What is Fever
In a healthy individual, the optimum body temperature for regulation and proper functioning
is around 37C (98.6F). Fever also called as pyrexia or controlled hyperthermia, is characterized
by elevated body temperature, which is a defense mechanism against infections and other foreign
substances. Fever is induced by pyrogenic substances that can be endogenous or exogenous,
external foreign substances like viruses and bacteria are examples of exogenous pyrogens. Fever
also develops due to the production of prostaglandins, which are needed to fight germs.
Persistent fever could be an underlying cause of several infectious diseases such as chikungunya,
malaria, typhoid??, dengue and many more diseases. It is the first major symptom that helps to
recognize diseases. The fever profile consists of blood tests that screens for the presence of
causative factors.
Malaria
Malaria is a parasitic infection caused by Plasmodium species and transmitted by female
Anopheles mosquitoes. Malarial parasites present in the infected mosquito's saliva are
transmitted to human blood through mosquito bites.
Malarial Antigen
A blood test examines the presence of malarial antigen in the blood released by the malarial
parasite. Positive result may indicate the risk and type of malaria.
Typhoid
Fever is majorly caused by Salmonella typhi (gram negative bacterium), Salmonella
paratyphi A and Salmonella paratyphi B. It spreads through contaminated food and water or
through close contact with someone who is infected. Signs and symptoms usually include
high fever, headache, abdominal pain, and either constipation or diarrhea.
Typhoid Test
This test determines the presence of antibodies produced by immune system of a person
exposed to typhoid bacterial proteins or typhoid DNA in the blood.
Dengue
Dengue virus belongs to the family of Flaviviridae, which is transmitted by the bite of infected Aedes
mosquitoes. It manifests as mild asymptomatic illness, or severe dengue hemorrhagic fever/ dengue
shock syndrome.
Dengue Antibody Test-IgG and IgM
A blood test that determines the presence of
antibodies produced by immune system of a person exposed to dengue viruses.
Complete Hemogram Test
A complete blood count test evaluates the overall health of an individual.
Malaria - Jinx to Mankind
Just a Fever! It always begins from here and we presume it isn't a cause for concern.
Malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. It is
caused by parasitic protozoans belonging to Plasmodium family. Infected female anopheles
mosquito is the transmission vector in Malaria. Although rare, malarial parasites can also be
transmitted by blood transfusion. The females of the anopheles genus of mosquito prefer to
feed on blood at night .
In humans, malaria is caused by
1.Plasmodium vivax
2.Plasmodium falciparam
3.Plasmodium malariae
4. Plasmodium ovale
Malaria Lifecycle The Vicious Circle
The malarial parasite life cycle involves two hosts, humans and female anopheles mosquitoes.
In humans, during a blood meal, malaria-infected mosquito injects sporozoites (found in infected
mosquito's salivary glands) into the blood gametocytes stream. Sporozoites rapidly leave the
circulation and infect the liver cells, reproduce asexually and produce daughter cells (merozoites)
which are released into the circulation. These merozoites invade the red blood cells and undergo Early
asexual multiplication in the erythrocytes, mosquito producing 8 to 24 new infective merozoites, stage
at which point the infected erythrocyte bursts and releases more merozoites and the infective
cycle continues. Blood stage parasite manifest the disease in human.
In female mosquitoes, the parasites multiplication is known as sporogonic Late cycle. The
gametocytes of male and female mosquito which are produced from the merozoites are stage
taken in during the blood meal. In the mosquito's stomach, male and female gametes fertilize
with each other to form zygote. These oocyst zygotes transform into cokinetes and cross the
midgut wall of the mosquito, where these ookinetes develop into oocysts. Further, oocysts
mature and divide many times to produce large numbers of small, elongated sporozoites that
migrate to the mosquito's salivary glands. Injection of sporozoites in another human host
continues the malarial life cycle.
High-risk population for malaria
Some population groups are at considerably higher risk of contracting malaria, and developing
severe disease than others. These include the following
Infants Infants born in regions prone to malaria are highly exposed to
this disease from approximately 3 months of age, as the immunity obtained from the mother
starts to decrease.
Children under 5 years of age
In high transmission areas, children under 5 years of age acquire partial immunity to the disease.
Majority of the malarial disease occur in these children without acquired immunity.
