Health Topics

What are opportunistic infections?

People with advanced HIV/AIDS are vulnerable to infections and malignancies that are called 'opportunistic infections' because they take advantage of the opportunity offered by a weakened immune system.

A partial list of the world's most common HIV-related opportunistic infections and diseases includes:

  • Bacterial diseases such as tuberculosis, MAC, bacterial pneumonia and septicaemia (blood poisoning)
  • Protozoal diseases such as toxoplasmosis, microsporidiosis, cryptosporidiosis, isopsoriasis and leishmaniasis
  • Fungal diseases such as PCP, candidiasis, cryptococcosis and penicilliosis
  • Viral diseases such as those caused by cytomegalovirus, herpes simplex and herpes zoster virus
  • HIV-associated malignancies such as Kaposi's sarcoma, lymphoma and squamous cell carcinoma.

Different conditions typically occur at different stages of HIV infection. In early HIV disease people can develop tuberculosis, malaria, bacterial pneumonia, herpes zoster, staphylococcal skin infections and septicaemia. These are diseases that people with normal immune systems can also get, but with HIV they occur at a much higher rate. It also takes longer for a person with HIV to recover than it takes for someone with a healthy immune system.

When the immune system is very weak due to advanced HIV disease or AIDS, opportunistic infections such as PCP, toxoplasmosis and cryptococcosis develop. Some infections can spread to a number of different organs, which is known as 'disseminated' or 'systemic' disease. Many of the opportunistic infections that occur at this late stage can be fatal.

Why is there still a need to prevent and treat opportunistic infections?

Highly Active Antiretroviral Therapy (HAART) can reduce the amount of HIV in someone's body and restore their immune system. The introduction of HAART has dramatically reduced the incidence of opportunistic infections among HIV-positive people who have received the drugs. Yet the prevention and treatment of opportunistic infections remains essential.

Around the world, millions of people living with HIV in resource-poor communities have no access to antiretroviral drugs. And even where the drugs are available, they do not entirely remove the need for preventing and treating opportunistic infections. Usually it is advisable for people with acute opportunistic infections to begin HIV treatment right away, especially if the infection is difficult to treat. However in certain cases it may be better to delay beginning HIV treatment and instead only to administer treatment for the opportunistic infection, especially if there are concerns about drug interactions or overlapping drug toxicities.

Those who have already started taking antiretrovirals may require other drugs in certain circumstances. In particular, some opportunistic infections may be unmasked shortly after starting HIV treatment as the immune system starts to recover, and these may require specific treatment. Measures to prevent and treat opportunistic infections become essential if antiretrovirals stop working because of poor adherence, drug resistance or other factors.

Providing prevention and treatment of opportunistic infections not only helps HIV-positive people to live longer, healthier lives, but can also help prevent TB and other transmissible opportunistic infections from spreading to others.

Prevention of HIV-related opportunistic infections

HIV-positive people can reduce their exposure to some of the germs that threaten their health. They should be especially careful around uncooked meat, domestic animals, human excrement and lake or river water. However there is no practical way to reduce exposure to the germs that cause candidiasis, MAC, bacterial pneumonia and other diseases because they are generally common in the environment.

Co-trimoxazole

Several HIV-related infections (including tuberculosis, bacterial pneumonia, malaria, septicaemia and PCP) can be prevented using drugs. This is known as drug prophylaxis. One particular drug called co-trimoxazole (also known as septra, bactrim and TMP-SMX) is effective at preventing a number of opportunistic infections and has been shown to significantly reduce mortality among HIV-positive individuals initiating antiretroviral therapy.

The World Health Organisation (WHO) recommends that, in resource-limited settings, the following groups of people should begin taking co-trimoxazole:

  • HIV-exposed infants and children, starting at 4-6 weeks after birth, or at first contact with health care, and continued until HIV infection is excluded
  • HIV-positive children less than 1 year old
  • HIV-positive children aged 1-4 years who have mild, advanced or severe symptoms of HIV disease, or a CD4 count below 25%
  • HIV-positive adults and adolescents who have mild, advanced or severe symptoms of HIV disease, or a CD4 count below 350 cells per ml
  • HIV-positive people with a history of treated PCP.

