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Preface
Training in infection-related specialities in the United Kingdom has undergone substantial
changes over the past years. Combination of specialities (microbiology, virology, tropical
medicine and infectious diseases) and the desire for infection specialists to increase clinical
activities and reduce laboratory-based practice have led to a fundamental change in
examination methodology. Our aim was to produce a book that mapped to the current
infection training curriculum in line with the examination style of ‘best of five’ answers.
We have designed this book to test the knowledge of candidates preparing for examin-
ations in infection specialities, but it is also our aim to have a broader appeal to other
specialities with infection as a core component of their training. The book has 300 ‘best of
five’ questions; along with the answers, there are detailed explanations and background to
the answers, including suggestions for further reading around the subject. Readers who
through this book identify curriculum areas where their understanding may be sub-optimal
can then focus their revision to optimise their learning.
We are both practising infection consultants supervising current infection trainees
preparing for examinations during busy clinical placements and have a deep understanding
of the stress that assessments can cause. We hope you enjoy the book and it provides
knowledge and guidance that will serve you beyond the examinations.
vii
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Chapter
Biology of Bacteria, Viruses,
Microbial and host cellular biology and interactions dictate the breadth of clinical infection
practice, from colonisation to invasion to infection. Understanding the classifications
used for bacteria, viruses, fungi and parasites aids clinical and laboratory diagnosis and
ultimately patient management. Understanding the common host responses to infective
agents at the cellular level enables appropriate clinical management both with direct acting
anti-infectives and other supportive therapy.
Questions
Q1.1 A 21-year-old female presents with a fever, and a novel viral infection is suspected.
Electron microscopy is performed. Which of the following might be present in
a virus?
A. Nucleus
B. An envelope
C. Metabolic pathways
D. Ribosomes
E. A cell wall
Q1.2 A 46-year-old male presents with a fever of unknown origin, and a whole blood
sample is sent to the virology laboratory for polymerase chain reaction testing.
The test identifies a DNA virus. Which of the following class of viruses
contain DNA?
A. Rhabdoviridae
B. Orthmyxoviridae
C. Enteroviridae
D. Flaviviridae
E. Parvoviridae
Q1.3 A 1-year-old male awaiting repair of a ventricular septal defect is being considered
for palivizumab prophylactic therapy for respiratory syncytial virus (RSV).
What type of virus is RSV?
A. Single-stranded ( ) RNA
B. Single-stranded (+) RNA
C. Double-stranded RNA
1
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2 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
D. Single-stranded DNA
E. Double-stranded DNA
Q1.4 A 21-year-old female presents with a fever and leucopaenia, and a viral infection is
suspected. Which of the following is a paramyxovirus?
A. Rubella virus
B. Influenza B virus
C. Polio virus
D. Nipah virus
E. Parvovirus B19
Q1.6 A 27-year-old female with sickle cell anaemia presents in aplastic crisis with a fever.
Her blood results demonstrate:
Haemoglobin 50 g/L
Reticulocyte count 0.1%
White cell count 12.3 × 109/L
Lymphocytes 8.6 × 109/L
CRP 34
Which genus is the most likely causative virus from?
A. Dependovirus
B. Henipahvirus
C. Pneumovirus
D. Parvovirus
E. Erythrovirus
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Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions 3
Q1.8 A 54-year-old male presents with fever, tachycardia and hypotension. A blood
culture is taken and becomes positive in 12 hours. The Gram stain is shown in
Figure 1.1.
Figure 1.1 Gram stain from a
positive blood culture. (A black
and white version of this figure
will appear in some formats. For
the colour version, please refer to
the plate section.)
Q1.9 A 54-year-old male presents with fever, tachycardia and hypotension. A blood
culture is taken and becomes positive in 12 hours, and Escherichia coli is
identified. It is demonstrated to have in vitro resistance to many penicillins and
cephalosporins. Through what mechanism is an extended-spectrum beta-lactamase
gene most likely to be present in this E. coli?
