“Samual Nzala is a-24-year-old gentleman brought by his family to the clinic because of a severe headache. The family reports that he has "malaria." His temperature is 39.7 degrees, but no parasites were seen on his MP (malaria parasite) slide. When the nurse spoke with him, he was lying on the bed in clinic with his eyes shut looking very uncomfortable. He keeps his eyes shut to the light and moves as little as possible. He did not feel well yesterday, but was working earlier this week with no problems. He has never had headaches before except when he has malaria. This is the worst headache he has ever had.”
"His family says that he has had no recent head injuries, and the nurse cannot detect any focal problems (weakness or numbness in one part of the body) that might be evidence of a mass lesion in the brain, or signs of stroke. However, she finds he has a very stiff neck and is unable to flex his head forward.
She believes Samual most likely has some type of meningitis."Adapted (with some details added) from Dr Gretchen Birbeck’s Where there is no neurologist — see resource section)
Meningitis, inflammation of the membranes covering the spinal cord or brain, is common in people with HIV — but may be caused by a variety of things. Samual’s symptoms: severe headache, fever, stiff neck, altered mental state or consciousness and sensitivity to light (photophobia) are hallmarks of meningitis—but not every symptom is always present and the clinical presentation may be non-specific. In people with HIV, meningitis may present with confusion only. On the other hand, depending on the cause or individual, there may be other complaints as well that could complicate diagnosis.
Symptoms may vary with the cause, which is most commonly an infection of some sort (either bacterial, mycobacterial (TB), amoebic, fungal or viral (see below)), but could also be due to physical injury (head trauma), subarachnoid haemorrhages, autoimmune conditions, cancers, or exposure to certain chemicals (Joynt). Some of these symptoms may not actually be due to involvement of the brain at all – for instance, sinusitis can cause a headache, severe dehydration due to malaria may cause altered mental state, and a stiff neck may occasionally be a feature of bacterial pneumonia.
This article will deal chiefly with the infections causing meningitis to which people with HIV may be more vulnerable —with a particular focus on cryptococcal, TB and pneumococcal meningitis.
Even with the roll-out of antiretroviral therapy (ART), being on the alert for meningitis is very important, because it may be the first illness that a person develops and is very dangerous.
Symptoms suggestive of meningitis must be treated as a medical emergency, since clinical deterioration can be very rapid and lead to death. Even when the initial presentation is initially subacute, as can be the case with cryptococcal meningitis, the consequences of delay are so grave that virtually any severe headache with a recent onset in a person with HIV may warrant a closer examination (Hakim).
In either case, prompt and appropriate attention can improve survival and reduce the risk of serious long-term complications.But often in resource limited settings, diagnosing meningitis in a very ill person (or getting the person with meningitis to a place where he or she can be diagnosed), and providing effective care and treatment can present a number of difficult challenges. And even when a case is diagnosed and treated, few programmes adequately address how to manage the long-term consequences of meningitis in the children and adults who survive the condition.
Prevalence of meningitis in resource-limited settings
Diagnosis of meningitis
Treatment of the infectious cause of meningitis
Treatment for the identifiable (or suspected) cause of meningitis should be the first priority in each patient with meningitis and HIV. However, good long-term outcomes can only be achieved by also eventually putting people on ART (and perhaps other preventive therapy — see prevention below), and by managing the patient’s increased intracranial pressure (through repeated lumbar punctures, appropriate analgesics for pain and other needs that may arise as a complication of meningitis (see caring for the patient below). However, the introduction of ART after a serious neurological infection does raise the potential for IRIS to develop — and as Dr Collin’s case suggests, many clinicians are unsure when is the best time to initiate ART in someone who has had meningitis (see below).
Reducing suffering in a person with meningitis and managing its long-term consequences
One thing that literature sometimes neglects to mention is the intense suffering that people with meningitis go through — such as the screaming patient that Dr Collins was caring for.
As frightening as lumbar punctures may sound to some, in the case of cryptococcal meningitis, they do provide real pain relief since much of the pain is due to high pressure around the brain. In fact, “simply relieving the pressure is the most potent and immediate form of pain relief,” said Dr. Venter.
But appropriate pain medication must be prescribed as well, commensurate to the level of pain that the individual is enduring (See the WHO analgesic ladder in the Resources section). (NSAIDS however should be avoided in patients on amphotericin B due to a risk of kidney toxicity).
In addition, A clinical guide to supportive and palliative care for HIV/AIDS in sub-Saharan Africa (see Resources section) recommends “other measures such as being in a quiet, dark room, having a cool cloth over the eyes, and having the neck massaged may be helpful.” It also stresses that adopting a palliative care approach also extends to addressing psychosocial issues related to the illness.
“Consider the implications of the person’s condition for his or her ability to continue to work. In addition, there have been unfortunate incidences of patients with dementia or delirium being thrown out of their homes or of being locked up in a small shed.”
This would likely result in the rapid death of someone with meningitis.
In addition, meningitis can also result in permanent brain damage, hearing loss, blindness, partial paralysis or learning disabilities in survivors — especially if diagnosis and treatment are delayed. Health systems aren’t prepared to manage such individuals, as the following case submitted by Dr Natalya Dinat, Director of Wits Palliative Care, at the University of Witwatersrand illustrates:
Prevention of meningitis
Given such challenges, as the old adage goes, prevention would certainly be better than a cure.
