Geoffrey C Onyemelukwe

Pattern of serum cytokine expression and T-cell subsets in sickle cell disease patients in vaso-occlusive crisis.

ABSTRACT The pathogenesis of sickle vaso-occlusive crisis (VOC) in sickle cell disease (SCD) patients involves the accumulation of rigid sickle cells and the stimulation of an ongoing inflammatory response, as well as the stress of infections. The immune response, via cytokine imbalances and deregulated T-cell subsets, also has been proposed to contribute to the development of VOC. In this study, a panel of high-sensitivity cytokine kits was used to investigate cytokines in the sera of SCD patients in VOC. The results were compared primarily with those for stable SCD patients and secondarily with those for normal healthy people who served as controls. The cytokines studied included interleukin-2 (IL-2), IL-4, and IL-10. Lymphocyte subsets of patients with VOC were also studied and were compared with those of both control groups (20 stable patients without crisis [SCD group] and 20 normal healthy controls [NHC]). The VOC group was notable for remarkably elevated levels of IL-4, among the three cytokines tested, compared with those for the SCD and NHC groups. Patients with VOC also differed from stable SCD patients and NHC by having notably lower IL-10 levels, as well as the lowest ratio of CD4+ to CD8+ T cells (0.7). The patterns of the proinflammatory cytokine IL-2 did not differ between VOC and stable SCD patients, but NHC had significantly lower IL-2 levels than both the VOC and SCD groups. Our results demonstrate coexisting levels, both high and low, of TH1- and TH2-type cytokines, as well as diminished levels of T-cell subsets in VOC. These results are discussed in an effort to better understand the importance of the immune system profile in the pathogenesis of sickle cell VOC. Since the possibility that a cytokine imbalance is implicated in the pathogenesis of sickle cell crisis has been raised, our results should prompt further investigation of the host immune response in terms of TH1 and TH2 balance in sickle cell crisis.

Seroprevalence of IgM and IgG Antibodies to Toxoplasma infection in healthy and HIV-positive adults from Northern Nigeria

INTRODUCTION We examined the seroprevalence of toxoplasma infection in HIV-negative and -positive adults from Zaria, Northern Nigeria, and assessed its relationship with demographic, clinical, and immunological findings. METHODOLOGY In a six-month cross-sectional study undertaken in 2008, sera of 219 adults, including 111 consecutive HIV-infected adults and 108 healthy HIV-negative adult volunteers from Zaria, Northern Nigeria, were examined for IgG and IgM antibodies to toxoplasma by ELISA. Clinical characteristics of the HIV-infected patients were documented. Differences in toxoplasma seropositivity between HIV-positive and negative adults were sought. The relationship between toxoplasma seropositivity and variables such as age, sex and antiretroviral (ART) status, as well as HIV clinical staging and CD4 cell counts were also determined. P < 0.05 was considered significant. RESULTS The seroprevalence of toxoplasma infection (IgG positive and or IgM positive) was 32.4% in HIV-negative healthy adults and 38.7% in HIV-infected adults (P > 0.05). The rate of IgM seropositivity was 4.6% in healthy adults and 1.8% in HIV-infected patients, while the rate of IgG seropositivity (without IgM seropositivity) was 28.7% in healthy adults and 37.8% in HIV-infected patients (p > 0.05). Toxoplasma seropositivity was not associated with age, sex, ART status, CD4 cell count or HIV clinical staging. Seventy-four percent of the toxoplasma seropositive HIV-infected patients were asymptomatic and no cases of toxoplasma encephalitis were identified. CONCLUSION Toxoplasmosis is equally prevalent in HIV-infected patients and healthy adults from similar environments in Northern Nigeria. It is imperative to develop public health policies to prevent toxoplasmosis in Nigeria, especially in HIV-infected patients.

Aflatoxins, B1, B2, G1, G2 in primary liver cell carcinoma

Aflatoxin B1, B2, G1, G2 levels were determined in sera of 20 patients with primary liver cell carcinoma (CC). Values of B1 above 0.15 microgram/ml were obtained in sera of three patients. Hepatitis B surface antigen (HBsAg) was detected in only 35% of patients. 50-90% of serum levels were cleared in 24 h in three patients studied. Although it is inconclusive as to the carcinogenic potential of aflatoxins in adult man, foodstuffs should be protected from excessive aflatoxin contamination.

Smoking prevention and cessation in the Africa and Middle East region: a consensus draft guideline for healthcare providers--executive summary.

Despite the abundance of scientific evidence confirming the health consequences of smoking and other forms of tobacco use, the tobacco epidemic remains an important public health problem and by 2030 it is predicted that more than 80% of tobacco deaths will be in developing countries. In Africa and the Middle East, many local factors contribute to the initiation and maintenance of tobacco use. Although efforts to reduce the mortality and morbidity associated with smoking and tobacco dependence are underway, there is a need for guidance on how to utilize appropriate tobacco control policies and psychology- and pharmacology-based therapies to counter tobacco dependence as recommended by the Framework Convention on Tobacco Control (FCTC). A group of tobacco cessation experts from public health services and/or academic institutions in Africa and the Middle East participated in a series of four meetings held in Cairo, Cape Town, and Dubai between May 2008 and February 2011 to develop a draft guideline tailored to their region. This article provides the background to the development of this draft smoking cessation guideline and discusses how the recommendations can be implemented and progress monitored to promote both primary prevention and cessation of tobacco use within our countries. The draft guideline for Africa and the Middle East provides an important resource in combating the devastating effects of tobacco use in these regions which can be further localized through engagement with local stakeholders in the countries of the region.

