Opportunistic infections

     Opportunistic Infections and Other
Conditions Associated with HIV Disease

An opportunistic infection (OI): An infection caused by an organism that does not usually cause disease in a health person with a normal immune system.
•  When the immune system is compromised such as through HIV infection, this creates an opportunity for the pathogen to cause disease.
•  Other examples of people with depressed immunity include very young children and very old people, patients with advanced cancer and/ or on chemotherapy following organ
transplantation.
•   OI complications can be general or divided into disease syndromes in the various systems such as
>gastrointestinal system,
>respiratory system,
>central nervous system,
>dermatologic (skin),
> head and neck,
>cardiovascular,
>genitourinary or renal.
•  OIs are important HIV indicator diseases and may be the trigger for an HIV diagnosis.
•   The natural history of HIV involves a progressive loss of CD4 T lymphocytes.
•   As CD4 level declines, risk of contracting OIs increases.
•   OIs may be bacterial, viral, fungal, or parasitic.
•  All body organs/systems can be affected.
•  People with HIV and AIDS are especially susceptible to OIs due to suppression of their immune system, psychological stress which can influence the immune system and depletion of nutritional status.

•  Treatment for OIs is an entry point into HIV diagnosis and care.
•  Treatment can improve survival and quality of life.
•  Diagnosis determines WHO staging and helps to identify whether a patient is eligible for ART.
•   OIs must be treated before starting ART.

Common Dermatologic Conditions in PLHIV
•  Skin rashes, sores, and generalized pruritis are most common
•   General causes include:
o Generalized papular pruritic eruption (PPE)
o Infestation with external parasites e.g. scabies
o Fungal skin infections (Dermatomycoses)
o Herpes zoster infection
o Herpes simplex infection
o Kaposi sarcoma (KS)
o Bacterial skin infection e.g. Impetigo
o Seborrheic dermatitis and Sebo-psoriasis Popular Pruritic Eruptions (PPE)
•   PPE is a WHO Stage 2 illness
•   Generally occur before other opportunistic infections
•   The lesions, mostly on the extremities, are common presenting signs of HIV
•   PPE may be an altered and hyperactive response to insect bites
•   Cause of intense itching in PLHIV
•   Antihistamines may relieve itching
•   PPE can occur at higher CD4 levels but worse with low CD4Herpes Zoster (Shingles)
•   Herpes Zoster is a WHO Stage 2 illness
•   Caused by reactivation of dormant Varicella zoster virus (VZV) infection
•   Primary infection with VZV is acquired through inhalation of droplets containing the virus
•   Primary infection results in varicella (chickenpox)
•   Recurrent infection results in herpes zoster (shingles) years after the first infection
•   Can occur at all CD4 levels
•   More frequent at lower CD4 counts (CD4 < 350)
•   Patients with low CD4 counts are more prone to recurrent episodes or multidermatomal involvement
•   Responds to acyclovir if begun within 72 hours of onset of symptoms
• Post-herpetic neuralgia is a serious complication
Molluscum Contagiosum (MC)
• A common, benign viral infection of the skin and mucous membranes caused by the molluscum contagiosum, a DNA pox virus
• 2-5 mm pearly umbilicated lesions
• Usually multiple lesions
• It typically affects children, but can also affect adults
• Not invasive, but patients feel uncomfortable and stigmatised
• Common at low CD4 < 100
• Extensive MC Is a WHO Stage 2 illness in children
• ART is the most effective treatment, with complete but slow disappearance of lesions
Seborrheic Dermatitis
• Inflammatory eruption usually affecting the scalp and face
• Can be seen at all stages of HIV infection
• Aetiology unclear but associated with Malassezia sp (ptyrosporum ovale)
• Lesions generally improve with ART
• Is a WHO Stage 2 Illness in adults

Kaposis Sarcoma
•  Common cancer in PLHIV aetiologically linked to Human Herpes Virus-8 (HHV 8) but KS can also occur in HIV-negative patients
• Can occur at any CD4 level
• Less extensive disease responds to ART
• Refer patients with severe disease to a hospital with experienced doctors
• Can be complicated by pulmonary involvement
• Varied presentations, which include cutaneous, mucosal, or visceral involvement

