HIV and Associated Infections in the ICU 137

and Acyclovir may improve HSV outcomes. After radiographic exclusion

of mass lesion or hydrocephalus, cerebrospinal fluid (CSF) collection for
suspected AIDS-related meningitis is indicated by relatively effective
therapies and reasonably high diagnostic yield of the procedure. Among
the typically identified organisms are Cryptococcus, and M. tuberculosis.
CSF analysis may also indicate the presence of lymphoma, another
common cause of AIDS-related meningitis.

CNS mass lesions may represent either malignancy or infection. Because

of its frequency, Toxoplasma gondii should be considered in patients with
<100 and new intraparenchymal lesions, even in the
absence of a classic ring-enhancing lesion. Alternate considerations
include bacterial abscesses, lymphoma, and tuberculosis. Similarities of
presentation may eventually warrant brain biopsy, though this decision is
best made in consultation with infectious disease and neurosurgical
subspecialists.

3. PREDICTORS OF ICU OUTCOMES AMONG HIV-

INFECTED PATIENTS

Numerous efforts have been made to establish prognostic markers for

critically ill AIDS patients. Table 2 reviews some of these studies, with
comment on patient population and study results.

To date, no measures are known to effectively predict ICU mortality among

HIV-infected patients (15). The hypothesis follows that severity of illness,
rather than HIV-related factors, primarily determines short-term outcomes.
This is cautiously supported by observations that acute physiology scores
(e.g., APACHE II or SAPS I and II) tend to outperform demographic or
laboratory data in predicting outcome (51-54). Still, in many reports
APACHE II scores underestimate ICU mortality in HIV disease. Further,
trends suggest that non-AIDS diagnoses portend better outcomes than do
admissions for P. carinii-related respiratory insufficiency, even when
correcting for severity of illness (13). Thus, no predictors of HIV-related
ICU admission outcome, have been conclusively identified.

Even in the presence of a validated scoring system for HIV outcomes, the
principals of care remain the same. Team members must control
nosocomial infection risk, minimize untoward effects of medications and
138 Tropical and Parasitic Infections in the ICU

interventions, and to allow the patient the greatest possible dignity and self-
determination.
HIV and Associated Infections in the ICU 139
140 Tropical and Parasitic Infections in the ICU
HIV and Associated Infections in the ICU 141

REFERENCES

1. Nakashima AK, Fleming PL. HIV/AIDS surveillance in the United States,

1981-2001. J Acquir Immune Defic Syndr 2003; 32 Suppl 1:S68-85.
2. UNAIDS/WHO global AIDS statistics. AIDS Care 2003; 15:144.
3. Torres RA, Barr M. Impact of combination therapy for HIV infection on
inpatient census. N Engl J Med 1997; 336:1531-1532.
4. Nuesch R, Geigy N, Schaedler E, et al. Effect of highly active antiretroviral
therapy on hospitalization characteristics of HIV-infected patients. Eur J Clin
Microbiol Infect Dis 2002; 21:684-687.
5. Ghani AC, Donnelly CA, Anderson RM. Patterns of antiretroviral use in the
United States of America: analysis of three observational databases. HIV Med
2003; 4:24-32.
6. Palella FJ, Jr., Delaney KM, Moorman AC, et al. Declining morbidity and
mortality among patients with advanced human immunodeficiency virus
infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338:853-
860.
7. Afessa B, Green B. Clinical course, prognostic factors, and outcome prediction
for HIV patients in the ICU. The PIP (Pulmonary complications, ICU support,
and prognostic factors in hospitalized patients with HIV) study. Chest 2000;
118:138-145.
8. De Palo VA, Millstein BH, Mayo PH, et al. Outcome of intensive care in
patients with HIV infection. Chest 1995; 107:506-510.
9. Rosen MJ, Clayton K, Schneider RF, et al. Intensive care of patients with HIV
infection: utilization, critical illnesses, and outcomes. Pulmonary Complications
of HIV Infection Study Group. Am J Respir Crit Care Med 1997; 155:67-71.
10. Wachter RM, Luce JM, Turner J, et al. Intensive care of patients with the
acquired immunodeficiency syndrome. Outcome and changing patterns of
utilization. Am Rev Respir Dis 1986; 134:891-896.
11. Wachter RM, Luce JM, Safrin S, et al. Cost and outcome of intensive care for
patients with AIDS, Pneumocystis carinii pneumonia, and severe respiratory
failure. Jama 1995; 273:230-235.
12. Rosen MJ. Intensive care of patients with HIV infection. Semin Respir Infect
1999; 14:366-371.
13. Morris A, Creasman J, Turner J, et al. Intensive care of human
immunodeficiency virus-infected patients during the era of highly active
antiretroviral therapy. Am J Respir Crit Care Med 2002; 166:262-267.
14. Casalino E, Mendoza-Sassi G, Wolff M, et al. Predictors of short- and long-
term survival in HIV-infected patients admitted to the ICU. Chest 1998;
113:421-429.
15. Curtis JR, Bennett CL, Horner RD, et al. Variations in intensive care unit
utilization for patients with human immunodeficiency virus-related
Pneumocystis carinii pneumonia: importance of hospital characteristics and
geographic location. Crit Care Med 1998; 26:668-675.
16. Randall Curtis J, Yarnold PR, Schwartz DN, et al. Improvements in outcomes
of acute respiratory failure for patients with human immunodeficiency virus-
related Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 2000;
162:393-398.
142 Tropical and Parasitic Infections in the ICU

