Giardia Antagonizes Beneficial Functions of Indigenous and Therapeutic Intestinal Bacteria during Malnutrition.

Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp . and an increase in Bifidobacterium spp . This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp . mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia , despite not inhibiting Lactobacillus colonization. These results highlight Giardia's potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.

Prevalence and Distribution of Cryptosporidium spp. and Giardia lamblia in Rural and Urban Communities of South Africa

Objective: Enteric diseases remain a serious health problem globally. High prevalence is evident in regions with poor socioeconomic conditions, poor sanitation, and inadequate clean water supply, such as South Africa. Designing an effective strategy, however, requires local knowledge, which can be particularly challenging to acquire in low-and middle-income countries. As the first step in this process, we investigated the prevalence and distribution of protozoan parasites Cryptosporidium and Giardia in the rural and urban gastrointestinal clinics of South Africa. Methods: A cross-sectional study was conducted to assess the prevalence of enteric parasites Cryptosporidium and G. lamblia in rural and urban communities of South Africa. Stool samples were collected from November 2013 to June 2015 from patients with diarrhea (n=227) and without diarrhea (n=257). DNA was extracted and a diagnostic Taqman qPCR assay was performed to detect these protozoan parasites, which was further confirmed by the Sanger sequencing of a few samples. Results: Of the 484 stool specimens collected, 34% (166/484) were positive for either Cryptosporidium spp. or Giardia lamblia parasites, with only 5% containing both parasites (22/484). In both study populations, Cryptosporidium was the most prevalent parasite (overall 25%) followed by Giardia (19%). Conclusion: This study discovered that both Giardia and Cryptosporidium parasites might contribute to diarrheal disease in South Africa and are more prevalent in rural communities. Future studies are needed to identify the source of the infection and design appropriate interventions to reduce the burden of the disease. Amaç: Enterik hastaliklar küresel olarak ciddi bir saglik sorunu olmaya devam etmektedir. Güney Afrika gibi düsük sosyo-ekonomik kosullarin, kötü sanitasyonun ve yetersiz temiz su kaynaklarinin oldugu bölgelerde yüksek prevalans görülmektedir. Ancak etkili bir strateji tasarlamak için, düsük ve orta gelirli ülkelerde edinilmesi özellikle zor olabilecek yerel bir bilgi gerektirmektedir. Bu süreçte biz ilk adim olarak, Güney Afrika'nin kirsal ve kentsel gastrointestinal kliniklerinde protozoan parazitler Cryptosporidium ve Giardia'nin prevalansini ve dagilimini arastirdik. Yöntemler: Güney Afrika'nin kirsal ve kentsel topluluklarinda Cryptosporidium ve G. lamblia enterik parazitlerinin sikligini arastirmak için kesitsel bir çalisma yapildi. Ishali olan (n=227) ve olmayan (n=257) hastalarin Kasim 2013-Haziran 2015 tarihleri arasinda diski örnekleri toplandi. DNA ekstrakte edildi ve bu protozoan parazitleri saptamak için tanisal bir Taqman qPCR tahlili kullanilarak, birkaç örnek Sanger dizilimi ile daha da dogrulandi. Bulgular: Toplanan 484 diski örneginin %34'ü (166/484) Cryptosporidium spp. veya Giardia lamblia parazitleri için pozitifti ve örneklerin sadece %5'i her iki paraziti de içeriyordu (22/484). Her iki çalisma popülasyonunda da Cryptosporidium en yaygin parazitti (toplam %25) ve bunu Giardia (%19) izledi. Sonuç: Bu çalisma, hem Giardia hem de Cryptosporidium parazitlerinin Güney Afrika'daki ishal hastaligina katkida bulunabilecegini ve kirsal topluluklarda daha yaygin oldugunu göstermistir. Hem enfeksiyonun kaynagini belirlemek hem de hastaligin yükünü azaltmak için uygun müdahaleleri tasarlamak için gelecekteki çalismalara ihtiyaç vardir.

Interleukin 10 (IL-10) Production and Seroprevalence of Entamoeba histolytica Infection among HIV-Infected Patients in South Africa.

Infections by the parasite E. histolytica are increasing in HIV-infected individuals. Interleukin (IL-10) plays an important role in maintaining the mucosal barrier. Therefore, the seroprevalence of E. histolytica was investigated in relation to the IL-10 serum concentration among HIV- infected patients. A total of 647 blood samples were collected from asymptomatic HIV-infected patients. The Entamoeba histolytica antigen (GALNAC lectin) and serum antibodies were assessed using specific ELISAs (TECHLAB, Virginia, USA). IL10 blood levels were measured using a commercial ELISA test, and the results were analyzed using parametric and non-parametric statistical tests. The Gal/GALNAC lectin was detected in only 0.5% (3/647) of individuals, and the antibodies against E. histolytica were detected in 65.2% (422/647) of the samples. A significant increase in IL-10 levels was found in 68.1% of patients who were sero-negative for E. histolytica antibodies compared to patients who were sero-positive. There is a high level of exposure to E. histolytica among HIV patients in South Africa, although the prevalence of amoebic liver abscesses might be low. This study revealed that elevated levels of IL-10 might be associated with a reduced risk of amebiasis.

Targeting Parasite-Produced Macrophage Migration Inhibitory Factor as an Antivirulence Strategy With Antibiotic-Antibody Combination to Reduce Tissue Damage.

