Kingdom of Saudi Arabia
Ministry of Health
Preventive Medicine Directorate
Plan of Action For
Prevention & Control of
Avian Influenza
Contents
Item
page
Contents
Introduction
Plan objectives
Plan components
Vaccination with human influenza vaccine
Usage of tamiflu medication
Health education
Treatment
Clinical course and prevention and control
Case definition of avian influenza
Infection control precautions in hospitals
Precautions when dealing with diseased patients
Laboratory sample taking and handling specimen
Keeping and transporting the specimens
Epidemiological surveillance forms
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4
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5
6
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7-10
11-12
13-15
15
16-17
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18-21
Introduction
Avian influenza is an infectious disease of birds and some mammals and it is caused by
A strains of the influenza virus. The ongoing outbreak is due to a highly pathogenic
strain (H5N1).
Fifteen subtypes of influenza viruses are known to infect birds thus providing an
extensive reservoir of influenza viruses potentially circulating in birds population. To
date all outbreaks of the highly pathogenic form have been caused by influenza A
viruses of subtypes H5N1 and spread in some countries of the South East Asia like Viet
Nam, Cambodia, Thailand, Indonesia and also in China, Russia and Kazakhstan.
Migratory waterfowl-most notably wild ducks-are the natural reservoir of avian
influenza viruses. Domestic poultry, including chickens and turkeys, are particularly
susceptible to epidemics of rapidly fatal influenza.
Direct or indirect contact of domestic flocks with mild migratory waterfowl has been
implicated as frequent cause of epidemics. Live birds market have also played an
important role in the spread of epidemics.
A part from being highly contagious, avian influenza viruses are readily transmitted
from farm to farm by mechanical means, such as by contaminated equipment, vehicles,
feed cages, or clothing. Highly pathogenic viruses can survive for long periods in the
environment, especially when temperatures are low.
The virus transmitted to human by direct contact with infected birds or infected surfaces
or equipments.
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Plan objectives
To protect the kingdom from importation of the avian influenza virus, through strict
regulations. Strict regulations can prevent importation of the virus to the kingdom and
also to delay the spread of the disease and reduce mortality in case of epidemics.
Plan components
1) Surveillance of the disease
2) Laboratory surveillance
3) Vaccination
4) Usage of Tamiflu medication for the disease prophylaxis.
5) Treatment
6) Health education.
7) Infection control in hospitals.
8) Coordination with other governmental sectors of concern (Ministry of
agriculture, Ministry of municipality).
9) None medical intervention
10 ) Needs.
11) Other regulations.
Details of the components
1) Disease surveillance:
▪ Surveillance of the disease during the whole year.
▪ The immediate notification of suspected cases (according to the case
definition of the WHO and the attached forms) from all hospitals
included private hospitals to the regional health directorates, and to the
infectious diseases department in the Ministry of Health.
▪ Epidemiological investigation for suspected cases to be carried out and
the investigation form to be sent to regional health affair and to the
infectious diseases department in MOH.
▪ Refer any suspected case at the border points to the nearest hospital
of MOH.
2) Laboratory surveillance
▪ Two laboratories have been chosen for the specimen analysis:
A) Central laboratory in Riyadh.
B) Regional laboratory in Jeddah
▪ Train specialist from these laboratories in the laboratories of NAMRO3
in the coordination with WHO East Mediterranean Regional Office EMRO.
▪ Availability of the laboratory reagents.
3) Vaccination
According to WHO recommendations human influenza vaccine can be used against
avian influenza (it will not protect humans from infection with avian influenza – rather
it minimizes the risk of co-infection and genetic re-assortment of human and avian
influenza viruses in humans). The vaccination will be for the high risk groups. Mass
vaccination of all inhabitants of affected area is not supported by current
epidemiological data.
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The high risk groups candidate for vaccination:
First: these groups should be vaccinated at the moment:
- Workers at poultry farms.
- Workers at laboratories who are handling the suspected specimen.
- Elderly (over 65 years of age) who are suffering from chronic diseases
(Cardiovascular, diabetes millets, immunosupressed illnesses, AIDS, organ
transplanted individuals).
- All health care workers in hospitals and primary care centers in the holey capital
( Mekka) and those who work in the surveillance units at the borders.
- Workers in Tuwafa groups
- Workers in borders (ports and airports) from different governmental sectors.
