Acute infection by Coxiella burnetii manifested in this case by Pneumonia. Coxiella infection is not transmitted by ticks. The contact can be with high probability at the time of delivery of an infected farm animal, in which the bacterium is disseminated in aerosols. The treatment of choice is with doxycycline in the acute phase (if meningitis is present, quinolones are preferred due to penetration of the blood-brain barrier). The combination of doxycycline plus hicroxychloroquine can be used, but for chronic Q fever (which is where elevation of antibodies against phase I antigens is observed and carries a higher risk of mortality).

Acute infection by Coxiella burnetii manifested in this case by Pneumonia. Coxiella infection is not transmitted by ticks. The contact [HIDDEN], in which the bacterium is disseminated in aerosols. The treatment of choice is with doxycycline [HIDDEN]. The combination of doxycycline plus hicroxychloroquine can be used, but for chronic Q fever (which [HIDDEN]).

A 38-year-old woman of veterinary profession, in charge of monitoring wild animals and assisting in the delivery of domestic livestock. She starts with a high fever with chills, headache, myalgia and non-productive cough that she interprets as a flu-like process. She presented with chest pain. Chest X-ray showed bilateral pulmonary infiltrates in lower fields. A serologic test was performed with elevated antibody titers against phase I antigens. Which of the following statements is TRUE?

The way of transmission of this entity is by ticks.

Both doxycycline and hydroxychloroquine are effective in treating acute forms of this disease.

In its acute form it also presents, generally, elevation of antibodies against phase I antigens.

Mortality in acute forms is almost nonexistent.

Importance of clinical history in the diagnosis of psittacosis: A case report.

Psittacosis, caused by the bacteria Chlamydia psittaci, is primarily a disease of birds that can be transmitted to humans. The clinical manifestations of the disease are wide, ranging from asymptomatic illness to fulminant psittacosis with multi-organ failure. The organism gets attached to the upper respiratory mucosa after inhalation and the majority remain asymptomatic. However, some people may develop symptoms of atypical pneumonia. Psittacosis usually presents with sudden onset fever with chills and rigor, headache, and myalgia. Here we present a case of a 35 years old female with a history of close contact with parrots who presented to the ER with complaints of high-grade fever and headache for 2 weeks which started 2 days after her parrots died. The disease usually manifests as flu-like symptoms or pneumonia and is included in the differential diagnosis of community-acquired pneumonia. Investigations reveal neutrophilia, raised erythrocyte sedimentation rate, C-reactive protein, and elevated liver enzymes which were consistent with the findings of our patient. Chest X-ray showed ill-defined consolidation in the right middle and lower lobes which were inconclusive. Hence, a CT chest was done which revealed patchy ground glass opacities with surrounding consolidation giving a reverse halo sign. Due to her contact with birds and CT findings which were suggestive of psittacosis, she was started on doxycycline and her condition improved thereafter. We highlight the importance of proper history taking and awareness on zoonotic diseases to the general public to prevent, diagnose and treat the disease effectively.

[Familial outbreak of psittacosis].

Three familial cases of psittacosis are reported. The first case was a 46-year-old woman, the second case, her 18-year-old daughter. Both of them often visited the house of the third case, a 49-year-old women, who was the elder sister of case 1 and who took care of the chick of a budgerigar which she kept in the house. Case 1 came to our hospital with abrupt onset of fever, headache, nausea and general malaise. Because she was suspected to have meningitis, she was admitted to the Department of Neurology. On admission, her chest X-ray film showed bilateral ground glass shadows. She also had hypoxemia and liver dysfunction. On learning of her history of contact with the chick, psittacosis was suspected. Case 2 suffered from fever and headache. Her chest X-ray film revealed opaque infiltration in the right lower lung field. Case 3 complained of fever, headache and vomiting. Her chest X-ray film showed fan-shaped faint shadows in the left upper, middle and lower lung fields. We interpreted these findings as showing psittacosis based on anamnesis. The result of the complement fixation (CF) antibody titer against chlamydia was 1:32 in cases 2 and 3, enabling a serological diagnosis of psittacosis. The corresponding result was 1:16 in case 1. Although the CF antibody titer showed no increase, we diagnosed the case clinically as psittacosis. It is difficult to correctly diagnose psittacosis only from the physical findings and chest X-ray films. Detailed anamnesis, in particular taking a history of exposure to birds, is an important clue for diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Q fever--still a query and underestimated infectious disease.

Coxiella burnetii (C.b.) is a strictly intracellular, Gram-negative bacterium. It causes Q fever in humans and animals worldwide. The animal Q fever is sometimes designated "coxiellosis". This infection has many different reservoirs including arthropods, birds and mammals. Domestic animals and pets, are the most frequent source of human infections. Q fever may appear basically in two forms, acute and chronic (persistent). The latter form of Q fever in animals is characteristic by shedding C.b. into the environment during parturition or abortion. Human Q fever results usually from inhalation of contaminated aerosols originating mostly from tissue and body fluids of infected animals. Q fever may appear in humans either in an acute form accompanied mainly by fever (pneumonia, flu-like disease, hepatitis) or in a chronic form (mainly endocarditis). Diagnosis of Q fever is based on isolation of the agent in cell culture, its direct detection, namely by PCR, and serology. Detection of high phase II antibodies titers 1-3 weeks after the onset of symptoms and identification of IgM antibodies are indicative to acute infection. High phase I IgG antibody titers >800 as revealed by microimmunofluorescence offer evidence of chronic C.b. infection. For acute Q fever, a two-weeks-treatment with doxycycline is recommended as the first-line therapy. In the case of Q fever endocarditis a long-term combined antibiotic therapy is necessary to prevent relapses. Application of Q fever vaccines containing or prepared from phase I C.b. corpuscles should be considered at least for professionally exposed groups of the population. Infections caused by C.b. are spread worldwide and may pose serious and often underestimated health problems in human but also in veterinary medicine. Though during the last decades substantial progress in investigation of C.b. has been achieved and many data concerning this pathogen has been accumulated, some questions, namely those related to the pathogenesis of the disease, remain open.

[Two cases of acute hepatitis associated with Q fever].

Q fever which is caused by Coxiella burnetii, is a worldwide zoonosis. Many species of wild and domestic mammals, birds, and arthropods, are reservoirs of C.burnetii in nature, however farm animals are the most frequent sources of human infection. The most frequent way of transmission is by inhalation of contaminated aerosols. The clinical presentation of Q fever is polymorphic and nonspecific. Q fever may present as acute or chronic disease. In acute cases, the most common clinical syndromes are selflimited febrile illness, granulomatous hepatitis, and pneumonia, but it can also be asymptomatic. Fever with hepatitis associated with Q fever has rarely been described in the literature. Herein we report two cases of C.burnetii hepatitis presented with jaundice. In May 2011, two male cases, who inhabited in Malkara village of Tekirdag province (located at Trace region of Turkey), were admitted to the hospital with the complaints of persistent high grade fever, chills and sweats, icterus, disseminated myalgia and headache. Physical examination revealed fever, icterus and the patient appeared to be mildly ill but had no localizing signs of infection. Radiological findings of the patients were in normal limits. Laboratory findings revealed leukocytosis, increased hepatic and cholestatic enzyme levels, and moderate hyperbilirubinemia- mainly direct bilirubin, whereas serum C-reactive protein and erythrocyte sedimentation rate were found normal. Blood and urine cultures of the patients yielded no bacterial growth. Serological markers for acute viral hepatitis, citomegalovirus and Epstein-Barr virus infections, brucellosis, salmonellosis, toxoplasmosis and leptospirosis were found negative. Acute Q fever diagnosis of the cases were based on the positive results obtained by C.burnetii Phase II IgM and IgG ELISA (Vircell SL, Spain) test, and the serological diagnosis were confirmed by Phase I and II immunofluorescence (Vircell SL, Spain) method. Both cases were treated with doxycycline for 14 days and became afebrile within four days. These cases were presented to emphasize that C.burnetii infection should be considered in the differential diagnosis of patients with fever and elevated serum transaminase levels, irrespective of the presence of abdominal pain and exposure to potentially infected animals.

Q Fever (Coxiella Burnetii).

Q fever is a zoonotic infectious disease caused by the <iCoxiella burnetii</i bacterium. It is an obligate intracellular pathogen with a high infection capacity that proliferates exclusively in an acidified medium, forming a lysosome-like vacuole. It presents a peculiar phenomenon called "antigenic phase variation," produced by a modification in the complexity of the membrane lipopolysaccharides. Q fever can be found worldwide and presents variable clinical features and geographical distribution. It mostly affects people in rural areas who are in contact with animals. The most common type of transmission to humans is via the inhalation of aerosols containing the pathogen, especially those formed from placental derivatives. Wild animals, domestic animals, and ticks are the principal reservoirs.Diagnosis is mainly made by indirect methods such as serology or by direct methods such as microbiological cultures or tests that detect the specific DNA. Typically, there are two clinical presentations: the acute disease, which is more frequent and often asymptomatic, and a persistent focalized infection in 4 to 5% of patients, generally with a poor evolution. Treatment of the acute form in both children and adults consists of administering doxycycline, while persistent focalized infection should be treated with at least two antibiotics, such as doxycycline and hydroxychloroquine. Several measures should be undertaken to minimize exposure among people working with animals or handling birth products. Different vaccines have been developed to prevent infection, though few data are available.

An outbreak of cat-associated Q fever in the United States.

Q fever is usually acquired by contact with aerosols generated during parturition of domestic ungulates (e.g., sheep, cows, goats). In the maritime provinces of Canada, parturient cats have also been implicated in its transmission. A 66-year-old woman from eastern Maine developed high fever, rigors, headache, myalgias, pulmonary infiltrates, and elevated hepatocellular enzymes, and the diagnosis of acute Q fever was confirmed serologically. She and 14 other family members had attended a family reunion in Maine 2 weeks earlier, when they were exposed to a parturient cat. All 11 adults and older children attending the reunion developed symptoms consistent with acute Q fever. Serum samples were obtained from 10 who attended the reunion and 8 who did not attend. Titers greater than or equal to 1:64 to Coxiella burnetii were present in all who attended the reunion but in none of those who did not. Cat-associated Q fever should be considered when sporadic cases of the disease occur in the United States.

