I.

CORONAVIRUS DISEASE 2019

A. ARTICLE

Why are deaths from coronavirus so high in Italy?

By Rachael Rettner

Italy now has the highest number of deaths from COVID-19 in the world.

Deaths from the new coronavirus in Italy continue to soar, with the country reporting 919 deaths
in a single day on Friday (March 27) — the biggest single-day death toll reported in any country
since the start of the outbreak. But why are deaths in Italy so high?

Italy now has the highest number of deaths in the world from COVID-19, the disease caused by
the new coronavirus. As of Friday (March 27), the country had reported more than 9,100 deaths,
according to worldometer, a website tracking COVID-19 cases. And the country's fatality rate
from COVID-19 — at 10% — is much higher than the global average of 3.4%, according to the
World Health Organization.

One factor affecting the country's death rate may be the age of its population — Italy has the
oldest population in Europe, with about 23% of residents 65 or older, according to The New
York Times. The median age in the country is 47.3, compared with 38.3 in the United States, the
Times reported. Many of Italy's deaths have been among people in their 80s, and 90s, a
population known to be more susceptible to severe complications from COVID-19, according to
The Local.

What's more, older adults appear to make up a greater proportion of cases in Italy, with about
37% of cases ages 70 and older, compared with 12% of cases in China, according to a paper on
the issue of deaths in Italy, published March 23 in the journal JAMA.

The overall mortality rate is always going to depend on the demographics of a population, said
Aubree Gordon, an associate professor of epidemiology at the University of Michigan. In this
case, the reported mortality rate is not "age standardized," which is a way to adjust for the
underlying demographics of a population, she said.

Given Italy's older population, "you would expect their mortality rate to be higher on average, all
else being held equal," compared with a country with a younger population, Gordon told Live
Science.

In addition, as people age, the chances of developing at least one condition that weakens their
immune system — such as cancer or diabetes — increases, said Krys Johnson, an epidemiologist
at the Temple University College of Public Health. Such conditions also make people more
susceptible to severe illness from coronavirus, she said.

Another issue may be the number of people in a given area who require medical care — having a
lot of severely ill people in a single region could potentially overwhelm the medical system,
Gordon said. She noted that this was likely the case in Wuhan, China, where the coronavirus
outbreak began and which saw the majority of COVID-19 cases in China. A recent report from
WHO found that the fatality rate was 5.8% in Wuhan, compared with 0.7% in the rest of the
country, Live Science previously reported.

Finally, the country may not be catching many of the mild cases of COVID-19. Often, as testing
expands within a community, more mild cases are found, which lowers the overall death rate,
Gordon said. This was the case in South Korea, which had tested more than 295,000 people as of
March 18 and had a death rate of about 1%, according to Business Insider.

"We probably don't know how many people have actually become infected," Johnson said.
People with more mild symptoms, or those who are younger, may not be going to get tested, she
said.

Indeed, although Italy initially conducted extensive testing of both symptomatic and
asymptomatic contacts of people with COVID-19, the Italian Ministry of Health issued more
stringent testing policies on Feb. 25, according to the JAMA paper. The policy prioritized testing
for people with severe symptoms and limited testing for asymptomatic people or those with mild
symptoms. This could result in an increase in the fatality rate because patients with more mild
symptoms are not getting tested, the paper said.

Italy has conducted a substantial number of tests — more than 134,000 as of March 17,
according to The New York Times. However there is likely "quite a sizeable outbreak" in the
area, which would need even more testing to identify, Gordon said.

Italy’s New Virus Cases Decline and WHO Sees Progress

By Marco Bertacche, John Follain, and Thomas Mulier

Italy appeared poised to extend its lockdown until Easter after it reported the smallest number of
new coronavirus cases in almost two weeks and the World Health Organization forecast some
stabilization in Europe as the most-afflicted country.

Italian Health Minister Roberto Speranza said in a statement late Monday that the government
would follow the recommendation of its scientific advisers to extend the lockdown from the
current deadline of April 3 until Easter at least.

New infections in the past 24 hours totaled 4,050, compared with 5,217 the previous day, civil
protection authorities said Monday at their daily news conference in Rome. This is the lowest
increase since March 17. Fatalities from the disease rose by 812 on Monday compared with 756
on Sunday, bringing the total to 11,591. Italy now has 101,739 total cases, the most after the U.S.

Mike Ryan, head of health emergencies at the WHO, said “our fervent hope” is that Italy and
Spain are approaching a peak, and that European lockdowns which started several weeks ago
will start to bear fruit. New cases now reflect exposure to the disease about two weeks earlier, he
said.

“In the same way when we’re told that we’re looking at galaxies through a telescope that we’re
seeing life from a billion years ago, we’re seeing a reality that existed before,” Ryan said. He
warned that countries need to step up efforts to find and isolate patients to really fight the
disease. “It won’t go down by itself. We need countries to focus on what is the strategy.”

Italian health authorities voiced the same line in a press conference on Monday. Still, restrictions
on economic activity to contain the coronavirus can’t last too long, Prime Minister Giuseppe
Conte said in an interview with Spain’s El Pais Monday. Once the curve of new infections has
started to descend Italy will study measures to ease restrictions, he added.

The head of Italy’s public health institute ISS, Silvio Brusaferro, said in an interview with la
Repubblica that he expects the lockdown to be extended to Easter. He added that, while there are
encouraging signs of a contagion slowdown, it’s too early to say and several days of diminished
number of cases are needed to call it a trend.
Cases in Lombardy, the region around Milan that’s most heavily hit, rose by 1,154 Monday to
42,161, the smallest advance since March 13. Deaths rose by 458, marking an increase from
Sunday, when 416 fatalities were recorded.

”There’s a significant drop in people going to the emergency rooms,” top Lombardy health
official Giulio Gallera said in a video message. “The deaths daily count will be the last one to
improve, unfortunately.”

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

Graziano Onder, MD, PhD1; Giovanni Rezza, MD2; Silvio Brusaferro, MD3

Only 3 cases of coronavirus disease 2019 (COVID-19) were identified in Italy in the first half of
February 2020 and all involved people who had recently traveled to China. On February 20,
2020, a severe case of pneumonia due to SARS-CoV-2 (severe acute respiratory syndrome
coronavirus 2) was diagnosed in northern Italy’s Lombardy region in a man in his 30s who had
no history of possible exposure abroad. Within 14 days, many other cases of COVID-19 in the
surrounding area were diagnosed, including a substantial number of critically ill patients.1 On
the basis of the number of cases and of the advanced stage of the disease it was hypothesized that
the virus had been circulating within the population since January.

Another cluster of patients with COVID-19 was simultaneously identified in Veneto, which
borders Lombardy. Since then, the number of cases identified in Italy has rapidly increased,
mainly in northern Italy, but all regions of the country have reported having patients with
COVID-19. After China, Italy now has the second largest number of COVID-19 cases2 and also
has a very high case-fatality rate.3 This Viewpoint reviews the Italian experience with COVID-
19 with an emphasis on fatalities.

Surveillance System and Overall Fatality Rate

At the outset of the COVID-19 outbreak, the Italian National Institute of Health (Istituto
Superiore di Sanità [ISS]) launched a surveillance system to collect information on all people
with COVID-19 throughout the country. Data on all COVID-19 cases were obtained from all 19
Italian regions and the 2 autonomous provinces of Trento and Bozen. COVID-19 cases were
identified by reverse transcriptase–polymerase chain reaction (RT-PCR) testing for the severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The fatality rate was defined as
number of deaths in persons who tested positive for SARS-CoV-2 divided by number of SARS-
CoV-2 cases. The overall fatality rate of persons with confirmed COVID-19 in the Italian
population, based on data up to March 17, was 7.2% (1625 deaths/22 512 cases).3 This rate is
higher than that observed in other countries2 and may be related to 3 factors.

