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Anorectal Gonorrhoea
Anorectal gonorrhoea is more common in women and homosexual men. It is usually
asymptomatic but constipation, anal pruritus, tenesmus, and rectal bleeding may be
seen as symptoms.
Ocular Gonorrhoea
Ocular gonorrhoea occurs due to autoinoculation with fingers infected with
urogenital site. Gonococcal conjunctivitis may be serious and has to be treated
promptly.
Neonatal Gonorrhoea
Newborns exposed to gonococci during birth may develop gonococcal ophthalmia
neonatorum. Prophylactic instillation of ophthalmic preparations like 1% silver
nitrate eye drops or erythromycin or tetracycline containing eye drops prevent
ophthalmia neonatorum but the treatment requires administration of systemic
antibiotics. The symptoms include non-specific conjunctivitis leading to corneal
ulceration and finally blindness if left untreated. Pharyngeal gonococcal colonisation
with coughing is seen in certain cases. Septic arthritis is another common symptom
in newborns.
Gonorrhoeal Arthritis
Gonorrhoeal arthritis and dermatological lesions may be seen as a result of
disseminated gonococcal infection (DGI).
Non-pharmacological Management
The transmission of gonorrhoea and other genital transmission can be effectively
stopped by proper usage of condoms. A diaphragm or cervical sponge with
nonoxynol 9 may be used for protection against gonorrhoea and chlamydia. All
patients should be advised to go for evaluation and treatment of their sex partners.
Patients should be advised against sexual intercourse till therapy is going on and the
patients and their partners are free from all symptoms. Public health education,
individual counselling of patients, and behaviour modification can help in prevention
of gonorrhoea. The sexually active persons as adolescents should be screened for
sexually transmitted infections.
Pharmacological Management
Ceftriaxone is the only recommended agent for treatment of gonorrhoea. It is
administered as a single dose intramuscularly and is effective in the treatment of
urethral, cervical, rectal and pharyngeal infections. Cefixime 400 mg oral dose may be
substituted if ceftriaxone is not available but it has less efficacy. Ceftriaxone is effective
in coexisting infections of syphilis and gonorrhoea. Concomitant treatment with
azithromycin or doxycycline is recommended for gonorrhoea patients as they may be
having coexisting chlamydial infections. Azithromycin is administered orally in a one
time dose of 1000 mg. Doxycycline is given orally in a dose of 100 mg twice a day in
cases of allergy to azithromycin.
Ceftriaxone is considered effective in pregnant women infected with gonorrhoea,
DGI, gonococcal meningitis, endocarditis and gonococcal infections in children.
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109
In order to prevent complications of ophthalmia neonatorum, prophylaxis is
recommended using topical ocular antimicrobials. Erythromycin 0.5% should be
instilled in each conjunctival sac immediately after birth.
The treatment of choice is mentioned in Table 8.4.
Table 8.4: Treatment of choice
Condition Treatment of choice Additional regimen
Uncomplicated gonorrhoea Ceftriaxone 125 mg IM single dose Treatment of chlamydia: Doxycycline
of urethra, cervix, rectum or or cefixime 400 mg PO single dose 100 mg PO BID for one week or
pharynx or quinolones like ciprofloxacin, azithromycin 1 g PO in single dose
ofloxacin or levofloxacin
Gonococcal conjunctivitis Ceftriaxone 1 g IM single dose Lavage of infected eye with saline
solution once
Gonococcal ophthalmia Ceftriaxone 25–50 mg/kg IV or IM Prophylaxis topical application of
neonatorum single dose. Dose not to exceed erythromycin 0.5% at birth
125 mg
Disseminated gonococcal Ceftriaxone 1 g IM or IV or If patients allergic to beta-lactam
infection cefotaxime 1 g IV drugs, then spectinomycin 2 g IM
KEY POINTS
• Gonorrhoea is a sexually transmitted disease caused by Neisseria gonorrhoeae.
