Pneumonia continues to exert a terrible toll on health, especially in childhood, where it is the leading infectious cause of death in under-fives. Airborne infections, whether viral, bacterial or fungal, are principally acquired by inhalation of pathogenic organisms, either directly from the environment as spores or attached to dust particles, or within aerosolized droplets and droplet nuclei generated by the respiratory tract mucosa. Some respiratory tract viral infections may also be transmitted by contaminated hands and fomites.
For most of the respiratory viruses the reservoir is human, and there is little demonstration of a capacity to cross species barriers effectively. However, the past 2 decades have witnessed several examples of the potentially devastating effects of cross-species viral transmission: in late 2002 a newly identified animal coronavirus causing a severe acute respiratory syndrome (SARS) gave rise to a major epidemic that disseminated globally through international air travel with alarming rapidity. A decade later another animal virus causing severe respiratory illness was identified in Saudi Arabia—Middle East Respiratory Syndrome coronavirus (MERS-CoV).
These two infections dramatically illustrate the unpredictable epidemic potential of zoonotic viruses that are able to transmit across species barriers and cause human respiratory infection. Indeed, perhaps the most alarming global health threat remains that of a novel transmissible and pathogenic avian influenza strain—for which there are a number of historical pandemic precedents. An array of measures have been developed to limit the pandemic potential of highly pathogenic avian influenza. These include continual sentinel site surveillance, prompt quarantine, flock vaccination and mass culling of domestic poultry when necessary. However, it is clear that humans will continue to be exposed to both old and new zoonotic viral infections for as long as we maintain close exposure to animals.
By contrast, few bacterial pneumonias are zoonotic in origin, the usual reservoir being the respiratory tract of human carriers. Thus, mass population gatherings, whether through displacement caused by strife and famine or voluntary pilgramages such as the Hajj, provide opportunities for transmission and may even play a role in promoting pathogen evolution. Vaccines directed against the virulent bacterial serotypes of Streptococcus pneumoniae have been introduced into mass childhood immunization campaigns, along with vaccines against Haemophilus influenzae serotype B, diphtheria toxin and whooping cough (Bordetella pertussis), and these have impacted significantly on the incidence of severe childhood pneumonia. Understandably, much attention is now focused on the evolution of serotype replacement and switching.
Tuberculosis (TB) is currently the leading infectious cause of death worldwide, with over 10 million estimated new cases in 2016, accounting for 1.4 million deaths. Primarily a disease of lower-income populations, its epidemiological map overlaps with that of HIV infection, particularly in sub-Saharan Africa, and TB causes one-third of HIV deaths. Concerted public health drives have reduced both TB incidence and mortality over the past 2 decades, but enormous challenges remain. Affordable diagnostics are insensitive, treatment courses prolonged, and one-quarter of the world’s population is latently infected and remains at persistent risk of reactivation; most worryingly, the prevalence of multi-drug resistance, with its associated difficulties and costs of treatment, is increasing.
The universal distribution of environmental fungi means that inhalation of spores is an unavoidable occurrence. Subsequent development of systemic and potentially life-threatening disease, however, is dependent upon the burden of exposure, the integrity of host immunity and the pathogenic potential of the particular fungal species inhaled—the epidemiology of which will reflect local climatic and geographical conditions.
Viral Infections
Coronaviruses
Fig. 4.1.
Electron micrograph of severe acute respiratory syndrome-coronavirus (SARS-CoV).
The morphology of an enveloped virus with protruding spikes is characteristic of coronaviruses. SARS-CoV was identified as the causative agent of a novel ‘severe acute respiratory syndrome’ (SARS). Originating in Guangdong Province, China in 2002, the outbreak continued for 8 months before it was contained; the economic cost of the epidemic was estimated at US$40 million.
From Sridhar, S., To, K.K.W., Chan, J.F.W., et al. A systematic approach to novel virus discovery in emerging infectious disease outbreaks. Journal of Molecular Diagnostics, 2015, Volume 17 (3), Pages 230–241 Figure 2. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology.
Fig. 4.2.
Lung changes in severe acute respiratory syndrome (SARS).
SARS in a previously healthy 43-year-old woman with dyspnoea and fever. Coronal CT shows bilateral ground-glass pneumonitis in lower lung zones. By the end of the SARS epidemic over 8000 cases had occurred across 37 countries, spread by global travel and person-to-person transmission. The novel infection carried a case mortality rate of over 9.5%
From Franquet, T. The normal chest. In: Grainger & Allison’s Diagnostic Radiology. 6th edition. Pages 246–266, Figure 12.30. Copyright © 2014 Elsevier Ltd.
Fig. 4.3.
The masked palm civet, Panguma larvata, a possible reservoir of the SARS-CoV.
This animal, a popular local culinary delicacy, was farmed in large numbers in Guangdong Province in 2002 at the time of the SARS outbreak. Although it was implicated as the likeliest original source of the epidemic after isolation of the virus from market animals, the civet probably represented an intermediate conduit from other animal species, including several species of Rhinolophus horseshoe bat, which probably comprise the natural reservoir. As with other zoonotic infections, SARS-CoV is unlikely to be eradicated globally and could still represent a recurrent threat to human health.
Courtesy, China Daily and H. Xiao.
Fig. 4.4.
Camels—a possible reservoir of Middle East respiratory syndrome coronavirus (MERS-CoV).
As with SARS, MERS-CoV is another zoonotic respiratory viral illness where bats have been implicated as the original reservoir, and camels have been proposed as the main zoonotic species providing human exposure. The mechanism of transmission is not yet elucidated, nor whether other animal reservoirs exist, but there are some temporal associations suggestive of a link with weaning of camel foals. Human-to-human transmission of MERS-CoV has occurred primarily in healthcare settings, with a mortality rate exceeding 35% in those with impaired immunity.
Courtesy, L. Freer. From Phillips, L.L. and Semple, J. In Auerbach’s Wilderness Medicine. Pages 617–645, Figure 30–35. Copyright © 2017 Elsevier Inc. All rights reserved.
Fig. 4.5.
Middle East respiratory syndrome-coronavirus (MERS-CoV) in a bronchoalveolar lavage specimen.
MERS-CoV antigen detection using an indirect immunofluorescent antibody stain showing virally infected human airway cells (green staining are MERS-CoV-positive cells, blue staining are uninfected respiratory epithelium). The emergence of a novel pathogen brings special challenges: the development of both an accurate clinical case definition and new diagnostic assays.
From Zumla, A., Hui, D.S., and Perlman, S. Middle East respiratory syndrome. Lancet Volume 386, Pages 995–1007, Figure 2. Copyright © 2015 Elsevier Ltd.
Influenza Viruses
Fig. 4.6.
Domestic ducks in an Asian wet market.
Migratory waterfowl are the natural reservoir for avian influenza viruses that can spread into domestic poultry causing up to 100% flock mortality within 48 hours. Intensive close-contact poultry farming encourages opportunities for viral recombination, mutational events and cross-species transmission; the virulent H5N1 strain caused deaths in 1997 and again in 2004 and 2005 in China and Vietnam, and necessitated destruction of millions of chicken and ducks.
©FAO/Hoang Dinh Nam.
Fig. 4.7.
Raw poultry in a Shanghai market.
The handling of contaminated, uncooked poultry as seen on this market stall, as well as contact with live birds, represents a potential risk for the spread of avian influenza viruses to humans. Infected humans, too, can harbour the virus widely throughout body tissues and fluids, including faeces, indicating a potential for human-to-human spread by fomites in crowded environments.
Fig. 4.8.
