Publications by authors named "Joseph Mulenga"

Purpose: Normative values of common sport-related concussion assessment tools may assist clinical diagnosis and management. However, current baseline normative values are not representative of athletic participants across international domains. This study develops healthy baseline norms on the Balance Error Scoring System (BESS), and King-Devick (K-D), providing baseline reference values for professional Zambian football athletes.

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Objective: Concussion is a global sport injury; however, this public health issue has yet to be studied across Africa. It is unknown if tests such as the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) Quick Test (QT) are culturally appropriate for implementation as part of a concussion screening protocol in Zambia or other African nations. Study objectives included: 1) establish that Zambian athletes are able to complete the iPad-based ImPACT QT with respect to language or cultural barriers that may exist, and 2) document baseline neurocognitive percentile ranks among Zambian football athletes on the ImPACT QT.

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Introduction: Couples' voluntary HIV counselling and testing (CVCT) is a high-impact HIV prevention intervention in Rwanda and Zambia. Our objective was to model the cost-per-HIV infection averted by CVCT in six African countries guided by an HIV prevention cascade framework. The HIV prevention cascade as yet to be applied to evaluating CVCT effectiveness or cost-effectiveness.

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Background: The impact and cost-effectiveness of couples' voluntary HIV counselling and testing (CVCT) has not been quantified in real-world settings. We quantify cost-per-HIV-infection averted by CVCT in Zambia from the donor's perspective.

Methods: From 2010 to 2016, CVCT was established in 73 Zambian government clinics.

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Aim: To characterize antiviral therapy eligibility among hepatitis B virus (HBV)-infected adults at a university hospital in Zambia.

Methods: Hepatitis B surface antigen-positive adults ( = 160) who were HIV-negative and referred to the hospital after a routine or clinically-driven HBV test were enrolled. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), platelet count, hepatitis B e-antigen, and HBV DNA were measured.

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Introduction: Attempts to conceive and pregnancy may increase HIV transmission to sex partners and infants. Our study evaluated the association between fertility intentions and HIV acquisition among Zambian HIV-serodiscordant couples.

Methods: We collected demographic, behavioral, clinical exposures, and data on fertility intentions in a cohort of HIV-serodiscordant couples in Lusaka, Zambia from 2005 to 2012.

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The article Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It?, written by Dvora Joseph Davey, William Kilembe, Kristin M. Wall, Naw Htee Khu, Ilene Brill, Bellington Vwalika, Elwyn Chomba, Joseph Mulenga, Amanda Tichacek, Marjan Javanbakht, W. Scott Comulada, Susan Allen, Pamina M.

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Objective: Evaluate the incidence and predictors of HIV acquisition from outside partners in serodiscordant couples.

Methods: Demographic, behavioral, and clinical exposures were measured quarterly in a cohort of serodiscordant cohabiting couples in Zambia from 1995 to 2012 (n = 3049). Genetic analysis classified incident infections as those acquired from the study partner (linked) or acquired from an outside partner (unlinked).

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Background: Studies have demonstrated the role of ulcerative and non-ulcerative sexually transmitted infections (STI) in HIV transmission/acquisition risk; less is understood about the role of non-specific inflammatory genital abnormalities.

Methods: HIV-discordant heterosexual Zambian couples were enrolled into longitudinal follow-up (1994-2012). Multivariable models estimated the effect of genital ulcers and inflammation in both partners on time-to-HIV transmission within the couple.

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In this paper we evaluate the effects of heavy alcohol consumption on sexual behavior, HIV acquisition, and antiretroviral treatment (ART) initiation in a longitudinal open cohort of 1929 serodiscordant couples in Lusaka, Zambia from 2002 to 2012. We evaluated factors associated with baseline heavy alcohol consumption and its association with condomless sex with the study partner, sex outside of the partnership, and ART initiation using multivariable logistic regression. We estimated the effect of alcohol consumption on HIV acquisition using multivariable Cox models.

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Background: We present temporal trends in self-reported and biological markers of unprotected sex and sex with concurrent partners in discordant couples receiving couples' voluntary HIV counselling and testing (CVCT).

Methods: Heterosexual Zambian HIV-serodiscordant couples were enrolled into longitudinal follow-up in an open cohort (1994-2012). Multivariable Anderson-Gill models explored predictors of self-report and biological indicators of unprotected sex within (including sperm on a vaginal swab, incident pregnancy or incident linked HIV infection) and outside (including self-report, STI and unlinked HIV infection) the union.

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Background: Some studies suggest that hormonal contraception, pregnancy, and/or breastfeeding may influence rates of HIV disease progression.