Patients with HIV/AIDS
HIV infection increases the risk of malarial infection, especially patients with immunosuppress
ion (reduction in the activation of the immune system). HIV infected adults in high transmission
areas may lead to complicated and severe malaria and death.
Pregnant women
Malaria in pregnant women is a major public health problem increasing the risk to maternal and
fetal health. This can lead to stillbirth, miscarriage, anemia, low birth weight and fetal death.
Migrants, Mobile populations and Frequent travelers
Migrants, refugees and other mobile population groups often lack partial immunity to malaria,
and have limited access to prevention, diagnostic testing and treatment services.
Signs and Symptoms of malaria
The signs and symptoms of malaria usually begin around 9 to 14 days after the bite by an infected
mosquito. The most common symptoms are Paroxysm i.e. cyclical occurrence of sudden coldness
followed by shivering and then fever and sweating, occurring every two days (tertian fever) in
P. vivax and P. ovale infections, and every three days
(quartan fever) for P. malariae and P. falciparum infection
High fever over 38C for more than few hours
Headache
Vomiting
Chills and rigors
Fatigue
Symptoms for severe and complicated malaria
High Fever
Prostration (inability to sit)
Breathing difficulties
Severe anemia
Generalized convulsions/fits
Inability to drink or vomiting
Dark or limited production of urine
Malaria, sometimes called the "King of Diseases" is a complex disease that, even under the
most optimistic scenario, will continue to be a major health threat for decades. Relapses are
important contributors to illness and morbidity in P. vivax and P. ovale infections. The malaria
parasite is able to evade and modulate the immune response. Therefore, immunity against the
malaria parasite is suboptimal. Complete eradication of malaria is a big challenge.
Different species of mosquito respond differently to medicines, exhibit drug resistance in
different ways, creating a foolproof vaccine against all malarial infections, are several challenges
making the attempts complex and difficult. Malaria, caused by single-cell parasite has the capacity
to invade and evolve in
varied ways that can escape the immune system.
A person recovered from malaria is not assured of protection from malarial infections in the
later stage of life. As the body cannot develop immunity because of the continuous change of
malaria parasite makes it very complex to create a vaccination. Even prolonged exposure to
insecticides can develop resistance towards insecticides by the mosquitoes.
Though it seems to be a daunting condition, there are various ways to be optimistic and bring
change in the environment. Educating and taking action on hygiene and sanitation can control
malaria. Travelers being aware of malaria risk and taking efforts for protective measures and
malarial prevention can help reduce its attributable mortality and morbidity. Regions with limited
financial resources face problems in preventing the infection, but implementing chemoprophylaxis
and permethrin-impregnated bed nets have helped against malaria in these regions. Therefore,
as such fever is a threat to one's life, do not leave your sickness ignored.
Thyrocare offers Fever Profile Testing for the qualitative analysis of malaria
antigen using advanced and sophisticated automated technology using immunoassay at highly
affordable rates.
Malarial Biomarkers
Malaria is one of the most common zoonotic transmissions reported in
tropical and subtropical zones of the globe. The protozoan causing this
ancient disease belongs to the family of genus Plasmodium. The Center
for Disease Control (CDC) has declared malaria to be an endemic, spreading
the infection in more than 100 countries. In 2019, India reported 3,38,494
malariarelated morbidity cases.
There are five species of Plasmodium that can cause this illness
- Plasmodium falciparum (P. falciparum)
- Plasmodium malariae (P. malariae)
- Plasmodium vivax (P. Vivax)
-Plasmodium ovale (P. ovale)
-Plasmodium knowlesi(P. knowlesi)
Although all of them are being transferred via Anopheles mosquito,
P. falciparum accounts for the highest mortality rate. Investigations
suggest that the in vivo proliferation of the pathogen is associated
with intracellular structural modifications and hijacking other healthy
red blood cells for survival.
Cerebral malaria is considered to be the most severe neurological
complication of infection with Plasmodium falciparum. It is a clinical
syndrome characterized by the clinical hallmark of coma which is
usually caused by parasitized red blood cells (PRBCs) sequestered
in cerebral microcirculation and the finding of asexual forms of the
parasite on peripheral blood smears. Mortality rate for this syndrome
is high and some surviving patients perpetuate brain injury that reflects
as long-term neurocognitive impairments
Moreover, the parasite has exhibited tremendous resistivity towards
various drugs, urging medical professionals and technologists to come
up with better advances in diagnosis and treatment that may help in
right choice of prophylaxis.