• It may affect the urinogenital tract, pharynx, anus or may get disseminated throughout the body.
• The disease may get transmitted from mother to child and cause gonococcal ophthalmia
neonatorum in neonates
• The drug of choice is ceftriaxone.
SYPHILIS
Syphilis is a chronic infectious, systemic disease caused by Treponema pallidum, usually
transmitted sexually and is characterised by episodes of active disease and periods of
latency.
Aetiology
The spirochaetales include three genera of pathogens for humans and other animals.
Out of that, Treponema pallidum subspecies pallidum causes venereal syphilis.
Treponema pallidum is a thin spiral organism with a cell body surrounded by a
trilaminar cytoplasmic membrane, a delicate peptidoglycan layer providing structural
rigidity and a lipid rich outer membrane. Endoflagella wind around the cell body
helping in motility. T. pallidum cannot be grown in vitro, and its genome sequencing
was done in 1998 after which it was better understood. The human is the only natural
host for T. pallidum.
Pathogenesis
Treponema pallidum penetrates mucous membrane or microscopic abrasions of skin
and reaches the systemic circulation in a few hours. It invades regional lymphatic and
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blood vessels. There is rapid transfer of the organism in the human body. The
unicellular organism divides approximately every 30 hours. The incubation period in
humans is around 3 to 6 weeks.
The primary lesion appears at the site of inoculation which heals spontaneously in
about six weeks.
The symptoms of secondary syphilis are seen after approximately 6 to 8 weeks of
healing of chancre. The secondary skin lesions are seen. Treponeme are found in
tissues like aqueous humour of the eye and cerebrospinal fluid. Clinical hepatitis,
glomerulonephritis, and generalised non-tender lymphadenopathy are seen in
secondary syphilis.
Almost 1/3rd of patients with untreated latent syphilis used to develop tertiary
disease in the pre-antibiotic era. The common types of tertiary disease were gumma,
cardiovascular syphilis, and symptomatic neurosyphilis.
Clinical Manifestations
Clinically, Syphilis can be Divided into:
• Incubating
• Primary
• Secondary
• Latent
• Tertiary
The incubation period is approximately three weeks. It is related to the size of the
inoculum and may range from 3 days to 3 months.
Primary syphilis shows chancre. It is usually a single painless papula which erodes
and heals spontaneously in a few weeks. The patient shows lymphadenopathy.
Secondary syphilis is a generalised illness which develops after about 2 to 8 weeks.
The untreated patients show lesions of the skin and mucous membranes. They may
be maculopapular, papular or pustular. Lymphadenopathy is also seen.
Latent syphilis is the period during which no clinical symptoms are seen but
serological tests are positive for syphilis.
Late tertiary syphilis is a slowly progressive disease and can affect any body system
even after many years. Late syphilis can be clinically classified as neurosyphilis,
cardiovascular syphilis or gummatous syphilis. Neurosyphilis has CNS involvement
which is asymptomatic initially and can be detected by evaluating CSF. The
symptomatic neurosyphilis patients may show focal or generalised seizures, visual
disturbances, altered reflexes, speech disturbances, dementia, and stroke. Cardiovascular
syphilis may show inflammation in blood vessels. Gumma syphilis is characterised by
development of hyperimmune granulomas called gummas involving the skin and the
bones.
Congenital syphilis is the transmission of Treponema pallidum from mother to
foetus. They may show early manifestations within first two years of life or late
manifestations which appear after two years of life and is non-infectious. The early
manifestations are infectious and similar to secondary syphilis in adults.
Pharmacological Management
The drug of choice for the treatment of syphilis is penicillin G. The other antibiotics
which are effective in the treatment of syphilis are tetracyclines, erythromycin,
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111
cephalosporins, aminoglycosides, and spectinomycin. These drugs can inhibit
T. pallidum only in very large doses.
Penicillin G benzathine is used in the treatment of early syphilis. The recommended
dose is 2.4 million units as single dose.
