universal access, that is
to say, systematically put all HIV-infected patients (adults or
infants) on prophylaxis without taking into account the CD4
count.
Co-trimoxazole 960 mg/day prophylaxis is maintained
among Adult patients on ARVs regardless of the trend in
CD4 count
Everyone with CD4 count below of 350 could be started
on ARVs. The new criteria however is that a patient is
started on ARV treatment when the CD4 count is 500.

WHEN AND HOW TO INITIATE TREATMENT IN AN ADULT PATIENT?
Not all HIV-infected patients need antiretroviral treatment
immediately.
Initiation of ARV treatment depends on three patient-related criteria:
 the clinical stage (WHO classification criteria),
 the immunological state,
 and the social status (especially given the importance of this aspect
on adherence)
When to Start ART in Children
 Every child infected by HIV under 5 years is eligible to ART
regardless of CD4 count and clinical stage
 ART Regimens did not change for children < 5 years

CRITERIA FOR CLINICAL AND IMMUNOLOGICAL ELIGIBILITY.
Confirmed HIV seropositivity and one of the following
two criteria:
Any patient >15 years with WHO Stage 3 and 4
regardless CD4 cell count
Any patient >15 years in WHO Stage 1, 2 with CD4 <
350/mm3
Any patient >15 years with HIV-TB co-infection
regardless CD4 cell count
Any patient with HIV-Hepatitis B co-infection
Any HIV-Positive Sex partner in discordant couple
regardless CD4 and WHO stage

THE 3 KEY FACTORS IN TREATMENT WHICH WILL
INFLUENCE ITS SUCCESS:
®The virus which may be more or less aggressive
depending on the subtype and species of infecting virus;
®The patient, depending on the associated pathologies
(co-infection with TB, hepatitis B, etc), his/her capacity
to adhere to treatment, his/her mode of life and the
support s/he receives;
®The antiretroviral drugs, which ideally should be
efficacious over a long time and with minimum side
effects.

THE DIFFERENT CLASSES OF ARVS
There are three main classes of ARVs in use in
Rwanda:
@Nucleoside reverse transcriptase inhibitors (NRTIs)
that competitively block reverse transcriptase .
@Non-nucleoside reverse transcriptase inhibitors
(NNRTIs) which block reverse transcriptase in a non
competitive manner.
@Protease Inhibitors (PI) which inhibit the Protease
enzyme.

WHEN AND HOW TO CHANGE THE TREATMENT
REGIMEN?
The clinician can change the treatment regimen
in 4 main situations:
Toxicity: a severe side effect (only one drug
must be substituted);
Treatment failure (the entire regimen must
be changed);
Pregnancy;
Drug interactions.

MAIN ARV COMBINATIONS
 2 NRTI + 1 NNRTI or 2 NRTI + 1 PI according to the case
 The association of 3 NRTIs is possible but because of the reduced
potency should not be considered except in cases of extreme
necessity or after expert opinion.
THE RECOMMENDED FIRST LINE REGIMEN
 There are four options recommended in first line regimen
(Adult)
NRTI NNRTI
1 Tenofovir (TDF) + Lamivudine (3TC)or FTC Efavirenz (EFV)
2 Tenofovir (TDF) + Lamivudine (3TC) or FTC Nevirapine (NVP)
3 Abacavir (ABC) + Lamivudine (3TC)or FTC Efavirenz (EFV)
4 Abacavir (ABC) + Lamivudine (3TC)or FTC Nevirapine (NVP)
FTC: EMTRICITABINE

Recommended Combinations for Second
line in Rwanda
AZT (Zidovudine) + 3TC (Lamivudine) + Lop/rit (Kaletra).
TDF (Tenofovir)+3TC (Lamivudine) + Lop/rit (Kaletra)
Regimen recommended after failure of the 2nd line
regimen
 In Rwanda, the 3rd line regimen combination is:
TDF/3TC/RAL/ETV/DRV/r
DRV: darunavir RAL: raltegravir ETV: etravirine R: ritonavir
TDF: tenofovir 3TC: lamivudine .
The 3rd line regimen must only be given upon expert
consultation and usually with the assistance of genotyping test.

STIs Management-Hepatitis B
All cases of co-infection (HIV-Hepatitis B) who need
hepatitis treatment (active hepatitis based on ALT)
should be put on ART regardless CD4 cell count and
the regimen should contain at least two agents
(TDF,3TC or FTC)
 Hepatitis B screening for HIV+ people (Ag HBs),

TREATMENT OF TB/HIV COINFECTED PATIENTS
SITUATION RECOMMANDATION
®Patient co-infected with HIV and TB Initiate anti-
TB treatment, Start the administration of an
association of ARV below between 2-8 weeks after
starting TB treatment.
TDF + 3TC + EFV
ABC +3 TC + EFV
®For pregnant women only: In the first quarter:
TDF + 3TC + Kaletra *
®After the first quarter
TDF + 3TC + EFV

HIV Prophylaxis In Pregnant Women
©A clinical evaluation (Stages WHO) and a
biological assessment including the CD4 count,
hemoglobin, liver function and the renal function
must be made before the start of the ARV
prophylaxis in PMTCT.
©Any woman with a CD4 count < 350 regardless of
her WHO clinical stage and any woman with a
WHO clinical stage of 3 or 4 regardless of her
CD4 count are eligible for ART. The treatment
should begin as early as possible no matter how
advanced the pregnancy.
©The regimen is composed of Tenofovir 300mg +
Lamivudine 300mg + Nevirapine 200mg: TDF
300+ 3TC300 + NVP200.

