Monica Smikle

Deficiency of HIV-Gag-Specific T Cells in Early Childhood Correlates with Poor Viral Containment

Perinatal HIV infection is characterized by a sustained high-level viremia and a high risk of rapid progression to AIDS, indicating a failure of immunologic containment of the virus. We hypothesized that age-related differences in the specificity or function of HIV-specific T cells may influence HIV RNA levels and clinical outcome following perinatal infection. In this study, we defined the HIV epitopes targeted by 76 pediatric subjects (47 HIV infected and 29 HIV exposed, but uninfected), and assessed the ability of HIV-specific CD8 and CD4 T cells to degranulate and produce IFN-γ, TNF-α, and IL-2. No responses were detected among HIV-uninfected infants, whereas responses among infected subjects increased in magnitude and breadth with age. Gag-specific responses were uncommon during early infancy, and their frequency was significantly lower among children younger than 24 mo old (p = 0.014). Importantly, Gag responders exhibited significantly lower HIV RNA levels than nonresponders (log viral load 5.8 vs 5.0; p = 0.005). Both the total and Gag-specific T cell frequency correlated inversely with viral load after correction for age, whereas no relationship with targeting of other viral proteins was observed. Functional assessment of HIV-specific T cells by multiparameter flow cytometry revealed that polyfunctional CD8 cells were less prevalent in children before 24 mo of age, and that HIV-specific CD4 cell responses were of universally low frequency among antiretroviral-naive children and absent in young infants. These cross-sectional data suggest that qualitative differences in the CD8 response, combined with a deficiency of HIV-specific CD4 cells, may contribute to the inability of young infants to limit replication of HIV.

HTLV‐1 associated polymyositis in Jamaica

The clinical, laboratory and epidemiological characteristics of 38 adult Jamaican patients with polymyositis were evaluated. Twenty‐four patients (63%) were human T‐lymphotropic virus 1 (HTLV‐1) seropositive and 14 patients (37%) were HTLV‐1 seronegative. Polymyositis runs a more protracted course in seropositive patients who had more frequent hospital admissions and a significantly longer duration of symptoms prior to presentation. Joint swelling, chest pain and dyspnoea were more frequent complaints among the seronegative patients. There was no significant difference between the two serological groups in muscle enzyme levels, antinuclear antibody positivity or frequency of Jo‐1 antibodies. HTLV‐1 infection may define a subgroup of polymyositis patients with a more insidious presentation and poorer response to corticosteroid therapy.

IgA antiphospholipid antibodies in HTLV-1-associated tropical spastic paraparesis.

A retrovirus, human T cell lymphotropic virus type 1 (HTLV-1), is an essential but not a sufficient aetiologic factor for tropical spastic paraparesis (TSP). Because some TSP patients have biological false positive tests for treponemal infections (BFP-STS), we used ELISA to study BFP-STS and anticardiolipin antibodies in 42 Jamaican TSP patients. The data indicate that in TSP anticardiolipin antibodies occur in about 26% of patients, are associated with biological false positive treponemal serology, are relatively restricted to the IgA isotype and may be induced by HTLV-1 or other non- treponemal infections.

Leptospirosis in suspected cases of dengue in Jamaica, 2002-2007.

Due to overlapping clinical features with other febrile illnesses, the diagnosis of leptospirosis is often overlooked, resulting in delay in treatment and increased mortality. In this study the prevalence of leptospirosis was determined in 590 patients with dengue-like illnesses using the Leptospira IgM dipstick and dengue enzyme-linked immunosorbent assays. Leptospira IgM antibodies were found in 27 (5.0%) patients. Dengue IgM negative (6.9% versus 2.5%, P < 0.05) and dengue IgG positive patients (8.0% versus 3.5%, P < 0.01) were more likely to be leptospira IgM positive. Fever, skin rash, central nervous system and respiratory involvement were the most common presenting features. The presence of arthralgia (P = 0.016), hepatitis (P = 0.000), jaundice (P = 0.003), splenomegaly (P = 0.041) and haematuria (P = 0.029) were associated with leptospirosis. In countries with an endemicity of leptospirosis and dengue it is important that patients with dengue-like illnesses, especially those with no serological evidence of current primary dengue infection, be investigated for leptospirosis.

