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Infectious Diseases Affecting the Mother


and Child
By Sherwin C. Mauricio

I. HIV (Human Immunodeficiency Virus) Infection
Prevalence
Worldwide:
According to estimates by WHO and UNAIDS, 35.3 million people were living
with HIV at the end of 2012. That same year, some 2.3 million people became newly
infected, and 1.6 million died of AIDS-related causes.
(http://www.who.int/features/qa/71/en/)
The World Health Organization (WHO)estimates that approximately 2.5 million
children were living with HIV infection as of 2009. In 2009 alone, 370,000 children were
newly infected. This is a drop of 24% from 5 years earlier.
(http://emedicine.medscape.com/article/965086-overview#a0101)
Philippines:
Officially, the Philippines is a low-HIV-prevalence country, with less than 0.1
percent of the adult population estimated to be HIV-positive. As of January 2013, the
Department of Health (DOH) AIDS Registry in the Philippines reported 10,514 people
living with HIV/AIDS.
Of the 10,514 HIV positive cases reported from 1984 to 2013, 92% (9,637) were
infected through sexual contact, 4% (420) through needle sharing among injecting drug
users, 1% (59) through mother-to-child transmission, <1% (20) through blood transfusion
and needle prick injury <1% (3). No data is available for 4% (375) of the cases.
(http://en.wikipedia.org/wiki/HIV/AIDS_in_the_Philippines)
Virus profile

HIV is a retrovirus that primarily infects components of the human immune
system such as CD4
+
T cells, macrophages and dendritic cells. It directly and indirectly
destroys CD4
+
T cells.
2

HIV is a member of the genus Lentivirus,
[59]
part of the family Retroviridae.
[60]

Lentiviruses share many morphological and biological characteristics. Many species of
mammals are infected by lentiviruses, which are characteristically responsible for long-
duration illnesses with a long incubation period.
[61]
Lentiviruses are transmitted as single-
stranded, positive-sense, enveloped RNA viruses. Upon entry into the target cell, the
viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a
virally encoded reverse transcriptase that is transported along with the viral genome in
the virus particle. The resulting viral DNA is then imported into the cell nucleus and
integrated into the cellular DNA by a virally encoded integrase and host co-factors.
[62]

Once integrated, the virus may become latent, allowing the virus and its host cell to
avoid detection by the immune system.
[63]
Alternatively, the virus may be transcribed,
producing new RNA genomes and viral proteins that are packaged and released from
the cell as new virus particles that begin the replication cycle anew.
[64]

Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus
that was originally discovered (and initially referred to also as LAV or HTLV-III). It is
more virulent, more infective,
[65]
and is the cause of the majority of HIV infections
globally. The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer people
exposed to HIV-2 will be infected per exposure. Because of its relatively poor capacity
for transmission, HIV-2 is largely confined to West Africa
http://en.wikipedia.org/wiki/HIV/AIDS
Pathophysiology
After the virus enters the body there is a period of rapid viral replication, leading
to an abundance of virus in the peripheral blood. During primary infection, the level of
HIV may reach several million virus particles per milliliter of blood.
[67]
This response is
accompanied by a marked drop in the number of circulating CD4
+
T cells. The acute
viremia is almost invariably associated with activation of CD8
+
T cells, which kill HIV-
infected cells, and subsequently with antibody production, or seroconversion. The CD8
+

T cell response is thought to be important in controlling virus levels, which peak and then
decline, as the CD4
+
T cell counts recover. A good CD8
+
T cell response has been
linked to slower disease progression and a better prognosis, though it does not eliminate
the virus.
[68]

Ultimately, HIV causes AIDS by depleting CD4
+
T cells. This weakens the
immune system and allows opportunistic infections. T cells are essential to the immune
response and without them, the body cannot fight infections or kill cancerous cells. The
mechanism of CD4
+
T cell depletion differs in the acute and chronic phases.
[69]
During
the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells
accounts for CD4
+
T cell depletion, although apoptosis may also be a factor. During the
chronic phase, the consequences of generalized immune activation coupled with the
gradual loss of the ability of the immune system to generate new T cells appear to
account for the slow decline in CD4
+
T cell numbers.
[70]

Although the symptoms of immune deficiency characteristic of AIDS do not
appear for years after a person is infected, the bulk of CD4
+
T cell loss occurs during the
first weeks of infection, especially in the intestinal mucosa, which harbors the majority of
the lymphocytes found in the body.
[71]
The reason for the preferential loss of mucosal
3

CD4
+
T cells is that the majority of mucosal CD4
+
T cells express the CCR5 protein
which HIV uses as a co-receptor to gain access to the cells, whereas only a small
fraction of CD4
+
T cells in the bloodstream do so.
[72]
A specific genetic change that alters
the CCR5 protein when present in both chromosomes very effectively prevents HIV-1
infection.
[73]

HIV seeks out and destroys CCR5 expressing CD4
+
T cells during acute
infection.
[74]
A vigorous immune response eventually controls the infection and initiates
the clinically latent phase. CD4
+
T cells in mucosal tissues remain particularly
affected.
[74]
Continuous HIV replication causes a state of generalized immune activation
persisting throughout the chronic phase.
[75]
Immune activation, which is reflected by the
increased activation state of immune cells and release of pro-inflammatory cytokines,
results from the activity of several HIV gene products and the immune response to
ongoing HIV replication. It is also linked to the breakdown of the immune surveillance
system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4
+