Targeting virulence factors represents a promising alternative approach to antimicrobial therapy, through the inhibition of pathogenic pathways that result in host tissue damage. Yet, virulence inhibition remains an understudied area in parasitology. Several medically important protozoan parasites such as Plasmodium, Entamoeba, Toxoplasma, and Leishmania secrete an inflammatory macrophage migration inhibitory factor (MIF) cytokine homolog, a virulence factor linked to severe disease. The aim of this study was to investigate the effectiveness of targeting parasite-produced MIF as combination therapy with standard antibiotics to reduce disease severity. Here, we used Entamoeba histolytica as the model MIF-secreting protozoan, and a mouse model that mirrors severe human infection. We found that intestinal inflammation and tissue damage were significantly reduced in mice treated with metronidazole when combined with anti-E. histolytica MIF antibodies, compared to metronidazole alone. Thus, this preclinical study provides proof-of-concept that combining antiparasite MIF-blocking antibodies with current standard-of-care antibiotics might improve outcomes in severe protozoan infections.

Parasite-Produced MIF Cytokine: Role in Immune Evasion, Invasion, and Pathogenesis.

Protozoan parasites represent a major threat to health and contribute significantly to morbidity and mortality worldwide, especially in developing countries. This is further compounded by lack of effective vaccines, drug resistance and toxicity associated with current therapies. Multiple protozoans, including Plasmodium, Entamoeba, Toxoplasma, and Leishmania produce homologs of the cytokine MIF. These parasite MIF homologs are capable of altering the host immune response during infection, and play a role in immune evasion, invasion and pathogenesis. This minireview outlines well-established and emerging literature on the role of parasite MIF homologs in disease, and their potential as targets for therapeutic and preventive interventions.

Entamoeba Species in South Africa: Correlations With the Host Microbiome, Parasite Burdens, and First Description of Entamoeba bangladeshi Outside of Asia.

Background: Diarrhea is frequent in communities without clean water, which include low-income South African populations in Giyani and Pretoria. In these populations, the amount of diarrhea caused by Entamoeba histolytica, inclusive of all ages, sexes, and human immunodeficiency virus status, is uncertain. Infection with E. histolytica can modulate the host microbiota, and a key species indicative of this is the Prevotella copri pathobiont. Methods: A cross-sectional study of patients attending gastroenterology clinics was conducted to determine the frequency and burden of 4 Entamoeba species and P. copri. Results: Entamoeba species were present in 27% of patients (129/484), with E. histolytica detected in 8.5% (41), E. dispar in 8% (38), E. bangladeshi in 4.75% (23), and E. moshkovskii in 0%. This is the first description of E. bangladeshi outside Bangladesh. In E. histolytica-positive samples, the levels of both the parasite and P. copri were lower in nondiarrheal samples, validating the results of a study in Bangladesh (P = .0034). By contrast, in E. histolytica-negative samples positive for either of the nonpathogenic species E. dispar or E. bangladeshi, neither P. copri nor Entamoeba levels were linked to gastrointestinal status. Conclusions: Nonmorphologic identification of this parasite is essential. In South Africa, 3 morphologically identical Entamoeba were common, but only E. histolytica was linked to both disease and changes in the microbiota.

PREVALENCE OF TOXOPLASMA GONDII IGG AND IGM AND ASSOCIATED RISK FACTORS AMONG HIV-POSITIVE AND HIV-NEGATIVE PATIENTS IN VHEMBE DISTRICT OF SOUTH AFRICA.

BACKGROUND: Toxoplasma gondii is a zoonotic parasite that has arisen as an important opportunistic infection that causes morbidity and mortality especially in HIV positive patients. This study was carried out to determine the sero-prevalence of T. gondii (IgG and IgM) and the associated risk factors among HIV positive and negative patients in Northern South Africa. MATERIALS AND METHODS: The study was conducted in the Vhembe District in Limpopo province from April 2012 to January 2013. A well-structured questionnaire was used to collect socio-demographic information and possible risk factor information on toxoplasmosis from participants. A total of 161 blood samples of both HIV positive and negative patients visiting the local clinics in the Vhembe district were collected. Serum samples were tested for IgG and IgM against T. gondii using commercially available ELISA protocol. RESULTS: The prevalence of T. gondii IgG was 31.7% while that of T. gondii IgM was 4.9%. The prevalence of T. gondii IgG was higher in HIV positive patients (38%) compared to 16.7% among HIV negative patients (p=0.001). Toxoplasma gondii IgG antibodies were more common in patients who were not taking ARV's (46.2%) compared to those who were taking ARV's (35.2%) (P<0.001). CONCLUSIONS: The present study has shown a high prevalence of T. gondii (IgG) among patients attending different HIV clinics in the Vhembe district with no current infections among pregnant women. In addition to the sero-positive status of the patient to HIV, other significant risk factors for toxoplasmosis included high viral load, non-adherence to ARV therapy and age (>25 years).

Entamoeba histolytica-Encoded Homolog of Macrophage Migration Inhibitory Factor Contributes to Mucosal Inflammation during Amebic Colitis.

Understanding the mechanisms by which Entamoeba histolytica drives gut inflammation is critical for the development of improved preventive and therapeutic strategies. E. histolytica encodes a homolog of the human cytokine macrophage migration inhibitory factor (MIF). Here, we investigated the role of E. histolytica MIF (EhMIF) during infection. We found that the concentration of fecal EhMIF correlated with the level of intestinal inflammation in persons with intestinal amebiasis. Mice treated with antibodies that specifically block EhMIF had reduced chemokine expression and neutrophil infiltration in the mucosa. In addition to antibody-mediated neutralization, we used a genetic approach to test the effect of EhMIF on mucosal inflammation. Mice infected with parasites overexpressing EhMIF had increased chemokine expression, neutrophil influx, and mucosal damage. Together, these results uncover a specific parasite protein that increases mucosal inflammation, expands our knowledge of host-parasite interaction during amebic colitis, and highlights a potential immunomodulatory target.