® Any woman with impaired renal function or likely to have impaired renal
function will receive : Abacavir 300mg + Lamivudine 150mg + Nevirapine
200mg: ABC + 3TC +NVP
® Any HIV-positive pregnant woman with a CD4 count between 350 and 500 will receive
triple therapy from the 14th week: The ARV regime is Tenofovir 300mg +
Lamivudine 300mg + 600mg Efavirenz: TDF +3TC + EFV
® HIV-positive pregnant women with a CD4 count > 500 (non eligible for Arv
treatment)
® The ARV regime is Tenofovir 300mg + Lamivudine 300mg + Efavirenz 600mg:
TDF +3TC + EFV
® All HIV-positive pregnant women who were exposed to single-dose Nevirapine during
their previous pregnancy will receive Tenofovir 300mg + Lamivudine 300mg +
Lopinavir/Ritonavir (Kaletra) 250mg: TDF +3 TC + Lop/r
® All children born to HIV-positive mothers, whether the mothers breastfeed or not,
will receive Nevirapine (NVP) syrup during the first six weeks of life.

POST EXPOSURE PROPHYLAXIS
 The patient from whom the exposure originated should be considered:
 His HIV sero-status.
 His clinical and immunological status vis-à-vis HIV infection.
 His earlier HIV treatment regimens.
In order to ensure maximum benefit from prophylaxis, treatment should start as early as
possible, within the first 6 hours following the exposure, without waiting for results of
HIV serology of the source person. A limit of 48 hours is reasonable in seeking maximum
efficacy.
 Duration of treatment is for 4 weeks (28 days). An initial prescription of 1 to 2 weeks
and weekly consultations enable close monitoring and psychological support so as to
strengthen adherence to treatment.
 The new recommended therapeutic regimen is:
TDF (Tenofovir) + 3TC / FTC (Lamivudine or Emtricitabine) + LPV/r (Kaletra)
TDF (Tenofovir) + 3TC/ FTC (Lamivudine or Emtricitabine + EFV (Efavirenz)
 If there is no TDF or a contraindication: AZT (Zidovudine) + 3TC (Lamivudine) +
LPV/r (Kaletra).

HIV STAGING BY WHO
 Clinical stage I
Asymptomatic
Generalized lymphadenopathy
Performance scale1: asymptomatic, normal activity
CD4 COUNT IS GREATER THAN 200PER CUBIC
MILLIMETER
 Clinical stage II
@Weight loss, less than 10% of body weight
@Minor muco-cutaneous manifestations( prurigo, fungal
nail infections, recurrent oral ulcerations)
@Herpes zoster within the last five years
@Recurrent upper respiratory tract infections
@CD4 COUNT IS GREATER THAN 200PER CUBIC
MILLIMETER

PERFORMANCE SCALE2: SYMPTOMATIC, NORMAL
ACTIVITY
 Clinical stage III
©Weight loss, more than 10% of body weight
©Unexplained chronic diarrhea, more than 1month
©Unexplained prolonged fever ( intermittent or constant)
, more than 1month
©Oral candidiasis
©Oral hairy leukoplakia
©Pulmonary tuberculosis
©Severe bacterial infections
©Performance scale 3:bedridden
©CD4 COUNT IS LESS THAN 200 CUIC MILLIMETER

 Clinical stage IV
@HIV wasting syndrome
@Pneumocystis carinii pneumonia
@Toxoplasmosis of the brain
@Cryptosporidiosis with diarrhea more than 1month
@Cryptococcosis, extrapulmonary
@Cytomegalovirus diseaseof an organ other than liver,
spleen or lymph node
@Lymphoma
@Extra pulmonary tuberculosis
@Kaposi’s sarcoma
@HIV encephalopathy
@Performance scale 4: bedridden
@CD4 COUNT LESSER THAN 200 CUBIC MILLIMETER

REFERENCES
@NATIONAL GUIDELINES FOR COMPREHENSIVECARE OF PEOPLE
LIVING WITH HIV IN RWANDA (NATIONAL GUIDELINES ON M
@ ANAGEMENT OF HIV IN RWANDA-Edition 2011)
@http: //hivdb.stanford.edu/cgi.bin/nrtiResiNote.cgi Stanford University,
Division of Infectious Diseases, Stanford, CA, USA
www.newtimes.rw (world AIDS special report )
@Emedicine.medscape.com
@www.cdc.gov
@Semiology lecturer notes
@www.aidsmap.com

Bacterial drug resistances phenomena
Anti-TB drug resistance

TUBERCULOSIS
®Tuberculosis (TB) is an infectious bacterial
disease caused by Mycobacterium
tuberculosis that are most commonly
affects the lungs, but it can also affect other
parts of the body, such as the brain, the
kidneys, or the spine.
®It is spread by people with active respiratory
disease through the air by coughing,
sneezing or even talking.