Fatality Rate and Population Age

The demographic characteristics of the Italian population differ from other countries. In 2019,
approximately 23% of the Italian population was aged 65 years or older. COVID-19 is more
lethal in older patients, so the older age distribution in Italy may explain, in part, Italy’s higher
case-fatality rate compared with that of other countries. The Table shows the age-specific fatality
rate in Italy compared with that of China.4

The overall case-fatality rate in Italy (7.2%) is substantially higher than in China (2.3%). When
data were stratified by age group, the case-fatality rate in Italy and China appear very similar for
age groups 0 to 69 years, but rates are higher in Italy among individuals aged 70 years or older,
and in particular among those aged 80 years or older. This difference is difficult to explain. The
distribution of cases is very different in the 2 countries: individuals aged 70 years or older
represent 37.6% of cases in Italy and only 11.9% in China. In addition, a relevant number of
cases in Italy are in people aged 90 years or older (n = 687), and this age group has a very high
fatality rate (22.7%); data on cases in those aged 90 years or older were not reported in China. In
addition, the report from the WHO-China Joint Mission on Coronavirus Disease 2019 Mortality,
which presents data on 2114 COVID-19 related deaths among 55 924 laboratory-confirmed cases
in China, reported a fatality rate among patients aged 80 years or older that was similar to the
rate in the Italian sample (21.9% in China vs 20.2% in Italy).5

Thus, the overall older age distribution in Italy relative to that in China may explain, in part, the
higher average case-fatality rate in Italy.

Definition of COVID-19–Related Deaths

A second possible explanation for the high Italian case-fatality rate may be how COVID-19–
related deaths are identified in Italy. Case-fatality statistics in Italy are based on defining
COVID-19–related deaths as those occurring in patients who test positive for SARS-CoV-2 via
RT-PCR, independently from preexisting diseases that may have caused death. This method was
selected because clear criteria for the definition of COVID-19–related deaths are not available.

Electing to define death from COVID-19 in this way may have resulted in an overestimation of
the case-fatality rate. A subsample of 355 patients with COVID-19 who died in Italy underwent
detailed chart review. Among these patients, the mean age was 79.5 years (SD, 8.1) and 601
(30.0%) were women. In this sample, 117 patients (30%) had ischemic heart disease, 126
(35.5%) had diabetes, 72 (20.3%) had active cancer, 87 (24.5%) had atrial fibrillation, 24 (6.8%)
had dementia, and 34 (9.6%) had a history of stroke. The mean number of preexisting diseases
was 2.7 (SD, 1.6). Overall, only 3 patients (0.8%) had no diseases, 89 (25.1%) had a single
disease, 91 (25.6%) had 2 diseases, and 172 (48.5%) had 3 or more underlying diseases. The
presence of these co morbidities might have increased the risk of mortality independent of
COVID-19 infection.

COVID-19–related deaths are not clearly defined in the international reports available so far, and
differences in definitions of what is or is not a COVID-19–related death might explain variation
in case-fatality rates among different countries. To better understand the actual causes of death,
the ISS is now reviewing the complete medical records of all patients with positive RT-PCR
results who have died in Italy.

Testing Strategies

A third possible explanation for variation in country-specific case-fatality rates are the differing
strategies used for SARS-CoV-2 RT-PCR testing. After an initial, extensive testing strategy of
both symptomatic and asymptomatic contacts of infected patients in a very early phase of the
epidemic, on February 25, the Italian Ministry of Health issued more stringent testing policies.
This recommendation prioritized testing for patients with more severe clinical symptoms who
were suspected of having COVID-19 and required hospitalization. Testing was limited for
asymptomatic people or those who had limited, mild symptoms. This testing strategy resulted in
a high proportion of positive results, ie, 19.3% (positive cases, 21 157 of 109 170 tested as of
March 14, 2020), and an apparent increase in the case-fatality rate because patients who
presented with less severe clinical disease (and therefore with lower fatality rate) were no longer
tested (case-fatality rate changed from 3.1% on February 24 to 7.2% on March 17). These more
mild cases, with low fatality rate, were thus no longer counted in the denominator.
Other countries have different testing strategies. For example, the Republic of Korea has adopted
a strategy of widely testing for SARS-CoV-2. This may have led to the identification of a large
number of individuals who had mild or limited symptoms, but a much lower case-fatality rate
compared with Italy (1.0% vs 7.2%) because many patients with mild disease who would not be
tested in Italy were included in the denominator in Korea.2

Conclusions

In conclusion, the current data illustrate that Italy has a high proportion of older patients with
confirmed COVID-19 infection and that the older population in Italy may partly explain
differences in cases and case-fatality rates among countries. Within Italy, COVID-19 deaths are
mainly observed among older, male patients who also have multiple comorbidities. However,
these data are limited and were derived from the first month of documented COVID-19 cases in
Italy. In addition, some patients who are currently infected may die in the near future, which may
change the mortality pattern.

From a research perspective, the comparisons discussed highlight the need for transparency in
reporting testing policies, with clear reporting of the denominators used to calculate case-fatality
rates and the age, sex, and clinical co morbid status of affected persons when comparing
COVID-19 case and mortality rates between different countries and regions. Finally, because the
outbreak is new, continued surveillance, with transparent and accurate reporting of patient
characteristics and testing policies, is needed from multiple countries to better understand the
global epidemiology of COVID-19.

B. INTRODUCTION

Written by Vince Mcleod

The COVID-19 coronavirus pandemic has led to mass scientific conference cancellations, travel
restrictions, social distancing, and other unprecedented prevention measures. How did we get to
this point?

A novel coronavirus outbreak was first documented in Wuhan, Hubei Province, China in
December 2019. As of this writing, it has now been confirmed on six continents and in more
than 100 countries. As the world’s health systems funnel resources into learning about, treating,
and preventing infections in humans, new information is released daily. In this two-part article
series, we will first provide some history on coronaviruses to put this disease outbreak in
perspective, and discuss global health security and planning for pandemic response. Secondly,
we will offer guidance from the best trusted sources for prevention and planning in the
workplace and at home.

What are coronaviruses?

Coronaviruses are a large family of zoonotic viruses that cause illness ranging from the common
cold to severe respiratory diseases. Zoonotic means these viruses are able to be transmitted from
animals to humans. There are several coronaviruses known to be circulating in different animal
populations that have not yet infected humans. COVID-19 is the most recent to make the jump to
human infection.

Common signs of COVID-19 infection are similar to the common cold and include respiratory
symptoms such as dry cough, fever, shortness of breath, and breathing difficulties. In more
severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure,
and death.

The COVID-19 infection is spread from one person to others via droplets produced from the
respiratory system of infected people, often during coughing or sneezing. According to current
data, time from exposure to onset of symptoms is usually between two and 14 days, with an
average of five days.

Two other recent coronavirus outbreaks have been experienced. Middle East Respiratory
Syndrome (MERS-CoV) of 2012 was found to transmit from dromedary camels to humans. In
2002, Severe Acute Respiratory Syndrome (SARS-CoV) was found to transmit from civet cats to
humans.

