Unlike bacteria, viruses are non-living particles which require a living host cell's machinery to replicate. They have small DNA or RNA genomes enclosed within a protein capsid (protective coat)[1]. Depending upon the lifecycle of the virus and method of replication, infections may either be acute (short-term as seen in the common cold), latent (cycles of infection as explained in Herpes) or chronic progressive (slow, insidious infection with a long incubation period and often very severe/fatal effects, as seen in HIV)[1].
Herpes
Herpes, as caused by the large enveloped Herpes Simplex Virus, refers to the large, swollen infectious blisters (which later burst to become crusty brown sores)[1,2]. These can be found on either the mouth (cold sores usually result from HSV-1) or the genitals (genital herpes usually result from HSV-2), and typically results from skin-to-skin contact with one of the sores, particularly during sex (including oral sex)[1,2]. After successfully 'defeating' the active infection (associated with disappearance of the sores), it hides in a dormant/latent state in the dorsal root ganglion of the nerve associated with that region of skin, only to reactivate in periods of immune suppression (usually stress, extended UV exposure, chemotherapy or AIDS)[1,2].
While transmission is common during active infection (with sores visible), transmission during latency is rare (but has been recorded)[2]. Approximately 15-20% of individuals in the 15-49 age bracket are estimated to be living with HSV-2 infection, and this number is much greater for HSV-1[3].
Diagnosis involves taking a swab of one of the lesion and laboratory analysis (results are most reliable if taken within four days of developing the sore)[2]. While there is no cure for Herpes, the use of paracetamol/other painkillers/anaesthetic jelly for the pain, antiseptic/salt solutions to prevent secondary bacterial infection of the sore and antiviral medications (particularly if recurrent episodes are frequent) may reduce the symptoms and morbidity associated with life-long infection[2]. Sexual activity should be avoided if either you or your partner exhibit any signs of active infection.
HIV
The earliest case of Human Immunodeficiency Virus (HIV) in
humans was actually reported in 1959, although the subsequent Acquired
Immune Deficiency Syndrome (AIDS) was only seen in 1981 (in five
otherwise-healthy homosexual young American men)[1,4]. Isolation of the
virus in 1983 allowed the development of government recommendations to prevent
transmission and vaccination research programs; efforts are hindered
due to rapid adaption and incredible diversity throughout the four
genetically-distinct groups (HIV-1 M, HIV-1 O, HIV-1 N and HIV-2)[1]. Modes of transmission include blood contact
(intravenous drug use, blood transfusions, in-surgery exposure and
needlestick accidents), sexual (oral, vaginal and anal sex) and from
infected pregnant mother to child, and this is promoted by the presence
of genital lesions (particularly co-infection with syphilis and
herpes)[5].
HIV is now a worldwide pandemic, with ≈2.3 million new cases (≈1.6 million or ≈70% in Sub-Saharan Africa), ≈1.6 million deaths (≈1.2 million or ≈75% in Sub-Saharan Africa) and ≈35 million infected globally (≈25 million, or ≈71% in Sub-Saharan Africa) every year; in countries such as Botswana, Lesotho and Swaziland over 20% of adults are infected[4].
Of all the adults living with HIV, ≈60% of the females and ≈40% of the
males are aged 15-24[4]. In Western Australia, this number is much lower, with ≈120 notifications per year, with a 4:1 ratio of males:females and no Aboriginal cases[6]. Half of all Western Australian infections were in homosexual males[6].
Primary infection with HIV is
characterised by glandular fever/flu-like illness with malaise, joint
and muscle pains, swollen lymph nodes and rash in >70% of infected
individuals (with a window period, where infection cannot be identified,
of 5.3 days)[1,4]. After only 2-6 weeks, the infection continues
without symptoms for ≈10 years without treatment (although the
individual is sill infectious)[1]. The emergence of symptoms such as
fevers, night sweats, diarrhoea, weight loss, thrush, Kaposi’s sarcoma (a type of endothelial cancer),
leukaemias, shingles (requires previous chickenpox infection), herpes
reactivation, pneumonia, confusion and other symptoms of serious opportunistic infections are indicative of immune suppression associated with AIDS[1,6].
The eventual loss of immunity leads to the infection of the
respiratory, gastrointestinal and nervous systems which leads to
disability, a loss of livelihood and death[1,5].
Detection
involves a simple blood test and laboratory analysis; this can further
determine both the viral load and the concentration of the affected CD4+
T-helper cell population (these indicate not only the presence of
infection but can monitor the rate of disease progression)[1,4]. This disease progression is significantly affected by host factors (receptor
mutations such as CCR5Δ32, and hereditary immune system variability
such as B27, B57 or B35 haplotypes), viral factors (relative competence)
and co-infection with certain disease (particularly Tuberculosis and
Hepatitis C)[4,7].
