Plasma concentrations of transforming growth factor beta 1 in non-progressive HIV-1 infection correlates with markers of disease progression.

The human immunodeficiency virus (HIV) infection shows variable rate of disease progression. The underlying biological and molecular mechanisms involved in determining progression of HIV infection are not fully understood. The aims of this study were to determine plasma concentrations of active TGF ß 1, Th1 and Th2 cytokines in patients with non-progressive and those with progressive HIV-1 infection, as well as to determine if there is an association of these cytokines to disease progression. In a cross-sectional study of 61 HIV-1 infected individuals categorized according to disease progression as having non-progressive HIV-1 infection (n=14) and progressive infection (n=47), plasma levels of active TGF ß 1, INF-γ, TNF-α, IL-10, IL-1ß, IL-12p70 and IL-13 were compared with HIV uninfected healthy controls (n=12). Plasma concentration of these cytokines was measured using a highly sensitive luminex200 XMAP assay. Pearson correlation test was used to assess the correlation of cytokines with CD4+ and CD8+ T cells, CD4:CD8 ratio and plasma HIV-1 RNA in the different study groups. Plasma concentrations of TGF ß 1 and IL-10 were significantly decreased while IL-1ß, IL-12p70 and TNF-α were increased in patients with non-progressive HIV-1 infection compared to patients with progressive infection. Plasma levels of TGF ß 1 and IL-10 showed an inverse correlation with CD8+ T cell counts and CD4:CD8 ratios in patients with non-progressive HIV-1 infection, while plasma HIV-1 RNA positively correlated with CD4+ T cell counts. Plasma levels of TNF-α, IL-1ß, IL-12p70 and IL-13 positively correlated with CD4+ T cell counts and inversely correlated with plasma HIV-1 RNA, CD8+ T cell count and CD4:CD8 ratio in patients with non-progressive infection. The correlation of cytokines to the state of T-lymphocyte and plasma HIV-1 RNA found in this study may provide insight into the role of cytokines in both progressive and non-progressive HIV-1 infection. Additionally, these findings may have implications for systemic cytokine-based therapies in HIV-1 infection.

THE EVALUATION OF DOMESTIC DUCKS AS POTENTIAL RESERVOIR OF AVIAN INFLUENZA VIRUS IN POST HPAI H5N1 OUTBREAK AREA, SUNYANI MUNICIPALITY, BRONG AHAFO REGION OF GHANA.

BACKGROUND: Avian influenza (AI) is an important zoonotic disease responsible for significant losses in most sub-Saharan countries. However, the role of poultry other than chicken in the epidemiology of the disease, especially after the first AI outbreak in Ghana, has not been fully elucidated. The obiective of this study is to determine whether the AI virus infection that was reported in the area in May 2007 was circulating silently in ducks in nine randomly selected farms in the Sunyani Municipality, Ghana. MATERIALS AND METHODS: The sample size was calculated using Epi info version 3.4.1 at 95% confidence level, absolute precision of 5% and assuming 0.5 prevalence of Avian Influenza A virus in ducks. Samples collection was done simultaneously with questionnaire administration to farmers. A total of 526 samples made up of 384 cloacal swabs and 142 feather tissues from ducks from a commercial duck farm, seven backyard holdings and one live birds market in six randomly selected communities in the Sunyani Municipality, Brong Ahafo region of Ghana. The samples were processed and subjected to Influenza Type A Matrix Gene analysis using RRT-PCR. RESULTS: All the 526 samples subiected to Influenza Type A Matrix Gene analysis using RRT-PCR were negative for Influenza Type A viruses. However, it was observed that bio-security practices which are keys to reintroduction of the virus in the area were not adhered to in 89 % of the sites investigated. Our finding also revealed that only the commercial farm investigated in this study complied with fifteen (78.9%) of the nineteen different farm practices observed. CONCLUSION: Though AI was not detected in the ducks sampled, there is the need for continuous surveillance and education of stakeholders on standard bio-security and farm management practices in the area.

CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.

Suitability of a rapid immunochromatographic test for detection of antibodies to human immunodeficiency virus in Ghana, West Africa.