©TB organisms resistant to the antibiotics
used in its treatment are widespread and
occur in all countries surveyed.
©Drug resistance emerges as a result of
inadequate treatment and once TB
organisms acquire resistance they can
spread from person to person in the
same way as drug-sensitive TB.

Multidrug-resistant
Tuberculosis (M-DR TB)
@Multi-drug resistant tuberculosis (MDR-TB) is
a particularly complicated form of TB
@ is caused by an organism, characterized by
resistance to at least two most effective anti-TB
drugs
@Drugs are isoniazid and rifampicin, the two
most potent TB drugs.

EXTENSIVELY DRUG -RESISTANT
TUBERCULOSIS (XDR TB)
®Extensively drug resistant TB (XDR TB) is a
rare type of MDR TB that is resistant to
isoniazid and rifampin, plus any
fluoroquinolone and at least one of three
injectable second-line drugs (i.e., amikacin,
kanamycin, or capreomycin).
® XDR TB is of special concern for persons
with HIV infection or other conditions that
can weaken the immune system.

TB RE-TREATMENT
 Retreatment of tuberculosis occurs after a
person may, or may not, have completed the
scheduled treatment course for TB
 It can occur because of endogenous
reactivation or exogenous re-infection.
 An episode of retreatment TB could be a
consequence of a TB relapse or a re-
infection with a new TB strain.

Retreatment categories
© Retreatment TB after treatment completed: the
patient had completed the course of treatment but no
proof of cure is provided by the sputum smear test,
but the patient now smear positive.
© Retreatment TB after cure: the patient was treated
and became smear-negative on completion of the
treatment and now smear positive.
© Retreatment after default or interruption: the
patient interrupted the initial treatment for 2 or more
months. The patient may be smear-positive or smear-
negative, but still has active TB according to clinical or
radiological assessment.
© Retreatment after failure: The patient is on
treatment but remained smear-positive 5 months or
later after commencing TB treatment.

TB RELAPSE
@TB relapse is defined as a patient who has become
(and remained) culture negative while receiving
therapy
@Patient after completion of therapy becomes
culture positive again or has clinical or
radiographic deterioration that is consistent with
active tuberculosis.
@The selection of any empirical TB treatment for
patients with relapse should be based on the prior
treatment regimen and severity of disease.

EPIDEMIOLOGY OF TB RESISTANCE
® Epidemiology is “The study of the distribution
and determinants of health-related states or
events in specified populations, and the
application of this study to the control of
health problems” (John Last).
® An understanding of the epidemiology of
multidrug resistant tuberculosis (MDR-TB)
and the extensively drug-resistant tuberculosis
(XDR-TB) is critical for effective control of the
global burden of tuberculosis (TB) which is
caused by the organisms belonging to the
Mycobacterium tuberculosis complex.

Global epidemiology of MDR-TB
 Globally, around 50 000 cases of MDR-TB were
notiﬁed to WHO in 2010, mostly by European
countries and South Africa.
 This represented 18% of the 290 000 (range, 210
000– 380 000) cases of MDR-TB estimated to
exist among patients with pulmonary TB who
were notiﬁed in 2010.
 The proportion of TB patients estimated to have
MDR-TB that were actually diagnosed was under
10% in all of the 27 high MDR-TB countries
outside the European Region, with the notable
exception of South Africa where 81% of estimated
cases were diagnosed.

®15 high MDR-TB burden countries in the
European Region, the proportion of
estimated cases that were diagnosed ranged
from 24% (in Tajikistan) to over 90% of
cases (in Belarus and Kazakhstan).
®In Russian Federation, which ranks third in
terms of estimated numbers of cases of
MDR-TB at the global level, the proportion
of estimated cases that were diagnosed was
44% in 2010.

PREVENTION STRATEGIES OF TB RESISTANCE
@The most important way to prevent the spread of drug-
resistant TB is to take all TB drugs exactly as prescribed
by the health care provider. No doses should be missed
and treatment should not be stopped early.
@ People receiving treatment for TB disease should tell
their health care provider if they are having
trouble taking the drugs.
@Health care providers can help prevent drug-
resistant TB by quickly diagnosing cases, following
recommended treatment guidelines, monitoring
patients’ response to treatment, and making sure
therapy is completed.

 Another way to prevent getting drug-resistant TB is to
avoid exposure to known drug-resistant TB
patients in closed or crowded places such as
hospitals, prisons, or homeless shelters.
 People who work in hospitals or health-care settings
where TB patients are likely to be seen should consult
infection control or occupational health experts.
 Interrupt spread of MDR-TB by early detection,
effective treatment and containment of cases, and
identification of new cases among contacts.
PREVENTION STRATEGIES OF TB RESISTANCE

Treatment (Management)
@First-treatment (adults from 15 years)
@2 RHZE / 4 RH
@(total duration: 6 months)
@ Indications: New cases
H = isoniazid
R= rifampicin
Z = pyrazinamide
E= ethambutol.

