Short-course therapy for tuberculosis in infants and children. Infectious Diseases and Immunization Committee,Canadian Paediatric Society.

OBJECTIVE: To improve efficacy of and compliance with therapy for tuberculosis in children. OPTIONS: Short-course (6-month) multi-drug therapy, either non-supervised or directly supervised, versus long-course (more than 6-month) multi-drug therapy. OUTCOMES: Success (more than 90% of cases cured without relapse or serious side effects), development of drug resistance and compliance with treatment. EVIDENCE: Review of published reports of efficacy trials of tuberculosis therapy in children, side effects and compliance studies; consensus of expert opinion. VALUES: Values were assigned to the evidence by the Infectious Disease and Immunization Committee of the Canadian Paediatric Society through review of the data and consensus. BENEFITS, HARMS AND COSTS: Improved efficacy and compliance with short-course protocols should lower the rate of treatment failure among children in Canada and the cost of tuberculosis care. RECOMMENDATIONS: A short-course (6-month) protocol of four drugs for the first 2 months and two drugs for the subsequent 4 months is recommended to treat pulmonary tuberculosis or extrapulmonary disease causing lymphadenopathy. Tuberculous meningitis, disease involving bones and joints and tuberculosis with HIV infection require longer courses of treatment. Asymptomatic tuberculosis should be treated with daily doses of isoniazid for 9 months. Intermittent directly observed therapy is recommended if compliance cannot be ensured. Routine liver function testing is not recommended for prepubescent children taking isoniazid, but monthly assessment for clinical symptoms and periodic liver function evaluation is advised in adolescent women, especially post partum. VALIDATION: This report was reviewed by the directors of the Canadian Paediatric Society, the Hepatitis and Special Pathogens Division of the Laboratory Centre for Disease Control and the Canadian Thoracic Society. The recommendations are similar to those of the American Academy of Pediatrics. SPONSOR: The recommendations were developed and endorsed by the Infectious Disease and Immunization Committee of the Canadian Paediatric Society.     

Evaluation of the efficacy of chloroquine chemoprophylaxis for vivax malaria among Republic of Korea military personnel

Chloroquine has been used massively for vivax malaria prophylaxis and treatment in the Republic of Korea (ROK) military personnel from 1997. Although prophylaxis is generally regarded as successful among ROK military, prophylaxis failure has been repeatedly reported. Before the prophylaxis program was started on July 4th 2011, which was completed on October 16th 2011, by the ROK military, more than 60% of malaria cases were attributed to new infection or long-latency relapse. During the prophylaxis program, the authors re-examined the efficiency of chloroquine chemoprophylaxis in ROK military during the last 6 months of 2011 by measuring compliance and whole blood chloroquine levels in 41 malaria patients immediately before instituting antimalarial therapy between July and December. Three patients (7.3%) showed good compliance, and had whole blood total chloroquine levels above the minimally inhibitory concentration (100 ng/mL). However, 28 (69.3%) of these 41 patients when admitted to hospital showed poor or no compliance with prophylaxis; 4 of the 28 (14.3%) were stationed outside the mass prophylaxis region, and 5 (17.9%) subjects were infected after the prophylaxis program had finished. These findings indicate that the current malaria control program should be carefully reconsidered, in terms of, individual instruction, current chemoprophylaxis program regimens, and schedules to improve the efficacy of prophylaxis in the ROK military.     

Profit-sharing in health care institutions.