Although COVID-19 has already shown some similarities to recent coronavirus outbreaks, there
are differences and we will learn much more as we deal with this one. SARS cases totaled 8,098
with a fatality rate of 11 percent as reported in 17 countries, with the majority of cases occurring
in southern mainland China and Hong Kong. The fatality rate was highly dependent on the age
of the patient with those under 24 least likely to die (one percent) and those over 65 most likely
to die (55 percent). No cases have been reported worldwide since 2004.

According to the World Health Organization (WHO), as of 2020, MERS cases total more than
2,500; have been reported in 21 countries, and resulted in about 860 deaths. The fatality rate may
be much lower as those with mild symptoms are most likely undiagnosed. Only two cases have
been confirmed in the United States, both in May of 2014 and both patients had recently traveled
to Saudi Arabia. Most cases have occurred in the Arabian Peninsula. It is still unclear how the
virus is transmitted from camels to humans. Its spread is uncommon outside of hospitals. Thus,
its risk to the global population is currently deemed to be fairly low.

At this writing, we are about three months into the COVID-19 outbreak. The WHO officially
declared it a pandemic on March 11, 2020. Countries experiencing the greatest number of cases
include China, Iran, Italy, and the Republic of Korea. Although the United States ranks eighth,
currently, with under 2,000 confirmed cases, insufficient testing does not provide a clear and
complete picture. Therefore, we need to take immediate and serious actions to: first, protect
ourselves, family, loved ones and others in our communities; and second, act to contain the
spread by preparing our homes, workplaces, and businesses.
II. MICROBIAL GROWTH (Protozoa)

A. INTRODUCTION

The Protozoa are considered to be a subkingdom of the kingdom Protista, although in the
classical system they were placed in the kingdom Animalia. More than 50,000 species have been
described, most of which are free-living organisms; protozoa are found in almost every possible
habitat. The fossil record in the form of shells in sedimentary rocks shows that protozoa were
present in the Pre-cambrian era. Anton van Leeuwenhoek was the first person to see protozoa,
using microscopes he constructed with simple lenses. Between 1674 and 1716, he described, in
addition to free-living protozoa, several parasitic species from animals, and Giardia lamblia from
his own stools. Virtually all humans have protozoa living in or on their body at some time, and
many persons are infected with one or more species throughout their life. Some species are
considered commensals, i.e., normally not harmful, whereas others are pathogens and usually
produce disease. Protozoan diseases range from very mild to life-threatening. Individuals whose
defenses are able to control but not eliminate a parasitic infection become carriers and constitute
a source of infection for others. In geographic areas of high prevalence, well-tolerated infections
are often not treated to eradicate the parasite because eradication would lower the individual's
immunity to the parasite and result in a high likelihood of reinfection.

Many protozoan infections that are unapparent or mild in normal individuals can be life-
threatening in immune suppressed patients, particularly patients with acquired immune
deficiency syndrome (AIDS). Evidence suggests that many healthy persons harbor low numbers
of Pneumocystis carinii in their lungs. However, this parasite produces a frequently fatal
pneumonia in immunosuppressed patients such as those with AIDS. Toxoplasma gondii, a very
common protozoan parasite, usually causes a rather mild initial illness followed by a long-lasting
latent infection. AIDS patients, however, can develop fatal toxoplasmic encephalitis.
Cryptosporidium was described in the 19th century, but widespread human infection has only
recently been recognized. Cryptosporidium is another protozoan that can produce serious
complications in patients with AIDS. Microsporidiosis in humans was reported in only a few
instances prior to the appearance of AIDS. It has now become a more common infection in AIDS
patients. As more thorough studies of patients with AIDS are made, it is likely that other rare or
unusual protozoan infections will be diagnosed.

Acanthamoeba species are free-living amebas that inhabit soil and water. Cyst stages can be
airborne. Serious eye-threatening corneal ulcers due to Acanthamoeba species are being reported
in individuals who use contact lenses. The parasites presumably are transmitted in contaminated
lens-cleaning solution. Amebas of the genus Naegleria, which inhabit bodies of fresh water, are
responsible for almost all cases of the usually fatal disease primary amebic meningoencephalitis.
The amebas are thought to enter the body from water that is splashed onto the upper nasal tract
during swimming or diving. Human infections of this type were predicted before they were
recognized and reported, based on laboratory studies of Acanthamoeba infections in cell cultures
and in animals.

The lack of effective vaccines, the paucity of reliable drugs, and other problems, including
difficulties of vector control, prompted the World Health Organization to target six diseases for
increased research and training. Three of these were protozoan infections—malaria,
trypanosomiasis, and leishmaniasis. Although new information on these diseases has been
gained, most of the problems with control persist.
B. STRUCTURE

Most parasitic protozoa in humans are less than 50 μm in size. The smallest (mainly intracellular
forms) are 1 to 10 μm long, but Balantidium coli may measure 150 μm. Protozoa are unicellular
eukaryotes. As in all eukaryotes, the nucleus is enclosed in a membrane. In protozoa other than
ciliates, the nucleus is vesicular, with scattered chromatin giving a diffuse appearance to the
nucleus, all nuclei in the individual organism appear alike. One type of vesicular nucleus
contains a more or less central body, called an endosome or karyosome. The endosome lacks
DNA in the parasitic amebas and trypanosomes. In the phylum Apicomplexa, on the other hand,
the vesicular nucleus has one or more nucleoli that contain DNA. The ciliates have both a
micronucleus and macronucleus, which appear quite homogeneous in composition.

The organelles of protozoa have functions similar to the organs of higher animals. The plasma
membrane enclosing the cytoplasm also covers the projecting locomotory structures such as
pseudopodia, cilia, and flagella. The outer surface layer of some protozoa, termed a pellicle, is
sufficiently rigid to maintain a distinctive shape, as in the trypanosomes and Giardia. However,
these organisms can readily twist and bend when moving through their environment. In most
protozoa the cytoplasm is differentiated into ectoplasm (the outer, transparent layer) and
endoplasm (the inner layer containing organelles); the structure of the cytoplasm is most easily
seen in species with projecting pseudopodia, such as the amebas. Some protozoa have a
cytosome or cell “mouth” for ingesting fluids or solid particles. Contractile vacuoles for
osmoregulation occur in some, such as Naegleria and Balantidium. Many protozoa have
subpellicular microtubules; in the Apicomplexa, which have no external organelles for
locomotion, these provide a means for slow movement. The trichomonads and trypanosomes
have a distinctive undulating membrane between the body wall and a flagellum. Many other
structures occur in parasitic protozoa, including the Golgi apparatus, mitochondria, lysosomes,
food vacuoles, conoids in the Apicomplexa, and other specialized structures. Electron
microscopy is essential to visualize the details of protozoal structure. From the point of view of
functional and physiologic complexity, a protozoan is more like an animal than like a single cell.
Figure 77-1 shows the structure of the bloodstream form of a trypanosome, as determined by
electron microscopy.

C. CLASSIFICATION

In 1985 the Society of Protozoologists published a taxonomic scheme that distributed the
Protozoa into six phyla. Two of these phyla—the Sarcomastigophora and the Apicomplexa--
contain the most important species causing human disease. This scheme is based on morphology
as revealed by light, electron, and scanning microscopy. Dientamoeba fragilis, for example, had
been thought to be an ameba and placed in the family Entamoebidae. However, internal
structures seen by electron microscopy showed that it is properly placed in the order
Trichomonadida of flagellate protozoa. In some instances, organisms that appear identical under
the microscope have been assigned different species names on the basis of such criteria as
geographic distribution and clinical manifestations; a good example is the genus Leishmania, for
which subspecies names are often used. Biochemical methods have been employed on strains
and species to determine isoenzyme patterns or to identify relevant nucleotide sequences in
RNA, DNA, or both. Extensive studies have been made on the kinetoplast, a unique
mitochondrion found in the hemoflagellates and other members of the order Kinetoplastida. The
DNA associated with this organelle is of great interest. Cloning is widely used in taxonomic
studies, for example to study differences in virulence or disease manifestations in isolates of a
single species obtained from different hosts or geographic regions. Antibodies (particularly
monoclonal antibodies) to known species or to specific antigens from a species are being
employed to identify unknown isolates. Eventually, molecular taxonomy may prove to be a more
reliable basis than morphology for protozoan taxonomy, but the microscope is still the most
practical tool for identifying a protozoan parasite.

