Treatment of Latent TB

Treatment of latent tuberculosis infection: An update. 

Lobue. Respirology (2010) 15, 603–622

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1843.2010.01751.x/abstract


This article provides a good review of existing trials conducted on the efficacy, safety, cost effectiveness, and compliance of latent TB treatment regimens. 


The author concludes that: 

As long as 9months INH remains the standard therapy, LTBI treatment will remain expensive with a greater than desirable risk of adverse events and have suboptimal public health impact, because of poor acceptance by many patients and providers. At the moment, this regimen is considered the regimen of first choice, but two acceptable alternatives are 4 months of INH plus rifampin or 4 months rifampin mono-therapy. Of the two alternatives, the 2-drug regimen has been tested in more trials, and has equivalent completion, toxicity, and effectiveness as 6–9 months INH. Therapy with 4 months rifampin alone has significantly better completion, and signifi- cantly lower toxicity than INH. These are very impor- tant advantages, but effectiveness remains uncertain as this regimen has not been tested as extensively in randomized trails. 

Treatment for people with exposure to MDR-TB remain poorly studied. Current recommendations (CDC and Francis J. Curry National Tubercu- losis Center) are based on expert opinion of likely susceptible drugs based on MDR-TB's resistance patterns but are not evidence-based; there have been no clinical trials for the use of these regimens in contacts of patients with MDR TB. 

CDC Guideline:

Candidates for the Treatment of LTBI

Persons in the following high-risk groups should be given treatment for LTBI if their reaction to the Mantoux tuberculin skin test is ≥5mm:

• HIV-infected persons
• Recent contacts of a TB case
• Persons with fibrotic changes on chest radiograph consistent with old TB
• Patients with organ transplants
• Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF-aantagonists)

In addition, persons in the following high-risk groups should be considered for treatment of LTBI if their reaction to the Mantoux tuberculin skin test is ≥10 mm:

• Recent arrivals (< 5 years) from high-prevalence countries
• Injection drug users
• Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities)
• Mycobacteriology laboratory personnel
• Persons with clinical conditions that make them high-risk
• Children under 4 years of age, or children and adolescents exposed to adults in high-risk categories

Has Oseltamivir Been Shown to Be Effective for Treatment of H5N1 Influenza?

EDITORIAL COMMENTARY

Has Oseltamivir Been Shown to Be Effective for Treatment of H5N1 Influenza?

http://www.journals.uchicago.edu/doi/full/10.1086/656317
This issue of JID features an article by Adisasmito et al. It reviews previous clinical report, case series etc to determine whether oseltamivir is effective for treatment of H5N1 influenza.

In total, 308 cases were identified from 12 countries: 41 from Azerbaijan, Hong Kong SAR, Nigeria, Pakistan, and Turkey (from clinical records); 175 from Egypt and Indonesia (from various sources); and 92 from Bangladesh, Cambodia, China, Thailand, and Vietnam (from various publications). Overall crude survival was 43.5%; 60% of patients who received 1 dose of oseltamivir alone (OS⁺) survived versus 24% of patients who had no evidence of anti‐influenza antiviral treatment (OS⁻) ( ). Survival rates of OS⁺ groups were significantly higher than those of OS⁻ groups; benefit persisted with oseltamivir treatment initiation 6–8 days after symptom onset. Multivariate modeling showed 49% mortality reduction from oseltamivir treatment.

It is interesting to note that 14 cases in the Adisasmito report were treated with higher than standard dosages and 7 (50%) survived; 20 were treated for longer than 5 days (median, 7 days) and 15 (75%) survived. In view of the need for better treatment and the safety data available on higher dosages (150 mg twice daily) and longer durations of oseltamivir treatment, it seems reasonable to adopt the WHO proposed treatment of a higher dosage and duration of 10 days for H5N1 influenza and possibly all cases of influenza pneumonia. Finally, parenteral treatment with either the unapproved peramivir or zanamivir preparations may be best for this severe disease.

In summary, the combined experience with oseltamivir treatment by Adisasmito et al supports the belief that oseltamivir given orally at approved dosages for 5 days is beneficial for treatment of H5N1 influenza, particularly if treatment is started early in the course of illness. However, improvement in therapy is needed, and available data suggest oral therapy with a higher dosage (150 mg twice daily) and a longer duration (7–10 days) or parenteral therapy with peramivir or zanamivir are likely to improve on the standard oral oseltamivir treatment regimen.