While
no cure for HIV exists, treatment acts to reduce disease progression
and symptoms, and takes the form of Highly-Active AntiRetroviral
Treatment (HAART)[1,4,7]. HAART uses a variety of drugs which prevent
various stages of the viral replication cycle, ranging from preventing
entry (Entry and Fusion Inhibitors) to interfering with the insertion of
the viral genome into the host genome (Reverse Transcriptase and
Integrase Inhibitors) and finally to inhibiting the formation of
functional proteins and hence viral particles (Protease
Inhibitors)[1,4]. Unfortunately the development of
drug-resistance mutations throughout the course of treatment often
results in the eventual ineffectiveness of current therapy; thus drugs
can be expected to only last a maximum of 30-40 years even if
stringently adhered to[1,7].
Hepatitis B
The Hepatitis B Virus (HBV) is commonly
transmitted from one person to another via infected blood (needle
sharing, tattooing, renal dialysis, organ transplantation and blood
transfusion) or other body fluids (saliva, sweat, semen, vaginal fluid,
breast milk, urine, faeces), thereby allowing spread during sexual
intercourse and during pregnancy, birth and breast-feeding (from mother
to child)[1]. Interestingly, infection can occur following simple close
contact (saliva and sweat are common in environments such as classrooms,
prisons and families; this mode of transmission is relatively
small)[1]. High-risk groups (without consideration of vaccination)
include injecting drug users, health-care workers, homosexual men, the
sexually promiscuous, prisoners, immigrants from endemic
regions/travellers, dialysis/blood transfusion recipients (where
screening is poor) and indigenous populations[8].
HBV
is considered endemic to a region if the prevalence is more than 5%,
and is seen in the North American Tundra, Amazon, Eastern Europe and
Mediterranean, South-East Asia, East-Asia and the Pacific Basin (except
New Zealand and Japan)[8,9]. More than 2 billion people are infected
worldwide, 350 million live with chronic infection and approximately 1
million deaths occur every year[9]. In Western Australia, there are ≈600 notifiable infections every year, ≈40 of which are new cases[6].
While
most acute cases are asymptomatic (only 1% of neonates, 10% of children
aged 1-5 and 30% of older individuals show acute symptoms), these occur
1-3 months after exposure[7,8] Common signs and symptoms include
fever, extreme tiredness (often for weeks or months), a loss of
appetite, nausea, vomiting, joint and muscle pain, and yellowing of the
eyes and skin (jaundice results from damage to the liver during viral
replication)[1,8,9]. Only 1% of chronically-infected individuals
experience the catastrophic and rapid liver damage (70% mortality)
associated with fulminant hepatitis[8].
Clearance
of the acute infection is highest in those with functional immune
systems and typically occurs within six months; 80-90% of neonates, 30%
of young children aged 1-5 and 5% of healthy adults later develop
chronic infection[8,9]. Chronic infection and resulting inflammation
lead to either progressive liver damage (cirrhosis leading to liver
failure in 20%) or liver cancer (HBV-related hepatocellular carcinoma is
responsible for 80% of liver cancers and occurs in 5% of those with
chronic infection)[1,8,9]. Factors promoting disease progression
include concurrent HIV infection, alcoholism or excessive alcohol use,
drug use (some drugs are toxic to the liver) and exposure to other
environmental toxins[1,8].
Since
the development of the recombinant HBV vaccine in 1982 (more than 95%
effective), 92% of UN Member states have initiated vaccination programs
(with only 48% provide neonatal vaccinations)[9]. As immunity declines
steadily during mid-life, revaccination is effective, and in the case of
accidental exposure, an 'antidote' is available (must be administered
within 48 hours)[1,8].
Diagnosis
requires a simple blood test and laboratory analysis, and the presence
of specific markers can determine the type of infection (acute, chronic
persistent or chronic active)[1,8]. Treatment for acute or chronic
infection involves the use of antivirals such as adefovir, dipivoxil and
lamivudine[1].If an individual knows they are infected, they need to be
extremely vigilant regarding cleanliness to prevent exposure to others
(always use sexual protection, do not share needles, advise appropriate
health professionals, cover wounds, clean up bodily fluid spills and
don't share toothbrushes or drink containers), as the HBV can remain
infectious up to 7 days outside of humans[8].
Hepatitis
D refers to 8 related 'strains' of small virus-like particles which
require concurrent HBV infection for transmission (therefore
distribution is limited to endemic HBV regions[1,8]. When an individual
contracts both HBV and HDV simultaneously, it produces a characteristic
severe acute disease with a low risk of chronic infection[1]. In
contrast, superinfection (when an HBV carrier is later infected with
HDV) produces acute hepatitis and almost always leads to the development
of cirrhosis and liver failure over 10-20 years[1,8].