T cells during the acute phase of disease
http://en.wikipedia.org/wiki/HIV/AIDS
Signs and Symptoms
Children born with HIV infection rarely have symptoms for the first few months. If
the children remain untreated, only about 20% develop problems during the first or
second year of life. For the remaining 80% of children, problems may not appear until
age 3 or later even without treatment. With the use of effective anti-HIV drugs, children
with HIV infection do not necessarily develop any symptoms of HIV infection. The
symptoms of HIV infection acquired during adolescence are similar to those in adults.
The first signs of HIV infection in children are usually slowed growth and a delay
of maturation, recurring diarrhea, lung infections, or a fungal infection of the mouth
(thrush). Sometimes children have repeated episodes of bacterial infections, such as a
middle ear infection (otitis media), sinusitis, or pneumonia.
A variety of symptoms and complications can appear as the child's immune
system deteriorates. About one third of HIV-infected children develop lung inflammation
(lymphocytic interstitial pneumonitis), with cough and difficulty breathing.
Children born with HIV infection commonly have at least one episode of
Pneumocystis pneumonia in the first 15 months of life if they are not receiving anti-HIV
drugs. More than half of untreated children infected with HIV develop the pneumonia at
some time. Pneumocystis pneumonia is a major cause of death among children and
adults with AIDS.
In a significant number of HIV-infected children, progressive brain damage
prevents or delays developmental milestones, such as walking and talking. These
children also may have impaired intelligence and a head that is small in relation to their
body size. Up to 20% of untreated infected children progressively lose social and
language skills and muscle control. They may become partially paralyzed or unsteady on
their feet, or their muscles may become somewhat rigid.
4

Anemia (a low red blood cell count) is common among HIV-infected children and
causes them to become weak and tire easily. About 20% of untreated children develop
heart problems, such as rapid or irregular heartbeat, or heart failure.
Less commonly, untreated children develop inflammation of the liver (hepatitis) or
inflammation of the kidneys (nephritis). Cancers are uncommon in children with AIDS,
but non-Hodgkin lymphoma and lymphoma of the brain may occur somewhat more often
than in uninfected children. Kaposi's sarcoma, an AIDS-related cancer that affects the
skin and internal organs, is extremely rare in children.
http://www.merckmanuals.com/home/childrens_health_issues/viral_infections_in
_infants_and_children/human_immunodeficiency_virus_hiv_infection_in_children.html
Diagnosis
Detection of antibody to HIV is the usual first step in diagnosing HIV infection.
The 2010 Panel on Antiretroviral Therapy and Medical Management of HIV-Infected
Children
[4]
recommendations for diagnosing infants include the following:
Because of the persistence of the maternal HIV antibody, infants
younger than 18 months require virologic assays that directly detect HIV in order
to diagnose HIV infection
Preferred virologic assays include HIV bDNA polymerase chain
reaction (PCR) and HIV RNA assays. The HIV PCR DNA qualitative test is
usually less expensive.
Further virologic testing in infants with known perinatal HIV
exposure is recommended at 2 weeks, 4 weeks, and 4 months
An antibody test to document seroreversion to HIV antibodynegative status in
uninfected infants is no longer recommended.
In older children and adults, an enzyme-linked immunosorbent assay (ELISA) to
detect HIV antibody, followed by a confirmatory Western blot (which has increased
specificity), should be used to diagnose HIV infection.
Rapid HIV tests, which provide results in minutes, simplify and expand the
availability of HIV testing. Their sensitivity is as high as 100%, but they must be followed
with confirmatory Western blotting or immunofluorescence antibody testing, as with
conventional HIV antibody tests.
http://emedicine.medscape.com/article/965086-overview
5

http://depts.washington.edu/ghivaids/reslimited/case1/discussion.html
Classification
The World Health Organization first proposed a definition for AIDS in 1986.
[12]

Since then, the WHO classification has been updated and expanded several times, with
the most recent version being published in 2007.
[12]
The WHO system uses the following
categories:
Primary HIV infection: May be either asymptomatic or associated
with acute retroviral syndrome.
[12]

Stage I: HIV infection is asymptomatic with a CD4
+
T cell count
(also known as CD4 count) greater than 500 per microlitre (l or cubic mm) of
blood.
[12]
May include generalized lymph node enlargement.
[12]

Stage II: Mild symptoms which may include minor mucocutaneous
manifestations and recurrent upper respiratory tract infections. A CD4 count of
less than 500/l.
[12]

Stage III: Advanced symptoms which may include unexplained
chronic diarrhea for longer than a month, severe bacterial infections including
tuberculosis of the lung, and a CD4 count of less than 350/l.
[12]

