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1st August 2023
Common Infections in Immunocompromised Hosts
Causes of Immunocompromisation
Immunocompromisation, or immunodeficiency, refers to a state in which the ability of a person’s immune system to combat disease is either diminished or absent. It is most often secondary (Table 4). Primary immunodeficiency is rare and due to congenital developmental defects or genetic abnormalities present from birth (Table 5).
Immunocompromised patients are more likely to be severely affected by common pathogens and more vulnerable to certain pathogens that rarely cause illness in patients with fully-functioning immune systems, i.e. opportunistic infections. Many of these are associated with HIV, as explained in the previous section.
Selected causes of acquired immunodeficiency
| Infectious diseases | Predominantly HIV |
| Autoimmune diseases | Systemic lupus erythematosus Rheumatoid arthritis Type 1 diabetes Addison’s disease |
| Haematological diseases | Malignancies leading to myelosuppression |
| Trauma or surgery | Damage to the spleen, subsequent splenectomy |
| Immunosuppressive drugs | Corticosteroids Anti-TNF drugs Cytotoxic chemotherapy |
Table 4: Selected causes of acquired immunodeficiency
Selected causes of primary immunodeficiency
| Condition | Features |
|---|---|
| DiGeorge syndrome | Caused by T lymphocyte deficiency due to congenital developmental failure of parathyroid glands, aortic arch and thymus (where T lymphocytes are developed). Presents with characteristic facies, hypoparathyroidism, cardiac defects and susceptibility to infections in the early months of life. |
| Hyper IgM syndrome | An X-linked defect in the CD40 ligand gene affects both B and T lymphocytes, meaning only immature IgM antibodies can be produced by B lymphocytes. Leads to susceptibility to opportunistic infections. |
| Selective IgA deficiency | The most common primary immunodeficiency syndrome is found in 1 in 600 northern Europeans. The exact aetiology is unknown and has variable clinical features – it can present at any age, typically with recurrent pyogenic infection. |
Table 5: Selected causes of primary immunodeficiency
Bacterial Infections
| Infection | Clinical features | Management |
|---|---|---|
| Tuberculosis (mycobacterium tuberculosis) | Areas with high rates of TB also often have high rates of HIV, and immunosuppression caused by HIV predisposes to TB infection. HIV infection often also causes the reactivation of latent TB.
TB in immunocompromised individuals can present in atypical ways – such as more prominent hilar lymphadenopathy and the absence of the characteristic cavitating lesions. Extrapulmonary manifestations are also more common. Mantoux testing and sputum sampling are less reliable in immunosuppressed individuals – culturing for acid-fast bacilli with Ziehl-Neelsen stain remains the best diagnostic test. |
Standard management with anti-TB drugs of rifampicin, isoniazid, pyrazinamide and ethambutol, although extended courses may be given.
Potential for interaction with antiretroviral drugs – each case should be considered individually. Paradoxical inflammatory reactions, or immune reconstitution inflammatory syndrome (IRIS), can be seen in patients with TB who are started on antiretrovirals. Presents as an acute exacerbation of TB symptoms. Managed by withholding ART temporarily and continuing anti-TB drugs. |
| Mycobacterium avium complex (MAC) | An atypical mycobacterium which presents only when patients are heavily immunosuppressed (i.e. CD4 count of less than 50).
MAC causes fever, malaise, weight loss and sweats and is associated with anaemia and diarrhoea. Diagnosed through culturing blood, lymph nodes and bone marrow samples. |
Generally resistant to anti-TB drugs.
Most common treatment is a combination of ethambutol, rifabutin and clarithromycin. |
| Pneumonia (including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, and Moraxella catarrh,alis amongst other species) | Pneumonia is a common infection in immunocompromised individuals – should be considered in any respiratory illness, especially associated with cough, fever and systemic upset.
Illness is more likely to become disseminated in immunocompromised individuals. Should also consider more atypical causes of pneumonia and common community-acquired pathogens. |
Antimicrobials, as per local guidance. |
Viral Infections
| Infection | Clinical features | Management |
|---|---|---|
| Herpesviruses | Herpes simplex virus (HSV) has two types – HSV-1 and HSV-2. HSV-1 causes what is commonly known as “cold sores” HSV-2 is implicated in genital herpes.