Zidovudine (AZT) is the first antiretroviral agent to be licensed for the treatment of human immunodeficiency virus (HIV) infection. Since the initial placebo-controlled trial showing improved survival among patients with acquired immunodeficiency syndrome (AIDS) or symptomatic HIV infection (AIDS-related complex [ARC]) zidovudine has been evaluated in other stages of HIV infection. This review offers physicians who treat patients with HIV infection a comprehensive analysis of the current data on the clinical efficacy of zidovudine in various stages of HIV infection and on zidovudine''s adverse effects. After a search of MEDLINE for pertinent articles published since 1985, controlled studies and studies of long-term zidovudine therapy, of zidovudine therapy for HIV-related conditions and of the incidence and management of adverse reactions were evaluated. In addition, abstracts from international meetings were reviewed. No significant difference in clinical outcome was found between high-dose and low-dose zidovudine therapy, but there were significantly fewer toxic effects in the low-dose group. In two other studies zidovudine was found to delay disease progression in patients with asymptomatic or mildly symptomatic HIV infection who had an absolute CD4 count of less than 0.5 x 10(9)/L; the low incidence of adverse reactions may have been due to either the early stage of the infection or the low dose used. The demonstration of zidovudine-resistant isolates after at least 6 months of therapy has yet to be correlated with clinical deterioration. When to begin zidovudine therapy among asymptomatic patients with a CD4 count of less than 0.5 x 10(9)/L remains unclear. Zidovudine can be used safely to delay progression to AIDS or ARC in certain patients with asymptomatic or mildly symptomatic HIV infection and can prolong survival in those with more severe infection. Further studies are necessary to identify indicators that could better define when to start treatment and how to alleviate toxic effects. Combination therapy with such agents as interferon alpha may become the preferred choice of therapy to prevent toxic effects and zidovudine resistance. Zidovudine prophylaxis has been used after HIV exposure. Although studies with animal models have had encouraging results infection has occurred despite immediate prophylaxis and thus further investigation is required.     

Successful salvage therapy with Daptomycin for osteomyelitis caused by methicillin-resistant Staphylococcus aureus in a renal transplant recipient with Fabry-Anderson disease

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disorder that presents with hemolytic anemia, marrow failure and thrombophilia. During acute attacks, corticosteroid can alleviate the hemolytic paroxysm, but the prolonged administration induces serious toxicity including immunosuppression. So American thoracic society (ATS) for tuberculosis (TB) recommends prophylactic anti-TB medication in patients with a long-term steroid therapy. However, in the patient who was treated for active TB in the past, there are no guidelines of the test for determining patients who have latent TB infection (LTBI) and no recommendations of TB prophylaxis if there is no evidence of reactivation at present. A 40-year-old male patient presented with fever and aggravated weakness for a week. He was diagnosed with PNH a month ago and took corticosteroid for 3 weeks. In the past, he was diagnosed with pulmonary TB and completely cured after treatment. According to guideline, he was not indicated with TB prophylaxis. However, he caught miliary TB, progressed to acute respiratory distress syndrome. We experience this embarrassing case, and emphasize the need to investigate multicentral TB prevalence and to make the guidelines of anti-TB medication in subgroups of hematologic diseases including PNH.     

Growth factor-enriched autologous plasma improves wound healing after surgical debridement in odontogenic necrotizing fasciitis: a case report

Introduction

Intracranial tuberculomas are a rare complication of tuberculosis occurring through hematogenous spread from an extracranial source, most often of pulmonary origin. Testicular tuberculosis with only intracranial spread is an even rarer finding and to the best of our knowledge, has not been reported in the literature. Clinical suspicion or recognition and prompt diagnosis are important because early treatment can prevent patient deterioration and lead to clinical improvement.

Case presentation

We present the case of a 51-year-old African man with testicular tuberculosis and multiple intracranial tuberculomas who was initially managed for testicular cancer with intracranial metastasis. He had undergone left radical orchidectomy, but subsequently developed hemiparesis and lost consciousness. Following histopathological confirmation of the postoperative sample as chronic granulomatous infection due to tuberculosis, he sustained significant clinical improvement with antituberculous therapy, recovered fully and was discharged at two weeks post-treatment.

Conclusion

The clinical presentation of intracranial tuberculomas from an extracranial source is protean, and delayed diagnosis could have devastating consequences. The need to have a high index of suspicion is important, since neuroimaging features may not be pathognomonic.     

Management of extra-pulmonary tuberculosis (excluding miliary and meningeal) in south and west Wales (1976-8).

