Correction: Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

[This corrects the article DOI: 10.1371/journal.pmed.1003793.].

The role of modelling and analytics in South African COVID-19 planning and budgeting.

BACKGROUND: The South African COVID-19 Modelling Consortium (SACMC) was established in late March 2020 to support planning and budgeting for COVID-19 related healthcare in South Africa. We developed several tools in response to the needs of decision makers in the different stages of the epidemic, allowing the South African government to plan several months ahead. METHODS: Our tools included epidemic projection models, several cost and budget impact models, and online dashboards to help government and the public visualise our projections, track case development and forecast hospital admissions. Information on new variants, including Delta and Omicron, were incorporated in real time to allow the shifting of scarce resources when necessary. RESULTS: Given the rapidly changing nature of the outbreak globally and in South Africa, the model projections were updated regularly. The updates reflected 1) the changing policy priorities over the course of the epidemic; 2) the availability of new data from South African data systems; and 3) the evolving response to COVID-19 in South Africa, such as changes in lockdown levels and ensuing mobility and contact rates, testing and contact tracing strategies and hospitalisation criteria. Insights into population behaviour required updates by incorporating notions of behavioural heterogeneity and behavioural responses to observed changes in mortality. We incorporated these aspects into developing scenarios for the third wave and developed additional methodology that allowed us to forecast required inpatient capacity. Finally, real-time analyses of the most important characteristics of the Omicron variant first identified in South Africa in November 2021 allowed us to advise policymakers early in the fourth wave that a relatively lower admission rate was likely. CONCLUSION: The SACMC's models, developed rapidly in an emergency setting and regularly updated with local data, supported national and provincial government to plan several months ahead, expand hospital capacity when needed, allocate budgets and procure additional resources where possible. Across four waves of COVID-19 cases, the SACMC continued to serve the planning needs of the government, tracking waves and supporting the national vaccine rollout.

Mobilizing resources with an investment case to mitigate cross-border malaria transmission and achieve malaria elimination in South Africa.

South Africa's effort to eliminate malaria is significantly challenged by a large number of imported malaria cases, especially from neighbouring Mozambique. The country has a funding gap to achieve its malaria elimination goals (prior to 2019) and is ineligible to receive a national allocation from the Global Fund. The findings of an IC were utilised to successfully mobilise resources for malaria elimination in South Africa in 2018. A five-step resource mobilisation strategy was implemented to highlight financing challenges and leverage the economic evidence from an IC for malaria elimination in South Africa. South Africa's malaria programme implements control and elimination activities in three malaria-endemic provinces (KwaZulu Natal, Limpopo, and Mpumalanga). Driven by the IC findings, the South African government took an unprecedented step and increased total domestic malaria financing by approximately 36%, from the 2018/19 to the 2019/20 financial years through the creation of a new conditional grant for malaria. The IC findings predicted that malaria control in southern Mozambique is a prerequisite to eliminate malaria in South Africa. Based on this, the South African government also allocated funding towards a co-financing mechanism to support malaria control efforts in southern Mozambique. The IC findings assisted the South African National Department of Health to make a convincing case to key government decision-makers to invest in national malaria elimination and maximise economic returns in the long run. The South African government is the first in Southern Africa to mobilise a significant increase in domestic malaria financing to address the financial sustainability of both national and regional malaria elimination efforts. Continued surveillance activities will be required to prevent the re-establishment of malaria transmission even after malaria elimination is achieved in South Africa. Information sharing and close collaboration with provincial and national government officials were key to the successful outcome.

A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa.