High-risk and multiple human papillomavirus (HPV) infections in cancer-free Jamaican women

BackgroundVaccines, that target human papillomavirus (HPV) high risk genotypes 16 and 18, have recently been developed. This study was aimed at determining genotypes commonly found in high-risk and multiple-HPV infections in Jamaican women. Two hundred and fifty three (253) women were enrolled in the study. Of these, 120 pregnant women, aged 15–44 years, were recruited from the Ante Natal Clinic at the University Hospital of the West Indies and 116 non-pregnant, aged 19–83, from a family practice in Western Jamaica. Cervical cell samples were collected from the women and HPV DNA was detected using Polymerase Chain Reaction and Reverse Line Hybridization. HPV genotypes were assessed in 236 women. Data were collected from January 2003 to October 2006.ResultsHPV DNA was detected in 87.7% (207/236) and of these 80.2% were positive for high-risk types. The most common high-risk HPV types were: HPV 45 (21.7%), HPV 58 (18.8%), HPV 16 (18.4%), HPV 35 (15.0%), HPV 18 (14.5%), HPV 52 (12.0%) and HPV 51(11.1%). Other high-risk types were present in frequencies of 1.4% – 7.2%.Multivariate regression analyses showed that bacterial vaginosis predicted the presence of multiple infections (OR 3.51; CI, 1.26–9.82) and that alcohol use (OR 0.31; CI, 0.15–0.85) and age at first sexual encounter (12–15 years: OR 3.56; CI, 1.41–9.12; 16–19 years, OR 3.53, CI, 1.22–10.23) were significantly associated with high risk infections. Cervical cytology was normal in the majority of women despite the presence of high-risk and multiple infections.ConclusionHPV genotype distribution in this group of Jamaican women differs from the patterns found in Europe, North America and some parts of Asia. It may be necessary therefore to consider development of other vaccines which target genotypes found in our and similar populations. HPV genotyping as well as Pap smears should be considered.

Comparisons of high-risk cervical HPV infections in Caribbean and US populations

BackgroundDisparities in cervical cancer incidence and mortality rates exist among women of African ancestry (African-American, African-Caribbean and African). Persistent cervical infection with Human papillomavirus (HPV) is associated with cervical dysplasia and if untreated, could potentially progress to invasive cervical cancer. Very few studies have been conducted to examine the true prevalence of HPV infection in this population. Comparisons of cervical HPV infection and the type-specific distribution of HPV were performed between cancer-free Caribbean and US women.ResultsThe Caribbean population consisted of 212 women from Tobago and 99 women from Jamaica. The US population tested, consisted of 82 women from Pittsburgh. The majority of the US subjects was Caucasian, 74% (61/82) while 12% (10/82) and 13% (11/82) were African-American or other ethnic groups, respectively. The age-adjusted prevalence of any HPV infection among women from Tobago was 35%, while for Jamaica, it was 81% (p < 0.0001). The age-adjusted prevalence of HPV infection for Caribbean subjects was not statistically significantly different from the US (any HPV: 47% vs. 39%, p > 0.1; high-risk HPVs: 27% vs. 25%, p > 0.1); no difference was observed between US-Blacks and Jamaicans (any HPV: 92% vs. 81%, p > 0.1; high-risk HPV: 50% vs. 53%, p > 0.1). However, US-Whites had a lower age-adjusted prevalence of HPV infections compared to Jamaican subjects (any HPV: 29% vs. 81%, p < 0.0001; high-risk HPV: 20% vs. 53%, p < 0.001). Subjects from Jamaica, Tobago, and US-Blacks had a higher proportion of high-risk HPV infections (Tobago: 20%, Jamaica: 58%, US-Blacks: 40%) compared to US-Whites (15%). Similar observations were made for the presence of infections with multiple high-risk HPV types (Tobago: 12%, Jamaica: 43%, US-Blacks: 30%, US-Whites: 8%). Although we observed similar prevalence of HPV16 infections among Caribbean and US-White women, there was a distinct distribution of high-risk HPV types when comparisons were made between the ethnic groups.ConclusionThe higher prevalence of cervical HPV infections and multiple high-risk infections in Caribbean and US-Black women may contribute to the high incidence and prevalence of cervical cancer in these populations. Evaluation of a larger sample size is currently ongoing to confirm the distinct distribution of HPV types between ethnic groups.