Stage IV or AIDS: severe symptoms which include toxoplasmosis
of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi's
sarcoma. A CD4 count of less than 200/l.
[12]

http://en.wikipedia.org/wiki/HIV/AIDS

Management
Drug Treatment:
Children are treated with most of the same anti-HIV drugs as adults (see
xref.discussed-in Treatment), typically a highly active antiretroviral therapy (HAART)
combination of two or more reverse-transcriptase inhibitors and a protease inhibitor.
However, not all of the drugs used for adults are available to small children, in part
because some are not available in liquid form. It may be difficult for parents and children
to follow complicated drug regimens, which can limit the effectiveness of therapy. In
6

general, children develop the same types of side effects as adults but usually at a much
lower rate. However, the side effects of drugs may also limit the treatment. A doctor
monitors the effectiveness of treatment by regularly measuring the amount of virus
present in the blood and the child's CD4
+
cell count. Increased numbers of virus in the
blood may be a sign that the virus is developing resistance to the drugs or that the child
is not taking the drugs. In either case, the doctor may need to change the drugs.
The replication cycle of HIV and the point of action of the antiretroviral drugs

1. HIV binds to CD4 cell surface molecules, entry into the cell also requires binding
to co-receptorsCXCR4 and CCR5). This step can be inhibited by fusion/entry
inhibitors.
2. HIV is uncoated inside the cell and reverse transcriptase copies genomic RNA
into DNA, making errors at a frequence of about one per replication cycle.
Reverse transcriptase inhibitors were the first class of HIV inhibitors to be
used as drugs.
3. Viral DNA can integrate into DNA and become a part of the cellular genome. This
step makes the infection irreversible, and may mean that eliminating the virus
from an infected individual is not possible. Integrase inhibitors are designed to
block this step of infection.
4. The virus uses cellular machinery to synthesize viral proteins. Several of these
are long amino acid chains which must be cleaved by a specific viral protease
before new viral particles can become active. Protease inhibitors block viral
maturation at this step.
Prevention of Opportunistic Infections:
To prevent Pneumocystis pneumonia, doctors give trimethoprim-
sulfamethoxazole to all children with proven HIV infection and a significantly impaired
immune system and to all infants who were born to HIV-infected women beginning at 4
to 6 weeks of age (continued until testing shows the infants are not infected). Children 5
years old and older who cannot tolerate trimethoprim-sulfamethoxazole can be given
7

pentamidine. Dapsone is an alternative drug for children younger than 5 years who
cannot tolerate trimethoprim-sulfamethoxazole Children with a significantly impaired
immune system also are given azithromycin or clarithromycin to prevent Mycobacterium
avium complex infection. Rifabutin is an alternative drug. Children with recurring
bacterial infections may be given immune globulin by vein once a month.


Vaccination:
Nearly all HIV-infected children should receive the routine childhood
vaccinations, including diphtheria, tetanus, and pertussis (DTaP); inactivated polio
vaccine; Haemophilus influenzae; Streptococcus pneumoniae; and hepatitis B. Vaccines
containing live viruses such as the oral polio virus, varicella, and measles-mumps-
rubella can cause a severe or fatal illness in children with HIV whose immune system is
very impaired. However, the measles-mumps-rubella vaccine and varicella vaccine are
recommended for children with HIV infection whose immune system is not severely
impaired. Yearly influenza immunization is also recommended for all HIV-infected
children over 6 months of age. However, the effectiveness of any vaccination will be less
in children with HIV infection.
http://www.merckmanuals.com/home/childrens_health_issues/viral_infections_in
_infants_and_children/human_immunodeficiency_virus_hiv_infection_in_children.html

Nursing Management
Nursing Priorities
1. Prevent/minimize development of new infections.
2. Maintain homeostasis.
3. Promote comfort.
4. Support psychosocial adjustment.
5. Provide information about disease process/prognosis and treatment needs.
Discharge Goals
1. Infection prevented/resolved.
2. Complications prevented/minimized.
3. Pain/discomfort alleviated or controlled.
4. Patient dealing with current situation realistically.
5. Diagnosis, prognosis, and therapeutic regimen understood.
6. Plan in place to meet needs after discharge.
References:
http://depts.washington.edu/ghivaids/reslimited/case1/discussion.html
8

http://emedicine.medscape.com/article/965086-overview#a0101
http://en.wikipedia.org/wiki/HIV/AIDS
http://en.wikipedia.org/wiki/HIV/AIDS_in_the_Philippines
http://www.biology.arizona.edu/immunology/tutorials/aids/treatment.html
http://www.merckmanuals.com/home/childrens_health_issues/viral_infections_in_infants
_and_children/human_immunodeficiency_virus_hiv_infection_in_children.html
http://www.who.int/features/qa/71/en/

II. Severe acute respiratory syndrome (SARS)
Severe acute respiratory syndrome (SARS) is a serious form of pneumonia. It is
caused by a virus that was first identified in 2003. Infection with the SARS virus causes
acute respiratory distress (severe breathing difficulty) and sometimes death.
SARS is a dramatic example of how quickly world travel can spread a disease. It
is also an example of how quickly a connected health system can respond to a new
health threat.
Background Information:
World Health Organization (WHO) physician Dr. Carlo Urbani identified SARS as
a new disease in 2003. He diagnosed it in a 48-year-old businessman who had traveled
from the Guangdong province of China, through Hong Kong, to Hanoi, Vietnam. The
businessman and the doctor who first diagnosed SARS both died from the illness.
In the meantime, SARS was spreading. Quickly it infected thousands of people
around the world, including people in Asia, Australia, Europe, Africa, and North and
South America. Schools closed throughout Hong Kong and Singapore. National
economies were affected.
The WHO identified SARS as a global health threat, and issued a travel advisory.
WHO updates closely tracked the spread of SARS. It wasn't clear whether SARS would
become a global pandemic.
The fast global public health response helped to stem the spread of the virus. By
June 2003, the number of new cases was down enough that on June 7, the WHO
stopped its daily reports. But even though the number of new cases dwindled and travel
advisories began to be lifted, every new case had the potential to spark another
outbreak.
SARS appears to be here to stay. It has changed the way that the world
responds to infectious diseases during a time of widespread international travel. The
2003 outbreak had an estimated 8,000 cases and 750 deaths. Deaths occurred mainly
in older patients.