Q Fever: an old but still a poorly understood disease.

Q fever is a bacterial infection affecting mainly the lungs, liver, and heart. It is found around the world and is caused by the bacteria Coxiella burnetii. The bacteria affects sheep, goats, cattle, dogs, cats, birds, rodents, and ticks. Infected animals shed this bacteria in birth products, feces, milk, and urine. Humans usually get Q fever by breathing in contaminated droplets released by infected animals and drinking raw milk. People at highest risk for this infection are farmers, laboratory workers, sheep and dairy workers, and veterinarians. Chronic Q fever develops in people who have been infected for more than 6 months. It usually takes about 20 days after exposure to the bacteria for symptoms to occur. Most cases are mild, yet some severe cases have been reported. Symptoms of acute Q fever may include: chest pain with breathing, cough, fever, headache, jaundice, muscle pains, and shortness of breath. Symptoms of chronic Q fever may include chills, fatigue, night sweats, prolonged fever, and shortness of breath. Q fever is diagnosed with a blood antibody test. The main treatment for the disease is with antibiotics. For acute Q fever, doxycycline is recommended. For chronic Q fever, a combination of doxycycline and hydroxychloroquine is often used long term. Complications are cirrhosis, hepatitis, encephalitis, endocarditis, pericarditis, myocarditis, interstitial pulmonary fibrosis, meningitis, and pneumonia. People at risk should always: carefully dispose of animal products that may be infected, disinfect any contaminated areas, and thoroughly wash their hands. Pasteurizing milk can also help prevent Q fever.

Acute chest syndrome

Diagnosis The diagnosis of acute chest syndrome is made difficult by its similarity in presentation with pneumonia. Both may present with a new opacification of the lung on chest x-ray. The presence of fevers, low oxygen levels in the blood, increased respiratory rate, chest pain, and cough are also common in acute chest syndrome. Diagnostic workup includes chest x-ray, complete cell count, reticulocyte count, ECG, and blood and sputum cultures. Patients may also require additional blood tests or imaging (e.g. a CT scan) to exclude a heart attack or other pulmonary pathology. Prevention Hydroxyurea is a medication that can help to prevent acute chest syndrome. It may cause a low white blood cell count, which can predispose the person to some types of infection. Treatment Broad spectrum antibiotics to cover common infections such as Streptococcus pneumoniae and mycoplasma, pain control, and blood transfusion. Acute chest syndrome is an indication for exchange transfusion.

[Successful treatment of a patient with fulminant psittacosis].

A previously healthy 40-year-old woman was admitted with severe dyspnea, cough and slight fever. Chest X-ray film revealed bilateral widespread opaque infiltration with ground glass shadows around it. The laboratory examination showed moderate hepatic and muscular injury with disseminated intravascular coagulation. In addition her arterial blood gas showed severe hypoxemia (PaO2: 25 Torr under room air). Moreover, about 1 week prior to admission, 2 baby budgerigars she had been raising for half a year died. Because of this history and multi-organ injuries, this disease was considered to be acute pneumonia owing to fulminant psittacosis causing acute respiratory failure. On the first day of admission, she was intubated and ventilated mechanically with an oxygen concentration (FIO2) of 100%. Subsequently, treatment with intravenous minocycline (400 mg/day), heparin for D.I.C. and corticosteroid were started. Abnormal findings in both chest X-ray and several laboratory parameters improved gradually though fever continued for a week. On the 14th day of her hospital stay, she was weaned from the ventilator successfully and the administration of corticosteroid and heparin tapered. On the 41st day, she was discharged without any symptoms. Results of complement fixation (CF) antibodies against chlamydia on paired sera showed a significant rise from 1:32 to 1:256. Moreover, both IgG and IgM antibodies for Chlamydia psittaci with microplate immunofluorescent antibody technique (MFA) showed an 8 times' rise during 10 days after admission. The definitive diagnosis was made with positive isolation of C. psittaci from both the throat swab of this patient and the spleen and liver of the dead budgerigar by the cell culture method. Psittacosis should always be borne in mind as a possible cause of fulminant pneumonia with acute respiratory failure, and such a situation can be handled successfully if emergency care including mechanical ventilation is available.

[Subacute extrinsic allergic alveolitis with lesion edema].

Extrinsic allergic alveolitis may have a chronic, subacute or acute course. Its fulminant form with interstitial edema is unusual. An 11-year-old girl was referred to our intensive care unit because she suffered from high fever. Chest X-rays showed bilateral alveolitis. History revealed home exposure to several birds for many years, and episodes of dyspnea and fever for a few months. Diagnosis of extrinsic allergic alveolitis was confirmed by strongly positive results of precipitins to avian antigens. In addition, a paramyxovirus influenzae was recovered from broncho-alveolar lavage. Treatment, including high dose steroids, hydroxychloroquine, and suppression of antigenic exposure allowed weaning from mechanical ventilation after 50 days. Severe pulmonary restriction was disclosed by lung function testing following weaning and slow improvement occurred 5 months later, despite persistent interstitial lesions on chest X-rays. Extrinsic allergic alveolitis may mimic an acute respiratory distress syndrome. Documenting bird exposure in such a case helps to achieve appropriate diagnosis which requires early administration of steroids in order to improve vital and functional prognosis.

[A family outbreak of Chlamydia psittaci infection].

A family outbreak (3 cases) of Chlamydia psittaci infection was reported. The first case, a 56-year-old man was admitted with fever and general fatigue. Chest X-ray film revealed a consolidation in the right lower lung. One month before admission he had purchased 2 parakeets (chick) and one parakeet died. On learning of his history of contact with the chick, psittacosis was suspected. After administration of fixation (CF) antibody titer against chlamydia rose to 1:128 and IgA titer against Chlamydia psittaci by microimmunofluorescence antibody technique (MAF) rose to 1:128 in 21 days after admission. The second case, the wife of the first, a 53-year-old woman had a fever and a cough about two weeks before the admission of the first case. At the time of her husband was admitted, she attended the outpatient department. The chest CT X-ray film showed a ground glass appearance in both lower lung fields. The third case, the daughter of the first, didn't have any signs. Chest X-ray film was normal. But IgM titer against Chlamydia psittaci by MAF rose to 1:16 and IgA titer against Chlamydia psittaci by MAF rose to 1:128. This case was considered as inapparent infection.

Imported brucellosis and Q-fever coinfection in Croatia: a case report.

The brucellosis and Q-fever coinfection is very rarely reported. To our knowledge, this is the first case report of concomitant brucellosis and Q-fever, most likely imported in Croatia. A 30-year-old male agricultural worker was hospitalized on 22 April 2017 after a ten days fever up to 40°C with chills, shivering, excessive sweating, general weakness, loss of appetite and headache. A month and a half prior to the hospitalization he lost 18 kg of body weight. Three weeks before hospitalization the patient returned from Kupres (Bosnia and Herzegovina) where he was working for the past year on a sheep farm and consumed unpasteurized dairy products of sheep origin. At admission, his condition was moderately severe due to pronounced dehydration. Routine laboratory tests showed slightly elevated erythrocyte sedimentation rate, anemia, thrombocytopenia and elevated liver transaminases. The chest X-ray showed an inhomogeneous infiltrate of the lower right lung. Three sets of blood culture were cultivated. After 48 hours incubation, bacterial growth was detected in aerobic bottles. Gram-stained smear revealed small, gram-negative coccobacilli. Specimens were subcultured on blood and chocolate agar plates. Using a Vitek GN identification card, the isolated organism was identified as Brucella melitensis. 16S rRNA gene sequencing of the isolate confirmed it as a Brucella sp. Rose-Bengal test was positive, while Wright agglutination test showed a significant increase in antibody titer from 80 to 640 in paired sera. Using indirect immunofluorescence assay (IFA), Coxiella burnetii phase II IgM/IgG titers were 50 and 1024, respectively indicating acute Q-fever. The patient was treated with doxycycline and rifampicin. So far, there has been no relapse or signs of chronic infection.

Farmer's lung

Signs and symptoms Acute Stage: After four to eight hours symptoms such as headache, irritating cough, and shortness of breath upon physical exertion, appear. Subacute Stage: Symptoms persist without further exposure, and increase in severity. Symptoms include: shortness of breath upon exertion, chronic coughing, physical weakness, occasional fever and sweating, decrease in appetite, aches and pains. Chronic Stage: Debilitating effects are now considered long-term. Symptoms include: severe shortness of breath, chronic coughing, physical weakness, occasional fever and sweating at night, decrease in appetite, and general aches and pains. These symptoms develop between four and eight hours after exposure to the antigens. In acute attacks, the symptoms mimic pneumonia or flu. In chronic attacks, there is a possibility of the victim going into shock and dying from the attack.

Q Fever -- Differential Diagnosis

Patients with acute viral infections, such as Epstein-Barr virus, cytomegalovirus, influenza, hepatitis A, B, or C virus, have similar presenting complaints, such as febrile illness, hepatitis, and myalgia. Serological tests and PCR assays are used to identify these infections. Atypical pneumonia caused by Legionella and Mycoplasma needs to be considered. They can be ruled out by detecting urine antigen or serum antibody titers. Tick-borne illnesses such as Lyme disease, relapsing fever, and Rocky Mountain spotted fever manifest with fever and headache with or without a rash. Anaplasmosis and ehrlichiosis present with fever, headache, and hepatitis, with a lesser incidence of rash. Tick-borne diseases are detected via PCR and/or serology. Zoonotic diseases such as brucellosis and leptospirosis can manifest as an acute flu-like illness with a history of exposure to animals or animal products.

[Diffuse panbronchiolitis with myeloperoxidase-specific antineutrophil cytoplasmic antibody-related vasculitis].