17. Ledergerber B, Egger M, Opravil M, et al. Clinical progression and virological

failure on highly active antiretroviral therapy in HIV-1 patients: a prospective
cohort study. Swiss HIV Cohort Study. Lancet 1999; 353:863-868.
18. Masur H. Critically Ill Immunosuppressed Host. In: Parrillo JE, Dellinger RP,
eds. Critical Care Medicine: Principles of DIagnosis and Management in the
Adult St. Louis: Mosby, 2001; 1089-1108
19. Dasgupta A, Okhuysen PC. Pharmacokinetic and other drug interactions in
patients with AIDS. Ther Drug Monit 2001; 23:591-605.
20. Soni N, Pozniak A. Continuing HIV therapy in the ICU. Crit Care 2001; 5:247-
248.
21. French M, Price P. Immune restoration disease in HIV patients: aberrant
immune responses after antiretroviral therapy. J HIV Ther 2002; 7:46-51.
22. Wendel KA, Alwood KS, Gachuhi R, et al. Paradoxical worsening of
tuberculosis in HIV-infected persons. Chest 2001; 120:193-197.
23. Wislez M, Bergot E, Antoine M, et al. Acute respiratory failure following
HAART introduction in patients treated for Pneumocystis carinii pneumonia.
Am J Respir Crit Care Med 2001; 164:847-851.
24. Morris A, Wachter RM, Luce J, et al. Improved survival with highly active
antiretroviral therapy in HIV- infected patients with severe Pneumocystis
carinii pneumonia. Aids 2003; 17:73-80.
25. Reilly JM, Cunnion RE, Anderson DW, et al. Frequency of myocarditis, left
ventricular dysfunction and ventricular tachycardia in the acquired immune
deficiency syndrome. Am J Cardiol 1988; 62:789-793.
26. Berger JR, Sabet A. Infectious myelopathies. Semin Neurol 2002; 22:133-142.
27. Ullrich R, Zeitz M, Heise W, et al. Small intestinal structure and function in
patients infected with human immunodeficiency virus (HIV): evidence for HIV-
induced enteropathy. Ann Intern Med 1989; 111:15-21.
28. Call SA, Heudebert G, Saag M, et al. The changing etiology of chronic diarrhea
in HIV-infected patients with CD4 cell counts less than 200 cells/mm3. Am J
Gastroenterol 2000; 95:3142-3146.
29. Bini EJ, Cohen J. Impact of protease inhibitors on the outcome of human
immunodeficiency virus-infected patients with chronic diarrhea. Am J
Gastroenterol 1999; 94:3553-3559.
30. Nannini EC, Okhuysen PC. HIV1 and the gut in the era of highly active
antiretroviral therapy. Curr Gastroenterol Rep 2002; 4:392-398.
31. McArthur JC. Neurologic manifestations of AIDS. Medicine (Baltimore) 1987;
66:407-437.
32. Suffredini AF, Ognibene FP, Lack EE, et al. Nonspecific interstitial
pneumonitis: a common cause of pulmonary disease in the acquired
immunodeficiency syndrome. Ann Intern Med 1987; 107:7-13.
33. Beck JM, Rosen MJ, Peavy HH. Pulmonary complications of HIV infection.
Report of the Fourth NHLBI Workshop. Am J Respir Crit Care Med 2001;
164:2120-2126.
34. Singh F, Rudikoff D. HIV-Associated Pruritus: Etiology and Management. Am
J Clin Dermatol 2003; 4:177-188
35. Koutsilieri E, Scheller C, Sopper S, et al. Psychiatric complications in human
immunodeficiency virus infection. J Neurovirol 2002; 8 Suppl 2:129-133.
36. Ratner L. Human immunodeficiency virus-associated autoimmune
thrombocytopenic purpura: a review. Am J Med 1989; 86:194-198.
HIV and Associated Infections in the ICU 143

