Cholera and car accidents.
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Biomedical subjects
Publications and source records attributed to Sven Britton.
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Dendritic cells (DCs) are important target cells for human cytomegalovirus (HCMV) infection, and the virus has been shown to hamper the differentiation and maturation pathways of these cells in vitro. In the present study, we examined the function of monocyte-derived DCs obtained from immunocompetent individuals undergoing symptomatic HCMV infection in terms of immunophenotypic characteristics, pinocytosis, lymphocyte stimulation capacity, and cyto-chemokine secretion in comparison with DCs obtained from healthy controls. Immature and lipopolysaccharide (LPS)-stimulated DCs obtained from patients actively infected with HCMV expressed significantly lower levels of major histocompatibility complex (MHC) class II molecules. The inhibition of expression of MHC class II molecules by HCMV appeared to be functionally relevant, as mature DCs obtained from patients with HCMV mononucleosis were inefficient in stimulating proliferation of allogenic lymphocytes. Finally, the pattern of cyto-chemokines secreted by DCs obtained from patients with HCMV mononucleosis was characterized by a proinflammatory profile with an increased production of interleukin (IL)-1beta, tumor necrosis factor alpha, CC chemokine ligand 2 (CCL2) and CCL3, and reduced secretion of IL-10 upon LPS stimulation. During symptomatic HCMV infection in the immunocompetent host, DCs exhibit an impaired immunophenotype and function. These effects may contribute to the viral-induced immunomodulation, which is often observed in HCMV-infected patients.
The present study monitored the changes in human immunodeficiency virus (HIV) viral load using a reverse transcriptase (RT) assay and an HIV-1 RNA based assay, and relates these data to the dynamics of CD4 cell counts. The samples examined originate from a prospective study of HIV-1 subtype C infected, untreated Ethiopians followed twice yearly over a period of up to 5 years. The ExaVir Load test, version 1, was used for isolation and quantitation of HIV-1 RT in plasma. The RT activities recovered were compared to the HIV-1 RNA copy numbers, which had been determined previously by the NucliSens HIV-1 QT Test. There was a significant correlation between the data obtained in the two tests (r = 0.65, P < 0.0001). During follow-up, the median RT and RNA levels increased more or less in parallel up to approximately four times the values at admittance. CD4 cell counts, which had also been determined previously, decreased slowly but continuously from approximately 310 to 190 CD4 cells/ml. In the majority of individual patients, there was an inverse correlation between CD4 T-cell counts and RT activity, and with the RNA copy number, and the data obtained by either test could be used to predict CD4 T-cell counts. The ExaVir Load test thus provides data equivalent to the estimation of the number of HIV-1 RNA copies for the prediction of CD4 T-cell counts. It is based on a simple technique, can be run in any routine diagnostic laboratory, and is a competitive alternative for use in resource limited settings.
OBJECTIVES: To determine the prevalence of intestinal helminth infections in active tuberculosis patients and their healthy household contacts and to assess its association with active TB in an area endemic for both types of infections. METHODS: Smear-positive pulmonary TB patients and healthy household contacts were tested for intestinal helminths using direct microscopy and the formol-ether concentration techniques. Three consecutive stool samples were examined before the start of TB chemotherapy. Sputum microscopy was done using the sodium hypochlorite concentration techniques. Participants were also tested for HIV by commercial sandwich enzyme linked immunosorbent assay. RESULTS: The study population consisted of 230 smear-positive TB patients and 510 healthy household contacts. The prevalence of intestinal helminths was 71% in patients and 36% in controls. HIV seroprevalence was significantly higher in patients than in controls (46.7%vs. 11.6%, P < 0.001). Conditional logistic regression analysis showed a strong association between TB and intestinal helminth infection (OR = 4.2, 95% CI 2.7-5.9, P < 0.001), and between TB and HIV infection (OR = 7.8, 95% CI 4.8-12.6, P < 0.0001). The odds of being a TB patient increased with the number of helminth species per person: in individuals with mono-infection it was 4.3 (95% CI 2.8-6.8); in people infected with two species was 4.7 (95% CI 2.5-8.7), and in patients infected with three or more helminths was 12.2 (3.9-52.6). CONCLUSION: Intestinal helminth infection may be one of the risk factors for the development of active pulmonary TB in addition to HIV infection. This finding may have important implications in the control of TB in helminth endemic areas of the world.