A 46-year-old woman was referred to our department in July 1996 with complaints of fever and myalgia in her calves. She had a 20-year history of purulent sputum; diffuse panbronchiolitis had been diagnosed in 1983. Physical examination revealed low-pithed rhonchi over the lung fieldis and hypesthesia of the right leg. She had a white blood cell count of 16,100/mm3, including 4% eosinophils, and a platelet count of 80.0 x 10(4)/mm3. The serum IgE level was 2,200 U/ml, and the cold hemagglutinin titer was high. Pulmonary-function tests showed mixed ventilatory dysfunction, and arterial blood gas analysis revealed a PaO2 of 55.8 Torr on room air. Pseudomonas aeruginosa was cultured from her sputum. A chest X-ray film and CT scan showed diffuse nodular shadows and bronchiectatic changes with mild hyperinflation. An infiltrative lesion in right S6 area could also be seen. Administration of broad-spectrum antibiotics did not alleviate her symptoms. The level of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) in serum was 245 EU/ml, and 67Ga scintigraphy showed marked accumulation in the abdomen. Abdominal angiography demonstrated a bead-like appearance and irregularities in the peripheral branches of the hapatic artery, the splenic artery, the cystic artery, and the superior mesenteric artery. Because of the high MPO-ANCA level and the angiographic abnormalities, MPO-ANCA-related vasculitis was diagnosed. She was treated with 1 g of methylprednisolone daily for 3 days, followed by 60 mg of prednisolone and 50 mg of cyclophosphamide daily. Her condition improved dramatically, and the MPO-ANCA level became almost normal. During treatment, her blood pressure rose markedly with a normal serum creatinine level and normal urinalysis. Plasma renin activity was 13.3 ng/ml/hr. Renal angiography showed stenoses and irregularities in the peripheral branches of renal arteries bilaterally. These findings led to a diagnosis of renovascular hypertension due to vasculitis. Her blood pressure was controlled with an angiotensin-converting enzyme inhibitor and a calcium antagonist. Vasculitis associated with chronic supportive lung disease has occasionally been reported, which suggests a casual relation between chronic respiratory infection and ANCA-related vasculitis. Systemic vasculitis should be taken into account as a potential complication of chronic suppurative lung disease.

[A case of psittacosis with wandering infiltrates developing to acute respiratory distress syndrome].

A 52-year-old woman visited a local hospital with a high fever, non-productive cough and general fatigue. Her chest X-ray showed infiltrate in the right middle lung field. Computed tomography scans revealed ground-glass opacity and surrounding ring-shaped air-space consolidation, the "reversed halo sign". Cefpirom was administered, but her symptoms persisted and the infiltrate migrated to the left upper lobe. As cryptogenic organizing pneumonia was suspected, she was then treated with intravenously pulsed methylprednisolone followed by prednisolone. Despite these therapies, acute respiratory failure occurred and she was therefore transferred to our hospital. On admission, severe hypoxemia and diffuse bilateral infiltrates on chest images suggested acute respiratory distress syndrome. As we obtained information that a parakeet had recently died at her home, minocycline was administered, resulting in prompt improvement of the symptoms, respiratory insufficiency and pulmonary infiltrates. Finally, elevated antibody titers against Chlamydophila psittasi confirmed a diagnosis of Psittacosis. Sequential chest computed tomography scans in this case indicate that absorption of marginal air-space consolidation with extended central ground glass attenuation in concordance with a new infiltrate on another lung field appeared to create wandering infiltrate. Wandering infiltrate on chest X-ray in psittacosis may be a sign of disease progression.

Blastomycosis

a flu-like illness with fever, chills, arthralgia (joint pain), myalgia (muscle pain), headache, and a nonproductive cough which resolves within days. an acute illness resembling bacterial pneumonia, with symptoms of high fever, chills, a productive cough, and pleuritic chest pain. a chronic illness that mimics tuberculosis or lung cancer, with symptoms of low-grade fever, a productive cough, night sweats, and weight loss. a fast, progressive, and severe disease that manifests as ARDS, with fever, shortness of breath, tachypnea, hypoxemia, and diffuse pulmonary infiltrates. skin lesions, usually asymptomatic, can be verrucous (wart-like) or ulcerated with small pustules at the margins. bone lytic lesions can cause bone or joint pain. prostatitis may be asymptomatic or may cause pain on urinating. laryngeal involvement causes hoarseness. 40% immunocompromised individuals have CNS involvement and present as brain abscess, epidural abscess or meningitis.

Hantavirus pulmonary syndrome

Signs and symptoms Initially, HPS has an incubation phase of 2–4 weeks, in which patients remain asymptomatic. Subsequently, patients can experience 3–5 days of flu-like prodromal phase symptoms, including fever, cough, muscle pain, headache, lethargy, shortness of breath, nausea, vomiting and diarrhea. In the following 5–7 day cardiopulmonary phase, the patient's condition rapidly deteriorates into acute respiratory failure, characterized by the sudden onset of shortness of breath with rapidly evolving pulmonary edema, as well as cardiac failure, with hypotension, tachycardia and shock. In this phase, patients may develop acute respiratory distress syndrome. It is often fatal despite mechanical ventilation and intervention with diuretics. After the cardiopulmonary phase, patients can enter a diuretic phase of 2–3 days characterized by symptom improvement and diuresis. Subsequent convalescence can last months to years. As of 2017, patient mortality in the USA from HPS is 36%.

Q fever: current concepts.

Persons with Q fever usually present with severe retrobulbar headache, a fever to 104 degrees F or higher with shaking chills, general malaise, myalgia, chest pain, and sometimes pneumonia and hepatitis. Cattle, sheep, goats, and ticks are the primary reservoirs of the etiologic agent, Coxiella burnetii. Humans are usually infected by inhaling infectious aerosols. Because C. burnetii can survive for long periods in the environment, it poses a continuing health hazard once it is disseminated. Q fever usually occurs sporadically, but large outbreaks are frequently observed throughout the world, particularly among abattoir workers and personnel working in research centers. Q fever endocarditis follows a chronic course and is frequently fatal. Tests for antibodies to C. burnetii are required for confirmation of the diagnosis. Tetracyclines remain the mainstay of treatment for acute Q fever, and tetracyclines in combination with other antibiotics have been advocated for patients with Q fever endocarditis. Vaccines for Q fever have been proven effective in clinical trials.

SARS-CoV-2 Infection and COVID-19 in 5 Patients in Ecuador After Prior Treatment with Hydroxychloroquine for Systemic Lupus Erythematosus.

BACKGROUND This case series describes 5 patients with SARS-CoV-2 infection and COVID-19 in Ecuador who had been treated with hydroxychloroquine for systemic lupus erythematosus (SLE) prior to their COVID-19 illness. CASE REPORT Case #1 reports a 29-year-old woman who had been treated with 200 mg of hydroxychloroquine per day for 1 year and presented with flu-like symptoms, chest pain, fever, odynophagia, asthenia, dry cough, and chills. Case #2 was a 34-year-old woman whose treatment for SLE included 200 mg of hydroxychloroquine per day since 2017. She arrived at the clinic with a dry cough, asthenia, and myalgias. Case #3 was a 24-year-old woman who had been using 200 mg of hydroxychloroquine per day since 2010. She presented with asthenia, myalgias, headaches, hypogeusia, and anosmia. Case #4 was a 39-year-old woman taking 200 mg of hydroxychloroquine every day for SLE who presented with dyspnea, chest pain, odynophagia, hypogeusia, anosmia, diarrhea, and fever. Case #5 was a 46-year-old woman who had been taking 200 mg of hydroxychloroquine since 2019. She came to our hospital complaining of chest pain, fever, and dyspnea. In all 5 patients, SARS-CoV-2 infection was confirmed with a nasopharyngeal SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test using the Cepheid/GeneXpert system. CONCLUSIONS All 5 of our patients with SLE who were taking hydroxychloroquine presented with SARS-CoV-2 infection and symptoms of COVID-19. This case series provides support for a lack of prevention of COVID-19 by hydroxychloroquine.

Diagnosis and treatment of Q fever: attempts to clarify current problems in Japan.

"Q fever" is a generic term for infection caused, mostly in the form of pneumonia or bronchitis, by Coxiella burnetii (Q-fever Coxiella), a pathogen closely related to Rickettsia and Legionella. Q fever is an influenza-like, transient febrile infectious disease that is common to humans and animals; it develops after the transmission of the infectious agent from livestock or pet animals, but person-to-person transmission is rare. In Europe and the United States, it is ranked fourth or fifth as an underlying cause of community-acquired pneumonia. Many patients with Q fever have a good prognosis, and their mortality is about 1%-2% when left untreated. However, because some patients may take a long time to be cured or may have a chronic condition with poor prognosis, patients with definitely diagnosed Q fever or those strongly suspected of having Q fever are strongly recommended to receive treatment. The definite diagnosis of Q fever is made based on a significant increase in serum antibody titers, the determination of which often requires considerable time, and therefore patients must be monitored for a certain period. Q-fever Coxiella, an obligate intracellular parasite, is basically not susceptible to beta-lactam antibiotics, which barely permeate into the cells, but the parasite is susceptible to tetracyclines, macrolides, and quinolones, with these agents being sufficiently permeable into the cells. However, there are many cases of spontaneous cure, and it is likely that beta-lactam treatment may have been involved in these cases. Vaccination against Q fever is not common in Japan.

A 15-year-old with chest pain: An unexpected etiology.