37. Little RF, Wilson WH. Update on the Pathogenesis, Diagnosis, and Therapy of
AIDS-related Lymphoma. Curr Infect Dis Rep 2003; 5:176-184.
38. Scadden DT. AIDS-related malignancies. Annu Rev Med 2003; 54:285-303
39. Masur H, Ognibene FP, Yarchoan R, et al. CD4 counts as predictors of
opportunistic pneumonias in human immunodeficiency virus (HIV) infection.
Ann Intern Med 1989; 111:223-231.
40. Jones JL, Hanson DL, Dworkin MS, et al. Surveillance for AIDS-defining
opportunistic illnesses, 1992-1997. MMWR CDC Surveill Summ 1999; 48:1-
22.
41. Wolff AJ, O’Donnell AE. Pulmonary manifestations of HIV infection in the era
of highly active antiretroviral therapy. Chest 2001; 120:1888-1893.
42. Montaner JS, Lawson LM, Levitt N, et al. Corticosteroids prevent early
deterioration in patients with moderately severe Pneumocystis carinii
pneumonia and the acquired immunodeficiency syndrome (AIDS). Ann Intern
Med 1990; 113:14-20.
43. Consensus statement on the use of corticosteroids as adjunctive therapy for
pneumocystis pneumonia in the acquired immunodeficiency syndrome. The
National Institutes of Health-University of California Expert Panel for
Corticosteroids as Adjunctive Therapy for Pneumocystis Pneumonia. N Engl J
Med 1990; 323:1500-1504.
44. Limper AH, Offord KP, Smith TF, et al. Pneumocystis carinii pneumonia.
Differences in lung parasite number and inflammation in patients with and
without AIDS. Am Rev Respir Dis 1989; 140:1204-1209.
45. Wright TW, Gigliotti F, Finkelstein JN, et al. Immune-mediated inflammation
directly impairs pulmonary function, contributing to the pathogenesis of
Pneumocystis carinii pneumonia. J Clin Invest 1999; 104:1307-1317.
46. Kumar SD, Krieger BP. CD4 lymphocyte counts and mortality in AIDS patients
requiring mechanical ventilator support due to Pneumocystis carinii pneumonia.
Chest 1998; 113:430-433.
47. Schein RM, Fischl MA, Pitchenik AE, et al. ICU survival of patients with the
acquired immunodeficiency syndrome. Crit Care Med 1986; 14:1026-1027.
48. Confalonieri M, Calderini E, Terraciano S, et al. Noninvasive ventilation for
treating acute respiratory failure in AIDS patients with Pneumocystis carinii
pneumonia. Intensive Care Med 2002; 28:1233-1238.
49. Barnes PF, Bloch AB, Davidson PT, et al. Tuberculosis in patients with human
immunodeficiency virus infection. N Engl J Med 1991; 324:1644-1650.
50. Daley CL, Small PM, Schecter GF, et al. An outbreak of tuberculosis with
accelerated progression among persons infected with the human
immunodeficiency virus. An analysis using restriction-fragment-length
polymorphisms. N Engl J Med 1992; 326:231-235.
51. Rosenberg AL, Seneff MG, Atiyeh L, et al. The importance of bacterial sepsis
in intensive care unit patients with acquired immunodeficiency syndrome:
implications for future care in the age of increasing antiretroviral resistance.
Crit Care Med 2001; 29:548-556.
52. Brown MC, Crede WB. Predictive ability of acute physiology and chronic
health evaluation II scoring applied to human immunodeficiency virus-positive
patients. Crit Care Med 1995; 23:848-853.
144 Tropical and Parasitic Infections in the ICU