A. Transduction
B. Transformation
C. Conjugation
D. Constitutively
E. De novo mutation
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4 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
Q1.11 A 35-week pregnant female recalled a flu-like illness 2 days prior to delivery. She was
treated for peri-partum sepsis, and her new-born child was born in poor condition
and admitted to the neonatal intensive care department. Blood cultures (and subse-
quently cerebrospinal fluid) grew the organism depicted in Figure 1.2.
Q1.12 A 34-year-old man presents with a fever, and an aerobic blood culture bottle grows
a Gram-negative rod. Which one of the following organisms is a strict aerobe?
A. Bacteroides fragilis
B. Kluyvera spp.
C. Proteus vulgaris
D. Prevotella melaninogenica
E. Pseudomonas aeruginosa
Q1.13 A 42-year-old patient presents with septic shock and is found to have a soft tissue
infection. Which component of the cell wall of Gram-positive bacteria may
contribute to the development of septic shock in Gram-positive infections?
A. Capsular protein
B. Endotoxin
C. Peptidoglycan
D. Phospholipid
E. Teichoic acid
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Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions 5
Q1.14 A 23-year-old female presents with a urinary tract infection. Which of the
following is true about urease producing bacteria?
A. Urease acidifies the urine rendering neutrophils inactive
B. Escherichia coli is urease positive
C. Acidifying the urine can lead to precipitation of struvite calculi
D. Morganella morganii is potentially a urea-splitting bacteria
E. Are commensal organisms that prevent hepatic encephalopathy
Q1.16 A 21-year-old female presents with necrotising fasciitis. Which of the following is
not a virulence factor of Staphylococcus aureus?
A. Lecthinase
B. Toxic shock syndrome toxin-1
C. Panton-Valentine leukocidin
D. Enterotoxin A
E. DNase
Q1.17 A 31-year-old male returns from Ethiopia and presents with a recurrent febrile illness.
What is the cause of the relapsing nature of fever in Borrelia recurrentis infection?
A. Antigenic drift
B. Antigenic shift
C. Rapidly developing antibody resistance
D. Antigenic variation
E. Encapsulation
Q1.18 A 16-year-old male presents with respiratory distress. Which organism produces a
toxin similar in action to that of Corynebacterium diphtheriae?
A. Bordetella pertussis
B. Pseudomonas aeruginosa
C. Serratia marcescens
D. Haemophilius influenzae
E. Clostridium tetani
Q1.19 An 18-year-old female presents with difficulty swallowing. A throat swab demon-
strates club-shaped organisms with differential staining. Corynebacterium diphther-
iae is suspected. What are Corynebacterium diphtheriae volutin granules made of?
A. Carbohydrate
B. Protein
C. Lipid
D. Phosphate
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6 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
Q1.20 A 45-year-old female presents with a heart block following a minor dog bite to the
palm of her hand (Figure 1.3).
Figure 1.3 Clinical appearance of the right
hand following a minor dog bite.
Corynebacterium ulcerans is isolated from the wound, and an Elek test is positive.
How does diphtheria toxin act?
A. ADP ribosylation of EF2
B. Ergosterol synthesis inhibition
C. Peptidoglycan disruption
D. Protein synthesis inhibition at the ribosome
E. Acetyl choline esterase inhibition
Q1.21 A 50-year-old male who underwent traumatic splenectomy two years ago
presents with tachypnoea, tachycardia and hypoxia. A mucoid Streptococcus
pneumoniae is subsequently grown (Figure 1.4).
Figure 1.4 Growth on blood agar
incubated in an aerobic environment
at 37°C for 24 hours. (A black and
white version of this figure will appear
in some formats. For the colour
version, please refer to the plate
section.)
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Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions 7
Q1.22 A 56-year-old male is diagnosed with native valve endocarditis. A blood culture
grows a Gram-positive cocci on both blood agar and MacConkey agar, which is
ampicillin resistant. What is the likely identification of this organism?
