Dr David Itua Uhuebor

A South African relevant , comprehensive,

current,

evidence-based,

level

appropriate

paper to the emergency department medical

staff at a tertiary
Cape

Town

level provincial hospital in

concerning

specific,

life

threatening, HIV related medical emergencies

that present to the Emergency Department
(ED), with reference to presentation, diagnosis
and resuscitation.

Page 1 of 16

Introduction
Human Immunodeficiency Virus (HIV), is endemic in South Africa with an
estimated 5.24 million individuals which is 10.5% of the total population
infected as at 2010 with Western Cape in which Cape town metro belongs
accounting for 3.8% of this population.1, 2
These potentially life threatening conditions that bring them to the emergency
department maybe broadly grouped into HIV related Pulmonary emergencies,
emergencies involving the Central nervous system (CNS), Diarrheal diseases
and Ocular related emergencies.
Pulmonary Emergencies
There is a higher prevalence of pulmonary infection in HIV infected patients
than the general population. HIV positive patients have a higher risk by an
estimated 25 folds3, 4.
HIV positive patients that present at the emergency department with serious
respiratory problems usually present with lower respiratory tract infections
such as pneumonia.
The pneumonia usually of bacteria origin, typically by pneumococcus or
haemophylus influenza and atypically by chlamydia or legionella. Bacterial
pneumonia is a leading cause of respiratory disease presentation in
Emergency department with an incidence of 5.5 per 100 person-years among
HIV positive patients5, 6. Increase is further noted among intravenous drug
users who are infected with HIV 7. Although bacterial pneumonia can occur at
any stage of the disease, there is an associated increase in occurrence of
bacterial pneumonia and worsening immunosuppression 8.
Streptococcocal pneumonia appears to be the most common cause of
bacterial pneumonia in HIV positive patients 8. However there is increasing
Page 2 of 16

incidence of bacterial pneumonia from pseudomonas aeruginosa in patients

with HIV9.
Pneumonia secondary to mycobacterium tuberculosis is the major pulmonary
infection complicating HIV infection10. Pulmonary tuberculosis may be seen in
HIV infected patients at the emergency department at any level of
immunosuppression. However, presentation is commonly seen at CD4 counts
below 350.
The most common cause of pulmonary infection in HIV infected patients is
pneumocystis jiroveci pneumonia11. Pneumocystis jiroveci pneumonia is an
AIDS defining illness in 60% of patients and 80% of HIV positive patients will
at some point become infected 12 ,13.
One the most common endemic fungal lung infection in HIV infected patients
is histoplasmosis. Focal pneumonia is most commonly seen in patients with
CD4 count greater than 250. Disseminated histoplasmosis disease is seen in
HIV positive patients with CD4 count less than 100. Blastomycosis is an
uncommon but serious lung complication in HIV infected patients

14, 15

With cryptococcosis, disease dissemination is seen commonly. The lung is

the infection portal and the second most clinically relevant site of infection 16.
Aspergillus lung infection occurs in HIV infected patients with CD4 count less
than 100

17

. Although less common, with an incidence of approximately 1%,

has two forms of pulmonary disease in HIV infected patients that may present
to the emergency department- invasive pulmonary aspergillosis, which
accounts for greater than 80% of cases, and tracheobronchial aspergillosis 17.
Respiratory viruses such as influenza are a common cause of respiratory
illness in adults with HIV18.