- Workers in the Harams in Mekka and Al - Medina.
Second: in case of epidemic in the kingdom add the below categories ( first
defense line)
▪ All health workers in all governmental and private hospitals.
▪ Workers in police, traffic, borders and security forces.
▪ Workers in civil defense.
▪ All workers in airports, airplanes, trains, transnational buses, ships..
▪ Saudi army soldiers.
▪ National Guard.
▪ Health staff in Red Crescent
4) Usage of tamiflu for prophylaxis from avian influenza
Tamiflu capsules can be used for prophylaxes in the beginning of outbreak to the
closed contacts, to patients and to the high risk groups who were mentioned below:
First: at the time of epidemic prophylaxis should be given to:
- Workers in poultry farms
- Workers of laboratories who are handling the suspected specimen.
- Elderly (over 65 years of age) who are suffering from chronic diseases
(Cardiovascular, diabetes millets, immunosupressed illnesses, AIDS, organ
transplanted individuals).
If the epidemic is before Hajj time the following should take prophylaxes
- All health services worker who work in the hospitals and primary care
centers in the Holley capital ( Mekka) and those who work at the
border points.
- Workers in Tuwafa groups
- Workers in border points from different governmental sectors.
- Workers in the Haram in Mekka and Al-Medina.
Secondly: if the epidemic spread to more parts of the kingdom to add the
following categories:
- All health workers in the governmental and private hospitals
- Health staff in Red Crescent.
- Workers in police, traffic, borders and security forces.
- Workers in civil defense.
- All workers in airports, airplanes, trains, transnational buses, ships..
- Saudi arm forces.
- National guard.
Prophylaxis Usage of Tamiflu
The prophylactic dose of tamiflu capsule is 75 mg once daily orally for at least 7
days.
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5) Health Education
▪ Educate all health staff about the disease, the importance of the immediate
notification of any suspect case and the ways of infection control and precautions.
▪ Education the public about the disease transmission and prevention.
▪ Announce to the public in case of pandemic the limitation of the vaccine and
treatment and it will be given to the first line defense group.
▪ The importance for the authorities to gain the trust of the public for given the right
information through a professional qualified teem.
6) Treatment
For patients of avian influenza the following treatment is recommended:
- Treat the symptoms like fever, cough, sore throat and others.
- Antiviral medication can be used for treatment and prophylaxes for the most risky
groups like (first contacts with patients, working in
laboratories.etc). The drug of choice is Tamiflu capsules ( 75mg
twice daily for 5 days)
7) Infection Control in The Hospitals
▪ Strictly follow the regulations of infection control in hospitals and laboratories
▪ Precautions of respiration and intestinal discharge transmission of the virus.
▪ Usage of surgical mask for the medical teem.
▪ Put the patient in a single negative pressure room.
8) Coordination with other governmental sectors of concern:
To exchange the information with other governmental sectors like
Ministry of Agriculture, Ministry of commerce and Ministry of
Municipality, to make necessary regulations to prevent the importation
of the virus through birds (chicken, turkey .
9) None medical interference regulations to stop the spread of the disease.
- Close schools.
- Limitation of crowdness
- To limit traveling and unnecessary movements.
- Isolation of the patients contacts for 7-10 days.
10) Needs
▪ Availability of human influenza vaccine to be used for emergencies and at Hajj
season.
▪ Availability of antiviral medication like Tamiflu capsules or syrups.
▪ Availability of laboratories reagents to make the necessary tests.
11) Other regulations
a) Communicate with other governmental sectors to make the vaccine
available for their employees (Ministry of defense, National guard,
Ministry of interior affairs, general security service)
b) Communicate with ministry of Hajj to reassure the interior citizens and residents.
who are going to hajj to be vaccinated with influenza human vaccine.
c) Make announcement in the newspapers for the travelers to hajj to be
vaccinated with influenza vaccine.
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Avian Influenza
Clinical Course and Guidelines
For Prevention and Control
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Avian influenza
Avian influenza is an infectious disease of birds caused by A strains of the influenza
virus the highly pathogenic strain of which is H5N1. The disease, which was first
identified in Italy more than 100 years ago, occurs worldwide. Migratory birds -most
notably wild ducks- are the natural reservoir of avian influenza viruses. Domestic
poultry, including chickens and turkeys, are particularly susceptible to epidemics of
rapidly fatal influenza.
