Pneumocystis Pneumonia

 Pneumocystis Pneumonia.

P. K. Ghatak, MD

In 1980 the medical community was challenged by an outbreak of a new disease that was rampant in homosexual communities in the major US cities. Within a few months, it was found to be a viral infection. The patients were in the immune suppressed individuals and the virus was called HIV (human immunodeficient virus). An interstitial pneumonia was almost a constantly coexisted with the HIV infection. The organism was Pneumocystis jirovecii, a unicellular fungus, and the pneumonia was called PJP pneumonia.

The history of Pneumocystis interesting.

In 1090 Dr. Chagas was in pursuit for the causative organisms of Trypanosomiasis of South America. He discovered a few tiny organisms in the respiratory tract of some of the victims. He thought those were immature Trypanosome trophozoites. In 1909 Antonio Carnii found 3 cysts in the lung of children which were similar to Chagas' trypanosome but he did not think they were trypanosomes. In 1910 Delano of Pasture institute discovered similar cysts in a rat's lung and found that the organism had many features of a protozoan and named it Pneumocystis carnii. In 1999 molecular analysis of mRNA and mitochondria of the pneumocystis was conducted by Otto Jiroveci, a parasitologist from Czechoslovakia. He identified Galactosaminogalactan a signature for a fungus. The organism now classified as a unicellular fungus. Pneumocystis exists in nature in three morphological stages – Protozoite, Sporozoite and Cysts (spores). Distinct genomic variability exists between host specific member of the genera. For the humans, the pathogenic organism is called pneumocystis jirovecii. It was so named to, honor Otto Jiroveci's work.

PJP pneumonia.

This fungus in ubiquitous, and exists as a parasite in lungs of mammals and humans. The children acquire this fungus by 3 to 4 years of age. It spreads from person to person by being airborne. In good health, no adults or children show any ill effects of this parasitic fungus.

In severely immunodeppressed individuals, with a CD4 cell count of less than 200 micro L, the pneumocystis becomes an opportunist pathogen. In the lung, it produces an interstitial pneumonia. The infiltrates are perihiliar distribution is called a bat wing pattern. Like a viral interstitial pneumonia, the patients become severely hypoxic due to low oxygen diffusion capacity with a wide A-a gradient. Most severe infections produce acute respiratory syndrome. Various systemic symptoms develop due to tissue hypoxemia, specially cerebral manifestations. Other non-pulmonary features are – a. severe bone marrow depression producing pancytopenia, b. lymphadenopathy. c. cotton-wool exudates in the retina, d. thyroid gland enlargement and gastrointestinal symptoms.

Common symptoms are – fever, unproductive cough, chest pain, shortness of breath, cyanosis and tachycardia.

Diagnosis:

High LDH is a characteristic feature. Pneumocystis trophozoites and cysts are recovered by warm saline induced sputum and from Broncho alveolar lavage fluids.

Treatment:

Severely ill patients requires tracheal intubation and mechanical ventilation.

PJP are very sensitive to Trimethoprim-Sulfa-Methoxazol(TMP-SMX). Usually given by IV in acute situation. In tablet form, it is used as chemoprophylaxis. Alternative to TMP-SMX chemoprophylaxis are Dapsone, Atovaquone and aerosolized Pentamidine.

Prognosis:

Before Retroviral therapy, the mortality from PJP pneumonia was 80-90 %.  The mortality is 10 to 20%.at present.

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Amoebiasis

 

Amoebiasis:

Diseases caused by Entamoeba histolytica and other species.

P.K. Ghatak, MD

Amoeba: it is a unicellular organism. The cytoplasm of the amoeba is jelly like and contains mitochondria, other organelle, a large nucleus and various sized vacuoles. The cytoplasm is encased within a double layered membrane. The outer layer of the membrane is tough and elastic. Amoeba crawls in a peculiar fashion and known as amoeboid movement. There are microvilli attached to the outer membrane which prevent the amoeba in getting tucked to any solid surface and the outpouring foot processes – pseudopods, help them float in water. Amoeba surrounds food particles by encircling it with pseudopods and incorporate it in its cytoplasm and forms a vacuole and after digesting it with various enzymes, the waste is eliminated. Amoeba propagates by binary division. In rare occasions, it produces multiple identical daughters. The cellular form of the amoeba is called trophozoites, and it also has a cyst form. The cysts are infective form.

