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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2612_Библиотеки_им_академика_М_И_Перельмана
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Latent TB Balance the risk of development of active disease with the possible
https://t.me/med1917
side eects of treatment. Consider treatment in all at risk of active disease:
transplantation, chemotherapy, biological agents, eg anti-
CKD including dialysis, silicosis, bariatric surgery, and recent close contact with pul-
monary/ laryngeal
Treat with
isoniazid (with pyridoxine).
If concerns about hepatotoxicity then
preferred. In severe liver disease, seek specialist advice. If interactions with rifamycins
are a concern (eg
TB. Oer HIV, hepatitis B and C testing prior to treatment.
3
months of isoniazid (with pyridoxine) and rifampicin OR 6 months of
3
months of isoniazid and rifampicin may be
HIV, transplant) then
6
months of isoniazid may be preferred.
TNF (p
261
HIV,
), diabetes,
Active TB All forms of active TB are statutorily notifiable in the UK. This includes
both clinical and culture diagnoses. Notification is via your local public health protection team (
specialist
• Active CNS disease (including spinal cord involvement): continuation phase of
treatment is extended from
• CNS and pericardial disease: use adjunctive high- dose steroids (with weaning and
withdrawal during the intensive treatment period).
• Drug- resistant TB.
Adherence is important for treatment to be eective and to prevent drug resistance. Directly observed therapy (
for
multidrug- resistant disease, patient request.
Universal access to diagnosis and treatment of
developed an ‘End
incidence by
www.gov.uk/ hea lth- pro tect ion- team). Treatment is given under the care of a
TB clinician/ service according to table
4
to 10 months.
TB, homelessness, drug/ alcohol misuse, prison, psychiatric or cognitive disorder,
TB’ strategy aiming to reduce TB deaths by
90
% by
2035
DOT) should be considered if: previous treatment
(www.who.int/ tb/ strat egy/ en).
9.10
. Exceptions include:
TB is part of social justice. WHO has
90
% by
2030
, and TB
Drug- resistant TB
NAAT (p
390
for drug resistance: previous
) for drug resistance should be requested for all patients with risk factors
birth or residence in a country where ≥
Drug resistance may be:
• To any single agent in table
• Multidrug- resistant TB (MDR- TB): resistant to rifampicin and isoniazid.
• Extensively drug- resistant TB (XDR- TB): resistant to rifampicin, isoniazid, one inject-
able agent (capreomycin, kanamycin or amikacin), and one fluoroquinolone.
Seek expert advice for all drug- resistant cases
Test for resistance to
TB treatment, contact with drug- resistant disease,
5
% new cases are drug resistant (fig
9.10
.
2
nd- line drugs. Remember infection control measures.
9.10
391
9 Infectious diseases
).
Fig 9.
10
Percentage of new TB cases with multidrug- resistant TB.
Reproduced with permission from World Health Organization, Global tuberculosis report
Health Organization
0–2.9
3
–
5.9
–
11
6
12
–
19
20
2020
. http:// www.who.int/ tb/ publi cati ons/ global _ rep ort/ en/
2020
. © World
9 Infectious diseases
Influenza
AND
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392
Influenza is common throughout the world, aecting ~5– 10% of adults, and 20– 30%
of children each year. In most, it is a self- limiting illness. Complications can be lifethreatening in the elderly, pregnant women, and those with chronic disease. There
4
million cases of severe influenza and ~
are ~
Seasonal influenza
Acute viral infection of lungs and airways. Rapid person- to- person spread by aerosolized droplets and contact. Infectivity from
three subtypes of virus:
binations of virus surface proteins, eg
the winter in temperate countries. Acquired immunity is specific to the virus subtype.
Presentation Incubation: 1– 4d. Fever, dry cough, sore throat, coryzal symptoms,
headache, malaise, myalgia, conjunctivitis, eye pain
clude pneumonia, exacerbation of chronic lung disease, croup, otitis media,
sitis, encephalitis, Reye syndrome (encephalopathy + fatty degenerative liver failure).
Diagnosis Clinical: acute onset + cough + fever has positive predictive value
79
%. Testing in outbreaks, complicated influenza, and public health surveillance.
>
Includes: viral
PCR, rapid antigen testing, viral culture of clinical samples (throat
swab, nasal swab, nasopharyngeal washings, sputum).
Tre at me nt
• Uncomplicated influenza: supportive. Antivirals only if high risk of complications
48
h):
(within
• Chronic disease: lung, heart, kidney, liver, CNS, DM.
• Immunosuppression: immunodeficiency, current or planned or within
6
months of immunosuppressive therapy, HIV.
• Pregnancy. • >65yrs. • BMI >40. • <6 months old.