“Approaches to reducing the incidence include the deployment of effective antiretroviral therapy in areas where HIV co-infection is common, vaccination, and prophylactic antibiotic therapy,” wrote Scarborough and Njalale from Malawi.
- Vaccination for the major causes of bacterial pneumonia is recommended in people with HIV, even though the protection offered may not be as great as in the general population, particularly in those with lower CD4 cell counts (Spach). However, data from one study with the 23-valent pneumococcal polysaccharide vaccine in Africa found that vaccination was associated with an increased risk of pneumoccoccal disease (French). However, recent studies have shown PCV-7 (7-serotype conjugate pneumococcal vaccine) to be safe and efficacious when used in children infected with HIV, and WHO now recommends that countries with a high prevalence of HIV prioritise the introduction of this vaccine (http://www.who.int/entity/wer/2007/wer8212.pdf). In addition, good national vaccination policies could also reduce the overall burden of bacterial pneumonia through “the herd effect.” (Klugman)
- Cotrimoxazole prophylaxis has been shown to reduce the frequency of bacterial infections — even in Zambia, where there is a high level of background antibiotic resistance (Mulenga http://www.aidsmap.com/en/news/DFC83829-056C-4C24-94FE-BAB37FA7BDE0.asp).
- Isoniazid preventive therapy (IPT) reduces the incidence of TB and making it a part of the essential package of care offered to people with HIV could potentially reduce the risk of TB meningitis as well (see HATIP # 96).
- Fluconazole prophylaxis: The use of prophylaxis to prevent cryptococcal meningitis and other infections is more controversial. Although several randomised studies have shown that fluconazole and itraconazole reduces the incidence of cryptococcal disease in people with advanced HIV disease, and one study even demonstrated a survival benefit, none of these studies have been conducted in sub-Saharan Africa (Chang, Chetchotisakd). In addition, concerns have been raised about the potential drug interactions (as with nevirapine), the potential for teratogenicity, and the risk of developing fluconazole-resistant thrush infections.
So WHO’s draft guidelines on the Essential Prevention and Care Interventions for PLHIVs, includes a recommendation to consider fluconazole prophylaxis in areas where cryptococcal disease is common for severely immunocompromised people with HIV (WHO clinical stage 4 or CD4 < 100 cells) but the level of recommendation is ‘optional.’
The SAHCS guidelines stress that the priority should rather be to get people with such low CD4 cell counts on ART as soon as possible.
“ART is the most effective intervention to treat AIDS, and is the most potent mechanism to prevent both primary and secondary recurrences of cryptococcosis.” However, it concedes that “primary prevention… with fluconazole may have a limited role in patients with CD4 counts below 100 cells where delays in access to ART are anticipated.”
Unfortunately, such delays are common in South Africa… and can have serious consequences, as the final case from Dr Dinat illustrates.
Resources for palliative and supportive care for people with disabilities
- The AIDSMAP Palliative Care Portal: http://www.aidsmap.com/cms1038390.asp
- The African Palliative Care Association: http://www.apca.co.ug/
- The Hospice Palliative Care Association South Africa: http://www.hospicepalliativecaresa.co.za/
- The International Association for Hospice and Palliative Care: http://www.hospicecare.com
- The International Children’s Palliative Care Network: http://www.icpcn.org.uk/ (in particular, see their international directory)
- The Association for the Physically Disabled (APD) helps South Africans with physical disabilities: http://www.apd.org.za/
- The Child Rights Information Network: http://www.crin.org/index.asp
- Foundation for Hospices in Sub-Saharan Africa (FHSSA): www.fhssa.org
- The International Federation of Red Cross and Red Crescent Societies: http://www.ifrc.org
- The Elizabeth Glaser Pediatric AIDS Foundation: http://www.pedaids.org
- The WHO pain ladder: http://www.who.int/cancer/palliative/painladder/en
- A Clinical Guide to Supportive and Palliative Care for HIV/AIDS in Sub-Saharan Africa addresses the many aspects of palliative care that are key in caring for the person living with HIV/AIDS from an African perspective: to read online: http://www.fhssa.org/i4a/pages/Index.cfm?pageID=3361
- A very clear and easy to use resource manual for nurses and other cadre of health staff: “Where there is no neurologist,” by Dr Gretchen Birbeck is available online: http://neurology.msu.edu/downloads/where%20there%20is%20no%20neurologist_whole%20book.pdf
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Contributing Clinical Advisers
Dr Doug Wilson,
KwaZulu Natal, South Africa
Dr Francois Venter
Reproductive Health and HIV Research Unit
University of the Witwatersrand, Johannesburg, South Africa
Dr Graeme Meintjes
GF Jooste Hospital
Cape Town, South Africa
Dr. Somnuek Sungkanuparph
Mahidol University, Bangkok, Thailand
Dr. Gretchen Birbeck
Michigan State University
Principal Investigator: for the
Rural ART adherence in Zambia (RAAZ) study
Contributing Palliative Care Advisers
Dr. Joan Marston
Paediatric Palliative Care Manager for Hospice Palliative Care
Association of South Africa
Chair of the International Children’s Palliative Care Network in South Africa
Dr. Natalya Dinat
Director of Wits Palliative Care,
University of Witwatersrand,
Chris Hani Baragwanath Hospital
Johannesburg, South Africa
Dr Karilyn Collins
Muheza Hospice Care
Teule Hospital, Muheza Tanzania