Re-treatment
®2 SRHZE/ 1 RHZE / 5 RHE (total
duration: 8 months).
®Indications: relapses, failures to first
treatment, patients who return to
treatment after default, « other» cases
previously treated.

N: B (*) never give
Streptomycin to pregnant
women.
N: B (**) Patients > 50 years:
0.5-0.75 g/day maximum

First Treatment of Children between 0 - 14Years of
age: 2 (RHZ) E/ 4 (RH)

 Retreatment:
2 S (RHZ)E / 1 (RHZ)E / 5 (RH)E.
 Tuberculosis Meningitis and osteo-
articular TB:
2 (RHZE) / 10 (RH).
 In case of meningitis, give the maximum
dosage according to patient’s weight:
 Babies weighting less than 5 kg: Use the
dosages below according see dosages below

Multidrug-resistant
tuberculosis:
6 months of Kanamycin,
Pyrazinamide, Levofloxacin,
Prothionamid, Cycloserin (Km-
Z-Lfx-Pto-Cs) followed 14
months of Km-Z-Lfx-Pto-Cs,

TREATMENT REGIMENS FOR
MULTI-RESISTANT TB (CONT’D)

GROUPS OF DRUGS TO TREAT MDR-TB

GROUPS OF DRUGS TO TREAT MDR-TB
(CONT’D)

DOTS: INTERNATIONALLY RECOMMENDED
STRATEGY FOR TB CONTROL
The DOTS framework is organized around
the five components of the DOTS strategy
because the underlying principles are the
same:
® Sustained political commitment
® A rational case-finding strategy including
accurate, timely diagnosis through quality-
assured culture and DST

@Appropriate treatment strategies that use
second-line drugs under proper case
management conditions
@ Uninterrupted supply of quality-assured anti-
tuberculosis drugs
@Standardized recording and reporting system
@ Each of these components involves more
complex and costly operations than those for
controlling drug-susceptible TB.
@However, addressing drug-resistant TB usually
strengthens the national TB control programme.

SPECIAL CONSIDERATIONS FOR DOTS-PLUS
DOTS-Plus is more complex than the
basic DOTS strategy. For DOTS-Plus to
be successful, special attention is needed
for the following:
Quality-assured laboratory capacity
(smear, culture and DST);
Treatment design;
Adherence to difficult-to-take
regimens for long periods;

Side-effect management;
Drug procurement;
Recording and reporting; and
Human and financial resource
constraints.
SPECIAL CONSIDERATIONS FOR DOTS-PLUS

MDR-TB AND THE MECHANISMS OF
RESISTANCE
©Genetic and molecular analysis of drug
resistance in MTB suggests that resistance is
usually acquired by the bacilli either by
alteration of the drug target through
mutation or by titration of the drug through
overproduction of the target.
©MDRTB results primarily from accumulation
of mutations in individual drug target genes.

Resistance to INH
@Evidence suggests that INH inhibits the biosynthesis
of cell wall mycolic acids, thereby making the
mycobacteria susceptible to reactive oxygen radicals
and other environmental factors.
@Activation of INH to an unstable electrophilic
intermediate requires the enzyme catalase-peroxidase
(KatG, coded by katG) and an electron sink (hydrogen
peroxide),
@although hydrazine formed after INH spontaneously
decomposes may also mediate activation of INH.

®Nevertheless, KatG is the only enzyme
capable of activating INH, and
consequently, KatG mutant MTB strains
are invariably INH resistant.
®Mutations in the oxyR regulon, from which
AhpC is divergently transcribed, could
explain the acquisition of INH resistance in
the remaining INH-resistant isolates.

Resistance to RIF
 RIF had long been believed to target the
mycobacterial RNA polymerase and thereby
kill the organism by interfering in the
transcription process.
 Levin and Hatful demonstrated that RIF
specifically inhibited the elongation of full-
length transcripts and had virtually no
effect on the initiation of transcription.

©The rpoB locus from MTB was characterized and
mutations conferring the resistant trait were
identified.
©Most mutations were determined to be restricted to
an 81-bp core region and are dominated by single
nucleotide changes, resulting in single amino acid
substitutions, although inframe deletions and
insertions also occur at lower frequencies.
©Changes in the codons Ser531 and His526 have been
documented in more than 70% of the RIF-resistant
isolates.
©RIF’s permeability and mutations in alternate
subunits of RNA polymerase may also be involved in
conferring the resistance phenotype.

Resistance to EMB
 Synergy resulting from co-administration of
EMB and other drugs gave further evidence
for the involvement of EMB in obstructing
the formation of cell wall.
 The synergistic effect was explained as a
consequence of increased permeability of
the mycobacterial cell wall leading to
increased drug uptake.