A. Enterococcus faecalis
B. Enterococcus faecium
C. Streptococcus pneumoniae
D. Streptococcus bovis
E. Streptococcus anginosus
Q1.24 A 56-year-old female with urosepsis is not improving despite treatment with an
intravenous third-generation cephalosporin. Which bacteria are most likely to
harbour an extended-spectrum beta-lactamase gene?
A. Klebsiella pneumoniae
B. Enterobacter cloacae
C. Citrobacter freundii
D. Morganella morganii
E. Proteus mirabilis
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8 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
Q1.26 A 54-year-old male presents with a flitting rash and an eosinophilia eight weeks
after return from the tropics. Which of the following infections require an
intermediate snail host?
A. Diphylobothriasis
B. Schistosomiasis
C. Echinococcosis
D. Paragonamiasis
E. Strongyloidiasis
Q1.27 A 31-year-old male presents with diarrhoea several days after return from
Nigeria. Entamoeba is seen on stool microscopy. Which of the following is
a non-pathogenic variant of Entamoeba histolytica?
A. Entamoeba dispar
B. Escherichia coli
C. Entamoeba hartmanni
D. Endolimax nana
E. Enterobacter cloacae
Q1.28 A 21-year-old female presents with a fever, adenopathy and a rash. Blood tests
demonstrate a lymphocytosis. Serological diagnosis of a primary viral infection
may be made by detection of which viral-specific immunoglobulin?
A. IgA
B. IgD
C. IgE
D. IgM
E. IgG
Q1.29 A 23-year-old male student has been recently admitted with invasive meningococcal
disease. He has made a good recovery but gives a history of a previous episode
of meningococcal septicaemia when he was 15 years old. There is no history of
other recurrent infections. Which immunodeficiency is most likely in this patient?
A. Adenosine deaminase deficiency
B. C7 deficiency
C. Job’s syndrome
D. Myeloperoxidase deficiency
E. Selective IgM deficiency
Q1.30 An 18-year-old male with chronic granulomatous disease (CGD) has recurrent
staphylococcal infection. What is the mechanism behind this?
A. Chemotaxis inhibition
B. Defect in phagocyte oxidase
C. Lack of C3d receptor
D. Failure of phago-lysosome fusion
E. IgM deficiency
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Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions 9
Q1.32 A 31-year-old male presents with acute hepatitis. He is found to have hepatitis C,
but subsequently clears this infection. Which pattern of cytokines is produced
by TH1 lymphocytes?
A. IL4 and IL10
B. TNF-β and IL1
C. IL2 and IFN-γ
D. IL1 and IL12
E. IL4, IL5, IL6 and IL13
Answers
A1.1 Answer B: An envelope
Viruses (Latin for toxin) contain DNA or RNA but not both. The central ribonucleic core
is surrounded by a protective shell (not a cell wall) of repeating protein units called
capsomeres. This has a symmetry which is either helical or icosahedral. Viral particles
contain polymerases and integrases but no true metabolic pathways. As completed virions
move from the host cell nucleus to the cytoplasm or from the cytoplasm to the
extracellular space, an external lipid-containing envelope may be added to the
nucleocapsid.
Further Reading
Abrescia NGA, Bamford DH, Grimes JM, Stuart DI. Structure unifies the viral universe. Ann Rev
Biochem. 2012;81:795–782.
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10 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
I II III IV V VI VII
Double- Single- Double- Single- Single- Single- Double-
stranded stranded stranded stranded stranded stranded (+) stranded
DNA DNA RNA (+) RNA ( ) RNA reverse reverse
transcriptase transcriptase
RNA DNA
Adeno Parvo Reo Picorna Orthomyxo Retro Hepadna
Herpes Toga Paramyxo
Pox Flavi Rhabdo
Papilloma Corona Filo
Calici Arena
Hepe Bunya
Data from Baltimore (1971).
Further Reading
Baltimore D. Expression of animal virus genomes. Bacteriol Rev. 1971;35(3):235–241.
