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:           Stephen J Rogerson (Australia)

European Collaborators:   Clara Menendez (Spain)

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


Objective:

Both P. falciparum and P. vivax are common in PNG, and show varying levels of resistance to current drugs, such as chloroquine and sulphadoxine-pyrimethamine (SP). At delivery, around 40% of women show evidence of damage to the placenta from malaria. Malaria is a major cause of low birth weight babies and of severe anaemia in mothers.  The study was set up to examine whether repeated (three throughout the pregnancy) doses of Intermittent Preventive Treatment in pregnancy (IPTp) with SP and azithromycin, an antibiotic that in previous studies has shown some effect against the malaria parasite as well as against a number of sexually transmitted infections, improves babies’ birth weights compared to a single treatment dose of SP and chloroquine.

Method:

The study took place in Madang District, PNG, as a partnership between the PNG Institute of Medical Research and the University of Melbourne’s Department of Medicine. Almost 2800 women were enrolled over two years, at the local hospital and nearby health centres.

Results:

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.  The results were shared with WHO_ERG in July 2013 and will be considered at a meeting in 2017 on control strategy in Asia and the South Pacific.

Publications

Moore BR, Benjamin JM, Auyeung SO, Salman S, Yadi G, Griffin S, Page-Sharp M, Batty KT, Siba PM, Mueller I, Rogerson SJ, Davis TM. Safety, tolerability and pharmacokinetic properties of co-administered azithromycin and piperaquine in pregnant Papua New Guinean women. Br J Clin Pharmacol. 2016 Jul;82(1):199-212. doi: 10.1111/bcp.12910. Epub 2016 Mar 27.

Karl, S, Li Wai Suen C. S. N, Unger H. W, Ome-Kaius, M, Mola, G, White, L, Wangnapi, R. A, Rogerson, S. J.  Preterm or Not – An evaluation of estimates of gestational age in a cohort of women from rural Papua New Guinea. PLoS One. 2015 May 6;10(5):e0124286. doi: 10.1371/journal.pone.0124286. eCollection 2015. 

Ome-Kaius M, Unger HW, Singirok D, Wangnapi RA, Hanieh S, Umbers AJ, Elizah J, Siba P, Mueller I, Rogerson SJ, 2015.  Determining effects of areca (betel) nut chewing in a prospective cohort of pregnant women in Madang Province, Papua New Guinea. BMC Pregnancy Childbirth. 2015 Aug 19;15:177. doi: 10.1186/s12884-015-0615-z 

Teo A, Hasang W, Randall LM, Unger HW, Siba PM, Mueller I, Brown GV, Rogerson SJ. Malaria preventive therapy in pregnancy and its potential impact on immunity to malaria in an area of declining transmission. Malar J. 2015 May 26;14:215. doi: 10.1186/s12936-015-0736-x. 

Umbers AJ, Unger HW, Rosanas-Urgell A, Wangnapi RA, Kattenberg JH, Jally S, Silim S, Lufele E, Karl S, Ome-Kaius M, Robinson LJ, Rogerson SJ, Mueller I, 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. 2015 Oct 19;14(1):412. doi: 10.1186/s12936-015-0927-5. 

Unger H. W, Ome-Kaius M, Wangnapi R. A, Umbers A. J, Hanieh S, Li Wai Suen C.S.N, Robinson, L. J, Rosanas-Urgell, A, Wapling, J, Lufele, E, Kongs, C, Samol, P, Sui, D, Singirok, D, Bardaji, A, Schofield, L, Menendez, C, Betuela, I, Siba, P, Mueller, I and Rogerson, S. J.  Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial. BMC Med. 2015 Jan 16;13:9. doi: 10.1186/s12916-014-0258-3.

Unger H. W, Ome-Kaius, M, Karl, S, Singirok, D, Siba, P, Walker, J, Wangnapi, R. A, Mueller, I, Rogerson, S.J.  Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea.  BMC Pregnancy Childbirth. 2015 Apr 3;15:83. doi: 10.1186/s12884-015-0511-6.

