PCP: Still With Us
Left Field by Patricia Nell Warrenbuy xanax online without prescription
Even though we know a bit more about this pathogen, questions about treatment still persist.buy diazepam without prescription
In my last Left Field, I wrote about the return of Kaposi’s sarcoma. Another blast from the past that’s still around is pneumocystis pneumonia—due in part to growing resistance to drug treatments as well as its extraordinary ability to take advantage of weakened immune systems. For many of us who were around in the early 1980s, a chill goes down our spine at the mention of PCP, since this opportunistic form of pneumonia was a fatal factor in many early cases of AIDS. In the thirty years since it was first diagnosed in PWAs, big changes have jarred the picture of what we know about this disease, and how it can be treated. Yet PCP is still somewhat mysterious, and a growing threat in parts of the world where it hasn’t been a major threat before. ambien for sale
In 1909, Carlos Chagas, probably first to report on the organism, said he believed it to be a parasitic protozoan, member of the trypanosome family. Trypanosomes emerge from a tiny cyst, to cause an array of diseases in animals and humans, including sleeping sickness. A year later, Brazilian scientist Antonio Carini also described the organism, and it was named P. carinii after him. Scientists found it thriving from the polar regions to the tropics, but only in mammals, because it apparently prefers a temperature range of 35 to 41 degrees C, the mammalian comfort zone. Thus the organism isn’t found in birds or reptiles. buy zolpidem no prescription
The disease first drew attention during World War II, when the typical cysts showed up in European children whose immune systems were severely suppressed owing to the privations they’d suffered. Chest X-rays revealed a distinctive tangled whiteness in the lower lungs that suggested growing fibrosis of lung tissues. Yet before 1980, in the U.S., PCP cases numbered only in the hundreds annually. Most of these were people whose immune systems had landslided owing to cancer-related immunotherapy, or to treatment with immunosuppressants after receiving organ transplants. buy soma online no prescription
It is challenging to diagnose PCP definitively. The patient starts with fever, difficulty breathing and a dry cough—but the cough produces no sputum that can be analyzed. So lab specimens have to be extracted using more invasive methods like bronchoscopy, lung rinse or biopsy. Microscope viewing reveals those tiny rounded cysts that give the disease its name, each with a black spot on it—they are scattered through a magnified landscape of lung-tissue inflammation, fibrosis, and damage to the alveoli, or air sacs. The tiny sacs are laced with blood vessels. When oxygen is breathed into the lungs, it passes through the sac walls into blood vessels; from there, oxygen makes its way to the entire body. By a reverse process, the bloodstream freights its waste product of carbon dioxide back to the lungs, where it filters through the sac walls into the alveoli, and is breathed out of the body. As advancing P. jirovecii flourishes inside more and more air sacs, it impedes this crucial process, to the point where a patient can actually turn blue with cyanosis. ultram online no prescription
Once this disease began to be scrutinized in PWAs, an additional type of calcification—bubbly or plate-like calcium hardening—was noted in the lungs. This was believed by some researchers to be related to HIV’s activity in some way. valium online without prescription
By the late 1980s, science was intensifying its interest in PCP, when well over 100,000 cases had exploded throughout the AIDS epidemic. Obviously the proliferation of individuals with devastated immune systems provided fertile fields of lungs where the organism could do its digging. It seems to thrive best when the CD4 count goes below 200. buy alprazolam without prescription
Unfortunately the organism is difficult to study. It refuses to grow as an in-vitro culture in the lab. Eventually, however, with the growth of DNA study of pathogens, scientists noticed that one particular bit of DNA flagged it as a red-yeast type of fungus—though the organism refused to grow on the culture mediums used to grow red yeast in the lab. Scientists also learned that the cysts eventually rupture, each releasing eight spores. Last but not least, it was also determined that the type of pneumocystis found in humans was different from a form of pneumocystis found in rats. As a result, this human organism has been formally renamed Pneumocystis jirovecii, or PJP. But the old PCP acronym is still often used. provigil online no prescription
Investigators are still not sure whether jirovecii spores are spread by direct physical contact, or whether they might be coughed out and go airborne, to simply be inhaled. Ongoing investigation suggests transmission by direct contact. On the other hand, in a Swiss study reported in January 2003 Emerging Infectious Diseases, the Swiss team had this to say about transmission: “We report a molecular typing and epidemiologic analysis of Pneumocystis carinii pneumonia (PCP) cases diagnosed in our geographic area from 1990 to 2000. Our analysis suggests that transmission from patients with active PCP to susceptible persons caused only a few, if any, PCP cases in our setting.” Hospital practice today is to isolate cases of PCP from any non-PCP patients who have depressed immune systems. buy phentermine without prescription