BACKGROUND: While some evidence has been demonstrated the cost-effectiveness of routine hepatitis A vaccination in middle-income countries, the evidence is still limited in other settings including in South Africa. Given this, the evidence base around the cost of care for hepatitis A needs to be developed towards considerations of introducing hepatitis A vaccines in the national immunisation schedule and guidelines. OBJECTIVES: To describe the severity, clinical outcomes, and cost of hepatitis A cases presenting to two tertiary healthcare centers in Cape Town, South Africa. METHODS: We conducted a retrospective folder review of patients presenting with hepatitis A at two tertiary level hospitals providing care for urban communities of metropolitan Cape Town, South Africa. Patients included in this folder review tested positive for hepatitis A immunoglobulin M between 1 January 2008 and 1 March 2018. RESULTS: In total, 239 folders of hepatitis A paediatric patients < 15 years old and 212 folders of hepatitis A adult patients [Formula: see text] 15 years old were included in the study. Before presenting for tertiary level care, more than half of patients presented for an initial consultation at either a community clinic or general physician. The mean length of hospital stay was 7.45 days for adult patients and 3.11 days for paediatric patients. Three adult patients in the study population died as a result of hepatitis A infection and 29 developed complicated hepatitis A. One paediatric patient in the study population died as a result of hepatitis A infection and 27 developed complicated hepatitis A, including 4 paediatric patients diagnosed with acute liver failure. The total cost per hepatitis A hospitalisation was $1935.41 for adult patients and $563.06 for paediatric patients, with overhead costs dictated by the length of stay being the largest cost driver. CONCLUSION: More than 1 in every 10 hepatitis A cases (13.3%) included in this study developed complicated hepatitis A or resulted in death. Given the severity of clinical outcomes and high costs associated with hepatitis A hospitalisation, it is important to consider the introduction of hepatitis A immunisation in the public sector in South Africa to potentially avert future morbidity, mortality, and healthcare spending.

Assessing the effectiveness of malaria interventions at the regional level in Ghana using a mathematical modelling application.

Supporting malaria control with interfaced applications of mathematical models that enables investigating effectiveness of various interventions as well as their cost implications could be useful. Through their usage for planning, these applications may improve the prospects of attaining various set targets such as those of the National Strategic Plan policies for malaria control in Ghana. A malaria model was adapted and used for simulating the incidence of malaria in various regions of Ghana. The model and its application were developed by the Modelling and Simulation Hub Africa and calibrated using district level data in Ghana from 2012 to 2018. Average monthly rainfall at the zonal level was fitted to trigonometric functions for each ecological zone using least squares approach. These zonal functions were then used as forcing functions. Subsequently, various intervention packages were investigated to observe their impact on averting malaria incidence by 2030. Increased usage of bednets but not only coverage levels, predicted a significant proportion of cases of malaria averted in all regions. Whereas, improvements in the health system by way of health seeking, testing and treatment predicted a decline in incidence largely in all regions. With an increased coverage of SMC, to include higher age groups, a modest proportion of cases could be averted in populations of the Guinea savannah. Indoor residual spraying could also benefit populations of the Transitional forest and Coastal savannah as its impact is significant in averting incidence. Enhancing bednet usage to at least a doubling of the current usage levels and deployed in combination with various interventions across regions predicted significant reductions, in malaria incidence. Regions of the Transitional forest and Coastal savannah could also benefit from a drastic decline in incidence following a gradual introduction of indoor residual spraying on a sustained basis.

Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

BACKGROUND: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. METHODS AND FINDINGS: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. CONCLUSIONS: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

Investment case for malaria elimination in South Africa: a financing model for resource mobilization to accelerate regional malaria elimination.

BACKGROUND: Malaria continues to be a public health problem in South Africa. While the disease is mainly confined to three of the nine provinces, most local transmissions occur because of importation of cases from neighbouring countries. The government of South Africa has reiterated its commitment to eliminate malaria within its borders. To support the achievement of this goal, this study presents a cost-benefit analysis of malaria elimination in South Africa through simulating different scenarios aimed at achieving malaria elimination within a 10-year period. METHODS: A dynamic mathematical transmission model was developed to estimate the costs and benefits of malaria elimination in South Africa between 2018 and 2030. The model simulated a range of malaria interventions and estimated their impact on the transmission of Plasmodium falciparum malaria between 2018 and 2030 in the three endemic provinces of Limpopo, Mpumalanga and KwaZulu-Natal. Local financial, economic, and epidemiological data were used to calibrate the transmission model. RESULTS: Based on the three primary simulated scenarios: Business as Usual, Accelerate and Source Reduction, the total economic burden was estimated as follows: for the Business as Usual scenario, the total economic burden of malaria in South Africa was R 3.69 billion (USD 223.3 million) over an 11-year period (2018-2029). The economic burden of malaria was estimated at R4.88 billion (USD 295.5 million) and R6.34 billion (~ USD 384 million) for the Accelerate and Source Reduction scenarios, respectively. Costs and benefits are presented in midyear 2020 values. Malaria elimination was predicted to occur in all three provinces if the Source Reduction strategy was adopted to help reduce malaria rates in southern Mozambique. This could be achieved by limiting annual local incidence in South Africa to less than 1 indigenous case with a prediction of this goal being achieved by the year 2026. CONCLUSIONS: Malaria elimination in South Africa is feasible and economically worthwhile with a guaranteed positive return on investment (ROI). Findings of this study show that through securing funding for the proposed malaria interventions in the endemic areas of South Africa and neighbouring Mozambique, national elimination could be within reach in an 8-year period.