9


Incidence
Probable cases of SARS by country, 1 November 2002 31 July
2003.
Country or Region Cases Deaths
SARS cases dead
due to other causes
Fatality
(%)
China * 5,328 349 19 6.6
Hong Kong * 1,755 299 5 17
Canada 251 44 0 18
Taiwan ** 346 37 36 11
Singapore 238 33 0 14
Vietnam 63 5 0 8
United States 27 0 0 0
Philippines 14 2 0 14
Mongolia 9 0 0 0
Macau * 1 0 0 0
Kuwait 1 0 0 0
Republic of Ireland 1 0 0 0
Romania 1 0 0 0
Russian Federation 1 0 0 0
Spain 1 0 0 0
Switzerland 1 0 0 0
South Korea 4 0 0 0
Total 8273 775 60 9.6
(*) Figures for the People's Republic of China exclude the Special
Administrative Regions (Macau SAR, Hong Kong SAR), which are
reported separately by the WHO.
(**) Since 11 July 2003, 325 Taiwanese cases have been 'discarded'.
Laboratory information was insufficient or incomplete for 135 discarded
cases; 101 of these patients died.
Source:WHO.
[14]

Causes, and risk factors
SARS is caused by a member of the coronavirus family of viruses (the same
family that can cause the common cold). It is believed the 2003 epidemic started when
the virus spread from small mammals in China.
When someone with SARS coughs or sneezes, infected droplets spray into the
air. You can catch the SARS virus if you breathe in or touch these particles. The SARS
10

virus may live on hands, tissues, and other surfaces for up to 6 hours in these droplets
and up to 3 hours after the droplets have dried.
While the spread of droplets through close contact caused most of the early
SARS cases, SARS might also spread by hands and other objects the droplets has
touched. Airborne transmission is a real possibility in some cases. Live virus has even
been found in the stool of people with SARS, where it has been shown to live for up to 4
days. The virus may be able to live for months or years when the temperature is below
freezing.
With other coronaviruses, becoming infected and then getting sick again (re-
infection) is common. This may also be the case with SARS.
Symptoms usually occur about 2 to 10 days after coming in contact with the
virus. There have been some cases where the illness started sooner or later after first
contact. People with active symptoms of illness are contagious, but it is not known for
how long a person may be contagious before or after symptoms appear.
Symptoms
The hallmark symptoms are:
Cough
Difficulty breathing
Fever greater than 100.4 degrees F (38.0 degrees C)
Other breathing symptoms
The most common symptoms are:
Chills and shaking
Cough -- usually starts 2-3 days after other symptoms
Fever
Headache
Muscle aches
Less common symptoms include:
Cough that produces phlegm (sputum)
Diarrhea
Dizziness
Nausea and vomiting
Runny nose
Sore throat
In some people, the lung symptoms get worse during the second week of illness,
even after the fever has stopped.
Table 1. Clinical features of children with severe
acute respiratory syndrome*
11

Features No. of Children (%)
Fever 19 (90.5)
Malaise 13 (61.9)
Loss of appetite 12 (57.1)
Chills 10 (47.6)
Cough 9 (42.9)
Dizziness 8 (38.1)
Rhinorrhea 7 (33.3)
Sputum 3 (14.3)
Dyspnea/tachypnea 3 (14.3)
Headache 3 (14.3)
Myalgia 2 (9.5)
Diarrhea 2 (9.5)
Sore throat 1 (4.8)
Rash 1 (4.8)
* from Chiu: Severe acute respiratory syndrome
in children: experience in a regional hospital in
Hong Kong
Signs and tests
Your health care provider may hear abnormal lung sounds while listening to your
chest with a stethoscope. In most people with SARS, changes on a chest x-ray or chest
CT show pneumonia, which is typical with SARS.
Tests used to diagnose SARS might include:
Arterial blood tests
Blood clotting tests
Blood chemistry tests
Chest x-ray or chest CT scan
Complete blood count (CBC)
Tests used to quickly identify the virus that causes SARS include:
Antibody tests for SARS
Direct isolation of the SARS virus
Rapid polymerase chain reaction (PCR) test for SARS virus
12

All current tests have some limitations. They may not be able to easily identify a
SARS case during the first week of the illness, when it is most important.