• Complicated influenza includes lower respiratory tract infection, exacerbation of
any underlying medical condition, all needing hospital admission. Give antiviral
inhibitors of influenza neuraminidase within
1
Oseltamivir: PO or NG. Adult dose: 75mg BD. 5d course. 1st line in UK.
2
Zanamivir: inhaled (10mg BD, 5d course, confirm technique), nebulized, or IV
(respiratory disease aecting nebulizer delivery,
sistance (eg
A(H1N
sorption of oseltamivir.
Retrospective observational data, and animal studies of oseltamivir and zanamivir show
no evidence of harm in pregnancy. Supportive treatment for all. Extracorporeal membrane oxygenation (
injury due to influenza.
ECMO) has been used to support gas exchange in severe acute lung
Prevention
• Post- exposure prophylaxis: if high risk (see ‘Treatment’)
cination: oseltamivir
oseltamivir resistance) for
• Annual vaccination in UK: all high risk (see
‘Treatment’), children >
p
403
. Personal hygiene remains a key pillar of
See
prevention (
fig
9.11
).
Pandemic influenza Seasonal influenza is subject
to antigenic drift: small genetic changes during replication which can be accounted for in the annual
vaccine. Antigenic shift is a major change in influenza
A resulting in new haemagglutinin (H) and neuramin-
idase proteins (
N) for which there is no pre- existing
immunity in the population. Any non- human influenza
viruses which transfer to humans are novel. If they
also have, or develop, capacity for rapid human- tohuman transmission, a pandemic results.
500 000
deaths worldwide/ yr.
1
A, B, and C. Type A influenza is subdivided according to com-
1
)), poor clinical response to oseltamivir, concerns re GI ab-
PO OD (inhaled zanamivir OD if
10
d.
2
yrs, healthcare workers.
d prior, to ~7d after symptoms. Includes
A(H1N
1
), A(H
3N2
). Seasonal epidemics peak during
± photophobia. Complications in-
48
h (see also BOX ‘Hide and seek’):
ITU). Used if: oseltamivir re-
not protected by vac-
Fig 9.
11
A woman coughing or
sneezing without a handkerchief
in an oce with three other oce
workers.
Lithograph after H.M. Bateman.
Wellcome Collection, Public
D&V, myo-
Domain Mark.
4
Sailing the choppy waters of pandemic disease
SPAR
SPAR
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Pandemic respiratory disease is the stormy sea of clinical medicine. Like sailors,
we know that choppy waters lie ahead, but we cannot predict their exact timing
or nature. To prepare a boat for the tempestuous waters, the mast is key; without
it the sails are unsupported and progress will flounder. The mast of pandemic
influenza is a tall, vertical
swell, and allows sailors to climb up high to see what lies on the horizon. When
preparing for pandemic influenza, we must make for ourselves a
fit for the storm ahead:
• Surveillance, planning, and communication: worldwide influenza virological sur-
veillance has been conducted through the
alert mechanism for viruses with pandemic potential and defines methodologies for assessing antiviral susceptibility. Cooperation between international
and national public health bodies is required for an understanding of clinical
characteristics and disease spread. Communication to the individual (public and
social media) is needed with advice about self- isolation, when and how to seek
medical help, personal hygiene (
• Protect: vaccine development and production capacity (stockpiling), adequate
personal protective equipment (apron, gloves, well- fitting mask), antiviral administration according to robust evidence and susceptibility.
• Animals: limiting/ eliminating the animal reservoir of virus by culling, restricting
animal movement and trade, vaccination of livestock.
• Research: virus characteristics, disease severity predictors, epidemiological
risk factors, antiviral development, targeting of treatment and vaccination,
increased- spectrum vaccines with longer- lasting immunity, eective healthcare
worker protection, evidence- based social distancing measures.
Hide and seek
In
2009
, there was justifiable global concern about a ‘swine flu’ pandemic.
Based on a Cochrane review in
oseltamivir, billions were spent stockpiling the drug worldwide.
In fact, the positive conclusion was driven mainly by data from an industryfunded summary of
needed access to these missing data. The ensuing fight for information was
5
years. The oer of a secret contract, with secret terms, and se-
to take
crecy about methods, was declined. These are not acceptable methods for
10
trials, of which only two had been published.5 Cochrane
meta- analysis. Inconsistencies began to arise in conclusions about eectiveness; being able to see all the data started to become increasingly important.
But even the largest phase
December
2009
, Cochrane could only declare that paucity of data undermined
previous findings.
This battle for data became part of ‘Alltrials’: a campaign for transparency in
clinical trials. ~
find them. You can run your own drug trial, choose what to publish, and watch
how the data become skewed at:
After half a decade, the clinical study reports were released. These are nor-
50
% of all clinical trials remain unpublished. The hunt goes on to
mally used to provide authorities with a detailed trial report.
not easy fodder for meta- analysis. And the conclusion: oseltamivir shortens
symptoms by <
unreliably reported.