Three species of amoeba are pathogenic for humans.

Entamoeba histolytica. It is the primary amoeba causing intestinal diseases and its various other sequels.

Acanthamoeba. It causes keratitis of the eyes. People wearing contact lenses are susceptible to infection with this amoeba and if keratitis is not properly treated it can produce corneal ulcer and loss of vision.

Naegleria fowleri is responsible for a highly fetal disease, amoebic meningoencephalitis.

Entamoeba histolytica.

Humans are the primary host and in endemic areas the local people develop a partial immunity and 90 % of infections produce no symptoms because perhaps the people develop a kind of parasitic tolerance with the amoeba colonies in the colon mucosa. People who are immune depressed or on immune suppressed therapy, specially steroids, are venerable to severe illness. Visitors are susceptible to acute amoebic dysentery and often develop symptoms after returning home. The amoebic cysts are infectious and the mode of infection is oral-fecal route. The incubation period is 2 to 4 weeks.

The cysts pass unchanged from the stomach to the terminal ilium, and in here the cysts break open and release young trophozoites. Trophozoites release protein digestive enzymes and phagocytize the surface enterocytes. The amoeba is antigenic to humans. The body responds by both innate and acquired immune systems. This results in acute inflammation and minute abscess formation in the colon. As abscess ruptures forming ulcers. Ulcers causes in mucus dysentery, abdominal cramps and frequency of bowel movements. Low grade fever and other systemic symptoms also develop.

Direct extension of colon infection to the right lobe of the liver, through the right hemidiaphragm, produces liver abscess and then to right lower lobe consolidation of the lung and lung abscess and pleural effusion.

Complications and sequels.

The following complication may develop -

Colon perforation, toxic megacolon, fulminant colitis - specially in the immune compromised victims. Chronic non-dysentery colitis – specially common in local population. A localized mass formation in the colon called Ameboma. Anal and perianal fistula. In some cases the amoeba borrows through the colon wall and enters blood circulation and distant organs are infected. This may result in peritonitis, ascites, pericarditis and pleurisy. Fallopian tube and uterine amoebic ulcers, left lobe of the liver abscess, abscess of the spleen and the brain.

Naegleria fowleri.

N.fowleri lives in warm water of lakes, ponds and untreated swimming pools. It enters the body through the nose. The amoeba penetrates the cribriform plate of the roof of the nose and enters the base of the brain, and a meningo-encephalitis follows. Because of the presence of a blood brain barrier, no amoeba killing agent can be used to control the infection. This ends in a catastrophe, the fatality rate is over 90 %.

Diagnosis:

Examination of stool for amoeba cysts used to be the only reliable method. In the past over diagnosis of Entamoeba histolytica had happened due to another amoeba, Entamoeba dispar, which is far more common intestinal parasite and it does not cause any human diseases, but the cysts are identical with the pathogenic amoeba species. The PCR can be used to detect amoebic systemic infections. At present, distant infections and the brain infections depend on this test.

Treatment:

In the past Metronidazole was used indiscriminately and now in endemic area the amoeba is resistant to it. Other imidazole compounds also fell to the same fate. Emetine injections are discontinued because of cardiotoxicity. Chloroquine and other synthetic quinine compounds are in use in tissue invasive types of lesions like abscess in the liver etc. Broad spectrum antibiotics are sometimes combined with Chloroquine.

A chat below, taken from CDC showing recommendation for Entamoeba histolytica infection:

Table. Recommended Treatment for Entamoeba histolytica Infection in Adults

Infection Type	Agent	Dosage
Asymptomatic	Paromomycin	25 to 30 mg/kg/d in 3 divided doses for 7 days
Invasive disease	Metronidazole	750 mg 3 times daily for 10 days or 2.4 g once daily for 2–3 days
Invasive disease	Tinidazole	2 g once daily for 3 days
Amebic liver abscesses	Metronidazole	750 mg 3 times daily for 10 days
Amebic liver abscesses	Tinidazole	2 g once daily for 3–5 days
Amebic liver abscesses	Chloroquine*	600 mg once daily for 2 days, then 300 mg once daily for 14 to 21 days

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Giardiasis

 

Giardiasis.