Further Reading
Andabaka T, Nickerson JW, Rojas-Reyes MX, Rueda JD, Bacic Vrca V, Barsic B. Monoclonal antibody
for reducing the risk of respiratory syncytial virus infection in children. Cochrane Database Syst
Rev. 2013;4:CD006602.
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Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions 11
Further Reading
Virtue ER, Marsh GA, Wang LF. Paramyxoviruses infecting humans: the old, the new and the
unknown. Future Microbiol. 2009;4(5):537–554.
A1.5 Answer B: HPV-16 and HPV-18 are associated with genital cancers
HPV is a DNA virus from the papillomavirus family, of which there are numerous serotypes.
Serotypes 6 and 11 most frequently cause ano-genital warts, while serotypes 16 and 18 are
linked with ano-genital cancers. The E6 and E7 early viral proteins are considered
oncogenic, inhibiting tumour suppression genes: E6 inhibits p53, while E7 inhibits p53, p21
and RB. Diagnosis is through PCR on sample obtained during colposcopy.
Further Reading
Cutts FT, Franceschi S, Goldie S, Castellsague X, de Sanjose S, Garnett G, Edmunds WJ, Claeys P,
Goldenthal KL, Harper DM, Markowitz L. Human papillomavirus and HPV vaccines: a review.
Bull World Health Organ. 2007;85(9):719–726.
Further Reading
Rogo LD, Mokhtari-Azad T, Kabir MH, Rezaei F. Human parvovirus B19: a review. Acta Virol.
2014;58(3):199–213.
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12 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
The global annual incidence of hepatitis C is estimated at four million, of whom 18–34%
will spontaneously clear the virus. Acute infection with hepatitis C is clinically mild and may
even be unrecognised or undiagnosed; acute resolution is not associated with any long-term
sequelae. The remainder of the patients are deemed to have chronic hepatitis C, which is
now the leading cause of end-stage liver diseases and liver-related deaths in much of the
world. Progression of liver fibrosis in chronic hepatitis C is extremely variable, and is
influenced by viral, host and environmental factors.
Further Reading
Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol. 2014;61(S1):S58–S68.
Further Reading
Public Health England. UK Standards for Microbiology Investigations TP39: Staining procedures.
2015. Available at: www.gov.uk/government/publications/smi-tp-39-staining-procedures
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Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions 13
In this case, Escherichia coli does not constitutively harbour an extended-spectrum beta-
lactamase (ESBL) gene in their chromosomal genetic material, and the development of a de
novo ESBL gene would be rare. Similarly, in the context of both this organism (E. coli) and
this family of resistance genes (ESBL), transduction and transformation is unlikely. Instead,
it is conjugation, and the transmission of plasmids with their additional genetic material,
which will bring to the host E. coli lineage the ability to produce ESBL proteins and confer
resistance to many penicillins and cephalosporins.
Further Reading
Holmes AH, Moore LSP, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, Guerin PJ, Piddock LJ.
Understanding the mechanisms and drivers of antimicrobial resistance. Lancet. 2016;387
(10014):176–187.
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14 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
aid identification for clinical and epidemiological purposes; however, laboratory identification
can be complex. Salmonella isolates can exist in two “H” phases; phase I being motile and
phase II being non-motile (the latter as in this case). Isolates that are non-motile on primary
culture may be switched to a motile phase using a Cragie tube or the Jameson plate.
Somatic “O” antigens are heat stable and alcohol-resistant, but flagellar “H” antigens are
heat-labile. Some surface antigens in Salmonella may mask somatic antigens, meaning
bacteria will not agglutinate with somatic “O” antisera – one specific surface antigen is the
“Vi” antigen. The “Vi” antigen may only occur in three Salmonella serovars (out of over
2000): Typhi, Paratyphi C and Dublin, but is variably detected. Other non-lactose
fermenting coliforms can cause diarrhoea, including Shigella species, but as a rule these do
not produce hydrogen sulphide.