Disease in birds
Infection causes a wide spectrum of symptoms in birds, ranging from mild illness to a
highly contagious and rapidly fatal resulting in severe epidemics.
Transmission in birds
Infected birds shed the virus in their saliva, nasal secretions, and feces. Susceptible
birds become infected when they have contact with contaminated excretions or surfaces
that are contaminated with excretions. Direct or indirect contact of domestic flocks with
wild migratory waterfowl has been implicated as frequent cause of epidemics. Live
birds market have also played an important role in the spread of epidemics.
A part from being highly contagious, avian influenza viruses are readily transmitted
from farm to farm by mechanical means, such as by contaminated equipment, vehicles,
feed cages, or clothing. Highly pathogenic viruses can survive for long periods in the
environment, especially when temperatures are low.
Disease in humans
Avian influenza viruses do not normally infect species other than birds and pigs. The
first documented infection of humans with an avian influenza virus occurred in Hong
Kong in 1997, when the H5N1 strain caused severe respiratory disease in 18 humans, of
whom 6 died. The infection of humans coincided with an epidemic of highly pathogenic
avian influenza, caused by the same strain, in Hong Kong’s poultry population. Since
December 2003 and till now four countries in the South East Asia notified human cases
of avian influenza H5N1 (Indonesia, Viet Nam, Thailand, Cambodia).
Mode of transmission from bird to humans
Direct contact with infected poultry or surfaces and objects contaminated by their
droppings, is considered the main route of human infection. Exposure risk is considered
highest during slaughter, defeathering, butchering, and preparation of poultry for
cooking.
Why H5N1 is of particular concern
Of the 15 avian influenza virus subtypes, H5N1 is of particular concern for several
reasons. H5N1 mutates rapidly and has a documented propensity to acquire genes from
viruses infecting other animal species. In addition, laboratory studies have demonstrated
that isolates from this virus have a high pathogenicity and can cause severe disease in
humans. Birds that survive infection excrete virus for at least 10 days, orally and in
faeces, thus facilitating further spread at live poultry markets and by migratory birds.
The epidemic of highly pathogenic avian influenza causes by H5N1, which began in
mid-December 2003 in the republic of Korea and is now being seen in other Asian
countries, is therefore of particular public health concern. H5N1 variants demonstrated
a capacity to directly infect humans in 1997, and have done so again in Viet Nam in
January 2004. The spread of infection in birds increases the opportunities for direct
infection of humans. If more humans became infected over time, the likelihood also
increases that humans, if concurrently infected with human and avian influenza strains,
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could serve as the “mixing vessel” for the emergence of a novel subtype with sufficient
human genes to be easy transmitted from person to person. Such an event would mark
the start of an influenza pandemic.
Cumulative Number of Confirmed Human Cases of Avian influenza (H5N1)
Reported To WHO, 10 October 2005:
Date of onset
26.12.00310.03.004
19.07.00408.10.004
16.12.004To date
Total
Indonesia
Viet Nam
Thailand
Cambodia
Totals
Cases
Deaths
Cases
Deaths
Cases
Deaths
Cases
Deaths
Cases
Deaths
0
0
23
16
12
8
0
0
35
24
0
0
4
4
5
4
0
0
9
8
5
3
64
21
0
0
4
4
73
28
5
3
91
41
17
12
4
4
117
60
Incubation period
2 to 3 days (range 1-7 days)
Symptoms and signs
. Fever > 38° C
. Cough
. Sore throat
. Rhinorrhoea
. Shortness of breath, respiratory failure, pneumothorax
. x-ray changes compatible with pneumonia
. Peripheral leukocytes were normal or decreased.
. Lymphopenia
. Mild to moderate elevation in hepatic transaminases.
Diagnosis:
Depends on clinical picture and positive lab. Investigation of one or more of the
following:
. Positive viral culture for influenza A/H5
. Positive polymerase chain reaction ( PCR) for influenza A/H5
. Positive immunofluorescence antibody ( IFA ) for influenza A/H5 using monoclonal
antibodies
. 4-Fold rise in H5- specific antibody titer in paired serum samples
Treatment
a. Patient:
- Take respiratory and blood specimens for lab. Investigations.