The kinetics of potential surrogate markers in HIV-positive (HIV+) and HIV-negative (HIV-), smear-positive tuberculosis (Tb+) patients in Gondar, Ethiopia (n = 60) was investigated. Clinical symptoms, sputum conversion, sedimentation rate (SR), HIV viral load and serum levels of TNF-alpha were determined before and 8 weeks after treatment initiation. The co-infection rate of HIV was 45%. There were significantly higher initial levels of SR and TNF-alpha in HIV+/Tb+ patients (79 +/- 29 mm/h and 13.5 +/- 7.6 pg/ml), than in HIV-/Tb+ patients (60 +/- 23 mm/h and 6.8 +/- 5.9 pg/ml, P<0.001). In HIV-/Tb+ patients, there was a marked decrease in SR compared with co-infected patients (46% [33 +/- 24 mm/h at week 8] vs. 24% [61 +/- 27 mm/h at week 8]). The HIV viral load (4.99 [range 3.70-5.92] to 4.90 [range 3.96-5.78] log10 copies/ml from week 0 to 8) and TNF-alpha (13.5 +/- 7.6 to 12.0 +/- 6.0 pg/ml) remained high in HIV+/Tb+ patients. In Tb patients, SR was significantly increased in HIV+ compared with HIV- patients. Additionally, TNF-alpha and HIV viral load remained elevated in HIV+/Tb+ patients following treatment despite clinical improvement comparable to HIV-/Tb+ patients.
We hypothesized that the ability of BCG vaccination to protect against Mycobacterium tuberculosis is less in hosts exposed to chronic helminthes infection compared to unexposed individuals. To test this hypothesis we evaluated the efficacy of BCG vaccination in protecting against M. tuberculosis challenge in Schistosoma mansoni pre-infected mice by analyzing their ability to limit the replication of TB bacilli in the lung and liver and the histology of lung sections. The results show that BCG vaccinated mice with prior S. mansoni infection show significantly higher number of colony forming units of TB bacilli as well as significant reduction in air exchange area in the lung compared to controls. In addition, spleen cells from S. mansoni infected mice were found to produce significantly less IFN-gamma and nitric oxide when stimulated in vitro with PPD and several fold higher soluble egg antigen (SEA) and Concanavalin A induced IL-4 and IL-5 secretion. Taken together, our data show that S. mansoni infection reduces the protective efficacy of BCG vaccination against M. tuberculosis possibly by attenuation of protective immune responses to mycobacterial antigens and/or by polarizing the general immune responses to the Th2 profile.
408 non-selected samples were obtained from healthy, adult individuals donating blood at the Ethiopian Red Cross Society-National Blood Transfusion Service. All samples were screened for HIV using the Vironostika Ag/Ab test, the Amplicor DNA PCR and examined for the presence of HIV reverse transcriptase (RT) using the ExaVir Load test (version 2). A panel of supplementary tests was used to evaluate the HIV status of the discordant samples and to confirm positivity. One aim was to assess an RT based test for screening for HIV in comparison with other more conventional tests. An HIV-prevalence of 3.4 % (14/408) was found. The Vironostika Ag/Ab test produced 391 negative, and according to the supplementary testing, 14 true- and three false- positive test results. The corresponding figures for the Amplicor DNA PCR test was 384 negative, 14 true- and two extra probably false -positive samples. In addition, the DNA PCR generated eight indeterminate results. The colorimetric version of the ExaVir load test exhibited 100 % specificity and detected RT in 13 of the true positive samples, but failed to detect one sample containing 200 HIV RNA copies /mL. This sample was detectable in the fluorimetric version of the test. The detection of RT activity in addition to the currently used markers would seem to have a potential for use in blood screening.
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Tuberculous lymphadenitis (TBLN) is a diagnostic challenge in sub-Saharan Africa, where there is a high rate of human immunodeficiency virus (HIV) infection. This study aimed to find ways to improve the diagnosis in Butajira, rural Ethiopia, where TBLN constitutes 40% of the total tuberculosis (TB) diagnosis. Among 147 clinically suspected cases, 107 (72.8%) were confirmed as TBLN by fine-needle aspiration (FNA) cytology and acid-fast bacillus (AFB) smear examination. Of the remaining 40 cases, denoted non-tuberculous lymphadenitis (NTBLN) after this smear examination, 37 (92.5%) showed a cytological pattern with neutrophil aggregates. The clinical manifestations were similar and cervical lymph nodes were the most affected in these 2 groups. 24 of the 107 TBLN cases (22.4%) and 9 (22.5%) of the other cases were seropositive for HIV infection (p > 0.5). FNA cytology combined with AFB smear examination is a good alternative to histology in rural Ethiopia where the expertise in taking biopsies is very limited. Polymerase chain reaction for Mycobacterium tuberculosis complex DNA was positive in 15 of 23 cases tested with NTBLN cytology, showing that an additional independent criterion for the presence of M. tuberculosis is needed for diagnosis in lymphadenitis cases of this kind. These findings could help to strengthen the diagnostic algorithm suggested by the National TB Control Program.