Elements of the Parasitic Lifecycle Responsible for Transmission
On this World Mosquito Day, CDC has urged people to pay attention to
the mosquito Anopheles stephensi, responsible for the quick spread of
infections in many man-made habitats.
Earlier there was an urgent need to understand the parasitic lifecycle
and its mode of transmission but now scientists have diverted their
attention towards the relevance of finding specific biomarkers for
quick diagnosis.
Symptomatic Assessment in a ResourceLimited Setting
Traditional diagnostic methods were mostly dependant on the
symptomatic exhibition of a condition; such as fever, chills,
extreme headache, fatigue, muscular pain, nausea, vomiting,
and loss of appetite.
These symptoms, if ignored for a longer period, turn out to be fatal
within a short time. However, at the same time, they are also found
to be overlapping with other common health challenges like pneumonitis,
tuberculosis, and other gastrointestinal issues. At the same time, in areas
that are declared with endemic species by world health authorities; some
people can often go asymptomatic, further escaping the clinical evaluation
of malaria. Some patients have reported severe health challenges like
respiratory distress due to pulmonary edema, severe anemia, acute
kidney failure, hypoglycemia,etc
Previously, it was challenging to diagnose malaria on time, causing
significant morbidity and mortality associated with the same.
Estimates have suggested that the numbers of clinical illnesses
reported are above five billion episodes. The data has further
pinpointed the fact that more than 60% of the reported cases
are from the poor, underdeveloped parts of the world that are
still struggling to get better diagnostic facilities and medical support.
Thus, while poverty struck areas of the world are still looking for better
medical facilities, clinical scientists are working on game changing
biomarkers as tools in diagnosis and treatment.
Available Biomarkers
Although, science and technology have experienced vast advancements
over time, and diagnosing malaria is not an exception, it is undeniable that
the majority of diagnostic procedures available today are still dependent
on the age-old process of blood smear analysis. Accordingly, current
biomarker testings available for rapid detection of malaria parasites are listed
Nucleic Acid Amplification Testing
Fortunately, with aggressive scientific research, contemporary methods are now
available based on nucleic acid amplification of circulating pathogenic
DNA that is more sensitive, faster, and accurate as compared to classic
methods. Studies have further supported that genomic assessment
methods are very accurate in detecting even the lowest pathogenic
load, such as 5 parasites per microlitre.
Rapid Testing Using Immunological Lateral Flow Devices
It is possible to detect pathogenic parasites from circulating blood
using lateral flow immunochromatography assay. Theoretically, this
approach has been proposed to be more rapid, sensitive, and accurate
in detecting the very minute level of parasitic antigen. The method has
also gained high scientific acknowledgment due to its ability to detect
antigenic receptors for many parasitic generations that have been
difficult earlier using a light microscope. Moreover, with this
method it is possible to detect the parasite from saliva and/ or urine
of the infected person; and hence, can resolve major challenges
associated with sampling of blood even, with a reported sensitivity
of around 73% that can be increased to 83% in highly infected patients.
Urine Malaria Rapid Detection Method
It is a recently developed technique that can detect the histidine-rich
protein II (HRP-II)
biomarker of P. falciparum. The method requires urine sample and hence has
been acknowledged as non-invasive method of detection. Investigations have
indicated that the method is highly efficient with high sensitivity and specificity
as compared to other existing methods. Some other studies have further
suggested that with the current method, it is possible to detect 120 parasites/L;
and is found to be 50% higher in comparison to other methods from a similar
domain. However, further optimization is still mandatory to avoid false positive
detection due to void sampling, like morning urine with a higher antigenic titer.
Loop-Mediated Isothermal Amplification (LAMP)
This is one of the most promising and widely assessed diagnostic techniques,
capable of detecting even the minutest concentration of human Plasmodium
spp. The method is also commercially available in the form of LAMP kits and
can detect direct as well as indirect infections associated with P. falciparum
as well as P. vivax, and is further classified as one of the high-throughput
techniques. Studies have indicated that from any given sample including
blood, saliva, and/or urine; the technique can help detect low as 2.5
parasites/uL in a very cost-efficient manner.
Multiplex Biomarkers & Future Prospects
With technological evolution, it is now possible to sense presence of pathogenic
parasites from any given sample i.e. blood and/or urine, using self-contained
analytical devices without the need for any processing steps. The technology
incorporates nanoscience; which further enables the detection of monoclonal
antibodies against the pathogenic antigen. The assay is found to be highly
sensitive with the detection limit at 0.00005%. Scientists are relying on these
one-step detection techniques to overcome traditional diagnostic challenges
due to the paucity of specific biomarkers.