A 15-year-old female with no significant past medical history presented to the emergency department with 1 day of substernal and pleuritic chest pain, chills, cough, and hematuria. She also had swelling of the face and ankles that resolved by presentation. She was found to have elevated troponin and brain natriuretic peptide during initial workup. Electrocardiogram was normal, but there were significant pleural effusions on chest x-ray. She was strep positive and had blood pressure up to 150/90, prompting admission for cardiac monitoring and cardiology consultation. Blood pressure decreased down to 125/72 without intervention. She was afebrile with unlabored breathing and normal saturations. She was clear to auscultation bilaterally, with no abdominal distension or hepatosplenomegaly, and edema was not evident on exam. There was mild erythema to the bilateral tonsillar pillars. Initial considerations included viral myocarditis, pericarditis, and atypical nephritic syndrome. Workup revealed elevated antistreptolysin antibodies, low C3 complement, negative antineutrophil cytoplasmic antibodies, and negative flu testing. Renal sonography was unremarkable. Cardiology recommended echocardiography, which confirmed pleural effusions but revealed no cardiac abnormalities. Urinalysis revealed hematuria and mild proteinuria. Diagnosis was found to be post-streptococcal glomerulonephritis complicated by fluid overload and left ventricular strain secondary to hypertensive emergency. Post-streptococcal glomerulonephritis is the most common cause of acute glomerulonephritis in children. The mechanism of disease is a proliferation and inflammation of the renal glomeruli secondary to immunologic injury, with deposition of immune complexes, neutrophils, macrophages, and C3 after complement activation. This leads to hematuria, proteinuria, and fluid overload. Edema is present in 65%-90% of patients, progressing to pulmonary involvement in severe cases. Cardiac dysfunction secondary to fluid overload is a potentially fatal outcome in the acute setting. Physicians should consider post-streptococcal glomerulonephritis for patients presenting with hypertension, cardiac/pulmonary pathology, or symptoms of acute heart failure in the context of strep infection.

Coxiella burnetii (Q fever) pneumonia.

Pneumonia is one manifestation of acute Q fever following infection with Coxiella burnetii. Fever, headache, and myalgia dominate the clinical picture of Q fever pneumonia. Cough is nonproductive and may be absent despite the presence of pneumonia. While in most instances pneumonia results in an illness of mild-to-moderate severity, on occasion it is rapidly progressive and results in respiratory failure. Infection occurs as a result of inhalation of contaminated aerosols. Infected cattle, sheep, and goats are the usual reservoirs for this zoonosis. In some areas, infected parturient cats serve as the reservoir, and in such instances, rounded opacities are seen on the chest radiograph. The diagnosis of C. burnetii pneumonia is usually confirmed by demonstration of a fourfold or greater rise in antibody titer. Treatment is usually with a tetracycline or rifampin for 7 to 10 days.

A 47-Year Old Woman With Rapidly Progressive Hypoxemic Respiratory Failure.

A 47-year-old Hispanic woman presented to a pulmonology clinic with 2 weeks of cough productive of white sputum and worsening dyspnea on exertion, requiring increasing supplemental oxygen. In addition, she reported fatigue, night sweats, diffuse myalgias, and extremity weakness. She denied hemoptysis, fevers, chills, weight loss, or rash. Her medical history is significant for undifferentiated rapidly progressive hypoxemic respiratory failure 2 years before her current presentation. At that time, she presented to the ED with 3 weeks of progressive shortness of breath and cough. Chest CT imaging showed bilateral infiltrates concerning for infection, and she was treated empirically for community-acquired pneumonia. She developed worsening hypoxemic respiratory failure despite broadening of her antibiotics and subsequently required intubation. Her course was further complicated by pulseless electrical activity arrest with return of spontaneous circulation and development of shock requiring multiple vasopressors. Because of difficulty with oxygenation, she was referred to our center for extracorporeal membrane oxygenation evaluation and was ultimately started on venous-arterial extracorporeal membrane oxygenation. Bronchoscopy with BAL was negative for bacterial, viral, and fungal origins, and initial autoimmune evaluation (antinuclear antibody and rheumatoid factor) was negative, except an elevated creatine kinase (CK) to 3,000. Her course was complicated by heparin-induced thrombocytopenia, and as a result she suffered limb ischemia requiring amputation of her left lower extremity. Elevated CK at that time was attributed to compartment syndrome before amputation. The patient recovered clinically with supportive care and was ultimately discharged on 2 L supplemental oxygen, with a diagnosis of acute respiratory failure of unclear origin. The patient had stability in her clinical symptoms until this current presentation.

[Investigation of Coxiella burnetii and Brucella seropositivities in patients presenting with acute fever].

Tokat province and Kelkit Valley located in the Black Sea region of Turkey are endemic areas for brucellosis and Crimean-Congo hemorrhagic fever. Since the risk factors are similar, the probability of Coxiella burnetii seroposititivity is assumed to be also high in this area. The aim of this study was to investigate Q fever and brucellosis seropositivity in patients with acute fever. A total of 53 patients (37 male, 16 female; age range: 18-65 years, mean age: 47.13 ± 16.40 years) who were admitted to the emergency room and infection diseases outpatient clinics of Gaziosmanpasa University hospital with acute fever between June 2011-June 2012 were included in the study. Symptoms, physical examination findings and laboratory test results of the patients were recorded. In addition, their place of residence, relationship with rural area, and history of contacts with animals were questioned. The presence of C.burnetii phase II lgM and lgG antibodies were investigated by indirect immunofluorescent antibody assay, and Brucella spp. antibodies by Rose Bengal and standard tube agglutination methods in the serum samples of patients. C.burnetii seropositivity was determined in 19 (36%) of the patients, and 2 (4%) of them were diagnosed as acute Q fever with the positivity of both lgG and lgM antibodies. Among the seropositive and seronegative patients, there was no statistically significant differences in terms of age, gender, animal contact, occupation, place of residence and relationship with rural-life (p> 0.05). Acute fever was attributed to pneumonia in 10 patients and of them five were found positive for phase II lgG antibodies. There was no significant difference between C.burnetii seropositive and seronegative patients in terms of the presence of pneumonia (p= 0.30). In two patients diagnosed as acute Q fever no signs of pneumoniae were detected in the chest X-rays; one of these cases was resided in the city and the other in the rural area while both had contact with animals. The most frequently detected symptoms in patients with acute Q fever were malaise, fatigue, chills, cough, sputum, dyspnea, nausea, abdominal pain and diarrhea. Brucella seropositivity was detected in 6 (11%) patients and four of them were diagnosed as acute brucellosis. Four of the Brucella seropositive patients were also found positive for C.burnetii. Sixteen (84%) of C.burnetii seropositive patients were male and 3 (16%) were female. Eleven of them were living in the village and eight in the city, however six out of eight urban patients had a history of relation with rural-life, resulting a total of 17 (89%) rural-contacts. In addition, 79% (15/19) of seropositive cases had the history of animal contact most commonly with cattle and sheep (11/15; 73%). When the laboratory findings were compared, serum ferritin levels were found to be significantly higher in patients with acute Q fever then those seronegative patients (874 ng/ml mean value vs. 150 ng/mL mean value; p= 0.04), however there was no significant difference between the other laboratory parameters (p> 0.05). Our data indicated that Q fever seropositivity was quite high in Tokat region and the reason may be attributed to entwined life between rural and urban areas. In conclusion in the patients presenting with acute fever, brucellosis and Q fever should be considered in differential diagnosis, since both infections are endemic in that area of Turkey.

Histoplasmosis -- History and Physical -- Acute Pulmonary Histoplasmosis

Primary infections are frequently asymptomatic, or the patients tend to ignore mild flu-like symptoms. The major determinant of symptoms is the inoculum size. The typical incubation period is seven to 21 days. High fever, headache, nonproductive cough, and chest pain are the main symptoms. This chest pain is not pleuritic and is in the anterior chest and is believed to be due to enlargement of mediastinal or hilar lymph nodes. Most of the symptoms resolve in 10 days. Rheumatologic manifestations can occur such as arthralgias, erythema nodosum or erythema multiforme in a small number of patients (6%, mostly women). This syndrome appears to be less frequent in histoplasmosis when compared to coccidioidomycosis. Imaging shows patchy diffuse pneumonitis and hilar lymphadenopathy. There is no granulomatous inflammation as cellular immunity matures by two weeks in primary infection. During the acute pulmonary infections, a skin test may be positive in more than 90% of cases, antibody to H. capsulatum may be present in 25% to 85% of cases, the urinary antigen may be positive in 20% of cases, and sputum culture from lungs may be positive in less than 25% of cases.

Nitrofurantoin

Pulmonary toxicity The pulmonary toxicity caused by nitrofurantoin can be categorized into acute, subacute, and chronic pulmonary reactions. The acute and subacute reactions are thought to be due to a hypersensitivity reaction and often resolve when the drug is discontinued. Acute reactions have been estimated to occur in about one in 5000 women who take the drug. These reactions usually develop 3–8 days after the first dose of nitrofurantoin, but may occur from a few hours to a few weeks after starting the drug. Symptoms include fever, dyspnea, chills, cough, pleuritic chest pain, headache, back pain, and epigastric pain. Chest radiograph will often show unilateral or bilateral infiltrates similar to pulmonary edema. Treatment includes discontinuation of the nitrofurantoin, which should result in symptom improvement within 24 hours.

Neurology_Adams

Q fever, unlike the other rickettsioses, is not associated with an exanthem. In the few cases with which we are familiar, the main symptoms were those of a low-grade meningitis. Rare instances of encephalitis, cerebellitis, and myelitis are also reported, possibly as postinfectious complications. There is usually a tracheobronchitis or atypical pneumonia (one in which no organism can be cultured from the sputum) and a severe prodromal headache. In these respects, the pulmonary and neurologic illnesses resemble that of the other main cause of “atypical pneumonia,” M. pneumoniae. The Q fever agent (Coxiella) should be suspected if there are concomitant respiratory and meningoencephalitic illnesses and there has been exposure to parturient animals, to livestock (including abattoir workers, who are also exposed to Brucella and anthrax), or to wild deer or rabbits. The diagnosis can be made by the finding of a severalfold increase in specific immunofixation antibodies. Patients who survive

Q-uestioning the Diagnosis: An Educational Case Report.

