Monday, March 7, 2016

Drug Resistant Bacteria

Drug Resistant Bacteria
(you may die only from a sore throat)

Bulan April tahun 2006, seorang pelajar putri berusia 16 tahun mengeluh sakit tenggorokan setelah pulang berlibur bersama keluarganya. Sakitnya tidak dirasakan berat, ia bahkan masih bisa berpergian ke mall. Baru beberapa hari kemudian kondisinya mulai menurun, ada demam tinggi, lemas, ada keluhan “back pain”. Setelah beberapa kali ke dokter akhirnya si remaja putri didiagnosis “pneumonia” (radang paru) dan harus segera masuk RS. Setelah dirawat di RS selama 2 hari, diketahui kalau radang parunya disebabkan oleh MRSA (Methicillin-resistant Staphylococcus aureus). Ini adalah golongan bakteri yang sudah ber-evolusi melalui seleksi alamiah, dan berakibat si bakteri memiliki resistensi terhadap berbagai antibiotik termasuk golongan penicillins (methicillin, dicloxacillin, nafcillin, etc) dan golongan cephalosporins. Otomatis hal ini mengakibatkan golongan bakteri MRSA ini lebih susah untuk diobati dengan standard antibiotik biasa.

Setelah mengetahui penyakitnya, dokterpun menenangkan orang tua sang pelajar putri. Mereka masih menaruh kepercayaan dengan ilmu kedokteran yang sudah maju, dan tentu antibiotik yang tepat bisa digunakan untuk melawan MRSA tersebut. Sayangnya kenyataan berbicara lain.  Hasil scan menunjukkan kondisi paru parunya terus memburuk, tidak ada perbaikan sehingga bahkan harus dimasukkan tube ke dalam tenggorokannya untuk membantunya bernafas. Dokter yang menangani menyerah, tidak bisa lagi menaikkan kadar oksigen dalam tubuhnya dan ia dirujuk ke RS yang lebih besar. Sementara itu, kondisi dan kesadarannya terus menurun sehingga berada dalam keadaan koma. Si pelajar putri yang sebelumnya sehat, “an honor student”, dan juga jago berenang ini tiba tiba harus bergantung pada alat alat bantu penunjang kehidupan yang dipasang di sekujur tubuhnya. Akhirnya 4 bulan setelah berjuang melawan penyakitnya di RS, Rebecca Lohsen, meninggal dunia. Ibunya yang juga seorang perawat, antara percaya dan tidak menyaksikan hidup putrinya direngut oleh bakteri yang selama ini dianggap sudah bisa ditaklukan oleh obat obatan modern.
Nearly 4 months after she mentioned that sore throat, she died”.
Kisah selengkapnya bisa dibaca disini:
http://www.idsociety.org/Templates/nonavigation.aspx?Pageid=12884901901&id=32212257007

Kasus lain dilaporkan pada tahun 2009 di journal Clinical Infectious Diseases. Sebuah RS di New York melaporkan kasus infeksi yang disebabkan oleh bakteri Klebsiella pneumonia. Sebenarnya ini bakteri ini umum jadi penyebab infeksi nosocomial di RS, sayangnya kali ini si bakteri memiliki resistensi terhadap semua antiobiotik yang biasanya digunakan terhadap bakteri tersebut. Dokter di RS tersebut menyebut bakteri ini sebagai “panresistant K. pneumonia”. Akhirnya dokter di RS tersebut mendeskripsikan penyebab kematian dari pria berusia 67 tahun yang dirawat di sana sebagai akibat dari panresistant klebsiella dan mereka mengakui mereka tidak punya pengobatan efektif yang bisa digunakan.
Berikut kutipan dari journalnya:
It is a rarity for a physician in the developed world to have a patient die of an overwhelming infection for which there are no therapeutic options. These cases were the first instance in our clinical experience in which we had no effective treatment to offer. Trends in urban hospitals are often the harbinger of the future. We share these cases to highlight some troubling issues that soon may be relevant to increasing numbers of physicians and patients across the United States.”

Begitupula di tahun 2011, seorang pasien dibawa ke RS rujukan di National Institutes of Health Clinical Center di Maryland. Ia diketahui terinfeksi bakteri Klebsiella yang memiliki resistensi terhadap beberapa antibiotik poten yang ada saat itu. Selama di RS ia harus masuk ruang isolasi dan penjenguknya harus mengenakan gaun khusus serta sarung tangan. Untunglah setelah satu bulan dirawat akhirnya ia bisa keluar dari RS dengan selamat. Sebulan berikutnya, ada pasien lain yang terkena bakteri Klebsiella yang sama dengan pasien pertama tadi, disusul pasien pasien baru di minggu minggu berikutnya. Saat itu total ada 18 pasien yang terinfeksi dan 6 diantaranya gagal diselamatkan dengan pengobatan (antibiotik) yang ada.