The
22
nd edition,
(
1
d and hospitalization is not reduced. Other complications were
WHO includes oseltamivir on its WHO Model List of Essential Medicines
2021
) which means it is considered ecacious, safe, cost- eective,
and a minimum requirement for basic healthcare. Does this stand up to independent scrutiny? The evidence base is certainly tarnished. But a pandemic is not
RCT. And the threshold of evidence to reverse policy decisions may be dierent
a
from the threshold needed to introduce them. If a new influenza pandemic looms,
millions more will be thrown in, for now.
which produces maximum drive through the
WHO for >
fig
9.11
).
2008
, which showed reduced complications with
III
trial of the drug had never been published. In
www.alltri als.net/ news/ the- econom ist- publ icat ion- bias
50
yrs. It oers a global
160 000
393
framework
9 Infectious diseases
pages are
9 Infectious diseases
Human immunodeficiency virus (
HIV
Kilometers
https://t.me/med1917
394
HIV is a retrovirus which infects and replicates in human lymphocytes (CD
): diagnosis
and macrophages. This leads to progressive immune system dysfunction, opportunistic infection, and malignancy = acquired immunodeficiency syndrome (
virus is transmitted via blood, sexual fluids, and breast milk. Virus subtypes include
HIV
1
(global epidemic) and HIV2 (less pathogenic, predominantly West Africa).
Epidemiology
38
million adults and children are estimated to be living with HIV worldwide
~
fig
9.12
), with
690 000
(
of the mortality (
UK: estimated ~
deaths/ yr. Africa has most of the disease (~26 million), most
440 000
/ yr), and ~1% of the world’s wealth.
100 000
living with HIV (= 1.7/
1000
). ~17% of those with HIV in UK are
unaware of their infection.
4
+ T cells)
AIDS). The
Prevalence (%) by WHO region
Eastern Mediterranean:
Western Pacific:
0.1
[<
0.3 [0.2–0.3
0.1–0.2
South-East Asia:
Fig 9.
12
Adult HIV prevalence (15– 49 years).
Reproduced with permission from World Health Organization, ‘Adult HIV prevalence (15– 49 years),
Patho physiology
HIV binds, v ia its GP
120
cytes, and macrophages. These ‘
replicates, producing billions of new virions. These are released, and in turn infect new
CD
4
cells. As infection progresses, depletion or impaired function of CD4 cells leads to
immune function.
HIV is a retrovirus: it encodes reverse transcriptase, allowing DNA
copies to be produced from viral
tion rate, which contributes to treatment resistance.
Prevention
Sexual transmission Consistent and correct use of (male and female) condoms
90
transmission by ~
HIV status) is unsafe due to inaccuracies in HIV status (which is only as reliable as a
person’s last test) and failure to disclose. It does not consider transfer of treatment
resistance, other
%. Serosorting (the restriction of unprotected sex depending on
STIS, or hepatitis.
Post- exposure prophylaxis (
ART) after potential HIV exposure (sexual or occupational) should be considered an
(
emergency method of
exposure. Not recommended if exposure is to a person on
and sustained (>
UK is Truvada
in
6
months) undetectable (<
®
(tenofovir/ emtricitabine) plus raltegravir for 28 days (refer to
local guidelines). Test for
Pre- exposure prophylaxis (PrEP) ART in those at high risk of acquiring HIV including
serodierent relationships without suppression of viral load, condomless anal sex in
MSM. Trials (PROUD, IPERGAY) show an
commissioned in the UK since
Ver tic al tran smi ssi on All pregnant women living with HIV should have commenced
ART by
24
wks. Caesarean delivery indicated if viral load >50 copies/ mL (and if safe
and available). Neonatal
Europe:
0.4 [0.4–0.4
0.1
[<
0.1–0.1
]
]
]
]
0.5 [0.4–0.5
]
Americas:
Africa:
http:// gama pser ver.who.int/ map Libr ary/ Files/ Maps/ HIV_ ad ult_ prev alen ce_ 2 017.png
4.2 [3.7–4.8
Global prevalence:
]
by
WHO region’. ©World Health Organization
0.8
% [
0.7–0.9
]
0875 1,7503,500
enve lope glycop rotein, to CD4 rece ptors on hel per T cells, mono -
CD
4
cells’ migrate to lymphoid tissue where the virus
RNA. This is error prone, meaning a significant muta-
PEP
) The short- term use of antiretroviral therapy
HIV prevention. Can be given up to
200
copies/ mL) viral load. 1st- line PEP6
HIV
8– 12
weeks after exposure.