But sick people might not be the only vectors of PCP. Many apparently healthy individuals without any symptoms of the disease have been found to have a low density of P. jirovecii in their lungs. Some of these people might even have been infected in childhood from some yet-unidentified source in the environment. A British study published in 2002 in Journal of Clinical Microbiology suggests that mother-to-child transmission of PCP is possible. klonopin online no prescription
Not surprisingly, one of the early drugs investigated in PCP studies was chloroquine, then a drug of choice for malaria, another disease caused by a protozoan parasite. During the early years of the AIDS epidemic, we heard a lot about pentamidine aerosols—the explosion of demand for pentamidine was dramatized in the bestselling book And the Band Played On. But pentamidine was found to have severe side effects, so it is not much used today, save in severe cases where patients don’t tolerate the first-line drugs. Pentamidine’s administration is also more technically complex and costly. ativan for sale
Today most PCP treatment relies on a member of the sulfonamide family of antibiotics—trimethoprim/sulfamethoxazole, sold under brand names like Bactrim or Septra. These drugs can be taken orally; they are widely used in treating bacterial and protozoan infections as well. They have their own side effects, notably allergies. In severe cases, steroids are also used to combat the inflammation. tramadol online no prescription
PCP continues to confound science. To this day, its complete life cycle has never been observed, since it evidently takes place within the living lung. If it has a lair somewhere in the environment, this hiding place has not yet been identified. Though officially classified as a fungus, it doesn’t respond to conventional fungus treatments. Today, according to Medscape, PCP is still the most common opportunistic infection in people with HIV/AIDS. In severe cases, it is still life-threatening, and treatment can’t be delayed. Patients who smoke face an added barrier to recovery.
Statistics show that PCP outcomes are still dicey. According to UpToDate: “In the absence of appropriate antibiotic therapy, the mortality rate from PCP in non-HIV-infected patients is 90 to 100 percent. The outcomes in non-HIV-infected patients treated for PCP are generally worse than in HIV-infected patients; mortality from PCP in patients with HIV infection is approximately ten to twenty percent compared with thirty-five to fifty percent in those without HIV. Patients with cancer have the highest mortality rates.”
Worse yet—by 1998, investigators were already noticing that P. jirovecii was developing resistance to Bactrim/Septra. In that year, PubMed issued the first open cautionary: “While resistance does not appear to be happening on a large scale, it is a concern because no other drug has the same beneficial effects of B/S. Research is needed for simple, low-toxicity treatments and prophylactic drugs for PCP, before resistance becomes a common problem.”
That was thirteen years ago. Recent publications confirm that resistant mutations of P. jirovecii may be on the march. A European study cited on PubMed Central in 2004 had this to report: “Most drugs used for prevention and treatment of Pneumocystis jirovecii pneumonia target enzymes involved in the biosynthesis of folic acid, i.e., dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR)…..The emergence of P. jirovecii drug resistance has been suggested recently by the association between failure of sulfa prophylaxis and mutations in the gene encoding DHPS….Moreover, similar mutations in other microbial pathogens are known to confer sulfa resistance. Alteration of DHFR enzyme is a common resistance mechanism in clinically important microbial pathogens, such as Plasmodium falciparum [the most lethal form of malaria] and Streptococcus pneumonia.”
PCP’s incidence in Africa, where it used to occur more sparsely, is growing. In a four-year African study cited recently by PubMed, the organs of deceased African miners were autopsied in order to learn more about occupational diseases that may have killed them. An astounding eighty-nine percent had undiagnosed PCP. The study warned, “The high rate of undiagnosed PJP is cause for concern. Clinicians should have a heightened awareness for PJP in Africa, particularly as the disease is treatable at low cost and effective prophylaxis is available.”
In recent years, the world has also seen an ominous rise in the number of drug-resistant strains of HIV itself, which opens the door to growing ineffectiveness of the ARVs of choice, and a parallel rise in the number of opportunistic infections. Altogether, these shifts on the magnified landscape of P. jirovecii are not good news for any human who presents with this still-somewhat-mysterious form of pneumonia.
Pneumocystis Pneumonia, Third Edition (Lung Biology in Health and Disease), Peter Walzer and Melanie T. Cushion, editors (Informa Healthcare, 2004)
“Mutations in the Pneumocystis jirovecii DHPS gene confer cross-resistance to sulfa drugs.” PubMed, February 2005
Author of fiction bestsellers and provocative commentary, Patricia Nell Warren has her writings archived at www.patricianellwarren.com. Reach her by e-mail at firstname.lastname@example.org.
Copyright © 2011 by Patricia Nell Warren. All rights reserved.