D. LIFE CYCLE STAGES

During its life cycle, a protozoan generally passes through several stages that differ in structure
and activity. Trophozoite (Greek for “animal that feeds”) is a general term for the active, feeding,
multiplying stage of most protozoa. In parasitic species this is the stage usually associated with
pathogenesis. In the hemoflagellates the terms amastigote, promastigote, epimastigote, and
trypomastigote designate trophozoite stages that differ in the absence or presence of a flagellum
and in the position of the kinetoplast associated with the flagellum. A variety of terms are
employed for stages in the Apicomplexa, such as tachyzoite and bradyzoite for Toxoplasma
gondii. Other stages in the complex asexual and sexual life cycles seen in this phylum are the
merozoite (the form resulting from fission of a multinucleate schizont) and sexual stages such as
gametocytes and gametes. Some protozoa form cysts that contain one or more infective forms.
Multiplication occurs in the cysts of some species so that excystation releases more than one
organism. For example, when the trophozoite of Entamoeba histolytica first forms a cyst, it has a
single nucleus. As the cyst matures nuclear division produces four nuclei and during excystation
four uninucleate metacystic amebas appear. Similarly, a freshly encysted Giardia lamblia has the
same number of internal structures (organelles) as the trophozoite. However, as the cyst matures
the organelles double and two trophozoites are formed. Cysts passed in stools have a protective
wall, enabling the parasite to survive in the outside environment for a period ranging from days
to a year, depending on the species and environmental conditions. Cysts formed in tissues do not
usually have a heavy protective wall and rely upon carnivorism for transmission. Oocysts are
stages resulting from sexual reproduction in the Apicomplexa. Some apicomplexan oocysts are
passed in the feces of the host, but the oocysts of Plasmodium, the agent of malaria, develop in
the body cavity of the mosquito vector.

E. REPRODUCTION

Reproduction in the Protozoa may be asexual, as in the amebas and flagellates that infect
humans, or both asexual and sexual, as in the Apicomplexa of medical importance. The most
common type of asexual multiplication is binary fission, in which the organelles are duplicated
and the protozoan then divides into two complete organisms. Division is longitudinal in the
flagellates and transverse in the ciliates; amebas have no apparent anterior-posterior axis.
Endodyogeny is a form of asexual division seen in Toxoplasma and some related organisms.
Two daughter cells form within the parent cell, which then ruptures, releasing the smaller
progeny which grow to full size before repeating the process. In schizogony, a common form of
asexual division in the Apicomplexa, the nucleus divides a number of times, and then the
cytoplasm divides into smaller uninucleate merozoites. In Plasmodium, Toxoplasma, and other
apicomplexans, the sexual cycle involves the production of gametes (gamogony), fertilization to
form the zygote, encystation of the zygote to form an oocyst, and the formation of infective
sporozoites (sporogony) within the oocyst.

Some protozoa have complex life cycles requiring two different host species; others require only
a single host to complete the life cycle. A single infective protozoan entering a susceptible host
has the potential to produce an immense population. However, reproduction is limited by events
such as death of the host or by the host's defense mechanisms, which may either eliminate the
parasite or balance parasite reproduction to yield a chronic infection. For example, malaria can
result when only a few sporozoites of Plasmodium falciparum—perhaps ten or fewer in rare
instances—are introduced by a feeding Anopheles mosquito into a person with no immunity.
Repeated cycles of schizogony in the bloodstream can result in the infection of 10 percent or
more of the erythrocytes—about 400 million parasites per milliliter of blood.

F. NUTRITION AND TRANSPORT PROCESS

The nutrition of all protozoa is holozoic; that is, they require organic materials, which may be
particulate or in solution. Amebas engulf particulate food or droplets through a sort of temporary
mouth, perform digestion and absorption in a food vacuole, and eject the waste substances. Many
protozoa have a permanent mouth, the cytosome or micropore, through which ingested food
passes to become enclosed in food vacuoles. Pinocytosis is a method of ingesting nutrient
materials whereby fluid is drawn through small, temporary openings in the body wall. The
ingested material becomes enclosed within a membrane to form a food vacuole.

Protozoa have metabolic pathways similar to those of higher animals and require the same types
of organic and inorganic compounds. In recent years, significant advances have been made in
devising chemically defined media for the in vitro cultivation of parasitic protozoa. The resulting
organisms are free of various substances that are present in organisms grown in complex media
or isolated from a host and which can interfere with immunologic or biochemical studies.
Research on the metabolism of parasites is of immediate interest because pathways that are
essential for the parasite but not the host are potential targets for antiprotozoal compounds that
would block that pathway but be safe for humans. Many antiprotozoal drugs were used
empirically long before their mechanism of action was known. The sulfa drugs, which block
folate synthesis in malaria parasites, are one example.

The rapid multiplication rate of many parasites increases the chances for mutation; hence,
changes in virulence, drug susceptibility, and other characteristics may take place. Chloroquine
resistance in Plasmodium falciparum and arsenic resistance in Trypanosoma rhodesiense are two
examples.

Competition for nutrients is not usually an important factor in pathogenesis because the amounts
utilized by parasitic protozoa are relatively small. Some parasites that inhabit the small intestine
can significantly interfere with digestion and absorption and affect the nutritional status of the
host; Giardia and Cryptosporidium are examples. The destruction of the host's cells and tissues
as a result of the parasites' metabolic activities increases the host's nutritional needs. This may be
a major factor in the outcome of an infection in a malnourished individual. Finally, extracellular
or intracellular parasites that destroy cells while feeding can lead to organ dysfunction and
serious or life-threatening consequences.

Protozoa demonstrate a wide range of feeding strategies of which four types are represented by
the protozoa found in wastewater treatment systems. Certain members of the Phytomasti-
gophorea are primary producers and capable of photoautotrophic nutrition, in addition to the
more usual chemoheterotrophic nutrition.

Heterotrophy among the flagellated protozoa contributes to the process of biochemical oxygen
demand (BOD) removal, and uptake of soluble organic material occurs either by diffusion or
active transport. Protozoa that obtain their organic material in such a way are known as
saprozoic, and are forced to compete with the more efficient heterotrophic bacteria for the
available BOD. Amoebae and ciliated protozoa are also capable of forming a food vacuole
around a solid food particle (which include bacteria) by a process known as phagocytosis. The
organic content of the particle may then be utilized after enzymic digestion within the vacuole, a
process which takes from 1 to 24 hours. This is known as holozoic or phagotrophic nutrition, and
does not involve direct competition with bacteria, which are incapable of particle ingestion.

The final nutritional mode practised by the protozoa is that of predation. These predators are
mainly ciliates, some of which are capable of feeding on algae (and are thus herbivores), as well
as other ciliate and flagellate protozoal forms.