In a retrospective survey of the management of extrapulmonary tuberculosis lymph node and genitourinary tuberculosis were found more commonly than bone and joint or gynaecological disease. Only 29% of patients received 18 moths'' chemotherapy while 31% received nine to 12 months'' treatment with rifampicin and isoniazid regimens and 34% had short-course chemotherapy with other regimens. Five patients were not offered any chemotherapy after diagnosis, and in five patients the diagnosis was overlooked because of administrative errors. One patient died from tuberculosis (renal). Poor drug compliance appeared less of a problem than in pulmonary tuberculosis. Only 14% of patients had their disease managed solely by consultants who were not specialists in chest disease. Liaison with a chest consultant did not necessarily ensure chemotherapy for 18 moths.     

Serum triglycerides, the liver and the pancreas

Massive hypertriglyceridaemia associated with fatty liver and abdominal pain or frank pancreatitis (the chylomicronaemia syndrome) is uncommon, but clinically important and under-recognized. It may arise as a result of severe genetic defects in lipolysis or, more commonly, from a moderate primary hypertriglyceridaemia that is exacerbated by a secondary cause. The latter include several drugs, among which the protease inhibitors, used for the treatment of human immunodeficiency virus infection, are increasingly apparent. In the acute situation plasma exchange, fat-free parenteral nutrition and acute insulin treatment, even in nondiabetic persons, may be valuable. A potentially major advance in prophylaxis is the use of high-dose antioxidant therapy, which has been shown to reduce attacks of pancreatitis even in the absence of a reduction in serum triglycerides. Asymptomatic patients with abnormal liver function tests are common in the lipid clinic, and can be a difficult group in which to make management decisions. Among those who are not taking excessive amounts of alcohol, many will have nonalcoholic steatohepatitis. The care of these patients is discussed, but there remains considerable uncertainty regarding their optimum management and prognosis.     

Tuberculosis chemoprophylaxis.

The incidence of tuberculosis in the United States, after decreasing for many years, has recently begun to climb at an alarming rate. This rise is due mainly to excess cases in high-risk groups including human immunodeficiency virus-infected patients, the elderly, the foreign born, and the homeless. In the United States tuberculosis has been associated with a 10% mortality despite adequate treatment. The tuberculin skin test is a safe and inexpensive test for detecting tuberculous infection. To improve its predictive value the diagnostic criteria for classifying a positive reaction have recently been revised. High-risk populations should be screened to identify those persons who would most benefit from preventive treatment. Isoniazid therapy taken for 6 to 12 months is a safe and highly effective means of preventing tuberculous infection from developing into active disease. The most worrisome toxicity of isoniazid, fatal hepatitis, is extremely rare; when patients are monitored closely the incidence of death from hepatotoxicity is less than 0.01%.     

Causes and prevention of calcium-containing renal calculi.

Kidney stones are common, and recurrences are the rule. At least 90% of patients with kidney stones probably have some identifiable metabolic risk factor. Effective prophylaxis is often available, but with the relatively low rate of recurrence, compliance with the treatment may be a problem. Studies are required to determine the cost-effectiveness of metabolic investigation and prophylactic therapy versus the possible need for repeated treatment by means of extracorporeal lithotripsy, especially in patients having a first calcium oxalate stone.     

An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori

OBJECTIVES: To provide Canadian primary care physicians with an evidence-based clinical management tool, including diagnostic and treatment recommendations, for patients who present with uninvestigated dyspepsia. RECOMMENDATIONS: The management tool has 5 key decision steps addressing the following: (1) evidence that symptoms originate in the upper gastrointestinal tract, (2) presence of alarm features, (3) use of nonsteroidal anti-inflammatory drugs (NSAIDs), (4) dominant reflux symptoms and (5) evidence of Helicobacter pylori infection. All patients over 50 years of age who present with new-onset dyspepsia and patients who present with alarm features should receive prompt investigation, preferably by endoscopy. The management options for patients with uninvestigated dyspepsia who use NSAIDs regularly are: (1) to stop NSAID therapy and assess symptomatic response, (2) to treat with NSAID prophylaxis if NSAID therapy cannot be stopped or (3) to refer for investigation. Gastroesophageal reflux disease can be diagnosed clinically if the patient''s dominant symptoms are heartburn or acid regurgitation, or both; these patients should be treated with acid suppressive therapy. The remaining patients should be tested for H. pylori infection, and those with a positive result should be treated with H. pylori-eradication therapy. Those with a negative result should have their symptoms treated with optimal antisecretory therapy or a prokinetic agent. VALIDATION AND EVIDENCE: Evidence for resolution of the dyspepsia symptoms was the main outcome measure. Supporting evidence for the 5 steps in the management tool and the recommendations for treatment were graded according to the strength of the evidence and were endorsed by consensus of committee members. If no randomized controlled clinical trials were available, the recommendations were based on the best available evidence. LITERATURE REVIEW: Evidence was obtained from MEDLINE searches for pertinent articles published from 1966 to October 1999. The searches focused on dyspepsia, diagnosis and treatment. Additional articles were retrieved through a manual search of bibliographies and abstracts from international gastroenterology conferences.     

