Prevention Strategy for Papua New Guinea

Intermittent preventive treatment with azithromycin-containing regimens for the prevention of malarial infections and anaemia and the control of sexually transmitted infections in pregnant women in Papua New Guinea

Project Coordinator:           Prof Stephen J Rogerson (University of Melbourne, Australia)

European Collaborators:   Prof Clara Menendez (IS Global, Spain)

Site PI's:                                Drs Ivo Mueller and Peter Siba (IMR, PNG)

Objective

To examine whether repeated (three throughout the pregnancy) doses of intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) and azithromycin improves babies’ birth weights compared to a single treatment dose of SP and chloroquine.

Study design

A randomised control trial of IPTp, in the form of three-monthly doses of SP and AZ given twice daily for two days, compared to a single dose of SP and chloroquine followed by two doses of placebo in women enrolled at 14-26 weeks gestation. The study took place in Madang District, Papua New Guinea. Almost 2800 women were enrolled over two years, at the local hospital and nearby health centres.

Results and Conclusion

SP plus azithromycin was associated with a reduction in low birth weight and preterm delivery; maternal parasitaemia and active placental malaria as well as reduced carriage of gonorrhoea. SPAZ was efficacious and safe in reducing LBW, possibly acting through multiple mechanisms including the effect on malaria and on sexually transmitted infections.

Impact of the research

During the trial the Ministry of Health in Papua New Guinea adopted a regime of three monthly SP doses. The results were shared with WHO ERG in July 2013 and at a meeting in 2017 on control strategy in Asia and the South Pacific

VIVAX Working Group Meeting; 9th-11th October 2017, Bali

Publications

Wangnapi, R. A., et al. (2015). "Prevalence and risk factors for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis infection in pregnant women in Papua New Guinea." Sex Transm Infect 91(3): 194-200.

Unger, H. W., et al. (2015). "Azithromycin-containing intermittent preventive treatment in pregnancy affects gestational weight gain, an important predictor of birthweight in Papua New Guinea - an exploratory analysis." Matern Child Nutr

Unger, H. W., et al. (2015). "Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial." BMC Med 13: 9.

Unger, H. W., et al. (2015). "Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea." BMC Pregnancy Childbirth 15: 83.

Unger, H. W., et al. (2015). "Fetal size in a rural melanesian population with minimal risk factors for growth restriction: an observational ultrasound study from Papua New Guinea." Am J Trop Med Hyg 92(1): 178-186

Unger, H. W., et al. (2015). "Impact of intermittent preventive treatment in pregnancy with azithromycin-containing regimens on maternal nasopharyngeal carriage and antibiotic sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus: a cross-sectional survey at delivery." J Clin Microbiol 53(4): 1317-1323.

Umbers, A. J., et al. (2015). "Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria." Malar J 14: 412.

Teo, A., et al. (2015). "Malaria preventive therapy in pregnancy and its potential impact on immunity to malaria in an area of declining transmission." Malar J 14: 215.

Ome-Kaius, M., et al. (2015). "Determining effects of areca (betel) nut chewing in a prospective cohort of pregnant women in Madang Province, Papua New Guinea." BMC Pregnancy Childbirth 15: 177.

Karl, S., et al. (2015). "Preterm or not--an evaluation of estimates of gestational age in a cohort of women from Rural Papua New Guinea." PLoS One 10(5): e0124286

Teo, A., et al. (2014). "Decreasing malaria prevalence and its potential consequences for immunity in pregnant women." J Infect Dis 210(9): 1444-1455.

Ludlow, L. E., et al. (2014). "Peripheral blood mononuclear cells derived from grand multigravidae display a distinct cytokine profile in response to P. falciparum infected erythrocytes." PLoS One 9(1): e86160

Bolnga, J. W., et al. (2014). "Insights into maternal mortality in Madang Province, Papua New Guinea." Int J Gynaecol Obstet 124(2): 123-127

Umbers, A. J., et al. (2013). "Does malaria affect placental development? Evidence from in vitro models." PLoS One 8(1): e55269

Ome, M., et al. (2013). "A case of ultrasound-guided prenatal diagnosis of prune belly syndrome in Papua New Guinea--implications for management." BMC Pediatr 13: 70.

Hamura, N. N., et al. (2013). "The impact of tubal ectopic pregnancy in Papua New Guinea--a retrospective case review." BMC Pregnancy Childbirth 13: 86.

Salman, S., et al. (2010). "Pharmacokinetic properties of azithromycin in pregnancy." Antimicrob Agents Chemother 54(1): 360-366.

Benjamin JM., et al. (2015). "Population pharmacokinetics, tolerability, and safety of dihydroartemisinin-piperaquine and sulfadoxine-pyrimethamine-piperaquine in pregnant and nonpregnant Papua New Guinean women." Antimicrob Agents Chemother. 2015 Jul;59(7):4260-71.

Benjamin JM., et al. (2015). "Safety, tolerability and pharmacokinetic properties of coadministered azithromycin and piperaquine in pregnant Papua New Guinean women." Br J Clin Pharmacol. 2016 Jul;82(1):199-212