Cessation of Cryptosporidium-associated diarrhea in an acquired immunodeficiency syndrome patient after treatment with hyperimmune bovine colostrum

Ungar, Beth L. P.; Ward, Douglas J.; Fayer, Ronald; Quinn, Carole A.

doi:10.1016/0016-5085(90)90842-o

Cited by 168 publications

(83 citation statements)

References 18 publications

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“…Individuals who are hypogammaglobulinemic 23 or are IgA deficient 24 are at increased risk of developing a chronic C. parvum infection. Furthermore, exogenous antibody in the form of hyperimmune colostrum has had positive effects in some cases of chronic cryptosporidiosis [25][26][27] in immunocompromised individuals and decreases the intensity of infection when administered to healthy volunteers prior to challenge. 28 However, reconstitution studies in athymic or severe combined immunodeficiency (SCID) mice show no effect of B cells on the course of Cryptosporidium infection, 29 and immunocompromised individuals are capable of producing increased levels of secretory IgA in the face of persistent infection.…”

Section: Discussionmentioning

confidence: 99%

Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G.

Chappell

Okhuysen²,

Sterling

et al. 1999

The American Journal of Tropical Medicine and Hygiene

189

159

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Abstract. A 50% infectious dose (ID 50 ) of 132 Cryptosporidium parvum oocysts was previously determined in serologically negative individuals (ELISA). In this study, 17 healthy adults with pre-existing anti-C. parvum serum IgG were challenged with 500-50,000 oocysts. Infection and diarrhea were associated with the higher challenge doses. The ID 50 was 1,880 oocysts, Ͼ 20-fold higher than in seronegative volunteers. Fecal oocysts were detected in only seven (53.8%) of 13 individuals with clinical cryptosporidiosis, indicating that the host response may effectively decrease the number of oocysts produced. Subjects with the highest absorbances prior to challenge had little to no increase in IgG following challenge, whereas volunteers with lower reactivities showed significant postchallenge increases. This suggests that an upper limit of serum IgG was present in some subjects, while others were further stimulated by an additional exposure. These data indicate that prior exposure to C. parvum provides protection from infection and illness at low oocyst doses.Cryptosporidium parvum is a recognized cause of diarrheal illness in waterborne outbreaks [1][2][3] and in individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). 4 The increased awareness of cryptosporidiosis in the general population and in specialized settings, such as day care centers, as well as the seriousness of the disease in immunosuppressed individuals have earned Cryptosporidium a place on the list of emerging diseases that are a threat to the public health. 5 Furthermore, no effective chemotherapeutic agent has been demonstrated to prevent or cure C. parvum infections. Thus, there is considerable interest in the development of immunotherapies designed to limit infection. To rationally design such interventions, it is important to understand the major immunologic mechanisms that are operative in self-limited disease. Animals 6-8 and humans 9 with intact immune systems are typically capable of clearing the parasite within 1-3 weeks after infection. Several studies with experimental animal models have demonstrated that most species are refractory to a second oocyst challenge. 7,8 Indeed, adult animals exposed to the parasite for the first time are relatively resistant to infection and often have only a transient period of oocyst shedding with few to no symptoms. In contrast, healthy adult volunteers can experience infections and diarrheal illnesses when oocyst challenges are at least one year apart. 10 Many studies in animals 11-15 and humans [16][17][18][19] have documented the presence of antibodies to C. parvum infection. However, these investigations in humans were carried out in serologic surveys or in select persons experiencing diarrhea and only after the infections were diagnosed. Thus, the observations were necessarily limited by the lack of information on the immune status and exposure history prior to the exposure. Also, differences among the studies in antigen preparations used in the testing and definiti...

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Section: Discussionmentioning

confidence: 99%

Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G.