All protozoa rely on phagocytosis for their energy and carbon for building cellular material (Fig.
4.2). This involves the enclosure of a solid food particle in a vacuole, which is covered with a
membrane and in which digestion occurs. Dissolved nutrients are removed from the vacuole
leaving the indigestible remains behind. These are removed from the cell by fusion of the
vacuole with the cell surface membrane. The typical lifetime of a food vacuole is around 20
minutes, although this time reduces if the cell is not feeding.

In addition to phagocytosis, there are other mechanisms by which a protozoan can obtain energy
and cellular building blocks. Some protozoa participate in symbiotic relationships with
photosynthetic organisms, whereas others are thought able to take up dissolved nutrients. It is
doubtful, however, if this latter mechanism plays any role for the free-living protozoa outside of
a laboratory culture.

Although phagocytosis is practised by all the protozoa there are a number of different feeding
patterns which are exploited to capture the solids particle and these can be classified into three
categories, namely: filter feeders, raptorial feeders and diffusion feeders. Filter feeding involves
the creation of a feeding current, which is then passed through a device which acts to filter out
the solids particles in the water. In the flagellates this is a collar of straight, rigid tentacles. For
the ciliates the water is passed through an arrangement of parallel cilia. The clearance between
the tentacles in the collar and the parallel ciliates, dictates the size of particle that is retained.
This is typically between 0.3 and 1.5 μm and helps to explain why the presence of a healthy
ciliate population in an activated sludge plant generates such a crystal clear effluent with a
reduced number of faecal indicator bacteria.
III. EPIDEMIOLOGY AND PUBLIC HEALTH

A. MICROBIAL GROWTH IN VITRO

a. Factors that affect microbial growth

1. Availability of nutrients- living organisms require nutrients. Appropriate nutrients must be

available to survive in particular environment.

2. Moisture- all living organisms require water to carry out their normal metabolic processes
and most will die in environments containing too little moisture.

3. Temperature every microorganisms growth temperature

 Thermophiles- organisms that love heat (minimum growth temperature: 25C, optimum
growth temperature: 50-60°C, maximum growth temperature: 113°C)

 Mesophiles- microbes that grow best at moderate temperatures (minimum growth

temperature: 10°C, optimum growth temperature: 20-40°C, maximum growth
temperature: 45 C)

 Psychrophiles- prefer cold temperatures. They thrive in cold ocean water.(minimum

growth temperature:-50C, optimum growth temperature: 10-20°C, maximum growth
temperature: 30C)

 Psychroduric- microbes that prefer warmer temperatures, but can tolerate or endure very
cold temperatures and can be preserved in the frozen state.

4. pH- refers to the acidity and alkalinity of a solution. Most microbes prefer a neutral or
slightly alkaline growth medium (pH 7.0 to 4)

 Acidophiles Such as those that can live in highly acidic environments such as pH 2 to 5)

 Alkaliphiles- prefer an alkaline environment 9 pH greater than 8.5), such as is found

inside the intestine (pH 9)

5. Gaseous atmosphere- to grow a particular microorganism in the laboratory, it is necessary to

provide the atmosphere that it requires.

b. Encouraging the growth of microorganisms in vitro (events outside the body)

 Culture-the growth of organisms obtained in a culture medium after its incubation period

 Culture medium- any material where microorganisms may thrive for their nourishment
and reproduction

 Incubation period- is the time needed to let previously inoculated culture media to show a
distinct colony or colonies within a desired temperature. It is also the time needed for the
microorganisms to adapt, grow and multiply in a new environment.

 Colony- a group of microorganisms growing together characteristically in a culture

medium

 Inoculum- the fished colony hanging on a wire loop, cotton swabs that is ready for
transfer to another culture medium for cultivation.
  Types of culture:

1. Contaminated culture- a culture that accidentally contains one or more group of

microorganisms which should not be there at all.

2. Mixed culture- there are two or more desired species of microorganism living in
the culture medium

3. Pure culture- a culture that contains only one group of microorganisms.

c. Culturing bacteria in the laboratory

Bacterial growth refers to an increase in the number of organisms rather than an increase in their
size. When each bacterial cell reaches ts optimum size, it divides by binary fission into two
daughter cells. On solid medium, binary fission continues through many generations until a
colony is produced. A bacterial colony is a mound or pile of bacteria containing millions of cels.
Binary fission continues for as long as the nutrient supply, water, and space allow and ends when
the nutrients are depleted or the concentration of cellular waste products reaches a toxic level.
Colony development on agar surfaces helps in the identification of the cultured microorganism.
Typically, depending on the medium used, individual species of microorganisms form colonies
of characteristic size and shape. Even when mixed population has been properly cultured, one
can distinguish one from the other based on overall appearance of the colonies.

d. Culture media

The media that are used in microbiology laboratories to culture bacteria are referred to as
artificial media or synthetic media, because they do not occur naturally: rather, they are prepared
in the laboratory.

They are number of ways of categorizing the media that are used to culture bacteria:

 Chemically defined medium is one in which all the ingredients are known this is because
the medium was prepared in the laboratory by adding a certain number of grams of each
of the components(carbohydrates, amino acids, salts)

 Complex medium is one in which the exact contents are not known. Complex media
contain ground up or digested extracts from animal organs hearts, liver, and brains), fish,
yeasts, and plants which provide the necessary nutrients, vitamins and minerals.

 Liquid media also known as broths are contained in tubes. Ex thiolycollate broth is very
popular iquid medium for use in the laboratory. THIO supports the growth of all
categories of bacteria from obligate aerobes to obligate anaerobes.

 Solid media- are prepared by adding agar to liquid media and then pouring the media into
tubes or Pétri dishes, where the media solidifies. Bacteria are then grown on the surface
of the agar- containing solld media., A gar is a complex polysaccharide that is obtained
from a red marine alga; it is used as a solidifying agent, much like gelatin is used as a
solidifying agent in the kitchen.

 Enriched medium is a broth or slid medium containing a rich supply of special nutrients
that promotes the growth of fastidious organisms (complex nutritional requirements) it is
usually prepared by adding extra nutrients to a medium called nutrient agar.
  Ex. Blood agar (nutrient agar plus 5% sheep red blood cells) and chocolate agar (nutrient
agar plus powdered hemoglobin) Chocolate agar is used to culture important, fastidious,
bacterial pathogens, like Neisseriae gonomhoeae and Haemophilus infuenzae.

 Selective medium has added inhibitors that discourage the growth of certain organisms
without inhibiting growth of an organism being sought.

 Ex. MacConkey agar inhibits the growth of gram positive bacteria and thus is selective
for gram-negative bacteria.

 Phenylethyl alcohol (PEA agar and colistin-nalidixic acid (CAN) agar inhibit the growth
of Gram-negative bacteria and thus are selective for gram-positive bacteria

 Thayer Martin agar and Martin Lewis agar (chocolate agars containing extra nutrients
plus several antimicrobial agents) are selective for Neisseria gonorhoeae. Only salt-
tolerant (haloduric) bacteria can grow on mannitol salt agar (MSA)

 Differential medium- permits the differentiation of organisms that grow on tne medium.

o EX MacConkey agar is frequenty used to differentiate among various gram-negative

bacili that are isolated from fecal specimens.

o Gram-negative bacteria able to ferment lactose (an ingredient of MacConkey agar)

produce pink colonies. Whereas those unable to ferment lactose produce colorless
colonies.

o It differentiates between lactose-fermenting and non-lactose fermenting gram

negative bacteria.

o Mannitol salt agar is used to screen tor Staphylococcus aureus, not only will S. aureus
arow on MSA b ccs aureus pink medium to yellow because of its ability to ferment
mannitol.

o Blood agar is also a differential medium because it is used to determine the type of
hemolysis that bacterial isolate produces.

e. Inoculation of culture media

Inoculation of a liquid medium involves adding a portion of the specimen to the medium.
Inoculation of a solid or plated medium involves the use of a sterile inoculating loop to apply a
portion of the specimen to the surface of the medium, process called streaking.