86
2020
PEP is given from birth–
% reduction in HIV incidence. PrEP has been
. Results of a large- scale PrEP trial (IMPACT) awaited.
4
72
h (ideally <24h) after
ART with a confirmed
wks old with formula- feeding.
2017
2018
.
Presentation
HIV
ELISA
HIV
PCR
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With symptoms of early
• Primary
tion (= seroconversion illness, acute retroviral syndrome). Maintain a high index
of suspicion. Oer
like symptoms and an erythematous/ maculopapular rash. Consider primary
infection is symptomatic in ~80%, typically 2– 4 weeks after infec-
HIV testing to anyone (regardless of risk) presenting with flu-
as a dierential in any combination of fever, rash, myalgia, pharyngitis, mucosal
ulceration, lymphadenopathy, and headache/ aseptic meningitis. Diagnosis of pri-
HIV is a unique opportunity to prevent transmission (viral load and genital
mary
shedding).
expert help regarding viral load testing (see
• Persistent generalized lymphadenopathy = swollen/ enlarged lymph nodes >1cm in
HIV antibody testing may be negative but HIV RNA levels are high— seek
two or more non- contiguous sites (not inguinal) persisting for >
follicular hyperplasia caused by
In the asymptomatic, latent phase of chronic
In the UK there is universal testing in sexual health clinics, antenatal services,
drug dependency programmes, and in patients with
lymphoma. Where
HIV prevalence is >
admissions units should be considered. Any request for a
With complications of immune system dysfunction See pp
HIV testing
The prognosis for patients with
serious illnesses for which doctors routinely test.
dierently. Any doctor can consent for a
detail how results will be given. Written consent is unnecessary. Arrange follow- up
with a local
tive for the first time.
•
• Rapid point- of- care testing Immunoassay kit which gives a rapid result from a
HIV/ GUM service within
for
antibody and antigen (p24) 4th- generation assays test for HIV anti-
24
body and p
testing between infection and the production of measurable antigen/ antibody) to
average ~
antigen. This reduces the ‘window period’ (time of false- negative
10
days. Diagnosis in UK is confirmed by a confirmatory assay.
finger- prick or mouth swab. Only
confirmation.
• Viral load Quantification of HIV RNA. Used to monitor response to ART. Not diag-
nostic due to possibility of a false- positive result care if used to test for symptomatic primary
still required.
• Nucleic acid testing/ viral
to test for vertical transmission in neonates as placental transfer of maternal antibodies can aect
• CD4
count Cannot diagnose HIV. Used to monitor immune system function and dis-
ease progression in patients with
criteria for
See www.aids map.com for available HIV testing and country- specific resources.
HIV in the ‘window period’— confirmation of seroconversion is
ELISA antibody testing up to
AIDS.
Needle- stick injury
Risk of HIV transmission from a single needle- stick exposure from a person with
HIV not on ART is ~
1
in
300
Prevent
• Use ‘safer sharps’ (incorporates a mechanism to minimize accidental injury).
• Do not recap unprotected medical sharps.
• When using sharps, ensure there is a disposal container nearby.
Manage
• Encourage the wound to bleed, ideally under running water (do not suck).
• Was h wi th s oap a nd r unn ing water , do not scr ub.
• Seek advice from occupational health/ infection control (or A&E outside of working
hours) regarding source testing and post- exposure prophylaxis (
HIV
infection
HIV testing later in topic).
3
HIV infection. Excl ude TB, infection, and malignancy.
HIV in the UK is much better than for many other
2
CE- marked kits should be used. Needs serological
Qualitative test for the presence of viral RNA. Used
HIV
infection
2/ 1000
HIV test: explain the benefits of testing and
TB/ hepatitis B/ hepatitis C/
universal testing by GPS and medical
HIV testing6 should not be viewed
wks (preferably <48h) for patients testing posi-
18
months of age.
HIV. <
200
cells/ microlitre is one of the defining
months. Due to
HIV test should be met.
396– 9
.
(lower than risks of hepatitis B and C transmission).
p
394
).
395
HIV
9 Infectious diseases
9 Infectious diseases
Complications of
HIV
HBV
https://t.me/med1917
396
infection
Complications of HIV can be divided into:
• Complications of immune dysfunction (opportunistic infection/ malignancy).
• Complicating comorbidity.
• Complications of treatment, ie adverse drug eects (see pp
398– 9
The dierential diagnosis for symptoms presenting in a person living with
table
9.11
given in
the presentation may not relate to the patient’s
Table 9.