53. Bonarek M, Morlat P, Chene G, et al. Prognostic score of short-term survival in

HIV-infected patients admitted to medical intensive care units. Int J STD AIDS
2001; 12:239-244.
54. Alves C, Nicolas JM, Miro JM, et al. Reappraisal of the aetiology and
prognostic factors of severe acute respiratory failure in HIV patients. Eur
Respir J 2001; 17:87-93.
9
African Trypanosomiasis

Hayden T. White
Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa

INTRODUCTION

African trypanosomiasis (sleeping sickness) results from infection due to

organisms of the genus trypanosoma (order kinetoplastidae and family
trypanosomatidae)(1). These organisms are digenetic parasites whose life
cycle involves 2 hosts: a definitive mammalian host and an intermediate
arthropod host (which is responsible for dissemination of the organism).
They are classified into 2 groups; stercoraria and salivaria. Stercoraria
comprises species that develop in the arthropod’s hind gut (reduviid bug)
and are therefore found in the bug’s feces. This includes the causative
agent of Chaga’s disease or American trypanosomiasis, Trypanosoma
cruzi. Salivaria include species that are found in the salivary glands of the
tsetse fly (Glossina species) and are transmitted via inoculation into
mammalian skin. The species infecting humans is known as Trypanosoma
brucei. The brucei complex consists of the subspecies gambiense (west
African trypanosomiasis, WAT) and rhodesiense (east African
trypanosomiasis, EAT). Another subspecies, T. brucei brucei infects
cattle, goats and sheep but not humans. While it has become useful to
classify African sleeping sickness in terms of the 2 subspecies, it should
be recognized that many different strains exist which are capable of
infecting man (2).
146 Tropical and Parasitic Infections in the ICU

MORPHOLOGY

The trypanosomiasis parasite is characterized by the presence of a free

flagellum arising from the kinetoplast (an organelle containing DNA) and
an undulating membrane that gives the organism motility (3,4). The
organism exists in different stages in the various hosts. The epimastigote
stage occurs in the insect vector (5,6). This stage is not infective to
humans but transforms into the infective metacyclic trypanosome, which
is considered the young form of trypomastigote. The trypomastigote is the
mature form and is found in the blood of mammalian hosts. Polymorphic
forms may be present and represent the brucei complex. If the species is
monomorphic, then T. cruzi is diagnosed.

EPIDEMIOLOGY

The distribution of human trypanosomiasis follows that of the vector, the

tsetse fly. Thirty-six countries in sub-Saharan Africa are considered to be
endemic with some 50 million people at risk. Approximately
are infested with tsetse, severely limiting the agricultural potential of
these areas. Sleeping sickness has reached epidemic proportions in
Angola, Uganda and the Sudan. Although 25000 new cases are reported
annually, it is estimated that the true figure is closer to 300000 (7). During
the 1960’s the prevalence of sleeping sickness in most African countries
had been reduced to < 0.1%. However, civil unrest over the past few
decades and the subsequent decline in control programs has resulted in a
marked increase in the prevalence of disease. Some areas have reported
figures as high as 18%. Nowhere is this more evident then in the
Democratic Republic of the Congo. The recent war has led to estimates
that over 100000 people will die annually from trypanosomiasis. Another
example is Angola, where 60% of the population in the north of the
country has evidence of past or present infection. Civil wars and the
breakdown of health services are the primary reasons for the resurgence of
sleeping sickness in much of Africa.