Current practice
Ann Biol Clin 2011; 69 (5): 605-8
Respiratory cryptosporidiosis in two patients with
HIV infection in a tertiary care hospital in Morocco
Copyright © 2017 John Libbey Eurotext. Téléchargé par un robot venant de 88.99.165.207 le 16/06/2017.
Cryptosporidiose respiratoire chez deux patients infectés par le VIH
dans un hôpital de soins tertiaire au Maroc
Abdelali Tali
Amal Addebbous
Souad Asmama
Laila Chabaa
Laila Zougaghi
Centre hospitalier Mohammed VI,
hôpital Ibn Tofayl Gueliz, laboratoire des
analyses médicales, Marrakech,
Morocco
<[email protected]>
Abstract. Respiratory cryptosporidiosis is recognized as a late-stage complication in persons with AIDS. We report two cases of respiratory cryptosporidiosis
in patients with HIV infection. The first patient was a 46-year-old person with
chronic diarrhea, a two-month history of low-grade fever, progressive dyspnea
and productive cough. The search for acid-fast bacillus, Pneumocystis jirovecii,
Toxoplasma gondii and Cryptococcus sp. in sputum was negative on several
samples. The modified Ziehl has shown oocysts of Cryptosporidium sp. in
induced sputum. The patient’s death occurred, due to electrolytes disorders. The
second patient was a 45-year-old person hospitalized for chronic fluid diarrhea,
complicated with weight loss, dry cough, dyspnea stage II and low-grade fever.
The patient was HIV-positive with low CD4 count and pancytopenia. Acid-fast
oocysts of Cryptosporidium sp. were observed in stool samples and induced
sputum. The patient was treated daily with azithromycin 500 mg resulting of
disappearance of gastrointestinal and respiratory disorders.
Key words: AIDS, Cryptosporidium
Résumé. La cryptosporidiose respiratoire est décrite comme une complication tardive chez les personnes atteintes du sida. Nous rapportons deux cas de
cryptosporidiose respiratoire chez les patients infectés par le VIH. Le premier
patient était un homme de 46 ans, souffrant de diarrhée chronique, avec une
fièvre modérée, une dyspnée progressive et une toux productive. La recherche
de bacilles acido-alcoolo-résistants, Pneumocystis jirovecii, Toxoplasma gondii
et Cryptococcus sp. dans les crachats était négative sur plusieurs échantillons.
La coloration de Ziehl modifiée a montré des oocystes de Cryptosporidium sp.
dans l’expectoration induite. La mort du patient est survenue dans un contexte de
troubles hydro-électrolytiques. Le second patient était hospitalisé pour diarrhée
chronique compliquée d’une perte de poids, toux sèche, une dyspnée stade II
et une fièvre modérée. Le patient était VIH-positif et pancytopénique. Cryptosporidium sp. a été observé dans des échantillons de selles et de l’expectoration
induite. Le patient a été traité quotidiennement par 500 mg d’azithromycine,
permettant la disparition des troubles gastro-intestinaux et respiratoires.
doi:10.1684/abc.2011.0626
Article received 20 April 2011,
accepted 16 June 2011
Mots clés : sida, Cryptosporidium sp.
Cryptosporidiosis is a zoonotic disease that causes clinical symptoms in both humans and animals; it is a
gastrointestinal illness caused by protozoa of the genus
Cryptosporidium. There are many species of Cryptosporidium but Cryptosporidium parvum and Cryptosporidium
hominis (formerly known as C. parvum anthroponotic
genotype or genotype 1) are the most prevalent species
in humans’ diseases [1]. Cryptosporidium infection is
transmitted by the fecal-oral way; it results from the
ingestion of Cryptosporidium oocysts through the consumption of fecally contaminated food or water or through
direct person-to-person or animal-to-person contact. The
oocysts are infectious immediately upon being excreted in
feces [1].
To cite this article: Tali A, Addebbous A, Asmama S, Chabaa L, Zougaghi L. Respiratory cryptosporidiosis in two patients with HIV infection in a tertiary care hospital
in Morocco. Ann Biol Clin 2011; 69(5): 605-8 doi:10.1684/abc.2011.0626
605
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Current practice
Cryptosporidium causes intracellular infections, predominantly in the epithelial cells of intestine. Mild to moderate
self-limited diarrhea is common in healthy persons, but
patients with immune dysfunction can have prolonged
diarrhea due to severe intestinal injury. Extra-intestinal
involvement with Cryptosporidium has been stated in AIDS
patients [2]. A few cases of pulmonary cryptosporidiosis with concomitant gastrointestinal infection have been
reported in literature. We report two cases of respiratory
localization of Cryptosporidium sp. in Human Immunodefiency Virus (HIV)-infected patients.