New approaches in the diagnosis and treatment of latent tuberculosis infection

With nearly 9 million new active disease cases and 2 million deaths occurring worldwide every year, tuberculosis continues to remain a major public health problem. Exposure to Mycobacterium tuberculosis leads to active disease in only ~10% people. An effective immune response in remaining individuals stops M. tuberculosis multiplication. However, the pathogen is completely eradicated in ~10% people while others only succeed in containment of infection as some bacilli escape killing and remain in non-replicating (dormant) state (latent tuberculosis infection) in old lesions. The dormant bacilli can resuscitate and cause active disease if a disruption of immune response occurs. Nearly one-third of world population is latently infected with M. tuberculosis and 5%-10% of infected individuals will develop active disease during their life time. However, the risk of developing active disease is greatly increased (5%-15% every year and ~50% over lifetime) by human immunodeficiency virus-coinfection. While active transmission is a significant contributor of active disease cases in high tuberculosis burden countries, most active disease cases in low tuberculosis incidence countries arise from this pool of latently infected individuals. A positive tuberculin skin test or a more recent and specific interferon-gamma release assay in a person without overt signs of active disease indicates latent tuberculosis infection. Two commercial interferon-gamma release assays, QFT-G-IT and T-SPOT.TB have been developed. The standard treatment for latent tuberculosis infection is daily therapy with isoniazid for nine months. Other options include therapy with rifampicin for 4 months or isoniazid + rifampicin for 3 months or rifampicin + pyrazinamide for 2 months or isoniazid + rifapentine for 3 months. Identification of latently infected individuals and their treatment has lowered tuberculosis incidence in rich, advanced countries. Similar approaches also hold great promise for other countries with low-intermediate rates of tuberculosis incidence.     

Tuberculosis in patients with human immunodeficiency virus infection. Review of current concepts.

Tuberculosis is a frequent complication of human immunodeficiency virus (HIV)-induced immunosuppression. The diagnosis of extrapulmonary tuberculosis in patients with evidence of HIV infection qualifies as a criterion of the acquired immunodeficiency syndrome. Demographic characteristics of patients with tuberculosis and HIV infection vary by region and reflect the degree to which patients with Mycobacterium tuberculosis infection adopt behaviors that put them at risk for HIV infection. The clinical features of tuberculosis in patients with HIV infection are atypical. Extrapulmonary disease, tuberculin anergy, and unusual findings on chest radiographs occur most frequently when tuberculosis afflicts patients with other clinical evidence of HIV infection at the time tuberculosis is diagnosed. Treatment is effective for tuberculosis in HIV-seropositive patients, and isoniazid prophylaxis is recommended for HIV-infected patients with positive tuberculin skin tests.     

Azole Resistance in Aspergillus fumigatus—Current Epidemiology and Future Perspectives

Azole resistance in Aspergillus fumigatus isolates is increasingly reported in different nosologic contexts with variable prevalence in different countries. Mutations in the target of triazoles are widely described in azole-resistant clinical isolates. The recovery of mutated/resistant isolates is described either in patients undergoing long-term azole treatment or after inhalation of environmentally acquired resistant isolates. Acquisition in patients during azole therapy highlights the capacity of this fungus to adapt to its environment, but it has a low impact in terms of public health, as interhuman transmission of A. fumigatus is uncommon. Environmentally acquired resistant isolates may propagate and affect populations at risk. The use of triazoles as first-line therapy or prophylaxis could lead to selection of resistant isolates in patients, because most isolates harbor azole cross-resistance. Although mold-active triazoles have provided major progress in the prophylaxis and treatment of Aspergillus infection, the increase of azole resistance could question their use in humans.     