Hepatitis C
The Hepatitis C Virus (HCV), unlike HBV, is
transmitted from one person to another via infected blood (not through
saliva, sweat, urine and faeces and rarely
through sexual fluids such as semen or vaginal secretions)[10,11]. As
a result, typical infection occurs during needle-sharing, accidental
needlestick injury, tattooing/piercings, sexual activity (only if damage to the soft mucosal lining and blood contact occurs), sharing infected
personal items (razors, toothbrushes, etc) and during birth (viral
particles can infect the neonate during delivery with a 5% transmission
rate)[11].
WHO
estimates that ≈3% of the world's population are infected, with 150-170
million people currently living with symptomatic HCV infection; this
number is remains relatively constant despite 3-4 million new (acute)
cases and 350,000 deaths each year[11]. 'Strains' 1a and 1b are
responsible for ≈60% of global infection (predominate in Westernised
countries)[10]. Groups with particularly high infection risk include
intravenous drug users, sex workers (from drug use), health-care
workers, recipients of poorly-screened blood/organ transplants
(including haemophiliacs), tattoo artists (and their consumers) and
children born to infected mothers[10,11]. Worldwide epidemiological data
is scarce and unreliable[1,10,11], although in Western Australia there are ≈1100 cases every year, ≈125 of which are newly-acquired; males have twice the prevalence than females, and Aboriginals have a seven-fold higher rate[6].
After
an incubation period of 6-10 weeks, acute infection produces a milder
form of hepatitis than HBV (symptoms such as weight loss, vague stomach
discomfort, nausea and vomiting, fever, tiredness and jaundice occur in
only 20-25% of infected individuals)[1,10,11]. While ≈20% clear the
virus following acute infection, ≈15% become lifelong (infectious yet
asymptomatic) carriers and the
remaining ≈65% experience progressive liver disease up to 20-30 years
after exposure[1,10,11]. Approximately 20% of those suffering chronic
liver disease (a result of excessive inflammation in response to viral
infection) will develop cirrhosis (≈¼ then develop hepatocellular
carcinoma each year, with another ¼ experiencing liver failure per
annum)[1,11]. Fulminant hepatitis is extremely rare in HCV[10]. Factors
affecting HCV disease progression include concurrent HBV and HIV
infection, alcohol use and abuse (threefold risk increase with
alcoholism), fatty liver, HCV strain virulence, drug use and exposure to
other environmental toxins[10]. In developed countries, HCV-related liver
failure is the primary cause for liver transplant (70% 5-year survival
rate in Europe)[1,10]
Detection
involves a simple blood test and laboratory analysis[10]. No vaccine currently exists for HCV as the high genetic variability of the virus makes it difficult to target. Current treatment involves combined antiviral treatment with pIFNα
and ribavarin. which c This clears the virus in
45-80%
of chronic carriers (factors include ethnicity, host immune
factors, concurrent HIV infection and the type of HCV[1]. A patient is cured when they show no detectable virus in blood 6-12 months after
stopping antiviral therapy.
Genital Warts
Warts (also called verrucae) are small raised
lumps of the skin resulting from one of the many Human Papillomaviruses
(HPVs).With more than 100 strains, they vary in their preferred site of
infection (ranging from skin to the soft mucosal linings), their
symptoms and signs and (in some select strains) their ability to cause
cancers[1]. The four main types of warts are plantar warts, verrucae
vulgaris, flat warts and venereal warts (strains which produce the
latter type are considered STIs)[1].
More
than half of all sexually-active individuals are infected with at least
one strain of HPV in their lifetime, with half of all cases occurring
in sexually-active youths in the 15-24 age bracket[1]. Major risk
factors include early age of first sexual contact, promiscuity and
promiscuity of sexual partners and immunosuppression (ultimately
infection with HPV). Minor risk factors include the use of oral
contraceptives, smoking, number of children, family history, coinfection
with other STIs and lack of circumcision in male partner[1,12]. With an
incubation time of 1-6 months, the vast majority of HPV infections have
no adverse effects and are eventually cleared by the immune system (90%
within 2 years); strains 6 and 11 are responsible for ≈90% of genital
warts[1,12,13].
However,
HPV is also responsible for more than 99% of all cervical cancers, with
≈70% resulting from the high-risk strains 16 and 18[1]. More than half a
million women develop cervical cancer every year, and ≈90% of the
≈300,000 deaths each year occur in developing countries. Cervical cancer
results from the insertion of viral oncogenes into host cervical cells,
promoting uncontrolled cell growth and development of precursor
lesions. While the vast majority may remain benign for 10-20 years, some
may become invasive and malignant, producing cervical cancer[12]. In a
similar way, HPV-16 and HPV-18 are also the leading causes of anal
(90%), oropharyngeal (>12%) and vulval, penile and vaginal cancers
(40%)[12].