Kenapa ada bakteri yang bisa resisten terhadap antibiotik?
MRSA dan bakteri lainnya yang resisten terhadap antibiotik seperti klebsiella di atas sebenarnya adalah hasil dari pengobatan modern. Rebecca dan pasien pasien lain yang meninggal dunia gagal diselamatkan karena semua orang lain yang sakit sebelum mereka telah terlebih dahulu banyak diobati dengan menggunakan antibiotik. 

Antibiotik bekerja dengan membunuh bakteri penyebab infeksi. Komposisi kimia dari banyak antibiotik sebenarnya berasal, atau mirip dari senyawa yang dihasilkan oleh si bakteri sendiri untuk berkompetisi membunuh bakteri lain. Jadi secara natural, bakteri bakteri ini harus berusaha bertahan hidup dengan mengambangkan resistensi terhadap senyawa kimia tersebut.
Bakteri yang berhasil bertahan hidup bisa kembali menyerang orang lain, yang kemudian diberi lagi antibiotik dan seterusnya dan seterusya. Ini merupakan ‘booster” buat si bakteri. Mirip proses evolusi, segolongan bakteri yang selamat dari antibiotik ini akan terus berkembang menjadi lebih kuat dan memiliki resistensi terhadap bermacam antibiotik. Akhirnya, pada saat si bakteri menyerang Rebecca dan pasien2 lain di atas, bakteri tersebut sudah merupakan hasil produk adaptasi yang mempunyai “pharmaceutical tool kit” dan tidak bisa lagi dikendalikan dengan antibiotik yang umum kita kenal.


Resistensi obat juga bisa terjadi dengan cara mutasi dimana si bakteri mengambil kemampuan resistensi tersebut dari bakteri lain yang bisa bertahan hidup. Contohnya, kita semua memiliki bakteri di dalam usus yang tidak berbahaya (harmless bug) dan kebetulan memiliki gen resistensi terhadap obat. Bakteri pathogen yang masuk lalu bisa mengambil kemampuan resistensi dari bakteri usus tersebut dan akhirnya memiliki resistensi juga.

Tidak semua bakteri juga mengalami proses evolusi dan menjadi resisten terhadap antibiotik. Treponema pallidum, misalnya, bakteri penyebab syphilis ini masih bisa dikendalikan dengan penicillin meskipun di lain pihak sudah banyak bermunculan bakteri bakteri yang resisten terhadap penicillin. Penggunaan chloroquine di India masih efektif untuk malaria vivax meskipun sudah mulai terjadi resistensi di negara lain. Hal ini mungkin bisa jadi petunjuk yang baik untuk mempelajari bagaimana mencegah resistensi obat.

Bagaimana menghadapi resistensi obat tersebut?
Yang pasti sudah waktunya kita juga harus berpartisipasi ikut membatasi perkembangan kuman atau bakteri yang memiliki resistensi terhadap obat obatan. Salah satu strategi yang bisa dilakukan yaitu mengubah pola pikir terhadap infeksi. Seperti pepatah umum yang sudah lama kita kenal “mencegah lebih baik dari mengobati”. Kasus infeksi sedapat mungkin sejak awal dicegah (first care) dengan menjaga kebersihan atau dengan vaksin.

Strategi lain yang sangat penting dengan membatasi penggunaan obat (antibiotik) sebagai “driver” dari evolusi bakteri itu sendiri. Setiap kali bakteri berhadapan dengan antibiotik, secara natural terjadi seleksi alamiah yang mengasilkan bakteri hidup yang memiliki resistensi terhadap antibiotik tersebut. Itu sebabnya penggunaan antibiotik tidak bisa bebas sembarangan dan harus memakai resep dokter. “We need to hold back our drugs for only the important cases; only use drugs when there is clinical need”.
Seringkali dokter mengobati pasien dengan tujuan utama supaya pasien cepat sembuh secepatnya (as healthy as possible, as fast as possible). Mereka tidak perduli dengan konsekuensi adanya evolusi bakteri dari obat obatan yang diberikan, yang mungkin saja bisa mengakibatkan resistensi dan fatal di pasien pasien berikutnya. Saat ini resistensi obat semakin meluas, sudah waktunya kita juga harus berevolusi, mengubah pola pikir bahwa mengobati penyakit dengan menggunakan obat obatan seperti antibiotik yang ada sekarang pasti beres.