Fungal infections following treatment with monoclonal antibodies and other immunomodulatory therapies

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in a wide range of important physiologic processes and has a pathologic role in some diseases. TNF antagonists (infliximab, adalimumab, etanercept) are effective in treating inflammatory conditions. Antilymphocyte biological agents (rituximab, alemtuzumab), integrin antagonists (natalizumab, etrolizumab and vedolizumab), interleukin (IL)-17A blockers (secukinumab, ixekizumab) and IL-2 antagonists (daclizumab, basiliximab) are widely used after transplantation and for gastroenterological, rheumatological, dermatological, neurological and hematological disorders. Given the putative role of these host defense elements against bacterial, viral and fungal agents, the risk of infection during a treatment with these antagonists is a concern. Fungal infections, both opportunistic and endemic, have been associated with these biological therapies, but the causative relationship is unclear, especially among patients with poor control of their underlying disease or who are undergoing steroid therapy. Potential recipients of these drugs should be screened for latent endemic fungal infections. Cotrimoxazole prophylaxis could be useful for preventing Pneumocystis jirovecii infection in patients over 65 years of age who are taking TNF antagonists, antilymphocyte biological agents or who have lymphopenia and are undergoing concomitant steroid therapy. As with other immunosuppressant drugs, TNF antagonists and antilymphocyte antibodies should be discontinued for patients with active infectious disease.     

Penicillium marneffei Infection in Immunocompromised Host

Penicillium marneffei (PM) was first described in 1973, causing human infection in a patient with Hodgkin Lymphoma. In the HIV/AIDS epidemic, it has been described as one of the important opportunistic infection following tuberculosis and cryptococcosis in endemic region of Southeast Asia and Southern China. Immunocompromised patients acquire penicilliosis through inhalation of conidia, resulting in disseminated disease characterized by prolonged fever, pancytopenia, hepatosplenomegaly, and classic cutaneous presentation of umbilicated papular eruption. Nowadays, rare manifestations such as fungemia, pneumonia, enterocolitis, genital ulcers, oral ulcer, and central nervous system infection have been reported. Over the past decade, molecular and genomic studies have revealed more knowledge of PM, and vaccines are under development. Modern era PM has become a serious threat in immunocompromised travelers, rather than HIV/AIDS patient in the endemic area, who receive an effective prophylaxis strategy along with the highly active antiretroviral therapy (HAART) initiation.     

Duloxetine: a summary of published clinical experience

Effective oral therapy for genuine stress urinary incontinence (SUI) in women has, to date, been an unattainable goal. Although oral pharmacologic agents have been used for this condition, none has ultimately been successful, because of side effects, lack of efficacy, or problematic compliance with drug ingestion. The availability of an effective oral agent for SUI would increase the range of therapeutic options for symptom management and possibly make treatment accessible to more women who otherwise feel that surgical therapy is not an option because of social, personal, or medical reasons. Duloxetine is a selective serotonin (5-HT) and norepinephrine reuptake inhibitor that has been shown to increase rhabdosphincter activity. Rhabdosphincter contractility changes are thought to occur as the result of increased stimulation of alpha(1)-adrenergic and 5-HT(2) receptors in the sacral spinal cord, resulting in increased efferent pudendal nerve activity, producing increased pelvic floor tonus. Two large-scale studies have been completed employing subjective and objective outcomes to assess the therapeutic index of duloxetine as a therapy for SUI.     