Chest radiographs of a child with H5N1 avian influenza.
These chest radiographs demonstrate progressive right lower zone consolidation from Day 5 (A) to Day 8 (B) with extension into the left lung fields.
Courtesy, Dr T. H. Tran and Dr J Farrar.
Henipaviruses
Fig. 4.9.
Pteropus fruit bat (flying fox), reservoir of Nipah virus.
Nipah virus infection was first recognized in Malaysia in 1998, causing an acute form of encephalitis with a mortality rate of about 50%. Occurring especially among pig farmers in a wide geographical area extending from from west Bengal and Bangladesh through to Malaysia and Singapore, the reservoir is the fruit bat. The bats, which appear to be asymptomatically infected, excrete viable virus in their urine and saliva. Pigs are believed to acquire infection by eating contaminated fruit dropped by scavenging bats; in Malaysia it is thought that humans acquired Nipah virus infection through close contact with the pigs, and transmission from farm to farm was primarily by the transport of infected pigs. Control was rapidly effected by using appropriate protective equipment and by a cull of over 1 million pigs. In Bangladesh it is unclear whether humans are infected directly by contact with contaminated foodstuffs or by aerosol of bat urine. An outbreak in Kerala in 2018 highlighted the ongoing potential for emergence of Nipah in new environments within the home range of the Pteropus bats.
Copyright © 2013 Joe Mcdonald, Visuals Unlimited/Science Photo Library.
Hantaviruses
Fig. 4.10.
The deer mouse, Peromyscus maniculatus, reservoir for the North American hantavirus Sin Nombre virus.
Over a dozen different Hantavirus species may cause human disease. Each is associated with a single wild rodent species reservoir. Two forms of acute febrile disease exist: Old World haemorrhagic fever with renal syndrome (HFRS) and New World hantavirus pulmonary sydrome (HPS). Present in the excreta of infected rodents, human transmission is believed to occur primarily through aerosol inhalation. Hantaviruses show tropism for vascular endothelial cells of the heart, lungs, kidneys and reticuloendothelial system causing intense local capillary leak. Organ function support may be required, but no specific antiviral treatment currently exists.
From Shandro, J. R. et al. Wilderness-Acquired Zoonoses. In: Auerbach's Wilderness Medicine 7th edition. Pages 692–728, Figure 34–30. Copyright © 2017 Elsevier Inc. All rights reserved. From Centers for Disease Control and Prevention Public Health Image Library. Courtesy, J. Gathany.
Fig. 4.11.
Acute pulmonary oedema in Hantavirus haemorrhagic fever with renal syndrome (HFRS).
Three chest radiographs of a 21-year-old man who presented with fever, shortness of breath and oliguria. Progressive resolution of the interstitial pulmonary oedema in response to haemodialysis is apparent, over a 10-day period. Day 0 (A), Day 7 (B), Day 10 (C).
From Müller, N. L. and Silva, C. I. S. Imaging of the Chest 1st edition. Pages 391–407, Figure 18.7. Copyright © 2008 Elsevier. Courtesy, Dr. K. S. Lee, Samsung Medical Center, Seoul, Korea.
Measles
Fig. 4.12.
Koplik’s spots.
Koplik’s spots are pathognomonic of measles. They are found on mucous membranes during the prodromal stage and although they may occur anywhere in the mouth, they are most easily detected on the mucosa of the cheeks opposite the molar teeth. They resemble course grains of salt on the surface of the inflamed membrane (arrows). Histologically, the spots consist of small necrotic patches in the basal layers of the mucosa, with exudation of serum and infiltration by mononuclear cells.
From Dockrell, D. H., Sundar, S., Angus, B. J. and Hobson, R. P. et al. Davidson’s Principles and Practice of Medicine. Pages 293–386, Figure 13.7B. Copyright © 2014 Elsevier.
Fig. 4.13.
Typical exanthem of measles.
As the morbilliform rash spreads cephalocaudally from face to trunk and then to the extremities, increasingly irregular macules in the proximal areas become more confluent to leave ‘islands’ of unaffected skin, most easily seen on light skin.
From Dockrell, D. H., Sundar, S., Angus, B. J. and Hobson, R. P. Davidson’s Principles and Practice of Medicine. Pages 293–386, Figure 13.7A. Copyright © 2014 Elsevier.
Fig. 4.14.
Measles in twins.
Measles is one of the most important causes of childhood mortality in the tropics, even though a safe and highly cost-effective vaccine exists. It is estimated that in 1980 measles caused 2.6 million childhood deaths globally, with local epidemics sometimes recording 50% mortality rates; in 2014 the mortality figure had dropped to below 115,000. However given the extreme infectiousness of measles virus, reducing mortality further will depend on ensuring that vaccine coverage includes the 15% of infants who have not even received one vaccine dose by their first birthday. Severe disease tends to occur in malnourished children, and not infrequently precipitates kwashiorkor. The twin on the left shows typical post-measles desquamation but is otherwise recovering. The other twin has post-measles encephalitis.
Courtesy, Professor R. Hendrickse.
Fig. 4.15.
Measles in an African child.
The desquamating skin rash of measles was accompanied by herpes simplex stomatitis and rhinitis in this child, who died from respiratory complications. Streptococcal infections (both S. pneumoniae and S. pyogenes) are associated with post-measles complications.
Courtesy, Professor W. E. Farrar.
Varicella zoster virus
Fig. 4.16.
Disseminated varicella zoster in the context of immune compromise.
Humans are the only known host for varicella zoster virus (VZV) infection. Airborne transmission of the neurotropic virus is highly efficient, with an attack rate of nearly 90% in susceptible household contacts. After the primary manifestation of chickenpox, latent viral infection persists in dorsal root ganglia, but may reactivate presenting as the painful vesicular monodermatomal eruption of shingles. Rarely, multi-dermatomal dissemination occurs, and is strongly associated with compromised cell-mediated immunity, the commonest cause of which globally is HIV-1 infection. Secondary bacterial infection is a common complication, as in this case with peri-oral impetigo.
From Dias, F. M., Marcel, F., Oliveira, J. et al. Exuberant varicella-zoster exanthema and pneumonia as clinical clue for HIV infection. Journal of Pediatrics, Volume 166, Issue 1, Page 199, Figure 1.
Fig. 4.17.
Varicella zoster (VZV) pneumonitis.
Both primary and reactivating VZV infection may include neurological, ophthalmological and visceral complications. VZV pneumonitis, typically occurring within one week after the onset of skin lesions, carries a high mortality rate of up to 40%, and is characterized by a dry cough and increasing dyspnoea. This chest radiograph of the same patient as Fig. 4.16 shows typical multifocal nodular shadowing.
From Dias, F. M., Marcel, F., Oliveira, J. et al. Exuberant varicella-zoster exanthema and pneumonia as clinical clue for HIV infection. Journal of Pediatrics, Volume 166, Issue 1, Page 199, Figure 2.
Bacterial Infections
Pneumococcal Infection
Fig. 4.18.
Streptococcus pneumoniae in sputum.
Microscopy of a Gram-stained sputum sample from a patient with pneumonia, demonstrating the characteristic morphology of Streptococcus pneumoniae bacteria as elongated Gram-positive cocci, usually grouped in pairs and short chains (arrowed). A neutrophil is also visible.
Courtesy, Dr. K. van Horn. From Kumar, V. et al. General Pathology of Infectious Diseases. In: Robbins Basic Pathology, Tenth Edition. Copyright © 2018 by Elsevier Inc. All rights reserved. Figure 9.3.
Fig. 4.19.
Lobar pneumonia.