Further Reading
Public Health England. UK Standards for Microbiology Investigations B30: Investigation of faecal
specimens for enteric pathogens. 2014. Available at: https://assets.publishing.service.gov.uk/
government/uploads/system/uploads/attachment_data/file/343955/B_30i8.1.pdf
Further Reading
National Institute for Health and Care Excellence. Neonatal infection: antibiotics for prevention and
treatment NICE guidance. 2012. Available at: www.nice.org.uk/guidance/cg149
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Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions 15
found in the oral cavity) were originally classified in the Bacteroides genus. Kluyvera spp. has
been put forward as a new member of the Enterobacteriales and as such is only a facultative
anaerobe. P. aeruginosa is an obligate aerobe.
Further Reading
Moore LSP, Cunningham J, Donaldson H. A clinical approach to managing Pseudomonas aeruginosa
infections. Br J Hosp Med (Lond). 2016;77(4):C50C54.
Further Reading
Ginsburg I. Role of lipoteichoic acid in infection and inflammation. Lancet Infect Dis.
2002;2(3):171–179.
Further Reading
Clericetti CM, Milani GP, Lava SAG, Bianchetti MG, Simonetti GD, Giannini O. Hyper-ammonaemia
associated with distal renal tubular acidosis or urinary tract infection: a systematic review. Pediatr
Nephrol. 2018;33(3):485–491.
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16 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
comprises three parts: O antigen, core oligosaccharide and Lipid A. Lipid A is associated
with the toxicity of Gram-negative bacteria. It is the innermost of the three regions of the
lipopolysaccharide molecule, and its hydrophobic nature allows it to anchor the LPS to the
outer membrane. Lipid A (and LPS) is believed to activate cells via the Toll-like receptor
system. The polysaccharide components produce immunogenicity.
Further Reading
Van Amersfoort ES, Van Berkel TJC, Kuiper J. Receptors, mediators, and mechanisms involved in
bacterial sepsis and septic shock. Clin Microbiol Rev. 2003;16(3):379–414.
Further Reading
Spaulding AR, Salgado-Pabón W, Kohler PL, Horswill AR, Leung DYM, Schlievert PM.
Staphylococcal and Streptococcal superantigen exotoxins. Clin Microbiol Rev.
2013;26(3):422–447.
Tong SY, Davis JS, Eichenberger E et al. Staphylococcus aureus infections: epidemiology,
pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015;28
(3):603–661
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Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions 17
Antigenic shift and antigenic drift are the mechanisms through which influenza changes
its genetic structure and epitopes over time. Slipped strand mispairing can function as
mechanism for phase variation in Escherichia coli. Transposons have varied roles in
infectious diseases, but perhaps of most clinical relevance are responsible for transfer of anti-
microbial resistance genes.
Further Reading
Elbir H, Raoult D, Drancourt M. Relapsing fever borreliae in Africa. Am J Trop Med Hyg.
2013;89(2):288–292.
Boutellis A, Mediannikov O, Bilcha KD, Ali J, Campelo D, Barker SC, Raoult D. Borrelia recurrentis in
head lice. Ethiopia. Emerg Infect Dis. 2013;19(5):796–798.
Further Reading
van ‘t Wout EF, van Schadewijk A, van Boxtel R, Dalton LE, Clarke HJ, Tommassen J, Marciniak SJ,
Hiemstra PS. Virulence factors of Pseudomonas aeruginosa induce both the unfolded protein and
integrated stress responses in airway epithelial cells. PLoS Pathog. 2015;11(6):e1004946.
Further Reading
Pallerla SR, Knebel S, Polen T, Klauth P, Hollender J, Wendisch VF, Schoberth SM.
Formation of volutin granules in Corynebacterium glutamicum. FEMS Microbiol Lett.
2005;243(1):133–140.
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18 Chapter 1: Biology of Microorganisms & Host–Pathogen Interactions
Further Reading
Moore LSP, Leslie A, Meltzer M, Sandison A, Efstratiou A, Sriskandan S. Corynebacterium ulcerans
cutaneous diphtheria. Lancet Infect Dis. 2015;15(9):1100–1107.
