Stability of a monovalent rotavirus vaccine after exposure to different temperatures observed in KwaZulu-Natal, South Africa

Background: Rotavirus infection and its associated hospitalization of children less than 5 years old in middle- and low-income countries remains a public health challenge. We hypothesized that the Rotarix®potency is affected by non-optimal temperatures which translates into reduced vaccine effectiveness in these settings.Objective: To assess the effect of non-optimal temperatures on the potency of the Rotarix® vaccine in South Africa.Methods: Rotarix® vaccine was exposed to temperatures reflecting breaches in the cold chain. Vero cells (ATCC CCL-81) grown in a 24-well tissue culture plates were infected with Rotarix® vaccine viruses after exposure to non-optimal temperatures and the potency of the vaccine was determined using the plaque assay. Results: Exposure of the Rotarix® vaccine to seasonal temperatures in KwaZulu-Natal for 6 hours and to extreme temperatures of 40oC for 72 hours as well as to -20oC and -80oC for 12 hours did not affect the potency of the vaccine beyond its expected standard of >7 x 105 PFU/ml.Conclusion: This study revealed that the Rotarix® vaccine remains potent even after exposure to non-optimal temperatures. However, this study only explored the effect of a constant ‘adverse’ temperature on vaccine potency and not the effect of temperature fluctuations.Keywords: Monovalent rotavirus vaccine, KwaZulu-Natal, South Africa

Determinants of Symptomatic Vulvovaginal Candidiasis among Human Immunodeficiency Virus Type 1 Infected Women in Rural KwaZulu-Natal, South Africa

Introduction. We sought to determine the association between HIV-induced immunosuppression, virologic correlates, and vulvovaginal candidiasis (VVC). Methods. This is a retrospective cohort study, where HIV infected and uninfected women were studied with VVC being the primary outcome. Ninety-seven HIV-infected and 101 HIV-uninfected women were enrolled between June and December 2011. Cases of VVC were confirmed. HIV RNA load was determined by RT-PCR and CD4 counts were obtained from medical records. Results. Fifty-two of 97 (53.6%) HIV-infected and 38/101 (37.6%) HIV-uninfected women were diagnosed with VVC (P=0.032). The relative risk for VVC amongst HIV-infected patients was 1.53 (95% CI: 1.04–2 P=0.024). Cases of VVC increased at CD4+ T cell count below 200 cells/mm3 (P<0.0001) and plasma HIV RNA load above 10 000 copies/mL (P<0.0001). VVC was associated with increased genital shedding of HIV (P=0.002), and there was a linear correlation between plasma HIV load and genital HIV shedding (r=0.540; R2=0.292; P<0.0001). Women on HAART were 4-fold less likely (P=0.029) to develop VVC. Conclusion. CD4 counts below 200 cells/mm3 and plasma HIV loads ≥10 000 copies/mL were significantly associated with VVC

Understanding the host epigenetics in Mycobacterium tuberculosis infection

Epigenetics denotes to study the heritable changes occurred in the gene function without any changes in DNA sequence. These epigenetic changes are known to be governed by various factors viz. stress, infection, nutrients, drugs and toxicological agents etc. Recently, it has been identified that different microorganisms can cause the epigenetic changes in host. In this review we intend to address about the epigenetic changes occurred in host by Mycobacterium tuberculosis (M.tb) infection and then elaborate the current state of research about how Mtb. modulates host epigenome. M.tb induced epigenetic modifications which either leads to promote host defense or M.tb survival. Therefore, M.tb can be considered as potential modulator of host epigenome and consequently, these epigenetic changes can be beneficial or disastrous to M.tb. Currently, there is huge advances in sequencing technology and this can lead to a better understanding of the roles of epigenetics in the tuberculosis and other infectious diseases. Subsequently, therapeutic targeting of the epigenome can be potentially helpful in treatment of Mtb infection

Cellular architecture of spinal granulomas and the immunological response in tuberculosis patients coinfected with HIV