Chest radiograph demonstrating right upper lobe consolidation with air bronchograms in a 43-year-old woman with lobar pneumonia. Globally, two-thirds of children with bacterial pneumonia fail to access effective low-cost antibiotics, and public health measures have focussed on early breast-feeding, nutritional supplementation, household ventilation improvements and, more recently, immunisation.
From Muller, N. L. High Yield Imaging: Chest. Pages 130–131, Figure 1. Copyright © 2009, Elsevier.
Fig. 4.20.
Pneumococcal meningitis.
Directly stained cerebrospinal fluid from a young infant brought to hospital unconscious after a seizure. Numerous lanceolate (lancet-blade shaped) pneumococci are clearly visible, mostly in pairs and with many displaying the characteristic circumferential ‘halo’ caused by a thick capsule. Neutrophil polymorphs show ingested bacteria.
The incidence of invasive pneumococcal disease is substantially increased in the context of immunosuppression such as uncontrolled HIV infection. Recent introduction of childhood conjugate pneumococcal immunisation schemes directed against the most pathogenic serotypes has profoundly reduced the incidence of invasive disease in both children and adults. The sustained benefit of such vaccine strategies depends on the lesser pathogenicity of the replacement serotypes which become more prevalent through vaccine-induced selective pressure.
Courtesy, Dr. S. Morris-Jones
Meningococcal Infection
Fig. 4.21.
Distribution of the ‘meningococcal meningitis belt’ in Africa.
Until recent immunization initiatives, meningococcal meningitis occured in 2–10 yearly epidemic cycles in the so-called ‘meningitis belt’ of tropical Africa, the zone lying between approximately 5° and 15° north of the equator, which is characterized by an annual rainfall of between 300 mm and 1100 mm. Infection was historically primarily with N. meningitidis serogroup A in this zone, but introduction of the MenAfriVac has dramatically reduced disease incidence due to serogroup A wherever it has been used. In order for the efficacy of vaccination strategies to be sustained, monitoring and vigilance of serogroup switching will be needed. Effective vaccines are currently available against serogroups A, B, C, W135 and Y and can be deployed according to local epidemiology.
From Memish, Z. A., Goubeaud, A., Bröker, M., et al. Invasive meningococcal disease and travel. Journal of Infection and Public Health, 2010, Volume 3, Issue 4, Pages 143–151, Figure 1. Source: WHO, Geneva. http://www.who.int/ith/en/; 2009 [accessed 15.06.10].
Fig. 4.22.
Rash of acute meningococcaemia.
The rash typically consists of irregular, scattered, non-blanching petechiae, which tend to be peripherally distributed. The lesions, variable in size, may be macular, papular or clearly purpuric.
Courtesy, Professor W. E. Farrar.
Fig. 4.23.
Meningococcal septicaemia.
Non-blanching and necrotic lesions on the hand of an African patient with meningococcal septicaemia.
Fig. 4.24.
Subconjunctival petechial haemorrhages.
As early petechial lesions may be masked on pigmented skin, conjunctival examination is frequently rewarding, as in this case where numerous subconjunctival petechiae were visible in a Nigerian boy with meningococcal meningitis and meningococcaemia.
Courtesy, Professor D. A. Warrell.
Fig. 4.25.
Direct microscopy with Gram stain of cerebrospinal fluid.
Neisseria meningitidis is a Gram-negative, bean-shaped diplococcal organism.
Other Bacterial Infections
Fig. 4.26.
Child with subconjunctival haemorrhage due to whooping cough.
Whooping cough is caused by the Gram-negative bacillus Bordetella pertussis, and severe disease occurs mostly in young children and infants. The catarrhal phase is commonly characterized by paroxysms of coughing and apnoea, but frank pneumonia is a relatively frequent complication. Subconjunctival haemorrhages are a common accompaniment of the severe coughing spasms, but the haemorrhages resolve rapidly with recovery. Pertussis has been successfully incorporated into a combined diphtheria and tetanus toxoid vaccine (DTP) as part of the WHO Expanded Programme on Immunization since 1974.
From Sadoh, A. E., Oladokun, R. E. Re-emergence of diphtheria and pertussis: implications for Nigeria. Vaccine, © 2012 Elsevier Ltd, Volume 30, Issue 50, Pages 7221–7228, Figure 1.
Fig. 4.27.
Map showing global diphtheria, tetanus and pertussis (DTP) immunization coverage rates in infants, 2016.
The recommended three-dose primary immunization schedule for DTP has achieved an estimated 86% global coverage. 2017/18 outbreaks of diphtheria in humanitarian crises in war-affected Yemen and Rohingya refugees fleeing Myanmar for camps in Bangladesh reflect inadequate vaccination coverage and ideal conditions for transmission with overcrowding and undernutrition.
Courtesy, World Health Organization; http://www.who.int
Fig. 4.28.
Pseudomembrane in a patient with respiratory diphtheria.
Diphtheria is caused by a potent phage-encoded toxin released from the bacterium Corynebacterium diphtheriae. Infection results in a sore throat with a characteristic leathery grey membrane and typically swollen cervical adenopathy. Occasionally airway obstruction may occur, and systemic effects of the toxin may be life-threatening with cardiac arrhythmias and nerve paralysis. Treatment is with antitoxin and clearance of carriage using a macrolide or penicillin.
From: Guerrant, R. L. Walker, D. H., Weller, P. F. Tropical Infectious Diseases: Principles, Pathogens and Practice. Pages 223–227, Figure 34.3. Copyright © 2011 Elsevier.
Fig. 4.29.
Healing cutaneous diphtheria.
Although usually causing respiratory disease, diphtheria may also be acquired by contact from droplets or contaminated surfaces. Ulcers have characteristic appearance with a rolled crater edge, as in this healing case in a Congolese woman. Her strain was toxigenic but did not produce sufficient toxin to cause systemic disease.
Courtesy, Dr. S. Morris-Jones.
Fig. 4.30.
Rheumatic heart disease of the mitral valve.
Streptococcus pyogenes (Group A Streptococcus) causes bacterial pharyngitis, but may produce the non-suppurative complications of acute rheumatic fever and glomerulonephritis. Rheumatic fever is believed to occur as a result of molecular mimicry: antibodies and T cells raised in response to streptococcal antigens cross-react with human cardiac tissue proteins. The precise role of bacterial and host susceptibility factors remains unclear. Rheumatic heart disease is the leading cause of cardiovascular death during the first five decades of life in low- and middle-income countries. Typical features of chronic rheumatic valvular disease are shown with commissural fusion (arrows) and retraction of the anterior valve leaflet.
From Marijon, E., Mirabel, M., Celermajer, D. S., Jouven, X. Rheumatic heart disease. Lancet, 2012 Volume 379, Issue 9819, Pages 953–964, Figure 2.
Fig. 4.31.
Acute post-streptococcl glomerulonephritis.
Deposition of streptococcal antigens on the glomerular basement membrane lead to antibody-mediated immune complexes and glomerulonephritis. Cutaneous streptococcal strains appear more commonly nephritogenic than pharyngeal strains, although identification of responsible antigens remains elusive. Glomerular microscopy exhibits diffuse endocapillary proliferation and neutrophil infiltration.
After Marsh FP. Postgraduate Nephrology. Oxford: Butterworth Heinemann; 1985.
Fig. 4.32.
Chest radiograph of a patient with Q fever pneumonia.
Coxiella burnetii is an extremely hardy bacterium that causes abortion in ruminant mammals. It is shed into the environment via faeces, urine, milk and placental tissue in which the bacterial burden is particularly high. Bacteria may remain viable for months in soil. Humans become infected by inhalation of infected aerosols, sometimes carried in dust by the wind, and present acutely with pneumonia, often with headache and transaminitis.