Antibiotik pertama kali ditemukan dan dipakai sejak tahun 1928, hampir 100 tahun yang lalu. Kita harus berupaya memikirkan dan menemukan strategi baru untuk menghadapi bakteri bakteri hasil evolusi.
“Drugs WERE magic bullets. They aren’t now”

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Summary from the lectures: “Drug Resistance” Epidemics-The Dynamics of Infectious Diseases -The Pennsylvania State University.
Reports:
Azza Elemam, Joseph Rahimian, and William Mandell
Infection with Panresistant Klebsiella pneumoniae: A Report of 2 Cases and a Brief Review of the Literature. Clin Infect Dis. (2009) 49 (2): 271-274 

Images:
* By NIAID – NIH  http://www.niaid.nih.gov/topics/antimicrobialResistance/Understanding/Pages/drugResistanceDefinition.aspx, Public Domain, https://commons.wikimedia.org/w/index.php?curid=41858152
* http://whyfiles.org/shorties/090antibio_resist/

                  

Friday, January 15, 2016

Cancer Prevention: Infection, Vaccination, Screening

Cancer Prevention
~ Part II ~

Four cancer-related risk factors have been summarized in the previous article:

Here are other things that we should aware, infections that link to cancer, and cancer screening and vaccination.

5. Infections and cancer
In 1981, only two infections that have links to cancer including the hepatitis B virus (HBV) which is known to cause liver cancer, and the Epstein-Barr virus (EBV) which was linked to Burkitt’s lymphoma. Today, 11 infectious agents are well established as human carcinogens. In 2008, about two million of the 12.7 million new cancer cases worldwide, which means about 16% of the total, were attribute to chronic infection.
There are seven viruses, one bacterium, and three parasitic worms that act as cancer agents.
1. Epstein-Barr virus (EBV)
A type of herpes virus which causes non-cancerous condition called infectious mononucleosis (or mono, or the kissing disease) and also associated with some forms of cancer such as Hodgkin’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma, and type of lymphoma that occurs in people who undergone organ transplantation called post transplant lymphoproliferative disorder. In addition to kissing, EBV can be passed from person to person by coughing, sneezing, or by sharing drinking or eating utensils.

2. Hepatitis B virus (HBV) and hepatitis C virus (HCV)
These two are leading causes of the hepatocellular carcinoma, the most common form of liver cancer. Both of HBV and HCV can cause the long-term (chronic) infections that increase a person’s chance of liver cancer. HBV and HCV are spread from person to person through sharing needles (such as injection drug use), unprotected sex, or childbirth. Once an infection is found, treatment and preventive measures can be used to slow liver damage and reduce cancer risk.

3. Human papilloma virus (HPV)
HPV is an interesting group of viruses with more than 100 different types. Some of them cause non-cancerous conditions such as warts on the hands and feet, and genital warts. Others are sexually transmitted, and in some cases, cause cervical cancer, cancers of the anus, vagina, penis, and vulva. 13 types out of 100 types of HPV are classified as carcinogenic. HPV type 16 and 18 are nearly always present in cervical cancer tumors and can also cause a type of throat cancer called oropharyngeal cancer. Recent research shows that oropharyngeal cancer caused by HPV infection can be considered a different form of cancer than that caused by HPV negative oropharyngeal cancer. HPV positive and HPV negative tumors develop along different molecular pathway and evidence suggests that patients with HPV positive tumors survive longer after treatment compared than those with patients with smoking related oropharyngeal carcinoma.

4. Human T-cell lymphotropic virus type 1 (HTLV-1)
This virus belogs to a class of viruses called retroviruses. Although it is something like HIV which is another human retrovirus, HTLV-1 can not cause AIDS.  It is mainly endemic in Japan, the Carribean, and Central Africa. It causes a type of lymphoma and leukemia in about 5% of the people who are infected.

5. Human Herpes virus eight (HHV-8, also known as Kaposi’s sarcoma)
Kaposi’s sarcoma is a cancer that occurs mainly in people with weakened immunities such as those with advanced AIDS or people who have undergone solid organ transplantation or bone marrow transplantation. HHV-8 infection is life-long (as with other herpes viruses), but it does not appear to cause disease in most healthy people. Thus, having a weekened immune system appears to be one such factor.

6. HIV type one
HIV does not appear to cause cancer directly. It infects and destroys white blood cells known as helper T-cells, which weakens the body’s immune system. Advanced HIV disease (AIDS) is defined by a severely damaged immune system. The loss of immunity allows preexisting latent viral infections such as Kaposi’s sarcoma, EBV, or HPV that has been suppressed by the immune system to become active. This, in turn, can lead to AIDS-defining cancers.