Case 1
A 46-year-old male was hospitalized for chronic fluid
diarrhea evolving for two months and associated with a
productive cough and progressive dyspnea (stage III). The
diagnosis of HIV infection has been confirmed before
the discovery of esophageal candidiasis by a gastroscopy
performed on the occasion of uncontrollable vomiting, dysphagia to solids and retrosternal pain. The clinical examination found a patient panting at 30 cycles per minute,
weight of 43 kg and dehydrated. The chest X-ray exam
was normal but abdominal ultrasound showed acalculous
cholecystitis.
For the laboratory examination, iterative search for acid-fast
bacillus (AFB) in sputum was negative. Parasitological testing of stool samples, performed by modified Ziehl-Neelsen
method, showed the existence of acid-fast oocysts of Cryptosporidium sp. (figure 1). Induced sputum was negative
in examination for Pneumocystis jirovecii, Toxoplasma
gondii, Cryptococcus sp. and AFB. However, the modified
Ziehl has shown oocysts of Cryptosporidium sp. (figure 2).
Then, the diagnosis of respiratory cryptosporidiosis has
been adopted. The CD4 + cell count was 70 cells/mm3 and
the CD8 + cell count was 1,443 cells/mm3 .
While the high active anti-retroviral therapy (HAART)
has been instituted, the patient was treated daily
with azithromycin 500 mg for cryptosporidiosis, fluconazole 150 mg for two weeks for esophageal candidiasis,
and cotrimoxazole prophylaxis for toxoplasmosis and
pneumocystosis. The evolution was marked by a new hospitalization, one month later, for recurrent of gastrointestinal
and respiratory symptoms. The parasitological testing of
stool and sputum samples showed the persistence of oocysts
of Cryptosporidium sp. The death occurred as a result of
electrolytes disorder.
Case 2
Figure 1. Oocysts of Cryptosporidium sp. in stool examination,
Ziehl-Neelsen modified (× 400).
Figure 2. Oocysts of Cryptosporidium sp. in induced sputum, ZiehlNeelsen modified (× 400).
606
Forty-five-year-old man, hospitalized for chronic fluid diarrhea, complicated with weight loss, dry cough and dyspnea
with stage II, all lasting for one month with low fever
(38 ◦ C). Physical examination was unremarkable, and chest
X-ray was normal. However, the patient was HIV-positive
on ELISA and western blot. Cell blood count showed a pancytopenia: anemia (95 g/L), thrombocytopenia (108 G/L)
and leukopenia of 1,86 G/L; the CD4 + cell count found
75 cells/mm3 .
Parasitological testing of stool samples showed the existence of Cryptosporidium sp. oocysts and Blastocystis
hominis. Iterative AFB examinations in sputum were negative. However, the modified Ziehl showed oocysts of
Cryptosporidium spin sputum (figure 3). The diagnosis of
respiratory cryptosporidiosis was established.
The patient was treated with azithromycin (500 mg a
day) for cryptosporidiosis and cotrimoxazole prophylaxis
for toxoplasmosis and pneumocystosis. The HAART in
this case was a combination of two nucleoside reverse
Ann Biol Clin, vol. 69, n◦ 5, septembre-octobre 2011
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Cryptosporidiosis and HIV
Figure 3. Oocysts of Cryptosporidium sp. in induced sputum, ZiehlNeelsen modified (× 400).
transcriptase inhibitors and a non-nucleoside: stavudine,
lamivudine and efavienz. The evolution was noted by a total
recovery with disappearance of the fever, the gastrointestinal symptoms and the respiratory disease.
Discussion
Cryptosporidiosis is a gastrointestinal protozoan infection
is commonly diagnosed in immunocompromised patients,
essentially in developing countries. Therefore, the rapid dissemination of HIV has increased considerably the incidence
and the prevalence of Cryptosporidiosis. Cryptosporidium
sp. is responsible for potentially severe opportunistic infections with a morbidity rate that’s directly proportional to
the depth of immunodepression. Its frequency ranged from
14 to 24% [3].
In Morocco, the prevalence of AIDS seems to be underestimated with 20,000 HIV-seropositive patients (less
than 1% of the population). Unfortunately, no data are
available concerning the incidence of cryptosporidiosis in
this population [4].
Infection with Cryptosporidium sp. results in a wide range
of manifestations, from asymptomatic infections to severe,
life-threatening illness. The mean incubation period is
seven days (range from two to 10 days). Diarrhea is the most
frequent symptom, and can be associated with dehydration,
weight loss, abdominal pain, fever, nausea and vomiting. In
immunocompetent persons, symptoms are usually shortlived (one to two weeks). Conversely, they can be chronic
and more severe in immunocompromised patients, especially those with CD4 + counts of less than 200 cells/mm3 ,
as a result of the autoinfestation [1, 5].
While the small intestine is the most commonly affected
site, symptomatic Cryptosporidium infections have also
Ann Biol Clin, vol. 69, n◦ 5, septembre-octobre 2011
been reported in other organs including hepatic ducts,
lungs and possibly conjunctiva [6, 7]. These extra-intestinal
localizations have been rarely reported. However, a few
reports of pulmonary cryptosporidiosis in HIV/AIDS cases
have been mentioned in literature [8, 9]. We believe that the
frequency of respiratory localizations of Cryptosporidium
sp. remains underestimated. Moreover, the pathogenesis of
this infection remains unknown but it precedes usually the
fatal issue of associated opportunistic infections [10, 11].