Methods: From 1994 to 2012, HIV discordant couples recruited at couples' voluntary HIV counseling and testing centers in Lusaka were followed 3-monthly. Multivariate survival analyses explored associations between time-varying contraception, pregnancy, and breastfeeding and 2 outcomes among HIV-positive women: (1) time to death and (2) time to antiretroviral treatment (ART) initiation.

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Objectives: To investigate the effect of seasonal variation on adult clinical laboratory parameters in Rwanda, Zambia, and Uganda and determine its implications for HIV prevention and other clinical trials.

Methods: Volunteers in a cross-sectional study to establish laboratory reference intervals were asked to return for a seasonal visit after the local season had changed from dry to rainy or vice versa. Volunteers had to be clinically healthy, not pregnant and negative for HIV, Hepatitis B and C, and syphilis infection at both visits.

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Article Synopsis
  • The study indicates that Zambian individuals with HIV-1 superinfection show low binding and neutralizing antibody responses to their initial HIV-1 strain, potentially making them more vulnerable to re-infection.
  • Researchers found that these superinfected individuals also have reduced antibody-dependent cellular cytotoxicity (ADCC) activity, which is essential for killing virus-infected cells, when compared to non-superinfected individuals.
  • Despite the low ADCC activity, superinfected individuals maintain similar levels of antibodies that react to CMV, indicating they can still develop and keep virus-specific antibodies.
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Background: Human leukocyte allele (HLA) class I polymorphism has the greatest impact of human genetic variation on viral load set point. A substantial part of this effect is due to the action of HLA-B and HLA-C alleles. With few exceptions the role of HLA-A molecules in immune control of HIV is unclear.

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Background: Syphilis continues to be a common sexually transmitted infection, despite the availability of inexpensive and effective treatment. Infection in human immunodeficiency virus (HIV)-discordant couples is important because syphilis increases the risk of HIV acquisition. Current US treatment guidelines recommend 1 dose of benzathine penicillin for early syphilis, irrespective of HIV status, but data from coinfected patients are limited.

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Initial studies of 88 transmission pairs in the Zambia Emory HIV Research Project cohort demonstrated that the number of transmitted HLA-B associated polymorphisms in Gag, but not Nef, was negatively correlated to set point viral load (VL) in the newly infected partners. These results suggested that accumulation of CTL escape mutations in Gag might attenuate viral replication and provide a clinical benefit during early stages of infection. Using a novel approach, we have cloned gag sequences isolated from the earliest seroconversion plasma sample from the acutely infected recipient of 149 epidemiologically linked Zambian transmission pairs into a primary isolate, subtype C proviral vector, MJ4.

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Background: The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb) responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion.

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Objectives: Hypothesising that couples' voluntary counselling and testing (CVCT) promotions can increase CVCT uptake, this study identified predictors of successful CVCT promotion in Lusaka, Zambia.

Design: Cohort study.

Setting: Lusaka, Zambia.

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A critical step in HIV-1 transmission studies is the rapid and accurate identification of epidemiologically linked transmission pairs. To date, this has been accomplished by comparison of polymerase chain reaction (PCR)-amplified nucleotide sequences from potential transmission pairs, which can be cost-prohibitive for use in resource-limited settings. Here we describe a rapid, cost-effective approach to determine transmission linkage based on the heteroduplex mobility assay (HMA), and validate this approach by comparison to nucleotide sequencing.

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Human leukocyte antigen alleles influence the immune response to HIV-1. Signal peptides cleaved from those alleles bind to HLA-E and mediate natural killer cell function. Signal peptides of HLA-A and HLA-C proteins carry methionine (Met) at anchor position 2 (P2); those of HLA-B carry Met or threonine (Thr).

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Background: HIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner.

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Objective: To describe symptoms, physical examination findings, and set-point viral load associated with acute HIV seroconversion in a heterosexual cohort of HIV-discordant couples in Zambia.

Design: We followed HIV serodiscordant couples in Lusaka, Zambia from 1995 to 2009 with HIV testing of negative partners and symptom inventories 3 monthly, and physical examinations annually.

Methods: We compared prevalence of self-reported or treated symptoms (malaria syndrome, chronic diarrhea, asthenia, night sweats, and oral candidiasis) and annual physical examination findings (unilateral or bilateral neck, axillary, or inguinal adenopathy; and dermatosis) in seroconverting vs.

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The predominant mode of HIV-1 infection is heterosexual transmission, where a genetic bottleneck is imposed on the virus quasispecies. To probe whether limited genetic diversity in the genital tract (GT) of the transmitting partner drives this bottleneck, viral envelope sequences from the blood and genital fluids of eight transmission pairs from Rwanda and Zambia were analyzed. The chronically infected transmitting partner's virus population was heterogeneous with distinct genital subpopulations, and the virus populations within the GT of two of four women sampled longitudinally exhibited evidence of stability over time intervals on the order of weeks to months.

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