MalariaViruses

Malaria is a parasitic infection spread by Anopheles mosquitoes. The Plasmodium parasite that causes malaria is neither a virus nor a bacterium – it is a single-celled parasite that multiplies in red blood cells of humans as well as in the mosquito intestine.

When the female mosquito feeds on an infected person, male and female forms of the parasite are ingested from human blood. Subsequently, the male and female forms of the parasite meet and mate in the mosquito gut, and the infective forms are passed onto another human when the mosquito feeds again.

Malaria is a significant global problem. There are approximately 216 million cases of the disease worldwide, killing about 655,000 people every year. Malaria is prevalent in Africa, Asia, the Middle East, Central South America, Hispaniola (Haiti and the Dominican Republic), and Oceania (Papua New Guinea, Irian Jaya, and the Solomon Islands). However, malaria is most prevalent in Africa where 60% of all cases are reported. In Canada, malaria is most often caused by travel to and from endemic areas.

Each year, up to 1 million Canadians travel to malaria-endemic areas. This results in 350 to 1,000 annual cases of malaria in Canada and 1 to 2 deaths per year.

Although the parasite has progressively developed resistance to several older anti-malarial medications, there are still many safe and effective medications both for treatment and prevention.

There are four species of the Plasmodium parasite that can cause malaria in humans: P. falciparum, P. vivax, P. ovale, and P. malariae.The first two types are the most common. Plasmodium falciparum is the most dangerous of these parasites because the infection can kill rapidly (within several days), whereas the other species cause illness but not death. Falciparum malaria is particularly frequent in sub-Saharan Africa and Oceania.

Causes of Malaria

You can only get malaria if you're bitten by an infected mosquito, or if you receive infected blood from someone during a blood transfusion. Malaria can also be transmitted from mother to child during pregnancy.

The mosquitoes that carry Plasmodium parasite get it from biting a person or animal that's already been infected. The parasite then goes through various changes that enable it to infect the next creature the mosquito bites. Once it's in you, it multiplies in the liver and changes again, getting ready to infect the next mosquito that bites you. It then enters the bloodstream and invades red blood cells. Eventually, the infected red blood cells burst. This sends the parasites throughout the body and causes symptoms of malaria.

Malaria has been with us long enough to have changed our genes. The reason why many people of African descent suffer from the blood disease sickle cell anemia is because the gene that causes it also confers some immunity to malaria. In Africa, people with a sickle cell gene are more likely to survive and have children. The same is true of thalassemia, a hereditary disease found in people of Mediterranean, Asian, or African American descent. (See the article on "Anemia" for more information.)

Symptoms and Complications of Malaria

Symptoms usually appear about 12 to 14 days after infection. People with malaria have the following symptoms:

• abdominal pain
• chills and sweats
• diarrhea, nausea, and vomiting (these symptoms only appear sometimes)
• headache
• high fevers
• low blood pressure causing dizziness if moving from a lying or sitting position to a standing position (also called orthostatic hypotension)
• muscle aches
• poor appetite

In people infected with P. falciparum, the following symptoms may also occur:

• anemia caused by the destruction of infected red blood cells
• extreme tiredness, delirium, unconsciousness, convulsions, and coma
• kidney failure
• pulmonary edema (a serious condition where fluid builds up in the lungs, which can lead to severe breathing problems)

P. vivax and P. ovale can lie inactive in the liver for up to a year before causing symptoms. They can then remain dormant in the liver again and cause later relapses.P. vivax is the most common type in North America.

Dengue Viruses

Viruses are tiny agents that can infect a variety of living organisms, including bacteria, plants, and animals. Like other viruses, the dengue virus is a microscopic structure that can only replicate inside a host organism. Who discovered the dengue virus? How many types of dengue viruses are there, and what do we know about them? How does the dengue virus infect a cell and replicate itself? In this section, we will explore the answers to these questions.

Discovery of the Dengue Viruses

The dengue viruses are members of the genus Flavivirus in the family Flaviviridae. Along with the dengue virus, this genus also includes a number of other viruses transmitted by mosquitoes and ticks that are responsible for human diseases. Flavivirus includes the yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses.

In 1943, Ren Kimura and Susumu Hotta first isolated the dengue virus. These two scientists were studying blood samples of patients taken during the 1943 dengue epidemic in Nagasaki, Japan. A year later, Albert B. Sabin and Walter Schlesinger independently isolated the dengue virus. Both pairs of scientists had isolated the virus now referred to as dengue virus 1 (DEN-1). Is DEN-1 the only type of dengue virus?

The Dengue Serotypes

Dengue infections are caused by four closely related viruses named DEN-1, DEN-2, DEN-3, and DEN-4. These four viruses are called serotypes because each has different interactions with the antibodies in human blood serum. The four dengue viruses are similar — they share approximately 65% of their genomes — but even within a single serotype, there is some genetic variation. Despite these variations, infection with each of the dengue serotypes results in the same disease and range of clinical symptoms.