- Put the patient in a single room with negative pressure. If a single room is not
available, cohort confirmed cases should be put in multi-bed rooms or wards and
preferably be separated by physical barrier (e.g. curtain, partition).
- Antiviral drugs (neuraminidase inhibitors) like oseltamivir (Tamiflu) should be
initiated as early as possible 75 mg orally twice daily for 5 days..
- Broad spectrum antibacterial drugs to cover for the secondary bacterial infections.
-.Avoid administration of salicylates (such as aspirin) in individual under 18 years
of age. Use paracetamol or ibuprofen for management of fever as clinically
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indicated. Do not use amantadine or rimantadine or ribavirin.
b. Contacts:
- All contacts should be put in direct surveillance and monitor their health for 7 days.
- Advice them to check their body temperature twice a day.
- If they develop a sudden high fever (> 38° C) and more and sore throat they should
start antiviral treatment.
c. Health Staff who were involve in caring for a patient with A(H5N1):
- Should receive training on the mode of transmission, the appropriate infection
control precautions.
- Check temperature twice daily and monitor self for respiratory symptoms especially
cough.
- Antiviral prophylaxis with Tamiflu 75 mg daily for at least 7 days.
- Use personal protection equipments (PPE) e.g. gloves, high efficiency mask, longsleeved cuffed gown, cap, plastic apron if splashing of blood, body fluids,
excretions and secretions is anticipated.
Preventive Measure
1- Educate the public about the mode of transmission and the appropriate control
precautions.
2- Cullers and transporters should be provided with appropriate (PPE).
3- All persons who have been in close contact with infected animals should wash
their hands frequently with soap and water. Cullers and transporters should
disinfect their hands after the operation.
4- Antiviral prophylaxis treatment with Tamiflu 75 mg daily for at least 7 days for
individuals under high risk (cullers, transporters, veterinarians, workers in
laboratories dealing with A (H5) virus, health workers caring for patient with
avian influenza ).
5- The above risk group should be vaccinated with the current WHO recommended
influenza vaccine to avoid simultaneous infection by human influenza and avian
influenza and to minimize the possibility of a re-assortment of the virus gene.
6- Appropriate infection control precautions should be carried out in hospitals and
laboratories.
7- Intersector coordination (Ministry of Agriculture, Ministry of Municipality,
Ministry of Trading and Industry).
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Avian Influenza A/H5 Case Definition
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Avian Influenza A/H5 Case Definition
Patient under investigation ( suspect case )
Any individual presenting with fever (temperature >38° C)
AND one or more of the following symptoms:
Cough,
Sore throat,
Shortness of breath.
Possible influenza A/H5 case
i. Any individual presenting with fever (temperature >38° C)
AND one or more of the following symptoms:
Cough,
Sore throat,
Shortness of breath.
AND one or more of the following:
. Laboratory evidence for influenza A by a test that does not sub-type the virus.
. Having been in contact during the 7 days prior to the onset of symptoms with a
confirmed case of influenza A/H5 while this case was infectious.
. Having been in contact during the 7 days prior to the onset of symptoms with
birds, including chickens that have died of an illness.
. Having worked in a laboratory during the 7 days prior to the onset of symptoms
where there is processing of samples from persons or animals that are
suspect of having highly pathogenic avian influenza (HPAI) infection.
OR
ii. Death from an unexplained acute respiratory illness
AND one or more of the following;
. Residing in area where HPAI is suspected or confirmed.
. Having been in contact during the 7 days prior to the onset of symptoms with a
confirmed case of influenza A/H5 while this case was infectious.
Probable influenza A/H5 case
Any individual presenting with fever (temperature >38° C)
AND one or more of the following symptoms:
Cough,
Sore throat,
Shortness of breath.
AND limited laboratory evidence for influenza A/H5 (H5 specific antibodies detected in
a single serum specimen).
Confirmed influenza A/H5 case
An individual with an acute respiratory febrile illness for whom laboratory testing
demonstrates one or more of the following:
. Positive viral culture for influenza A/H5
. Positive PCR for influenza A/H5
. Immunofluorescence antibody (IFA) test positive using influenza A/H5
monoclonal antibodies.
. 4-fold rise in influenza A/H5 specific antibody titre in paired serum samples.