Page 3 of 16

HIV positive patients are known to be at an increased risk from influenza

related pulmonary complication19.
The most frequent parasitic pneumonia affecting HIV positive patients is from
toxoplasma gondii20. Active pulmonary toxoplasmosis is commonly seen in
patients with CD4 counts less than a 10020.
HIV infected patients with pulmonary complications may present to the
emergency department with history of cough, fever and shortness of breath.
Patients with pneumocystis pneumonia may present with spontaneous
pneumothorax21. These symptoms may have varying degree of severity at
presentation

and

differences

in

symptomatology

from

that

of

an

immunocompetent person and these are also influenced by the level of

immunosuppression with the CD4 count used as the indicator 22, 23.
An HIV infected patient with severe immunosuppression presenting with
pneumococcal pneumonia will be much sicker in appearance. The cough of
bacterial pneumonia will differ from that of pneumocystis in that the symptoms
are more of acute onset, approximately 5 days compared to 14 days for
pneumocystis- usually of insidious onset and may also present with marked
shortness of breath and oral thrush. The presence of associated marked
weight

loss,

bloody

sputum

and

drenching

night

sweats

makes

mycobacterium tuberculosis a likely culprit. Although these symptoms may

also be seen in HIV infected patients with pulmonary complication secondary
to malignancies22, 23.
Due to the overlap in radiographic images of the various pneumonia,
radiographic

appearance

may

only

provide

differential

diagnosis 24.

Pulmonary complications from pneumocystis carinii, fungal and bacterial

pneumonia may show lobar infiltrates on chest X-ray. With pneumocystis
carinii pneumonia, the X-ray could be normal in atleast one-third of cases 25.
Page 4 of 16

The presence of pneumothorax increases the risk of pneumothorax 21. With

mycobacterium tuberculosis, Xray findings may show linear or nodular
infiltrates, usually apical with hilar lymphadenopathy

23

. Pulmonary

tuberculosis, fungal and neoplasms may show small nodules. Large nodules
may be as a result of fungal or norcardial infection 23. Cavitatory lesions with
pleural effusion on chest radiograph may be indicative of pulmonary
tuberculosis. However, these may also be seen in bacterial infection and
Kaposi sarcoma23.
Fibreoptic bronchoscopy can be used to diagnose pulmonary complications in
HIV infected patients24.
Sputum smear microscopy may be used in the diagnosis of pulmonary
tuberculosis. However, more cases are diagnosed with the use of sputum
culture26,

27

. Sputum microscopy may also be used in the diagnosis of

pneumocystis pneumonia28.
Blood culture and blood serum antigen detection is used in the diagnosis of
bacterial pneumonia and cryptococcal pneumonia respectively 22, 29.
Treatment of bacterial pneumonia in HIV positive patients is similar to
treatment in patients who are uninfected 22. Bacterial pneumonia can be
treated with a cephalosporin, cefotaxime29.
Trimethoprim sulphamethoxazole is the treatment of choice and can be given
intravenously or orally. Patients who cannot tolerate or are unresponsive to
trimethoprim

sulphamethoxazole

can

be

treated

with

intravenous

penthamidine and dapsone, clinidamycin and primaquine and atovaquone 30.

Prednisolone in addition maybe administered in severe episodes of
pneumocystis carinii pneumonia 23. It reduces occurrence respiratory failure
and mortality in a subgroup of patients with PaO 2 less than 70mmHg and A-a
gradient greater than 35mmHg31.
Page 5 of 16

Cryptococcal pneumonia and pulmonary aspergillosis is treated with is

treated with fluconazole and voriconazole respectively32, 33.

Central Nervous system emergencies

Central nervous system emergencies maybe divided into two categories;
primary illness resulting directly from the human immunodeficiency virus
infection and secondary illness which result from other known causes, usually
opportunistic34. The common causes include HIV encephalopathy (dementia),
myelopathy, distal sensory polyneuropathy (DSP), cerebral toxoplasmosis,
tubercular meningitis, progressive multifocal leukoencephalopathy (PML),
Cryptococcal meningitis and cerebral lymphoma23, 34.
HIV dementia is an AIDS defining illness. It is seen in patients with advanced
disease, patients with CD4 counts below 200 cells/mm3 usually35.
Patients presentation may be behavioural, cognitive or motor affectation.
They may present with leg weakness and loss of balance, forgetfulness and
psychosis36, 37.
HIV dementia is as of now, a diagnosis of exclusion. There are no
neuroimaging or laboratory investigations specific for HIV dementia 34.
Antiretroviral drugs particularly high dose zidovudine is effective in reversing
or slowing the progression of dementia38.
The most common opportunistic infection that results in focal cerebral mass
lesion in HIV positive patients with advanced immunosuppression is from
toxoplasma gondii. The risk of cerebral toxoplasmosis infection is increased
with CD4 count less than 5023.