Fig. 4.33.
Echocardiogram of Q fever endocarditis.
Individuals with underlying valve disease may develop chronic Q fever endocarditis. Onset may be insidious with worsening heart failure. This archaeologist with mitral valve prolapse had probably been infected during professional digs in the Middle East. Note the thickened posterior mitral valve leavlet (PMVL) compared with the anterior MVL. (Courtesy, Dr. S. Morris-Jones.)
Tuberculosis
The overlap between tuberculosis (TB) and HIV in some, but not all, regions of the world is demonstrated in Fig. 4.34 and Fig 4.35. Integrated control programmes are essential to tackle the bi-directional interaction between these two infections. Incidence rates (cases per 100,000 people per year) as shown in Fig. 4.34 indicate the concentration of disease within countries, but population size will also dictate the absolute number of cases that health systems have to address. China and India account for half of all TB cases globally. Fig. 4.36 highlights the emerging issue of multi-drug resistant TB, the diagnosis and management of which poses additional problems. The countries most affected are frequently those with the least resourced healthcare facilities (Fig. 4.37).
Fig. 4.38.
Positive tuberculin skin test (TST).
Other diagnostic tests provide alternatives to the direct visualization or culture of the M. tuberculosis organism. The tuberculin skin test, usually performed as a Mantoux test and previously as a Heaf (or tine) test, measures the delayed-type hypersensitivity response to an intradermal injection of purified protein derivative (PPD) of M. tuberculosis, and is an indicator of prior exposure to this organism. TST is conventionally injected into the volar surface of the forearm and the site examined 48–72 hours later for induration; this figure shows a positive reaction in a patient with active tuberculosis. In higher-income settings, interferon-gamma release assays (IGRAs) may be preferred to the TST, as they involve a single blood sample and have superior specificity over the TST. Sensitivities of both TST and IGRAs tests are compromised in active infection or immunosuppression.
Courtesy, J. Coronel.
Fig. 4.39.
Mycobacterium tuberculosis in sputum.
Mycobacterium tuberculosis is a remarkable bacterium that may infect any organ of the body; the lungs and associated lymph nodes are most commonly affected, reflecting the initial acquisition route. Diagnosis may be confirmed by the microscopic demonstration of acid-fast bacilli, as seen in this sputum specimen. Microscopy does not provide information on the drug susceptibility of the organism. Images using (A) Ziehl–Neelsen stain, (B) Auramine dye. Auramine staining improves sensitivity when bacillary burden is low, but requires a fluorescent microscope.
B, Courtesy, Dr. S. Morris-Jones.
Fig. 4.40.
Mycobacterium tuberculosis growing on solid medium.
Isolation of dry, beige, crumbly colonies of M. tuberculosis grown from a sputum sample on Lowenstein-Jensen medium. The incubation period for M. tuberculosis on solid media typically takes 10–11 days longer than with liquid culture, but may have lower contamination rates.
Courtesy, S. Froman and A. Gaytan. From Pfyffer, G. E., Inderlied, C., B. (2010). Mycobacteria. In J. Cohen, S. M. Opal, W. G. Powderly (Eds.), Infectious Diseases, Pages 1777-1800, Figure 174.12. Elsevier Ltd.
Fig. 4.41.
Characteristic cording of colonies of Mycobacterium tuberculosis growing in liquid medium in the Microscopic Observation of Drug Susceptibility (MODS) assay.
Colonies of M. tuberculosis are visible in the culture liquid within 7 days of incubation at 37oC. Resistance to first-line anti-tuberculous agents has become an important management issue in some regions (Fig. 4.36), and availability of rapid susceptibility testing is an urgent requirement. The WHO-endorsed non-commercial MODS assay offers low-cost, liquid culture TB detection and rapid drug-susceptibility testing direct from sputum, without the need for a primary isolation and secondary culture. Alternative commercial phenotypic and genotypic methodologies have also been rolled out at scale, yet the delivery of universal drug susceptibility testing remains a distant prospect due to budgetary and infrastructure constraints.
Courtesy, Professor D. A. J. Moore.
Fig. 4.42.
Rapid molecular testing for Mycobacterium tuberculosis.
Development and marketing of a commercial polymerase chain reaction test to detect M. tuberculosis and the principal mutations conferring rifampicin resistance directly from unprocessed sputum samples within 2–3 hours (A) may represent a huge technological advance, but for many low-income settings its impact is limited by the requirement for electricity, capital and recurring costs of equipment and single-use cartridges, and the struggle to link diagnosis to initiation of effective TB treatment. (B).
A, B: Courtesy, Dr. S. Morris-Jones.
Fig. 4.43.
Phlyctenular conjunctivitis.
This rare nodular disorder of the conjunctiva is found in children and young adults and is an allergic response to a sensitizing antigen. A broad range of infectious triggers are recognized, including bacterial, fungal and parasitic helminthic agents. In this 6-year-old girl examination revealed axillary and supraclavicular lymphadenopathy. Acid–fast bacilli were seen on a node aspirate along with granulomata. The ocular abnormalities had completely resolved within 5 weeks of the start of antituberculous therapy.
From Sharma, K., Kalakoti, P., Juneja, R. et al. Re-emphasizing Thygeson’s warning: conjunctival phlyctenulosis as presenting sign of impending clinical tuberculosis. Canadian Journal of Ophthalmology, 2014, Volume 49, Issue 6, Pages e135–e137, Figure 1.
Fig. 4.44.
Pulmonary tuberculosis with cavitation.
Prevention of pulmonary tuberculosis is essential for tuberculosis control, as this is the form of disease responsible for onward transmission of the infection. Infectiousness is dependent on the bacillary burden and the ability to aerosolize infectious droplets. Patients with cavitatory disease on the chest radiograph, as shown here in the right upper lobe, are more likely to be smear-positive on sputum microscopy and to pose a greater infectious risk to their contacts.
Courtesy, UCL Hospitals Radiology
Fig. 4.45.
Chest radiograph of drug-resistant pulmonary tuberculosis.
Resistance of Mycobacterium tuberculosis to rifampicin and isoniazid defines multi-drug-resistant (MDR) tuberculosis. Additional resistance to a fluoroquinolone and one of the class of second-line injectable agents defines extensively drug-resistant disease (XDR-TB), as in the case of this young woman from Mumbai. (Courtesy, UCL Hospitals Radiology.)
Fig. 4.46.
Chest radiograph showing response to treatment.
Chest radiograph of the same patient as Fig. 4.45 after 9 months of treatment. The lung fields have cleared with residual right apical fibrosis and loss of lung volume. Thick-walled cavities may provide barriers to effective drug penetration and surgery is sometimes required. (Courtesy, UCL Hospitals Radiology.)
Fig. 4.47.
Chest radiograph showing right lower zone consolidation and unilateral pleural effusion.
This young woman presented with a month of weight loss and increasing breathlessness. Her unilateral pleural effusion was heavily lymphocytic and, along with pleural tissue and blood, yielded cultures that were positive for Mycobacterium tuberculosis. An HIV test was positive. The strongest risk factor for tuberculosis is infection with HIV (see Fig. 4.34, Fig. 4.35), though diabetes mellitus confers a threefold increase in risk and global prevalence is tenfold greater than HIV and continuing to rise.
Courtesy, UCL Hospitals Radiology.
Fig. 4.48.
Tuberculous cervical lymphadenitis.