Q fever is a zoonotic infection that may lead to acute or long-term renal injury. Given its rare incidence, Q fever is not often considered on the initial differential diagnosis for glomerular disease which can lead to delays in treatment. This case highlights the importance of avoiding early diagnostic closure and revisiting the differential diagnosis in the setting of an atypical clinical presentation or response to treatment. A 52-year-old female was referred for assessment of possible glomerulonephritis. She described a 3-month history of bilateral lower extremity rash, intermittent knee pain with swelling, and a 2-year history of subjective fevers. Urinalysis showed persistent microscopic hematuria, and her creatinine was elevated at 94 umol/L (baseline 59 umol/L). Her initial investigations included an elevated C-reactive protein (CRP) and rheumatoid factor with a weakly positive anti nuclear antibody (ANA). Kidney biopsy was consistent with an immune complex mesangial proliferative glomerulonephritis. Light microscopy showed diffuse global mesangial hypercellularity. Immunofluorescence was positive for trace mesangial IgG and kappa, 1+ IgM, lambda and C1q, and 2+ C3. Electron microscopy showed mesangial electron dense deposits. These findings were felt to be most in keeping with mesangial proliferative lupus nephritis; however, it was acknowledged that clinical and laboratory findings supporting this diagnosis were lacking. Following treatment with oral prednisone her symptoms resolved, and renal function improved. However, she was unable to taper off prednisone completely without her symptoms returning. Additional immunosuppressive therapies were trialed, but she remained steroid dependent with disease flares related to prednisone tapers. Her atypical response to treatment led to consideration of alternative diagnoses, and further investigation revealed positive Q fever serology (phase-I IgG 1:1892, phase II IgG 1:8192, phase-I and -II IgM < 1:16). She was diagnosed with long-term Q fever and was treated with doxycycline and hydroxychloroquine. She remained on treatment for 2 years. During this time, her symptoms resolved, hematuria disappeared, and her creatinine returned to baseline. Following cessation of therapy, her Q fever IgM titres rose, and she was restarted on doxycycline and hydroxychloroquine indefinitely. (1) Keeping a broad differential diagnosis in the setting of atypical clinical features or unexpected response to therapy is important for ensuring accurate diagnosis and appropriate treatment. (2) Clinical improvement in relation to immunosuppressive therapy does not preclude an infectious cause of glomerular disease.

[Acute bronchiolitis due to Mycoplasma pneumoniae and successfully treated with steroids].

A high fever, coughing, stridor, and dyspnea developed in a 52-year-old woman on October 19, 1995. She went to a local clinic and was treated with oral penicillin and intravenous cefpirome. The symptoms worsened, and she was admitted to our hospital on October 26. Coarse crackles and wheezing were heard in both lung fields. The white blood cell count was 9000/mm3 and arterial blood gas analysis revealed a PaO2 of 49.8 Torr on room air. A chest roentgenogram obtained on admission showed a few small bibasilar nodular infiltrates, and a chest CT scan showed thickened bronchial walls along with small nodules having a centrilobular distribution. Of the cells in bronchoalveolar lavage fluid, 88% were neutrophils, but tests for bacteria and mycobacteria were negative. The cold-agglutinin titer was 1:512. The Mycoplasma pneumoniae antibody titer (IIIA) was 1:640 and viral serology tests were negative. Acute bronchiolitis due to M. pneumoniae was diagnosed and treatment with intravenous minocycline was started. The symptoms (coughing, fever, and stridor) resolved and the small nodules on chest CT scan disappeared, but hypoxemia remained. At the same time, an obstructive ventilatory defect (FEV1% 62.8%) and abnormal ventilation/perfusion lung scans were noted. Development into bronchiolitis obliterans was suspected, so administration of methyl prednisolone (1 g/day for 3 days) and prednisolone was started. The response to steroids was good. Pulmonary function improved and the arterial PaO2 at the time of discharge was 86 Torr (room air). Use of steroid therapy in the early phase of bronchiolitis obliterans seemed to be effective.

[Acute and chronic Q fever; epidemiology, symptoms, diagnosis and therapy of infection caused by Coxiella burnetii].

Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium. Domestic ungulates and parturient cats are the primary reservoirs of infection. The animals excrete the bacterium in urine, faeces, milk and amniotic fluid. After desiccation the micro-organism spreads via aerosols. After inhalation or ingestion and an incubation period of 2-6 weeks acute Q fever may develop with atypical pneumonia and hepatitis as major clinical symptoms. The infection also may present as a flu-like illness or remain asymptomatic. Generally, the prognosis is favourable. However, endocarditis or another chronic form of Q fever occasionally develops with possibly fatal outcome. Diagnosis relies upon serologic testing with an indirect immunofluorescence method. Doxycycline is the antibiotic of choice in the treatment of Q fever. Endocarditis needs therapy for years with the addition of rifampin or hydroxychloroquine. Q fever is poorly recognised due to the variety of clinical presentations.

[Q fever as a cause of acute hepatitis accompanying fever].

Q fever is a zoonotic infection caused by Coxiella burnetti, which has been previously regarded as an uncommon infectious disease in Korea but is sporadically reported recently. Common manifestations of acute Q fever usually present as influenza-like illness, pneumonia and occasionally hepatitis. Herein, we report 4 cases of acute Q fever as a cause of acute hepatitis and fever. All patients had fever and non-specific symptoms, and laboratory test showed acute hepatitis. Antibody surveys for many virus infections and bacterial cultures were negative. Finally, they were diagnosed acute Q fever by an indirect microimmunofluorescence test. Liver biopsy in 3 patients revealed granuloma including one with typical fibrin-ring. All patients had complete resolution of symptoms and signs with doxycycline treatment. Q fever should be considered in the differential diagnosis of patients with fever of unknown origin with acute hepatitis in Korea.


As of 2018, there are four dosing schedules for treatment of latent TB infection recommended by the CDC using isoniazid (INH), rifapentine (RPT) or rifampin (RIF). All treatments are effective. Health care providers should prescribe the shorter treatments, which are more convenient, whenever possible. The shortest combination would be Isoniazid + Rifapentine for three months or Rifampicin for four months. However, the fact that he is taking acenocoumarol means that the indication for this patient is Isoniazid for 9 months, since there is interaction between the rifamycin derivatives (rifapentine and rifampicin).

As of 2018, there are four dosing schedules for treatment of latent TB infection recommended by the CDC using isoniazid (INH), rifapentine (RPT) or rifampin (RIF). All treatments are effective. Health care providers should prescribe the shorter treatments, which are more convenient, whenever possible. The shortest combination would be Isoniazid + Rifapentine for three months or Rifampicin for four months. However, the fact that he is taking acenocoumarol means that the indication for this patient is Isoniazid for 9 months, [HIDDEN].

A 62-year-old patient who consults because of close contact in recent weeks with a person with active tuberculosis. Mantoux test is positive (12 mm). His history includes treatment with oral anticoagulants (acenocoumarol) for a deep vein thrombosis a few months ago. He does not report fever or cough and is asymptomatic. Chest X-ray is normal. Which of the following treatments is the most advisable?

Isoniazid and rifampicin, for three months.

Isoniazid and rifapentine, for three months.

Pulmonary vein thrombosis secondary to tuberculosis in a non-HIV infected patient.

Our patient is a 67-year-old male with a past medical history significant for hypertension and hyperlipidemia came to a hospital with hemoptysis. He was also having cough and shortness of breath for the last 1 month. He said that his hemoptysis was about 1 cup per day mixed with yellowish sputum. He noticed around 20 pounds of weight loss in the last 1 month. He also complained of night sweats but had no fever. He had no history of travel outside the USA. He has never been incarcerated before, but he endorsed that his son has been to Jail before and he visited him twice a year in patient's home. But he also said that his son has never been diagnosed with TB. He smoked 1.5 packs per day for the last 50 years and quit smoking 2 months ago. His medication include hydrochlorothiazide, lisinopril, gabapentin, aspirin and trazodone. On examination, vital signs were within the normal range except a hearty rate of 106 beats/minute. He had slightly pale conjunctiva, non-icteric sclera and had wet tongue and buccal mucosa. There was decreased air entry with crepitations in the right side of the posterior chest but no wheezes or rales. No peripheral lymphadenopathy, no peripheral edema or sign of fluid collection in the abdomen. Chest x ray showed multiple cavitary lesion in the right upper lobe area. CT scan of the chest with PE protocol showed pulmonary venous partial thrombosis in the right upper lobe. Multiple cavitary lesions with hilar and mediastinal lymphadenopathy. There are also smaller nodular lesions in the left chest too. Small right pleural effusion with multiple calcified granulomata in the left upper lobe. QuantiFERON gold test was found to be positive. Sputum AFB smear was found to be strongly positive and it is sensitive to rifampin. Echocardiography showed no valvular lesions with preserved ejection fraction (>65%) and normal right ventricular size and normal right ventricular systolic pressure. Liver enzymes and renal function tests were found within the normal limit. HIV test was negative. Patient was started with intensive phase anti-tuberculosis treatment with rifampin, isoniazid, ethambutol, pyrazinamide with vitamin B6. He was also started with anticoagulation with heparin and warfarin considering the tuberculosis being the cause of the pulmonary vein thrombosis. Patient was also given supportive treatment and he made a gradual improvement and was discharged with anti-tuberculosis treatment and warfarin. Patient needed to be placed on a higher dose of warfarin as it was difficult to keep him therapeutic with lower doses. He was also advised to follow with infectious disease and anticoagulation clinic. Patient was found to have a significant increase in liver enzymes and bilirubin on follow up and the anti-TB medications were stopped to be restarted one by one with a follow up of his liver enzymes and liver function tests. He was also continued with warfarin.

Tuberculosis management

It is possible to test urine for isoniazid and rifampicin levels to check for compliance. The interpretation of urine analysis is based on the fact that isoniazid has a longer half-life than rifampicin: urine positive for isoniazid and rifampicin patient probably fully compliant urine positive for isoniazid only patient has taken his medication in the last few days preceding the clinic appointment, but had not yet taken a dose that day. urine positive for rifampicin only patient has omitted to take his medication the preceding few days, but did take it just before coming to clinic. urine negative for both isoniazid and rifampicin patient has not taken either medicine for a number of days

[Branch retinal vein occlusion in a 20-year-old patient].