Importance of using Sterile Technique:

 Sterile technique is practiced when it is necessary to exclude all microorganisms from a

particular area, so that the area will be sterile. Such unwanted microbes are referred to as
contaminants.

 Minimizes the possibility of contamination and protects the laboratory worker from
becoming infected.
Incubation

After media are inoculated, they must be incubated. Incubator contains the appropriate
atmosphere and moisture level and is set to maintain the appropriate temperature. To cuture most
human pathogens, the incubation is set at 35 to 37°C.

Types of Incubator

 A carbon dioxide incubator- concentration of 5 to 10% carbon dioxide to isolate

capnophiles.

 A non Co2 incubator is an incubator containing room air; thus it contains atmosphere
devoid of oxygen.

 An anaerobic incubator is an incubator containing an atmosphere devoid of oxygen.

f. Bacterial population growth curve

A population growth curve for any particular species of bacteria may be determined by growing
a pure culture of the organism in a liquid medium at a constant temperature.

The growth curve four phases:

 Lag phase- bacteria absorb nutrients, synthesize enzymes and prepare for cell division.
The bacteria do not increase in number during the lag phase

 Logarithmic growth phase- the bacteria multiply rapidly that he number of organisms
doubles with each generation time. Growth rate is the greatest during the log phase. The
log phase is always brief unless the rapidly dividing culture is maintained by constant
addition of nutrients and frequent removal of waste products.

 Stationary phase -as the nutrients in the liquid medium are used up bacteria build up, the
rate of division slows, such that number bacteria that are dividing equals the number that
are dying.

 Death phase as overcrowding occur the concentration of toxic waste products continues
to increase and the nutrient supply decreases. The microorganisms die at a rapid rate.

B. MICROBIAL GROWTH IN VIVO

Selective Toxicity- The drug cause greater harm to microorganisms than to the human host.
Penicillin

 It is the first antibiotic discovered by Fleming

 Bactericidal

 Natural antibiotic

 Narrow spectrum (G +ve).

 Inhibit cell wall synthesis by interfering with the synthesis and cross linking of
peptidoglycan.

 Destroyed by gastric acid. and by β-lactimase.

  Cause allergic reaction lead to anaphylactic shock

Antimicrobial Agents

 Antibacterial Agent- Drugs used to treat bacterial infections.

 Antifungal Agent- Drugs used to treat fungal infections.

 Antiprotozoal Agent- Drugs used to treat protozoal infections.

 Antiviral Agent- Drugs used to treat viral infections.

Antibiotics- Are primarily antibacterial agents and are used to treat bacterial diseases.

 Natural Antibiotics:

Produced by certain molds and bacteria usually living in the soil.

Penicillin and cephalosporin are examples of antibiotics produced by molds.

Bacitracin, eryhtromycin and chloramphenicol are examples of antibiotics produced by

bacteria.

 Semisynthetic Antibiotics

e.g. semisynthetic penicillin such as ampicillin and carbenicillin

 Synthetic Antibiotic

chemically designed in the lab

Ideal Qualities of Antimicrobial Agent

Characteristics of a good drug:

 Kill or inhibit the growth of pathogens.

 Cause no damage to the host.

 Cause no allergic reaction in the host.

 Stable to store in solid or liquid form.

 Stay in target tissues for a long time to be effective.

 Kill the pathogen before they become resistant to it.

How Antimicrobial Agents Work

The antimicrobial agent must target a metabolic process or structure present in the pathogen and
not in the host.

Classification of Antibacterial Agents:

Based on mechanisms of action (Target site) of antibiotics are:

 Inhibition of the cell wall synthesis (production).

 Damage to the cell membrane.

  Inhibition of the nucleic acid synthesis (DNA or RNA).

 Inhibition of protein synthesis.

 Inhibition of enzyme activity.

Based on activity of the drug:

 Bacteriostatic Agent

Stop bacteria from growing and multiplying.

Used only in healthy people.

 Bactericidal Agents

Kill the bacteria.

Used in healthy and immune compromised people.

Based on the Antibiotic effect spectrum:

 Narrow-spectrum Antibiotics

Vancomycin works on Gram positive bacteria only.

Colistin works on Gram negative bacteria only.

 Broad-spectrum Antibiotics
E.g. Ampicillin.

.Multidrug Therapy

The simultaneous use of two or more drugs to kill all the pathogens and prevent resistant
pathogens from growing.

e.g. Treatment of Tuberculosis (Tb)- 4 drugs are used.

Antifungal and Antiprotozoal Agents

Antimicrobial drugs against fungal and protozoal pathogens are difficult to use because they are
eukaryotic cells like our cells so they tend to be toxic to the patient.

 Mechanisms of action of Antifungal Agents are:

Binding to cell membrane sterols

Inhibiting sterols synthesis.

Inhibiting nucleic acid synthesis.

e.g. Amphotericin B

 Mechanisms of action of Antiprotozoal Agents are:

Inhibiting nucleic acid synthesis.

Inhibiting protozoal metabolism. e.g. Metronidazole

Antiviral Agents

Until recent years there were no drugs for the treatment of viral diseases. Antiviral drugs are
especially very difficult to produce because viruses are intracellular pathogens. Only few drugs
have been found to be effective in certain viral diseases. They work by inhibiting viral
replication within cells.

Acyclovir for the treatment of HSV.

“Cocktail” of drugs including lamivudine for HIV.

Resistance of Bacteria

 Intrinsic Resistance

Some bacteria have natural resistance to some drugs because the drug cannot enter the bacterial
cells or the bacterium doesn’t have the target site specific to the drug.

 Acquired Resistance

1. Chromosomal Mutation

As cells replicate, spontaneous mutations occur at a relatively low rate. Such

mutations can ulter the binding site at which the antibiotic binds. As a result the
antibiotic cannot enter the bacterial cell.

2. Gen Transfer

Genes encoding resistance to antibiotic can spread to different strains, species, and
even genera. Ex. Plasmids.

Antimicrobial Resistance (Superbugs)

When microorganisms (mainly bacteria) become resistant to one or more antimicrobial

agent.

They make it difficult to treat the disease.

The worst resistance is Multidrug Resistance= resistance to many different antimicrobial

drugs.

Examples:

MRSA:Methicillin Resistant Staphylococcus aureus.

VRSA:Vancomycin Resistant Staphylococcus aureus.

MRTB: Multi-drug Resistant Mycobacterium tuberculosis.

β-Lactamase resistant Streptococcus pneumoniae

Slowing Down Emergence and Spread of Antimicrobial Resistance.