Human papilloma virus (HPV) infection is associated with HIV-1 infection and AIDS in HIV-infected adult patients from Zaria, Northern Nigeria.

In order to provide preliminary information on the association between cumulative HPV-infection and HIV-1infection, we assayed serum IgG antibodies to HPV in 63 HIV-1 infected adults and 26 apparently healthy HIV-negative adults in Zaria, Northern Nigeria. One (3.8%) of the healthy adults and 26 (41.3%) of the HIV-patients were HPV IgG seropositive. On multivariate analyses, CD4-cell count<200cells/ul was the only independent predictor of HPV IgG seropositivity among HIV-infected patients. Our results suggest that in HIV-infected patients, HPV-infection is associated with significant immunosuppresion or AIDS.

Clinical presentation and outcome of toxoplasma encephalitis in HIV-infected patients from Zaria, Northern Nigeria: a case series of 9 patients.

Toxoplasma encephalitis (TE) is the most common cause of focal deficits in patients living with HIV/AIDS. Among 257 HIV-infected adult patients seen between January 2006 and December 2010 in a tertiary hospital in Zaria, northern Nigeria, 9 (3.5%) patients had clinical, serological, and brain imaging evidence of TE. All 9 patients had CD4 count of less than 50 cells/mm3. Of the 9 patients, 7 were antiretroviral therapy (ART)-naive, while 2 were cases of ART-induced TE-immune reconstitution inflammatory syndrome. After administering intravenous dexamethasone for cerebral decompression and specific antitoxoplasma therapy, symptoms and signs resolved in 8 patients within 4 to 14 days, but 1 patient died. Our data suggest that even in the ART era in Nigeria, TE remains a fairly common cause of morbidity among HIV-infected patients due to late HIV diagnosis and significant immunosuppression at diagnosis. Early HIV diagnosis, early initiation of highly active ART, and routine prophylaxis against TE are imperative in combating the challenge of HIV/AIDS-related TE in Nigeria.

Joint Annual Meeting of the, Swiss Society of Pneumology, Swiss Society of Pediatric Pneumology, Swiss Society for Thoracic Surgery, Swiss Underwater and Hyperbaric Medical Society, Crans-Montana, April 25–27, 2012

Background: Current in-vitro techniques used to investigate the pathophysiology of pulmonary diseases are mostly performed on rigid cell culture plates or porous membranes. Such in-vitro models do poorly reproduce the in-vivo conditions of the lung, in particular the mechanical stretching induced by the respiratory movements. Recent advances in microfabrication technology make it possible to mimic the blood stream by perfusing continuously a cell culture, and even reproducing the mechanical movements of the lung by using thin polymeric membranes. In this study, we present a microfluidic system equipped with a thin stretchable membrane able to mimic the mechanical stress of the alveolar membrane. Methods: A microfluidic microsystem composed by two microchannels structured by polydimethylsiloxane (PDMS) and a thin PDMS membrane was fabricated by rapid prototyping using soft lithography. PDMS is a biocompatible material with excellent gas permeability and mechanical stretching capabilities. The thin membrane located between the two microchannels separates them in two separate chambers that can each be connected individually. Alveolar epithelial cells (A549) were cultured on the fibronectin coated polymeric membrane. Microscopic observations were performed to assess the cell morphology and their viability, using annexin-V and PI staining. The breathing cycles were mimicked by creating a pressure difference between the two microchannels. Results: Very thin and functional PDMS membranes could be fabricated with a thickness of only 10 um. Preliminary experiments reveal that they can be deflected in physiological range by increasing the pressure in one of the microchannels, while the pressure in the second channel stays the same. Alveolar epithelial cells could be cultured on the membrane and reached confluence in about 24 h. Microscopic observations show that the cell viability stays very high during the whole experiment (48 h). Conclusions: We could demonstrate the fabrication of very thin PDMS membranes suited for alveolar epithelial cell cultures. The polymeric membranes could easily be stretched by pressure variations. These preliminary results are promising; further experiments will focus on the effects of the breathing on the epithelial layer.

Human Herpesvirus 8 Infections and AIDS-Associated Kaposi Sarcoma in Zaria, Northern Nigeria

Background/Objectives: Studies on human herpesvirus 8 (HHV8) infection in patients with AIDS-associated Kaposi sarcoma (AIDS-KS), from Nigeria are lacking. We examined the seroprevalence of HHV8 infection in patients with AIDS-KS presenting to Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria, and also described their clinical presentation. Methods: A total of 20 (11 males and 9 females) histologically confirmed adults with AIDS-KS were recruited consecutively in 2007. The clinical types of lesions, associated diseases, and the AIDS clinical trial group staging of AIDS-KS were noted. Anti-lytic HHV8 antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Results: Kaposi sarcoma skin lesions were diverse but mostly nodules (19 cases) and papules (16). Majority (18 cases) had poor risk AIDS-KS, with 10 (50%) patients having concomitant opportunistic infections and 3 (15%) patients having generalized skin lesions. Females had a more severe disease. Seventeen patients (85%) were HHV8-seropositive. Conclusion: AIDS-KS is associated with high HHV8 infection and presents with a variety of skin manifestations that are often aggressive, advanced, and worse in females.