 It was identified that arabinosyl transferase is the
primary target for EMB helped unravel the genetic
basis for EMB resistance.
 EMB interacts with the EmbCAB proteins encoded by
the embC, embA, and embB genes, leading to
inactivation of arabinogalactan synthesis.
 Mutations in the embB locus cause alterations in
EmbB, possibly leading to an altered target for EMB.
Alternatively.
 Hyper expression of the EmbCAB proteins could
lead to EMB resistance.

Resistance to PZA
 PZA, active against semi-dormant bacilli not affected
by any other drug, has strong synergy with INH and
RIF and shortens the chemotherapeutic schedule for
anti-tubercular treatment from 9 to 12 months to 6
months.
 Transformation of Pzase resistant strains with
functional construct of MTB pncA gene restored
susceptibility to PZA, providing further evidence that
mutations in the pncA gene were responsible in
conferring the resistant phenotype.

©Subsequent characterization of the pncA
gene from clinical isolates of MTB
confirmed these findings.
©Mutations Including missense alterations,
nucleotide insertions or deletions, and
termination mutations have been found in
the pncA gene from PZA resistant MTB
isolates.

Resistance to Fluoroquinolones
 DNA gyrase (Gyr), a member of the type II DNA
topoisomerases, is the primary target for FQ action.
 Gyr introduces negative supercoils in closed circular
DNA molecules and is a heterotetramer (A2B2), coded
by gyrA and gyrB respectively.
 FQs, synthetic derivatives of nalidixic acid, act by
inhibiting DNA supercoiling and relaxation activity of
Gyr without affecting the ATPase activity and enhance
the rate of DNA cleavage by Gyr.
 Cloning and expression of the MTB gyrA and gyrB
genes allowed mapping of mutations that confer
resistance to FQs.

® Mutations were found to be clustered in a small
region in GyrA that is close, approximately 40
residues amino terminal, in the linear amino acid
sequence to the active site tyrosine, other single
amino substitutions, for residues 88 to 94, were also
identified in ciprofloxacin-resistant MTB isolates.
® Alternative mechanisms to gyrA mutations,
including changes in cell wall permeability and active
quinolone efflux pumping, have also been proposed
and could account for the low-level resistance among
MTB isolates.

Resistance to Streptomycin and Other
Inhibitors of Protein Synthesis
© SM, one of the oldest drugs known to be active against MTB,
disrupts the decoding of aminoacyl-tRNA and thus inhibits
mRNA translation or causes inefficient translation.
© Two distinct classes of mutations including point mutations
in S12 ribosomal protein, encoded by rpsL gene113), and
mutations in the rrs operon encoding the 16S rRNA (114).
© Point mutations in the rpsL gene result in single amino acid
substitutions (114-117) that affect higher order structures of
16S rRNA and thereby confer SM resistance.

® Related aminoglycosides such as kanamycin,
amikacin, and paromomycin demonstrate no
® Obvious cross-resistance to SM and thus are
alternatives in cases of SM resistance.
® Viomycin and capreomycins are bacteriostatic agents
that act by binding to the 50S ribosomal subunit and
inhibit the translocation reaction.
® Although cross-resistance between viomycin and
capreomycin does occur, the exact mechanism for
acquisition of drug resistance is not known.

REFERENCES
 Article: Epidemiology of Multidrug Resistant
Tuberculosis (MDR-TB) Dhammika Nayoma
Magana-Arachchi
 Rwanda ministry of health: Clinical
treatment guidelines
 Guidelines for the programmatic
management of drug-resistant tuberculosis
 Who guidelines for tuberculosis treatment,
fourth edition.

Plasmodial resistances phenomena

INTRODUCTION
® Malaria is a mosquito-borne infectious disease of
humans and other animals caused by parasitic
protozoans (a type of single cell microorganism) of the
Plasmodium type.
® Malaria causes symptoms that typically include fever,
fatigue, vomiting and headaches.
® In severe cases it can cause yellow skin, seizures, coma or
death.
® These symptoms usually begin ten to fifteen days
after being bitten
® Commonly, the disease is transmitted by the bite of an
infected female Anophele mosquito.
® Four species of Plasmodium can infect and be spread by
humans: P. vivax, P. ovale. P. malariae P.
falciparum

MALARIA TRANSMISSION CYCLE
Parasite undergoes
sexual reproduction in
the mosquito
Some merozoites
differentiate into male or
female gametocyctes
Erythrocytic Cycle:
Merozoites infect red
blood cells to form
schizonts
Dormant liver stages
(hypnozoites) of P.
vivax and P. ovale
Exo-erythrocytic (hepatic) Cycle:
Sporozoites infect liver cells and
develop into schizonts, which release
merozoites into the blood
MOSQUITO
HUMAN
Sporozoites injected into
human host during
blood meal
Parasites
mature in
mosquito
midgut and
migrate to
salivary
glands

RETREATMENT
©The therapy of the same disease in a
patient, with the same agent or procedure
repeated after initial treatment, or with an
additional or alternate measure or follow-
up.
©It does not include therapy which requires
more than one administration of a
therapeutic agent or regimen.
© Retreatment is often used when the
original one was inadequate, harmful, or
unsuccessful