Accounting for regional transmission variability and the impact of malaria control interventions in Ghana: a population level mathematical modelling approach.

BACKGROUND: This paper investigates the impact of malaria preventive interventions in Ghana and the prospects of achieving programme goals using mathematical models based on regionally diverse climatic zones of the country. METHODS: Using data from the District Health Information Management System of the Ghana Health Service from 2008 to 2017, and historical intervention coverage levels, ordinary non-linear differential equations models were developed. These models incorporated transitions amongst various disease compartments for the three main ecological zones in Ghana. The Approximate Bayesian Computational sampling approach, with a distance based rejection criteria, was adopted for calibration. A leave-one-out approach was used to validate model parameters and the most sensitive parameters were evaluated using a multivariate regression analysis. The impact of insecticide-treated bed nets and their usage, and indoor residual spraying, as well as their protective efficacy on the incidence of malaria, was simulated at various levels of coverage and protective effectiveness in each ecological zone to investigate the prospects of achieving goals of the Ghana malaria control strategy for 2014-2020. RESULTS: Increasing the coverage levels of both long-lasting insecticide-treated bed nets and indoor residual spraying activities, without a corresponding increase in their recommended utilization, does not impact highly on averting predicted incidence of malaria. Improving proper usage of long-lasting insecticide-treated bed nets could lead to substantial reductions in the predicted incidence of malaria. Similar results were obtained with indoor residual spraying across all ecological zones of Ghana. CONCLUSIONS: Projected goals set in the national strategic plan for malaria control 2014-2020, as well as World Health Organization targets for malaria pre-elimination by 2030, are only likely to be achieved if a substantial improvement in treated bed net usage is achieved, coupled with targeted deployment of indoor residual spraying with high community acceptability and efficacy.

Estimating the risk of declining funding for malaria in Ghana: the case for continued investment in the malaria response.

BACKGROUND: Ghana has made impressive progress against malaria, decreasing mortality and morbidity by over 50% between 2005 and 2015. These gains have been facilitated in part, due to increased financial commitment from government and donors. Total resources for malaria increased from less than USD 25 million in 2006 to over USD 100 million in 2011. However, the country still faces a high burden of disease and is at risk of declining external financing due to its strong economic growth and the consequential donor requirements for increased government contributions. The resulting financial gap will need to be met domestically. The purpose of this study was to provide economic evidence of the potential risks of withdrawing financing to shape an advocacy strategy for resource mobilization. METHODS: A compartmental transmission model was developed to estimate the impact of a range of malaria interventions on the transmission of Plasmodium falciparum malaria between 2018 and 2030. The model projected scenarios of common interventions that allowed the attainment of elimination and those that predicted transmission if interventions were withheld. The outputs of this model were used to generate costs and economic benefits of each option. RESULTS: Elimination was predicted using the package of interventions outlined in the national strategy, particularly increased net usage and improved case management. Malaria elimination in Ghana is predicted to cost USD 961 million between 2020 and 2029. Compared to the baseline, elimination is estimated to prevent 85.5 million cases, save 4468 lives, and avert USD 2.2 billion in health system expenditures. The economic gain was estimated at USD 32 billion in reduced health system expenditure, increased household prosperity and productivity gains. Through malaria elimination, Ghana can expect to see a 32-fold return on their investment. Reducing interventions, predicted an additional 38.2 clinical cases, 2500 deaths and additional economic losses of USD 14.1 billion. CONCLUSIONS: Malaria elimination provides robust epidemiological and economic benefits, however, sustained financing is need to accelerate the gains in Ghana. Although government financing has increased in the past decade, the amount is less than 25% of the total malaria financing. The evidence generated by this study can be used to develop a robust domestic strategy to overcome the financial barriers to achieving malaria elimination in Ghana.