The commonest form of extrapulmonary tuberculosis involves the lymph nodes, most often the cervical and supraclavicular nodes. Usually relatively painless, caseating ‘cold abscesses’ may discharge necrotic pus. Lymphoma is one of the most important differential diagnoses.
Courtesy, Dr. W. Newsholme.
Fig. 4.49.
Aspiration of tuberculous supraclavicular abscess.
Aspiration may be performed for immediate symptom relief and, when possible, should be used to confirm the diagnosis and obtain the isolate susceptibility profile.
Courtesy, Dr. W. Newsholme.
Fig. 4.50.
Tuberculous pericarditis.
Tuberculous pericardial involvement often produces a large pericardial effusion in the early stages; subsequent constriction may reduce the heart shadow. This HIV-positive patient presented with fevers, night sweats and shortness of breath. His chest radiograph shows a massively enlarged cardiac shadow and a left pleural effusion; fully drug-susceptible M. tuberculosis was cultured from pericardial fluid and lymph node tissue.
Courtesy, UCL Hospitals Radiology.
Fig. 4.51.
Peritoneal and omental tuberculosis.
This Afro-Caribbean woman presented with signs of small bowel obstruction on a background of a 12-month history of weight loss and altered bowel habit. Appearances at laparotomy were interpreted as disseminated intra-abdominal malignancy. Peritoneal biospies demonstrated necrotizing granulomata, and fully drug-susceptible Mycobacterium tuberculosis was isolated in culture. She made a full recovery on anti-tuberculous therapy. A preoperative CT scan of her pelvis demonstrates a thickened and nodular peritoneum and widespread thickened small intestinal mucosa.
Courtesy, UCL Hospitals Radiology.
Fig. 4.52.
Tuberculosis of the breast.
A lactating mother was thought to have developed a large right breast galactocoele, but CT imaging demonstrated contiguity with a loculated right pleural effusion; culture of the aspirate confirmed the diagnosis of tuberculosis.
Courtesy, UCL Hospitals Radiology.
Fig. 4.53.
Extensive pleuro-vertebral tuberculous disease.
A man with psychiatric illness presented with a large lump over the left side of his back. The CT scan demonstrates the remarkable ability of tuberculosis to track through tissue planes. Although encroaching on the spinal canal, no neurological deficit ensued as the tuberculous abscess tracked from the eroded T8/9 vertebral bodies to pass between the rib spaces and create a large chest wall collection (see Fig. 4.54).
Courtesy, UCL Hospitals Radiology.
Fig. 4.54.
Tuberculous chest wall collection.
Aspiration of several litres of purulent necrotic material yielded a positive culture of Mycobacterium tuberculosis.
Courtesy, UCL Hospitals Radiology.
Fig. 4.55.
Tuberculous psoas abscess.
Abdominal swelling initially mistaken as a fibroid was subsequently found to be an anterior extension of a huge abscess in the left psoas muscle. In most cases of psoas abscess there is also involvement of the lower lumbar spine, since the psoas muscle originates from anterior and lower surfaces of the transverse processes of all lumbar vertebrae. It is unusual for psoas abscesses to present with such prominence anteriorly.
Fig. 4.56.
Bilateral psoas abscesses.
Plain lumbar radiograph shows marked reduction in the size of the L3/4 disc space and prominent bulging psoas shadows.
Courtesy, UCL Hospitals Radiology.
Fig. 4.57.
Spondylodiscitis and psoas abscesses.
Magnetic resonance imaging of same patient as Fig. 4.56 shows the spondylodiscitis and huge bilateral psoas abscesses due to tuberculosis.
Courtesy, UCL Hospitals Radiology.
Fig. 4.58.
Gum hyperpigmentation in Addison’s disease due to tuberculous adrenal involvement.
This patient presented with fever and collapse and was found to be grossly hypoadrenal. Tuberculosis is probably still the commonest cause of hypoadrenalism worldwide; this may often be induced by the initiation of rifampicin therapy, which induces liver enzymes to metabolize glucocorticosteroids more rapidly. The CT scan of this patient’s abdomen showed a large adrenal on the right and calcification on the left.
Fig. 4.59.
Tuberculosis of the spine (Pott’s disease).
The spinal column is a common bony site for involvement by tuberculosis. Vertebral involvement may cause severe deformity as seen in this young African patient.
Courtesy, Professor J. Cohen. From Friedland, J. S. Tuberculosis. In: Cohen, J., Powderly, W., eds. Infectious Diseases. 2nd edition. Edinburgh: Mosby, 2004, Pages 401–418.
Fig. 4.60.
Thoracic spine of patient with Pott’s disease.
Computerized tomographic imaging shows that the kyphosis associated with Pott’s disease is caused by the destruction of the intervertebral disc with consequent loss of disc space and the anterior wedge-shaped erosion of the adjacent vertebral bodies causing angulation (gibbus).
Courtesy, UCL Hospitals Radiology.
Fig. 4.61.
Vertebral body destruction in tuberculosis.
This sagittal view shows collapse of the anterior T6 vertebral body, a T7 intraosseous abscess and a prevertebral inflammatory abscess stripping the longitudinal ligament. The most dangerous consequence of vertebral tuberculosis is involvement of the spinal cord.
Courtesy, UCL Hospitals Radiology.
Fig. 4.62.
Skull MRI cranial tuberculosis.
A taxi driver reported hitting the back of his head and subsequently developing a slowly enlarging non-painful scalp mass. Imaging studies illustrated a mass that had destroyed the occipital bone and was compressing the cerebral cortex. M. tuberculosis was isolated from aspirated necrotic granulomatous tissue.
Courtesy, UCL Hospitals Radiology.
Fig. 4.63.
Chest radiograph in miliary tuberculosis.
Miliary tuberculosis occurs when there is haematogenous spread of mycobacteria. Pulmonary involvement is demonstrated radiographically by bilateral reticulonodular parenchymal shadowing. In the case of this 15-year-old Sudanese boy, there was also a spinal focus as shown in Fig. 4.61.
Courtesy, UCL Hospitals Radiology.
Fig. 4.64.
Pathology of miliary tuberculosis.
Langhans giant cells (larger arrow) are derived from the fusion of epithelioid cells and have multiple nuclei arranged in a characteristic horseshoe shape. Lymphocytes and plasma cells are also present in granulomas, and together surround areas of indistinct caseating necrosis (smaller arrow). (Haematoxylin and eosin stain.)
Fig. 4.65.
Tuberculous meningitis.
In infants, miliary tuberculosis and meningitis have a high mortality. This 3-month-old Nepalese infant with tuberculous meningitis and demonstrating pronounced head retraction died despite intensive anti-tuberculous chemotherapy. Tuberculous meningitis in infants results in permanent neurological sequelae in at least 50% of cases.
Courtesy, Brig. Gen. G. O. Cowan.
Fig. 4.66.
Cerebrospinal fluid (CSF) of patient with tuberculous meningitis.
Bacilli of Mycobacterium tuberculosis can be seen as acid fast bodies in this Ziehl-Neelsen stain of a CSF preparation.
From Thwaites, G. (2014). Tuberculosis In J. Farrar, J. P. Hotez, T. Junghanss, G. Kang, D. Lalloo, N. J. White (Eds.), Manson's Tropical Diseases, Pages 468-505, Figure 40-11C. Elsevier Ltd.
Fig. 4.67.
Tuberculomata and tuberculous meningitis.
Multiple sub-arachnoid tuberculomata developed along the meninges in a patient who had been treated for drug-resistant tuberculous meningitis that required ventriculo-peritoneal shunt insertion. The size of individual tuberculomata may vary over time, and may reflect intracranial paradoxical reactions.
