Prolonged cryptosporidiosis during primary HIV infection

Journal of Infection (1995)

30, 5 1 - 5 3

CASE REPORT

Prolonged Cryptosporidiosis During Primary HIV Infection Peter J. Moss 1, Robert C. Read 1, Goura Kudesia 2 and Michael W. McKendrick 1 1Department of Infectious Diseases and Medicine, Royal Hallamshire Hospital, Glossop Road, Sheffield, $10 2JF and 2Public Health Laboratory, Northern General Hospital, Sheffield, $5 7AU, U.K. Accepted for publication 10 June 1994

Primary infection with the human immunodeficiency virus causes profound immunosuppression with a decrease in lymphocyte numbers and function. However, this immunosuppression is transient and most individuals regain normal immune function. Infection with opportunist pathogens during the period of immunosuppression is rare. We report a case of severe prolonged cryptosporidiosis complicating primary HIV i@ction. This has not previously been described. A review of other cases of opportunist infections in primary HIV infection suggests that various pathogens may take advantage of the transient immunosuppression. This has important implications for the diagnosis and management of acute HIV infection, and for the diagnostic criteria currently used for AIDS.

Introduction Infection with the h u m a n immunodeficiency virus (HIV) is becoming increasingly c o m m o n in developed countries, and a broad spectrum of syndromes caused by acute HIV infection has now been reported. Recently it has been recognised that opportunist infections can occur during the period of HIV seroconversion, though such reports are rare. We describe a patient with primary HIV infection who presented with severe prolonged Cryptosporidium diarrhoea, an infection that is included in the CDC surveillance case definition of AIDS. 1 The association of severe cryptosporidiosis with primary HIV infection has not been described before.

Case Report A 59-year-old caucasian m a n was admitted shortly after his return from sub-Saharan Africa where he had been working for m a n y years. During the 2 months before presentation he had experienced increasingly severe watery diarrhoea, abdominal cramps and general malaise. Laboratory tests performed in Africa 4 weeks before his return revealed Cryptosporidium oocysts in his stool; he was also found to have an absolute lymphopenia (0.5 x 109/1; normal range 1.0-4.8 x 109/1) but the remainder of his blood profile was normal and no malarial parasites were seen. At presentation to our unit he gave a short history of

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fever and headache in addition to persistent diarrhoea. On clinical examination his temperature was 38 °C and he had a scanty macular truncal rash and generalised abdominal tenderness. Initial laboratory investigations revealed a total WBC count of 3.6 x 109/1 with a lymphopenia (0.76 x 109/1). Haemoglobin estimation and platelet count were normal. No malarial parasites were seen. C-reactive protein was 58 my/1 (normal <5 my/l). Liver enzyme values were abnormal (AST 101 u/l; normal range 10-34u/1: ALT 153u/1; normal range 7-33 u/l: 7GT 217/1; normal range 7-49u/1): bilirubin was 19 Ixmol/1 (normal <19 #mol/1), and all other biochemistry was normal. Chest X-ray was clear. Stool examination revealed large numbers of Cryptosporidium oocysts, urine microscopy was normal and sputum was negative for acid-fast bacilli on microscopy. During the next few days he continued to have intermittent high fever (up to 38.5 °C) and watery diarrhoea. The lymphocyte count rose gradually, reaching 2.38 x 109/1 a week after admission; other haematological parameters did not change significantly. His liver enzymes improved, and a week after admission AST was 26 u/l, ALT 37 u/1 and GT 117 u/1. Urine, sputum, blood and bone m a r r o w cultures were negative. Serology for Hepatitis A and B, Brucella spp., Mycoplasma spp., Chlamydia spp., Coxiella burnetii, Influenza A and B, adenovirus, Epstein-Barr virus, cytomegalovirus, Rickettsia spp., Toxoplasma, Entamoeba histolytica and Echinococcus granulosus was negative. Auto-antibody results were negative. Widal agglutination showed positive titres at 120 to AH, at 60 to BH, BO and TO, and at 30 to AO and TH. An ultrasound scan of the abdomen suggested the © 1995 The British Society for the Study of Infection

52

Cryptosporidiosis and Primary HIV Infection

Table 1. The results of serial serologicaltests for human immunodeficiencyvirus. Days from admission

Abbott 1+ 2

Behring 1+ 2

Wellcozyme HIV Ag Abbott pg/ml HIV F.LISAINDEX*

0 7

2(+ve) 7.5(+ve)

0.56(-ve) 0.98(eq.)