Mycobacterium tuberculosis (M.tb) and HIV are individually responsible for the most deaths worldwide among all infectious agents, and coinfection with M.tb and HIV is a significant public health challenge in the developing world. Although the lung is the primary target organ for tuberculosis (TB), M.tb can also cause extrapulmonary tuberculosis (EPTB) such as in the bones and joints. Treatment of EPTB is much more challenging than treatment of pulmonary TB. The hallmark of the host immune response against TB is the formation of organized structures called granulomas that are infiltrated with immune cells and are rich in cytokines and chemokines. Inside granulomas, the host confines the M.tb bacteria to a particular region of the organ and avoids dispersion. In this study, we analyzed immune cells in bone granulomas of patients with EPTB that are also coinfected with HIV. We found that HIV-infected TB patients have dispersed bone granulomas, with reduced T cell numbers and a concomitant increase in plasma cells. Additionally, HIV-infected patients exhibited dramatically increased serum levels of IgM and IgG1 antibodies, which is indicative of T-cell-independent B-cell activation and mucosal T-cell activation, respectively. Interestingly, we also observed that CD29+ stem cells are increased in HIV–TB coinfection, suggesting a link with HIV infection. Therefore, our work provides new insights into the architecture of spinal TB granulomas and the role of B-cells and humoral immunity against a highly infectious intracellular pathogen. We propose that our findings will inform biomarker identification for EPTB and possibly the development of related therapeutics and/or vaccines to protect HIV-infected patients against disseminated TB

Simultaneous inhibition of T helper 2 and T regulatory cell differentiation by small molecules enhances bacillus Calmette-Guerin vaccine efficacy against tuberculosis

Tuberculosis affects nine million individuals and kills almost two million people every year. The only vaccine available, Bacillus Calmette-Guerin (BCG), has been used since its inception in 1921. Although BCG induces host-protective T helper 1 (Th1) cell immune responses, which play a central role in host protection, its efficacy is unsatisfactory, suggesting that additional methods to enhance protective immune responses are needed. Recently we have shown that simultaneous inhibition of Th2 cells and Tregs by using the pharmacological inhibitors suplatast tosylate and D4476, respectively, dramatically enhances Mycobacterium tuberculosis clearance and induces superior Th1 responses. Here we show that treatment with these two drugs during BCG vaccination dramatically improves vaccine efficacy. Furthermore, we demonstrate that these drugs induce a shift in the development of T cell memory, favoring central memory T (Tcm) cell responses over effector memory T (Tem) cell responses. Collectively, our findings provide evidence that simultaneous inhibition of Th2 cells and Tregs during BCG vaccination promotes vaccine efficacy

High prevalence and incidence of asymptomatic sexually transmitted infections during pregnancy and postdelivery in KwaZulu Natal, South Africa.

CAPRISA, 2015.Abstract available in pdf

Stability of a monovalent rotavirus vaccine after exposure to different temperatures observed in KwaZulu-Natal, South Africa

Background: Rotavirus infection and its associated hospitalization of children less than 5 years old in middle- and low-income countries remains a public health challenge. We hypothesized that the Rotarix\uaepotency is affected by non-optimal temperatures which translates into reduced vaccine effectiveness in these settings. Objective: To assess the effect of non-optimal temperatures on the potency of the Rotarix\uae vaccine in South Africa. Methods: Rotarix\uae vaccine was exposed to temperatures reflecting breaches in the cold chain. Vero cells (ATCC CCL-81) grown in a 24-well tissue culture plates were infected with Rotarix\uae vaccine viruses after exposure to non-optimal temperatures and the potency of the vaccine was determined using the plaque assay. Results: Exposure of the Rotarix\uae vaccine to seasonal temperatures in KwaZulu-Natal for 6 hours and to extreme temperatures of 40oC for 72 hours as well as to -20oC and -80oC for 12 hours did not affect the potency of the vaccine beyond its expected standard of &gt;7 x 105 PFU/ml. Conclusion: This study revealed that the Rotarix\uae vaccine remains potent even after exposure to non-optimal temperatures. However, this study only explored the effect of a constant \u2018adverse\u2019 temperature on vaccine potency and not the effect of temperature fluctuations. DOI: https://dx.doi.org/10.4314/ahs.v19i2.22 Cite as: Asowata OE, Ashiru OT, Sturm AW, Moodley P. Stability of a monovalent rotavirus vaccine after exposure to different temperatures observed in KwaZulu-Natal, South Africa. Afri Health Sci.2019;19(2): 1993-1999. https://dx.doi.org/10.4314/ahs.v19i2.2