Page 6 of 16

The onset of symptoms may be sub-acute. They present at the emergency

department with headache, confusion, altered consciousness, fever and focal
neurological deficit. As disease advance they may present with hemiparesis,
motor weakness, ataxia, cranial nerve

palsies and speech disturbances.

Nausea and vomiting maybe present with increasing intracranial pressure 23,34.
Cerebral toxoplasmosis can be diagnosed with serological studies for antitoxoplasma antibody. An elevated serum IgG level can be indicative of an
acute infection especially in the presence of supporting clinical symptoms 23.
Imaging studies such as contrast enhanced magnetic resonance imaging
(MRI) or computed tomography can be used to diagnose cerebral
toxoplasmosis. They usually show multiple ring enhancing lesions in the
cerebral cortex, basal ganglion and corticomedullary junction 23,34.
Cerebral toxoplasmosis is treated primarily with pyrimethamine and
sulfadiazine. Patients who are allergic to sulphonamides may be treated with
atovaquone. Intravenous trimethoprim sulphamethxazole at 10mg and 50mg
per kilogram respectively is administered in severely ill patient who cannot
tolerate orally23,34.
Corticosteroids like dexamethasone is used when radiological evidence of
cerebral oedema and intracranial hypertension 34.
Tuberculosis meningitis as part of extra pulmonary tuberculosis is seen in coinfected patients with CD4 counts less than 200 23.They are seen at the
emergency department with non-specific symptoms of headache, nausea and
vomiting in addition to fever and signs of meningeal irritation. The patients
may have hemiparesis, seizures, cranial palsies to 3rd and 6th nerve 23,34.
Diagnosis is made with a lumber puncture. It shows an elevated protein and
low glucose. There is pleocytosis with predominantly lymphocyte. Treatment
is essentially with the use of anti-tuberculosis drugs. The unconscious patient
Page 7 of 16

maybe admitted to the intensive care unit and the airway secured secured
using an endotracheal tube23.
The common fungus responsible for infection in HIV positive patients with
advanced infection is Cryptococcus neoformans. It is seen in ten percent of
patients39.
There is may be absence of nuchal rigidity and other signs of meningism.
Patients may present at the emergency department with a sub-acute history
of fever and non-specific constitutional symptoms such as nausea and
malaise. Cryptococcal meningitis is associated most commonly with
headache, altered mental state, neck stiffness, vomiting and photophobia 23,39.
Diagnosis of cryptococci meningitis can be made through analysis of
cerebrospinal fluids obtained through a lumber puncture for Indian ink and
antigen test. The opening cerebrospinal fluid pressure is usually elevated in
cryptococcal meningitis39.
Treatment of cryptococcal meningitis involves the use of intravenous
amphotericin B for about two weeks followed by the use of fluconazole as
maintenance and secondary prophylaxis 23.
Diarrhoea emergencies
The leading abdominal complaint seen in HIV positive patient is diarrhoea. It
is experienced by over ninety percent of patients with AIDS 23. The diarrhoea
may be severe, persistent or recurrent and incidence increases with
worsening immune status23. A number of organism may be responsible for the
diarrhoea in HIV positive patients. Commonly isolated enteric organism from
HIV infected patients include; Salmonella Spp, enterohaemorrhagic and
enteroinvasive Escherichia coli, Campylobacter Spp, Shigella flexneri and
other Shigella Spp, Vibro cholera, Clostridium difficile, Staphylococcus aureus