A 20-year-old patient from India was referred because visual acuity of the left eye had deteriorated four weeks ago. A left branch retinal vein occlusion (BRVO) had been diagnosed in an external eye clinic. His best corrected visual acuity was 1,0 in the right eye but only 0.3 in the left. Intraocular pressure was normal. Fundoscopy of the left eye confirmed the finding of a left BRVO. Fluorescein angiography showed evidence of a retinal vasculitis resulting in an ischemic BRVO. Full blood count showed leucocytosis. Chest X-ray, thoracic CT and an Interferon-Gamma Release Assay (IGRA) were suggestive of systemic tuberculosis (TB). Antituberculosis treatment with ethambutol, isoniazid, rifampicin and pyrazinamide was administered for 4 months followed by maintenace therapy of isoniazid and ethambutol for 6 months. 6 months after treatment visual acuity of the left eye had improved; the findings of lung TB had regressed. BRVO associated with ocular TB is a rare presentation of retinal vasculitis. This rare manifestation of a BRVO emphasizes the need of thorough systemic evaluation in young patients with BRVO.

Tuberculosis in the elderly.

Although the cause of the steady increase in tuberculosis (TB) notifications in England and Wales since 1987 is multifactorial, the elderly have made an appreciable contribution. From 1987-1989 the increase was 6% for all ages combined, but 13% in females and 16% in males over the age of 75. Tuberculosis in the elderly therefore remains an appreciable problem. Although the characteristic presentation of chronic cough, malaise and weight loss, with cavitatory changes in the upper lobes still predominates in the elderly, there has been an increased incidence of cryptic miliary disease in which the onset is insidious and chest X-ray often normal. The diagnosis must often be made on suspicion and treatment started before a positive diagnosis is obtained. The elderly are more likely to suffer adverse effects from the anti-tuberculous chemotherapy than the younger population and greater care must be taken. Drug resistance is uncommon in the elderly in the UK. Isoniazid, rifampicin and pyrazinamide are appropriate for the initial two months of treatment. Rifampicin and isoniazid should be continued for a further four months for disease at virtually any site, with the exception of TB meningitis, when a further 10 months therapy should be given. In the UK, preventative therapy in the form of isoniazid or rifampicin and isoniazid probably has no place in disease control in an elderly population; tuberculin tests are frequently negative, even in the presence of active disease, as elderly patients are often anergic.

Tuberculosis

Latent TB Latent TB is treated with either isoniazid or rifampin alone, or a combination of isoniazid with either rifampicin or rifapentine. The treatment takes three to nine months depending on the medications used. People with latent infections are treated to prevent them from progressing to active TB disease later in life. Education or counselling may improve the latent tuberculosis treatment completion rates.

Tuberculosis

The recommended treatment of new-onset pulmonary tuberculosis, , is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months. Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative. Treatment with anti-TB drugs for at least 6 months results in higher success rates when compared with treatment less than 6 months, even though the difference is small. Shorter treatment regimen may be recommended for those with compliance issues. There is also no evidence to support shorter anti-tuberculosis treatment regimens when compared to a 6-month treatment regimen. However recently, results from an international, randomized, controlled clinical trial indicate that a four-month daily treatment regimen containing high-dose, or “optimized,” rifapentine with moxifloxacin (2PHZM/2PHM) is as safe and effective as the

Tuberculosis management

Tuberculosis management refers to the medical treatment of the infectious disease tuberculosis (TB). The standard "short" course treatment for TB is isoniazid (along with pyridoxal phosphate to obviate peripheral neuropathy caused by isoniazid), rifampicin (also known as rifampin in the United States), pyrazinamide, and ethambutol for two months, then isoniazid and rifampicin alone for a further four months. The patient is considered to be free of living bacteria after six months. For latent tuberculosis, the standard treatment is six to nine months of daily isoniazid alone or three months of weekly (12 doses total) of isoniazid/rifapentine combination. If the organism is known to be fully sensitive, then treatment is with isoniazid, rifampicin, and pyrazinamide for two months, followed by isoniazid and rifampicin for four months. Ethambutol need not be used. Drugs

[A cases of isoniazid-induced lupus].

A case of isoniazid (INH)-induced lupus occurring in a 62-year-old man is presented. He visited our hospital in May 1986 and a cavitary lesion was found in the right upper lobe on a chest roentgenogram. He had no previous history of treatment with antituberculotic agents. Though acid-fast bacilli were not found in his sputum, pulmonary tuberculosis was strongly suspected and INH, rifampicin and ethanbutol were administered. Four days after starting the treatment, minimal left pleural effusion was seen on chest X-ray film. Three months later he began to complain polyarthralgia in his digital joints. In a pleural effusion many lymphocytes were found; and the antinuclear antibody (ANA), the anti-extractable nuclear antigens (ENA) antibody, and the RNase resistant anti-ENA antibody were positive, and their titres were 20x, 1000x and 1000x, respectively, and the immune complex (IC) was 16.0 micrograms/ml (LT5). In blood serum, the ANA test the anti-ENA antibody and the RNase resistant anti-ENA antibody were positive with titres 40x, 640x and 640x respectively; and the IC was 14.0 micrograms/ml, and the RA test was positive. The improvement of clinical findings and disappearance of auto-antibodies seen after stopping INH confirmed the diagnosis as INH-induced lupus.

Latent tuberculosis

There are several treatment regimens currently in use: 9H — isoniazid for 9 months is the gold standard (93% effective, in patients with positive test results and fibrotic pulmonary lesions compatible with tuberculosis). 6H — Isoniazid for 6 months might be adopted by a local TB program based on cost-effectiveness and patient compliance. This is the regimen currently recommended in the UK for routine use. The U.S. guidance excludes this regimen from use in children or persons with radiographic evidence of prior tuberculosis (old fibrotic lesions) (69% effective). 6 to 9H2 — An intermittent twice-weekly regimen for the above 2 treatment regimens is an alternative if administered under Directly observed therapy (DOT). 4R — rifampicin for 4-months is an alternative for those who are unable to take isoniazid or who have had known exposure to isoniazid-resistant TB. 3HR — Isoniazid and rifampin may be given daily for three months.

Miliary tuberculosis

The tuberculin skin test, commonly used for detection of other forms of tuberculosis, is not useful in the detection of miliary tuberculosis. The tuberculin skin test fails due to the high numbers of false negatives. These false negatives may occur because of higher rates of tuberculin anergy compared to other forms of tuberculosis. A case of miliary tuberculosis in an 82-year-old woman: Treatment The standard treatment recommended by the WHO is with isoniazid and rifampicin for six months, as well as ethambutol and pyrazinamide for the first two months. If there is evidence of meningitis, then treatment is extended to twelve months. The U.S. guidelines recommend nine months' treatment. "Common medication side effects a patient may have such as inflammation of the liver if a patient is taking pyrazinamide, rifampin, and isoniazid. A patient may also have drug resistance to medication, relapse, respiratory failure, and acute respiratory distress syndrome."

InternalMed_Harrison

The earliest recorded human case of TB dates back 9000 years. Early treatment modalities, such as bloodletting, were replaced by sanatorium regimens in the late nineteenth century. The discovery of streptomycin in 1943 launched the era of antibiotic treatment for TB. Over subsequent decades, the discovery of additional agents and the use of multiple-drug regimens allowed progressive shortening of the treatment course from years to as little as 6 months with the regimen for drug-susceptible TB. Latent TB infection (LTBI) and active TB disease are diagnosed by history, physical examination, radiographic imaging, tuberculin skin test, interferon γ release assays, acid-fast staining, mycobacterial cultures, and/or new molecular diagnostics. LTBI is treated with isoniazid (optimally given daily or twice weekly for 9 months), rifampin (daily for 4 months), or isoniazid plus rifapentine (weekly for 3 months) (Table 205e-1).

InternalMed_Harrison

For active or suspected TB disease, clinical factors, including HIV co-infection, symptom duration, radiographic appearance, and public health concerns about TB transmission, drive diagnostic testing and treatment initiation. Multiple-drug regimens are used for the treatment of TB disease (Table 205e-2). Initially, an intensive phase consisting of four drugs—isoniazid, rifampin, pyrazinamide, and ethambutol—given for 2 months is followed by a continuation phase of isoniazid and rifampin for 4 months, for a total treatment duration of 6 months. The continuation phase is extended to 7 months (for a total treatment duration of 9 months) if the 2-month course of pyrazinamide is not completed or, for patients with cavitary pulmonary TB, if sputum cultures remain positive beyond 2 months of treatment (delayed culture conversion).

Tuberculous meningitis

Treatment The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids help reduce the risk of death in those without HIV. Steroids can be used in the first six weeks of treatment, A few people may require immunomodulatory agents such as thalidomide. Hydrocephalus occurs as a complication in about a third of people with TB meningitis. The addition of aspirin may reduce or delay mortality, possibly by reducing complications such as infarcts. References External links Tuberculosis Meningitis

InternalMed_Harrison

is inexpensive. In this setting, the drug is taken daily or intermittently (i.e., twice weekly) as DOT for 9 months. The 9-month course is more efficacious than the 6-month course (75–90% vs ≤65%), but extension of treatment to 12 months is not likely to provide further protection. A 6-month course of daily or intermittent isoniazid is considered second-line, but acceptable, therapy. A recent large open-label, multicenter, randomized, controlled trial showed that weekly DOT with isoniazid and rifapentine, administered over 3 months, was not inferior to daily isoniazid given for 9 months and had a higher treatment completion rate than the single-drug regimen.