Pathophysiology
SARS coronavirus (CoV) is transmitted primarily through droplets, entering the
human body via the respiratory tract mucosa and causing viraemia. Angiotensin-
converting enzyme 2 (ACE2) has been identified as a functional receptor for SARS-CoV.
The incubation period is 2 to 10 days and the risk of transmission is greater during the
second week of illness, which correlates with the timing of peak viral load. The possibility
of fomite transmission and airborne transmission cannot be excluded, although the role
of faecal-oral or faecal-respiratory spread seems to be of minor importance.
After establishment of infection, SARS-CoV causes tissue damage by (1) direct
lytic effects on host cells and (2) indirect consequences resulting from the host immune
response. Autopsies demonstrated changes that were confined mostly to pulmonary
tissue, where diffuse alveolar damage was the most prominent feature. (See the image
below.)

Pathologic slide of pulmonary tissue infected with severe acute respiratory
syndromeassociated coronavirus. Diffuse alveolar damage is seen along with a
multinucleated giant cell with no conspicuous viral inclusions. Courtesy of the US
Centers for Disease Control and Prevention.
Multinucleated syncytial giant cells were thought to be characteristic of SARS but
were rarely seen. Angiotensin-converting enzyme-2 (ACE-2), being a negative regulator
of the local rennin-angiotensin system, was thought to be a major contributor to the
development of this damage.
The other mechanism was thought to be the induction of apoptosis. The SARS-
CoV3a and 7a proteins have been demonstrated to be inducers of apoptosis in
various cell lines.
Immunologically, SARS is characterized by a phase of cytokine storm, with
various chemokines and cytokines being elevated.
Treatment
13

People who are thought to have SARS should be checked right away by a health
care provider. If they are suspected of having SARS, they should be kept isolated in the
hospital.

Pharmacological Therapy
General principles: Anti-bacterial therapy for community-acquired pneumonia in
accordance with standard guidelines should always be administered before laboratory
confirmation of SARS-CoV infection. Where effective anti-viral therapy is available, it
should be started as early as possible after diagnosis, and even empirically if suspicious
clinical features and especially epidemiological links are present. Since critically ill
patients are deemed to have already progressed from the viral replicative phase to the
immunopathological phase, concomitant institution of an immunomodulatory therapy
should also be considered. Since there are no consensus regarding the most optimal
treatment regimen in these respects, we will thus review the more commonly used
agents and discuss their relative merits based on published reports. When respiratory
failure eventually sets in, oxygen supplementation, assisted ventilation and intensive
supportive treatments will be required.
Antiviral therapy: Ribavirin was the most commonly used empirical antiviral agent
for SARS. It is a broad-spectrum purine nucleoside analogue which inhibits both RNA
and DNA viruses by interfering with nucleic acid synthesis. There is experimental
evidence to show that it has immunomodulatory effects in the treatment of mouse
coronavirus hepatitis. Subsequently, it was found that ribavirin has no direct in vitro
activity against SARS-CoV. Higher doses given intravenously resulted in more frequent
and severe adverse effects including haemolytic anaemia, elevated transaminase levels
and bradycardia.
Lopinavir-ritonavir co-formulation (Kaletra

, Abbott Laboratories, USA) is a


protease inhibitor for the treatment of human immunodeficiency virus (HIV) infection. It
can inhibit the coronaviral proteases, thus blocking the processing of viral replicase
polyprotein and preventing the replication of viral RNA. Ritonavir inhibits lopinavir
metabolism thus increasing its serum concentration, but it has no activity against SARS-
CoV. In a retrospective analysis in Hong Kong, 31 patients who had received Kaletra as
rescue therapy together with high dose corticosteroids had no difference in rates of
oxygen desaturation, intubation and mortality compared with a matched cohort.
However, when given as initial treatment in combination with ribavirin in another
subgroup of 44 patients, there were significant reductions in the need for rescue pulsed
corticosteroid therapy, intubation rate and overall mortality. In addition to the prevalence
of diarrhoea among these patients which may render oral drugs more appropriate and
useful, synergism between kaletra and ribavirin might have contributed to the benefits
since either drug alone has only weak anti-viral activities. Another Hong Kong study of
41 SARS patients treated with a combination of lopinavir/ritonavir and ribavirin compared
with 111 patients (historical controls) treated with ribavirin only showed that adverse
clinical outcomes (ARDS or death) were significantly lower in the treatment group than in
the historical controls at day 21 after symptom onset. Further randomised placebo
controlled trials are required.
14

Interferons are a family of cytokines with important roles in the cellular immune
response. Interferon has been used for SARS treatment in China and Canada. In an
open-label uncontrolled study, nine patients treated with corticosteroids plus interferon
alfacon-1 (Infergen