Courtesy, UCL Hospitals Radiology.
Fig. 4.68.
Tuberculous involvement of the brain stem.
Cerebral tuberculosis may mimic neoplasia, as in this patient where stereotactic biopsy confirmed Mycobacterium tuberculosis infection.
Fig. 4.69.
Post-mortem appearance of tuberculosis of the base of the brain.
This post-mortem specimen shows the gelatinous and fibrinous material that collects particularly at the base of the brain in tuberculous meninigitis.
Fig. 4.70.
Chest radiograph with left upper zone plombage.
In Europe and the United States during the era before antituberculous therapy, surgery was sometimes an effective treatment for cavitatory disease. Plombage involved deflation of the infected lung by the extrapleural insertion of acrylic spheres as shown in this radiograph of an elderly English woman.
Courtesy, UCL Hospitals Radiology.
Fig. 4.34.
Estimated global tuberculosis incidence rates for of all forms of tuberculosis, 2016.
From Global Tuberculosis Report, 2017. World Health Organization, Page 31, Figure 3.4. http://www.who.int/tb/publications/global_report/en/
Fig. 4.35.
Estimated global rates of HIV prevalence in active tuberculosis cases, 2016.
From Global Tuberculosis Report, 2017. World Health Organization, Page 32, Figure 3.5 http://www.who.int/tb/publications/global_report/en/
Fig. 4.36.
Percentage of new tuberculosis cases with Rifampicin resistant or multi-drug resistant tuberculosis, 2016.
From Global Tuberculosis Report, 2017. World Health Organization, Page 46, Figure 3.20. http://www.who.int/tb/publications/global_report/en/
Fig. 4.37.
Global distribution of Gross National Income per capita (in US Dollars), 2017.
From The World Bank https://data.worldbank.org/products/wdi-maps
Leprosy
Fig. 4.71.
Global distribution of new leprosy case detection, 2016.
Leprosy is caused by a very slow-growing mycobacterium, Mycobacterium leprae, and is presumed to be transmitted through droplets during close contact. The infection primarily affects the skin, the peripheral nerves, and the eyes, and untreated will cause permanent damage to these organs. Since 1981 multi-drug therapy (MDT) of dapsone, rifampicin and clofazamine has been recommended, and resistance has not been documented to the drugs when used in combination. MDT has been made available free of charge since 1995, and over the subsequent 20 years prevalence rates have dropped by over 99%. The current global strategy is to reduce new acquisiton cases, especially in children, thereby reducing disability. Disease prevalence is disproportionately distributed across the world, with 14 countries responsible for reporting 94% of the global burden and three (India, Brazil and Indonesia) accounting for over 80%. In some small-population countries, transmission appears to remain intense.
From Weekly Epidemiolgical Record, World Health Organization, 2016, Volume 92, Issue 35, Pages 501–520, Map 1.
Fig. 4.72.
The spectrum of immunological reponse to leprosy.
Both the bacteriological and clinical features of infection are determined by the type of immunological response. In tuberculoid leprosy (TT) the cell-mediated immunity TH1-type response is robust and few or no Mycobacterium leprae bacilli are detectable (paucibacillary disease). At the other immunological extreme lies lepromatous leprosy (LL), characterized by a TH2 immune response type, where bacterial clearance is ineffective and lesions are multibacillary. Leprosy bacilli may disseminate widely throughout the body. Whereas the immune response is stable at both of these extremes, most leprosy cases present with features of the immunologically less stable borderline disease (BT, BB or BL), and type 1 leprosy reactions are an important feature.
From Goldman, L., Schafer, A. I. Goldman-Cecil Medicine. Pages 2042–2046, Figure 326-1. Copyright © 2016 Elsevier.
Fig. 4.73.
Mycobacterium leprae bacilli.
Acid–fast bacteria in a slit-skin smear preparation using Ziehl–Neelsen stain. The organism cannot be cultured in vitro; slit-skin smear microscopy and, if available, histology of skin biopsy will supplement clinical diagnosis and aid disease classification. Numerous bacilli are visible in this smear from a patient with lepromatous leprosy.
Fig. 4.74.
Rapid progression of lepromatous leprosy in the era before chemotherapy.
Across societies and throughout history including the present day, leprosy has been associated with profound social stigma, arising from its ability to inflict gross disfigurement and inexorable disability. These photographs from the early 1930s show the dramatic changes in appearance of a 13-year-old Hawaiian over a 2-year period.
From Cruz, A. T. (2019). Leprosy and Buruli ulcer: the major cutaneous mycobacterioses. In J. D. Cherry, G. J. Harrison, S. L. Kaplan, W. J. Steinbach, P. J. Hotez Feigin and Cherry's Textbook of Pediatric Infectious Diseases, Pages 1392–1418, Figure 98-11. Elsevier, Inc.
Fig. 4.75.
Mucosal infiltration and septal destruction in lepromatous leprosy (LL).
Local-level epidemiology demonstrates case clustering within households and families. This suggests that transmission requires close and prolonged exposure and is believed to be via inhalation of infected aerosols. The facial CT scan from this Trinidadian woman with LL showed early destruction of the septal cartilage and pronounced mucosal thickening due to bacillary infiltration. Such patients may shed over 10 million bacilli from nasal secretions each day. Host genetics may also play a role in susceptibility to the development of disease following exposure.
Courtesy, UCL Hospitals Radiology.
Fig. 4.76.
Cutaneous manifestations of lepromatous leprosy (LL).
Numerous ill-defined nodules and poorly demarcated indurated plaques on the arms of a patient with LL. Leprosy patients often first present to healthcare facilities with long-standing skin complaints.
From Fragola, Jr L. A. et al. Dermatology Essentials. Pages 591–602, Figure 62.3B. Copyright © 2012 Elsevier. Courtesy, L. A. Fragola, Jr.
Fig. 4.77.
Facial lepromatous leprosy (LL).
The ‘leonine’ facies of LL caused by extensive bacillary infiltration of the facial dermis; the face of this Ethiopian man demonstrates many characteristic features including skin corrugation from chronic oedema, nodular thickening of the ears, madarosis (loss of eyelashes and eyebrows) and a collapsed nasal septum.
Fig. 4.78.
Histology of a skin nodule in lepromatous leprosy.
This high-power section shows many ‘foamy’ histiocytes. No organisms are visible on staining with haematoxylin and eosin.
Fig. 4.79.
Ziehl–Neelsen staining of a lepromatous leprosy skin nodule.
Appropriate Ziehl–Neelsen staining demonstrates huge numbers of (pink) acid–fast bacilli, many of them packed inside vacuolated macrophages.
Fig. 4.80.
Neuropathic pathology in lepromatous leprosy.
Subclinical peripheral neuropathy occurs earlier in lepromatous than tuberculoid leprosy, with loss of temperature perception one of the modalities first affected. Progressive nerve damage results in a vicious cycle of trauma-related ulcers, infection, followed by bone and tissue loss.
Courtesy, Professor S. Lucas.
Fig. 4.81.
Histology of nerve bundles in lepromatous leprosy.
Neuropathy in lepromatous leprosy is by direct bacillary invasion of the Schwann cells leading to demyelination. Acid–fast bacilli of Mycobacterium leprae are visible in globi (arrowed) within the nerve fibres. (High power x1000, modified Ziehl–Neelsen stain.)
From Kumar, N. et al. Comprehensive electrophysiology in leprous neuropathy – is there a clinico-electrophysiological dissociation?, Clinical Neurophysiology, 2016, Volume 127, Pages 2747–2755, Figure 2F.
