Beyene Petros

Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts

To assess possible differences in immune status, proportions and absolute numbers of subsets of CD4+ and CD8+ T cells were compared between HIV− healthy Ethiopians (n = 52) and HIV− Dutch (n = 60). Both proportions and absolute numbers of naive CD4+ and CD8+ T cells were found to be significantly reduced in HIV− Ethiopians compared with HIV−Dutch subjects. Also, both proportions and absolute numbers of the effector CD8+ T cell population as well as the CD4+ CD45RA− CD27− and CD8+ CD45RA− CD27− T cell populations were increased in Ethiopians. Finally, both proportions and absolute numbers of CD4+ and CD8+ T cells expressing CD28 were significantly reduced in Ethiopians versus Dutch. In addition, the possible association between the described subsets and HIV status was studied by comparing the above 52 HIV− individuals with 32 HIV+ Ethiopians with CD4 counts > 200/μl and/or no AIDS‐defining conditions and 39 HIV+ Ethiopians with CD4 counts < 200/μl or with AIDS‐defining conditions. There was a gradual increase of activated CD4+ and CD8+ T cells, a decrease of CD8+ T cells expressing CD28 and a decrease of effector CD8+ T cells when moving from HIV− to AIDS. Furthermore, a decrease of naive CD8+ T cells and an increase of memory CD8+ T cells in AIDS patients were observed. These results suggest a generally and persistently activated immune system in HIV−Ethiopians. The potential consequences of this are discussed, in relation to HIV infection.

Distribution of lymphocyte subsets in healthy human immunodeficiency virus-negative adult Ethiopians from two geographic locales.

ABSTRACT Immunological values for 562 factory workers from Wonji, Ethiopia, a sugar estate 114 km southeast of the capital city, Addis Ababa, Ethiopia, were compared to values for 218 subjects from Akaki, Ethiopia, a suburb of Addis Ababa, for whom partial data were previously published. The following markers were measured: lymphocytes, T cells, B cells, NK cells, CD4+ T cells, and CD8+ T cells. A more in depth comparison was also made between Akaki and Wonji subjects. For this purpose, various differentiation and activation marker (CD45RA, CD27, HLA-DR, and CD38) expressions on CD4+ and CD8+ T cells were studied in 60 male, human immunodeficiency virus-negative subjects (30 from each site). Data were also compared with Dutch blood donor control values. The results confirmed that Ethiopians have significantly decreased CD4+ T-cell counts and highly activated immune status, independent of the geographic locale studied. They also showed that male subjects from Akaki have significantly higher CD8+ T-cell counts, resulting in a proportional increase in each of the CD8+ T-cell compartments studied: naı̈ve (CD45RA+CD27+), memory (CD45RA−CD27+), cytotoxic effector (CD45RA+CD27−), memory/effector (CD45RA−CD27−), activated (HLA-DR+CD38+), and resting (HLA-DR−CD38−). No expansion of a specific functional subset was observed. Endemic infection or higher immune activation is thus not a likely cause of the higher CD8 counts in the Akaki subjects. The data confirm and extend earlier observations and suggest that, although most lymphocyte subsets are comparable between the two geographical locales, there are also differences. Thus, care should be taken in extrapolating immunological reference values from one population group to another.

Chloroquine-resistant Plasmodium vivax malaria in Debre Zeit, Ethiopia.

BackgroundPlasmodium vivax accounts for about 40% of all malaria infection in Ethiopia. Chloroquine (CQ) is the first line treatment for confirmed P. vivax malaria in the country. The first report of CQ treatment failure in P. vivax was from Debre Zeit, which suggested the presence of chloroquine resistance.MethodsAn in vivo drug efficacy study was conducted in Debre Zeit from June to August 2006. Eighty-seven patients with microscopically confirmed P. vivax malaria, aged between 8 months and 52 years, were recruited and treated under supervision with CQ (25 mg/kg over three days). Clinical and parasitological parameters were assessed during the 28 day follow-up period. CQ and desethylchloroquine (DCQ) blood and serum concentrations were determined with high performance liquid chromatography (HPLC) in patients who showed recurrent parasitaemia.ResultsOf the 87 patients recruited in the study, one was lost to follow-up and three were excluded due to P. falciparum infection during follow-up. A total of 83 (95%) of the study participants completed the follow-up. On enrolment, 39.8% had documented fever and 60.2% had a history of fever. The geometric mean parasite density of the patients was 7045 parasites/μl. Among these, four patients had recurrent parasitaemia on Day 28. The blood CQ plus DCQ concentrations of these four patients were all above the minimal effective concentration (> 100 ng/ml).ConclusionChloroquine-resistant P. vivax parasites are emerging in Debre Zeit, Ethiopia. A multi-centre national survey is needed to better understand the extent of P. vivax resistance to CQ in Ethiopia.