, InterMune Inc., USA) showed better oxygen saturation, faster


radiographic resolution and lesser need for supplemental oxygen compared to 13 given
corticosteroids alone. In vitro testing showed that interferon was more potent than
interferon or , being effective even when administered after SARS-CoV infection in
cell culture.
Traditional Chinese herbal medicine has been used concomitantly with other
drugs to treat SARS in mainland China with good results reported. However, its value in
critically ill patients has not been reported. Glycyrrhizin, an active component derived
from liquorice roots, is effective against SARS-CoV in vitro. Its clinical utility remains
uncertain. Another herbal compound, Baicalin, also demonstrates anti-SARS-CoV
activity in vitro (unpublished data).
Immunomodulatory therapy: In the absence of an effective antiviral agent in the
2003 outbreak, most physicians had opted to use immunomodulatory agents, most
commonly corticosteroids, in the treatment of SARS. It is generally agreed that
corticosteroids should not be used during the early viral replicative phase, and that its
administration should best coincide with the onset of the immunopathological phase.
Clinico-radiological surrogate criteria have been used to indicate the onset of this
immune hyperactive phase, thus providing a practical guide to the timing of starting
corticosteroids. Corticosteroid dosages should be high enough, especially in the severe
cases, to abort the cytokine storm, and maintained for long enough to prevent the
rebound phenomenon. This may be achieved by using a weight-adjusted and
radiographic extent-modified dosages for a period of 23 weeks.
In one-third to half of SARS patients, fever may recur while on
immunomodulatory treatment due to superimposed infections, too rapid tailing of
corticosteroids or persistently severe and uninhibited cytokine storm. Empirical anti-
pseudomonal antibiotics should then be given first. If there is no apparent clinical
response, opportunistic infections like fungal infection should be excluded. If fever is
accompanied by obvious respiratory deterioration in the absence of superimposed
pulmonary or systemic infection, most patients can be presumed to be suffering from a
severe recrudescence of the SARS illness. In such critically ill SARS patients, further
escalation of immunomodulation is warranted. Such deterioration could sometimes occur
very rapidly; immediate administration of pulsed methylprednisolone therapy at 500
1000 mg per day intravenously for 2 days, followed by tapering doses in the subsequent
weeks, has been associated with improved outcome. Up to one-third to one-half of
critically ill SARS patients may benefit from this strategy. Because radiographic
abnormalities may lag behind clinical improvement, persistent radiographic shadows per
se, when accompanied by clinical improvement, do not warrant additional
corticosteroids.
Human gamma immunoglobulins have been used in selected SARS patients who
continued to deteriorate despite treatment. An IgM-enriched immunoglobulin product
(Pentaglobin

, Biotest Pharma GmbH, Germany) has been used in Hong Kong and
mainland China. Pentaglobin at 5mg/kg/day for three days given to 12 patients who
deteriorated despite repeated rescue methylprednisolone and ribavirin therapy had
15

shown some improvement in radiographic scores and oxygen requirement. It has been
reported that the use of combined methylprednisolone and high-dose intravenous
immunoglobulin (0.4g/kg) daily for three consecutive days in 15 probable SARS patients
with acute lung injury (ALI) or ARDS had resulted in lower mortality and a trend towards
earlier recovery. Randomized controlled trials in larger numbers of patients are required
to confirm its efficacy.
Based on the assumption that the neutralizing immunoglobulins in convalescent
plasma can curb increases in viral load, convalescent plasma collected from recovered
SARS patients has been used in Hong Kong to treat severely ill patients not responding
to corticosteroids. Some clinical benefits were reportedly observed in a small number of
patients.
Management of SARS-related respiratory failure
Despite all efforts, at least 50% of SARS patients would still develop acute
hypoxemic respiratory failure, with up to 80% requiring supplemental oxygen. Overall,
20-30% of patients had been admitted into ICU, and 10-20% eventually required
intubation and mechanical ventilation. Both non-invasive and invasive ventilatory support
has been applied to critically ill SARS patients.
Non-invasive ventilation (NIV): NIV delivers continuous positive airway pressure
(CPAP) or bi-level pressure support through a tight-fitting facial or nasal mask. It was
commonly employed in many Chinese hospitals and our own centre in Hong Kong. Early
application may be beneficial because it could rapidly improve vital signs, oxygenation
and tachypnoea, and may reduce the need for increasing dosages of corticosteroids for
progressive respiratory failure. It could avoid intubation and invasive ventilation in up to
two-thirds of critically ill SARS patients. Use of NIV in immunocompromised subjects of
other diseases has reported similarly reduced rates of endotracheal intubation and
serious complications. NIV in SARS may be of particular benefit, since high dose
corticosteroids per se would already predispose to ventilator-associated pneumonia, and
risks to healthcare workers (HCW) could also be markedly reduced through obviating the
need for intubation, a potentially highly infectious procedure. Patients who respond to
NIV will usually do so within 24 hours, non-responders who will eventually need
endotracheal intubation can thus be identified early.
NIV is indicated in the presence of ALI and early ARDS when oxygen saturation
(SpO
2
) could not improve to more than 93% despite >5 litres per minute of oxygen;
persistent tachypnoea of at least 30 breaths per minute; and progressive radiographic
deterioration in the lungs. The usual contraindications to NIV apply, including impaired
consciousness, uncooperative patient, high aspiration risk, and haemodynamic
instability. SARS-related respiratory failure responds readily to NIV given at low
pressures. CPAP of 4-10 cm H
2
O, or bi-level pressure support with inspiratory positive
airway pressure (IPAP) of <10 cm H
2
O and expiratory positive airway pressure (EPAP)
of 4-6 cm H
2
O are reasonable starting pressures. Higher pressures should be avoided
whenever possible, because it may increase the risk of pneumothorax and
pneumomediastinum, which are frequently spontaneous complications of SARS even
without assisted positive pressure ventilation.
16