Fig. 4.82.
Gynaecomastia in leprosy.
This condition, which is relatively common in adult males with long-standing lepromatous leprosy, follows testicular bacillary infiltration and subsequent atrophy.
Fig. 4.83.
Ocular involvement in leprosy.
Leprosy is a common cause of blindness globally, with 40% of leprosy patients suffering ocular disability. Involvement of the nerves providing muscular innervation leads to miosis, while sensory impairment can lead to corneal ulceration. Conglomerations of dead bacilli may lodge in the anterior chamber and produce pathognomonic ‘iris pearls’; a single such pearl is visible here, accompanied by iris atrophy.
From Salmon, J., Bowling, B. Uveitis. In Kanski’s Clinical Ophthalmology, 8th Edition. Pages 395–465, Figure 11.74C. Copyright © 2016 Elsevier Limited. All rights reserved.
Fig. 4.84.
Clofazimine-induced discolouration in leprosy.
Clofazimine, used as part of multi-drug treatment for lepromatous leprosy, is an iminophenazine dye that discolours the skin purple-grey, as shown in this man’s face.
From James, W. D., Berger, T., Elston, D. Hansen's Disease. In: Andrews' Diseases of the Skin, 12th edn. Pages 331–342, Figure 17.12. Copyright © 2016 by Elsevier, Inc. All rights reserved.
Fig. 4.85.
Lesion of tuberculoid leprosy on the buttock.
A typical lesion of tuberculoid (TT) leprosy in a Nigerian man. The lesion is very well demarcated with an inflamed reddish border surrounding an area of hypopigmentation and loss of sensation. Sweating may also be diminished in the centre of such lesions, which are therefore often slightly drier than the surrounding skin. A slit-skin smear had been performed and was microscopy negative (paucibacillary leprosy).
Courtesy, Dr S. Morris-Jones.
Fig. 4.86.
Ulnar nerve involvement.
Damage to peripheral nerves in tuberculoid leprosy leads to weakness and wasting. As in this case, the paralysis and atrophy of the hand muscles innervated by the ulnar nerve result in the characteristic picture of the ‘main de prédicateur’.
Fig. 4.87.
Loss of extremities in late tuberculoid leprosy.
Neurotrophic atrophy eventually leads to the loss of phalanges, especially following trauma resulting from the anaesthesia. The hands, as seen in this Liberian man, or feet may be affected with devastating implications for function.
Courtesy, Dr S. G. Browne.
Fig. 4.88.
Nerve thickening in tuberculoid leprosy.
The presence of thickened peripheral nerves is a common feature of tuberculoid leprosy. In this Congolese boy, the great auricular nerve is prominent whereas the associated macule overlying the mandible is barely visible.
From Guerrant, R., Walker, D., Weller, P. Tropical Infectious Diseases: Principles, Pathogens and Practice, 3rd Edition. Figure 37.6. Copyright © 2011 Elsevier.
Fig. 4.89.
Nerve bundle in tuberculoid leprosy.
Enlarged nerve fibres in tuberculoid leprosy demonstrating well-formed granulomas, intense cellular infiltration and frank necrosis. (Low power x50, haematoxylin and eosin.)
From Kumar, N. Malhotra, H. S., Garg, R. K., et al. Comprehensive electrophysiology in leprous neuropathy – is there a clinico-electrophysiological dissociation?, Clinical Neurophysiology, 2016, Volume 127, Pages 2747–2755, Figure 2A.
Fig. 4.90.
Borderline tuberculoid (BT) leprosy.
In borderline leprosy more skin lesions are found than in the TT form, but they may still be well demarcated, as on this man’s back. Many patients with leprosy first present with skin complaints that may be misdiagnosed as fungal dermatophyte or treponemal infections.
Fig. 4.91.
Type 1 reversal reaction.
Reversal reactions may occur before, during or after treatment and are commoner in immunologically unstable borderline leprosy. Type 1 reversal reactions are believed to be due to increased cell-mediated recognition, accounting for the sudden and painful increased inflammation in pre-existing skin lesions. There is intense erythema and oedema on this woman's facial plaque.
From Bolognia, J. L., Schaffer, J., Duncan, K., Ko, C. Dermatology Essentials. Pages 591–602, Figure 62.8A. Copyright © 2014 Elsevier.
Fig. 4.92.
Type 2 reversal reaction, erythema nodosum leprosum (ENL).
ENL is believed to be the result of an immune complex-mediated vasculitis. It is characterized by the appearance of an erythematous papulo-nodular rash, usually accompanied by marked systemic upset with fever and arthralgia.
From Fragola, Jr L. A. et al., Dermatology, 3rd edn. Pages 1221–1242, Figure 75.9B. Copyright © 2012 Elsevier. Courtesy, L. A Fragola, Jr.
Fig. 4.93.
Lucio’s phenomenon.
This rare manifestation of lepromatous leprosy is largely confined to Central America. A necrotizing cutaneous vasculitis, it is characterized by crops of bullous and ulcerating nodules.
From James, W. D., Berger, T., Elston, D. Andrews’ Diseases of the Skin, 12th Edition. Pages 331–342, Figure 17.11. Copyright © 2016 Elsevier.
Fungal Infections
Fig. 4.94.
Pneumocystis pneumonia (PCP).
Pneumocystis jirovecii is a major cause of life-threatening pneumonia in patients with reduced cell-mediated immunity, such as those with advanced HIV infection. Chest radiography typically shows bilateral interstitial opacification (‘ground glass’) in the perihilar region with sparing of the peripheral lung fields. Acquisition is inhalational, although the main risks remain unclear. Most of the population have been exposed by late childhood and asymptomatic low-burden lung colonization is common.
Courtesy, UCL Hospitals Radiology.
Fig. 4.95.
Pneumocystis cysts in a bronchoalveolar lavage (Gomori silver stain).
As Pneumocystis jirovecii cannot be cultured, definitive diagnosis is by demonstration of characteristic fungal cysts by methenamine silver stains on deep respiratory tract specimens. Molecular detection methods are in development.
From Fristche, T. Human Immunodeficiency Virus Infection and the Acquired Immunodeficiency Syndrome: Diagnosis and Management. In: Atlas of Sexually Transmitted Diseases and AIDS, 4th edn. © 2010, Elsevier Limited. All rights reserved. Pages 256–286, Figure 15–28. Courtesy, T. Fritsche, Division of Laboratory Medicine, Marshfield Clinic Health System, Marshfield, WI.
Fig. 4.96.
Geographic distribution of the endemic mycoses.
There are two variety forms of Histoplasma capsulatum (var. capsulatum and var. duboisii); they have different geographical distributions and clinical presentations. (From Murray, P.R., Rosenthal, K.S., Pfaller, M.A. (2016). Systemic mycoses caused by dimorphic fungi. In Medical Microbiology, Pages 627-642.Figure 64.2. Elsevier Inc.
Fig. 4.97.
Talaromycosis (penicilliosis) in HIV infection.
The Chinese bamboo rat is the only known non-human host for the dimorphic fungus Talaromyces (formerly Penicillium) marneffei, explaining the restricted geographical distribution of infection. Acquisition is believed to occur when contaminated soil or water is aerosolized and inhaled during heavy rainstorms. Infections in the immunocompromised typically present with respiratory, cutaneous or reticuloendothelial manifestations. Numerous intracellular sepate yeasts are visible in this respiratory specimen. (Wright’s stain.)
From Magill, A. J., Ryan, E. T., Soloman, T., Hill, D. R. Hunter’s Tropical Medicine and Emerging Infectious Diseases. Pages 644–646, Figure 85.4. Copyright © 2012 Elsevier.