According to WHO guidelines, treatment of HIV-positive children should continue until at least age five. In general treatment of adults and children should continue indefinitely, though it may sometimes be stopped following successful antiretroviral treatment.

Some of the worst affected countries may choose to treat all infants and children born to mothers confirmed or suspected of living with HIV, until HIV infection is excluded. They may also choose to treat everyone who is diagnosed with HIV, regardless of symptoms or CD4 count.

Drug prophylaxis is sometimes recommended even for those who have started ART if they have very weak immune systems or are otherwise considered to be especially vulnerable. They may be advised to stop taking the drugs if their immune system recovers.

For people who have already contracted an opportunistic infection and undergone successful treatment, secondary prophylaxis may be advisable to prevent recurrence. This applies to diseases such as tuberculosis, salmonella, cryptococcosis and PCP.

Treatment of HIV-related opportunistic infections

Some opportunistic infections are easier to treat than others. Effective treatment depends on health services being able to procure, store, select and administer the necessary drugs and to provide related treatment, care and diagnostic services to monitor health status and treatment response.

A few opportunistic infections and symptoms such as candidiasis of the mouth, throat or vagina (thrush), herpes zoster (shingles) and herpes simplex can be managed effectively through home based care. In a home-based care setting diagnosis is made by observing symptoms.

Some opportunistic infections may be diagnosed by observation or using a microscope, and treated where there is minimal health infrastructure. Such infections include pulmonary tuberculosis and cryptococcal meningitis.

In a medium infrastructure setting, the facilities available include X-ray equipment and culture facilities. Using these, opportunistic infections such as extra-pulmonary tuberculosis, cryptosporidiosis, isopsoriasis, PCP and Kaposi's sarcoma can be diagnosed and treated.

Opportunistic infections such as toxoplasmosis, MAC and cytomegalovirus infection can be diagnosed and treated in places with advanced infrastructure. Treating these infections is often impossible in resource poor countries. Many developing countries lack the advanced equipment and infrastructure (such as CT scanning) needed to treat these more complex infections.

Individual opportunistic infections

The following are just a few of the conditions that particularly affect people living with HIV.

Bacterial pneumonia

Pneumonia can be caused by various bacteria. Symptoms among HIV-positive people are much the same as in those without HIV infection, and include chills, rigours, chest pain and pus in the sputum.

Because other forms of respiratory infection, including PCP, are common among HIV-infected people, doctors must be certain of diagnosis before administering antibiotics. This may require a chest radiograph, blood cultures, a white blood cell count and tests to eliminate other infections. Treatment is usually aimed at the most commonly identified disease-causing bacteria.

Candidiasis

There are two main types of candidiasis: localised disease (of the mouth and throat or of the vagina) and systemic disease (of the oesophagus, and disseminated disease). HIV-positive women commonly acquire the mouth and throat variant (usually known as thrush or oral candid). It is believed to occur at least once in the lifetime of all HIV-infected patients. Oro-pharyngeal candid (OPC) in HIV-positive patients indicates a decline in immunodeficiency and, when ART is absent, is a sign of the onset of AIDS. However, the vaginal variant is a common occurrence among HIV-negative women.

While OPC is not a cause of death, it causes severe discomfort. The symptoms of candidiasis of the vagina include itching and possibly a thick vaginal discharge. Candidiasis of the mouth and throat can cause oral pain and make swallowing difficult, the main symptom is creamy white legions in the mouth that can be scraped away. Oesophageal candidiasis is a more serious condition which can cause pain in the chest that increases with swallowing. Disseminated candidiasis causes fever and symptoms in the organs affected by the disease (for example, blindness when it affects the eyes), and can be life threatening.

Localised disease may be treated at first with relatively inexpensive drugs such as nystatin, miconazole or clotrimazole. Systemic candidiasis requires treatment with systemic antifungal agents such as fluconazole, ketoconazole, itraconazole or amphotericin.

Cryptococcosis

Cryptococcosis is caused by a fungus that primarily infects the brain. It most often appears as meningitis and occasionally as pulmonary or disseminated disease. Untreated cryptococcal meningitis is fatal.