RECURRENCE: RELAPSE/ RECRUDESCENCE/RE-
INFECTION
 Depending upon the cause, recurrence can be classified as either
recrudescence, relapse, or reinfection.
 Recrudescence is when symptoms return after a symptom-free
period. Symptoms of malaria can recur after varying symptom-free
periods. It is caused by parasites surviving in the blood as a result of
inadequate or ineffective treatment.
 Relapse is when symptoms reappear after the parasites have been
eliminated from blood but persist as dormant hypnozoites in liver
cells. Relapse commonly occurs between 8–24 weeks and is
commonly seen with P. vivax and P. ovale infections; Can produce
periodic relapses up to 5 years
 P. vivax malaria cases in temperate areas often involve
overwintering by hypnozoites, with relapses beginning the year
after the mosquito bite.

©Re-infection means the parasite that caused the past
infection was eliminated from the body but a new
parasite was introduced.
©Reinfection happens in those who have recently
survived an infection, those who have not been
appropriately treated, disease may recur months
later.
©although recurrence of infection within two
weeks of treatment for the initial infection is
typically attributed to treatment failure
©People may develop some immunity when exposed to
frequent infections

TREATMENT FAILURE OF MALARIA
 A distinction must be made between a failure to clear malarial
parasitaemia or resolve clinical disease following a treatment
with an antimalarial drug and true antimalarial drug
resistance.
 While drug resistance can cause treatment failure, not all
treatment failure is due to drug resistance.
 Many factors can contribute to treatment failure:
 incorrect dosing,
 non-compliance with duration of dosing regimen,
 poor drug quality, drug interactions,
 poor or erratic absorption, and misdiagnosis.
 Probably all of these factors, while causing treatment failure
(or apparent treatment failure) in the individual, may also
contribute to the development and intensification of true drug
resistance through increasing the likelihood of exposure of
parasites to suboptimal drug levels.

Malaria treatment and
drug-resistance
Epidemiology-
mechanisms of
resistance –and-
management

EPIDEMIOLOGY
 Malaria occurs in over 90 countries worldwide.
 According to figures provided by the World Health
Organization (3), 36% of the global population live in areas
where there is risk of malaria transmission, 7% reside in
areas where malaria has never been under meaningful
control, and 29% live in areas where malaria was once
transmitted at low levels or not at all, but where significant
transmission has been re-established .
 The development and spread of drug-resistant strains of
malaria parasites has been identified as a key factor in this
resurgence and is one of the greatest challenges to malaria
control today.

Malaria distribution and reported
case of resistance or treatment failure

Countries with falciparum malaria
Few countries deployed ACTs
in selected provinces/districts
Adoption of ACT as first-line
treatment in 2000

Countries with falciparum malaria
Countries which adopted ACT
as 1st-line treatment
ACT as first-line malaria treatment
in 2006

Contine
nt
Countries Drug Line
AFRICA
Burundi, Cameroon, Côte d'Ivoire, DRC, Eq.Guinea, Gabon, Ghana,
Guinea, Liberia, Madagascar, Senegal, ST&P, Sierra Leone, Sudan (S),
Zanzibar
AS + AQ 1st
Angola, Benin, Burkina Faso, Comoros, Ethiopia, Gambia, Guinea
Bissau, Kenya Mali, Namibia, Niger, Nigeria, Rwanda, Uganda, S. Africa,
Tanzania, Togo, Zambia
AL 1st
Côte d'Ivoire, Gabon, Mozambique, Sudan (N), ST&P, Zanzibar AL 2nd
Mozambique, Sudan (N), South Africa (Mpumalanga) AS + SP 1st
ASIA
Cambodia, Thailand AS + MQ 1st
Bangladesh, Bhutan, Laos, Myanmar AL 1st
Indonesia AS + AQ 1st
Afghanistan, India (5 Provinces), Iran, Tajikistan, Yemen AS + SP 1st
Viet Nam DP 1st
Papua New Guinea AS + SP 2nd
Philippines, Iran AL 2nd
SOUTH
AMERICA
Ecuador, Peru AS + SP 1st
Bolivia, Peru, Venezuela AS + MQ 1st
Brazil, Guyana, Suriname AL 1st
30% deploying
AQ=amodiaquine; AL=artemether/lumefantrine; AS=artesunate; DP=dihydroartemisinin/piperaquine;
MQ=mefloquine; SP=sulfadoxine/pyrimethamine
60% deploying
71% deploying
More countries are deploying ACTs

MALARIA MANAGEMENT ACCORDING RWANDA
CLINICAL STGs
SIMPLE MALARIA
® First line treatment
 Artemisinin combination therapy (ACT)
 Artemether 20 mg and Lumefantrine 120 mg, twice a day for 3 days
 Paracetamol: 15mg/ kg TID
@ Contraindications
 Children weighing less than 5 kg
 First trimester pregnancy
 Allergy to one of the two drugs in the combination
 Severe liver or renal disease
© Alternative:
 Oral Quinine sulphate 10 mg / kg TID for 7 days;
Simple malaria with minor digestive symptoms
 Artesunate IV: 2.4 mg/kg (time = 0) then at 12 hour, then daily thereafter
 If no more vomiting, change to oral Artemether- Lumefantrine twice a day
for three consecutive days