In case abnormalities are found in CSF in late latent syphilis, the recommended dose
is 7.2 million units total of penicillin G benzathine.
If the patient is allergic to penicillin, a two-week course of therapy with tetracycline
or doxycycline is recommended for early syphilis patients. A four-week dosage is
recommended for late latent syphilis in case of HIV infected persons. The nonpenicillin regimens should be used with caution if compliance or follow-up cannot be
ensured in patients with allergy to penicillin and HIV infected. In late syphilis, the
patient should be desensitised and treated with penicillin.
IV administration of aqueous crystalline penicillin G is recommended for patients
of neurosyphilis.
The only recommended agent for the treatment of syphilis in pregnancy is
penicillin. In case the patient is allergic to penicillin, then desensitisation should be
carried out and penicillin therapy should be administered.
Mild reactions with fever, chills, headache, myalgia, tachycardia, increased
respiration rate, transient adenopathy may be seen. This is called the JarischHerxheimer reaction. This is thought to be a response to release of antigen by the
Treponema due to rapid lysis of organisms by antibiotics.
KEY POINTS
• Syphilis is a chronic infectious, systemic disease caused by Treponema pallidum, usually
transmitted sexually.
• It is characterised by episodes of active disease and periods of latency.
• Clinically, syphilis is of incubating, primary, secondary, latent and tertiary types.
• The drug of choice for the treatment of syphilis is penicillin G.
8.6 MALARIA
Malaria is a mosquito-borne infectious disease caused by the protozoan of the genus
Plasmodium. Four species of the genus Plasmodium which cause malaria in humans
are: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale.
Life Cycle of Malarial Parasite
The life cycle of a malarial parasite involves two hosts (Fig. 8.1). The following are the
stages in the life cycle:
1. A malaria-infected female Anopheles mosquito inoculates sporozoites into the
human host during a blood meal.
2. Sporozoites infect liver cells and grow into schizonts, which break to release
merozoites.
3. The parasites first replicate in the liver (exo-erythrocytic schizogony), after which
they undergo asexual multiplication in the erythrocytes (erythrocytic schizogony).
4. Merozoites infect red blood cells, which become the ring stage trophozoites and
mature into schizonts. These schizonts rupture to release merozoites.
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Fig. 8.1: Malaria life cycle and primary areas of drug activity
5. Some parasites develop into gametocytes, which are the sexual erythrocytic stages.
The parasites in the blood stage are responsible for the symptoms of the disease.
During a blood meal, the Anopheles mosquito ingests the gametocytes, male
(microgametocytes) and female (macrogametocytes). The parasites’ multiplication
in the mosquito is known as the sporogonic cycle. In the gut of the mosquito, the
microgametes penetrate the macrogametes, forming zygotes. The zygotes become
motile and elongated (ookinetes), which invade the gut wall of the mosquito where
they develop into oocysts. The oocysts grow, rupture, and release sporozoites,
which migrate to the mosquito’s salivary glands. When the Anopheles mosquito
takes a blood meal on another human, the saliva is injected together with the
sporozoites, which begin a new cycle.
Pathophysiology
When saliva is injected with sporozoites during a blood meal by the Anopheles
mosquito, an individual gets infected. Sporozoites spread through the
bloodstream to the liver, resulting in the development of exoerythrocytic forms
(tissue schizonts, hypnozoites) within hepatocytes. Merozoites are released from
tissue schizonts into the circulation approximately 1 to 2 weeks later, which
invade the red blood cells. P. falciparum merozoites proliferate within
erythrocytes of all ages, whereas other malarial species are restricted to certain
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subpopulations. Within erythrocytes, merozoites consume haemoglobin and
mature into ring trophozoite, and schizont stage parasites or into sexual male and
female gametocytes by asexual replication. After 48 hours, the schizont-infected
red cells rupture to release merozoites, which cause erythrocytic invasion. When
the gametocyte-infected red cells are ingested by Anopheles mosquitoes,
fertilisation of male and female forms takes place within the mosquito gut and
sporozoites develop, which travel to the mosquito’s salivary glands, completing
the infectious cycle. P. falciparum or P. malariae infections do not relapse. However,
P. ovale and P. vivax hypnozoites can become active weeks to months after the
initial infection has resolved.
