Tuberculosis remains a major global public health problem despite the modest infectious disease control efforts. Timely and accurate diagnosis is pivotal to the reduction in tuberculosis related morbidity and mortality. In addition, drug resistant form of tuberculosis is a serious threat to the efforts at tuberculosis control and eradication. Hence; there is the need for efficient methods of Mycobacterium tuberculosis infection diagnosis and treatment. There are major advances in the laboratory diagnostic methods for detection of Mycobacterium tuberculosis which seeks to complement or replace the existing conventional methods in a view to reduction in under-diagnosis and improved infectious disease management. Chest computer tomographies, Cephid GeneXpert, Line probe are some of the Mycobacterium tuberculosis diagnostic advances while chest x-ray, sputum microscopy/culture represent some of the conventional methods of evaluation of both Mycobacterium tuberculosis infection and its multi-resistant strain. Intriguingly, the conventional tuberculosis diagnostics though time consuming and inefficient, its use still predominates in high disease burden settings. Meanwhile, the slow transition to use of advanced tuberculosis diagnostic methods seems to have an economic undertone. The seemingly lack of cutting edge advanced Mycobacterium tuberculosis diagnostics in high disease burden countries is attributable to their suboptimal health financing model and over reliance on the donor organizations thereby retarding progress in tuberculosis eradication.
Tuberculosis is a chronic granulomatous bacterial infection with a global occurrence [1, 2, 3]. This preventable and curable infectious disease has afflicted man since antiquity . Many parts of the world especially the developing nations are still witnessing a rise in the number of new tuberculosis cases with its attendant consequences . This rising prevalence trend of
Estimates have it that every minute someone somewhere gets infected with
The current epidemiological profile of tuberculosis in Sub-Saharan Africa seems to have an established association of the disease with poverty and social deprivation [3, 5, 8]. Similarly, the burden of tuberculosis remains an obstacle to socioeconomic development with a staggering direct and indirect cost of health financing [3, 9, 10]. The relationship between tuberculosis and social deprivation in addition to the adverse socioeconomic developmental effect of tuberculosis creates a vicious cycle of disease, poverty and poor productivity among the most disadvantaged in the society.
The main stay of
2. Aim and objectives
This chapter is an exploratory study of existing tuberculosis diagnostics aimed at highlighting the conventional and advanced methods of
This chapter is a descriptive research on the evolutionary trend of tuberculosis diagnosis. Available literature would be used to identify existing methods of
4. Literature review
4.1 Global burden of tuberculosis
World Health Organization reported that 6.3 million cases of tuberculosis were notified in 2016 which might be under-estimation owing to the non-health seeking behavior and poor documentation in some regions . This tuberculosis epidemiological pattern calls for sustained surveillance and prompt treatment to improve the disease related morbidity and mortality .
The rising number of drug-resistant form of tuberculosis poses an additional challenge on the inadequate resources allocated to healthcare delivery. In the year 2015, over 100 countries reported extensively drug-resistant tuberculosis . Estimates by the WHO revealed that 490,000 individual developed multidrug-resistant tuberculosis in the year 2016 and only a fraction received treatment . The threat of drug-resistant tuberculosis as affirmed by 2016 global report on tuberculosis may possibly be a consequence of inappropriate anti-tuberculosis medication use . This emerging menace of drug resistant tuberculosis if not properly managed could retard the progress made in the fight against tuberculosis.
The global distribution of tuberculosis infection is in close association with poverty, immunosuppression and social deprivation [3, 5, 8, 17]. Sub Saharan Africa has the world highest tuberculosis incidence of 356 per 100,000 populations per year [2, 3]. Similarly, the social and clinical determinants of tuberculosis which include HIV infection, diabetes mellitus, under-nutrition, migration and smoking have been reported to preferentially afflict the young adult population [3, 5]. Nevertheless, tuberculosis infection generally has no age, gender, racial or regional bias.