Further Reading
Engholm DH, Kilian M, Goodsell DS, Andersen ES, Kjærgaard RS. A visual review of the human
pathogen Streptococcus pneumoniae. FEMS Microbiol Rev. 2017;41(6):854–879.
Further Reading
Public Health England. Standards for Microbiological Investigation ID 4: identification of
Streptococcus species, Enterococcus species and morphologically similar organisms. 2014.
Available at: www.gov.uk/government/publications/smi-id-4-identification-of-streptococcus-
species-enterococcus-species-and-morphologically-similar-organisms
A1.23 Answer C: Organism is isolated from throat for several days following infection
Bordetella spp. are small Gram-negative coccobacilli of the phylum proteobacteria and are
highly fastidious obligate aerobes. Bordetella pertussis is an exclusive human pathogen.
Transmission occurs by direct contact or respiratory aerosol droplets. It is highly contagious
with over 90% of household contacts developing disease. The incubation period averages
7–10 days (range 5–21 days). Activity tends to peak at the ages of 3–4 years. Bacteria
initially adhere to ciliated epithelial cells in the nasopharynx causing an initial catarrhal
phase, which lasts for 1–2 weeks during which large numbers of bacteria can be recovered
from the pharynx. Paroxysms of cough increase in frequency and severity as illness
progresses for 2–6 weeks. During this stage toxins cause ciliostasis and facilitate the entry
of bacteria to tracheal/bronchial ciliated cells. B. pertussis also produces a lymphocytosis-
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Hän tunkee voimiensa takaa ympäröivää ihmismuuria, itkee ja
rukoilee.
Kaikki on turhaa. Ihmiset hänen ympärillään eivät ymmärrä häntä.
Tuskassaan ei hän muista ainoatakaan saksan sanaa. Vihdoin saa
hän
huudetuksi: Kinder, Kinder!
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Itse hän ei käsitä miten, mutta hänelle käy selväksi, että laiva ei
tule enää. Se laiva, joka toi hänet, oli viimeinen ja lapset — jäivät.
Hän ei tiedä miten kauan hän onkaan siinä seisonut. Koko ajan on
häntä likistetty, tungettu ja survottu. Lapsi sylissä itkee haikean
lohduttomasti…
— Älä ole huolissasi. Kyllä minä tiedän, mitä sanon. Minä tiedän,
etten enää voi olla mitään sinulle. — Kun olisin voinut, ei minulla
vielä ollut sitä hyvää tahtoa, jota nyt.
— Älä ajattele niin paljon, Elena! Ehkä silloin piankin voit vahvistua
ja tulla terveeksi.
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Elena näki nyt ensi kertaa tuon hienon, vanhan naisen, jonka
läheisestä ystävyyssuhteesta poikaan hän viime aikoina oli kuullut
paljon puhuttavan. Illan kuluessa kääntyi puhe äidinrakkauteen. "Se
on itsekkäisyyttä, sulaa itsekkäisyyttä", lennätti Elena tulemaan kuin
uhalla.
— Minä odotan sinua aina, aina, kun olet poissa. — Taas pitkä
intohimoinen puristus.
Toinen, mitä hän itkee? Itkeekö hän äitiyden rikkautta vaiko toisen,
ennen aavistamattoman tunteen raskautta? Itkeekö ehkä sitä, ettei
lapsen lailla saa antaa valtaa sydämensä ikävöiville vaatimuksille?
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Seuraavana päivänä suunniteltiin ulkomaanmatkaa talossa.
Lääkäri oli sanonut Aljoschan sydäntä heikoksi. Poika oli vietävä
vahvistumaan. Silloin vahvistuisi sydänkin.
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Äiti ja poika ovat aina yhdessä. Ainoastaan joskus, kun äiti hyvin
pyytää, jättää Aljoscha äidin leikkiäkseen ikätoverinsa Friedrichin
kanssa.
Onko se Jumala?
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