Kaposis Sarcoma in Children
• KS used to be rare in children
• In children, it commonly presents with generalised lymphadenopathy
• Can also present as black mucocutaneous lesions
• Confirmation requires examination of a small tissue from the lesion or lymph node HIV-Related Respiratory Illnesses
• Lung problems are common HIV-related respiratory illnesses.
• These include the ‘Big 3’:
o Bacterial Pneumonia
o Pneumocystis jiroveci pneumonia (PCP)
o Tuberculosis (TB) – This will be dealt in a separate session
Bacterial Pneumonia (BP)

• The clinical presentation of bacterial pneumonia includes fever, chills, purulent sputum and abrupt start
• It can occur at any CD4 count
• It is commonly caused by Streptococcus pneumonia, Hemophilus influenza and Staphylococcus aureus

• The diagnosis of bacterial pneumonia is through

o Clinical – history and examination (crepitations, increased respiratory rate, decreased air entry)
o Chest x-ray
o Full blood picture as a supportive (increased neutrophils)

• Treatment for bacterial pneumonia in PLHIV is the same as in PLHIV and include:
o Amoxicillin or
o Amoxicillin + Clavulanic acid
Pneumocystis Pneumonia (PCP)
• PCP is caused by the pathogen Pneumocystis jiroveci
• The susceptibility of developing PCP is greatly increased at CD4 counts below 200
• Clinical features of PCP include:
o Fever
o Dry cough of slow evolution
o Diagnosis is suspected based on clinical presentation and high index of suspicion
o Chest X-ray can be helpful in the diagnosis but the results can be varied including normal, interstitial infiltrates, pneumothorax, poor deep inspiration or occasionally pneumatocoeles

• Treatment of PCP is by Cotrimoxazole high dose (1920 mg 3times/day) for 21 days, and
prednisolone can be added if the patient has severe dyspnoea
• Note that, these patients need to be referred to hospitals for diagnosis and treatment
Other OIs Affecting the Lungs
• Several causes of respiratory symptoms can co-exist, including:
o Atypical bacteria (chlamydia and mycoplasma)
o Malignancies (Kaposi sarcoma, lymphoma)
o Toxoplasmosis
o Cytomegalovirus (CMV)
o Mycobacterium avium complex (MAC) at (CD4<100) and alsoCryptococcosis

HIV-Related CNS Disease
• HIV-related CNS diseases include:
o Bacterial meningitis (BM)
o Cryptococcal Meningitis (CRP)
o Tuberculous meningitis (TB)
o Toxoplasmosis
o Syphilis
o CNS lymphoma
Cryptococcal Meningitis
• Cryptococcal meningitis is caused by Cryptococcus neofomans, which is yeast (fungus)
• It occurs in soil and infection in humans is through inhalation
• It is a WHO Stage 4 illness in children and adults
• It occurs at CD4 < 50
• Symptoms of cryptococcal meningitis include:
o Sub-acute onset of fever
o Headache
o Altered mental status
o Sometimes neck stiffness
o 50% of patients with cryptococcal meningitis may also have pulmonary symptom
• Diagnosis of CM is done by examining cerebral spinal fluid (CSF) after performing a lumbar puncture with India ink positive (sensitivity 50-80%) and increased opening pressure

Treatment CM
Induction phase
  Fluconazole 1200mg for
Consolidation phase
  Fluconazole 800mg for 8weeks
Mentainance phase
   Fluconazole 200mg for a year