Presentation Dierential diagnosis
Fever Intraoral abscess, sinusitis, pneumonia, TB, endocarditis, menin-
Lymphadenopathy
Rash Drug reaction, herpes zoster, scabies, cutaneous cryptococcus or
Cough/
Diarrhoea
Abdominal pain
Dysphagia Candidiasis,
Liver enzymes Viral hepatitis (A, B, C, CMV, HSV, EBV), drug- induced liver injury
AKI Pre- renal due to sepsis/ dehydration, interstitial nephritis secondary
Headache/
seizures/ focal
neurology
Eye disease
Peripheral
neuropathy
. This is not exhaustive. Do not forget the usual dierentials,
HIV status.
11
Dierential diagnoses in HIV
SOB
gitis, encephalitis, pyomyositis, lymphoma, immune reconstitution
after commencement of
Pers istent general ized ly mphade nopath y (
plasmosis, cryptococcus, lymphoma, Kaposi’s sarcoma, local infection
histoplasmosis, Kaposi’s sarcoma, seborrhoeic dermatitis
Community- acquired pneumonia, Pneumocystis jirovecii, TB, bron-
chial compression (
Kaposi’s sarcoma (uncommon), cardiac failure (
pathy, infective pericardial eusion,
Salmonella, Shigella, Clostridium difficile, amoebiasis, Giardia,
Cryptosporidia,
TB, CMV colitis, pancreatitis (CMV, TB, or secondary to ART)
(anticardiac disease (pericardial eusion?)
to medication,
Meningitis (bacterial,
space- occupying lesion (toxoplasmosis, lymphoma, tuberculoma),
adverse drug reaction,
leukoencephalopathy (
Herpes zoster,
ART, CMV, HIV neuropathy, nutritional deficiency
HSV
TB or ART), HIV cholangiopathy, lymphoma, congestion due to
ART, any non- HIV cause
TB, lymphoma, Kaposi’s sarcoma), pulmonary
CMV, HIV enteropathy is a diagnosis of exclusion
HIV- associated nephropathy (proteinuria, CKD)
TB, cryptococcal, syphilis), empyema,
HIV encephalopathy, progressive multifocal
PML), stroke (HIV vasculopathy). See p
CMV retinitis (p
HIV vasculopathy)
434
)
p
395
), TB, syphilis, histo-
).
HIV is
HIV cardiomyo-
513
Complicating comorbidity
• Cardiovascular disease Risk of CVD. Includes individuals where risk traditionally
lower: young, normotensive, no
ART, accelerated pro- atherosclerotic inflammation by HIV. Management of CV
due to
risk factors though no data to guide lipid/
• Bone disease Risk of low bone mineral density and fragility fractures in HIV.
Contributing factors: side eect of
trition, smoking, alcohol, low vitamin
• TB All patients with TB and HIV need ART (as soon as TB treatment tolerated and
2
weeks if CD4 <
within
guidelines. Consider Truvada® plus efavirenz as
integrase inhibitors are decreased by rifampicin). See
• Hepatitis B (
• Hepatitis C (
HBV activity, eg tenofovir plus emtricitabine (not lamivudine or emtricitabine as
antia single agent due to potential for emergence of
lower
) Co- infection requires an ART regimen including antivirals with
HCV
) Ass ess al l for t reatm ent. Pegyla ted in terfe ron ecacy is less with
CD
4
cou nt. Treat to CD4 >
DM, non- obese. Contributing factors: dyslipidaemia
BP targets .
ART, increased prevalence of risk factors, eg poor nu-
D leve ls. R isk as sess and c onsid er bi spho spho nate.
100
cells/ microlitre). Seek expert advice and refer to local
500
cel ls/ microlitre with ART fir st.
1
st line in UK (serum levels of
ART, pp
398– 9
, TB, pp
HBV resi stanc e).
390– 1
.
Opportunistic disease
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ART is part of the treatment regimen of all opportunistic infections (see pp
• Pneumocystis jirovecii (‘Yee- row- vet- zee.’) Presentation: progressive SOB on
exertion, malaise, dry cough. Haemoptysis and pleuritic pain rare. Examination:
respiratory rate, often normal breath sounds. Investigation: SpO
and exertion).
sputum or
Tre at me nt:
course. Steroids in moderate– severe disease (P
line: pentamidine. Prophylaxis: co- trimoxazole if
• Candidiasis Oral or oesophageal. Pain in the tongue, dysphagia, odynophagia.
Diagnosed clinically or endoscopically. Treated with systemic ‘- azole’, eg fluconazole.
• Cryptococcus neoformans Com mon est syst emi c fu nga l in fect ion in HIV (5– 10% pre-
ART). Presentation: meningitis: headache, fever, meningism variable. Associated skin
(molluscum- like papules) and lung disease. Investigation:
stain (India ink),
high-dose liposomal amphotericin
flucytosine (
Normalize
• Toxoplasma gondii Toxoplasma abscesses are commonest cause of intracranial
mass lesions when
± seizures. Headache and vomiting if raised
sions on
CXR: classically perihilar infiltrates, but may be normal. Induced
BAL with nucleic acid amplification (more sensitive than staining).
