Browsing by Subject "Infectious disease control"

Now showing 1 - 11 of 11
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    A century of tuberculosis epidemiology in the northern and southern hemisphere: the differential impact of control interventions
    (Public Library of Science, 2015) Hermans, Sabine; Jr, C Robert Horsburgh; Wood, Robin
    BACKGROUND: Cape Town has one of the highest TB burdens of any city in the world. In 1900 the City of Cape Town, New York City and London had high mortality of tuberculosis (TB). Throughout the 20th century contemporaneous public health measures including screening, diagnosis and treatment were implemented in all three settings. Mandatory notification of TB and vital status enabled comparison of disease burden trajectories. METHODS: TB mortality, notification and case fatality rates were calculated from 1912 to 2012 using annual TB notifications, TB death certifications and population estimates. Notification rates were stratified by age and in Cape Town by HIV status (from 2009 onwards). RESULTS: Pre-chemotherapy, TB mortality and notification rates declined steadily in New York and London but remained high in Cape Town. Following introduction of combination chemotherapy, mean annual case fatality dropped from 45-60% to below 10% in all three settings. Mortality and notification rates subsequently declined, although Cape Town notifications did not decline as far as those in New York or London and returned to pre-chemotherapy levels by 1980. The proportional contribution of childhood TB diminished in New York and London but remained high in Cape Town. The advent of the Cape Town HIV-epidemic in the 1990s was associated with a further two-fold increase in incidence. In 2012, notification rates among HIV-negatives remained at pre-chemotherapy levels. CONCLUSIONS: TB control was achieved in New York and London but failed in Cape Town. The TB disease burden trajectories started diverging before the availability of combination chemotherapy in 1952 and further diverged following the HIV epidemic in 1990. Chemotherapy impacted case fatality but not transmission, evidenced by on-going high childhood TB rates. Currently endemic TB results from high on-going transmission, which has been exacerbated by the HIV epidemic. TB control will require reducing transmission, which is inexorably linked to prevailing socio-economic factors.
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    Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection
    (Public Library of Science, 2007) Radwanska, Magdalena; Cutler, Antony J; Hoving, J Claire; Magez, Stefan; Holscher, Christoph; Bohms, Andreas; Arendse, Berenice; Kirsch, Richard; Hunig, Thomas; Alexander, James
    Author Summary Leishmaniasis is a disease induced by a protozoan parasite and transmitted by the sandfly. Several forms of infection are identified, and the different diseases have wide-ranging symptoms from localized cutaneous sores to visceral disease affecting many internal organs. Animal models of human cutaneous leishmaniasis have been established in which disease is induced by infecting mice subcutaneously with Leishmania major. Different strains of inbred mice have been found to be susceptible or resistant to L. major infection. "Healer" C57BL/6 mice control infection with transient lesion development. The protective response to infection in this strain is dominated by type 1 cytokines inducing parasite killing by nitric oxide. Conversely, "nonhealer" BALB/c mice are unable to control infection and develop nonhealing lesions associated with a dominant type 2 immune response driven by cytokines IL-4 and IL-13. However, mice deficient in IL-4/IL-13 signaling are not protected against development of cutaneous leishmaniasis. Here we describe a BALB/c mouse where the ability to polarize to a dominant type 2 response is removed by cell-specific deletion of the receptor for IL-4/IL-13 on CD4 + T cells. These mice are resistant to L. major infection similar to C57BL/6 mice, which highlights the role of T helper 2 cells in driving susceptibility and the protective role of IL-4/IL-13 signaling in non-CD4 + T cells in BALB/c mice.
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    Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa
    (Public Library of Science, 2005) Barnes, Karen I; Durrheim, David N; Little, Francesca; Jackson, Amanda; Mehta, Ushma; Allen, Elizabeth; Dlamini, Sicelo S; Tsoka, Joyce; Bredenkamp, Barry; Mthembu, D Jotham
    In KwaZulu-Natal strengthening of vector control and a change in antimalarial treatment policy to use of artemether-lumefantrine has been associated with a decrease in malaria cases, admissions, and deaths.