Page 8 of 16

and yersnia enterolitica, isospora belli, giadia lamblia, cryptosporidium lavium

and cytomegalovirus39.
Patients may present with acute or chronic diarrhoea. Chronic diarrhoea
results in increasing mortality by causing malabsorption and malnutrition 23.
Diarrhoea is accompanied by abdominal cramps, nausea and intermittent
watery stool, usually non- bloody or mucoid. Clinical evaluation should include
assessment of level of hydration, and urine output, weight, pulse and blood
pressure23.
Diagnostic approached include examination of stool for ova and parasite and
endoscopic biopsy. Treatment is primarily rehydration with correction of
electrolyte imbalance. Negative nitrogen balance is remedied by offering high
energy and protein intake23,39.
Ocular Emergencies
One of the leading causes of ocular fatalities is cytomegalovirus retinitis. It is
most likely to occur in HIV positive patients with CD4 counts less than 50 cells
per microliter23. Cytomegalovirus retinitis will occur in 40% of patients with
advanced immunosuppression during the course of their disease 40. Infected
HIV positive patients present at the emergency department with symptoms of
decreased or blurred vision and may be associated with blind spots, visual
field loss, flashing lights and floaters. Diagnosis of cytomegalovirus retinitis
can be made by fundoscopy40,43. Examination of the fundus reveals peripheral
whitish exudates. Perivascular fluffy yellow-white retinal infiltrates; and focal
necrotizing retinitis with or without intra-retinal haemorrhage may be
present23. Long standing retinitis causes a bushfire pattern. This eventually
leads to formation of a granular white loading edge resulting in an atrophic
and gliotic scar then blindness23. Cytomegalovirus infection may alternatively
be diagnosed by a positive cytomegalovirus polymerase chase reaction and
positive antibodies to pp6523.

Page 9 of 16

None of the available medication used in the treatment of cytomegalovirus

retinitis can reverse the disease however, disease progression can be
halted23. The drugs used are gancyclovir, foscanet and cidofovir 41. The use of
gancyclovir is the treatment of choice and can be administered directly into
the eye, intravenously or orally. There is an induction phase and a
maintenance phase. Intravenous gancyclovir is given twice a day for three
weeks at 5mg per kilogram, then five to seven days a week. Oral treatment is
continued at 1000mg three times a day23. Treatment can be discontinued
when CD4 count increases over 200 cells23.

Primary HIV Infection

Acute retroviral syndrome is seen in 55%-92% of patients exposed to HIV 39.
They

have

mononucleosis

like

illness

with

fever

and

generalised

lymphadenopathy. A faster disease progression is associated with severity of

symptoms of seroconversion42.
Diagnosing primary HIV infection is made by detecting the p24 antigen or
detecting HIV viral RNA directly39. The routine enzyme linked immunoassay
(ELISA) used to diagnose HIV will test negative because it requires about 27
days post exposure to become positive 43. Treatment requires the use of
antiretroviral drugs39.

Conclusion
HIV positive patients may present with emergencies at any stage of the
disease. They are associated with several potentially life threatening
opportunistic infections and malignancies. They present new challenges to
the emergency doctor. Thus a high index of suspicion coupled with an
aggressive approach to diagnosis is crucial for successful management.
Page 10 of 16

References
1.www.statssa.gov.za/publications/P0302/P03022010.pdf
2.Shisana O, Rehle T, Simbayi LC, et al. South African National Hiv
Prevalence, Incidence, Behaviour and Communication

survey 2008: A

Turning Tide among Teenagers? Capetown 2009 :HSRS press

3.Hirschtick RE, Glassroth J, Jordan MC, et al.

Bacterial pneumonia in

persons infected with the human immunodeficiency virus.

N Engl J

Med 1995;333:845-51.
4.Feikin D, Feldman C, Schuchat A, et al. Global strategies to prevent
bacterial

pneumonia

in

adults

with

HIV

disease.