Are these four viruses all found in the same regions of the world? In the 1970s, both DEN-1 and DEN-2 were found in Central America and Africa, and all four serotypes were present in Southeast Asia. By 2004, however, the geographical distribution of the four serotypes had spread widely. Now all four dengue serotypes circulate together in tropical and subtropical regions around the world (Figure 1). The four dengue serotypes share the same geographic and ecological niche. Where did the dengue viruses first come from? Scientists hypothesize that the dengue viruses evolved in nonhuman primates and jumped from these primates to humans in Africa or Southeast Asia between 500 and 1,000 years ago.

The change in distribution of dengue serotypes

The distribution of dengue serotypes in 1970 (a) and 2004 (b).

© 2014 Nature Education All rights reserved. 

After recovering from an infection with one dengue serotype, a person has immunity against that particular serotype. Does infection with one serotype protect against future dengue infections with the other serotypes? Individuals are protected from infections with the remaining three serotypes for two to three months after the first dengue infection. Unfortunately, it is not long-term protection. After that short period, a person can be infected with any of the remaining three dengue serotypes. Researchers have noticed that subsequent infections can put individuals at a greater risk for severe dengue illnesses than those who have not been previously infected.

Dengue Virus Genome and Structure

The dengue virus genome is a single strand of RNA. It is referred to as positive-sense RNA because it can be directly translated into proteins. The viral genome encodes ten genes (Figure 2). The genome is translated as a single, long polypeptide and then cut into ten proteins.

Figure 2: Dengue virus genome

The dengue virus genome encodes three structural (capsid [C], membrane [M], and envelope [E]) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins.

© 2010 Nature Publishing Group Guzman, M. G. et al. Dengue: A continuing global threat. Nature Reviews Microbiology 8, S7–S16 (2010). doi:10.1038/nrmicro2460 All rights reserved. 

What are the roles of these ten proteins? Three are structural proteins: the capsid (C), envelope (E), and membrane (M) proteins. Seven are nonstructural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. These nonstructural proteins play roles in viral replication and assembly.

Figure 3: Dengue virus structure

The dengue virus has a roughly spherical shape. Inside the virus is the nucleocapsid, which is made of the viral genome and C proteins. The nucleocapsid is surrounded by a membrane called the viral envelope, a lipid bilayer that is taken from the host. Embedded in the viral envelope are E and M proteins that span through the lipid bilayer. These proteins form a protective outer layer that controls the entry of the virus into human cells.

© 2011 Nature Education All rights reserved. 

The structure of the dengue virus is roughly spherical, with a diameter of approximately 50 nm (1 nm is one millionth of 1 mm) (Figure 3). The core of the virus is the nucleocapsid, a structure that is made of the viral genome along with C proteins. The nucleocapsid is surrounded by a membrane called the viral envelope, a lipid bilayer that is taken from the host. Embedded in the viral envelope are 180 copies of the E and M proteins that span through the lipid bilayer. These proteins form a protective outer layer that controls the entry of the virus into human cells.

Dengue Virus Replication and Infectious Cycle

How does the virus behave once it enters the human body? The dengue viral replication process begins when the virus attaches to a human skin cell (Figure 4). After this attachment, the skin cell's membrane folds around the virus and forms a pouch that seals around the virus particle. This pouch is called an endosome. A cell normally uses endosomes to take in large molecules and particles from outside the cell for nourishment. By hijacking this normal cell process, the dengue virus is able to enter a host cell.

Figure 4: Dengue virus replication

The dengue virus attaches to the surface of a host cell and enters the cell by a process called endocytosis. Once deep inside the cell, the virus fuses with the endosomal membrane and is released into the cytoplasm. The virus particle comes apart, releasing the viral genome. The viral RNA (vRNA) is translated into a single polypeptide that is cut into ten proteins, and the viral genome is replicated. Virus assembly occurs on the surface of the endoplasmic reticulum (ER) when the structural proteins and newly synthesized RNA bud out from the ER. The immature viral particles are transported through the trans-Golgi network (TGN), where they mature and convert to their infectious form. The mature viruses are then released from the cell and can go on to infect other cells.

© 2005 Nature Publishing Group Mukhopadhyay, S., Kuhn, R. J., & Rossmann M. G. A structural perspective of the flavivirus life cycle. Nature Reviews Microbiology 3, 13–22 (2005). doi:10.1038/nrmicro1067 All rights reserved. 

Figure Detail

Once the virus has entered a host cell, the virus penetrates deeper into the cell while still inside the endosome. How does the virus exit the endosome, and why? Researchers have learned that two conditions are needed for the dengue virus to exit the endosome:

1. The endosome must be deep inside the cell where the environment is acidic.
2. The endosomal membrane must gain a negative charge.