Pulmonary cryptosporidiosis is observed in patients with
profound immunosuppression affecting mostly cellular
immunity. Therefore, a strong association between cryptosporidiosis and depleted CD4+ cell count has been
established in previous reports [12, 13]. In our reports, both
of cases had presented CD4+ of less than 100 cells/mm3 .
Respiratory cryptosporidiosis involves cough, dyspnea,
low fever and abnormal chest X-ray that shows an interstitial pneumopathy [14]. Both of our patients had a
diagnosis of simultaneous intestinal and pulmonary cryptosporidiosis. The first patient has presented a disseminated
cryptosporidiosis with possible localization in the biliary
tract; unfortunately, because of the death, no investigation
was undertaken to prove it.
Acid-fast staining methods are the most frequently used in
clinical laboratories for the diagnosis of cryptosporidiosis.
The modified Ziehl-Neelsen method shows 5 to 8 microns
acid-fact oocysts, rounded, colored in fuchsia pink, with a
thick wall and granular contents [14, 15]. For greatest sensitivity and specificity, immunofluorescence microscopy
is the method of choice, followed closely by enzyme
immunoassays. Molecular methods are a research tool [16].
Cryptosporidium sp. is not the only cause of respiratory disorders observed in HIV infected patients; co-infections with
cytomegalovirus (CMV), Mycobacterium and P. jirovecii
are very common [17]. In our patients, there was no evidence of P. jirovecii, T. gondii or AFB researched by
standard methods. Our technical platform did not allow
eliminating other causes of co-infections, particularly viral
infections. Therefore, we attribute the respiratory disorders
to Cryptosporidium sp. alone, which may explain the lack
of response to treatment by azithromycin in the first patient.
Among the most commonly used treatments against
cryptosporidiosis paromomycin, and azithromycin are
partially effective. For nitazoxanide (NTZ), effectiveness
was demonstrated in vitro and in vivo using several
animal models and finally in clinical trials. It significantly
shortened the duration of diarrhea and decreased mortality
in adults and in malnourished children. NTZ is not effective
without an appropriate immune response. In AIDS patients,
combination therapy restoring immunity along with
antimicrobial treatment of Cryptosporidium sp. infection
is necessary. Investigations are now focused on many
new potential treatments such as target molecular-based
607
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Current practice
immunotherapy, probiotic bacteria even that can’t totally
eradicate C. parvum and new synthetic isoflavone derivatives that demonstrated excellent activity against C. parvum
in vitro and in a gerbil model of infection. Newly synthesized nitro- or non nitro-thiazolide compounds, derived
from NTZ, have been recently shown to be at least as
effective as NTZ against C. parvum in vitro development
and are promising new therapeutic agents [18]. Despite
the two patients received the same therapy regimen (based
on azithromycin and HAART therapy), the first patient
died with electrolyte disorders and the second shows a
total recovery. Death in the first case might have been due
to the existence of other under-diagnosed opportunistic
infections (candidiasis) as well as the existence of disseminated cryptosporidiosis (acalculous cholecystitis). We
emphasize that there was no other anti-cryptosporidium
alternative treatment available in our hospital.
Conclusion
Early identification of the etiological agent of respiratory
disorders in patients with AIDS is very important as it
can help in the institution of appropriate therapy and the
reduction of morbidity and mortality in these patients.
Microbiology laboratories should be alerted to the possibility of Cryptosporidium sp. oocysts presence in respiratory
specimens from patients with advanced HIV/AIDS disease
and pulmonary involvement.
5. Tzipori S, Ward H. Cryptosporidiosis: biology, pathogenesis and
disease. Microbes Infect 2002 ; 4 : 1047-58.
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Pulmonary cryptosporidiosis in an AIDS patient: successful treatment with
paromomycin plus azithromycin. Int J STD AIDS 2005 ; 16 : 515-7.
9. Pellicelli AM, Palmieri F, Spinazzola F, D’Ambrosio C, Causo T,
De Mori P, et al. Pulmonary cryptosporidiosis in patients with acquired
immunodeficiency syndrome. Minerva Med 1998 ; 89 : 173-5.
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Ramirez LE, Lages-Silva E, et al. Seasonal profile and level of CD4+
lymphocytes in the occurrence of cryptosporidiosis and cystoisosporidiosis in HIV/AIDS patients in the Triângulo Mineiro region, Brazil. Rev Soc
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P, et al. Clinical cryptosporidiosis and human immunodeficiency virus
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Conflicts of interest: none.
14. Mercado R, Buck GA, Manque PA, Ozaki LS. Cryptosporidium
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Ann Biol Clin, vol. 69, n◦ 5, septembre-octobre 2011