Hill diarrhea, Beaver fever etc.

P.K. Ghatak, MD

Giardiasis consists of a number of gastrointestinal diseases caused by Giardia duodenalis. Giardia is a flagellated protozoan, present in the water of the lakes and small streams contaminated by human and certain animal feces.

Giardia exits in two forms - trophozoite and cyst forms. The cysts have a tough outer shell which protects and makes them survive a long time. The cysts are infective form, and humans are infected when they eat and drink contaminated food and water. The outer shell of the cysts dissolves in the small intestine and each cyst releases two giardia trophozoites The trophozoites live in the lumen of the intestine by attaching to the surface cells and also live in the crypts of intestinal villus processes. They extract food and nutrition from intestinal cells. Giardia multiply by binary fission.

The presence of giardia trophozoites inside the intestine provokes the body to react by activating CD4 cells and Interleukin-6 (IL-6) and other cytokines. The cytokines causes inflammation and giardia releases enzymes which breaks down proteins that binds surface cells of the intestine, This results in cell loss of enterocytes and destruction of villi. As a result of villus, atrophy and a reduction of the surface area of the small intestine occurs.

[Protozoa means “ The first animal “. It is a unicellular organism, having a central nucleus but lacks a well defined cell wall and organized mitochondria in the cytoplasm. Protozoa exhibits free movement and predation behavior and lives independent as a free agent and/or as a parasite.]

Diseases produced by Giardia.

A. Acute gastroenteritis. B. Chronic diarrhea. C. Malabsorption syndrome. D. Irritable bowl syndrome, lactose intolerance and other sequels.

Acute gastroenteritis.

Within 2 weeks following infection, patient develop acute explosive watery diarrhea of foul – fishy smelling stool, several times a day. The stool contains fakes of denuded intestinal epithelium and undigested fat, which floats on the surface. Campy abdominal pain is common, a low grade fever is seen in some cases. Weakness and debility follows. Diarrhea may last for weeks and can turn to a chronic condition.

Chronic diarrhea.

Without treatment, diarrhea in general does not subside. Frequency of liquid stool lessens. Nausea and anorexia develop.

Malabsorption syndrome.

Reduction in number and height of villi resembles changes seen in tropical sprue and gluten enteropathy. Loss of nutrients, vitamins and minerals results in general debility, loss of weight and patients become susceptible to frequent infections.

Sequels:

Intestinal bacterial overgrowth, specially the pathogenic group, results in increased IgA production. Immune reactions manifests as arthralgia, muscle pain and weakness, irritation and headaches. Some patients have aggravated immune disease like flair up of Cohn's disease.

Development of Irritable Bowl syndrome is thought to be an imbalanced growth of

beneficial / pathogenic bacterial colonies. Lactose intolerance is also common.

Diagnosis:

In acute diarrhea, the stool examination will detect Giardia trophozoites and few cysts. In chronic diarrhea in giardia trophozoites have time to change into cysts. Consequently, diagnosis depends on recognition of cysts in the stool. Fluorescence antibody testing increases detection of giardia.

In malabsorption, endoscopic small intestinal biopsy detects typical atrophic intestinal villi. Lymphocyte infiltration of crypts and giardia trophozoites.

Treatment:

In any stage of infection, Metronidazole and analogs of Metronidazole used to be very effective. But overuse and misuse resulted in drug resistance. In such cases, some are using Albendazole. The WHO recommends Quinacrine and related synthetic quinine tablets.

In pregnant women, Paromomycin is used. FDA recommends Nitozoxanid for children.

Prevention:

Because sheep, cattle, mask rates. beavers, dogs and other rodents are infected by giardia, it is difficult if not impossible to protects lakes and small streams that flow down the hills into the valley. Chlorination of water do not kill the cysts of giardia. Boiling water and microwave radiation will destroy giardia cysts. Basically, it is the task of Public health officials to educate people about waterborne diseases and how to protect themselves.

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