Reactivation of M. tuberculosis infection in trans-membrane tumour necrosis factor mice

Of those individuals who are infected with M. tuberculosis, 90% do not develop active disease and represents a large reservoir of M. tuberculosis with the potential for reactivation of infection. Sustained TNF expression is required for containment of persistent infection and TNF neutralization leads to tuberculosis reactivation. In this study, we investigated the contribution of soluble TNF (solTNF) and transmembrane TNF (Tm-TNF) in immune responses generated against reactivating tuberculosis. In a chemotherapy induced tuberculosis reactivation model, mice were challenged by aerosol inhalation infection with low dose M. tuberculosis for three weeks to establish infection followed chemotherapeutic treatment for six weeks, after which therapy was terminated and tuberculosis reactivation investigated. We demonstrate that complete absence of TNF results in host susceptibility to M. tuberculosis reactivation in the presence of established mycobacteria-specific adaptive immunity with mice displaying unrestricted bacilli growth and diffused granuloma structures compared to WT control mice. Interestingly, bacterial re-emergence is contained in Tm-TNF mice during the initial phases of tuberculosis reactivation, indicating that Tm-TNF sustains immune pressure as in WT mice. However, Tm-TNF mice show susceptibility to long term M. tuberculosis reactivation associated with uncontrolled influx of leukocytes in the lungs and reduced IL-12p70, IFNγ and IL-10, enlarged granuloma structures, and failure to contain mycobacterial replication relative to WT mice. In conclusion, we demonstrate that both solTNF and Tm-TNF are required for maintaining immune pressure to contain reactivating M. tuberculosis bacilli even after mycobacteria-specific immunity has been established.     

Treatment of Helicobacter pylori Infection: A Review of the World Literature

Background. None of the currently used anti- Helicobacter pylori drug regimens cures the infection 100%, and cure results still vary considerably. The present article reviews the effectiveness of currently used antimicrobial regimens, aimed to cure H. pylori infection.
Methods. Data collection started from the beginning of the anti- H. pylori -therapy era until May 1995. No attempt at formal metanalysis has been made, because many studies have been published only in abstract form. Attempts were made to exclude duplicates of studies by comparison to previously reported ones; the authors of suspected duplicates were contacted. After amalgamation of the number of included patients and the number of successfully treated patients, the mean values of eradication rates and the 95% confidence intervals were calculated.
Results. A total of 237 treatment arms were analyzed. Bismuth triple therapy continues to reach high eradication rates worldwide (78–89%). Side effects leading to diminished patient compliance and the marked decline of eradication efficacy in cases of metronidazole resistance are considered to be the major drawbacks of this therapy. Proton pump inhibitor (PPI) dual therapy is better tolerated with fewer side effects than is bismuth triple therapy. The mean eradication rates vary from 55 to 75%, and the extremes lie between 24 and 93%. PPI triple therapies have been shown to be very effective against H. pylori (eradication rates, 80–89%). Quadruple therapy leads to a mean eradication rate of 96%.
Conclusion. Based on efficacy, PPI triple or bismuth triple therapy are recommended as first-line treatment for H. pylori infection. Quadruple therapy could serve as second-line treatment for eradication of initial failures and in case of metronidazole resistance.     

Congenital toxoplasmosis: epidemiologic features and control.

Toxoplasmosis is caused by the parasite Toxoplasma gondii. It is acquired from undercooked meat or from food or fomites contaminated by cat feces. The disease can be transmitted to the fetus only during maternal parasitemia, which is associated with primary infection. Extrapolation from current data suggests that there are 140 to 1400 cases of congenital toxoplasmosis per year in Canada and that 70 to 280 of the infants are severely affected at birth; many of the others suffer sequelae later in life. Serologic diagnosis of primary infection in the mother is quite sensitive and specific. Diagnosis in the infant is more difficult and may take several months. Prenatal treatment of the woman and postnatal treatment of the infant are hampered by the lack of proven efficacy as well as ethical and compliance problems. Preventive serologic screening and prophylaxis have the same drawbacks. Educating young women to avoid infection is an inexpensive, low-risk intervention that would be the preferred preventive strategy if it could be shown to be effective. Immunization may prove to be the most cost-effective method of preventing congenital toxoplasmosis if a safe and effective vaccine is developed.