IV co- trimoxazole (convert to oral if favourable response).
CSF/ blood cryptococcal antigen. Tre at me nt : induction with single,
SE: haematological toxicity) and fluconazole. Maintenance fluconazole.
ICP wit h LPs/ shunt. Delay
CD
4
<
MRI ( lymphoma) with associated oedema. CSF PCR for T. gondii is spe-
B (SE: renal tubular damage and AKI) plus
ART
(ri sk of im mune re const itution).
200
cells/ microlitre. Presentation: focal neurological signs
<9.3kPa/ SpO2 <92%). 2nd
aO2
CD
4
<
200
cells/ microlitre.
LP with manometry. CSF
ICP. Investigation: ring- enhancing le-
398– 9
(compare rest
2
21
- day
14
cific but only moderately sensitive. Blood serology is not diagnostic as most cases
are a reactivation of previous infection. Treatment: consider in any brain mass le-
CD
4
<
200
sion with
• Cytomegalovirus (
Presentation: retinitis (blurred then loss of vision), encephalitis,
sophagitis, colitis), hepatitis, bone marrow suppression, pneumonia. Diagnosis:
CMV viral load, retinal lesions (p
serial
biopsy. Treatment: ganciclovir/ valganciclovir. Side eects: rash, diarrhoea, bone
myelosuppression.
• Cryptosporidium Common cause of chronic diarrhoea in HIV pre- ART.
Presentation: acute or sub- acute non- bloody, watery diarrhoea. Also cholangitis, pancreatitis. Investigation: stool microscopy (multiple samples as oocyst
excretion intermittent),
Treatment: supportive,
Oncogenic disease
• Lymphoma Increased risk of non- Hodgkin’s lymphoma in HIV. Includes: diuse
B- cell lymphoma, Burkitt’s lymphoma, primary CNS lymphoma. Presentation:
large
dependent upon area of involvement. Includes lymphadenopathy, cytopenia,
symptoms. Treatment: combined
CNS disease. Whole- brain radiotherapy for CNS disease if excess toxicity with
chemotherapy.
• Kaposi’s sarcoma Most common tumour in HIV and AIDS defining. Caused by
cell/ microlitre. Pyrimethamine, sulfadiazine, folinic acid.
CMV
) Severe primary or reactivated disease (p
434
), GI ulceration, ‘owl’s eye’ inclusions on
PCR, enzyme immunoassay, direct fluorescent antibody.
ART.
ART and chemotherapy. Rituximab for non-
GI disease (oe-
401
CNS
Kaposi sarcoma herpes virus (human herpes-
8
, p
401
virus
cosal lesions: patch, plaque, or nodular (
Visceral disease less common. Investigation:
histological confirmation. Treatment:
ART. Intralesional retinoids or vinblastine.
Radiotherapy for cosmesis/ pain. Chemotherapy
(+
). Presentation: cutaneous or mu-
ART) in advanced disease.
fig
9.13
).
397
).
d
9 Infectious diseases
).
Fig 9.
13
Palatal Kaposi’s sarcoma.
Copyright D. A. Warrell.
9 Infectious diseases
HIV
ART
Inf
virion
ation
https://t.me/med1917
398
: antiretroviral therapy (
ART7 is recommended for everyone with HIV, regardless of CD4 count.
Strategic Timing of AntiRetroviral Treatment (
4685
participants (
previous
• immediate ART
• deferred ART unti l CD4 <
Immediate initiation of ART reduced the risk of AIDS, serious non- AIDS events, or
death by
Aims of
tory techniques leading to immunological recovery, reduced clinical progression, and
reduced mortality. These aims should be met with the least possible side eects.
Mechanism of action (See fig
• CCR5 antagonists inhibit the entry of the virus into the cell by blocking the CCR5
co- receptor.
• Nucleos(t)ide and non- nucleoside reverse transcriptase inhibitors (NRTIs, NNRTIs)
inhibit reverse transcriptase and the conversion of viral
• Integrase strand transfer inhibitors (INSTIs) inhibit integrase and prevent HIV DNA
integrating into the nucleus.
• Protease inhibitors (PIs) inhibit protease, an enzyme involved in the maturation of
virus particles.
• Pharmacokinetic enhancers/ boosters increase the eectiveness of antiretroviral
drugs allowing lower doses, eg cobicistat, ritonavir.
215
ART. Randomized to:
57
% (CI 38– 70%) at 3 years.