Clinical Manifestations
Malaria has a typically nonspecific presentation that includes fever, malaise,
rigors, and diaphoresis in more than 80% of patients. The onset of symptoms
commonly occurs about two weeks after exposure. Anorexia, nausea, and
vomiting are observed in approximately 33% of patients, and diarrhoea, cough,
and abdominal pain are seen in around 16% of patients. As the disease progresses,
there is the development of splenomegaly and hepatomegaly. Cycling of fever
every 48 to 72 hours due to synchronised schizont rupture may occur, especially
with prolonged untreated illness. Falciparum malaria can rapidly become lifethreatening due to parasitized cells adhering to vascular endothelium, leading to
acute renal failure, symmetrical encephalopathy (i.e., cerebral malaria), and
pulmonary oedema.
Pharmacological Management
Prophylaxis: Antimalarial drugs are prescribed for residents of non-endemic areas
who wish to travel to an endemic area to prevent or reduce the symptoms caused by
malarial parasites. Chloroquine is the drug of choice (300 mg orally weekly).
Mefloquine is an alternative option for areas with a resistant strain.
Treatment of an acute attack: Microscopy of stained thick and thin blood films
confirms the diagnosis of malaria. The initial treatment of acute malaria is the same
irrespective of the species of parasite, unless the infection is severe and caused by
P. falciparum, particularly in children and non-immune subjects. It is the treatment of
relapsing malaria that differs.
Quinine: It is the main alkaloid obtained from the bark of the Cinchona tree. It has
been utilised for suppressive prophylaxis and clinical cure of all types of malaria since
it is actively schizonticidal. It is also weakly gametocidal for P. vivax and P. malariae,
but not for P. falciparum. Quinine by IV drip is the therapy of choice for acute attacks
of falciparum malaria in areas where chloroquine-resistant strains of P. falciparum
exist.
Adverse effects of quinine include cinchonism (flushed and wet skin, tinnitus,
blurred vision, impaired hearing, dizziness, vomiting, and diarrhoea), gastrointestinal
discomfort, bone marrow depression, blood disorders, renal failure, and hypersensitivity
reactions.
Chloroquine: It is a 4-aminoquinoline that is an excellent schizonticidal drug for all
types of malaria. It is very effective in treating acute attacks of vivax malaria. It
suppresses all types of malaria except the resistant strains of P. falciparum.
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The other two 4-aminoquinolines, namely hydroxychloroquine and amodiaquine,
are effective for the prevention and treatment of acute attacks of malaria caused by
P. vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum.
Primaquine: It is highly effective against the primary exoerythrocytic stages of
falciparum and vivax malaria. As a result, it is used to induce radical cures of relapsing
malaria. Since it is highly active against the gametocytes of all four species, it is used
to prevent malaria transmission.
Treatment of Chloroquine-sensitive Acute Malaria
Chloroquine phosphate 600 mg orally followed 6 hours later by 300 mg on day one;
300 mg once daily on days two and three.
OR
Amodiaquine hydrochloride 600 mg orally followed by 200 mg on day one; 400 mg
once daily on days two and three.
OR
Quinine sulphate 600 mg orally, 8-hourly for 3 days, followed by 600 mg twice daily
for the next 5–10 days.
Chloroquine-resistant Malaria
Quinine sulphate 600 mg orally tid for 5 days, followed by sulphadoxine-pyrimethamine
3 tablets as a single dose.
