Diagnosis of opportunistic infections: HIV co-infections - tuberculosis.

PURPOSE OF REVIEW: Tuberculosis (TB) incidence has declined ∼1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or underreported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for antiretroviral therapy initiation. This review describes advances in diagnosing TB, especially among HIV co-infected individuals, highlights national program's uptake, and impact on patient care. RECENT FINDINGS: The TB diagnostic landscape has been transformed over the last 5 years. Molecular diagnostics such as Xpert MTB/RIF, which simultaneously detects Mycobacterium tuberculosis (MTB) resistance to rifampicin, has revolutionized TB control programs. WHO endorsed the use of Xpert MTB/RIF in 2010 for use in HIV/TB co-infected patients, and later in 2013 for use as the initial diagnostic test for all adults and children with signs and symptoms of pulmonary TB. Line probe assays (LPAs) are recommended for the detection of rifampicin and isoniazid resistance in sputum smear-positive specimens and mycobacterial cultures. A second-line line probe assay has been recommended for the diagnosis of extensively drug-resistant (XDR)-TB Assays such as the urine lateral flow (LF)-lipoarabinomannan (LAM), can be used at the point of care (POC) and have a niche role to supplement the diagnosis of TB in seriously ill HIV-infected, hospitalized patients with low CD4 cell counts of less than 100 cells/µl. Polyvalent platforms such as the m2000 (Abbott Molecular) and GeneXpert (Cepheid) offer potential for integration of HIV and TB testing services. While the Research and Development (R&D) pipeline appears to be rich at first glance, there are actually few leads for true POC tests that would allow for earlier TB diagnosis or rapid, comprehensive drug susceptibility testing, especially when considering the very high attrition rates observed between biomarker discovery and product market entry. SUMMARY: In this review, we describe diagnostic strategies specifically for HIV and TB co-infected individuals. Molecular diagnostics in particular within the past 5 years have revolutionized and 'disrupted' this field. They lend themselves to integration of services with platforms capable of polyvalent testing. Impact on patient care is, however, still debatable. What has been highlighted is the need for health system strengthening and for true POC testing that can be used in active case finding.

Investigation and diagnosis of nontuberculous mycobacteriosis in a captive herd of aoudad (Ammotragus lervia).

An epizootic of nontuberculous mycobacteriosis occurred in a captive herd of aoudad (Ammotragus lervia) over a period of 18 mo. Each of the affected animals was subject to a thorough postmortem examination that included histopathology, tissue concentration and acid-fast staining, aerobic and anaerobic bacterial culture, mycobacterial culture, and real-time polymerase chain reaction specific for Mycobacterium tuberculosis DNA. Histopathologic lesions consistent with pulmonary mycobacteriosis, including the presence of acid-fast bacteria, were identified in two captive adult male aoudad. M. avium was isolated in culture from the pulmonary parenchyma, and M. parafortuitum was isolated from a mesenteric lymph node of a third animal, an adult female, euthanized subsequent to an illness characterized by progressive dyspnea and tachypnea. M. intracellulare was isolated within the bronchial lymph node of a fourth aoudad, an adult female that was euthanized due to chronic weight loss. Diagnostic testing of the 34 individuals in the herd included collection of blood for an interferon-gamma assay, intradermal tuberculin testing, and radiometric fecal culture for M. avium subsp. paratuberculosis. On the basis of this investigation, mycobacteriosis associated with M. bovis, M. tuberculosis, and/or M. avium subsp. paratuberculosis was ruled out and nontuberculous mycobacteriosis was confirmed in this herd.

Evidence of primary transmission of multidrug-resistant tuberculosis in the Western Province of Papua New Guinea.

OBJECTIVE: To review patient outcomes and the molecular epidemiology of multidrug-resistant tuberculosis (MDR-TB) strains isolated from patients living in the Western Province of Papua New Guinea (PNG) seeking treatment in Australia. DESIGN, SETTING AND PARTICIPANTS: Review of all cases of MDR-TB among people living in the open border region between the Western Province of PNG and the Torres Strait Islands of Australia who presented to health clinics in the region between 2000 and 2006. All cases of suspected TB were bacteriologically confirmed at the time of presentation by the Mycobacterium Reference Laboratory in Brisbane. MAIN OUTCOME MEASURES: Drug resistance patterns; drug use and duration; molecular typing of TB strains; patient outcomes. RESULTS: Between 2000 and 2006, 60 patients from the Western Province of PNG were diagnosed with TB, of which 15 had MDR-TB. Mortality was high, although no patient who was able to maintain access to supervised therapy died. All 15 MDR-TB isolates were Beijing-family strains showing the same unique mycobacterial interspersed repetitive unit (MIRU) profile, with the exception of a single strain that differed by a single repeat at one locus. Restriction fragment length polymorphism (RFLP) typing on 10 of these strains further differentiated them into two distinct clusters. CONCLUSION: Transmission of MDR-TB is occurring in the Western Province of PNG. Additional resources are urgently needed to interrupt the ongoing transmission of MDR-TB from the Western Province of PNG to the Torres Strait Islands. Good supervision and management of patient treatment, which includes ensuring a regular supply of second-line anti-TB drugs, are essential elements of TB control.

Nocardia paucivorans--a cause of disseminated nocardiosis.

We describe a 53-year-old man without discernable immunocompromise who presented with cerebral and cutaneous dissemination of primary pulmonary Nocardia paucivorans infection. This report also identifies 32 other patients in our health area with clinical isolates of N. paucivorans over the last 20 years, extending the reported spectrum of disease caused by this organism. At least 30% (10/33) of these patients had disseminated disease indicating a propensity of this species to disseminate.

Failure of commercial ligase chain reaction to detect Mycobacterium tuberculosis DNA in sputum samples from a patient with smear-positive pulmonary tuberculosis due to a deletion of the target region.

We report on a strain of Mycobacterium tuberculosis with a deletion in the protein antigen B gene overlapping the probe binding sites for the Abbott Diagnostics LCx M. tuberculosis (LCx-MTB) probe assay. A false-negative result with the LCx-MTB assay delayed a laboratory diagnosis of tuberculosis.