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Infection control precautions in hospitals
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Infection control precautions for influenza A(H5N1)
Infection control for influenza A(H5N1) involves a two-level approach:
1- Standard precautions which apply to all patients at all times, including those
who have influenza A(H5N1) infection. These include the following:
. hand washing and antiseptics (hand hygiene)
. use of personal protective equipment (PPE) when handling blood, body substances,
excretions and secretions.
. appropriate handling of patient care equipment and soiled linen.
. prevention of needle stick sharp injuries.
. environmental cleaning and spills management.
. appropriate handling of waste.
2- Additional precautions:
Additional (transmission-based) precautions are taken while still ensuring standard
precautions are maintained, these include:
a. Droplet precautions,
b. Contact precautions,
c. Airborne precautions including the use of high efficiency mask, negative
pressure rooms if available.
A combination of these precautions will give the appropriate infection control. The
precautions should be implemented while the patient is infectious:
. adult > 12 years of age: precautions to be implemented at time of admission
and continued until 7 days have lapsed since resolution of fever.
. children < 12 years of age: precautions to be implemented at time of
admission and continued until 21 days have lapsed since onset of illness.
The following precautions need to be taken:
- Implement and/or reinforce standard precautions.
- Place patient in a single room preferably negative pressure room.
- Ensure that anyone who enters the room wears appropriate PPE.
- Limit the movement and transport of the patient.
- Wear clean, non sterile gloves when entering the room.
- Wear clean, non sterile gown when entering the room if substantial contact with
the patient, environmental surfaces or items in the patient’s room is anticipated.
Who should use personal protective equipment?
- All health care workers who provide direct patient care e.g. doctors, nurses,
radiographers, physiotherapists.
- All support staff including medical aides and cleaning staff.
- All laboratory workers handling specimens from a patient being investigated for
influenza A(H5N1).
- All sterilizing service workers handling equipment that requires
decontamination and has come from a patient with influenza A(H5N1).
- Family members or visitors.
Cleaning and disinfection:
The virus is inactivated by 70% alcohol and by chlorine, therefore cleaning of
environmental surfaces with a neutral detergent followed by a disinfectant solution is
recommended.
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Staff health management:
Health care workers who are involved in caring for a patient with A(H5N1) should
receive training on the mode of transmission, the appropriate infection control
precautions.
It is recommended that all health care workers who are expected to have contact with
influenza A(H5N1) virus or an influenza A(H5N1) patient or contaminated environment
should take the following steps:
1- They should be vaccinated with the current WHO recommended human
influenza vaccine as soon as possible ( this will not protect against influenza
A(H5N1), but it will help to avoid simultaneous infection by human influenza
and avian influenza, also will minimize the possibility of re-assortment.
2- They should take one oseltamivir phosphate (tamiflu) tablet 75 mg daily for at
least 7 days beginning as soon as possible after exposure.
Self-management:
Observe good respiratory and hand hygiene at all times and:
1- Check temperature twice daily and self monitoring for respiratory symptoms
especially cough.
2- Where at all possible, keep a personal diary of contact.
3- In the event of a fever, immediately limit interactions and exclude yourself from
public areas. Notify this event.
Discharging the patient:
1- The infection control precautions should be implemented:
. 7 days after resolution of fever, for adult > 12 years of age.
. 21 days after onset of illness- for children < 12 years of age.
2- The patient and family should be educated about the appropriate precautions to
take when put in contact with chicken, birds.
3- Carry out appropriate cleaning and disinfection of the room after discharge.
Care of the deceased:
1- Follow standard precautions when caring for the deceased patient.
2- Wear full PPE.
3- The body should be fully sealed in an impermeable body bag prior to transfer to
the mortuary.
4- No leaking of body fluids should occur and the outside bag should be clean.
5- Transfer to the mortuary should occur as soon as possible after death.
6- If the family wishes to view the body they should wear gloves and gown.
7- Cultural sensitivity should be practiced.
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Specimen collection of a suspected avian influenza case
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Specimen collection of a suspected avian influenza case:
General recommendations
Following standard precautions, all specimens should be regarded as potentially
infectious and staff that take, collect or transport clinical specimens should adhere
rigorously to protective measures in order to minimize exposure.
These protective measures can be summarized as follows:
- Standard precautions should always be followed barrier protection (gowns,
gloves, eyes protection) whenever samples are obtained from patients.
- Good laboratory practices should be followed. Eating .smoking, drinking..etc are
prohibited in the laboratory working area.