Spatio-temporal heterogeneity of malaria morbidity in Ghana: Analysis of routine health facility data.

BACKGROUND: Malaria incidence is largely influenced by vector abundance. Among the many interconnected factors relating to malaria transmission, weather conditions such as rainfall and temperature are known to create suitable environmental conditions that sustain reproduction and propagation of anopheles mosquitoes and malaria parasites. In Ghana, climatic conditions vary across the country. Understanding the heterogeneity of malaria morbidity using data sourced from a recently setup data repository for routine health facility data could support planning. METHODS: Monthly aggregated confirmed uncomplicated malaria cases from the District Health Information Management System and average monthly rainfall and temperature records obtained from the Ghana Meteorological Agency from 2008 to 2016 were analysed. Univariate time series models were fitted to the malaria, rainfall and temperature data series. After pre-whitening the morbidity data, cross correlation analyses were performed. Subsequently, transfer function models were developed for the relationship between malaria morbidity and rainfall and temperature. RESULTS: Malaria morbidity patterns vary across zones. In the Guinea savannah, morbidity peaks once in the year and twice in both the Transitional forest and Coastal savannah, following similar patterns of rainfall at the zonal level. While the effects of rainfall on malaria morbidity are delayed by a month in the Guinea savannah and Transitional Forest zones those of temperature are delayed by two months in the Transitional forest zone. In the Coastal savannah however, incidence of malaria is significantly associated with two months lead in rainfall and temperature. CONCLUSION: Data captured on the District Health Information Management System has been used to demonstrate heterogeneity in the dynamics of malaria morbidity across the country. Timing of these variations could guide the deployment of interventions such as indoor residual spraying, Seasonal Malaria Chemoprevention or vaccines to optimise effectiveness on zonal basis.

Towards malaria control and elimination in Ghana: challenges and decision making tools to guide planning.

Ghana is classified as being in the malaria control phase, according to the global malaria elimination program. With many years of policy development and control interventions, malaria specific mortality among children less than 5 years old has declined from 14.4% in 2000 to 0.6% in 2012. However, the same level of success has not been achieved with malaria morbidity. The recently adopted 2015-2020 Ghana strategic action plan aims to reduce the burden of malaria by 75.0%. Planning and policy development has always been guided by evidence from field studies, and mathematical models that are able to investigate malaria transmission dynamics have not played a significant role in supporting policy development. The objectives of this study are to describe the malaria situation in Ghana and give a brief account of how mathematical modelling techniques could support a more informed malaria control effort in the Ghanaian context. A review is carried out of some mathematical models investigating the dynamics of malaria transmission in sub-Saharan African countries, including Ghana. The applications of these models are then discussed, considering the gaps that still remain in Ghana for which further mathematical model development could be supportive. Because of the collaborative approach adopted in their development, some model examples Ghana could benefit from are also discussed. Collaboration between malaria control experts and modellers will allow for more appropriate mathematical models to be developed. Packaging these models with user-friendly interfaces and making them available at various levels of malaria control management could help provide the decision making tools needed for planning and a platform for monitoring and evaluation of interventions in Ghana.

Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies.

Mass-screen-and-treat and targeted mass-drug-administration strategies are being considered as a means to interrupt transmission of Plasmodium falciparum malaria. However, the effectiveness of such strategies will depend on the extent to which current and future diagnostics are able to detect those individuals who are infectious to mosquitoes. We estimate the relationship between parasite density and onward infectivity using sensitive quantitative parasite diagnostics and mosquito feeding assays from Burkina Faso. We find that a diagnostic with a lower detection limit of 200 parasites per microlitre would detect 55% of the infectious reservoir (the combined infectivity to mosquitoes of the whole population weighted by how often each individual is bitten) whereas a test with a limit of 20 parasites per microlitre would detect 83% and 2 parasites per microlitre would detect 95% of the infectious reservoir. Using mathematical models, we show that increasing the diagnostic sensitivity from 200 parasites per microlitre (equivalent to microscopy or current rapid diagnostic tests) to 2 parasites per microlitre would increase the number of regions where transmission could be interrupted with a mass-screen-and-treat programme from an entomological inoculation rate below 1 to one of up to 4. The higher sensitivity diagnostic could reduce the number of treatment rounds required to interrupt transmission in areas of lower prevalence. We predict that mass-screen-and-treat with a highly sensitive diagnostic is less effective than mass drug administration owing to the prophylactic protection provided to uninfected individuals by the latter approach. In low-transmission settings such as those in Southeast Asia, we find that a diagnostic tool with a sensitivity of 20 parasites per microlitre may be sufficient for targeted mass drug administration because this diagnostic is predicted to identify a similar village population prevalence compared with that currently detected using polymerase chain reaction if treatment levels are high and screening is conducted during the dry season. Along with other factors, such as coverage, choice of drug, timing of the intervention, importation of infections, and seasonality, the sensitivity of the diagnostic can play a part in increasing the chance of interrupting transmission.