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    The effect of complete integration of HIV and TB services on time to initiation of antiretroviral therapy: a before-after study
    (Public Library of Science, 2012) Kerschberger, Bernhard; Hilderbrand, Katherine; Boulle, Andrew M; Coetzee, David; Goemaere, Eric; Azevedo, Virginia De; Cutsem, Gilles Van
    BACKGROUND: Studies have shown that early ART initiation in TB/HIV co-infected patients lowers mortality. One way to implement earlier ART commencement could be through integration of TB and HIV services, a more efficient model of care than separate, vertical programs. We present a model of full TB/HIV integration and estimate its effect on time to initiation of ART. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively reviewed TB registers and clinical notes of 209 TB/HIV co-infected adults with a CD4 count <250 cells/µl and registered for TB treatment at one primary care clinic in a South African township between June 2008 and May 2009. Using Kaplan-Meier and Cox proportional hazard analysis, we compared time between initiation of TB treatment and ART for the periods before and after full, "one-stop shop" integration of TB and HIV services (in December 2009). Potential confounders were determined a priori through directed acyclic graphs. Robustness of assumptions was investigated by sensitivity analyses. The analysis included 188 patients (100 pre- and 88 post-integration), yielding 56 person-years of observation. Baseline characteristics of the two groups were similar. Median time to ART initiation decreased from 147 days (95% confidence interval [CI] 85-188) before integration of services to 75 days (95% CI 52-119) post-integration. In adjusted analyses, patients attending the clinic post-integration were 1.60 times (95% CI 1.11-2.29) more likely to have started ART relative to the pre-integration period. Sensitivity analyses supported these findings. Conclusions/Significance Full TB/HIV care integration is feasible and led to a 60% increased chance of co-infected patients starting ART, while reducing time to ART initiation by an average of 72 days. Although these estimates should be confirmed through larger studies, they suggest that scale-up of full TB/HIV service integration in high TB/HIV prevalence settings may shorten time to ART initiation, which might reduce excess mortality and morbidity.
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    Exploring the seasonality of reported treated malaria cases in Mpumalanga, South Africa
    (Public Library of Science, 2013) Silal, Sheetal Prakash; Barnes, Karen I; Kok, Gerdalize; Mabuza, Aaron; Little, Francesca
    South Africa, having met the World Health Organisation's pre-elimination criteria, has set a goal to achieve malaria elimination by 2018. Mpumalanga, one of three provinces where malaria transmission still occurs, has a malaria season subject to unstable transmission that is prone to sporadic outbreaks. As South Africa prepares to intensify efforts towards malaria elimination, there is a need to understand patterns in malaria transmission so that efforts may be targeted appropriately. This paper describes the seasonality of transmission by exploring the relationship between malaria cases and three potential drivers: rainfall, geography (physical location) and the source of infection (local/imported). Seasonal decomposition of the time series by Locally estimated scatterplot smoothing is applied to the case data for the geographical and source of infection sub-groups. The relationship between cases and rainfall is assessed using a cross-correlation analysis. The malaria season was found to have a short period of no/low level of reported cases and a triple peak in reported cases between September and May; the three peaks occurring in October, January and May. The seasonal pattern of locally-sourced infection mimics the triple-peak characteristic of the total series while imported infections contribute mostly to the second and third peak of the season (Christmas and Easter respectively). Geographically, Bushbuckridge municipality, which exhibits a different pattern of cases, contributed mostly to the first and second peaks in cases while Maputo province (Mozambique) experienced a similar pattern in transmission to the imported cases. Though rainfall lagged at 4 weeks was significantly correlated with malaria cases, this effect was dampened due to the growing proportion of imported cases since 2006. These findings may be useful as they enhance the understanding of the current incidence pattern and may inform mathematical models that enable one to predict the impact changes in these drivers will have on malaria transmission.
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    Hitting a Moving Target: A Model for Malaria Elimination in the Presence of Population Movement
    (Public Library of Science, 2015) Silal, Sheetal Prakash; Little, Francesca; Barnes, Karen Irma; White, Lisa Jane
    South Africa is committed to eliminating malaria with a goal of zero local transmission by 2018. Malaria elimination strategies may be unsuccessful if they focus only on vector biology, and ignore the mobility patterns of humans, particularly where the majority of infections are imported. In the first study in Mpumalanga Province in South Africa designed for this purpose, a metapopulation model is developed to assess the impact of their proposed elimination-focused policy interventions. A stochastic, non-linear, ordinary-differential equation model is fitted to malaria data from Mpumalanga and neighbouring Maputo Province in Mozambique. Further scaling-up of vector control is predicted to lead to a minimal reduction in local infections, while mass drug administration and focal screening and treatment at the Mpumalanga-Maputo border are predicted to have only a short-lived impact. Source reduction in Maputo Province is predicted to generate large reductions in local infections through stemming imported infections. The mathematical model predicts malaria elimination to be possible only when imported infections are treated before entry or eliminated at the source suggesting that a regionally focused strategy appears needed, for achieving malaria elimination in Mpumalanga and South Africa.