Ex vivo cytokine mRNA levels correlate with changing clinical status of ethiopian TB patients and their contacts over time.

There is an increasing body of evidence which suggests that IL-4 plays a role in the pathogenesis of TB, but a general consensus on its role remains elusive. We have previously published data from a cohort of Ethiopian TB patients, their contacts, and community controls suggesting that enhanced IL-4 production is associated with infection with M. tuberculosis, rather than overt disease and that long-term protection in infected community controls is associated with co-production of the IL-4 antagonist IL-4d2, alongside elevated IL-4. Here, for the first time, we compare data on expression of IFN-γ, IL-4 and IL-4δ2 over time in TB patients and their household contacts. During the follow-up period, the TB patients completed therapy and ceased to display TB-like symptoms. This correlated with a decrease in the relative amount of IL-4 expressed. Over the same period, the clinical status of some of their contacts also changed, with a number developing TB-like symptoms or clinically apparent TB. IL-4 expression was disproportionately increased in this group. The findings support the hypothesis that elevated IL-4 production is generally associated with infection, but that TB disease is associated with a relatively increased expression of IL-4 compared to IFN-γ and IL-4δ2. However, the data also suggest that there are no clear-cut differences between groups: the immune response over time appears to include changes in the expression of IFN-γ, IL-4 and IL-4δ2, and it is the relative, not absolute levels of cytokine expression that are characteristic of clinical status.

Distribution and Clinical Manifestations of Cryptosporidium Species and Subtypes in HIV/AIDS Patients in Ethiopia

Background Cryptosporidiosis is an important cause for chronic diarrhea and death in HIV/AIDS patients. Among common Cryptosporidium species in humans, C. parvum is responsible for most zoonotic infections in industrialized nations. Nevertheless, the clinical significance of C. parvum and role of zoonotic transmission in cryptosporidiosis epidemiology in developing countries remain unclear. Methodology/Principal Findings In this cross-sectional study, 520 HIV/AIDS patients were examined for Cryptosporidium presence in stool samples using genotyping and subtyping techniques. Altogether, 140 (26.9%) patients were positive for Cryptosporidium spp. by PCR-RFLP analysis of the small subunit rRNA gene, belonging to C. parvum (92 patients), C. hominis (25 patients), C. viatorum (10 patients), C. felis (5 patients), C. meleagridis (3 patients), C. canis (2 patients), C. xiaoi (2 patients), and mixture of C. parvum and C. hominis (1 patient). Sequence analyses of the 60 kDa glycoprotein gene revealed a high genetic diversity within the 82 C. parvum and 19 C. hominis specimens subtyped, including C. parvum zoonotic subtype families IIa (71) and IId (5) and anthroponotic subtype families IIc (2), IIb (1), IIe (1) and If-like (2), and C. hominis subtype families Id (13), Ie (5), and Ib (1). Overall, Cryptosporidium infection was associated with the occurrence of diarrhea and vomiting. Diarrhea was attributable mostly to C. parvum subtype family IIa and C. hominis, whereas vomiting was largely attributable to C. hominis and rare Cryptosporidium species. Calf contact was identified as a significant risk factor for infection with Cryptosporidium spp., especially C. parvum subtype family IIa. Conclusions/Significance Results of the study indicate that C. parvum is a major cause of cryptosporidiosis in HIV-positive patients and zoonotic transmission is important in cryptosporidiosis epidemiology in Ethiopia. In addition, they confirm that different Cryptosporidium species and subtypes are linked to different clinical manifestations.

Role of incidental and/or cured intestinal parasitic infections on profile of CD4+ and CD8+ T cell subsets and activation status in HIV-1 infected and uninfected adult Ethiopians

Intestinal parasitic infections have been suggested to cause persistent immune activation leading to an unbalanced immune state. Such a state has been proposed to be a major factor in the pathogenesis of AIDS in an African context. The present study investigated the effect of incidental parasitic infection and treatment on the profile of T cell differentiation and activation markers on CD4+ and CD8+ T cells from HIV‐1 infected and uninfected adult Ethiopians. Cryopreserved PBMCs from 64 subjects (41 HIV‐negative and 23 HIV‐positive) with follow‐up visits at 6‐monthly intervals were used to compare the effect of incidental intestinal parasites and their treatment upon T cell subset profiles and activation status. The samples were stained with antibodies to various T cell differentiation and activation markers allowing naive, memory, effector, memory/effector, activated and resting CD4+ and CD8+ T cell subsets to be quantified by triple‐colour FACScan. Incidental intestinal parasitic infections resulted in a significant increase in memory CD4+ T cell numbers both in HIV‐negative and HIV‐positive subjects (P < 0·05). There was also a significant increase in the percentage of CD8+ HLA‐DR+ T cells (P < 0·05) in HIV‐positive subjects co‐infected with parasites. In HIV‐negative subjects, a significant decline in activated cells and a significant increase in resting CD8+ T cells (P < 0·05) was observed after treatment for parasites. These data suggest that intestinal parasitic infections could result in the alteration of T cell subset counts and also in the up‐regulation of T cell activation markers in

Characterization of peripheral blood lymphocyte subsets in patients with acute Plasmodium falciparum and P. vivax malaria infections at Wonji Sugar Estate, Ethiopia.