Mycology online - good collections of fungus database including pictures

Webpage - Mycology online published by University of Adelaide.
It contains photo gallery of fungus, description, identification, laboratory methods, and guidelines for therapy
http://www.mycology.adelaide.edu.au/

Survival of Hep C in syringes may explain high transmission amongst IVDUs

An article in JID published by Paintsil et al. 2010 hypothesized that the efficient transmission of HCV among IDUs may be partly due to the ability of the virus to remain viable in contaminated syringes for prolonged periods. (It is estimated that the probability of transmission of HCV per exposure to a contaminated syringe is 5‐fold to 20‐fold higher than that of HIV transmission).  

To test this hypothesis, they developed a microculture assay that allowed us to propagate HCV from small residual volumes contained in the dead space of syringes used by IDUs, and to determine the effects of storage at different temperatures for prolonged periods on the viability of HCV in syringes.

The authors found out that Insulin syringes failed to yield viable HCV beyond day 1 at all storage temperatures except 4°, in which 5% of syringes yielded viable virus on day 7; Tuberculin syringes yielded viable virus from 96%, 71%, and 52% of syringes after storage at 4°, 22°, and 37° for 7 days, respectively, and yielded viable virus up to day 63. 

Conclusions.The high prevalence of HCV among injection drug users may be partly due to the prolonged survival of viruses in syringes and the syringe type. . Our findings may be used to guide prevention strategies.

Further studies are also needed to determine whether higher HCV transmission amongst IVDU are due to differences in viral infectivity / inoculum size required to cause infection.  

http://www.journals.uchicago.edu/doi/full/10.1086/656212

Pneumococcal vaccination in HIV infected adults - would choice of vaccine differ?

J Infect Dis. 2010 Oct 1;202(7):1114-25.
http://www.ncbi.nlm.nih.gov/pubmed/20795819

In HIV infected patients, risk of pneumococcal infection is high and vaccination is recommended.  
The 23-valent pneumococcal vaccine is generally recommended for HIV-infected patients - previously recommended for patients with CD4 counts ≥200 cells/mm³, studies evaluating its efficacy have yielded mixed results (ACC Sep 1 2000, Jan 1 2001, and Jul 27 2005). Then, a study from AIDS clinical care suggested that protection benefit may be greatest in patients with CD4 <200 (http://www.medscape.com/viewarticle/563686). 


Nevertheless, immune response, even after revaccination with the 23-valent polysaccharide vaccine (PPV) are low among human immunodeficiency virus (HIV)-infected adults.

This study determined whether revaccination with the 7-valent pneumococcal conjugate vaccine (PCV) would enhance these responses.  HIV patients (median CD4 533cells/mm3 who's had PPV 3 - 8 years earlier were compared with non-HIV infected population, revaccinated wtih PCV or PPV.

RESULTS: HIV-infected persons demonstrated a higher frequency of positive antibody responses to PCV than to PPV (57% vs 36%) (P = .004) and greater mean changes in the immunoglobulin G concentration from baseline to day 60 for serotypes 4, 9V, and 19F (P < .05, for all), but not for serotype 14. However, by day 180, both outcomes were similar. Responses to PCV were greater in frequency and magnitude for all serotypes in HIV-uninfected adults, compared with those in HIV-infected adults.

CONCLUSIONS FROM AUTHOR: Among persons with HIV infection, revaccination with PCV was only transiently more immunogenic than PPV, and responses were inferior to those in HIV-uninfected subjects with primary vaccination. Pneumococcal vaccines with more robust and sustained immunogenicity are needed for HIV-infected adults.

What does the current 2009 AIDS guideline say:
Guideline now recommends pneumococcal vaccination when CD4 <200, but efficacy is not yet fully established. Re-vaccination after immune reconstitution CD4>200 can be considered but efficacy and duration of protection is not fully known. Revaccination every 5 years may be considered although definite data supporting this recommendation is lacking.

Use of HPV vaccine in HIV-infected men - Journal of Infectious Diseases

By Wilkin et. al. 2010

Use of HPV vaccine in men should be considered to prevent development of HPV related anal cancers. A

a single‐arm, open‐label, multicenter clinical trial was performed to assess the safety and immunogenicity of the quadrivalent HPV (types 6, 11, 16, and 18) vaccine in HIV‐1–infected men. 