 Alternative
@ children: Quinine dihydrochloride (Salt)
@ adult: oral Quinine sulphate 10 mg / kg TID for 7 days
SEVERE MALARIA
 Admit the patient
 First choice: Artesunate IV 2.4 mg/kg IV (time = 0), then at 12h
and 24h, then once a day for three days.
 Then continue with Artemisinin combination therapy (ACT):
Artemether 20 mg and Lumefantrine 120 mg, twice a day for 3
days
 Alternative: Quinine IV

THE PHARMACOLOGY OF ANTIMALARIALS
Class
Definition
Examples
Class Definition Examples Class Definition Examples
Blood
schizonticidal
drugs
Act on (erythrocytic) stage of the
parasite thereby terminating
clinical illness
Quinine, artemisinins,
amodiaquine, chloroquine,
lumefantrine, tetracyclinea ,
atovaquone, sulphadoxine,
clindamycina , proguanila
Tissue
schizonticidal
drugs
Act on primary tissue forms of
plasmodia which initiate the
erythrocytic stage. They block
further
development of the
infection
Primaquine, pyrimethamine,
proguanil, tetracycline
Gametocytocidal
drugs
Destroy sexual forms of the
parasite thereby preventing
transmission of infection to
mosquitoes
Primaquine, artemisinins,
quinineb
a Slow acting, cannot be used alone to avert clinical symptoms
b Weakly gametocytocidal

THE PHARMACOLOGY OF ANTIMALARIALS (cont.)
Class Definition
Examples
Class Definition
Examples
Class Definition
Examples
Hypnozoitocidal
drugs
These act on persistent
liver stages of P.ovale
and P.vivax which cause
recurrent illness
Primaquine,
tafenoquine
Sporozontocidal
drugs
These act by affecting
further development of
gametocytes into oocytes
within the mosquito thus
abating transmission
Primaquine, proguanil,
chlorguanil

PROPHYLAXIS
Currently in Rwanda, investments have been made in all areas of
malaria control:
® Vaccine and drug development,
® vector control, infrastructure development,
® and improving service delivery and accessibility where it is most
needed.
Two approaches with potential for immediate results are
@ Exposure reduction through long-lasting insecticide-treated
bed nets (LLINs),
@ indoor residual spraying, and larvicides,
@ early treatment using community health workers

PROPHYLAXIS cont’d
 Rwanda has undertaken an aggressive
community-based prevention and early
treatment strategy as part of its national
malaria control programme with excellent
preliminary results, including a 66%
reduction in childhood deaths attributed to
malaria and in pregnant women.

PROPHYLAXIS TREATMENT
 The prophylaxis of malaria lies in the use of
mosquito bednets,the use of antisecticides,
wear clothes long sleeves and pants, use of
repellants, sensitization to mosquito
bednets, especially for vulnerable
populations, etc
 Also, it is advised, to take preventive drugs,
when planning to come or travelling in
malaria-risk world regions:

PREVENTION IN RWANDA …..ctd
®Here in Rwanda ,
®the common preventive drug is
Mefloquine,
®sometimes combined with doxcycline
an antibiotic used to prevent malaria-
resistant to other drug, in chloroquine-
resistant areas.

ANTIMALARIAL DRUG
RESISTANCE DEFINITION
AND MECHANISMS OF
RESISTANCE

DEFINITION
@Antimalarial drug resistance has been defined as
the “ability of a parasite strain to survive and/or
multiply despite the administration and
absorption of a drug given in doses equal to or
higher than those usually recommended but
within tolerance of the subject”.
@This definition was later modified to specify that
the drug in question must “gain access to the
parasite or the infected red blood cell for the
duration of the time necessary for its normal
action”

MDR-XDR OF MALARIA
®The term drug-resistant malaria originally
referred to P.Falciparum strains to clroroquine,
SP, or both.
®MDR of P.Falciparum is strictly defined as
resistance to more than 2 antimalarial
compounds of different chemical classes.
®The emergence of artemisinin resistance
creates the need to define a new subgroup of
drug-resistant malaria:XDR-malaria

@XDR-malaria signifies a potential loss of
artemisinin, and highlights the threat of an
expand malaria endemic area with poor ACT
efficacy, similar to prior global spread of
antimalarial drug resistance for other
chemical classes

MECHANISMS OF RESISTANCE
©In general, resistance appears to occur through
spontaneous mutations that confer reduced
sensitivity to a given drug or class of drugs.
©For some drugs, only a single point mutation is
required to confer resistance, while for other drugs,
multiple mutations appear to be required.
©Provided the mutations are not deleterious to the
survival or reproduction of the parasite, drug
pressure will remove susceptible parasites while
resistant parasites survive.

 Over time, resistance becomes established in
the population and can be very stable,
persisting long after specific drug pressure is
removed.
 The biochemical mechanism of resistance
has been well described for chloroquine,
the antifolate combination drugs, and
atovaquone.

