Point-of-care testing and treatment of sexually transmitted infections to improve pregnancy outcomes in resource-limited, high-burden settings

Women in developing countries worldwide face a high and unacceptable burden of adverse pregnancy outcomes. Curable, genital sexually transmitted infections (STIs) are major contributors to this disease burden in many resource-limited settings, but the majority of these infections go untreated. Health services are unable to diagnose them because of limited laboratory facilities and the cost of conventional laboratory-based STI diagnostic tests. In the absence of such resources, diagnosis has relied on the clinical strategy known as 'syndromic management' that is recognised as having very poor sensitivity, particularly for women, in whom the vast majority of these STIs are asymptomatic. Newly available, highly accurate and easy to use point-of-care tests for the first time offer a real solution to this long-term health problem in developing countries.

We will undertake a world-first field trial to investigate the effectiveness of a comprehensive point-of-care testing and treatment strategy for curable STIs to improve pregnancy outcomes in resource-limited, high-burden settings. Our trial will also be the first to investigate new molecular point-of-care tests, based on the GeneXpert technology, for the routine diagnosis of chlamydia, gonorrhoea and trichomonas infections in resource-limited settings. This newly available technology will allow trained health staff to make correct diagnoses and to provide curative treatment during routine antenatal clinic visits.

Papua New Guinea is a unique environment in which to conduct this research because of the conjunction of (a) a high burden of both adverse pregnancy outcomes and curable STIs among pregnant women; and (b) recent and extensive experience by our team in the conduct of health intervention studies involving pregnant women and their children.

We will conduct a randomised trial among 4200 pregnant women attending 12 antenatal clinics in Eastern Highlands, Madang and Milne Bay Provinces. Participating clinics and their catchment communities will be randomly allocated to receive either routine antenatal care (control arm) or point-of-care STI testing and immediate treatment (intervention arm). Women in both arms of the trial will undergo an obstetric ultrasound examination to accurately estimate the duration of their pregnancy; be asked to attend a minimum of four antenatal follow-up visits; and receive a postnatal follow-up visit by the research team within 48 hours of giving birth. We will compare birth outcomes between antenatal women who were offered point-of-care STI testing and treatment with those who were not.

We will measure the difference in pregnancy outcomes among women in each arm of the trial in terms of the proportion of preterm birth (birth less than 37 weeks gestation) and low birth weight (birth weight less than 2500 grams). We will also evaluate the cost-effectiveness, health system implementation requirements, and acceptability of antenatal point-of-care STI testing and treatment compared to routine antenatal care in order to maximise the impact of our research and to inform future roll-out.

The trial will have a potentially major impact on public health policy and clinical practice in all low-resource, high-burden settings, and its findings could lead to significant gains in maternal and newborn health globally.

We will undertake a world-first field trial to investigate the effectiveness of a comprehensive point-of-care testing and treatment strategy for curable sexually transmitted genital infections (STIs) to improve pregnancy outcomes in resource-limited, high-burden settings.

Papua New Guinea is a unique environment in which to conduct this research because of the conjunction of (a) a high burden of both adverse pregnancy outcomes and curable STIs among pregnant women; and (b) recent and extensive experience by our team in the conduct of health intervention studies involving pregnant women and their children.
We will conduct a cluster randomised trial among 4200 pregnant women attending 12 antenatal clinics in three provinces. Participating clinics and their catchment communities will be randomly assigned to receive either routine antenatal care (control arm) or point-of-care STI testing and immediate treatment (intervention arm). Study participants in both arms of the trial will undergo an obstetric ultrasound examination to accurately estimate gestational age; be asked to attend a minimum of four antenatal follow-up visits; and receive a postnatal follow-up visit by the research team within 48 hours of giving birth in order to measure study outcomes. We will measure the difference in pregnancy outcomes among women in each arm of the trial in terms of the proportion of preterm birth (birth less than 37 weeks gestation) and low birth weight (birth weight below 2500 grams). We will also evaluate the cost-effectiveness, health system implementation requirements, and acceptability of antenatal point-of-care STI testing and treatment compared to routine antenatal care in order to maximise the impact of our research and to inform future roll-out. The trial will have a potentially major impact on public health policy and clinical practice in all low-resource, high-burden settings, and its findings could lead to significant gains in maternal and neonatal health globally.

Summary
We will establish a multidisciplinary, participatory communication and engagement strategy to ensure that our research has the maximum impact on potential beneficiaries at local, national and international level. We will recruit a dedicated project team member, with experience in community development, media and communications to implement the strategy with potential beneficiaries throughout the lifetime of the trial, based fulltime at the Papua New Guinea Institute of Medical Research in Goroka. Our strategy is described in detail in our Pathways to Impact Statement.

Who will benefit from this research?
We have identified five different types of potential beneficiaries:
a) Local communities engaged in the trial in Papua New Guinea (PNG), including local community members and stakeholders, study participants and their families.
b) The wider community / general public in PNG.
c) Health service providers, health managers, clinicians, public health professionals, policy makers at facility, district, provincial and national level.
d) Representatives of international development organizations and the donor community.
e) The wider international community / general public.

How will they benefit from this research?
Our research has the potential to directly improve the health of mothers and their newborn infants in PNG and other high-burden, resource-limited settings globally and to therefore directly impact on beneficiaries (a), (b) and (e). Adverse maternal and neonatal health are widely recognised as having important negative societal and economic consequences. The effective and widespread translation of our research findings into public health policy and practice could therefore also lead to improvements in wider human development indices in high-burden, resource-limited settings worldwide.

The finding that antenatal point-of-care STI testing and immediate treatment results in improved pregnancy outcomes would have a direct impact on health managers and policy makers at national and international level (beneficiaries c, d). Changes in public health priorities, health system financing, staff allocation and training, would be among the key prerequisites to effective future program implementation and roll-out. Our study includes robust health economics and health system research components designed to provide guidance applicable to many high-burden, resource-limited settings. Measures of cost-effectiveness, as well as cost and non-monetary implementation requirements, will give policy makers insights into value-for-money, and the health systems impact of new diagnostics. This information will be essential to future prioritisation and planning, and increases the likelihood of timely and appropriate translation of our findings into public health action.

Our research will also develop clinical skills and knowledge among research and clinic staff at participating trial sites (beneficiaries c); and develop clinical research capacity within PNG to undertake large-scale randomised trials to address public health priorities (beneficiaries c, d). Should our research provide a positive result, the network of clinical sites that participated in the trial would be ideally placed to lead a future national roll-out of antenatal point of care STI testing and treatment, and to provide the country with the necessary centres of clinical excellence from which to build a robust, effective and efficient national program (beneficiaries a, b). The experience gained in these initial 12 sites would in turn be of significant future benefit to other countries considering introducing this strategy to improve maternal and neonatal health in their own settings (beneficiaries d, e).