Predicting the impact of border control on malaria transmission: a simulated focal screen and treat campaign.

BACKGROUND: South Africa is one of many countries committed to malaria elimination with a target of 2018 and all malaria-endemic provinces, including Mpumalanga, are increasing efforts towards this ambitious goal. The reduction of imported infections is a vital element of an elimination strategy, particularly if a country is already experiencing high levels of imported infections. Border control of malaria is one tool that may be considered. METHODS: A metapopulation, non-linear stochastic ordinary differential equation model is used to simulate malaria transmission in Mpumalanga and Maputo province, Mozambique (the source of the majority of imported infections) to predict the impact of a focal screen and treat campaign at the Mpumalanga-Maputo border. This campaign is simulated by nesting an individual-based model for the focal screen and treat campaign within the metapopulation transmission model. RESULTS: The model predicts that such a campaign, simulated for different levels of resources, coverage and take-up rates with a variety of screening tools, will not eliminate malaria on its own, but will reduce transmission substantially. Making the campaign mandatory decreases transmission further though sub-patent infections are likely to remain undetected if the diagnostic tool is not adequately sensitive. Replacing screening and treating with mass drug administration results in substantially larger decreases as all (including sub-patent) infections are treated before movement into Mpumalanga. CONCLUSIONS: The reduction of imported cases will be vital to any future malaria control or elimination strategy. This simulation predicts that FSAT at the Mpumalanga-Maputo border will be unable to eliminate local malaria on its own, but may still play a key role in detecting and treating imported infections before they enter the country. Thus FSAT may form part of an integrated elimination strategy where a variety of interventions are employed together to achieve malaria elimination.

Towards malaria elimination in Mpumalanga, South Africa: a population-level mathematical modelling approach.

BACKGROUND: Mpumalanga in South Africa is committed to eliminating malaria by 2018 and efforts are increasing beyond that necessary for malaria control. Differential Equation models may be used to study the incidence and spread of disease with an important benefit being the ability to enact exogenous change on the system to predict impact without committing any real resources. The model is a deterministic non-linear ordinary differential equation representation of the dynamics of the human population. The model is fitted to weekly data of treated cases from 2002 to 2008, and then validated with data from 2009 to 2012. Elimination-focused interventions such as the scale-up of vector control, mass drug administration, a focused mass screen and treat campaign and foreign source reduction are applied to the model to assess their potential impact on transmission. RESULTS: Scaling up vector control by 10% and 20% resulted in substantial predicted decreases in local infections with little impact on imported infections. Mass drug administration is a high impact but short-lived intervention with predicted decreases in local infections of less that one infection per year. However, transmission reverted to pre-intervention levels within three years. Focused mass screen and treat campaigns at border-entry points are predicted to result in a knock-on decrease in local infections through a reduction in the infectious reservoir. This knock-on decrease in local infections was also predicted to be achieved through foreign source reduction. Elimination was only predicted to be possible under the scenario of zero imported infections in Mpumalanga. CONCLUSIONS: A constant influx of imported infections show that vector control alone will not be able to eliminate local malaria as it is insufficient to interrupt transmission. Both mass interventions have a large and immediate impact. Yet in countries with a large migrant population, these interventions may fail due to the reintroduction of parasites and their impact may be short-lived. While all strategies (in isolation or combined) contributed to decreasing local infections, none was predicted to decrease local infections to zero. The number of imported infections highlights the importance of reducing imported infections at source, and a regional approach to malaria elimination.