OR
Quinine sulphate 600 mg tid plus doxycycline 100 mg bid/clindamycin 10 mg/kg bid
for 7 days
OR
Sodium artesunate 100 mg orally, 12-hourly for 3 days, plus sulphadoxine 500 mg +
pyrimethamine 25 mg 3 tablets as a single dose on day one.
OR
Sodium artesunate 100 mg orally, 12-hourly for 3 days plus mefloquine 750 mg on day
2 and then 500 mg on day 3.
OR
Sodium artesunate 100 mg orally plus doxycycline 100 mg bid/clindamycin 10 mg/kg
bid for 7 days
OR
Atovaquone 250 mg + proguanil 100 mg combination, four tablets (single dose) daily
for 3 days.
Multidrug Resistant (MDR) Malaria
• Artesunate + SP (sulphadoxine and pyrimethamine)/mefloquine/amodiaquine
• Artemether + lumefantrine
• SP + chloroquine/amodiaquine/quinine/mefloquine
• Quinine + tetracycline/clindamycin
• Atovaquone + proguanil
• Chlorproguanil + dapsone
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115
Of these combinations, artesunate + SP (sulphadoxine and pyrimethamine) is used
in the National Malaria Programme of India.
Cerebral malaria, characterised by significant CNS symptoms, occurs as a
complication of P. falciparum infection and carries high mortality and needs
immediate treatment. Dexamethasone 4–6 mg is administered parenterally first,
which is every 4–6 hours, together with quinine hydrochloride 600 mg in 300 ml of
0.9% sodium chloride injection infused slowly over a period of at least one hour. This
dose of quinine is repeated every 6–8 hours (a maximum of 1.8 g total daily dose). The
patient should be switched to oral quinine sulphate after a positive clinical response.
Prevention of Malaria
Malaria can be prevented by taking antimalarial drugs when travelling to areas where
malaria is very common and by using protective measures against mosquito bites.
Mosquito bites can be prevented by the use of a mosquito net over the bed, applying
mosquito repellent to exposed skin and wearing long-sleeved clothing and long pants
when outdoors at night. The windows of the rooms should be covered with screens
to prevent mosquitoes from entering. There should be no stagnant water around
the house as mosquitoes thrive in stagnant water. WHO has recommended the use
of malaria vaccine in children of some African regions with moderate to high
P. falciparum transmission.
KEY POINTS
• Malaria is a mosquito-borne infectious disease caused by one of the protozoa: Plasmodium
falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale.
• The life cycle of a malarial parasite involves two hosts: Female Anopheles mosquito and man.
• The symptoms of malaria are fever, malaise, rigors, and diaphoresis.
• Malaria can be prevented by the use of antimalarial drugs or protective measures against mosquito bites.
8.7 HIV AND OPPORTUNISTIC INFECTIONS
Human Immunodeficiency Virus (HIV) infection and Acquired Immune Deficiency
Syndrome (AIDS)
Human Immunodeficiency Virus (HIV) is a retrovirus that can be divided into:
• HIV-1
• HIV-2
Both the types of HIV infections deplete the helper T-lymphocytes (CD4 cells/cubic
mm), resulting in continued damage to the immune system, which leads to the
occurrence of opportunistic infections (OIs) and malignancies.
HIV infection is a sexually transmitted disease. One can get infected with HIV
through infected blood, semen, or vaginal secretions. This can happen by having sex
with an infected partner, by sharing needles or through blood transfusions. It can spread
from an infected mother to child during pregnancy, childbirth, or breastfeeding.
The most severe stage of HIV (stage 3) is AIDS (acquired immunodeficiency
syndrome) and is a life-threatening condition. When people develop certain OIs or
their CD4 cell count drops below 200 cells per millilitre of blood, they are diagnosed
with AIDS.