Presents with painful ulcerative lesions. In immunocompromised individuals, there is a risk of disseminated disease, such as life-threatening hepatitis and encephalitis. Varicella zoster virus causes either chickenpox (primary infection) or shingles (reactivation). Chickenpox is characterised by rapid progression of maculopapular to vesicular and pustular rash. Human herpesvirus-8 (HHV-8) causes Kaposi’s sarcoma (see AIDS and Other Complications of HIV). |
Treatment, if required, is with the antiviral agent aciclovir.
Chickenpox is generally self-limiting. In immunocompromised (and pregnant) individuals, exposure can be treated prophylactically with aciclovir, and high-dose aciclovir is indicated to treat the disease. Prophylaxis with varicella-zoster immunoglobulin (VZIG) is indicated in immunocompromised individuals unable to take oral antivirals and neonates who are less than one week old. Aciclovir is indicated in shingles if present within 72 hours of onset. People aged over 70 are eligible for a shingles vaccination in the UK. |
| Epstein-Barr virus (EBV) | It can cause primary cerebral lymphoma and non-Hodgkin’s lymphoma.
It may also cause oral hairy leukoplakia – tongue disease, which presents as white ridged patches on lateral borders or buccal mucosa. |
Supportive treatment of general infection.
Anti-cancer treatment, if indicated. |
| Human papillomavirus (HPV) | Causes genital, plantar and oral warts.
HPV-16 and 18 are associated with an increased cervical, anal and oropharyngeal cancer risk. |
Vaccination is available. On routine childhood immunisation schedules for girls and boys aged 12-13, as well as a catch-up programme being offered.
HIV positive patients should be offered the vaccine. Warts can be treated with podophyllin topical agents, cryotherapy, cautery, or laser ablation. Anti-cancer treatment, if indicated. |
| JC virus | It Infects oligodendrocytes of the central nervous system and causes progressive multifocal leukoencephalopathy (PML) – leading to demyelination of the brain’s white matter.
Presents with progressive neurological or cognitive deficits – generally rapidly progressive. Characteristic multiple non-enhancing white matter lesions on MRI. The virus can be identified through PCR of CSF from the lumbar puncture. |
Supportive treatment. |
| Cytomegalovirus (CMV) | Presents in various forms, generally only seen when CD4 count is less than 100.
CMV colitis presents with abdominal pain, tenderness, bloody or non-bloody diarrhoea, and fever. An abdominal x-ray may show dilated large bowel. Sigmoidoscopy shows ulcerated mucosa, and histology demonstrates cytoplasmic inclusion bodies with a characteristic “owl’s eye” appearance. Neurological manifestations include encephalopathy and polyradiculopathy. CMV retinitis occurs when the CD4 count is less than 50. Presents as painful visual field loss associated with a headache – classically unilateral, may progress to bilateral. Clinical diagnosis through fundoscopy – characteristic “pizza pie” appearance of the retina. |
Ganciclovir is the treatment of choice and can be given orally or intravenously.
In CMV retinitis, if not fully treated, then the virus can become reactivated and cause permanent visual loss. |
Other Types of Infections
| Infection | Clinical features | Management |
|---|---|---|
| Pneumocystis jiroveci (fungal) | Most commonly causes pneumonia (PCP), characterised by the gradual onset of exertional shortness of breath, non-productive cough, fever, and malaise.
Patients may have normal oxygen saturations at rest but quickly desaturation on exertion. Chest x-ray shows characteristic bilateral perihilar infiltrates, and high-resolution CT shows ground glass changes. Diagnosis is confirmed through silver staining or bronchoalveolar lavage aspirate or PCR of fungal DNA from a serum sample. |
First line treatment is a 21 day course of intravenous co-trimoxazole, with intravenous pentamidine, dapsone or trimethoprim as alternatives.