Men with high‐grade anal intraepithelial neoplasia or anal cancer by history or by screening cytology or histology were excluded. Men received 0.5 mL intramuscularly at entry, week 8, and week 24. The primary end points were seroconversion to vaccine types at week 28, in men who were seronegative and without anal infection with the relevant HPV type at entry, and grade 3 or higher adverse events related to vaccination.

Results showed that vaccine was well tolerated, and showed successful seroconversion: for all 4 types: type 6 (59 [98%] of 60), type 11 (67 [99%] of 68), type 16 (62 [100%] of 62), and type 18 (74 [95%] of 78). No adverse effects on CD4 counts and plasma HIV‐1 RNA levels were observed.

Conclusions.The quadrivalent HPV vaccine appears safe and highly immunogenic in HIV‐1–infected men. Efficacy studies in HIV‐1–infected men, especially in preventing anal cancer, are warranted.   

http://www.journals.uchicago.edu/doi/abs/10.1086/656320

Good Medical PodCasts

These are free PodCasts that can be downloaded from the itunes, featuring online audio summaries of the latest launched medical journals. 

In Singapore however access to Podcasts are restricted. 

You can overcome this by signing up a 'UK / US account', and then search for these items for download. 

Alternatively, you can visit the journal's official website and listen online, for some of them.  

• USF Division of Infectious Diseases PodCst
• SCCM PodCast - iCritical Care
• New England Journal of Medicine
• JAMA
• Lancet Infectious Diseases
• Lancet
• BMJ

Candida Score (CS) for discriminating between candida colonisation and invasive candiasis (non neutropenic patients)

Leon.C et al. Crit Care Med 2009; 37: 1624-1633

A prospective multi-centre study assessing the usefulness of CS for discriminating between candida spp. colonisation versus invasive candidiasis (IC) in non neutropenic and critically ill patients, enrolled 1107 patients admitted for at least 7 days. 

Fungal diagnosis was confirmed based on cultures, serum 1-3-beta-D-glucan adn anti-candida antibodies (some patients). 

Score: (0 = absent, 1 = present)

TPN 1

Surgery 1

Multifocal colonisation 1

Severe sepsis 2

CS >3 is at increased risk of IC (8.5%); with sensitivity 77.6% and specificity 66.2%, Positive predictive value 13.8%, and negative predictive value 97.7%. 

Early antifungal therapy may be considered. 

Risks of higher scores: 4 (16.8%); 5 (23.6%). 

Risk is 2.3% only, if score <3 and author concludes that IC is highly improbable in such patients.

http://www.ncbi.nlm.nih.gov/pubmed/19325481

Ventilator management for hypoxemic respiratory failure attributable to H1N1 novel swine origin influenza virus

Ramsey.C.D. et al. Critical Care Medicine 2010: 38

This article looks into patients who develop severe respiratory failure from pandemic Novel H1N1 influenza needing mechanical ventilation.

Mechanical ventilation using lung-protective strategy and previous trials including the ARMA trial/ ARDS Network protocol, were reviewed here: with low tidal volumes (Vt 6ml/kg), plateau pressures (<30 - 35cm H2O), and optimal PEEP aiming SpO2 88-90%.  However, trials are lacking in H1N1 patient groups and the author comments that physician preference on ventilator settings vary.

In some patients with severe persistent hypoxaemia (SpO2 <88-90% with high PEEP and FIO2>0.8), alternative methods of ventilation are discussed, such as high-frequency oscillatory ventilation (HFOV), airway pressure release ventilation, and prone positioning, are reviewed.  At present, data of each of these methods are still very limited thus choice depends on perceived benefit v.s. risks.

The author discouraged the use of NIV, as it was not successful in the majority of severe hypoxia from H1N1 and majority of patients still required mechanical ventilation eventually.  There has been concerns that NIV can increase the risks of H1N1 transmission by generating more aerosol.  It "may be considered for patients with milder disease whose anticipated need for ventilatory support is short".  The author explained the reason for poor results of NIV in critically ill patients may be due to greater proportion of type 1 than type 2 respiratory failure, as NIV demonstrated more consistent benefit in avoiding intubation among patients with hypercapnic as opposed to hypoxaemic respiratory failure (e.g. CCF, COPD exacerbations, pulmonary edema, and immunocompromised).

http://journals.lww.com/ccmjournal/Fulltext/2010/04001/Ventilator_management_for_hypoxemic_respiratory.8.aspx

Change of Blog Title

Previously this blog was dedicated to MRCP exam resources, but it will be converted to a ID blog from today onwards