Factors associated with patterns of plural healthcare utilization among patients taking antiretroviral therapy in rural and urban South Africa: a cross-sectional study.

BACKGROUND: In low-resource settings, patients' use of multiple healthcare sources may complicate chronic care and clinical outcomes as antiretroviral therapy (ART) continues to expand. However, little is known regarding patterns, drivers and consequences of using multiple healthcare sources. We therefore investigated factors associated with patterns of plural healthcare usage among patients taking ART in diverse South African settings. METHODS: A cross-sectional study of patients taking ART was conducted in two rural and two urban sub-districts, involving 13 accredited facilities and 1266 participants selected through systematic random sampling. Structured questionnaires were used in interviews, and participant's clinic records were reviewed. Data collected included household assets, healthcare access dimensions (availability, affordability and acceptability), healthcare utilization and pluralism, and laboratory-based outcomes. Multiple logistic regression models were fitted to identify predictors of healthcare pluralism and associations with treatment outcomes. Prior ethical approval and informed consent were obtained. RESULTS: Nineteen percent of respondents reported use of additional healthcare providers over and above their regular ART visits in the prior month. A further 15% of respondents reported additional expenditure on self-care (e.g. special foods). Access to health insurance (Adjusted odds ratio [aOR] 6.15) and disability grants (aOR 1.35) increased plural healthcare use. However, plural healthcare users were more likely to borrow money to finance healthcare (aOR 2.68), and incur catastrophic levels of healthcare expenditure (27%) than non-plural users (7%). Quality of care factors, such as perceived disrespect by staff (aOR 2.07) and lack of privacy (aOR 1.50) increased plural healthcare utilization. Plural healthcare utilization was associated with rural residence (aOR 1.97). Healthcare pluralism was not associated with missed visits or biological outcomes. CONCLUSION: Increased plural healthcare utilization, inequitably distributed between rural and urban areas, is largely a function of higher socioeconomic status, better ability to finance healthcare and factors related to poor quality of care in ART clinics. Plural healthcare utilization may be an indication of patients' dissatisfaction with perceived quality of ART care provided. Healthcare expenditure of a catastrophic nature remained a persistent complication. Plural healthcare utilization did not appear to influence clinical outcomes. However, there were potential negative impacts on the livelihoods of patients and their households.

Exploring inequalities in access to and use of maternal health services in South Africa.

BACKGROUND: South Africa's maternal mortality rate (625 deaths/100,000 live births) is high for a middle-income country, although over 90% of pregnant women utilize maternal health services. Alongside HIV/AIDS, barriers to Comprehensive Emergency Obstetric Care currently impede the country's Millenium Development Goals (MDGs) of reducing child mortality and improving maternal health. While health system barriers to obstetric care have been well documented, "patient-oriented" barriers have been neglected. This article explores affordability, availability and acceptability barriers to obstetric care in South Africa from the perspectives of women who had recently used, or attempted to use, these services. METHODS: A mixed-method study design combined 1,231 quantitative exit interviews with sixteen qualitative in-depth interviews with women (over 18) in two urban and two rural health sub-districts in South Africa. Between June 2008 and September 2009, information was collected on use of, and access to, obstetric services, and socioeconomic and demographic details. Regression analysis was used to test associations between descriptors of the affordability, availability and acceptability of services, and demographic and socioeconomic predictor variables. Qualitative interviews were coded deductively and inductively using ATLAS ti.6. Quantitative and qualitative data were integrated into an analysis of access to obstetric services and related barriers. RESULTS: Access to obstetric services was impeded by affordability, availability and acceptability barriers. These were unequally distributed, with differences between socioeconomic groups and geographic areas being most important. Rural women faced the greatest barriers, including longest travel times, highest costs associated with delivery, and lowest levels of service acceptability, relative to urban residents. Negative provider-patient interactions, including staff inattentiveness, turning away women in early-labour, shouting at patients, and insensitivity towards those who had experienced stillbirths, also inhibited access and compromised quality of care. CONCLUSIONS: To move towards achieving its MDGs, South Africa cannot just focus on increasing levels of obstetric coverage, but must systematically address the access constraints facing women during pregnancy and delivery. More needs to be done to respond to these "patient-oriented" barriers by improving how and where services are provided, particularly in rural areas and for poor women, as well as altering the attitudes and actions of health care providers.