0.59(+ve) 0.28(+ve)

194(+ve) -re

10

13 19

ND ND ND

ND ND 8.5(+ve)

ND ND 0.16(+ve)

ND ND -ve

43

ND

ND

ND

ND

HW-LIA Innotest

Lymphocytes

x 109/1

x 109/1

CD8 x 109/1

ND GP41+ P24+ P17- P31 + / ND ND GP41 + + + P24 + + + P17+/P31 + / ND

0.76 1.84

ND ND

ND ND

2.2 1.9 ND

0.17 0.19 ND

1.76 1.48 ND

1.8

0.29

1.31

CD 4

* ELISAindex sample optical density/reference optical density. For Abbott and Behring ELISAindex of > 1 = positive. For WellcozymeELISAindex of <1 = positive. ND= Not done. =

presence of a cystic mass adjacent to the right kidney: aspiration revealed that this was an old haematoma (there was a history of previous trauma). He was given oral ciprotloxacin 500 mgm twice daily in view of the clinical possibility of enteric fever, but there was no significant response during the next 72 hours. Although he had initially denied any risk factors for HIV infection, it emerged on further questioning that he had been having regular unprotected sex with an African w o m a n for several months. We therefore requested HIV testing. The results of serial serology, absolute lymphocyte count and CDJCD8 count are shown in Table 1. The first blood sample (taken on the day of admission) was positive in two of the HIV 1 + 2 antibody tests (Abbott Diagnostic; Wellcozyme recombinant) but negative in a third (Behring). HIV antigen was detected (Abbott Diagnostic), indicating that the patient was viraemic. Later samples showed evidence of seroconversion in one of the assays (Behring) and an increase in anti-HIV antibodies in all the assays used. HIV antigen was not detected after the initial sample. The HIV ELISA findings were confirmed by a western blot type line assay (HIV-LIA, Innotest). These results indicate an acute seroconversion illness at the time of presentation. During the next week his fever and diarrhoea settled spontaneously, and 2 weeks after admission his stools were clear of Cryptosporidium. When reviewed 6 weeks after his initial presentation he remained well and his CD4 count had risen to 0.29 x 109/1. The CDJCD8 ratio had increased although it remained inverted. He has subsequently returned to work in Africa, and has had no further problems.

Discussion This patient had undoubted immunosuppression in association with HIV seroconversion, and during this period had prolonged cryptosporidiosis. Symptomatic infection with Cryptosporidium parvum for a period of greater than a m o n t h is a CDC AIDS defining illness, 1 and yet he made a good recovery with improvement in his immune status. Cryptosporidium parvum was first described as a h u m a n pathogen in 19 76, 2 and is found mainly in children and in the immunocompromised. It is sometimes found as a pathogen of otherwise healthy adults, usually acquired either from children or as a zoonosis; it is also transmitted in contaminated water. In such people the symptoms of vomiting and diarrhoea are usually short-lived and selflimiting, although faecal excretion of the micro-organism may persist for a further 1 to 2 weeks. 3 In the immunocompromised host the course and the illness is usually more prolonged and serious. Usually the development of cryptosporidiosis in an HIVpositive patient carries a poor prognosis. In a recent review the mean survival time after diagnosis was only 15 weeks, 4 although those patients with a higher absolute lymphocyte count did significantly better. In the patient described here Cryptosporidium cleared spontaneously from the stool as the lymphocyte count rose. The change in lymphocyte populations during acute HIV infection has been well documented. According to Cooper et al. 5 it can be divided into four distinct phases. Initially there is a fall in the absolute lymphocyte count, with no significant change in the subset ratios. Following this the CD8 count starts to rise relative to the CD4 count, with inversion of the CD4:CD8 ratio. The third phase is