Conclusively, despite the evolution of diagnostic techniques for more accurate
and better detection of pathogens; people are more inclined towards using
traditional technology even with limited sensitivity and specificity. This is
further limiting the process of complete eradication of malaria, especially
in asymptomatic individuals. Other developed techniques like rapid tests
and nucleic acid amplification tests are more confined to the fixed
population of people; demanding expert handling and basic biological
understanding, further rendering them not suitable for routine
implementations. This further compels the implementation of more
advanced techniques like multiplex biosensing systems, due to their
suitability in off-lab settings, high sensitivity, and specificity. With the
new approach provoking to find ultra-sensitive, field ready, and user
friendly methods; the scientific world is all set to live in the
malaria-free world!
Dengue
Dengue also termed as the Bone break fever", is a febrile illness that
can result in fatal outcome in severe cases. Caused by Flavivirus, it is spread by the mosquitoes belonging to
Aedes genus majorly the Aedes aegypti and Aedes albopictus. It is a vector borne disease and the status of the
host immune system, pathogen virulence, host genetic makeup, etc. greatly influence the rate of progression of
disease in an affected individual
Epidemiology and prevalence of dengue
Dengue is never reported as a singular case in any region or population group as its occurrence is always
seasonal and as an epidemic. India is believed to have more cases of dengue than any other country in the
world,
with major outbreaks in recent years. Mumbai is found to be one of the most affected city in
Maharashtra in the year 2014 due to erratic rains and weather changes. Many other states all
over India have also been reported to be affected with dengue; increased cases majorly from
the Northeast region of the country.
Mode of Transmission and Stages of Dengue
Viruses are infectious agents which have the ability to infect any host cell, utilise its machinery
and multiply to raise an infectious state The causative agent of dengue is transmitted through an
infected mosquito bite. When a mosquito bites a dengue infected person, the virus enters into mosquito
and undergoes a state of dormancy. Post this phase, the active virions enter the salivary gland of the
mosquito and thus result in making the vector highly infectious.
Symptoms of Dengue
- Fever
- Nausea
- Liver enlargement
- Failure of circulatory system
- Damage to blood vessels.
Risk factors of Dengue
1.Dengue virus is found to
efficiently survive in tropical
climates, and hence, people residing
in such regions are always at a
higher risk.
2. Presence of filth, stagnant water
bodies, unclean surroundings all become active breeding grounds
for mosquito larvae.
3. Also lack of awareness in diag
nosis leads to an increased risk factor. Differentiation between
febrile illness and dengue is very important for appropriate
and timely treatment.
Diagnosis of Dengue
On presenting symptoms of fever, headache accompanied by severe body ache, the first test recommended by
a physician will be a complete blood count (CBC). This test will highlight clinical status of the count
of blood cells and platelets which is extremely important for differential diagnosis of dengue. Reduction
in platelet count is one of the major signs of dengue and can aid the doctor to start a preliminary
antiviral
treatment. However, this condition can arise in other viral conditions as well and hence further specialised
tests like Enzyme linked immunosorbent assay (ELISA) may be recommended by the doctor to assess disease prognosis
as well as treatment efficiency. Serum IgG and IgM levels are estimated for confirmatory diagnosis of dengue.
Treatment of Dengue
There are no specific and dedicated treatment modalities available for dengue. Treating dehydration
and low platelet count condition is the only path to recovery. Treatment with general analgesics like
acetaminophen is done to provide relief from fever and pain.
Why is this vicious cycle not breakable?
Poor sanitation is one of the major causes of dengue in India. Unattended garbage and stagnant
water bodies become breeding grounds for mosquitoes thus making all classes of people susceptible
to this painful condition. The major preventive measures to be taken for dengue are as follows:
Drains should be kept free from
choke.
To avoid breeding of larva at home, clean the water in the saucer of potted plants.
Aedes mosquitoes is most active
during day time and hence avoid going near shrubs where adult mosquitoes rest during the day.
Dispose all the household garbage into bins which are properly covered.
Wear clothes and shoes which
completely cover especially when visiting dengue endemic areas.
Install mosquito screens on the windows and ensure use of repellents.