Lancet

Infect

Dis 2004;4: 445-55

5.Wallace JM, Hansen NI, Lavange L, et al. Respiratory disease trends in the
pulmonary complications of HIV Infection Study Cohort. Am J Respir Crit
Care Med 1997;155:72-80
6. Afessa B, Green W, Chiao J, et al. Pulmonary complications of HIV
infection: autopsy findings. Chest 1998;113:1225-29
7. Selwyn PA, Feingold AR, Hartel D, et al. Increased risk of bacterial
pneumonia in HIV-infected intravenous drug users without AIDS. AIDS
Page 11 of 16

1988;2:267-72
8.Hirschtick, R, Glassroth, J, Jordan, MC, et al. Bacterial pneumonia in
patients infected with human immunodeficiency virus. N Engl J Med
1995;333,845-851
9. Dropulik, LK, Leslie, JM, Eldred, LJ, et al Clinical manifestations and risk
factors of Pseudomonas aeruginosa infection in patients with AIDS. J Infect
Dis 1995;171,930-937
10. Everett KC, Fei MW, Huang L. Respiratory emergencies in HIV-infected
persons. Emerg Med Clin North Am 2010;28(2):283-98
11. Glatt AE, Chirgwin k, andesman SH. Treatment of infections associated
with human immunodeficiency virus. N Engl J Med 1988; 318: 1439-48
12. Update: acquired immunodeficiency syndromeUnited States. MMWR
Morb Mortal Wkly Rep. 1986;35:75766.
13. Update: acquired immunodeficiency syndromeUnited States. MMWR
Morb Mortal Wkly Rep. 1986;35:1721.
14. Kaplan JE, Benson C, Holmes KH, et al. Guidelines for prevention and
treatment of opportunistic infections in HIV-infected adults and adolescents:
recommendations from CDC, the National Institutes of Health, and the HIV
Medicine Association of the Infectious Diseases Society of America. MMWR
Recomm Rep 2009; 58: 1207
15. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines
for the management of blastomycosis: 2008 update by the Infectious
Diseases Society of America. Clin Infect Dis 2008; 46: 180112
16. Mirza SA, Phelan M, Rimland D, et al. The changing epidemiology of
cryptococcosis: an update from population-based active surveillance in 2
large metropolitan areas, 19922000. Clin Infect Dis 2003; 36: 789794
Page 12 of 16

17. Miller WT, Sais GJ, Frank I, et al. Pulmonary aspergillosis in patients with
AIDS. Clinical and radiographic correlations. Chest 1994; 105: 3744.
18. Garbino J, Inoubli S, Mossdorf E, et al. Respiratory viruses in HIV-infected
patients with suspected respiratory opportunistic infection. AIDS 2008; 22:
7015
19.Fiore AE, Uyeki TM, Broder K, et al. Prevention and control of influenza
with vaccines: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep 2010; 59: 168
20. Derouin F, Sarfati C, Beauvais B, et al. Prevalence of pulmonary
toxoplasmosis in HIV-infected patients. AIDS 1990; 4: 1036.
21. Metersky ML, Colt HG, Olson LK, et al. AIDS-related spontaneous
pneumothorax: risk factors and treatment. Chest. 1995;108:94651
22. Benito N, Moreno A, Miro J, et al. Pulmonary infections in HIV-infected
patients: an update in the 21st century. Mar 2012;39(3):730-745
23. Rewari BB, Purohit V, Chhabra RM, et al. Emergencies in HIV medicinePart 1. J Assoc Physicians India 2008 Sep;56:699-708.
24.Boiselle P,Tocino I, Hooley R, et al, chest radiograph interpretation of
pneumocystis carinii pneumonia, bacterial pneumonia, and pulmonary
tuberculosis in HIV- positive patients, accuracy, distinguishing features and
mimics. J thoracic imaging 1997; 12:47-53
25. Opravail M, Marincek B, Fuchs WA, et al. Shortcomings of chest
radiography in detecting Pneumocystis carinii pneumonia. J Acquir Immune
Defic Syndr 1994;7:3945