In West African countries such as Ghana, efficient human immunodeficiency virus (HIV) testing is a priority in the fight against AIDS. A new immunochromatographic rapid test, Determine HIV-1/2 (Abbott Diagnostics, North Chicago, Ill.), that detects antibodies against HIV type 1 (HIV-1) and/or HIV-2 was evaluated using Ghanaian blood samples. Two hundred four serum and/or plasma specimens were tested. HIV screening was done by a particle agglutination test and confirmed by a Western blot (WB) test as the "gold standard." The results revealed 125 HIV-seropositive AIDS patients, 75 HIV-seronegative healthy individuals, and 4 individuals for whom the HIV-1 result was indeterminate. The results obtained by the Determine HIV-1/2 assay and Diagnostic HIV SPOT (Genelabs), which is currently widely used in many districts in Ghana, were compared with those of the WB test, excluding the four HIV-1-indeterminate samples. The sensitivity of the Determine HIV-1/2 assay was 100%, compared with 98.0% for the HIV SPOT assay. The specificity was 100% for both tests. Determine HIV-1/2 is a single-step assay and was found to be rapid and easy to perform without any special equipment. It was highly sensitive and specific. The kit can be applied without electricity and water supplies, making it suitable for the detection of HIV antibodies especially in the rural areas of Ghana, West Africa.

Genetic analysis of HIV type 2 from Ghana and Guinea-Bissau, West Africa.

The phylogenetic variability of part of the long terminal repeat (LTR) region of HIV-2 strains isolated in 1995 from five individuals residing in Bissau, the capital city of Guinea-Bissau, and collected from seven persons from Kumasi, Ghana in 1996-1997, was analyzed. All Guinean samples and all but one Ghanaian sample clustered with HIV-2 subtype A. One Ghanaian sample (14%) was classified as HIV-2 subtype B. This study adds to previous reports on HIV-2 subtype distribution in West Africa indicating local prevalence of HIV-2 subtype B in Ivory Coast and neighboring Ghana.

Relationship between immunoclinical status and prevalence of viral sexually transmitted diseases among human immunodeficiency virus-1 seropositive patients in Ghana.

In view of the strong association between the acquired immunodeficiency syndrome (AIDS) and sexually transmitted diseases (STDs), we screened 182 human immunodeficiency virus (HIV)-1 infected patients over a 15-month period for serological markers to previously encountered or current STDs, most of viral etiology. The relationship between their immunological and clinical status and the prevalence of STDs was assessed and compared with that of 88 HIV-seronegative patients. Hepatitis B virus and Treponema pallidum were the most frequently occurring pathogens in both HIV-1-infected and HIV-seronegative patients. Hepatitis C virus (HCV) infection was also observed in both groups, but no HIV-seronegative patient was infected with human T-lymphotropic virus type 1 (HTLV-1). The Centers for Disease Control clinical staging of A1 through C3, representing asymptomatic to severe AIDS conditions, was observed in HIV-1 patients with or without STDs. A mean CD4 count of 288 cells per microliter (95% CI of 237-340 cells per microliter) in HIV-1 patients was significantly lower (P < 0.05) than that in HIV-seronegative individuals with 1019 cells per microliter (95% CI of 924-1115 cells per microliter), irrespective of whether subjects in either group had previous or current STDs. The mean CD4 count of patients with a single infection from HIV-1 was not significantly different (P = 0.36) from that of HIV-1 patients with multiple infections. HIV-1 infection alone appears to be responsible for the marked immunodeficiency status of seropositive patients observed in this study.

Seroreactivity clarification and viral load quantitation in HIV-1 and HIV-2 infections in Ghana.

In Ghana, West Africa, the prevalence of dual HIV-1 and HIV-2 infections remains to be clarified, and HIV viral load measurement is yet to be established. Conventional assays for HIV-1 RNA measurements have been limited specifically to HIV-1 subtype B, preventing their utilization for Ghana where HIV-1 subtypes A, D and G are prevalent. Therefore, we set out to distinguish the types of HIV infection existing in Ghana so as to determine the extent of actual dual infections, and to measure plasma HIV-1 RNA. Blood samples were collected from 563 sick and healthy Ghanaians who visited hospitals in 1996 and 1997. After T cells were counted, HIV antibody was screened and confirmed by six different commercial assays and one in-house test. Nested PCR was then used to verify HIV-1 and HIV-2 presence by type-specific primers. Plasma HIV-1 RNA was measured by an improved commercial RT-PCR assay, sensitive to all HIV-1 group M subtypes. HIV-1 alone (89%) clearly dominated over HIV-2 alone (2%), and HIV-1 and HIV-2 dual infections were found in 9%. Valid viral load measurements were obtained on test plasma representing the main HIV-1 subtype (A) prevailing in Ghana. A high amount of HIV-1 RNA (5.9 mean log10 RNA copies/ml) was observed in the typical stages of HIV infection represented by groups of CD44 cell counts. We have clarified the seroprevalence of HIV-1 and HIV-2 amongst HIV seropositives, and the high viral load of HIV-1 reflects its influence on AIDS in Ghana.