Seroprevalence of dengue virus antibodies in healthy Jamaicans

Dengue fever, a mosquito borne viral infection, is endemic to Jamaica. The seroprevalence of dengue IgG and IgM antibodies were determined in 277 healthy Jamaicans by enzyme linked immunosorbent assay (ELISA). The seroprevalence of dengue IgG antibodies was 100% (277/277) while dengue IgM antibodies were found in 3.6% (10/277). A statistically significant association was found between the presence of dengue IgM antibodies and gender (males 10/105, 9.5% vs females 0/172, 0.0%); chi(2) = 17.0, p=0.000.The high seroprevalence rate of dengue IgG antibodies and the presence of dengue IgM in the healthy population are in keeping with the endemicity of the virus in Jamaica. Therefore tests for dengue IgG antibodies are of limited usefulness in Jamaica and can be safely excluded from diagnostic testing as a cost saving measure. Serological diagnosis of current dengue infection should be centred around the dengue IgM tests although the limitations in the predictive values of such tests should also be considered. The results also suggest that the risk of emergence of the more severe forms of dengue, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) in the Jamaican population, due to the presence of enhancing antibodies, is high.

Biological false positive serological tests for syphilis in the Jamaican population.

A total of 19,067 sera were screened for biological false positive (BFP) reactivity by the Venereal Disease Research Laboratory (VDRL) test. Sera which were reactive in the VDRL test were confirmed by the fluorescent treponemal antibody absorption (FTA-ABS) test. BFP reactions were detected in 0.59% of the general population, 0.72% of pregnant women and 11.8% of patients with systemic lupus erythematosus (SLE). The rate of BFP reactors among pregnant women did not differ significantly from the general population. The female to male ratio of BFP in the general population was 2:1 whilst that in the group of patients with SLE was 8:1. The overall seroprevalence of syphilis was 2.2%.

Does a choice of condoms impact sexually transmitted infection incidence? A randomized, controlled trial.

Objective: The objective of this study was to assess whether providing a choice of condoms would increase condom acceptability, increase self-reported use, and decrease incident sexually transmitted infection. Study: We randomized 414 men presenting with urethral discharge in Jamaica to receive either the “standard” clinic condom or a choice of 4 different types of condoms. Men were treated presumptively at enrollment and followed up at 1, 2, 4, and 6 months. Results: Participants in the choice group had a strong preference (P <0.01) for the most popular condom available in Jamaica. This preference did not translate into higher condom use (P = 0.16). The 6-month cumulative probability of first incidence of gonorrhea, chlamydia, or trichomoniasis was slightly higher in the choice group (21%; 95% confidence interval [CI], 15–28%) versus the control group (17%; 95% CI, 11–23%); the difference in the survival curves was not significant (P = 0.35). Conclusion: A choice of condoms may increase perceived acceptability but not lead to increased condom use and subsequently lower sexually transmitted infection rates.

The Outcome of Lupus Nephritis in Jamaican Patients

We investigated the outcome of a cohort of black Jamaican patients with systemic lupus erythematosus (SLE) with nephritis. In 66 patients, 0 (0%), 15 (23%), 4 (6%), 32 (48%), 6 (9%), and 3 (5%) had classes 1, II, III, IV, V, and VI, respectively. Six (9%) had interstitial nephritis. The patients were placed in 2 groups for comparison. Group 1 (n = 36) consisted of classes III and IV and group 2 (n = 27), classes II and V, and interstitial nephritis. The patients in group 1 had significantly lower hemoglobin, higher mean serum creatinine, higher prevalence of hypertension, and chronicity scores. The duration of follow-up was similar between the 2 groups. The percent events free for ESRD or death at 1 year was 80.1% for group 1 and 77.4% for group 2; 2 years, 69.0% for group 1 and 77.4% group 2; 5 years, 69.0% for group 1 and 57.4% for group 2. The percent events free for death at 1 year was 93.4% in group 1 and 90.9% in group 2; at 2 years, 86.7% for group 1 and 90, 9% for group 2; and at 5 years was 86.7% for group 1 and 67.3% (29.5 to 88.0) for group 2. Sixteen patients (25.4%) developed ESRD or died. Prognosis was not different between the groups for ESRD or death (P = 0.22) or death alone (P = 0.63).