 Responsibilities of Physicians: must work to identify microbe and prescribe suitable

antimicrobials, must educate patients
  Responsibilities of Patients: need to carefully follow instructions

 Educate Public: must understand appropriateness and limitations of antibiotics;

antibiotics not effective against viruses

 Global Impacts: organism that is resistant can quickly travel to another country

 in some countries antibiotics available on non-prescription basis antibiotics fed to

animals can select for drug- resistant organisms

C. EPIDEMIOLOGY AND PUBLIC HEALTH

a. Introduction

Dengue is a mosquito-borne viral disease that has rapidly spread in all regions of WHO in recent
years. Dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti
and, to a lesser extent, Ae. albopictus. These mosquitoes are also vectors of chikungunya, yellow
fever and Zika viruses. Dengue is widespread throughout the tropics, with local variations in risk
influenced by rainfall, temperature, relative humidity and unplanned rapid urbanization. Dengue
causes a wide spectrum of disease. This can range from subclinical disease (people may not
know they are even infected) to severe flu-like symptoms in those infected. Although less
common, some people develop severe dengue, which can be any number of complications
associated with severe bleeding, organ impairment and/or plasma leakage. Severe dengue has a
higher risk of death when not managed appropriately. Severe dengue was first recognized in the
1950s during dengue epidemics in the Philippines and Thailand. Today, severe dengue affects
most Asian and Latin American countries and has become a leading cause of hospitalization and
death among children and adults in these regions. Dengue is caused by a virus of the
Flaviviridae family and there are four distinct, but closely related, serotypes of the virus that
cause dengue (DENV-1, DENV-2, DENV-3 and DENV-4). Recovery from infection is believed
to provide lifelong immunity against that serotype. However, cross-immunity to the other
serotypes after recovery is only partial, and temporary. Subsequent infections (secondary
infection) by other serotypes increase the risk of developing severe dengue. Dengue has distinct
epidemiological patterns, associated with the four serotypes of the virus. These can co-circulate
within a region, and indeed many countries are hyper-endemic for all four serotypes. Dengue has
an alarming impact on both human health and the global and national economies. DENV is
frequently transported from one place to another by infected travellers; when susceptible vectors
are present in these new areas, there is the potential for local transmission to be established. The
Philippines has been grappling to stem its worst dengue outbreak since 2012. According to the
Department of Health, a total of 271,480 dengue cases were reported from January to August 31,
2020, prompting the declaration of a national dengue epidemic. In 2012, 187,031 cases of
dengue were recorded. As of August 31 this year, an estimated 1,107 people have died of dengue
in the Philippines; almost half were children between five and nine years of age. At Manila's
Tondo Medical Center, where Katelyn was treated, 21 dengue patients were crowded into one
room in the paediatric ward. Two to three patients have to share a bed, with additional beds set
up in the corridors to deal with the overflow. "Children are particularly susceptible to dengue
because they have weaker immune systems compared to adults," said Amado Parawan, health
and nutrition officer at Save the Children Philippines.
b. Portal of Entry

A virus is a small parasite that can't reproduce by itself. Once it infects a susceptible cell, a virus
can direct the cell machinery to produce more viruses. When a mosquito bites an infected person,
it becomes infected. When that same infected mosquito bites another person, that person then
becomes infected with the disease.

Portal of Exit

Dengue Fever can affect any person,but especially a person with a weak immune system.Being
in tropical and subtropical areas around the world increases your risk of exposure to the virus.
The portal of exit of Dengue Fever, is when a mosquito bites an infected person. The mosquito
then carries the virus inside of it and can transfer it.

Mode of Transmission

This disease cannot spread directly from person to person. On the other hand, a mosquito can
transfer the disease.

c. Scenario

The Philippine health ministry has urged local officials to ramp up efforts to combat dengue
fever after the death toll from the epidemic reached 1,021.

The young have born the brunt of the outbreak, with children under the age of 10 accounting for
more than a third of the deaths recorded in the eight months up to August, when a national
epidemic of the mosquito-borne disease was declared.

Health undersecretary Rolando Enrique Domingo, who said 13,192 new cases and 38 deaths
have been recorded since 18 August, called on local governments to do more to find and destroy
mosquito breeding sites.

“What we need [to do] is to go down to the village level,” he said. “It also needs to be done
daily.

“We understand that sometimes it may be tiring, but the threat of dengue is continuous. We ask
for a little more effort because as we can see there are still a lot of cases.”

Domingo recommended insecticide fogging, especially in areas where cases have risen, and
advised people to wear insect repellent and clothes that cover the skin.

The government fears cases could rise further as the country enters typhoon season.

Following a national ban on a controversial vaccine blamed for children’s deaths, cases of
dengue fever in the Philippines have more than doubled compared with figures for the same
period last year.

The Department for Health has recorded 249,332 cases since the start of the year, dwarfing the
119,224 cases recorded in 2018. The figures are the highest since 2012.

The government is considering appeals to lift its ban on Dengvaxia, a drug developed by French
pharmaceutical firm Sanofi Pasteur that remains the only vaccine available against dengue.
However, many remain cautious due to claims that improper use in the country had led to
children’s deaths. The World Health Organization issued a conditional recommendation for the
vaccine in areas where dengue is highly endemic.

The Dengvaxia scandal has caused a widespread vaccine scare in the Philippines, resulting in
increased cases of dengue and measles. There is growing concern that polio could also return to
the country for the first time since 1993.

While the epidemic has already prompted some villages to double down against dengue, some
efforts appear to have been misguided. In Quezon City, a village chief reportedly released
hundreds of frogs into drainage canals in a bid to fight dengue, only to realise that the frogs were
invasive species that could disrupt the environment.

Dengue, a viral infection, is widespread throughout the tropics. The virus thrives in areas of rapid
urbanisation, poor sanitation and the absence of a vaccine.

The Department of Health has warned parents to monitor their children for fever accompanied by
severe headache, pain behind the eyes or muscle and joint pain lasting two days or more. Dengue
can lead to haemorrhaging and organ failure in severe cases.

Dengue is not confined to specific regions, although the highest number of cases have been
recorded in Western Visayas (42,694 cases) and southern Luzon (35,136 cases). Metropolitan
Manila reported 15,819 cases.

Esperanza Cabral, the former health secretary, told the Guardian that government efforts will
never be enough until the ban on Dengvaxia vaccine is lifted.

Cabral said: “The government has focused its campaign on reducing the number of mosquitoes
and on cleanliness. Doing just that will not work. We know there’s a vaccine that is not perfect
but is effective enough. Unfortunately, it is not available."

Cabral added that the government should work harder to restore public confidence in vaccines.
“We need to prevent the next epidemic,” he said.

d. Management of epidemic by DOH

A patient infected with dengue exhibits flu-like symptoms and a fever that runs for two to
seven days. The fever may go down temporarily after three days, making many patients think it
is over. However, this is a critical phase that must be monitored as it may progress to severe
dengue, according to Leila Jane Narag, the doctor overseeing the paediatric ward at the Tondo
medical facility. In reaction to the outbreak, the health department has intensified its dengue
prevention campaign, destroying mosquito breeding sites and ensuring adequate blood supply in
hospitals. Dengue is transmitted by the Aedes aegypti mosquito, common in all parts of the
Philippines. The rainy season, typically June to February, is the peak period for dengue as water
collects in blocked gutters and street drains, turning them into breeding grounds for mosquitoes.
According to Narag, reducing mosquito populations by cleaning water sources like wells and
water storage containers is essential to preventing further spikes in dengue cases. "A dengue
outbreak is not exactly a new phenomenon. We have seen this happen every four to five years
and it is often linked to changing weather patterns," said Rabindra Abeyasinghe, Philippines
representative for the WHO.

Management (based on patient type)

 Group A- patients who may be sent home

 These are patients who are able to:

o Tolerate adequate volumes of oral fluids

o Pass urine every 6 hours

o Do not have any of the warning signs particularly when the fever subsides

o Have stable haematocrit

 Group B- patient who should be referred for in-hospital management

Patients shall be referred immediately to in-hospital management if they have the

following conditions:

o Warning signs\

o Without warning signs but with co-existing conditions that may make dengue or
its management more complicated ( such as pregnancy, infancy, old age, obesity,
diabetes mellitus, hypertension, heart failure, renal failure, chronic haemolytic
diseases such as sickle- cell disease and autoimmune diseases, etc.)

o Social circumstances such as living alone or living far from health facility or
without a reliable means of transportation.

o The referring facility has no capability to manage dengue with warning signs
and/or severe dengue.