Mycobacteria consist of different pathogenic and saprophytic mycobacteria species that are isolated from humans and the general environment [18, 19]. The two broad groups of mycobacteria which are tuberculous and non-tuberculous mycobacteria share some features but are largely distinguishable by molecular analysis and the utilization of some microbiological test which include niacin reduction test, nitrate test, and urease test [18, 19]. Lack of identification of the species of mycobacteria infection from the outset has a clinical, management and prognostic implication. The importance of mycobacteria speciation lie in their differing epidemiology, response to anti-tuberculosis, course of disease and long term consequences [18, 19].
4.2 Pulmonary and extra-pulmonary tuberculosis
Literally, tuberculosis could affect any organ system of the body and clinical presentation depends on the site of involvement. The human host immune system influences the clinical pattern of tuberculosis presentation. Tuberculosis is generally described as pulmonary if it involves the lungs and extra-pulmonary when there is involvement of other body parts excluding the lungs [8, 20]. This disease has also been described as latent tuberculosis and active/open tuberculosis.
Research has shown that 95% of primary
Clinical manifestations of tuberculosis are body site-specific but may be sub-clinical thereby posing a diagnostic challenge with frequent missed clinical cases. Commonly, patients with tuberculosis have constitutional symptoms in addition to body site specific symptom(s) [8, 23, 24, 25]. The diagnostic challenge of tuberculosis is frequently observed among children and the elderly probably due to their unique immune constitution and the nature of their airway defense mechanism [22, 25, 26].
Clinical manifestation of pulmonary tuberculosis serves as a prototype of
The physical examination equally poses an additional diagnostic challenge as clinical findings could be non-specific and unhelpful in diagnosis. Pulmonary tuberculosis patients usually have respiratory system specific clinical signs of disease or complication that include crepitation, bronchial breath sound, amphoric adventitious sound and pleural rub [23, 24, 25]. Noteworthy is the clinical manifestation of extensive lung destruction by way of fibrosis and contraction of lung volume .
4.3 Tuberculosis detection methods
4.3.1 Sputum microscopy/culture
The goal of investigation is to make a speedy, definite and accurate diagnosis of
Sputum microscopy (Ziehl Neelsen) is a common method for microbiological profiling of
Although, sputum microscopy is cheap and can be rapidly performed, it is operator dependent and its cost-effectiveness is marred by a decreased sensitivity in pauci-bacillary states . This diagnostic limitation has made extra-pulmonary tuberculosis difficult to diagnose. The rate of false-positive results and inter-operator differences in reportage of sputum microscopy has also compelled the need to recognize molecular based investigation (Cephid GeneXpert) as the first line investigation for tuberculosis [15, 31]. Sputum microscopy is likely to continuously be a cornerstone investigation in the evaluation of tuberculosis patient in the resource constraint nations going by its cost-effectiveness. Hence, the need to improve its operational capacity by way of research and development.
Sputum culture for
Mycobacteria solid culture media which is typified by Lowenstein, Stonebrink, or Ogawa medium is the predominant and sometimes the only form of culture used in evaluation of tuberculosis [15, 32]. This mycobacteria culture is cheap, limits contamination but slow taking about 4–8 weeks to detection of culture growth. The merits of mycobacteria solid media culture is beclouded by the long transition to diagnosis which is inimical to tuberculosis control because it delays commencement of treatment. In contrast, liquid media which is represented by Bacteria Mycobacterial Growth Indicator Tube 960 and MB/Bact Alert 10 3D is more sensitive, faster in detection of growth and the gold standard for mycobacteria isolation . The study by Munyati et al., estimated cost of mycobacteria liquid culture (1–3 culture) to be in the range of $53–$163 . By this estimated cost it is considered to be impracticable to recommend mycobacteria liquid media culture in resource limited setting despite its cost-effectiveness in
4.3.2 Radiologic study
Radiographic profiling for tuberculosis is an indispensable investigation in the evaluation of infected patients. This investigative modality had a remarkable evolution from the use of the x-rays to the use of advanced imaging modalities which include the computer tomographic scan thereby upping the radiographic sensitivity and specificity [25, 30].