MECHANISM OF RESISTANCE: CHLOROQUINE RESISTANCE
® As the malaria parasite digests haemoglobin, large amounts of a toxic
by-product are formed.
® The parasite polymerizes this by-product in its food vacuole, producing
non-toxic haemozoin (malaria pigment).
® It is believed that resistance of P. falciparum to chloroquine is related to
an increased capacity for the parasite to expel chloroquine at a rate that
does not allow chloroquine to reach levels required for inhibition of haem
polymerization
® This chloroquine efflux occurs at a rate of 40 to 50 times faster among
resistant parasites than sensitive ones .
® Further evidence supporting this mechanism is provided by the fact that
chloroquine resistance can be reversed by drugs which interfere with this
efflux system.

MECHANISM OF ANTIFOLATES
PABA
DHF SYNTHETASE
DHF
DHF REDUCTASE
THF

MECHANISMS OF RESISTANCE: ANTIFOLATE COMBINATION DRUGS
 Antifolate combination drugs, such as sulfadoxine +
pyrimethamine, act through sequential and synergistic
blockade of 2 key enzymes involved with folate synthesis:
 Pyrimethamine and related compounds inhibit the step
mediated by dihydrofolate reductase (DHFR)
 while sulfones and sulfonamides inhibit the step mediated by
dihydropteroate synthase (DHPS).
 Specific gene mutations encoding for resistance to both
DHPS and DHFR have been identified.
 Specific combinations of these mutations have been associated
with varying degrees of resistance to antifolate combination
drug

MECHANISM OF RESISTANCE: ATOVAQUONE
@Atovaquone acts through inhibition of electron
transport at the cytochrome bc1 complex .
@Although resistance to atovaquone develops very
rapidly when used alone, when combined with a
second drug, such as proguanil or tetracycline,
resistance develops more slowly .
@Resistance is conferred by single-point mutations in
the cytochrome-b gene.

STRATEGIES TO DRUG RESISTANCE
PREVENTION
@Prevention strategies can be divided into:
 Those aimed specifically at preventing
malaria infection,
 and those aimed at reducing the likelihood
of development of drug resistance.
@To achieve these, five activities (strategies) are
proposed by GPARC (Global Plan for
Artemisinin Resistance Containment):

1. Stop the spread of resistant parasites.
 In areas for which there is evidence of artemisinin
resistance, an immediate comprehensive response using a
combination of malaria control and elimination measures is
needed to stop the survival and spread of resistant parasites.
2. Increase monitoring and surveillance to evaluate the
threat of artemisinin resistance.
 Regular monitoring and surveillance are essential to
rapidly identify new foci of resistant parasites and to provide
information for containment and prevention activities.
Countries endemic for malaria should undertake routine
monitoring of antimalarial drugs at sentinel sites every 24
months in order to detect changes in their therapeutic
efficacy .

3. Improve access to diagnostics and rational treatment
with ACTs.
 Programmes should ensure: consistent, accurate
diagnostic testing of suspected malaria cases; better
access to ACTs for confirmed cases; compliance with ACT
treatment; and removal from the market of oral
artemisinin-based monotherapies as well as substandard
and counterfeit antimalarial medicines.
4. Invest in artemisinin resistance-related research.
 Research is important to improve understanding of
resistance and the ability to manage it. Priority should be
given to research in five disciplines should be a priority:
laboratory research, research and development, applied
and field research operational research, and
mathematical modeling.

Chloroquine resistant malaria
 1.Quinine 600mg TDS for 7 days along with
 Pyrimethamine 75mg+sulfadoxine 1500mg
 2. Quinine 600mg TDS + Teracycline 250mg qid -7 days.
 3.Mefloquine 750mg stat followed by 500mg 12hr later.
 4. Artesunate 100mgBD on 1stday followed by 100mg OD -5
days
 5.Artesunate iv/im 120mg on 1st day followed by 60mg daily-4
days
 6.Artemether (im)-80mg BD 1st day followed then OD -4
days.
 7.Artemether (im)-150mg od -3 days.

5. Motivate action and mobilize
resources.
Successful implementation of
the GPARC will depend on
motivating many stakeholders
at global, regional and national
levels to support or conduct the
recommended activities.

TREATING DRUG RESISTANCE IN
P.FALCIPARUM
 Should be treated with
Quinine sulphate plus single dose of
Combination Drug Pyrimethamine and
Sulphodoxine ( Fansidar )
 Other Alternatives
 1 Quinine plus Doxycycline or Tetracycline
 2 Quinine plus Clindamycin
 Newer alternatives
1 Mefloquine and Halofantril.

REFERENCES
1.WHO Guidelines for the treatment of
malaria Second edition
2. Internal Medicine Clinical treatment
guidelines in Rwanda
3. Malaria National Treatment Guidelines.
4. Malaria Journal: Reduced paediatric
hospitalizations for malaria and febrile illness
patterns following implementation of community-
based malaria control programme in rural Rwanda
( August 2008)

Advanced pharmaceutical care and anti microbial resistance

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