A primer on immune responses and mechanisms

The immune response is how your body recognizes and defends itself against bacteria, viruses, and substances that appear foreign and harmful. Innate, or nonspecific, immunity is the defense system with which you were born. It protects you against all antigens. Innate immunity involves barriers that keep harmful materials from entering your body. An antigen-presenting cell (APC) is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T-cells. They are found in a variety of tissue types. Professional antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to helper T cells, while virus-infected cells (or cancer cells) can present antigens originating inside the cell to cytotoxic T cells There are two broad classes of immune responses—antibody responses and cell-mediated immune responses, and they are carried out by different classes of lymphocytes, called B cells and T cells, respectively. The way the body defends itself against substances it sees as harmful or foreign. In an immune response, the immune system recognizes the antigens (usually proteins) on the surface of substances or microorganisms, such as bacteria or viruses, and attacks and destroys, or tries to destroy, them

The general population cohort in rural south-western Uganda: a platform for communicable and non-communicable disease studies.

The General Population Cohort (GPC) was set up in 1989 to examine trends in HIV prevalence and incidence, and their determinants in rural south-western Uganda. Recently, the research questions have included the epidemiology and genetics of communicable and non-communicable diseases (NCDs) to address the limited data on the burden and risk factors for NCDs in sub-Saharan Africa. The cohort comprises all residents (52% aged ≥13years, men and women in equal proportions) within one-half of a rural sub-county, residing in scattered houses, and largely farmers of three major ethnic groups. Data collected through annual surveys include; mapping for spatial analysis and participant location; census for individual socio-demographic and household socioeconomic status assessment; and a medical survey for health, lifestyle and biophysical and blood measurements to ascertain disease outcomes and risk factors for selected participants. This cohort offers a rich platform to investigate the interplay between communicable diseases and NCDs. There is robust infrastructure for data management, sample processing and storage, and diverse expertise in epidemiology, social and basic sciences. For any data access enquiries you may contact the director, MRC/UVRI, Uganda Research Unit on AIDS by email to [email protected] or the corresponding author

Consent and community engagement in diverse research contexts: reviewing and developing research and practice

Consent and community engagement (CE) in health research are two aspects of a single concern—that research is carried out in a respectful manner where social value is maximized. There are important overlaps and interdependencies between consent and CE; for example, CE can provide insights into how best to tailor consent to context and can be an important component of consent processes. Engaging communities can also have intrinsic and instrumental value beyond consent; for example, as a means of showing respect and identifying appropriate ways of working respectfully. In this paper we critically examine how CE and consent processes are characterized, conducted, and evaluated in diverse health research contexts, and propose a preliminary research agenda to support future learning in these critical areas

Prevalence of severe mental distress and its correlates in a population-based study in rural south-west Uganda

BACKGROUND: The problem of severe mental distress (SMD) in sub-Saharan Africa is difficult to investigate given that a substantial proportion of patients with SMD never access formal health care.This study set out to investigate SMD and it's associated factors in a rural population-based cohort in south-west Uganda. METHODS: 6,663 respondents aged 13 years and above in a general population cohort in southwestern Uganda were screened for probable SMD and possible associated factors. RESULTS: 0.9% screened positive for probable SMD. The factors significantly associated with SMD included older age, male sex, low socio-economic status, being a current smoker, having multiple or no sexual partners in the past year, reported epilepsy and consulting a traditional healer. CONCLUSION: SMD in this study was associated with both socio-demographic and behavioural factors. The association between SMD and high risk sexual behaviour calls for the integration of HIV prevention in mental health care programmes in high HIV prevalence settings

Operational evaluation of a service for prevention of mother-to-child transmission of HIV in rural Uganda: barriers to uptake of single-dose nevirapine and the role of birth reporting.

SUMMARY OBJECTIVES: To determine factors associated with pregnant women being HIV positive, barriers to the uptake of single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT) and feasibility and effectiveness of reporting HIV-exposed infants born in facilities with no PMTCT services so as to receive NVP. METHODS: From 2002 to 2007, a sdNVP PMTCT service was implemented in 53 rural villages of south-west Uganda. Twenty-five of them were HIV-surveillance study villages. The proportions of mothers testing positive and mother and newborns receiving and ingesting sdNVP and associated factors were determined. RESULTS: Women with incomplete primary or no education, aged 25-34 years or not living with their partners were at increased risk of being HIV infected. Seventy-seven percentage of pregnant women with HIV (PWH) received therapy. Of the 63 PWH who received therapy and had surviving live births, only 39 (62%) reported births and received newborn prophylaxis within 72 h. Women were more likely to collect and ingest NVP if they were from study villages, preferred home administration of newborn NVP or presented at a more advanced stage of pregnancy. Newborns were more likely to be reported and receive NVP if mothers were aged 25-34 years, on antiretroviral therapy (ART) or came from study villages. CONCLUSIONS: The uptake of PMTCT services was unacceptably low. Asking PWH with less advanced pregnancies to return to collect NVP leads to missed opportunities especially if PWH are less educated. Birth reporting enabled the programme to provide NVP to some infants who otherwise would have missed. Antenatal, delivery and PMTCT services should be integrated

Mortality and its predictors among antiretroviral therapy naïve HIV-infected individuals with CD4 cell count ≥350 cells/mm(3) compared to the general population: data from a population-based prospective HIV cohort in Uganda.