BACKGROUND: We have previously suggested that helminthic infections make the host more susceptible to HIV infection and enhance its progression due to the chronic immune activation they cause. OBJECTIVE: To study the effect of antihelminthic treatment on HIV plasma viral load (VL) in HIV- and helminth-infected individuals living in Ethiopia. METHODS: Fifty-six clinically asymptomatic HIV-1-infected individuals, 31 (55%) of whom were also infected with helminths, were studied. All participants received antihelminthic treatment at baseline and at 3 and 6 months. Worm egg excretion, HIV plasma VL, and T-cell subsets were determined at baseline and 6 months after treatment. RESULTS: The mean age, number of CD4 T cells, and gender distribution were similar in the helminth-infected and -noninfected groups. At baseline, HIV plasma VL was strongly correlated to the number of eggs excreted (p <.001) and was higher in individuals infected with more than one helminth (5.28 +/- 0.35 versus 4.30 +/- 1.13 log RNA copies/mL, respectively; p =.16). After treatment of helminths, the 6-month change in HIV plasma VL was significantly different between the successfully treated group and the persistently helminth-positive group (p =.04) CONCLUSIONS: Helminth "load" is correlated to HIV plasma VL, and successful deworming is associated with a significant decrease in HIV plasma VL. The results of the current study, if confirmed in a larger study, may have important implications for slowing disease progression and reducing risks of transmission.
This study investigated whether peripheral nerve damage in patients with leprosy impairs local cellular immune responses, thereby reducing wound healing and leading to chronic skin ulceration. Anesthetic and contralateral sensitive skin sites in 42 patients with leprosy were compared for delayed-type hypersensitivity responses to purified protein derivative (PPD) of tuberculin. Leukocyte recruitment, epidermal activation, keratinocyte proliferation, and rates of wound healing after skin biopsy were compared. No significant differences in PPD-induced induration, epidermal activation and thickening or numbers of total T cells, CD8+ T cells, CD1a+ Langerhans cells, and proliferating Ki67+ keratinocytes were observed between anesthetic and sensitive skin sites. Similarly, rates of wound healing over 5 days after skin biopsy did not differ significantly. Thus, local leprosy-associated anesthesia does not appear to contribute to local immune compromise or impaired wound healing. Rather, chronic cutaneous ulceration in leprosy most likely results from repeated trauma associated with loss of sensation.
In a setting with a high prevalence of HIV we studied (i) the prevalence of pulmonary tuberculosis (PTB) and HIV; (ii) clinical and epidemiological characteristics of PTB; and (iii) the usefulness of standard procedures for diagnosing PTB. Of 509 consecutive outpatients evaluated on clinical suspicion of PTB in Addis Ababa, 33.0% were culture-verified as having PTB. PTB patients, non-TB patients and controls were HIV-1-positive in 57.1%, 38.5% and 8.3% of cases, respectively. Predictors for culture-verified PTB were age < 25 y, male gender and the presence of HIV and fever, whereas profound weight loss indicated HIV infection. Diagnosis of PTB based on clinical symptoms, sputum microscopy for acid-fast bacilli and chest radiography was sensitive (86.7%) but unspecific (64.1%). In HIV-positive patients both sensitivity and specificity were significantly lower (p < 0.05). HIV-related pulmonary infections are often misinterpreted as smear-negative PTB. HIV screening is therefore warranted not only in cases of verified TB but also as part of the diagnostic work-up in patients with respiratory symptoms suggestive of PTB. Also, increased awareness of, and improved diagnostic tools for, HIV-related pulmonary infections other than PTB are required, together with algorithms for patients with suspected PTB.
Diagnosis of latent Mycobacterium tuberculosis infection is considered essential for tuberculosis control but is hampered by the lack of specific reagents. We report that strong recognition of tuberculosis complex-specific antigen ESAT-6 by healthy household contacts of tuberculosis patients correlates with the subsequent development of active tuberculosis during a 2-year follow-up period.
A cross-sectional survey on onchocerciasis and intestinal helminthic infections was conducted in two villages around the town of Teppi, south-west of Ethiopia on a total of 308 subjects of which 180 indigenous and 128 migrant settlers aged 10 years and above who lived in the area for at least 5 years. Of the total study subjects, 65% were males. The majority (64%) of the study subjects were in the age range of 21-40 years. The results of stool and skin snip examinations for ova/parasite and microfilaria revealed that, 62% (190) and 81% (248) of the study subjects were positive for intestinal parasites and microfilariderma respectively. Fifty percent (154) of the total subjects in the two villages had both onchocerciasis and intestinal helminthic infections. However, 80% (94/118) of the stool negative subjects also had onchocerciasis indicating that onchocercal skin infection has no significant influence on the acquisition of intestinal helminthic infections or vice versa [(relative risk 1.04, 95% CI 0.91, 1.18) P > 0.05]. Sixty-five percent (161/248) of the total skin snip positive individuals had microfilarial load of > 10 mf/mg of skin snip. The proportion of multiple infections with 2 or more intestinal helminthes was recorded in 51% (96/190) of individuals positive for intestinal parasitosis. There was a significant (x2 = 8.41, P < 0.005) difference in the onchocerciasis infection rate among indigenous (88%) and migrant (75%). No direct association was observed between onchocerciasis and intestinal parasitosis in the two study groups (indigenous and migrant settlers). The public health significance of coexistence of the two diseases, and the need for intensive control measures are discussed.