• Note that patients with suspected cryptococcal meningitis need to be referred to hospitals for proper diagnosis and management Cerebral Toxoplasmosis
• Cerebral toxoplasmosis is caused by toxoplasma gondi (TG), a protozoa
• TG is a parasite of mammals and is transmitted when oocysts excreted by pets (cats) are ingested
• Infants and young children infected by their mothers, and older children and adults are exposed through eating undercooked meat
• Cerebral toxoplasmosis is clinical disease that results from reactivation and mainly affects the brain
• Patients with cerebral toxoplasmosis present with:
o Headache
o Mental status changes
o Weakness of a part of the body and progressive focal deficit
o Convulsions (seizures)
• It generally occurs with CD4 < 100
• Its differential diagnoses are tuberculoma, cerebral lymphoma and cryptococcoma
• Note that patients with suspected signs and symptoms of toxoplasmosis need to be referred to hospitals for investigations and management

Peripheral Neuropathy
• Peripheral neuropathy is a common HIV complication in Tanzania
• It is usually symmetrical, stocking-glove distribution (it starts in the hands and feet and then if it progresses, it works its way from there throughout the body)
• It may be caused by HIV itself, or it can be drug-induced (mainly d4T and INH) or
caused by alcoholism
o If the patient begins having peripheral neuropathy after starting ART or TB treatment, suspect drug toxicity (d4T or INH)
• The treatment for peripheral neuropathy is comprised of:
o Analgesic
o Vitamin B and (pyridoxine)
o Consider amytriptilline or carbamazepine if no relief on simple analgesics
• Refer the patient to hospital for proper evaluation and management
HIV-Related Gastrointestinal Disease
• The main gastrointestinal problems that occur in relation to HIV include:
o Oro-oesophageal diseases
o Candidiasis ‘thrush’
o Herpes simplex virus (HSV)
o Apthous ulcers
o CMV ulcers
o Kaposi sarcoma (KS)
o Diarrhoeal illnesses
Oro-Oesophageal Diseases
• Oro-oesophageal diseases can be caused by candida, which is visually diagnosed
• It occurs increasingly at CD4 < 300
• It occurs in two forms: oral candidiasis and oesophageal candidiasis
• It presents as oral candidiasis for patients in WHO stage 3, and its signs and symptoms include raw patches on the tongue or the palate
• Symptoms also may include burning pain, altered taste sensation, and dysphagia
• It is very important to examine HIV patients’ mouths
• Angular cheiliitis is a form of oral candidiasis
• Oesophageal candidiasis occurs in WHO stage 4
• Diagnosis of oral candida (otherwise known as thrush) is made on appearance alone
• Diagnosis of oesophageal thrush is based on presentation and response to empiric treatment
• Treatment for thrush includes Nystatin mouthwash (dissolved in half glass water) clotrimazole lozenges, and Fluconazole if oesophagitis or intractable oral thrush
Diarrhoeal Illness
• Diarrhoea is a common problem in PLHIV
• It is mainly caused by pathogens including
o Cryptosporidiosis (cryptosporidium parvum, which occurs at CD4 < 50)
o Isosporiasis (Isospora belli)
o Giardiasis (Giardia lamblia)
o Bacterial pathogens (Shigella, Salmonella)
• Some of the causes of non infectious diarrhoea are:
o Malignancies such as Kaposi sarcoma and lymphoma

o HIV damage to intestinal lining causing malabsorption and diarrhoea
o ARVs may be associated with diarrhoea
o ARVs protease inhibitors e.g. lopinavir/ritonavir
• A good anti-diarrhoeal drug is Loperamide, which can be used for persistent diarrhoea among adults with no obvious treatable causes
• Anti-diarrhoeals should not be used in a patient with obvious signs of an acute bacterial infection
• Assessment of hydration status is very important as replacement of fluids is the most important step in management of diarrhoea
• In case of acute diarrhoea, if the patient has mild or moderate dehydration, oral
rehydration solution is advised
• Severe dehydration is managed by admission and intravenous rehydration, and antibiotics guruin the case of bloody stools
Other HIV-Related Conditions
Cytomegalovirus (CMV) Retinitis
• Common among patients with advanced AIDS (CD4 < 50)
• It is WHO Stage 4 for children and adults
• Can cause painless blurring or loss of central vision (blind spots) and neurologic disease such as encephalitis/polyradiculopathy
• Refer the patient to hospital for investigation and treatment
Lymphadenopathies
• Several diseases can cause HIV related lymph node enlargement
• In HIV-infected patients, most common causes are:
o Persistent generalized lymphadenopathy
o TB lymphadenitis
o Kaposi sarcoma
o Malignant lymphoma
• Note: when managing lymph node enlargement, treat the underlying disease.
• In most cases these patients need referral to hospitals for proper diagnosis and management Lymphoma
• Cancers of the lymphnodes characterized by proliferation of abnormal B or T-cells
• Epstein Barr Virus (EBV) is aetiologically linked to non-Hodgkin’s tumours and Burkitt-type lymphomas
• Can spread to almost any part of the body’s organs or tissues including liver, bone marrow, spleen, or brain
• Common childhood type is Burkitt's lymphoma
• Cerebral or B-cell non Hodgkin’s lymphoma is a WHO stage 4 condition
• Two general types, both of which are seen in HIV infected patients:
o Non-Hodgkin’s lymphomas