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Pathophysiology
HIV, like other retroviruses, contains the enzyme reverse transcriptase and consists of
a lipid bilayer membrane surrounding the capsid. Its surface glycoprotein molecule
has a high affinity for the CD4 receptor protein found mainly on T-helper/inducer
lymphocytes. Monocytes and macrophages can also get infected as they possess CD4
receptors in low densities. The process of HIV entry is complex, and in addition to CD4
attachment, subsequent binding to co-receptors such as CCR-5 or CXCR-4 and
membrane fusion also occur.
The virus penetrates the host cell, sheds its outer coat, and releases the genetic
material. The reverse transcriptase enzyme helps in the conversion of the viral RNA
to DNA. The viral DNA is subsequently integrated into the host genome in the cell
nucleus, where it undergoes transcription and translation, allowing new viral proteins
to be produced. New virus particles are then assembled and come out of the host cell,
finally maturing into infectious virions under the influence of the protease enzyme.
Figure 8.2 shows the life cycle of HIV along with the sites of action of currently
available antiretroviral agents.
Immediately after primary HIV infection, there is a high rate of viral turnover. The
infection reaches a state of equilibrium where the infection may appear to be clinically
latent, but in fact, as many as 10,000 million new virions are produced each day.
Fig. 8.2: Life cycle of HIV and the sites of action of currently available antiretroviral agents
Infectious Disorders
117
As a result of chronic infection, cells possessing CD4 receptors, particularly the
T-helper lymphocytes, are depleted from the body. As a result, the individual becomes
susceptible to a variety of infections and tumours. The rate at which this immune
progression progresses is variable. Some individuals may rapidly develop severe
immunosuppression, whereas others may have been infected with HIV for many years
but still maintain a relatively intact immune system.
Clinical Manifestations
The clinical presentation of an acute primary HIV infection can be confused with that
of a typical viral illness; however, it should be suspected in people with a history of
high-risk behaviours or the presence of sexually transmitted diseases. Common signs
and symptoms are nonspecific and generally occur within days to weeks after the
initial exposure, and include fever, fatigue, myalgias, arthralgias, headache,
lymphadenopathy, pharyngitis, and oral lesions. A maculopapular rash is present in
40 to 80% of the persons during the acute illness.
The patients develop opportunistic infections, that is, infections that would
normally not cause disease in an immunocompetent host, for example, P. jirovecii
pneumonia or cytomegalovirus (CMV). For example, Kaposi’s sarcoma and nonHodgkin’s lymphoma are also observed in untreated HIV patients.
Non-pharmacological Management
No vaccine is available to prevent HIV infection. HIV educational programmes must
be conducted for the general population where they should be instructed about the
ways of transmission of the virus and how to prevent it. The level of support for AIDS
prevention and control should also be increased.
Pharmacological Management
The aims of therapy in HIV positive individuals are to:
• Improve the quality and length of life;
• Prevent deterioration of immune functions and/or restore immune functions;
• Treat and/or prevent opportunistic infections;
• Relieve symptoms.
Antiretroviral therapy: The decision to start antiretroviral therapy is guided by
CD4 cell count (less than 200 cells/ml), severity of clinical symptoms, and plasma viral
load (greater than 100,000 copies/ml). Generally, a combination of three antiretroviral
agents is prescribed to increase efficacy and reduce the development of drug-resistant
virus.
1. Nucleotide reverse transcriptase inhibitors (NRTI): These drugs inhibit the reverse
transcriptase of HIV and cause premature termination of chain elongation of DNA.
They block acute infection but are minimally active against chronically infected cells.
Azidothymidine (AZT, zidovudine): The drug is used in a dose of 200 mg orally
three times a day. It may cause GI upset, headache, myalgia, and insomnia. Serious
adverse drug reactions include severe anaemia, granulocytopenia, and
thrombocytopenia due to bone marrow suppression.
Didanosine (Videx): This drug has similar actions as AZT but a longer duration of action.
It is nontoxic to hemopoietic cells but can cause pancreatitis and peripheral neuropathy.