A normal x-ray does not rule out tuberculosis, and no radiological finding is a sine qua non for tuberculosis. This reality poses a diagnostic challenge for health care providers especially in the evaluation of tuberculosis among the immune-compromised. The x-ray imaging findings are predominantly abnormal in pulmonary tuberculosis among the immune-competent [30, 33]. The upper zone and apical lobe of the lower zone of the lungs are areas of predilection in pulmonary tuberculosis . In pulmonary tuberculosis, the commonest x-ray manifestation is parenchyma involvement which is depicted by linear opacities, cavitations and military shadows . Pleural effusion, pleural thickening, lymphadenopathy, and tuberculoma are the other extra-pulmonary manifestations that could be evident on the chest radiographic examination.
Following chronic inflammation from
Chest computer tomography (CT) provides a diagnostic advantage in detecting fine and equivocal lesions among tuberculosis patients when compared with x-ray films . The findings on chest CT which could represent an active disease or disease complications include features suggestive of consolidation, fibrosis, cavitations and honey combing . Similarly, the chest CT provides a clearer view of extra-pulmonary involvement of
4.3.3 Molecular methods
Tuberculin skin test for the latent tuberculosis is an ancient molecular investigation that still reserves a place in clinical practice . A major drawback of tuberculin skin test is its inability to differentiate the latent tuberculosis from an active disease. This diagnostic drawback has a therapeutic and prognostic implication. Line probe assay and Cephid GeneXpert System are the other advanced molecular investigations that have enabled detection of drug resistant tuberculosis . Cephid GeneXpert System has been recommended as the first choice tuberculosis investigation especially among suspected cases of multidrug resistant disease [34, 35]. This decision may have been predicated on the suitability of Cephid GeneXpert System for use in resource limited environment due to its adequate sensitivity, specificity and the minimal technical knowhow for its operation [34, 35]. However, this guideline should be cautiously recommended for developing nations because they may not cope with its financial implication.
Lipoarabinomannan (LAM) assay in urine has been commercially available for over 20 years but its deployment for use in tuberculosis diagnostics is slow . This molecular investigation is a point-of-care assay that enables detection of LAM which is a mycobacterial cell wall glycolipid antigen [36, 37]. Lipoarabinomannan assay in urine has enabled diagnosis of disseminated tuberculosis especially in pauci-bacillary state and among HIV patients. A meta-analytic study has reported a sub-optimal sensitivity for LAM assay in urine . However, subsequent improvement in LAM assay in urine by way of development of strip test version of this molecular investigation improved its sensitivity, specificity and cost-effectiveness.
4.3.4 Immunological methods
Immunological investigations for active tuberculosis include nucleic acid amplification tests and bacteriophage-based tests. These immunological investigations have allowed detection of nucleic acid sequence of
In contrast to smear microscopy/culture, nucleic acid amplification test has a greater positive predictive value (>95%), increase specificity and ability for rapid confirmation of infection . Nevertheless, the smear microscopy/culture still has relevance in modern clinical practice because of its high sensitivity and utility when drug sensitivity test of second line anti-tuberculosis is required .
In conclusion, there is need to complement and replace where necessary the conventional tuberculosis diagnostics with advanced cutting-edge microbiological, imaging, molecular and immunologic investigations for prompt and adequate diagnosis. The diagnostic and therapeutic advantages of advanced methods of mycobacteria detection call for its speedy deployment to priority areas to enhance accuracy and efficiency of clinical evaluation. The cost of procurement and maintenance of this advanced methods of tuberculosis diagnosis maybe beyond the reach of the health care systems of nations with high burden by tuberculosis. Hence, the reason why donor funding is crucial in provision and maintenance of advanced molecular and immunological tuberculosis diagnostics in high disease burden areas especially in sub-Saharan Africa [40, 41].