Classified by how quickly they spread: low-grade, intermediate-grade, or high-
grade
Intermediate and high-grade types of non-Hodgkin’s lymphoma are more
commonly found in AIDS
o Hodgkin’s Lymphoma

Presentation of Lymphoma
Non-CNS:
o Depends on area involved
o Usually lymphnode swellings
o Constitutional symptoms:
Fevers
Nightsweats
Weight loss
o CD4 range may vary widely
CNS:
o Confusion
o Lethargy
o Memory loss
o Hemiparesis
o Seizures
o Headaches
o Cranial nerve palsies
o Aphasia

Lymphomas are classified after taking a biopsy and analyzing it by histology
•    Refer patients with suspected lymphoma to hospital for diagnosis and treatment
HIV Wasting Syndrome
•     This is an involuntary weight loss of > 10% associated with intermittent or constant fever and/or chronic diarrhoea or fatigue lasting > 30 days in the absence of a defined cause
other than HIV-1 infection

  Wasting Syndrome
is a WHO Stage 4 condition that is only diagnosed after excluding other causes of weight loss such as TB, chronic diarrhoea.
•      Refer these patients to hospital for diagnosis and treatment as they might be having life threatening OIs.
Investigation
Biops
Chest x-ray
Ultrasound
CT scan
Treatment
Chemotherapy

Prevention of Opportunistic Infections in PLHIV Primary & Secondary OI
Prophylaxis
•     Most OIs are preventable and treatable
•     Primary prophylaxis is meant to prevent the opportunistic infection from occurring
•     Primary OI prophylaxis is used to prevent PCP and some pneumonias
• Secondary OI prophylaxis is used after treatment for an initial OI in order to prevent the OI from recurring
•    Same drugs are used for secondary prophylaxis, but in lower doses
•    May be required for life
Cotrimoxazole Prophylaxis
•    Greatly reduces the risk of Pneumocystis jiroveci pneumonia
Also reduces the risk of:
o Bacterial pneumonia
o Toxoplasmosis
o Malaria
o Isospora
o Salmonella bacteraemia

Tanzania Strategies for OI Prophylaxis
•    Strategies used in Tanzania include:
•    Cotrimoxazole Prophylaxis Therapy (CPT) to prevent Bacterial pneumonia,
pneumocystis pneumonia, Toxoplasmosis and other infections
•      Isoniazid Preventive Therapy (IPT) to prevent TB
•     Fluconazole for recurrent candidiasisis and after cryptococcal meningitis
• Non-medical hygienic measures
Hygienic Prevention of OIs
• Other important measures PLHIV should use to prevent OIs are:
o Practice good hand washing
o Keep a local antiseptic for minor injuries
o Use of insecticide-treated bed net to prevent malaria
o Use safe drinking water - drink boiled water
o Eat well-cooked food
o Wash fruits and vegetables with clean water
o Using condoms to help prevent STIs and re-infection with other strains of HIV
o Avoiding others with infections such as:
Flu, boils, impetigo
Herpes zoster, chickenpox
Pulmonary TB until after 2 weeks on treatment

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