Cryptococcosis is relatively easy to diagnose. However, its treatment (either amphotericin B with or without flucytosine or in mild cases with oral fluconazole) and secondary chemoprophylaxis are often impossible in developing countries because of high cost and limited availability of the drugs required.

It is recommended that ART should be administered to those diagnosed with cryptococcal disease. In the case of cryptococcal meningitis there are risks of initiating ART as there is evidence that immune reconstitution inflammatory syndrome (IRIS) may develop. HIV progression versus the onset of IRIS are risks that must be weighed when treating HIV and cryptococcosis meningitis.

Cryptosporidiosis and isosporiasis

Cryptosporidiosis (crypto) and isosporiasis are both caused by protozoan parasites. These diseases are easily spread by contaminated food or water, or by direct contact with an infected person or animal. Both crypto and isosporiasis cause diarrhoea, nausea, vomiting and stomach cramps. In people with healthy immune systems, these symptoms do not last more than about 14 days. However, if the immune system is damaged then they can continue for a long time. Diarrhoea can interfere with the absorption of nutrients and this can lead to serious weight loss.

To confirm diagnosis of either disease, the stool is normally checked for parasites and their eggs. There is no cure for crypto, but antiretroviral therapy to restore immunity can effectively clear up the infection. For isosporiasis, TMP-SMX (trimethoprim-sulfamethoxazole/Bactrim) is often the preferred treatment.

Cytomegalovirus

Cytomegalovirus (CMV) is a virus that infects the whole body. Infection usually occurs in childhood yet the virus remains dormant unless the immune system is suppressed. It most commonly appears as retinitis, which causes blurred vision and can lead to blindness, and also as gastrointestinal disease. CMV can also affect other organs such as the lungs or liver, and is capable of causing fever, diarrhoea, nausea, pneumonia-like symptoms and dementia.

CMV infection may be treated with drugs such as ganciclovir, valganciclovir, cidofovir and forscarnet. Before the roll out of ARV, studies identified that up to 40% of AIDS patients aquired CMV. Access to ARV’s now deter the chances of infection as immune systems can be supported. It is recommended to initiate ART following anti-CMV treatment in order to reduce the chance of a relapse.

Herpes simplex and Herpes zoster

The usual symptoms of herpes simplex virus infection (HSV, which causes sores around the mouth and genitals) and herpes zoster virus infection (or varicella zoster virus (VZV), which causes chickenpox (varicella) and shingles (zoster)) are not life-threatening but can be extremely painful. Both viruses are also capable of causing retinitis and, less often, encephalitis (which can be life-threatening). Herpes Zoster is transmitted usually through the respiratory route, whereas Herpes Simplex Virus is transmitted through contact with secretions from an infected area.

Both herpes simplex and herpes zoster are usually diagnosed by simple examination of the affected area, and may be treated with drugs such as acyclovir, famciclovir and valacyclovir.

Histoplasmosis

Histoplasmosis is a fungal infection that primarily affects the lungs but may also affect other organs. Infection occurs through inhalation of fungus spores. Symptoms can include fever, fatigue, weight loss and difficulty in breathing.

Disseminated histoplasmosis infection may be diagnosed using an antigen test, and can be fatal if left untreated. Treatment usually involves amphotericin B or itraconazole.

Kaposi's sarcoma

HIV-associated Kaposi's sarcoma causes dark blue lesions, which can occur in a variety of locations including the skin, mucous membranes, gastrointestinal tract, lungs or lymph nodes. The lesions usually appear early in the course of HIV infection.

Treatment depends on the lesions' symptoms and location. For local lesions, injection therapy with vinblastine has been used with some success. Radiotherapy can also be used, especially in hard-to reach sites such as the inner mouth, eyes, face and soles of the feet. For severe widespread disease, systemic chemotherapy is the preferred treatment.

Leishmaniasis

Leishmaniasis is transmitted by sandflies and possibly through sharing needles. The most serious of its four forms is visceral leishmaniasis (also know as kala azar) which is characterised by irregular bouts of fever, substantial weight loss, swelling of the spleen and liver and anaemia (occasionaly serious). In its more common forms, leishmaniasis can produce disfiguring lesions around the nose, mouth and throat, or skin ulcers leading to permanent scarring.