These two conditions allow the virus envelope to fuse with the endosomal membrane, and that process releases the dengue nucleocapsid into the cytoplasm of the cell.

Once it is released into the cell cytoplasm, how does the virus replicate itself? In the cytoplasm, the nucleocapsid opens to uncoat the viral genome. This process releases the viral RNA into the cytoplasm. The viral RNA then hijacks the host cell's machinery to replicate itself. The virus uses ribosomes on the host's rough endoplasmic reticulum (ER) to translate the viral RNA and produce the viral polypeptide. This polypeptide is then cut to form the ten dengue proteins.

The newly synthesized viral RNA is enclosed in the C proteins, forming a nucleocapid. The nucleocapsid enters the rough ER and is enveloped in the ER membrane and surrounded by the M and E proteins. This step adds the viral envelope and protective outer layer. The immature viruses travel through the Golgi apparatus complex, where the viruses mature and convert into their infectious form. The mature dengue viruses are then released from the cell and can go on to infect other cells.

Summary

The dengue virus is a tiny structure that can only replicate inside a host organism. The four closely related dengue viruses — DEN-1, DEN-2, DEN-3, and DEN-4 — are found in the same regions of the world. The dengue virus is a roughly spherical structure composed of the viral genome and capsid proteins surrounded by an envelope and a shell of proteins. After infecting a host cell, the dengue virus hijacks the host cell's machinery to replicate the viral RNA genome and viral proteins. After maturing, the newly synthesized dengue viruses are released and go on to infect other host cells.

Alat Bantu Pendengaran

Alat teknologi untuk mengatasi pendengaran – Alat bantu dengar atau had deria merupakan suatu alat akustik listrik yang dapat digunakan oleh manusia dengan gangguan fungsi pendengaran pada telinga.

Biasanya alat ini dapat dipasang pada bahagian dalam telinga manusia ataupun pada bagian sekitar telinga. Alat bantu dengar tersebut dibuat untuk memperkuat rangsangan bahagian sel-sel sensorik telinga bagian dalam yang rusak terhadap rangsangan suara dan bunyi-bunyian dari luar.

Alat Bantu dengar tersebut merupakan sebuah alat elektronik yang menggunakan batere dimana dalam pemakaiannya terdapat mikrofon yang mengubah gelombang dari suara tersebut menjadi energi listrik yang kemudian diterima amplifier yang dapat memperbesar volume suara dan mengirimkannya pada speaker yang ada pada bagian dalam telinga.

Jika ingin menggunakan alat Bantu dengar ini maka terlebih dahulu harus memeriksakan ambang pendengaran dengan alat yang dinamakan audiogram. Setelah itu barulah dapat ditentukan jenis dan model apa yang cocok digunakan untuk kasus kerusakan pendengaran yang dialami.

Beberapa macam alat bantu pada pendengaran sebagai berikut

1. Dipasang pada telinga (Open-Ear-Fitting/OEF)
Alat bantu pendengaran yang kecil disambungkan dengan wayar nipis dan penerima (receiver)yang mengarahkan bunyi ke dalam telinga.

– Selesa dan kecil
– Bunyi yang lebih semulajadi dan kurang tersumbat
– Penampilan yang bergaya dan berwarna-warni
– Sesuai untuk masalah pendengaran tahap ringan dan sederhana

2. Di belakang telinga (Behind-The-Ear/ BTE)
Alat pendengaran ini berbentuk melengkung dan diletakkan di belakang setiap telinga. Bunyi disampaikan melalui tiub ke dalam saluran telinga.

– amplifikasi yang tinggi untuk membantu masalah
pendengaran tahap ringan hingga tahap yang sangat teruk
– Saiz lebih besar dan mudah digunakan terutamanya
bagi mereka yang menghadapi kesukaran mengendalikan
objek kecil
– Jangka hayat bateri lebih lama

3. Dalam telinga/Dalam saluran telinga (In-The-Ear (ITE) / In-The-Canal (ITC))
Dibuat dengan acuan telinga khas dan dipasang dengan selesa di bahagian luar telinga atau saluran telinga

– Menghalakan bunyi secara terus ke dalam telinga untuk
memastikan prestasi yang optimum
– Selamat dan selesa di bahagian luar telinga
– Mudah dikendalikan
– Sesuai untuk masalah pendengaran tahap sederhana ke
tahap yang teruk

4. Dalam saluran telinga sepenuhnya (Completely-In-Canal (CIC)
Alat bantuan pendengaran kecil yang diletakkan dalam saluran telinga yang membolehkan bunyi terus masuk ke dalam telinga.

– Tersembunyi, sesuai untuk pelanggan yang mementingkan
penampilan
– Simulasi cara bunyi masuk ke dalam telinga memberikan
kualiti bunyi yang lebih semulajadi sound quality
– Sesuai untuk masalah pendengaran tahap ringan, sederhana
dan teruk