ART
ectious
sites, 35 countries) with HIV, CD4 >
350
To reduce the HIV viral load to a level undetectable by standard labora-
)
START
) study,
500
cells/ microlitre, no
cel ls/ microlitre or AIDS- defining illness.
9.14
.)
RNA into DNA.
CCR5 antagonist
Entry to cell
Matur
2015
NRTI
NNRTI
Fig 9.
14
Mechanism of action of ART.
Starting treatment Seek expert help.
1
Counselling: HIV transmission and sexual health, benefits of therapy (not cure),
adherence (lifelong), resistance, side eects of treatment, necessary monitoring, disclosure to partner/ family/ friends, partner testing.
2
Screen for infections and malignancy (pp
Treat or oer prophylaxis with co- trimoxazole if
TB see p
latent
bial treatment for opportunistic or serious infection (seek expert advice if drug
interactions or intracerebral disease).
3
Baseline tests: CD4, viral load, FBC, LFT, electrolytes, creatinine, pregnancy test,
viral genotype for drug resistance.
4
Review usual medications for possible drug interactions. Advise the patient to
check for drug interactions with any new medication.
See www.hiv- drugi nter acti ons.org
391
HIV RNA
Reverse
transcriptase
HIV DNA
INSTI
396– 7
). Includes TB, hepatitis B & C.
CD
. Aim to start ART within 2 weeks of initiation of antimicro-
4
PI
Proteins
<
200
cells/ microlitre. For
What to start
NNTRI
HIV
https://t.me/med1917
Use local guidelines. Get expert help.
For a treatment- naϊve patient consider two nucleoside reverse transcriptase inhibitors (= ‘
1
• NRTI backbone Ten o f o v i r & e m t r i c i t a b i n e ( c o m b in a t i o n t a b l e t = Truvada®),
NRTI backbone’) plus one of:
• ritonavir- boosted ‘protease inhibitor
• non- nucleoside reverse transcriptase inhibitor
• integrase inhibitor.
st- line drugs commonly used in the UK include:
abacavir & lamivudine (combination tablet = Kivexa®). Side eects:
anorexia, pancreatitis, hepatic dysfunction (severe lactic acidosis with hepatomegaly and hepatic steatosis reported, caution with hepatitis
density. Avoid abacavir if high risk of
• Protease inhibitors Atazanavir, darunavir. Side eects: hyperglycaemia, insulin re-
sistance (mainly
•
CNS toxicity, association with suicidality care in depression/ anxiety, adverse lipid
(
profile). Other side eects: rash,
• Integrase inhibitor Dolutegravir, elvitegravir, raltegravir. Side eects: rash, GI dis-
1
st- generation drugs), dyslipidaemia, jaundice, and hepatitis.
Rilpivirine (give with food, interaction with proton pump inhibitors), efavirenz
turbance, insomnia.
Monitor: adherence (see
logical response (viral load).
(values may not correlate with virological response, use viral load preferentially).
Adherence
Adherence to ART is associated with drug resistance, disease progression, and
death. Adherence support should be integral to
Assess Ask about adherence in a non- judgemental way. Do not blame. Explain the
reasoning behind your questions. Is non- adherence due to practical problems or
healthcare beliefs? Be ready to address both. What help would your patient like?
Intervene Normalize the situation— doubts and concerns about ART are common.
Find time for discussion/ information. Address concerns. Simplify the dosage
regimen (single tablet regimens, eg Atripla®), oer a multicompartment medication system. Link the taking of medication to a regular daily activity. Discuss side
eects: what are the risks/ benefits to changing dose or
Resource- limited settings
In many resource- limited settings, universal access to ART remains an objective
yet to be achieved. ~
50
it. Interim prioritization of those with symptomatic
microlitre may be appropriate as these patients are at high risk of mortality and
have most short- term benefit from
Equality in the treatment of
• Eective, acceptable, and reliable methods to reduce HIV transmission, including
treatment as prevention.
• Rapid, accurate, and low- cost diagnosis and monitoring.
• Standardization and simplification of ART regim ens.
• Evid ence- based ART to prevent the use of sub- standard protocols which com-
promise treatment and lead to the emergence of drug- resistant strains.
• Reduced ART cos ts and / or eective allocation of resources.
An
vaccine?
Vacc ines are the most e ective way to prevent infectious disease. They can also be
therapeutic, clearing a virus after infection.
duce an immune response sucient to confer protection. Research is ongoing into
neutralizing
and mechanisms to counter the mutational evolution of
HIV antibodies, peptides, genes, viral vectors, physiological ‘boosters’,
GI disturbance,
CVD. Avoid tenofovir if eGFR <
GI dis turba nce.
BOX ‘Adherence’), adverse eects (LFTS, glucose), viro-
CD
4
counts guide prophylaxis of opportunistic infection
ART provision.