Chappell

Okhuysen²,

Sterling

et al. 1999

The American Journal of Tropical Medicine and Hygiene

189

159

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“…In previous studies, bovine colostral antibody preparations produced against whole C. parvum organisms have demonstrated specific neutralizing activity in vitro and highly significant efficacy against infection in animal models when evaluated under controlled conditions (11,12,33,34,36,51). The efficacy of such preparations in persistently infected immunodeficient humans has been demonstrated but has been inconsistent in a limited number of studies, due in part to confounding patient and treatment variables (8,27,29,35,52,53). While these early observations provided the rationale to investigate passive antibody-based immunization for cryptosporidiosis, possible limitations to the use of polyclonal antibodies produced against uncharacterized whole C. parvum preparations include the relatively low content of specific neutralizing antibodies in the immunoglobulin fraction, logistical restraints on production in quantity, and lot-to-lot heterogeneity in therapeutic predictability (6,35,59).…”

mentioning

confidence: 99%

Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

2000

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The coccidian parasite Cryptosporidium parvum causes diarrhea in humans, calves, and other mammals. Neither immunization nor parasite-specific pharmaceuticals that are consistently effective against this organism are available. While polyclonal antibodies against whole C. parvum reduce infection, their efficacy and predictability are suboptimal. We hypothesized that passive immunization against cryptosporidiosis could be improved by using neutralizing monoclonal antibodies (MAbs) targeting functionally defined antigens on the infective stages. We previously reported that the apical complex and surface-exposed zoite antigens CSL, GP25-200, and P23 are critical in the infection process and are therefore rational targets. In the present study, a panel of 126 MAbs generated against affinity-purified CSL, GP25-200, and P23 was characterized to identify the most efficacious neutralizing MAb formulation targeting each antigen. To identify neutralizing MAbs, sporozoite infectivity following exposure to individual MAbs was assessed by enzyme-linked immunosorbent assay. Of 126 MAbs evaluated, 47 had neutralizing activity. These were then evaluated individually in oocystchallenged neonatal mice, and 14 MAbs having highly significant efficacy were identified for further testing in formulations. Epitope specificity assays were performed to determine if candidate MAbs recognized the same or different epitopes.

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“…The AIDS patients in advanced stage with severe chronic diarrhea had treated with polyclonal antibodies. After 21 days of treatment diarrhea was decreased in all patients, but all of them remained infected (Ungar et al 1990). This study designed to evaluate antibody production in infected newborn mice.…”

Section: Resultsmentioning

confidence: 91%

Immune response of newborn BALB/c mice to Cryptosporidium infection

et al. 2014

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Cryptosporidium parvum is a protozoan parasite which causes diarrheal in human and animals worldwide. Infection transmission has reported through oralfecal by infectious objects through foods and drinks. In this study we explored the immune response pathway in animal model for C. parvum to develop the new treatment way. Oocysts collected from fecal positive for C. parvum and diluted about 1:5 in sucrose solution. New born BALB/c mice (3 days) divided to 2 different groups. Control group hadn't received any oocyst, the test groups received 5 9 10 5 oocysts. 5 mice selected for each control group and 11 mice chosen for each test group. Blood collected from heart bleeds in days of 6, 9, 12 and 16. Protein concentrations determined by bio-photometer. Dot blotting used to find out total antibody concentrations oocyst antigen. Among the test and the control groups, blots appeared in test group which means antibody production, but not any blot observed in the control groups. The non-characteristic proteins in serum were measured by the biophotometer. In this study, we investigated antibody serum production against C. parvum oocysts in new born BALB/c mice. The detected antibody through dot blot technique was our aims which had conjugated to our characteristic antiserum. The recorded numbers for the controls by biophotometer related to the non characteristic proteins in serum. The results of this study can used to produce polyclonal or monoclonal antibodies against cryptosporidiosis.

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Cessation of Cryptosporidium-associated diarrhea in an acquired immunodeficiency syndrome patient after treatment with hyperimmune bovine colostrum

Cited by 168 publications

References 18 publications

Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G.

Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G.

Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

Immune response of newborn BALB/c mice to Cryptosporidium infection

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