56 research outputs found
Host immunity increases Mycobacterium tuberculosis reliance on cytochrome bd oxidase [preprint]
In order to sustain a persistent infection, Mycobacterium tuberculosis (Mtb) must adapt to a changing environment that is shaped by the developing immune response. This necessity to adapt is evident in the flexibility of many aspects of Mtb metabolism, including a respiratory chain that consists of two distinct terminal cytochrome oxidase complexes. Under the conditions tested thus far, the bc1/aa3 complex appears to play a dominant role, while the alternative bd oxidase is largely redundant. However, presence of two terminal oxidases in this obligate pathogen implies that respiratory requirements might change during infection. We report that the cytochrome bd oxidase is specifically required for resisting the adaptive immune response. While the bd oxidase was dispensable for growth in resting macrophages and the establishment of infection in mice, this complex was necessary for optimal fitness after the initiation of adaptive immunity. This requirement was dependent on lymphocyte-derived interferon gamma (IFNÎł), but did not involve nitrogen and oxygen radicals that are known to inhibit respiration in other contexts. Instead, we found that ÎcydA mutants were hypersusceptible to the low pH encountered in IFNÎł-activated macrophages. Unlike wild type Mtb, cytochrome bd-deficient bacteria were unable to sustain a maximal oxygen consumption rate (OCR) at low pH, indicating that the remaining cytochrome bc1/aa3 complex is preferentially inhibited under acidic conditions. Consistent with this model, the potency of the cytochrome bc1/aa3 inhibitor, Q203, is dramatically enhanced at low pH. This work identifies a critical interaction between host immunity and pathogen respiration that influences both the progression of the infection and the efficacy of potential new TB drugs
Reductions in abortion-related mortality following policy reform: evidence from Romania, South Africa and Bangladesh
Unsafe abortion is a significant contributor to worldwide maternal mortality; however, abortion law and policy liberalization could lead to drops in unsafe abortion and related deaths. This review provides an analysis of changes in abortion mortality in three countries where significant policy reform and related service delivery occurred. Drawing on peer-reviewed literature, population data and grey literature on programs and policies, this paper demonstrates the policy and program changes that led to declines in abortion-related mortality in Romania, South Africa and Bangladesh. In all three countries, abortion policy liberalization was followed by implementation of safe abortion services and other reproductive health interventions. South Africa and Bangladesh trained mid-level providers to offer safe abortion and menstrual regulation services, respectively, Romania improved contraceptive policies and services, and Bangladesh made advances in emergency obstetric care and family planning. The findings point to the importance of multi-faceted and complementary reproductive health reforms in successful implementation of abortion policy reform
Enhancing local medicine production in east and southern Africa
The policy brief identifies the barriers to local medicine production in East and Southern Africa (ESA) as: lack of supportive policies, capital and skills constraints, gaps in regulatory framework, small market size and weak research and development capacities. It provides highlights from case study work in selected countries, and references potential opportunities for strengthening local production. The paper proposes that African countries strengthen domestic capacities, co-operation between domestic private and public sectors within ESA countries, and regional co-operation across ESA countries to address bottlenecks
Enrolling adolescents in HIV vaccine trials: reflections on legal complexities from South Africa
<p>Abstract</p> <p>Background</p> <p>South Africa is likely to be the first country in the world to host an adolescent HIV vaccine trial. Adolescents may be enrolled in late 2007. In the development and review of adolescent HIV vaccine trial protocols there are many complexities to consider, and much work to be done if these important trials are to become a reality.</p> <p>Discussion</p> <p>This article sets out essential requirements for the lawful conduct of adolescent research in South Africa including compliance with consent requirements, child protection laws, and processes for the ethical and regulatory approval of research.</p> <p>Summary</p> <p>This article outlines likely complexities for researchers and research ethics committees, including determining that trial interventions meet current risk standards for child research. Explicit recommendations are made for role-players in other jurisdictions who may also be planning such trials. This article concludes with concrete steps for implementing these important trials in South Africa and other jurisdictions, including planning for consent processes; delineating privacy rights; compiling information necessary for ethics committees to assess risks to child participants; training trial site staff to recognize when disclosures trig mandatory reporting response; networking among relevant ethics commitees; and lobbying the National Regulatory Authority for guidance.</p
Maternal mental health in primary care in five low- and middle-income countries: a situational analysis
Policies and clinical practices relating to the management of gestational diabetes mellitus in the public health sector, South Africa â a qualitative study
BACKGROUND: Women with a prior gestational diabetes have an increased lifetime risk of developing type 2
diabetes. Although post-partum follow-up for GDM women is essential to prevent progression to type 2 diabetes, it
is poorly attended. The need for health systems interventions to support postpartum follow-up for GDM women is
evident, but there is little knowledge of actual current practice. The aim of this study was to explore current policies
and clinical practices relating to antenatal and post-natal care for women with GDM in South Africa, as well as
health sector stakeholdersâ perspectives on the barriers to â and opportunities for â delivering an integrated
mother - baby health service that extends beyond the first week post-partum, to the infantâs first year of life.