P. J. Moss et aL characterised by a sharp increase in the absolute CDs count, with further inversion of the CD4:CD8 ratio, while in the fourth phase lymphocyte concentrations fall towards normal. We observed this pattern of response in the patient described here. It has also been noted that there is profound lymphocyte hypo-responsiveness to mitogen and antigen following acute HIV infection, 6 which implies immune dysfunction as well as a numerical deficit in CD4 lymphocytes. This pattern of transient immunodeficiency probably occurs in all cases of acute HIV seroconversion. In the majority of individuals there is fairly rapid restoration of normal lymphocyte numbers and function followed by a long period of asymptomatic HIV carriage, although in a few cases there appears to be a persistently low CD4 count following acute infection, with rapid progression to AIDS. 7 Possibly because of the transient nature of the immunosuppression associated with acute HW infection, there have been very few reports of opportunist infections occurring during this period. Several cases of oesophageal candidiasis have been described; 8' 9 it is possible that the oesophageal ulceration seen during acute HIV infection (and apparently due directly to the virus) predisposes to infection with this particular organism. 1°' n In 1988 Isaksson et a1.12 reported a case of tuberculous meningitis developing only 8 weeks after primary HIV infection, and in retrospect this may well represent a complication of the immunosuppression of acute HIV. Ocular cryptococcosis (which is also a CDC AIDS defining condition) 1 has been seen immediately preceding documented HIV seroconversion, and is likely to be due to the same underlying cause. 13 More recently Vento et al. 14 reported three cases of primary HIV infection with severe transient CD 4 lymphocytopenia complicated by Pneumocystis carinii pneumonia: all three patients made a full recovery, with CD 4 counts returning to normal. This is the first time that cryptosporidiosis has been reported as a complication of primary HIV infection. It adds to the increasing list of opportunist pathogens that are known to take advantage of the transient immunosuppression which accompanies seroconversion. While it is obviously a rare occurrence, it is very important for doctors to be .aware of the possibility of opportunist infection in primary HIV. Careful clinical and serological

53

review is necessary to avoid misdiagnosing seroconverting patients with such infections as having A1DS, as by current case definitions the two are indistinguishable. There are also implications for the management of patients with primary HIV disease, whose illness may be complicated by the type of severe opportunist infections that physicians usually associate with AIDS.

References 1 Centers for Disease Control. Revision of CDC surveillance case definition for acquired immunodeficiency syndrome. M M W R 1987; 36 (Suppl.): 1. 2 Nime FA, Burek JD, Page DL, Holscher MA, Yardley JH. Acute enterocolitis in a human being infected with the protozoan Cryptosporidium. GastroenterologlJ 1976; 70: 592-598. 3 Jokipii L, Jokipii AMM. Timing of symptoms and oocyst excretion in h u m a n cryptosporidiosis. N EngI ] Med 1986; 315: 1643-1647. 4 McGowan I, Hawkins AS, Weller IV. The natural history of cryptosporidial diarrhoea in HIV infected patients. AIDS 1993; 7: 349-354. 5 Cooper DA, Tindall B, Wilson El, Imrie AA, Penny R. Characterization of T lymphocyte responses during primary infection with h u m a n immunodeficiency virus. J Infect Dis 1988; 157: 889-895. 6 Pedersen C, Dickmeiss E, Gaub ] et al. T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HW seroconverters. AIDS 1990; 4 : 5 2 3 526. 7 Weiss PJ, Brodine SK, Goforth RR et al. Initial low CD4 lymphocyte counts in recent h u m a n immunodeficiency virus infection and lack of association with identified coinfections. [ Infect Dis I992; 166: 1149-1153. 8 Chaffanjon P, Lafeuillade A, Quilichini R, Aubert L. Primo~infection a VIH a manifestations severes et inhabituelles. La Presse Medicale 1992; 21: 536-537. 9 Pena JM, Martinez-Lopez MA, Arnalich F, Barbado FJ, Vazquez JJ. Esophageal candidiasis associated with acute infection due to human immunodeficiency virus: case report and review. Rev Infect Dis i991; 13: 872-875. 10 Rabeneck L, Boyko W], McLean DM, McLeod WA, Wong KK. Unusual oesophageat ulcers containing enveloped virus-like particles in homosexual men. Gastroenterology 1986; 90: 1882-1889. 11 TindalI B, Hing M, Edwards P, Barnes T, Mackie A, Cooper DA. Severe clinical manifestations of primary HIV infection. AIDS 1989; 3: 747-749. I2 Isaksson B, Albert J, Chiodi F et al. AIDS two months after primary h u m a n immunodeficiency virus infection. J Infect Dis 1988; 158: 866-868. 13 Balmes R, Bialasiewicz AA, Busse H. Conjunctival cryptococcosis preceding h u m a n inmmnodeficiency virus seroconversion. Am ] Ophthalmol 1992; 113: 719-721. 14 Vento S, Di Perri G, Garofano T, Concia E, Bassetti l). Pnemnocystis carinii pnemnonia during primary HIV 1 infection. Lancet 1993; 342: 24-25.