Fig. 4.98.
Cutaneous talaromycosis.
Dissemination of talaromycosis (as here), histoplasmosis and cryptococcosis may each produce umbilicated cutaneous lesions that resemble molluscum contagiosum.
From Guerrant, R., Walker, D., Weller, P. Tropical Infectious Diseases: Principles, Pathogens and Practice. Pages 586–588, Figure 87.2. Copyright © 2011 Elsevier.
Fig. 4.99.
Talaromyces marneffei in culture on Sabouraud agar.
Talaromyces marneffei is a dimorphic fungus that exists as a septate yeast at 37oC (A), but as a mould at 25oC producing a distinctive red pigment (B).
A, B Courtesy, Dr S. Morris-Jones.
Fig. 4.100.
Cutaneous histoplasmosis.
Histoplasma capsulatum has a worldwide, primarily temperate distribution and is found in particular abundance in soil contaminated with bat or bird droppings. Presentation is usually with respiratory illness, but may develop into reticuloendothelial system dissemination in the context of immune compromise.
Courtesy, Dr S. Morris-Jones.
Fig. 4.101.
Intracellular Histoplasma capsulatum var. capsulatum.
Histoplasmosis caused by Histoplasma capsulatum var. capsulatum, distributed through North, Central and South America, typically causes a pulmonary syndrome after spore inhalation. Dissemination within the reticuloendothelial system occurs in those with impaired cellular immunity. Yeast forms are clearly visible in this tissue macrophage (Giemsa stain).
From Murray P. R., Rosenthal, K. S., Pfaller, M. A. (2016). Systemic mycoses caused by dimorphic fungi. In Medical Microbiology, Pages 627-642, Figure 64.10. Elsevier Inc.
Fig. 4.102.
African histoplasmosis.
African histoplasmosis, caused by H. capsulatum var. duboisii, produces mostly cutaneous or bony disease with large, destructive lesions.
Fig. 4.103.
Radiograph of pulmonary paracoccidioidomycosis.
Chronic pulmonary Paracoccidioides brasiliensis infection may result in fibrosis and eventual death from respiratory insufficiency.
Fig. 4.104.
Nasal lesions in paracoccidioidomycosis.
Mucosal lesions can affect the nasopharynx with granulomatous infiltration and crusted ulceration.
From Marques, S. A. Paracoccidioidomycosis. Clinics in Dermatology, 2012, Volume 30, Issue 6, Pages 610–615, Fig. 4. Copyright © 2012 Elsevier Inc.
Fig. 4.105.
Pseudotumoural form of paracoccidioidomycosis.
Fifteen years after an oropharyngeal infection, a 57-year-old Brazilian man presented with lumbar pain and massive weight loss. Initial examination suggested a colonic carcinoma, but CT imaging revealed a psoas abscess as well as calcification in the thickened ileocaecal region. Material removed during radical surgery confirmed Paracoccidioides brasiliensis infection.
Courtesy, Dr R. Chojniak and Revista da Sociedade Brasiliera de Medicina Tropical.
Fig. 4.106.
Classic ‘Pilot wheel’ appearance of Paracoccidioides brasiliensis.
Said to be reminiscent of a ship’s steering wheel, the peripheral buds of the yeast form provide a diagnostic appearance when identified in clinical samples.
From Negroni, R., Anstead, G. M., Graybill, J. R. Paracoccidioidomycosis. In: Tropical Infectious Diseases: Principles, Pathogens and Practice. 3rd edition. Pages 582–585, Fig. 86.1. Copyright © 2011, Elsevier Inc. All rights reserved.
Fig. 4.107.
Paracoccidioidomycosis in a Brazilian hild.
In children, Paracoccidioides brasiliensis infection is an infection of the reticuloendothelial system and induces an acquired immunodeficiency. Although rare before adolescence, this 4½-year-old boy demonstrated hepatosplenomegaly, ulcerating lymphadenopathy and generalized emaciation.
Courtesy, Dr G. L. Barbosa.
Fig. 4.108.
Radiograph of coccidioidomycosis.
Persistent left-sided parenchymal infiltration on the radiograph of this 74 year old man with a history of prostatic carcinoma and asbestos exposure. He had also recently visited relatives in Arizona.
Courtesy, UCL Hospitals Radiology.
Fig. 4.109.
Positron emission tomography of pulmonary coccidioidomycosis.
Imaging using a radionuclide glucose analogue provides information of physiological activity. Intense activity is seen in the left lower lobe mass of the same patient as in the previous Fig. 4.108.
Courtesy, UCL Hospitals Radiology.
Fig. 4.110.
Histopathological appearance of Coccidioides immitis in tissue.
The characteristic appearance of a spherical, thick-walled spherule containing small uninucleate endospores is seen on this silver Grocott stain of a biopsy from the pulmonary lesion seen in the previousFig. 4.109.
Courtesy, Dr. U. Mahadeva, Dr. D. Arul.
Fig. 4.111.
Cryptococcal meningo-encephalitis in advanced HIV infection.
Cryptococcus neoformans is a leading infectious cause of both morbidity and mortality in HIV-infected patients. This HIV-positive Zimbabwean man with cryptococcal meningitis has a left sixth cranial nerve paralysis.
Courtesy, Professor D. A. Warrell.
Fig. 4.112.
Cryptococcus neoformans in cerebrospinal fluid.
Cryptococcus neoformans and C. gattii are both encapsulated yeasts that are easily visualized in Indian ink preparations of cerebrospinal fluid (CSF). The organisms may also be cultured from CSF and blood or, more rarely, urine. Cryptococcal antigen agglutination assays perfomed on serum or CSF have been the mainstay of diagnosis, but the recent development of high-quality near-patient lateral flow assays has provided opportunities for screening and earlier case detection for initiation of prompt antifungal therapy.
From Mandell, G., Bennett, J., Doin, R. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. Pages 2934–2948, Figure 264-6. Copyright © 2011 Elsevier.
Fig. 4.113.
Chronic cryptococcal meningoencephalitis.
Infection with Cryptococcus neoformans or C. gattii, is most often manifested as a chronic meningitis as in this Papuan man. Infection, however, may localize in the lungs or disseminate to other organs such as the prostate, especially in immunocompromised individuals. In disseminated disease, cutaneous and lytic bone lesions are common.
Courtesy, Professor D. A. Warrell.
Fig. 4.114.
Invasive rhinocerebral mucormycosis.
Mucor is an environmental mould that may cause devastating opportunistic disease in those with compromised immunity, particularly diabetes mellitus. This diabetic lady presented with fever and facial pain which progressed rapidly to develop multiple cranial nerve palsies (II, III, IV and V). CT imaging confirmed an extensive sinusitis with orbital bone erosion and cavernous sinus invasion. Radical surgical debridement combined with prolonged antifungal therapy achieved resolution.
Courtesy, UCL Hospitals Radiology.
Fig. 4.115.
Typical appearance of Mucor.
Mucor colonies grow extremely fast, covering a Sabouraud plate within 72 hours (A); globular spore-bearing bodies (sporangia) and the virtual absence of hyphal septae are characteristic (B, Congo Red stain).
Courtesy, Dr S. Morris-Jones.
Fig. 4.116.
Surgical wound infection with Mucor.
This Indian patient required surgical debridement after a road traffic accident. Airborne Mucor contaminated the wound, leading to rapid tissue necrosis that required prompt limb amputation and prolonged antifungal therapy.
Courtesy, Dr L. Nabarro.