Signs
and symptoms of cervical cancer include the presence of visible white
tumours (in colposcopic examination), bleeding after sexual intercourse,
bleeding between periods, unusual vaginal discharge and ulceration and
pain (particularly during/after sexual activity)[12].
The
quadrivalent HPV vaccine (protects against types 6, 11, 16 and 18 with
almost >95% success after five years with no serious side effects)
has seen a significant decrease in the rate of infection and cervical
cancer development[1,13]. This vaccine is currently recommended for all
school-age children, and takes the form of three upper-arm injections
over a six-month period[13].
Pap
smears (cytological analysis) are still the most effective
population-scale screening method to detect precursor lesions if
performed properly (well-trained personnel using quality equipment)
every three years in those 25-50, (and every five
years in those 50-65 years of age)[12]. Colposcopy and tissue sampling
is then recommended in the case of positive Pap smear results for a
reliable diagnosis (and then should only be performed by trained and
skilled professionals)[12].
Removal of small, simple precursor lesions typically uses cryotherapy or loop
electrosurgical excision procedure, although these are ineffective with
invasive tumours and cannot be performed if the woman is pregnant or
has an active cervical infection (or PID)[12]. Cryotherapy uses a supercooled
metal disk to freeze-burn the mass with ≈90% success, while LEEP uses a
superheated thin wire to cut out and seal the tissue mass with ≈95%
success[12]. For mid-stage cervical cancers, surgical excision of the
infected region (cold knife conisation) is recommended (90-95% success
rate), although this requires hospitalisation and anaesthesia, and
cannot be performed if the woman is pregnant (damage to the cervix may
also lead to infertility) or has PID[12].
For
large or metastatic end-stage cancers both removal of the primary
tumour, surrounding tissue (often requiring removal of the cervix aka.
trachelectomy, womb aka. hysterectomy and sometimes in advanced cases
removal of surrounding infected immune tissue aka. lymphadenectomy by
trained gynaecological surgeons) and radio/chemotherapy is
essential[12].
References
- Willey JM, Sherwood LM, Woolverton CJ. Prescott's Microbiology. 8th ed. Singapore: McGraw-Hill; 2011.
- Department of Health (WA). Genital Herpes Fact Sheet [Internet]. Perth,
WA (Australia): Department of Health (WA); 2012 [cited 2014 Mar 29].
Available from: http://www.public.health.wa.gov.au/2/408/2/genital_herpes_fact_sheet.pm.
- Looker KJ, Garnett GP, Schmid GP. An estimate of the global prevalence and
incidence of herpes simplex virus type 2 infection. Bull World Health Organ.
2008 Oct;86(10):805-12.
- UNAIDS. UNAIDS report on the global AIDS epidemic 2013. Geneva: UNAIDS; 2013. Available from: http://www.unaids.org/en/resources/campaigns/globalreport2013/globalreport/.
- World Health
Organization. Global incidence and prevalence of selected
curable sexually transmitted infections – 2008. Geneva: World Health
Organization, Department of Reproductive Health and Research; 2012. Available
from: http://www.who.int/reproductivehealth/publications/rtis/stisestimates/en/index.html.
- Department of Health (WA). Quarterly Surveillance Report: Notifiable
Sexually Transmissible Infections and Blood-borne Viruses
in Western Australia - December 2013 [Internet]. Department of Health
(WA) - Public Health and Clinical Services; 2014 Feb [cited 2014 Mar
26]. Report No.: 11(1). Available from: http://www.public.health.wa.gov.au/cproot/5693/3/stibbv_2013_4th_quarterly_report.doc.
- Poropatich K, Sullivan DJ Jr. Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression. J Gen Virol. 2011 Feb;92(Pt 2):247-68.
- World Health
Organization. Hepatitis B. Geneva: World Health
Organization, Global Alert and Response Group; 2002 Available from: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/.
- World Health
Organization. Hepatitis B Fact Sheet [Internet]. Geneva (Switzerland): World Health
Organization, Global Alert and Response Group; 2013 [cited 2014 Mar 30]. Available from: http://www.who.int/mediacentre/factsheets/fs204/en/.
- World Health
Organization. Hepatitis C. Geneva: World Health
Organization, Global Alert and Response Group; 2003 Available from: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/.
- World Health
Organization. Hepatitis C Fact Sheet [Internet]. Geneva (Switzerland): World Health
Organization, Global Alert and Response Group; 2013 [cited 2014 Mar 30]. Available from: http://www.who.int/mediacentre/factsheets/fs164/en/.
-
- World Health Organization. Comprehensive cervical cancer control: a guide to essential practice. Geneva: World Health Organization; 2006. Available from: http://whqlibdoc.who.int/publications/2006/9241547006_eng.pdf.