Page 13 of 16

26. Benito N, Ra A, Moreno A, et al Pulmonary infiltrates in HIV-infected

patients in the highly active antiretroviral therapy in Spain. J Acquir Immune
Defic Syndr 2001; 27: 3543.
27. Monkongdee P, McCarthy KD, Cain KP, et al. Yield of acid-fast smear and
mycobacterial culture for tuberculosis diagnosis in people with human
immunodeficiency virus. Am J Respir Crit Care Med. 2009;180:9038.
28. Thomas CF, Limper AH. pneumocystis pneumonia. N Engl J Med 2004;
350:2487-98
29. Felmingham D, Grneberg RN, & the Alexander Project Group (1996). A
multicentre

collaborative

study

of

the

antimicrobial

susceptibility

of

community-acquired, lower respiratory tract pathogens 19921993: The

Alexander Project. Journal of Antimicrobial Chemotherapy 38, Suppl. A, 157
30. WILKIN A, FEINBERG J, University of Cincinnati Medical Center,
Cincinnati, Ohio. Pneumocystis carinii pneumonia:A clinical review. Am Fam
Physician 1999 Oct;60(6):1699-1708.
31. Walmsley S, Levinton C, Brunton J, et al. A multicentre randomized
double-blinded placebo-controlled trial of Pneumocystis carinii pneumonia
complicating the acquired immune deficiency syndrome. J Aquir Immune
Defic Syndr Hum Retrovirol 1995 Apr 1;8(4):348-357
32. Nez M, Peacock JE, Chin R. Pulmonary cryptococcosis in the
immunocompetent host. Therapy with oral fluconazole: a report of four cases
and a review of the literature. Chest 2000 Aug;118(2):527-34.
33. Camuset J, Nunes H, Dombret MC, et al. Treatment of chronic pulmonary
aspergillosis by voriconazole in non-immunocompromised patients. Chest
2007;131(5):1435-41

Page 14 of 16

34.Simpson DM, Berger JR. Neurologic manifestation of HIV infection. Med

Clin North Am 1996 Nov; 80(6): 1363-1394
35.Arnaudo E, Dalakas M, Shanske S, et al: Depletion of muscle
mitochondrial DNA in AIDS patients with zidovudine-induced myopathy.
Lancet 1991;337:508-510
36. Evans DL, Perkins DO. The clinical psychiatry of AIDS. Curr Opin
Psychiatry 1990;3:96-102
37. Navia BA, Jordan BD, Price RW. The AIDS dementia complex: Clinical
features. Ann Neurol 1986;19:517-524
38. Yarchoan R, Berg G, Brouwers P, et al: Response of human
immunodeficiency-virus-associated neurological disease to 3

-azido-3

-deoxythymidine. Lancet 1987; 1:132

39.Moran JM, House HR. HIV-related illnesses: The challenge of ED
management. Emergency Medicine Practice 2002;4:1
40. Kedhar SR, Jabs DA. Cytomegalovirus retinitis in the era of highly active
antiretroviral therapy. Herpes 2007;14:66-71
41.Freeman WR, Lerner CW, Mines JA, et al. A prospective study of the
ophthalmologic findings in the acquired immunodeficiency syndrome. Am J
Ophthalmol. 1984;97:133-42
42.Schacker TW, Hughes JP, Shea T, et al. Biological and virologic
characteristics of primary HIV infection. Ann Intern Med 1998;1228(8):613620

Page 15 of 16

43. Busch MP, Lee LL, Satten GA, et al. Time course of detection of viral and
serologic

marker

preceeding

human

immunodeficiency

virus

type1

seroconversion: implications for screening of blood and tissue donors.

Transfusion 1995;35(2):91-7

Page 16 of 16