BACKGROUND: Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART) naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm(3). OBJECTIVE: To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm(3) with mortality in the general Ugandan population and to investigate risk factors for death. DESIGN: Population-based prospective HIV cohort. METHODS: The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs). RESULTS: A total of 374 participants with CD4 ≥350 cells/mm(3) were followed for 1,328 person-years (PY) over which 27 deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95-29.66) among all participants and 16.43 (10.48-25.75) among participants aged 15-49 years. Mortality was higher in periods during which participants had CD4 350-499 cells/mm(3) than during periods of CD4 ≥500 cells/mm(3) although the difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95% CI: 0.71-3.25]. Compared to the general Ugandan population aged 15-49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm(3) (SMR: 223%, 95% CI: 127-393%) and 146% higher among participants with CD4 350-499 cells/mm(3) (246%, 117%-516). After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82-27.15) and decreasing body mass index (BMI) (aRR comparing categories ≤17.4 Kg/m(2) and ≥18.5 Kg/m(2): 6.11, 2.30-16.20). CONCLUSION: HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm(3) had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI

Effect of pregnancy on immunological and virological outcomes of women on ART: a prospective cohort study in rural Uganda, 2004-2009.

OBJECTIVES: Before antiretroviral therapy (ART) introduction, pregnancy was associated with a sustained drop in CD4 cell count in HIV-infected women. We examined the effects of pregnancy on immunological and virological ART outcomes. METHODS: Between January 2004 and March 2009, we studied HIV-infected women receiving ART in a prospective open cohort study in rural Uganda. We used random effects regression models to compare the CD4 counts of women who became pregnant and those who did not, and among the pregnant women before and after pregnancy. CD4 count and proportions with detectable viral load (≥400 copies/ml) were compared between the two groups using the Mann-Whitney rank sum test and logistic regression respectively. RESULTS: Of 88 women aged 20-40 years receiving ART, 23 became pregnant. At ART initiation, there were no significant differences between those who became pregnant and those who did not in clinical, immunological and virological parameters. Among women who became pregnant, CD4 cell count increased before pregnancy (average 75.9 cells/mm(3) per year), declined during pregnancy (average 106.0) but rose again in the first year after delivery (average 88.6). Among women who did not become pregnant, the average CD4 cell count rise per year for the first 3 years was 88.5. There was no significant difference in the proportions of women with detectable viral load at last clinic visit among those who became pregnant (8.7%) and those who did not (16.1%), P = 0.499. CONCLUSION: Pregnancy had no lasting effect on the immunological and virological outcomes of HIV-infected women on ART

Extraspousal partnerships in a community in rural Uganda with high HIV prevalence: a cross-sectional population-based study using linked spousal data.

BACKGROUND: The role of concurrent sexual partnerships in the HIV epidemic in sub-Saharan Africa is not well understood. Although most infections in Africa occur among married individuals, transmission may occur from both spousal and extraspousal partnerships. This article explores extraspousal partnerships as a form of concurrency, examining the association with HIV status, demographic characteristics, and sexual behaviors in a population-based cohort in rural Uganda. METHODS: Prevalence of extraspousal partnerships was estimated using cross-sectional data from 2008, and adjusted odds ratios (aOR) were estimated for factors associated with the prevalence of extraspousal partnerships using logistic regression. Among men who were not in polygynous marriages, we used linked spousal data to investigate the association between extraspousal partnerships and wives' serostatus. RESULTS: Extraspousal partnerships in the past year were reported by 17% of married men and 2% of married women. Among both men and women, extraspousal partnerships were associated with not knowing their partners' HIV status (men: aOR = 1.74; 95% CI: 1.13 to 2.67; women: aOR = 1.76; 95% CI: 1.13 to 2.75), and extraspousal partnerships were also associated with increased condom use for men. There was no evidence that men reporting extraspousal partnerships were at increased risk of HIV (aOR = 0.98; 95% CI: 0.48 to 2.01), or that a woman's risk of HIV was associated with her husband reporting extraspousal partnerships (aOR = 0.68; 95% CI: 0.29 to 1.57). CONCLUSIONS: For both men and women, extraspousal partnerships were associated with not knowing their partners' HIV status. There was no evidence of an association of extraspousal partnerships with HIV serostatus in this cross-sectional analysis