InternalMed_Harrison

As stated above, treatment failure should be suspected when a patient’s sputum smears and/or cultures remain positive after 3 months of treatment. In the management of such patients, it is imperative that the current isolate be urgently tested for susceptibility to firstand second-line agents. Initial molecular testing for rifampin resistance should be done if the technology is available. When the results of susceptibility testing are based on molecular methods and are expected to become available within a few days, changes in the regimen can be postponed until that time. However, if the patient’s clinical condition is deteriorating, an earlier change in regimen may be indicated. A cardinal rule in the latter situation is always to add more than one drug at a time to a failing regimen: at least two and preferably three drugs that have never been used and to which the bacilli are likely to be susceptible should be added. The patient may continue to take isoniazid and rifampin along

InternalMed_Harrison

should always receive their initial-phase regimen daily (see below). A continuation phase of once-weekly rifapentine and isoniazid has been shown to be equally effective for HIV-seronegative patients with noncavitary pulmonary TB who have negative sputum cultures at 2 months. Patients with cavitary pulmonary TB and delayed sputum-culture conversion (i.e., those who remain culture-positive at 2 months) should be tested immediately for drug-resistant TB, and a change of regimen should be considered. To prevent isoniazid-related neuropathy, pyridoxine (10–25 mg/d) should be added to the regimen given to persons at high risk of vitamin B6 deficiency (e.g., alcoholics; malnourished persons; pregnant and lactating women; and patients with conditions such as chronic renal failure, diabetes, and HIV infection, which are also associated with neuropathy). A full course of therapy (completion of treatment) is defined more accurately by the total number of doses taken than by the duration of

[Short-term therapy of lung tuberculosis using a fixed combination of isoniazid, rifampicin and pyrazinamide. Results after 2 years].

Treatment of tuberculosis should be as short and as simple as possible in order to improve patient compliance; and combinations of at least three drugs should be used in order to kill the different populations of mycobacteria and to avoid development of drug resistance.--In a controlled multicentre study two regimens were compared in 93 patients with newly-diagnosed pulmonary tuberculosis: 1) Six-month therapy (47 cases): Daily rifampicin and isoniazid, supplemented with pyrazinamide for the first 2 months. A tablet with a fixed combination of 120 mg rifampicin, 50 mg isoniazid and 300 mg pyrazinamide (Rifater) was used. 2) Present Swiss standard therapy (46 cases): Daily rifampicin, isoniazid and ethambutol for 2 months followed by rifampicin and isoniazid for 7 months.--The time-course of culture negativation and the frequency of adverse events were similar in the two groups. During a follow-up period of at least two years only one relapse was observed in the six-month regimen, 3 months after completion of treatment. This was one of three patients with pretreatment resistance to isoniazid. Nevertheless, two of them were cured with the six-month regimen containing Rifater.--Patient compliance, assessed during outpatient treatment by detecting isoniazid metabolites in the urine, was very good (93% of tests were positive in each group).--These results with a follow-up of more than 2 years, indicate that short-course therapy of 6 months duration with the fixed combination tablet may be recommended as treatment of choice in pulmonary tuberculosis except in cases of isoniazid resistance and other special situations (i.e. large cavitations, large number of viable bacilli).

Tuberculosis management

There are several treatment regimens available: 9H—Isoniazid for 9 months is the gold standard and is 93% effective. 6H—Isoniazid for 6 months might be adopted by a local TB program based on cost-effectiveness and patient compliance. This is the regimen currently recommended in the UK for routine use. The US guidance exclude this regimen from use in children or persons with radiographic evidence of prior tuberculosis (old fibrotic lesions). (69% effective) 6 to 9H2—A twice-weekly regimen for the above two treatment regimens is an alternative if administered under Directly observed therapy (DOT). 4R—Rifampicin for 4 months is an alternative for those who are unable to take isoniazid or who have had known exposure to isoniazid-resistant TB. 3HR—Isoniazid and rifampicin may be given for 3 months. 2RZ—The 2-month regimen of rifampicin and pyrazinamide is no longer recommended for treatment of LTBI because of the greatly increased risk of drug-induced hepatitis and death.

[Pulmonary tuberculosis: effectiveness and tolerance of a 6-month treatment schedule using 4 drugs].

255 patients diagnosed of pulmonary and/or pleural tuberculosis are prospectively studied. All patients received four drugs: isoniazine (INH), rifampin, pirazinamide and ethambutol during the first two months of treatment. Afterwards they continued for four months with two drugs in order to complete the six month treatment period. This schedule has been effective (0.7% of failures) in 99.3% of the patients. Two relapses were detected in the 229 patients who completed the two years follow up. 72 patients (28.2%) presented clinical secondary effects due to the treatment (40 cases of cutaneous affectation, 23 of gastrointestinal intolerance and 8 arthralgias respectively). Also, hyperuricemia was detected in 83% of the patients and a high transaminases level in 42.3%. In 13 patients treatment was cancelled or modified due to the secondary effects. In summary, this schedule of treatment has proved to be effective without an important frequency of serious secondary effects which can be objectively seen in the classical schedules of 9 months with 3 drugs (INH, RF, ET), nevertheless an increased frequency of minor secondary effects were detected.

[Venous thromboembolism in patients with acute tuberculosis].

Studies have demonstrated a link between tuberculosis and hypercoagulable state, with reported rates of 0,6%-10% venous thromboembolism (VTE) in all adults with tuberculosis. The present study aimed to evaluate the current incidence and characteristics of VTE in a large sample of patients with acute tuberculosis. We report a retrospective study about 26 patients who have confirmed tuberculosis complicated with VTE disease. Sixteen men and ten women were brought together. The mean age was 42.58 years. The thromboembolic complication revealed tuberculosis among 5 patients, appearing during hospitalization of 21 patients among which 16 of them receiving antituberculosis drug. We have listed 10 cases of immediate pulmonary thromboembolism and 16 cases of deep vein thrombosis complicated with pulmonary embolism in 6 cases. Oral anticoagulation drug were associated with heparin after a mean of 4.57 days. Duration average of achievement of an effective dose was of 21.05 days and we prescribe low molecular weight heparin for 6 months on 2 cases. There was favorable evolution among 14 patients, 4 of them have lost sight and the evolution was fatal by cataclysmic haemoptysis in one case, a patient died hepatocellular insufficiency and 6 died by pulmonary embolism. Immunological and hematological abnormalities are incriminated in the genesis of VTE disease during tuberculosis by creating hypercoagulate state. The accumulation of morbidity of these two affections as well as the difficulty of therapeutic care made by medical interaction ifampicin-anticoagulants aggravate the prognostic.

Tuberculosis management

documented) – 2 months of Isoniazid, Rifampin, Ethambutol and Streptomycin followed by 6 months of Isoniazid and Rifampin • One hepatotoxic drug – 2 months of Isoniazid, Ethambutol & Streptomycin followed by 10 months of Isoniazid and Ethambutol • No hepatotoxic drugs – 18–24 months of Streptomycin, Ethambutol and Quinolones Patients with liver disease should have their liver function tests monitored regularly throughout TB treatment.

Controlled trial of 4 three-times-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Second report: the results up to 24 months. Hong Kong Chest Service/British Medical Research Council.

Five 6-month antituberculosis regimens, allocated at random to patients with acid-fast bacilli in their sputum on microscopy, were studied. Four, given 3 times a week throughout, contained isoniazid and rifampicin together with 1. streptomycin, pyrazinamide and ethambutol, 2. streptomycin and pyrazinamide, but no ethambutol, 3. streptomycin and ethambutol, but no pyrazinamide, 4. pyrazinamide and ethambutol, but no streptomycin. The fifth was a daily regimen of isoniazid, rifampicin, pyrazinamide and ethambutol. All 833 patients with drug-sensitive strains of tubercle bacilli pretreatment had a favourable bacteriological response during chemotherapy, and the bacteriological relapse rate during 18 months after stopping chemotherapy was 1% for the three-times-weekly regimens containing streptomycin and pyrazinamide in addition to isoniazid and rifampicin (regimens 1 and 2, above) and for the daily regimen, 2% for the regimen of isoniazid, rifampicin, pyrazinamide and ethambutol three times a week (regimen 4), but 8% for the only regimen which did not contain pyrazinamide (regimen 3). The results achieved by the 4 pyrazinamide regimens were practically as good for the 110 patients with bacilli resistant to isoniazid, streptomycin, or both drugs pretreatment as they were for the patients with drug-sensitive strains.

Thromboembolism in <i>Mycobacterium tuberculosis</i> Infection: Analysis and Literature Review.

Tuberculosis is associated with hypercoagulation; however, there are few reports of cases thromboembolism and tuberculosis at the same time in the real world. The purpose of this study was to report the incidence and clinical course of thromboembolism in patients diagnosed with tuberculosis. We retrospectively analyzed the data of patients who were diagnosed with both tuberculosis and thromboembolism including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT) at Seoul National University Boramae Medical Center from January 2000 through March 2015. Among the 7905 tuberculosis patients, 49 (0.6%) exhibited PTE, DVT, or both at or after the time of tuberculosis diagnosis. All patients treated for tuberculosis started with isoniazid, ethambutol, rifampicin, and pyrazinamide. Eight patients were switched to treatment with second-line medication because of resistance or adverse events. About half of the patients (n = 21, 44.7%) had thrombosis at the time of tuberculosis diagnosis. Of 48 patients treated for thromboembolism, 36 received warfarin. A total of 20 patients improved symptom caused by thrombosis, and 10 patients were confirmed cure by image study such as computed tomography or doppler ultrasonography. Eight patients who were treated with warfarin had persistent thrombosis. Five patients (10.2%) experienced major bleeding that required hospitalization. All of these bleeding events were associated with warfarin therapy. Careful attention to PTE/DVT is needed at the time of diagnosis of tuberculosis and during anti-tuberculosis therapy. Warfarin therapy administered with anti-tuberculosis medication requires frequent monitoring to prevent major bleeding.