- Biological safety cabinets or other physical containment devices should used for
all manipulations that may cause splashes, droplets, or aerosols of infectious
materials.
- Adequate and conveniently located biohazard containers should be available for
disposal of contaminated material.
- Work surfaces must be decontaminated after any spill of potentially dangerous
material and at the end of the working day. Generally 5% bleach solution is
appropriate for dealing with bio-hazardous spillage.
Storage and transporting of human specimens for laboratory diagnosis of
suspected avian influenza
Specimen storage:
Specimens in viral transport medium for viral isolation should be kept at 4º C and
transported to the laboratory promptly. If specimen is transported to the laboratory
within 2 days, it may be kept at 4º C, otherwise it should be frozen at or below - 70º C
until it can be transported to the laboratory. Sera may be stored at 4º C for
approximately one week, but thereafter should be frozen at -20º C.
Specimen transport:
Transport of specimen should comply with the WHO guidelines for the safe transport of
infectious substances and diagnostic specimens.
- The receiving laboratory should be notified before shipment of specimens in
order to arrange for an import license for the specimen.
- All the specimen should be transported through DHL and telling them about
the precautions.
- All specimens to be transported must be packed in triple packaging consisting of
three packaging layers as indicated in the dangerous goods index.
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Epidemiological Surveillance Forms
18
Kingdom of Saudi Arabia
Ministry of health
Directorate of health affairs……
Hospital………………………..
Epidemiological Surveillance of a suspected case of avian
influenza
Name……………………………………….gender ……………………………
Nationality………………………………….age………………………………..
Place of arrival………………………passport No (non Saudis)………………
Date of arrival to the kingdom……………date of symptoms onset……………
Address in the kingdom …………………………………………………………
Telephone home …………………………telephone mobile……………………
Movement of the patient during the week before the onset of symptoms
(Countries which passed by) ……………………………………………………
……………………………………………………………………………………………
……………………………………………………………………………………………
……………………………………………………………………
Symptoms and signs at the entry points
Yes
No
Fever
□
□
Sore throat
□
□
Respiratory distress
□
□
Cough
□
□
Other symptoms (specify)………………………………………………………
…………………………………………………………………………………..
Provisional Diagnosis …………………………………………………………..
Date of sample collection………………………………………………………...
Date of result appearance ………………………………………………………..
Laboratory diagnosis……………………………………………………………..
Final diagnosis……………………………………………………………………
Name of the treating physician…………………………………………………..
Signature ……………………………………….Date …………………………..
This form should be filled by the treating physician and to be sent within 72 hours from
admission to the regional directorate of health affairs and to directorate of infectious diseases
(MOH) in Riyadh at fax 01-4028941
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Kingdom of Saudi Arabia
Ministry of health
Directorate of health affairs……
Hospital………………………..
Suspected avian influenza notification form
Name……………………………………….gender ……………………………
Nationality………………………………….age………………………………..
Place of arrival………………………passport No (none Saudis)………………
Date of arrival to the kingdom…………….date of symptoms onset……………
Address in the kingdom …………………………………………………………
Telephone home …………………………telephone mobile……………………
Symptoms and signs at the entry points
Yes
No
Fever
□
□
Sore throat
□
□
Respiratory distress
□
□
Cough
□
□
Other symptoms (specify)………………………………………………………
…………………………………………………………………………………..
Provisional Diagnosis …………………………………………………………..
This form should be send immediately from hospital to Regional Directorate of Health Affairs
and to Directorate of Infectious diseases (MOH) in Riyadh at fax 01-4028941
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Kingdom of Saudi Arabia
Ministry of health
Directorate of health affairs……
Hospital………………………..
Suspected avian influenza notification form the entry point
to the hospital
Name……………………………………….gender ……………………………
Nationality………………………………….age………………………………..
Place of arrival………………………passport No (none Saudis)………………
Date of arrival to the kingdom………………………..date of onset……………
Address in the kingdom …………………………………………………………
Telephone home …………………………telephone mobile……………………
Symptoms and signs at the entry points
Yes
No
Fever
□
□
Sore throat
□
□
Respiratory distress
□
□
Cough
□
□
Other symptoms (specify)………………………………………………………
…………………………………………………………………………………..
Provisional Diagnosis …………………………………………………………..
This form should be send immediately by fax to regional directorate of health affairs.
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