Treatment of leishmaniasis is with either a pentavalent antimony or liposomal amphotericin B in the case of visceral leishmaniasis. Sodium stibogluconate is used to treat cutaneous leishmaniasis. If left untreated, visceral leishmaniasis is usually fatal.

MAC

The germs of the mycobacterium avium complex (MAC) are related to the germ that causes tuberculosis. MAC disease generally affects multiple organs, and symptoms include fever, night sweats, weight loss, fatigue, diarrhoea and abdominal pain. It is not believed that person-to-person transmission occurs; the MAC organisms are present throughout the environment. Infection occurs through the respiratory or gastrointestinal tract, infecting individuals with severely inhibited immune systems.

MAC should be treated using at least two antimycobacterial drugs to prevent or delay the emergence of resistance. Such drugs include clarithromycin, azithromycin, ethambutol and rifabutin.

PCP

PCP is caused by a fungus, which was formerly called pneumocystis carinii but has now been renamed pneumocystis jirovecii. PCP is a frequent HIV associated opportunistic infection which occurred in 70%-80% of patients with AIDS prior to the widespread use of primary PCP prophylaxis and ART, which has led to a significant decline of cases. The symptoms are mainly pneumonia along with fever and respiratory symptoms such as dry cough, chest pain and dyspnoea (difficulty in breathing). Definitive diagnosis requires microscopy of bodily tissues or fluids.

Severe cases of PCP are initially treated with TMP-SMX or clindamycin and oral primaquine. Mild cases can be treated with oral TMP-SMX throughout. With both of these regimens, toxicity (notably allergic-type reactions) often requires changes in therapy.

Prevention of PCP is strongly recommended for HIV-infected persons with very weak immune systems wherever PCP is a significant health problem for HIV-infected persons, and also after their first episode of PCP. The preferred drug is usually TMP-SMX.

Toxoplasmosis

Toxoplasmosis (toxo) is caused by a protozoan found in uncooked meat and cat faeces. This microbe infects the brain and can cause raised intracranial pressure, which leads to headaches and vomiting. Other symptoms include confusion, motor weakness and fever. In the absence of treatment, disease progression results in seizures, stupour and coma. Disseminated toxo is less common, but can affect the eyes and cause pneumonia.

Definitive diagnosis of toxo requires radiographic testing (usually CT or MRI scan). The infection is treated with drugs such as pyrimethamine, sulfadiazine and clindamycin. Leucovorin may also be used to prevent the side-effects of pyrimethamine. Prophylaxis against toxo is through taking TMP-SMX.

Recommendations advise to HIV-positive individuals:

  • Avoid ingestion of undercooked meat
  • To wash hands after any contact with soil
  • To avoid emptying cat litter trays, or to empty trays daily and wash hands thoroughly after every disposal.

Tuberculosis

Tuberculosis (TB) is a bacterial infection that primarily infects the lungs. Tuberculosis is the leading HIV-associated opportunistic disease in developing countries. For people who are dually infected with HIV and TB, the risk of developing active tuberculosis is 30-50 fold higher than for people infected with TB alone. And because mycobacterium can spread through the air, the increase in active TB cases among dually infected people means:

  • more transmission of the TB germ
  • more TB carriers
  • more TB in the whole population.

Tuberculosis is harder to diagnose in HIV-positive people than in those who are uninfected. The diagnosis of TB is important because TB progresses faster in HIV-infected people. Also, TB in HIV-positive people is more likely to be fatal if undiagnosed or left untreated. TB occurs earlier in the course of HIV infection than many other opportunistic infections.

A proper combination of anti-TB drugs achieves both prevention and cure. Effective treatment quickly makes the individual non-contagious, which prevents further spread of the TB germ. The DOTS (directly observed short course) treatment strategy recommended by WHO treats TB in HIV-infected persons as effectively as it treats those without the virus. A complete cure takes 6 to 8 months and uses a combination of antibiotics. In addition to curing the individual, it also prevents further spread of the disease to others. This is why treating infectious cases of TB has important benefits for society as a whole.

Isoniazid preventive therapy is recommended as a health-preserving measure for HIV-infected persons at risk of TB, as well as for those with latent TB infection.

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