METHODS: Following a document review of policy and clinical practice guidelines, in-depth interviews were
conducted with 11 key informants who were key policy makers, health service managers and clinicians working in
the public health services in South Africaâs two major cities (Johannesburg and Cape Town). Data were analysed
using qualitative content analysis procedures.
RESULTS: The document review and interviews established that it is policy that health services adhere to
international guidelines for GDM diagnosis and management, in addition to locally developed guidelines and
protocols for clinical practice. All key informants confirmed that lack of postpartum follow-up for GDM women is a
significant problem. Health systems barriers include fragmentation of care and the absence of standardised
postnatal care for post-GDM women. Key informants also raised patient - related challenges including lack of
perceived future risk of developing type 2 diabetes and non-attendance for postpartum follow up, as barriers to
postnatal care for GDM women. All participants supported integrated primary health services but cautioned against
overloading health workers.
CONCLUSION: Although there is alignment between international guidelines, local policy and reported clinical
practice in the management of GDM, there is a gap in continuation of care in the postpartum period. Health
systems interventions that support and facilitate active follow-up for women with prior GDM are needed if high
rates of progression to type 2 diabetes are to be avoided
Are women with history of pre-eclampsia starting a new pregnancy in good nutritional status in South Africa and Zimbabwe?
Background
Maternal nutritional status before and during pregnancy is an important contributor to pregnancy outcomes and early child health. The aim of this study was to describe the preconceptional nutritional status and dietary intake during pregnancy in high-risk women from South Africa and Zimbabwe.
Methods
This is a prospective observational study, nested to the CAP trial. Anthropometric measurements before and during pregnancy and dietary intake using 24-h recall during pregnancy were assessed. The Intake Distribution Estimation software (PC-SIDE) was used to evaluate nutrient intake adequacy taking the Estimated Average Requirement (EAR) as a cut-off point.
Results
Three hundred twelve women who had pre-eclampsia in their last pregnancy and delivered in hospitals from South Africa and Zimbabwe were assessed. 73.7 and 60.2% women in South Africa and Zimbabwe, respectively started their pregnancy with BMI above normal (BMIââ„â25) whereas the prevalence of underweight was virtually non-existent. The majority of women had inadequate intakes of micronutrients. Considering food and beverage intake only, none of the micronutrients measured achieved the estimated average requirement. Around 60% of pregnant women reported taking folic acid or iron supplements in South Africa, but almost none did so in Zimbabwe.
Conclusion
We found a high prevalence of overweight and obesity and high micronutrient intake inadequacy in pregnant women who had the previous pregnancy complicated with pre-eclampsia. The obesity figures and micronutrient inadequacy are issues of concern that need to be addressed. Pregnant women have regular contacts with the health system; these opportunities could be used to improve diet and nutrition.
Trial registration
PACTR201105000267371
. Registered 06 December 2010
A comparative analysis of socioeconomic inequities in stunting: A case of three middle-income African countries
: Despite increased economic growth and development, and existence of various policies and
interventions aimed at improving food security and nutrition, majority of countries in sub-Saharan Africa have very
high levels of child malnutrition. The prevalence of stunting, an indicator of chronic malnutrition, is especially high. In this paper, we use Demographic and Health Survey datasets from three countries in the region that
obtained middle-income status over the last decade (Ghana, Kenya and Zambia), to provide a comparative
quantitative assessment of stunting levels, and examine patterns in stunting inequalities between 2007 and 2014
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic
This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic
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