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Hannah Akuffo

Publications and source records attributed to Hannah Akuffo.

7 recordsLinked to original sources
PubMed2007

FasL and TRAIL induce epidermal apoptosis and skin ulceration upon exposure to Leishmania major.

Receptor-mediated apoptosis is proposed as an important regulator of keratinocyte homeostasis in human epidermis. We have previously reported that Fas/FasL interactions in epidermis are altered during cutaneous leishmaniasis (CL) and that keratinocyte death through apoptosis may play a pathogenic role for skin ulceration. To further investigate the alterations of apoptosis during CL, a keratinocyte cell line (HaCaT) and primary human epidermal keratinocytes were incubated with supernatants from Leishmania major-infected peripheral blood mononuclear cells. An apoptosis-specific microarray was used to assess mRNA expression in HaCaT cells exposed to supernatants derived from L. major-infected cultures. Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression were significantly up-regulated, and apoptosis was detected in both HaCaT and human epidermal keratinocyte cells. The keratinocyte apoptosis was partly inhibited through blocking of Fas or FasL and even more efficiently through TRAIL neutralization. Up-regulation of Fas on keratinocytes in epidermis and the presence of FasL-expressing macrophages and T cells in dermis were previously reported by us. In this study, keratinocytes expressing TRAIL, as well as the proapoptotic receptor TRAIL-R2, were detected in skin biopsies from CL cases. We propose that activation of Fas and TRAIL apoptosis pathways, in the presence of inflammatory mediators at the site of infection, leads to tissue destruction and ulceration during CL.

Animals↗
PubMed2006

Surrogate markers of immunity to Leishmania major in leishmanin skin test negative individuals from an endemic area re-visited.

BACKGROUND: In the screening of vaccine candidates it is important to select candidates that evoke immune responses associated with protection. Valid surrogate markers against human leishmaniasis are still lacking. METHODS: A controlled injection of live Leishmania known as leishmanization, (LZ), was used to evaluate vaccine (alum-precipitated autoclaved Leishmania major with BCG) efficacy and more accurately define surrogate markers of immunity to leishmaniasis in humans. Cellular immune responses to this artificial infection were monitored in the volunteers prior to and 9 months post infection. Comparisons were made between those who developed a lesion after infection and those who did not. RESULTS: In the volunteers monitored there was no significant difference in LST, IFNgamma production, or source of IFNgamma between those who developed a lesion and those who did not after LZ, with the exception that ulcer development was associated with an enhanced number of IFNgamma secreting CD4(+) CD45RA(-) (memory) T cells. DISCUSSION: Ulcer development following LZ was lower than anticipated by a pilot study (47% versus 78%) using the same stabilate several years earlier. While this may be an effect of low viability/virulence of the LZ inocula, alternative explanations are also possible. The IFNgamma responses in the study subjects were significantly lower compared to volunteers with previous history of cutaneous leishmaniasis. The findings raise the possibility that the selection of LST-negative volunteers in an endemic area may bias the study towards potentially non/low L. major-reactive volunteers.

Adjuvants, Immunologic↗
PubMed2006

Are intestinal helminths risk factors for developing active tuberculosis?

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.

Adolescent↗
PubMed2005

Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis.

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.

Animals↗
PubMed2005

The contribution of the Fas/FasL apoptotic pathway in ulcer formation during Leishmania major-induced cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL), caused by the intracellular protozoan Leishmania major, is characterized by lesion formation and ulceration at the site of infection. The mechanism of ulcer formation during CL is not fully understood. The expression of Fas and FasL and the levels of apoptosis in skin biopsies and in restimulated blood mononuclear cells from patients with 1 to 7 months of L. major-induced CL were analyzed using immunohistochemistry and fluorescence-activated cell sorting analysis. The levels of soluble Fas and FasL were also analyzed by enzyme-linked immunosorbent assay. A substantial number of apoptotic keratinocytes were observed mainly in the superficial epidermis of morphologically active and healing CL skin samples. Fas expression was increased on epidermis in active CL, whereas Fas expression was similar in healing and healthy epidermis. FasL-expressing macrophages and T cells were found in subepidermal infiltrate, mainly in active disease. When CL peripheral blood mononuclear cells were restimulated with L. major, Fas was up-regulated on effector T cells, and high levels of sFasL were secreted. Supernatants from restimulated cultures induced apoptosis in human keratinocytes (HaCaT), possibly through Fas/FasL interactions. Our results indicate that FasL-expressing effector T cells and macrophages may act to induce apoptosis and ulcer formation in Fas-expressing keratinocytes during L. major infection.

Animals↗
PubMed2002

Diagnosis of onchocerciasis using highly specific and sensitive native proteins.

We describe a highly immunogenic low molecular weight fraction of proteins obtained from Onchocerca volvulus. It is comprised of a mixture of native proteins ranging in molecular weight from 10 to 40 kDa and is collectively designated PakF. Unlike other Onchocerca (and other filarial) antigens previously described, IgG4 antibody responses to this protein mixture were absent or low. In a simple, IgG-based dot blot assay, this mixture of native proteins showed high sensitivity, comparable to or better than that of other previously described recombinant proteins, when used to detect infected individuals in endemic areas of Ghana and Guatemala. The specificity was also high when evaluated using sera from patients with other filarial infections. Arguments are put forward to suggest that such a native fraction could present an interesting alternative to the use of well-defined molecules, which are expensive, labile or prone to denaturation, in endemic areas.

Animals↗