Corticosteroids may be given in severe cases, and ventilation may also be required. Prophylaxis with oral co-trimoxazole is commonly given to HIV patients with a CD4 count of less than 200 and to renal transplant patients. |
| Cryptococcus (fungal) | Cryptococcal meningitis is the most common presentation in HIV patients, although it may also cause pneumonia.
Causes a gradual onset illness, beginning with fever, headache and nausea, before progressing to changes in level of consciousness. Seizures, focal neurology, neck stiffness and photophobia are less commonly seen. Indian ink staining of CSF from lumbar puncture visualises organisms and confirms the diagnosis. |
Treatment is with intravenous liposomal amphotericin B. |
| Candida (fungal) | Most commonly due to Candida albicans yeast. Oral candidiasis is very common in HIV patients – characteristic creamy-white plaques on the tongue and oral mucosa.
Oesophageal candidiasis presents with painful swallowing and reduced oral intake, and may be able to visualise plaques at the back of the throat (though endoscopy may be required). Concurrent oral thrush often occurs. Diagnosis is generally clinical, although swabs can be taken. |
Oral candidiasis is treated with oral nystatin as the first line, followed by oral fluconazole for severe cases.
Oesophageal candidiasis is treated with oral fluconazole. |
| Aspergillus (fungal) | Aspergillus spores are air-borne and hence spread through inhalation. Rare even in HIV patients unless they have comorbid respiratory illness or additional immunosuppression with medications.
Causes both pneumonia and upper respiratory tract infection – commonly sinusitis. |
Antifungal agent voriconazole is the first line treatment, with liposomal amphotericin B or caspofungin as alternatives. |
| Histoplasmosis (fungal) | Rare in the UK, it is most prevalent in the Americas – especially the Ohio and Mississippi river valleys.
Often indolent in healthy individuals, but in those who are immunocompromised causes a pneumonia-type illness. |
First line treatment is with liposomal amphotericin B. |
| Toxoplasmosis (protozoa) | Many people are infected with Toxoplasma gondii – found in undercooked meat, cat faeces and may be transmitted vertically. However, it only manifests disease in immunocompromised individuals and is associated with HIV.
Encephalitis and cerebral abscesses are the most common form (cerebral toxoplasmosis). Presents with fever, headache, confusion and seizures and may be associated with focal neurological deficits. Characteristic multiple ring-enhancing lesions on contrast CT head scans, which can be confirmed through MRI. |
Minimum six week course of pyrimethamine intravenously, combined with sulfadiazine and folinic acid. |
| Cryptosporidiosis (protozoa) | The infection leads to a self-limiting diarrhoeal illness in people with a healthy immune system, but in immunocompromised individuals can cause a severe watery diarrhoea associated with acute abdominal pain, vomiting, and weight loss.
Cysts are formed, which attach themselves to the wall of the small bowel and can be seen with Kinyoun acid-fast stain to confirm the diagnosis. |
Supportive treatment. |
| Leishmaniasis (protozoa) | Endemic in South America, tropical regions of Africa, and the Mediterranean – so should be considered in immunocompromised individuals who have travelled to these areas.
Causes non-specific illness with fever, malaise, diarrhoea and weight loss. Severe illness can lead to splenomegaly, anaemia and thrombocytopenia. No reliable diagnostic test. |
First line treatment is with liposomal amphotericin B. |
Infections in Organ Transplant Patients
In order to reduce the risk of graft rejection, patients who receive organ transplants are generally prescribed strong immunosuppressive drugs. This leads to immunocompromise and means special consideration should be given to the risk of opportunistic infections in organ transplant patients. This is most commonly considered in the context of renal transplant patients.
Bacterial infections are generally seen in the first month post-transplantation, whereas in the weeks-months after, cytomegalovirus (CMV) is relatively frequent. Prophylaxis with valganciclovir may be given against CMV, although the evidence basis is unclear.
Routine prophylaxis is also indicated in renal transplant patients against Pneumocytis jirovecii and oral candidiasis with co-trimoxazole and nystatin, respectively.
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