Spread of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal Province, South Africa

Background In 2005 a cluster of 53 HIV-infected patients with extensively drug-resistant tuberculosis (XDR-TB) was detected in the Msinga sub-district, the catchment area for the Church of Scotland Hospital (CoSH) in Tugela Ferry, in KwaZulu-Natal province (KZN), South Africa. KZN is divided into 11 healthcare districts. We sought to determine the distribution of XDR TB cases in the province in relation to population density. Methods In this cross-sectional study, the KZN tuberculosis laboratory database was analysed. Results of all patients with a sputum culture positive for Mycobacterium tuberculosis from January 2006 to June 2007 were included. Drug-susceptibility test results for isoniazid, rifampicin, ethambutol, streptomycin, kanamycin and ofloxacin were available for all patients as well as the location of the hospital where their clinical diagnosis was made. Findings In total, 20858 patients attending one of 73 hospitals or their adjacent clinics had cultures positive for M. tuberculosis. Of these, 4170 (20%) were MDR-TB cases. Four hundred and forty three (11%) of the MDR tuberculosis cases displayed the XDR tuberculosis susceptibility profile. Only 1429 (34%) of the MDR-TB patients were seen at the provincial referral hospital for treatment. The proportion of XDR-TB amongst culture-confirmed cases was highest in the Msinga sub-district (19.6%), followed by the remaining part of the Umzinyati district (5.9%) and the other 10 districts (1.1%). The number of hospitals with at least one XDR-TB case increased from 18 (25%) to 58 (80%) during the study period. Interpretation XDR-TB is present throughout KZN. More than 65% of all diagnosed MDR-TB cases, including XDR-TB patients, were left untreated and likely remained in the community as a source of infection

Expression of toll-like receptor (TLR)-2 and TLR4 in monocytes following stimulations by genital secretions of HIV infected and uninfected women with symptomatic vulvo-vaginal candidiasis

Vulvo-vaginal candidiasis (VVC) is a common condition in human immunodeficiency virus (HIV)- infected women. Toll-like receptor (TLR) 2 and TLR4 are key pattern-recognition receptors of the innate immune system in sensing Candida albicans. The aim of this study was to assess the expression of TLR2 and TLR4 signaling pathways in HIV-infected and uninfected women with VVC. Cervico-vaginal fluids (CVF) were obtained from 7 HIV infected and 11 HIV uninfected clinic attendees in KwaZulu-Natal between June, 2011 and December, 2011. VVC was diagnosed clinically and confirmed by Gram stain and culture of genital samples. Monocytes were isolated from a healthy adult volunteer, pre-incubated with anti-TLR2, anti-TLR4 and a combination of anti-TLR2/anti-TLR4 monoclonal antibodies. Monocytes were then stimulated by CVF. Levels of cytokines were measured by Luminex® multiplex immunoassays. Compared with baseline concentrations, stimulation with CVF of HIV+VVC+ women post-TLR2 blockage increased IL-6, IL-10 and IL-13 production by 165.5, 162.5 and 106.7%, respectively. Using paired T-tests, there was a significant difference in the increase of the concentrations of IL-6 (P = 0.04), IL-10 (P = 0.003), and IL-13 (P = 0.031) when comparing stimulation by CVF of HIV+VVC+ versus stimulation by CVF of HIV-VVC+ patients. There was a linear correlation between genital HIV RNA loads and mean level production of IL-6 (r = 0.722; R2 = 0.679; P = 0.067) as well as IL-8 (r = 0.910; R2 = 0.833; P = 0.004). Findings suggest potential roles of TLR2 in the pathogenesis of VVC among HIV-infected women

Mycobacterium tuberculosis TlyA protein negatively regulates T helper (Th) 1 and Th17 differentiation and promotes tuberculosis pathogenesis

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M. tuberculosis have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor in several bacterial infections and is evolutionarily conserved in many Gram-positive bacteria, but its function in M. tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M. tuberculosis. We show that a TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1β and IL-10 cytokine responses, which sharply contrasts with the immune responses induced by wild type M. tuberculosis. Furthermore, compared with wild type M. tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with the TlyA mutant M. tuberculosis organisms exhibited increased host-protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host evasion factor, thereby contributing to its virulence