ABSTRACT We investigated the absolute counts of CD4+, CD8+, B, NK, and CD3+ cells and total lymphocytes in patients with acute Plasmodium falciparum and Plasmodium vivax malaria. Three-color flow cytometry was used for enumerating the immune cells. After slide smears were stained with 3% Giemsa stain, parasite species were detected using light microscopy. Data were analyzed using STATA and SPSS software. A total of 204 adults of both sexes (age, >15 years) were included in the study. One hundred fifty-eight were acute malaria patients, of whom 79 (50%) were infected with P. falciparum, 76 (48.1%) were infected with P. vivax, and 3 (1.9%) were infected with both malaria parasites. The remaining 46 subjects were healthy controls. The leukocyte count in P. falciparum patients was lower than that in controls (P = 0.015). Absolute counts of CD4+, CD8+, B, and CD3+ cells and total lymphocytes were decreased very significantly during both P. falciparum (P < 0.0001) and P. vivax (P < 0.0001) infections. However, the NK cell count was an exception in that it was not affected by either P. falciparum or P. vivax malaria. No difference was found in the percentages of CD4, CD8, and CD3 cells in P. falciparum or P. vivax patients compared to controls. In summary, acute malaria infection causes a depletion of lymphocyte populations in the peripheral blood. Thus, special steps should be taken in dealing with malaria patients, including enumeration of peripheral lymphocyte cells for diagnostic purposes and research on peripheral blood to evaluate the immune status of patients.

Prevalence of Giardia duodenalis and Cryptosporidium species infections among children and cattle in North Shewa Zone, Ethiopia

BackgroundGiardia and Cryptosporidium are the most common causes of protozoan diarrhea that lead to significant morbidity and mortality worldwide. The purpose of this study was to determine the prevalence of Giardia duodenalis and Cryptosporidium species infections among children and cattle, and to assess the potential risk of zoonotic transmission.MethodsThis cross-sectional study was conducted between January and April 2009 in Girar Jarso and Dera Districts of North Shewa Zone, Oromia Region, Ethiopia. A total of 768 stool specimens were collected and examined for intestinal parasites using direct wet mount with saline and formalin ether concentration methods. The modified Ziehl-Neelsen staining method was used for the detection of Cryptosporidium species. Statistical analysis was performed using SPSS software version 15.ResultsOut of 384 children examined, 53 (13.8%) and 28 (7.3%) were positive for Giardia and Cryptosporidium infections, respectively. Similarly, of the total 384 cattle examined, 9 (2.3%) were positive for Giardia duodenalis and 30 (7.8%) were positive for Cryptosporidium infection. The prevalence of giardiasis was significantly higher among children who had close contact with cattle 33 (18.7%) compared to children who had no contact with cattle 20 (9.6%) (P < 0.05). Higher number of Cryptosporidium infection was also recorded in children who had close contact with cattle 15 (8.5%). Difference in prevalence of giardiasis and cryptosporidiosis among children was not statistically significant between males and females. On the other hand, difference in the prevalence of giardiasis among children was statistically significant between age groups.ConclusionsHigher prevalence of Giardia duodenalis infection detected among children was significantly associated with contact with cattle and manure that the children had. Further analysis using molecular techniques is needed to explain the existence of zoonotic transmission in the study area.

Cryptosporidium and Giardia infection and drinking water sources among children in Lege Dini, Ethiopia

We assessed the prevalence of Cryptosporidium and Giardia infections among children using protected and unprotected water sources in the Lege Dini watershed, Eastern Ethiopia, in November 2005 and May 2006. Of 655 children examined, 80 (12.2%) were infected with Cryptosporidium and 231 (35.3%) with Giardia. No difference was observed in the prevalence of cryptosporidiosis and giardiasis (P > 0.05) between children drinking water from protected and unprotected sources.

The impact of a small-scale irrigation scheme on malaria transmission in Ziway area, Central Ethiopia

Objective  To assess the impact of a small‐scale irrigation scheme in Ziway area, a semi‐arid area in the Central Ethiopian Rift Valley, on malaria transmission.