InternalMed_Harrison

It is estimated that about 2 billion people, or nearly one-third of the human population, have been infected with M. tuberculosis. Although only a small fraction of these infections will progress toward active disease, new active cases will continue to emerge from this pool of “latently” infected individuals. Unfortunately, there is no diagnostic test at present that can predict which individuals with LTBI will develop active TB. Treatment of selected persons with LTBI aims at preventing active disease. This intervention (also called preventive chemotherapy or chemoprophylaxis) is based on the results of a large number of randomized, placebo-controlled clinical trials demonstrating that a 6to 9-month course of isoniazid reduces the risk of active TB in infected people by up to 90%. Analysis of available data indicates that the optimal duration of treatment is ~9 months. In the absence of reinfection, the protective effect is believed to be lifelong. Clinical trials have shown that

Isoniazid

Isoniazid can be used alone or in combination with Rifampin for treatment of latent tuberculosis, or as part of a four-drug regimen for treatment of active tuberculosis. The drug regimen typically requires daily or weekly oral administration for a period of three to nine months, often under Directly Observed Therapy (DOT) supervision. Non-tuberculous mycobacteria Isoniazid was widely used in the treatment of Mycobacterium avium complex as part of a regimen including rifampicin and ethambutol. Evidence suggests that isoniazid prevents mycolic acid synthesis in M. avium complex as in M. tuberculosis and although this is not bactericidal to M. avium complex, it greatly potentiates the effect of rifampicin. The introduction of macrolides led to this use greatly decreasing. However, since rifampicin is broadly underdosed in M. avium complex treatment this effect may be worth re-investigating.

Should we take a history of prior treatment, and check sputum status at 2-3 months when treating patients for tuberculosis?

Pinetown, South Africa (1975-1983). To determine the value of previous treatment history and sputum smear examination at 2-3 months in predicting treatment failure and relapse in tuberculosis patients treated with four drugs given twice weekly for six months under direct observation. Four cohort studies among 562 ambulant adults with culture positive pulmonary tuberculosis, designed to test the effectiveness of isoniazid 600-900 mg, rifampicin 600 mg, pyrazinamide 2-3 g, and streptomycin 1-2 g, given twice weekly. The same drug regimen was given to all patients irrespective of previous treatment history. Therapy was not changed if smears remained positive at 2-3 months. Positive predictive values of a history of previous treatment for a positive smear at 2-3 months (18.3%), treatment failure (5.2%), and relapse (9.4%) were poor. Although patients with positive smears at 2-3 months were more likely to fail therapy than patients with negative smears (relative risk=4.5, 95% Confidence Interval [CI]: 1.6-12.8), positive predictive value for treatment failure was only 12.5%. Although relapse was more frequent in patients with positive smears than those with negative smears (9.7% vs 6.2%; P=0.4), most patients who relapsed had been smear negative at 2-3 months (18/21). A four-drug rifampicin-containing regimen can safely be given twice weekly under direct observation to both new and retreatment cases, and the 2-3 month smear examination can safely be omitted.

[The treatment of pulmonary tuberculosis in a special hospital. Its evolution from 1948 to 1986].

Nine hundred and sixty six patients diagnosed of pulmonary and/or pleural tuberculosis and admitted to a specialized hospital from 1948 to 1986, have been retrospectively analyzed, investigating their treatment and evolution. Sixty two percent of patients did not fulfil pharmaceutical treatment as far as number and dose of drugs, evolving through the decades (50, 60, 70, and 80s) with a 100%, 82%, 37% and 3% respectively. A 13% of patients did not receive any chemotherapy, 16% underwent surgery, and 53% received a second treatment. Real or hidden monotherapy was given to 38% of patients. Isoniazide has been the most uniformly used drug. Streptomycin has been the most frequently underdosed used drug. Sputum culture turned negative in 42% and 51% of patients during the first 3 and 6 months respectively, with a 42% of positives persisting after one year and a 30% when discharged. A statistically significant difference is observed when comparing all the variables between admitted patients up to 1969 and from 69 to 86 in favor of the second period.

A controlled trial of individually-adapted short-course chemotherapy versus two-year scheme in original treatment of pulmonary tuberculosis. Report after a five-year follow-up.

Patients with culture-positive pulmonary tuberculosis were allocated at random into two groups for a three-phase regimen in original course chemotherapy. The first group was given rifampicin (RMP) plus isoniazid (INH) plus ethambutol until sensitivity tests were completed, then RMP plus INH until culture conversion, thereafter INH alone for four months. The second group received the same drugs until obtaining culture conversion, thereafter IHN alone for a period lasting two years after onset of chemotherapy. One hundred sixty-eight patients were available for the final assessment after a five-year follow-up after culture conversion. Two bacteriologic relapses occurred among the two-year scheme patients, none in the short-course patients.

Tuberculosis management

Drug regimens are similarly abbreviated in a semistandardised manner. The drugs are listed using their single letter abbreviations (in the order given above, which is roughly the order of introduction into clinical practice). A prefix denotes the number of months the treatment should be given for; a subscript denotes intermittent dosing (so 3 means three times a week) and no subscript means daily dosing. Most regimens have an initial high-intensity phase, followed by a continuation phase (also called a consolidation phase or eradication phase): the high-intensity phase is given first, then the continuation phase, the two phases divided by a slash. So, 2HREZ/4HR3 means isoniazid, rifampicin, ethambutol, pyrazinamide daily for two months, followed by four months of isoniazid and rifampicin given three times a week. In the US only, streptomycin is not considered a first line drug by ATS/IDSA/CDC because of high rates of resistance. The WHO have made no such recommendation.

A rare complication of pulmonary tuberculosis: a case report.

Pulmonary tuberculosis remains an important public health problem globally and one of the most prevalent infectious diseases in Sri Lanka. It can cause a wide variety of complications but hematological manifestations are rare. According to our literature survey, this is the first reported case of the disease associated with deep vein thrombosis in Sri Lanka. A 37 year old Sri Lankan Sinhalese female presented with fever of one month's duration with productive cough and two weeks painless left lower limb swelling. Chest X-ray showed bilateral inflammatory shadows with a cavitatory lesion on the right apical region. A computed tomographic pulmonary angiography scan excluded pulmonary embolism. She had rising mycoplasma antibody titre (four fold). Acute deep vein thrombosis of the left lower limb was confirmed by venous duplex. Pulmonary tuberculosis was confirmed with positive culture for Mycobacterium tuberculosis. She was treated with clarythromycin, enoxaparin, warfarin and anti tuberculus drugs. It was difficult to maintain her International Normalizing Ratio in the therapeutic range due to drug interactions and poor compliance. At five months of presentation she died of massive pulmonary embolism. Our case emphasizes that patients with severe pulmonary tuberculosis are at risk of developing thromboembolism and superadded infections. It should be noted that even though starting anti tuberculosis drugs improved haemostatic disturbances, achieving the target International Normalizing Ratio was difficult due to drug interactions. Therefore these patients should be closely followed up to prevent complications and death from pulmonary embolism.

Tuberculosis in neonates and infants: epidemiology, pathogenesis, clinical manifestations, diagnosis, and management issues.

Tuberculosis is one of the leading infectious causes of death and as such represents a major global health problem. Infants may develop congenital tuberculosis from an infectious mother or, most commonly, they may acquire postnatal disease by contact with an infectious adult source. Important epidemiologic, pathogenetic, and clinical data regarding the management of infantile disease are reviewed. Diagnostic evaluation includes tuberculin skin tests, chest radiography and other imaging studies, smears and cultures, examination of the cerebrospinal fluid, and polymerase chain reaction, as well as the more recent interferon-gamma assay. Pregnant women with a positive Mantoux skin test but normal chest x-ray should either start chemoprophylaxis during gestation or after delivery depending on the likelihood of being recently infected, their risk of progression to disease, as well as their clinical evidence of disease. Pregnant women with a positive Mantoux skin test and chest x-ray or symptoms indicative of active disease should be treated with non-teratogenic agents during gestation; all household contacts should also be screened. When tuberculosis is suspected around delivery, the mother should be assessed by chest x-ray and sputum smear; separation of mother and offspring is indicated only if the mother is non-adherent to medical treatment, needs to be hospitalized, or when drug-resistant tuberculosis is involved. According to the American Academy of Pediatrics, treatment of latent infection is highly effective with isoniazid administration for 9 months. This regimen may be extended to 12 months for immunocompromised patients. When drug resistance is suspected, combination therapies, which usually consist of isoniazid with rifampin (rifampicin), are administered until the results of susceptibility tests become available. Organisms resistant to isoniazid only may be treated with rifampin alone for a total of 6-9 months. All infants with tuberculosis disease should be started on four agents (isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) until drug susceptibility is assessed. For susceptible intrathoracic tuberculosis, isoniazid, rifampin, and pyrazinamide are administered for a total of 2 months, at which point pyrazinamide is withdrawn and the other two agents are continued for another 4-10 months depending on the severity of the disease. The same regimen may be applied in extrapulmonary tuberculosis with the exception of skeletal, miliary, and CNS disease, which require daily administration of isoniazid, rifampin, pyrazinamide, and streptomycin for 1-2 months, followed by isoniazid and rifampin daily or twice weekly for another 10 months. When drug-resistant tuberculosis is suspected, a regimen of isoniazid, rifampin, and pyrazinamide plus either streptomycin or ethambutol should be initially prescribed, until the results of susceptibility tests become available. HIV-seropositive infants with pulmonary tuberculosis should receive isoniazid, rifampin, pyrazinamide, and ethambutol or an aminoglycoside for 2 months, followed by isoniazid and rifampin for a total of at least 12 months. Apart from conventional antimycobacterial agents, novel therapeutic modalities, which stimulate the host immune system such as interleukin-2 (IL-2), IL-12, interferon-gamma, and tumor necrosis factor antagonists have been tested with promising results.

Rifapentine

Rifapentine was approved for medical use in the United States in 1998. It is on the World Health Organization's List of Essential Medicines. In many areas of the world it is not easy to get . Medical uses A systematic review of regimens for prevention of active tuberculosis in HIV-negative individuals with latent TB found that a weekly, directly observed regimen of rifapentine with isoniazid for three months was as effective as a daily, self-administered regimen of isoniazid for nine months. The three-month rifapentine-isoniazid regimen had higher rates of treatment completion and lower rates of hepatotoxicity. However, the rate of treatment-limiting adverse events was higher in the rifapentine-isoniazid regimen compared to the nine-month isoniazid regimen. Pregnancy