B/ C), bone mineral
30
ART regimen?
.
% of those in need of treatment for HIV do not receive
HIV or CD
4
count <
350
cells/
ART.
HIV requires:
HIV vaccines to date have failed to in-
HIV. See www.hvtn.org
399
9 Infectious diseases
9 Infectious diseases
Herpes viruses
OHCS
OHCS
https://t.me/med1917
400
Herpes simplex virus (
Includes HSV1 and HSV2. HSV1 infection in ⅔ of world’s population (~3.7 billion <50yrs),
HSV
2
in ~11% (~
and
face producing vesicles or ulcers. Lifelong latent infection when virus enters sensory
neurons at infection site. Can then reactivate, replicate, and infect surrounding tissue.
Disseminated infection if impaired
Presentation Primary infection: subclinical or sensory nerve (tingling) prodrome,
then vesicles, shallow ulcers. Systemic symptoms possible: fever, malaise, lymphadenopathy, erythema multiforme. Heals
unless immunosuppressed. Anatomy of infection:
• Herpes labialis: cold sore lesion at lip border, predominantly HSV1.
• Genital herpes: predominantly HSV2 (p
• Gingivostomatitis: fever, sore throat followed by tender oropharyngeal vesicles.
• Keratoconjunctivitis: corneal dendritic ulcers. Avoid steroids. See
• Herpetic whitlow: painful vesicles on distal phalanx due to inoculation through a
break in the skin.
• Herpes encephalitis: most common treatable viral encephalitis. Transfer of virus
from peripheral site to brain via neuronal transmission. Prodrome: fever, malaise,
headache, nausea. Then encephalopathy: general/ focal signs of cerebral dysfunction including psychiatric symptoms, seizure, focal neurology (temporal involve-
60
ment in ~
• Secondary infection of eczematous skin— eczema herpeticum. See
Diagnosis Clinical diagnosis. Confirmation required in encephalitis,
%), memory loss. Predominantly HSV1 in immunocompetent patients.
keratoconjunctivitis, or immunosuppression: viral
scraping. Also culture, immunofluorescence, serology.
Treatment Supportive for most oral HSV in healthy adults. Aciclovir: symptoms
and viral shedding, will not prevent latent infection: consider if primary
symptoms, immunocompromised, pregnancy.
HSV encephalitis suspected, mortality ~
Varicella zoster virus (
Primary infection transmitted by respiratory droplets. Incubation 14– 21d. Invades
respiratory mucosa, replicates in lymph nodes. Disseminates via mononuclear cells
to infect skin epithelial cells. Leads to virus containing vesicles = chicken pox. Virus
then remains dormant in sensory nerve roots. Reactivation is dermatomal = s hing les.
Presentation
• Chicken pox: prodrome 1– 2d: fever, malaise, head-
ache, abdominal pain. Then rash (
erythematous maculesvesicles, crust in ~
1– 2
Infectious
d pre- , to 5d post- rash development
(lesions scabbed). Complications in immunosuppression: encephalitis (cerebellar ataxia),
pneumonia, transverse myelitis, pericarditis, purpura fulminans/
• Shingles: painful, hyperaesthetic area, then
DIC.
macularvesicular rash in dermatomal distribution. Disseminated infection if immunosuppressed. Infectious until scabs appear.
Chicken pox risk in non- immune contacts. Complications: post- herpetic neuralgia,
Ramsay Hunt syndrome (
Diagnosis Clinical diagnosis unless immunosuppressed: viral PCR, culture,
immunofluorescence.
Treatment Oral aciclovir/ valaciclovir for uncomplicated shingles/ chicken pox
in adults, aim to give within
algia): give if within
suppressed, severe/ disseminated disease (including ocular).
Prevention Chicken pox vaccination: not routine in children in UK. Shingles vaccin-
ation given at aged
70
exposure in immunosuppression, pregnancy, neonates.
HSV
) (human herpesvirus 1 and 2)
400
million). Viruses multiply in epithelial cells of mucosal sur-
T- cell immunity: pneumonitis, hepatitis, colitis.
8– 12
d. Reactivation: usually less severe
408
).
p
334
p
446
PCR of CSF, swab, or vesicle
HSV, severe
Empirical IV aciclovir as soon as
70
VZV
% in untreated disease (p
) (human herpesvirus 3)
fig
9.1 5
): pruritic,
48
h.
VZV
Fig 9.
15
p
499
).
72
24
h of rash in shingles (risk post- herpetic neur-
h of onset in chicken pox. IV aciclovir if pregnant, immuno-
808
).
Chicken pox (VZV).
© D A Warrell.
to prevent reactivation. VZV immunoglobulin if non- immune
.
.
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