Invasive mechanical ventilation: When patients do not improve within one to two
days of NIV or continue to deteriorate, or if NIV is contraindicated, endotracheal
intubation and mechanical ventilation should be considered. Most centres adopted a
ventilatory strategy similar to that recommended for ARDS from other causes. Both
pressure and volume control ventilation may be employed. The tidal volume should be
kept low (e.g. 5-6 ml/Kg predicted body weight), and plateau pressures maintained
below 30 cm H
2
O. Because of a higher risk of barotraumas in SARS, the lowest positive
end-expiratory pressure (PEEP) which could achieve satisfactory alveolar recruitment
and oxygenation, usually 5-6 cm water, should be employed. Other adjunctive measures
employed in the usual ARDS cases had been tried in SARS, including: prone
positioning, high frequency oscillatory ventilation, nitric oxide, high PEEP and regular
lung recruitment, but their efficacy is uncertain.
Tracheostomy is required in patients requiring prolonged mechanical ventilation
and ICU stay. Strict adherence to infection control guidelines is mandatory in performing
tracheostomy in the ICU or operating room, as well as during subsequent changes of the
tracheostomy tube.
Complications
Respiratory failure
Liver failure
Heart failure
Prevention
Reducing your contact with people who have SARS lowers your risk for the
disease. Avoid travel to places where there is an uncontrolled SARS outbreak. When
possible, avoid direct contact with persons who have SARS until at least 10 days after
their fever and other symptoms are gone.
Hand hygiene is the most important part of SARS prevention.
Wash your hands or clean them with an alcohol-based instant hand sanitizer.
Cover your mouth and nose when you sneeze or cough. Droplets
that are released when a person sneezes or coughs are infectious.
Do not share food, drink, or utensils.
Clean commonly touched surfaces with an EPA-approved
disinfectant.
In some situations, masks and goggles may be useful for preventing the spread
of the disease. You may use gloves when handling any items that may have touched
infected droplets.
Clinical Course
The clinical course seems to be much milder and shorter among patients less
than 12 years of age (Hon, Chiu). In addition, the radiological changes are milder and
generally resolve more quickly than in teenagers. Compared with adults and teenagers,
SARS seems to have a less aggressive clinical course in younger children (Hon, Chiu).
17

The reason why children with SARS fare better than adults and adolescents infected
with the disease is unclear.
Expectations (prognosis)
The death rate from SARS was 9 to 12% of those diagnosed. In people over age
65, the death rate was higher than 50%. The illness was milder in younger patients.
Many more people became sick enough to need breathing assistance. And even
more people had to go to hospital intensive care units.
Public health policies have been effective at controlling outbreaks. Many nations
have stopped the epidemic in their own countries. All countries must continue to be
careful to keep this disease under control. Viruses in the coronavirus family are known
for their ability to change (mutate) in order to spread among humans.
Reference/s:
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004460/
http://www.sarsreference.com/sarsref/pedia.htm
http://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome
http://www.medsci.org/v01p0001.htm
http://emedicine.medscape.com/article/237755-overview#a0104
http://bestpractice.bmj.com/best-practice/monograph/904/basics/pathophysiology.html

Middle East Respiratory Syndrome (MERS)

Middle East Respiratory Syndrome (MERS) is an illness cause by a virus (more
specifically, a coronavirus) called Middle East Respiratory Syndrome Coronavirus
(MERS-CoV). MERS affects the respiratory system (lungs and breathing tubes). Most
MERS patients developed severe acute respiratory illness with symptoms of fever,
cough and shortness of breath. About 30% of them died.
Health officials first reported the disease in Saudi Arabia in September 2012.
Through retrospective investigations, health officials later identified that the first known
cases of MERS occurred in Jordan in April 2012. So far, all cases of MERS have been
linked to countries in and near the Arabian Peninsula. This virus has spread from ill
people to others through close contact, such as caring for or living with an infected
person. However, there is no evidence of sustained spreading in community settings.
MERS can affect anyone. MERS patients have ranged in age from younger than
1 to 94 years old.
CDC continues to closely monitor the MERS situation globally and work with
partners to better understand the risks of this virus, including the source, how it spreads,
and how infections might be prevented. CDC recognizes the potential for MERS-CoV to
spread further and cause more cases globally and in the U.S. We have provided
information for travelers and are working with health departments, hospitals, and other
partners to prepare for this.
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Symptoms & Complications
Most people confirmed to have MERS-CoV infection have had severe acute
respiratory illness with symptoms of:
fever
cough
shortness of breath
Some people also had gastrointestinal symptoms including diarrhea and
nausea/vomiting. For many people with MERS, more severe complications followed,
such as pneumonia and kidney failure. About 30% of people with MERS died. Most of
the people who died had an underlying medical condition. Some infected people had
mild symptoms (such as cold-like symptoms) or no symptoms at all; they recovered.
Based on what researchers know so far, people with pre-existing medical
conditions (also called comorbidities), may be more likely to become infected with
MERS, or have a severe case. Pre-existing conditions from reported cases for which we
have information have included diabetes; cancer; and chronic lung, heart, and kidney
disease. Individuals with weakened immune systems are also at higher risk for getting
MERS or having a severe case.
Based on information we have to date, the incubation period for MERS (time
between when a person is exposed to MERS-CoV and when they start to have
symptoms) is 2-14 days.
Transmission
MERS-CoV has spread from ill people to others through close contact, such as
caring for or living with an infected person. Infected people have spread MERS-CoV to
others in healthcare settings, such as hospitals. Researchers studying MERS have not
seen any ongoing spreading of MERS-CoV in the community.
All reported cases have been linked to countries in and near the Arabian
Peninsula. Most infected people either lived in the Arabian Peninsula or recently traveled
from the Arabian Peninsula before they became ill. A few people became infected with
MERS-CoV after having close contact with an infected person who had recently traveled
from the Arabian Peninsula.
Public health agencies continue to investigate clusters of cases in several
countries to better understand how MERS-CoV spreads from person to person.
Prevention & Treatment
Prevention
Currently, there is no vaccine to prevent MERS-CoV infection. CDC is discussing
with partners the possibility of developing one.
CDC routinely advises that people help protect themselves from respiratory
illnesses by taking everyday preventive actions:
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Wash your hands often with soap and water for 20 seconds, and
help young children do the same. If soap and water are not available, use an
alcohol-based hand sanitizer.
Cover your nose and mouth with a tissue when you cough or
sneeze, then throw the tissue in the trash.
Avoid touching your eyes, nose and mouth with unwashed hands.
Avoid personal contact, such as kissing, or sharing cups or eating
utensils, with sick people.
Clean and disinfect frequently touched surfaces such as toys and
doorknobs.
If you are caring for or living with a person confirmed to have, or being evaluated
for, MERS-CoV infection, see Interim Guidance for Preventing MERS-CoV from
Spreading in Homes and Communities.