Predominance of HIV-1 among patients with AIDS and AIDS-related complex in Ghana.

We determined the prevalence of HIV among AIDS and AIDS-Related Complex (ARC) patients seen within one year in two hospitals in southern Ghana. Subjects were screened by an ELISA procedure for anti-HIV antibodies. Specific identification of the HIV type was done with a particle agglutination (PA) kit. All PA-determined dual specimens were then confirmed by Western blotting and Pepti-Lav 1/2 monoepitope kit. Virus isolation was attempted from symptomatic patients by co-culturing patient peripheral blood monocyte cells (PBMCs) and CD4+ cell lines. PBMCs and HIV isolates were characterised by PCR. By ELISA, 43.5% of the subjects (253) had anti-HIV antibodies. Of these, 61 (24%) were HIV-1 positive and 42 (18.6%) were dually reactive by PA. However, only 19% were confirmed as true dually-infected cases by western blotting and Pepti-Lav through all 42 samples were HIV-1 positive on the two tests. No subject was infected with HIV-2 alone. Three viruses were isolated. By PCR two of them had both HIV-1 and HIV-2 proviral sequences while the third virus was HIV-1 only. HIV-1 prevalence now predominates over HIV-2 implying a switch in the HIV infection pattern in Ghana. Furthermore mixed infections exist. The predominance of HIV-1 infection in Ghana may indicate a similar trend in other parts of West Africa.

PIP: Recent studies have suggested that HIV-2 infection is becoming less prevalent in Ghana, while the prevalence of HIV-1 is increasing. To confirm such a modification in the HIV infection profile in Ghana, a 1-year serologic and molecular study was conducted among 253 patients from 2 hospitals in southern Ghana (Accra and Dzodze in the Volta region) with confirmed or suspected AIDS. All 253 serum specimens were screened with enzyme-linked immunosorbent assay (ELISA) and particle agglutination (PA); the 42 dually reactive specimens were subsequently confirmed by Western blot and Pepti-Lav tests. By ELISA, 110 samples (43.5%) were positive for anti-HIV antibodies; this rate was 39.2% in Accra and 81.0% in the Volta region. Of these, 61 (24.1%) were HIV-1 positive and 42 (18.6%) were dually reactive by PA. No case of HIV-2 alone was detected. Most dually reactive cases were a cross-reaction between genetically similar regions of the 2 HIV types. Only 19% of the 42 PA-diagnosed dually reactive specimens were confirmed by Western blot and Pepti-Lav as true cases of HIV-2 only infection, and all these specimens were strongly positive for anti-HIV-1 antibodies. 3 viruses were isolated. By polymerase chain reaction, 2 had both HIV-1 and HIV-2 proviral sequences, while the third was HIV-1 only. This study's findings provide support for the hypothesis that most individuals with antibodies to both HIV-1 and HIV-2 are probably infected with HIV-1 alone. Intensified population surveillance aimed at isolating more HIV strains in West Africa could reveal the true extent of HIV genomic variation and facilitate the design of more specific diagnostic kits.

Randomized, controlled trial of trivalent oral poliovirus vaccine (Sabin) starting at birth in Ghana.

To evaluate the efficacy of the schedule currently recommended for immunization with trivalent oral poliovirus vaccine (TOPV) (i.e., at birth, 6 weeks, 10 weeks, and 14 weeks after birth), we randomly assigned 452 infants into test (231 infants) and control (221 infants) groups. The test group received TOPV as currently recommended, and the dose at birth was omitted for the control group. At 10, 14, and 18 weeks of age, the levels of poliovirus neutralizing antibodies as well as seroconversion rates were consistently higher for the test group than for the control group. The final seroconversion rates against poliovirus types 1, 2, and 3 were 83.5%, 91% and 83%, respectively, for the test group and 75%, 83.2%, and 79.1%, respectively, for the control group. The TOPV immunization schedule starting at birth therefore produced better results. Seroconversion rates as well as antibody levels were highest in infants with low maternal antibodies.