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    Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults
    (Public Library of Science, 2011) Glennie, Sarah J; Sepako, Enoch; Mzinza, David; Harawa, Visopo; Miles, David J C; Jambo, Kondwani C; Gordon, Stephen B; Williams, Neil A; Heyderman, Robert S
    Objective Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. METHODS: Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-γ, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. RESULTS: We find that in asymptomatic HIV-infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4 + CD38 + PD-1 + and CD4 + CD25 high Foxp3 + Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. CONCLUSION: Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers.
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    Influence of Human Immunodeficiency Virus and other risk factors on tuberculosis
    (2015) Mahtab, Sana; Coetzee, David
    Introduction: Tuberculosis (TB) notification in South Africa has increased six fold over the last two decades mainly because of the Human Immunodeficiency Virus (HIV) epidemic. Globally, it was estimated that 73% of the TB cases were co-infected with HIV with more than 25% of this global co-infection burden being in South Africa alone. In 2012, globally 1.3 million deaths occurred due to TB; moreover 0.3 million were HIV-associated TB death. In 2010 TB was the leading cause of natural deaths in the population aged 15 to 24 years accounting for 14% of the total deaths in South Africa. In 2013 the proportion of patients with TB who were co-infected with HIV was extremely high at 62%.The outcome of co-infected patients was poorer than the outcome of HIV negative TB patients. However, there is little information available on the risk factors associated with TB treatment outcomes and the influence of co-infection. Method: A cross sectional study analysed Electronic TB Register (ETR.net) data from the Metro East Geographic Service Area (GSA) of the Cape Town Metro district. The dataset included adult patients aged 15 years or more, who initiated TB treatment between 1st July 2011 and 30th June 2012. In the descriptive analysis we analysed death separately but for the regression we merged death with unfavourable treatment outcome. Relative risks were used for measures of association. Univariate and multivariate analyses were performed using a generalized linear regression model. Statistically significant variables in the univariate analysis were included in the multivariate analysis. Findings: TB case notification in Eastern GSA was 922 per 100 000 population. Of the 12672 TB patients registered, 50% were co-infected with HIV. The incidence of death in co-infected was 5% versus 3% in uninfected, treatment success 67% versus 73% and unfavourable treatment outcome 28% versus 24%. The Khayelitsha sub-district had the highest proportion of the TB burden (37%) and of co-infection (65%). Fourteen percent of patients had extra-pulmonary TB (EPTB), 66% of whom were co-infected with HIV. In the multivariate analysis HIV (RR 1.2), retreatment (RR 1.4) and sputum smear microscopy not done (RR 1.4) were significantly associated with unfavourable treatment outcome. The sub districts Eastern (RR 0.9) and Northern (RR 0.7) were less likely to develop unfavourable outcome compared to Khayelitsha. In the stratified analysis, retreatment (RR 1.3) and smear not done (RR 1.3) were significant risk factors for an unfavourable treatment outcome in co-infected patients. Amongst HIV negative patients retreatment (RR 1.6) and smear not done (RR 1.6) were significant risk factors for an unfavourable treatment outcome. Conclusions: The incidence of TB is extremely high in the Eastern GSA of Cape Town however the prevalence of co-infection varies across the sub-districts. Although treatment outcomes have been improving, co-infection, retreatment and smear microscopy not done pre-treatment were factors significantly associated with an unfavourable treatment outcome. Eastern and Northern sub-districts were significantly more likely to have favourable treatment outcomes compared to Khayelitsha, where both TB incidence and HIV co-infection were greatest.