7. Merkel cell polyomavirus (MCV)
MCV was discovered in 2008 in samples from a rare and aggressive type of skin cancer called Merkel cell carcinoma. Nearly all Merkel cell cancers are now thought to be linked with this infection.

8. Helicobacter pylory
Helicobacter pylory is a bacterium that affects the stomach or small intestines and causes stomach cancer and gastric lymphoma, as well as gastric ulcers. Transmission occurs through close personal contact. Other factors include poverty, poor hygiene conditions, housing crowding, and the number of human children in the household. H.Pylory can lead to cancer because the infection causes chronic inflammation that induces growth and proliferation of stomach cels. This condition will alter gene excpression and facilitates gene mutation.

9. Three parasitic worms
Two of the worms are liver flukes, endemic in China, North and South Korea, and Southeast Asia. They can cause liver cancer. The flukes are transmitted through consumption of raw or undercooked infected fish includes dried, pickled, or salted fish.
The third wom is schistosomiases haematobium which is found on the African continent, and the Middle-East. It infects the upper small intestine and the bladder, causes urinary scistosomiases, an infection that can progress to bladder cancer.

6. Vaccination and Screening
Now, we have realized the importance of preventing cancer whenever possible. And then, when cancer does happen, it is most treatable if detected earlier. Vaccines are available and can protect agains two infections that are important cause of cancer worldwide. Hepatitis B virus (HBV) which is responsible for 50 to 90% of liver cancer, and Human papilloma virus (HPV) which causes virtually all cancers of the cervix and some cancers of the anus, vulva, vagina, penis, and oral pharynx. HPV types 16 and 18 are among the most common cancer causing infections. HBV vaccination is usually part of childhood vaccination. In 2010, 179 countries reported including HBV vaccination in their childhood vaccination program and nearly 70% of children wordwide receive three doses of the HBV vaccine. This should significantly reduce the incidence of liver cancer in coming decades. For HPV vaccine, it is best given to boys and girls at ages 11 to 12, but it can be given to those 9 to 26 years old. The vaccines are most effective when given to pre-teens, before they become sexually active. 

Checking for cancer or for conditions that might lead to cancer in people who have no symptoms is called screening. Screening tests are not meant to diagnose cancer. Sometimes screening test can find signs or symptoms of cancer before the person knows of the problem. In these cases, the person will be referred for further diagnostic test. Detecting cancer early is the key to surviving cancer. Chances of complete cure can be 95% or higher, for some cancers, if the cancer is found early. The evidence is strong that regular screening for breast, colorectal and cervical cancer can find cancer early. So if a person does have cancer, the longer he or she waits to get screened, the more likely that they will be diagnosed at later stage of cancer. And the later that cancer is diagnosed, the lower the chances of survival.
Cancers we can screen for include breast cancer, cervival cancer, and colorectal cancer. The most common method to screen for breast cancer is mammography. Women age 40 to 49 years old should talk with their healthcare provider about their risk of breast cancer and how often to have a mammogram. In addition, women should get regular clinical breast exams by their physicians as part of their annual exams. Cervival cancer is the fourth most common cancer in women worldwide. There are two tyes of approved cervival cancer screening test: PAP test and HPV test. New cervical cancer screening guidelines recommend annual PAP testing every three years for women age 21 to 65. Colorectal cancer is the third most common cancer wordwide. A stool blooed test (a test that identifies the presence of blood in a small sample of stool) should be done annually alone or with sigmoidoscopy or colonoscopy (uses a tube with a light to examine the lower one-third of the colon or the entire colon). If polyps are detected, the can be removed during the test and sent to a laboratory to test for cancer.

Here are some reasons commonly hear to avoid cancer screening test. Fear of finding cancer, fear of treatment, the cost of screening, not knowing what test to get or where to go for testing, embarrassment,waiting for symptoms to appear before going to get checked, thinking they are not at risk because they are older, or because they do not have family history.
Please note, cancer screening shows that most people usually do not have cancer, and this leads to peace of mind. For most of cancers, when caught earlier, the treatment is much less intensive. Also remember that being healthy and cancer free is beneficial to the whole family. Many cancers take years to grow in your body without causing pain or other symptoms, so it is important not to wait before you have symptoms. Only a small of percentage or people who develop cancer have a family history of cancer. In fact, three out of four people who are diagnosed with cancer do not have a family history. Thus, you should get screened even if no one in your family had cancer. Cancer does not just impact you. A cancer diagnosis can impact the whole family. Please remember that cancer screening can save your life.

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Summary from the lectures: “Introduction to the Science of Cancer” – The Ohio State University Comprehensive Cancer Center-James
* Additional data source:

Images:
Salam sehat,
Kathryn - Tokyo