Treatment
There is no specific antiviral treatment recommended for MERS-CoV infection.
Individuals with MERS can seek medical care to help relieve symptoms. For severe
cases, current treatment includes care to support vital organ functions.

References:
http://www.cdc.gov/coronavirus/MERS/about/prevention.html

A (H1N1)
Background
Swine influenza is a highly contagious respiratory disease in pigs caused by one
of several swine influenza A viruses. In addition, influenza C viruses may also cause
illness in swine. Current strategies to control swine influenza virus (SIV) in animals
typically include one of several commercially available bivalent swine influenza virus
vaccines.
Transmission of swine influenza viruses to humans is uncommon. However, the
swine influenza virus can be transmitted to humans via contact with infected pigs or
environments contaminated with swine influenza viruses. Once a human becomes
infected, he or she can then spread the virus to other humans, presumably in the same
way as seasonal influenza is spread (ie, via coughing or sneezing).
Signs and symptoms
20

Manifestations of H1N1 influenza are similar to those of seasonal influenza.
Patients present with symptoms of acute respiratory illness, including at least 2 of the
following:
Fever
Cough
Sore throat
Body aches
Headache
Chills and fatigue
Diarrhea and vomiting (possible)
In children, signs of severe disease include apnea, tachypnea, dyspnea,
cyanosis, dehydration, altered mental status, and extreme irritability.
[1]

See Clinical Presentation for more detail.
Diagnosis
The CDC criteria for suspected H1N1 influenza are as follows
:

Onset of acute febrile respiratory illness within 7 days of close
contact with a person who has a confirmed case of H1N1 influenza A virus
infection, or
Onset of acute febrile respiratory illness within 7 days of travel to a
community (within the United States or internationally) where one or more H1N1
influenza A cases have been confirmed, or
Acute febrile respiratory illness in a person who resides in a
community where at least one H1N1 influenza case has been confirmed.
Risk factors
If you've traveled to an area where many people are affected by
swine flu (H1N1 flu), you may have been exposed to the virus, particularly if you
spent time in large crowds.
Swine farmers and veterinarians have the highest risk of true
swine flu because of their exposure to pigs.
Management
Treatment is largely supportive and consists of bedrest, increased fluid
consumption, cough suppressants, and antipyretics and analgesics (eg, acetaminophen,
nonsteroidal anti-inflammatory drugs) for fever and myalgias. Severe cases may require
intravenous hydration and other supportive measures. Antiviral agents may also be
considered for treatment or prophylaxis.
The antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) are sometimes
prescribed to reduce the severity of symptoms, but flu viruses can develop resistance to
21

them. Some researchers recommend further study on both of these drugs due to
uncertainty about their effects beyond the initial reduction in symptoms.
Nursing Management
1. Administer analgesics, antipyretics, and decongestants, as ordered.
2. Follow droplet and standard precautions.
3. Provide cool, humidified air but change the water daily to prevent pseudomonas
superinfection.
4. Encourage the patient to rest in bed and drink plenty of fluids.
5. Administer I.V. fluids as ordered.
6. Administer oxygen therapy if warranted.
7. Regularly monitor the patients vital signs, including his temperature.
8. Monitor the patients fluid intake and output for signs of dehydration.
9. Watch for signs and symptoms of developing pneumonia.
10. Advise the patient to use mouthwash or warm saline gargles to ease sore throat.
11. Teach the patient the importance of increasing fluid intake to prevent
dehydration.
12. Suggest a warm bath or heating pad to relieve myalgia.
13. Review prevention of future influenza episodes with patient and the community.
References:
http://emedicine.medscape.com/article/1807048-overview#aw2aab6b2b2
http://www.mayoclinic.org/diseases-conditions/swine-flu/basics/risk-factors/con-
20034916