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    Limited Contribution of IL-36 versus IL-1 and TNF Pathways in Host Response to Mycobacterial Infection
    (Public Library of Science, 2015) Segueni, Noria; Vigne, Solenne; Palmer, Gaby; Bourigault, Marie-Laure; Olleros, Maria L.; Vesin, Dominique; Garcia, Irene; Ryffel, Bernhard; Quesniaux, Valérie F. J.; Gabay, Cem
    IL-36 cytokines are members of the IL-1 family of cytokines that stimulate dendritic cells and T cells leading to enhanced T helper 1 responses in vitro and in vivo ; however, their role in host defense has not been fully addressed thus far. The objective of this study was to examine the role of IL-36R signaling in the control of mycobacterial infection, using models of systemic attenuated M . bovis BCG infection and virulent aerogenic M . tuberculosis infection. IL-36γ expression was increased in the lung of M . bovis BCG infected mice. However, IL-36R deficient mice infected with M . bovis BCG showed similar survival and control of the infection as compared to wild-type mice, although their lung pathology and CXCL1 response were transiently different. While highly susceptible TNF-α deficient mice succumbed with overwhelming M . tuberculosis infection, and IL-1RI deficient mice showed intermediate susceptibility, IL-36R-deficient mice controlled the infection, with bacterial burden, lung inflammation and pathology, similar to wild-type controls. Therefore, IL-36R signaling has only limited influence in the control of mycobacterial infection.
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    Outbreak of multi-drug resistant Pseudomonas aeruginosa bloodstream infection in the haematology unit of a South African academic hospital
    (Public Library of Science, 2013) Mudau, Maanda; Jacobson, Rachael; Minenza, Nadia; Kuonza, Lazarus; Morris, Vida; Engelbrecht, Heather; Nicol, Mark P; Bamford, Colleen
    Objective: To describe an outbreak of multi-resistant Pseudomonas aeruginosa bloodstream infections (MRPA-BSI) that occurred in the haematology ward of a tertiary academic hospital in Cape Town, South Africa, and determine risk factors for acquisition of MRPA-BSI. METHODS: The outbreak investigation included a search for additional cases, review of patient records, environmental and staff screening, molecular typing using pulsed-field gel electrophoresis (PFGE) and Multi-locus sequencing (MLST) and a retrospective case-control study. RESULTS: Ten MRPA-BSI cases occurred in the haematology ward between January 2010 and January 2011. The case fatality rate was 80%. Staff screening specimens were negative for MRPA and an environmental source was not identified. PFGE showed that 9/10 isolates were related. MLST showed that 3 of these 9 isolates belonged to Sequence type (ST) 233 while the unrelated isolate belonged to ST260. CONCLUSION: We have described an outbreak of MRPA-BSI occurring over an extended period of time among neutropenic haematology patients. Molecular typing confirms that the outbreak was predominantly due to a single strain. The source of the outbreak was not identified, but the outbreak appears to have been controlled following intensive infection control measures.
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    Wind-driven roof turbines: a novel way to improve ventilation for TB infection control in health facilities
    (Public Library of Science, 2012) Cox, Helen; Escombe, Rod; McDermid, Cheryl; Mtshemla, Yolanda; Spelman, Tim; Azevedo, Virginia; London, Leslie
    Objective Tuberculosis transmission in healthcare facilities contributes significantly to the TB epidemic, particularly in high HIV settings. Although improving ventilation may reduce transmission, there is a lack of evidence to support low-cost practical interventions. We assessed the efficacy of wind-driven roof turbines to achieve recommended ventilation rates, compared to current recommended practices for natural ventilation (opening windows), in primary care clinic rooms in Khayelitsha, South Africa. METHODS: Room ventilation was assessed (CO 2 gas tracer technique) in 4 rooms where roof turbines and air-intake grates were installed, across three scenarios: turbine, grate and window closed, only window open, and only turbine and grate open, with concurrent wind speed measurement. 332 measurements were conducted over 24 months. FINDINGS: For all 4 rooms combined, median air changes per hour (ACH) increased with wind speed quartiles across all scenarios. Higher median ACH were recorded with open roof turbines and grates, compared to open windows across all wind speed quartiles. Ventilation with open turbine and grate exceeded WHO-recommended levels (60 Litres/second/patient) for 95% or more of measurements in 3 of the 4 rooms; 47% in the remaining room, where wind speeds were lower and a smaller diameter turbine was installed. CONCLUSION: High room ventilation rates, meeting recommended thresholds, may be achieved using wind-driven roof turbines and grates, even at low wind speeds. Roof turbines and air-intake grates are not easily closed by staff, allowing continued ventilation through colder periods. This simple, low-cost technology represents an important addition to our tools for TB infection control.