 Group C- patient with severe dengue. Requiring emergency treatment and urgent referral

These are patients with severe dengue who require emergency treatment and urgent
referral because they are in the critical phase of the disease and have the following:

o Severe plasma leakage leading to dengue shock and/or fluid accumulation with
respiratory distress;

o Severe haemorrhages;

o Severe organ impairment (hepatic damage, renal impairment, cardiomyopathy,

encephalopathy or encephalitis)

o Patients in Group C shall be immediately referred and admitted in the hospital

within 24 hours.

Program components

1. Surveillance

 Case Surveillance through Philippine Integrated Disease Surveillance and

Response (PIDSR)

 Laboratory-based surveillance/ virus surveillance through Research Institute for

Tropical Medicine (RITM) Department of Virology, as national reference
laboratory, and sub-national reference laboratories.
  Vector Surveillance through DOH Regional Offices and RITM Department of
Entomology

2. Case Management and Diagnosis

 Dengue Clinical Management Guidelines training for hospitals.

 Dengue NS1 RDT as forefont diagnosis at the h ealth center/ RHU level.

 PCR as dengue confirmatory test available at the sub-national and national

reference laboratories.

 NAAT-LAMP as one of confirmatory tests will be available at district hospitals,

provincial hospitals and DOH retained hospitals.

3. Integrated Vector Management (IVM)

 Training on Vector Management, Training on Basic Entomology for Sanitary

Inspector, Training on Integrated Vector Management (IVM) for health workers.

 Insecticide Treated Screens (ITS) as dengue control strategy in schools.

4. Outbreak Response

 Continuous DOH augmentation of insectides such as adulticides and larvicides to

LGUs for outbreak response.

5. Health Promotion and Advocacy

 Celebration of ASEAN Dengue Day every June 15

 Quad media advertisement

 IEC materials

6. Research

Health Secretary Duque emphasized that early detection is crucial in order to prevent deaths
resulting from dengue.

With 456 deaths as a result of dengue this year, the fatality ratio remains low at 0.4%. But with
the health department's goal to bring the numbers down to less than 0.2%, it urged the public to
observe the 4S strategy, which they say is the most effective way to prevent dengue. The strategy
consists of the following:

1. Search and destroy mosquito breeding places

2. Self-protective measures like wearing long sleeves and use of insect repellent

3. Seek early consultation on the first signs and symptoms of the disease

4. Say yes to fogging if there is an impending outbreak

Dengue is a mosquito-borne viral infection, contracted through a bite of Aedes aegypti and
Aedes albopictus mosquitoes carrying the dengue virus.
These mosquitoes can lay eggs in spaces or containers that hold stagnant water – bottle caps,
dish dryers, gutters, trash cans, old rubber tires. Even plant axils with stagnant water can be nests
for dengue-infected mosquitoes.

Symptoms of dengue include sudden onset of fever for 2 to 7 days, along with two of the
following: headache, body weakness, joint and muscle pains, pain behind the eyes, loss of
appetite, vomiting, diarrhea, and rashes.

Health care providers and family members should also be on the lookout for patients whose fever
comes back after dropping by at least 1°C or to almost normal between 3 and 6 days. Abdominal
pain or tenderness, persistent vomiting, edema (swelling), lack of energy, and bleeding in the
mouth or nose should also serve as warning signs.

Duque explained that dengue cases have been observed to peak every 3-4 years. The last peak
occurred in 2016. Given the pattern, the health department expects an increase in cases this year.
REACTION PAPER

COVID-19 is a new disease that is acquired from the new strand of SARS-CoV which
causes pandemic that led to economic crash, travel restrictions, social distancing, quarantines of
most nations, and unprecedented prevention measures. It was first recorded in Wuhan, Hubei
Province in China last December 31, 2019. Now, it has now been infected in more than 100
countries. Recently, Italy has the highest number of deaths from COVID-19 and second highest
confirmed cases in the world.

As of March 27, 2020, the country reported more than 9,100 deaths according to
worldometer, a website tracking COVID-19 cases. Just imagine how this disease can bring a
large number of deaths in just a month! The biggest single-day death toll was also documented
on this country with 919 deaths. This is shocking news because this reflects how COVID-19 can
be fatal to the human in just a day. When I heard this news, I feel so sad thinking their grieving
family of how they can handle the sorrows that they currently experiencing. The country’s
fatality rate from COVID-19 is 10% much higher than the global average of 3.4%, according to
World Health Organization. I questioned to myself why Italy has these numbers yet I expected
much to the China to worsen the crisis since the outbreak was originated there. I have searched
some articles in internet and I found something why Italy became the epicenter of the outbreak
after China. One factor affecting the country’s death rate it the age of its population. According
to the New York Times, The country has the oldest population in Europe with about 23% of
residents 65 or older. Many of the deaths were people in their 80’s and 90’s. Old ages are known
to be vulnerable from COVID-19 because of their conditions and lack of immune system.
Another factor is the number of people in a given area who require medical care. Having a lot of
severely ill people in a single region could potentially overwhelm the medical system, Gordon
said. It means number of people in a certain area who needs medical care could ruin the medical
system. In the case of Italy, hospitals can’t fully accommodate for the whole COVID patient
since they are outnumbered and it is already beyond the ratio of the actual number of patient
should it be in the facility. Ventilation in hospitals is also the main concern because a lot of
patients that were admitted were inside the hospital. I can’t imagine how those people can stay
with much exposure from COVID-19. Italy didn’t test many of the mild cases of COVID-19
which also sees as one of the factors of tremendous increase of confirmed cases and deaths in the
country. I believe mass testing is the most effective ways in combating COVID-19 as it was seen
in South Korea. The South Korea government conducted mass testing which tracks a lot of cases
related to COVID-19 and were immediately isolated and recovered. Currently, they are
progressing without the implementation of lockdown and this is the great job which showcases
how they are prepared to the crisis. Italy initially conducted testing only for contacts of people
with COVID-19. The readiness for the crisis was not seen and it is too late to conduct testing for
mild cases. In short, many mild diseases were not considered in denominator of testing in Italy
unlike in Republic of Korea. This is already a lesson for everybody that consideration of others
must observe. We don’t realize that those subjects are one of the main carriers of the disease.
Considering that Italy is one of the most visited countries in the world, much of the tourists who
travelled around the country were also carrying the disease. The first three cases of coronavirus
disease 2019 were recently traveled to China. The implementation of quarantine was too late as it
was conducted as the crisis was already in the peak. I’ll blame the government for their delays; a
lot of people were suffering and seeing a lot of coffins were displayed which really it hurts to
see. It is heartbreaking that some of them are actually do not anymore admit to the hospital as
their health care system is loaded.

It’s really heartbreaking to see those people who died from COVID-19 especially those
health care personnel and other frontlines who sacrificed their life to combat this deadly disease.
I salute for their commitment and action to serve people without hesitations and they deserve to
be called as hero of this battle. I’m irritated to the government because they didn’t do anything to
at least prevent the great curve of COVID-19 cases of their country. This is an enough evidence
how unprepared are they in facing this crisis. Yes, it’s too late, but they can still flatten the curve
by implementing appropriate actions to resolve this disaster. The best thing to do is to work the
government and the citizen together to fight against this invisible enemy.