Unger H.W, Aho, C, Ome-Kaius, M, Wangnapi, R.A, Umbers, A. J, Jack, W, Lafana, A, Michael, A, Hanieh, S, Siba, P, Mueller, I, Greenhill, A, R, Rogerson, S. J. I. 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. April 2015  vol. 53  no. 4  1317-1323 

Unger HW, Wangnapi RA, Ome-Kaius M, Boeuf P, Karl S, Mueller I, Rogerson SJ, 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. 2015 Sep 15. doi: 10.1111/mcn.12215. http://dx.doi.org/10.1111/mcn.12215

Unger, H. W., Karl, S., Wangnapi, R. A., Siba, P., Mola, G., Walker, J., Mueller, I., Ome, M., Rogerson, S.J. 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 2015; 92:178-186 

Bolnga JW, Hamura NN, Umbers AJ, Rogerson SJ, Unger HW. Insights into maternal mortality in Madang Province, Papua New Guinea. Int J Gynaecol Obstet. 2014 Feb;124(2):123-7. doi: 10.1016/j.ijgo.2013.08.012. Epub 2013 Nov 6.  

Ludlow, L. E., Hasang, W., Umbers, A. J., Forbes, E. K., Ome, M., Unger, H. W., Mueller, I., Siba, P. M., Jaworowski, A., Rogerson, S. J.  Peripheral blood mononuclear cells derived from grand multigravidae display a distinct cytokine profile in response to P. falciparum infected erythrocytes. PLoS One. 2014 Jan 22;9(1):e86160. doi: 10.1371/journal.pone.0086160. eCollection 2014

Teo A, Hasang W, Randall LM, Feng G, Bell L, Unger H, Langer C, Beeson JG, Siba P M, Mueller I, Molyneux M E, Brown GV, Rogerson SJ.  Decreasing Malaria Prevalence and Its Potential Consequences for Immunity in Pregnant Women. J Infect Dis. 2014 Nov 1;210(9):1444-55. doi: 10.1093/infdis/jiu264. Epub 2014 May 5.

Wangnapi R. A, Soso, S, Unger, H. W, Sawera, C, Ome, M, Umbers A. J, Ndrewei, N, Siba, P, Li Wan Suen, C. S. N, Vallely, A, Wapling, J, Ryan, C, Mueller, I, Rogerson, S. J.  Prevalence and risk factors for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis infection in pregnant women in Papua New Guinea. Sex Transm Infect. 2015 May;91(3):194-200. doi: 10.1136/sextrans-2014-051670. Epub 2014 Oct 13

Hamura NN, Bolnga JW, Wangnapi R, Horne AW, Rogerson SJ, Unger HW. The impact of tubal ectopic pregnancy in Papua New Guinea--a retrospective case review. BMC Pregnancy Childbirth. 2013 Apr 4;13:86. doi: 10.1186/1471-2393-13-86

Ome, M, Wangnapi, R, Hamura, N, Umbers, A. J., Siba, P, Laman, M., Bolnga, J, Rogerson, S, Unger, H. W.  A case of ultrasound-guided prenatal diagnosis of prune belly syndrome in Papua New Guinea--implications for management. BMC Pediatr. 2013 May 7;13:70. doi: 10.1186/1471-2431-13-70.

Umbers, A, J, Stanisic, D,I, Ome, M., Wangnapi, R, Hanieh, S, Unger, H, W, Robinson, L, J, Lufele, E, Baiwog, F, Siba, P, M., King. C, L., Beeson, J, G, Mueller, I, Aplin, J, D., Glazier, J, D, Rogerson, S, J. Does Malaria Affect Placental Development? Evidence from In Vitro Models, PLoS One. 2013;8(1):e55269. doi: 10.1371/journal.pone.0055269. Epub 2013 Jan 31.

Salman, S, Rogerson, S.J, Kose, K, Griffin, S, Gomorai, S, Baiwog, F, Winmai, J, Kandai, J, Karunajeewa, H.A., O'Halloran, S. J., Siba, P, Ilett, K.F, Mueller, I, Davis, T.M.E.  Pharmacokinetic properties of azithromycin in pregnancy. Antimicrobial agents and chemotherapy 2010, 54(1), pp. 360-366.