Risk factors and pregnancy outcomes associated with placental malaria in a prospective cohort of Papua New Guinean women

BACKGROUND: Plasmodium falciparum in pregnancy results in substantial poor health outcomes for both mother and child, particularly in young, primigravid mothers who are at greatest risk of placental malaria (PM) infection. Complications of PM include maternal anaemia, low birth weight and preterm delivery, which contribute to maternal and infant morbidity and mortality in coastal Papua New Guinea (PNG). METHODS: Placental biopsies were examined from 1451 pregnant women who were enrolled in a malaria prevention study at 14-26 weeks gestation. Clinical and demographic information were collected at first antenatal clinic visits and women were followed until delivery. Placental biopsies were collected and examined for PM using histology. The presence of infected erythrocytes and/or the malaria pigment in monocytes or fibrin was used to determine the type of placental infection. RESULTS: Of 1451 placentas examined, PM infection was detected in 269 (18.5%), of which 54 (3.7%) were acute, 55 (3.8%) chronic, and 160 (11.0%) were past infections. Risk factors for PM included residing in rural areas (adjusted odds ratio (AOR) 3.65, 95% CI 1.76-7.51; p </= 0.001), being primigravid (AOR 2.45, 95% CI 1.26-4.77; p = 0.008) and having symptomatic malaria during pregnancy (AOR 2.05, 95% CI 1.16-3.62; p = 0.013). After adjustment for covariates, compared to uninfected women, acute infections (AOR 1.97, 95% CI 0.98-3.95; p = 0.056) were associated with low birth weight babies, whereas chronic infections were associated with preterm delivery (AOR 3.92, 95% CI 1.64-9.38; p = 0.002) and anaemia (AOR 2.22, 95% CI 1.02-4.84; p = 0.045). CONCLUSIONS: Among pregnant PNG women receiving at least one dose of intermittent preventive treatment in pregnancy and using insecticide-treated bed nets, active PM infections were associated with adverse outcomes. Improved malaria prevention is required to optimize pregnancy outcomes

Strategies for Understanding and Reducing the Plasmodium vivax and Plasmodium ovale Hypnozoite Reservoir in Papua New Guinean Children: A Randomised Placebo-Controlled Trial and Mathematical Model

The undetectable hypnozoite reservoir for relapsing Plasmodium vivax and P. ovale malarias presents a major challenge for malaria control and elimination in endemic countries. This study aims to directly determine the contribution of relapses to the burden of P. vivax and P. ovale infection, illness, and transmission in Papua New Guinean children.; From 17 August 2009 to 20 May 2010, 524 children aged 5-10 y from East Sepik Province in Papua New Guinea (PNG) participated in a randomised double-blind placebo-controlled trial of blood- plus liver-stage drugs (chloroquine [CQ], 3 d; artemether-lumefantrine [AL], 3 d; and primaquine [PQ], 20 d, 10 mg/kg total dose) (261 children) or blood-stage drugs only (CQ, 3 d; AL, 3 d; and placebo [PL], 20 d) (263 children). Participants, study staff, and investigators were blinded to the treatment allocation. Twenty children were excluded during the treatment phase (PQ arm: 14, PL arm: 6), and 504 were followed actively for 9 mo. During the follow-up time, 18 children (PQ arm: 7, PL arm: 11) were lost to follow-up. Main primary and secondary outcome measures were time to first P. vivax infection (by qPCR), time to first clinical episode, force of infection, gametocyte positivity, and time to first P. ovale infection (by PCR). A basic stochastic transmission model was developed to estimate the potential effect of mass drug administration (MDA) for the prevention of recurrent P. vivax infections. Targeting hypnozoites through PQ treatment reduced the risk of having at least one qPCR-detectable P. vivax or P. ovale infection during 8 mo of follow-up (P. vivax: PQ arm 0.63/y versus PL arm 2.62/y, HR = 0.18 [95% CI 0.14, 0.25], p &lt; 0.001; P. ovale: 0.06 versus 0.14, HR = 0.31 [95% CI 0.13, 0.77], p = 0.011) and the risk of having at least one clinical P. vivax episode (HR = 0.25 [95% CI 0.11, 0.61], p = 0.002). PQ also reduced the molecular force of P. vivax blood-stage infection in the first 3 mo of follow-up (PQ arm 1.90/y versus PL arm 7.75/y, incidence rate ratio [IRR] = 0.21 [95% CI 0.15, 0.28], p &lt; 0.001). Children who received PQ were less likely to carry P. vivax gametocytes (IRR = 0.27 [95% CI 0.19, 0.38], p &lt; 0.001). PQ had a comparable effect irrespective of the presence of P. vivax blood-stage infection at the time of treatment (p = 0.14). Modelling revealed that mass screening and treatment with highly sensitive quantitative real-time PCR, or MDA with blood-stage treatment alone, would have only a transient effect on P. vivax transmission levels, while MDA that includes liver-stage treatment is predicted to be a highly effective strategy for P. vivax elimination. The inclusion of a directly observed 20-d treatment regime maximises the efficiency of hypnozoite clearance but limits the generalisability of results to real-world MDA programmes.; These results suggest that relapses cause approximately four of every five P. vivax infections and at least three of every five P. ovale infections in PNG children and are important in sustaining transmission. MDA campaigns combining blood- and liver-stage treatment are predicted to be a highly efficacious intervention for reducing P. vivax and P. ovale transmission.; ClinicalTrials.gov NCT02143934

Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial

A three-arm randomized trial conducted among infants in Papua New Guinea estimates the preventive effect against malaria episodes of intermittent preventive treatment, in an area where children are exposed to both falciparum and vivax malaria

Prevalence of malaria across Papua New Guinea after initial roll-out of insecticide-treated mosquito nets

To assess the population prevalence of malaria in villages across Papua New Guinea (PNG) following the first roll-out of free long-lasting insecticidal nets (LLIN).; Between October 2008 and August 2009, a household survey was conducted in 49 random villages in districts covered by the LLIN distribution campaign. The survey extended to 19 villages in sentinel sites that had not yet been covered by the campaign. In each village, 30 households were randomly sampled, household heads were interviewed and capillary blood samples were collected from all consenting household members for microscopic diagnosis of malaria.; Malaria prevalence ranged from 0% to 49.7% with a weighted average of 12.1% (95% CI 9.5, 15.3) in the national sample. More people were infected with Plasmodium falciparum (7.0%; 95% CI 5.4, 9.1) than with P. vivax (3.8%; 95% CI 2.4, 5.7) or P. malariae (0.3%; 95% CI 0.1, 0.6). Parasitaemia was strongly age-dependent with a P. falciparum peak at age 5-9 years and a P. vivax peak at age 1-4 years, yet with differences between geographical regions. Individual LLIN use and high community coverage were associated with reduced odds of infection (OR = 0.64 and 0.07, respectively; both P &lt; 0.001). Splenomegaly in children and anaemia were common morbidities attributable to malaria.; Malaria prevalence across PNG is again at levels comparable to the 1970s. The strong association of LLIN use with reduced parasitaemia supports efforts to achieve and maintain high country-wide coverage. P. vivax infections will require special targeted approaches across PNG

Insecticide-treated nets and malaria prevalence, Papua New Guinea, 2008-2014

To investigate changes in malaria prevalence in Papua New Guinea after the distribution of long-lasting Insecticide-treated nets, starting in 2004, and the introduction of artemisinin-based combination therapy in 2011.; Two malaria surveys were conducted in 2010-2011 and 2013-2014. They included 77 and 92 randomly selected villages, respectively. In each village, all members of 30 randomly selected households gave blood samples and were assessed for malaria infection by light microscopy. In addition, data were obtained from a malaria survey performed in 2008-2009.; The prevalence of malaria below 1600 m in altitude decreased from 11.1% (95% confidence interval, CI: 8.5-14.3) in 2008-2009 to 5.1% (95% CI 3.6-7.4) in 2010-2011 and 0.9% (95% CI 0.6-1.5) in 2013-2014. Prevalence decreased with altitude. Plasmodium falciparum was more common than P. vivax overall, but not everywhere, and initially the prevalence of P. vivax infection decreased more slowly than P. falciparum infection. Malaria infections were clustered in households. In contrast to findings in 2008-2009, no significant association between net use and prevalence was found in the later two surveys. The prevalence of both fever and splenomegaly also decreased but their association with malaria infection became stronger.; Large-scale insecticide-treated net distribution was associated with an unprecedented decline in malaria prevalence throughout Papua New Guinea, including epidemic-prone highland areas. The decline was accompanied by broader health benefits, such as decreased morbidity. Better clinical management of nonmalarial fever and research into residual malaria transmission are required

Risk factors and pregnancy outcomes associated with placental malaria in a prospective cohort of Papua New Guinean women

BACKGROUND: Plasmodium falciparum in pregnancy results in substantial poor health outcomes for both mother and child, particularly in young, primigravid mothers who are at greatest risk of placental malaria (PM) infection. Complications of PM include maternal anaemia, low birth weight and preterm delivery, which contribute to maternal and infant morbidity and mortality in coastal Papua New Guinea (PNG). METHODS: Placental biopsies were examined from 1451 pregnant women who were enrolled in a malaria prevention study at 14-26 weeks gestation. Clinical and demographic information were collected at first antenatal clinic visits and women were followed until delivery. Placental biopsies were collected and examined for PM using histology. The presence of infected erythrocytes and/or the malaria pigment in monocytes or fibrin was used to determine the type of placental infection. RESULTS: Of 1451 placentas examined, PM infection was detected in 269 (18.5%), of which 54 (3.7%) were acute, 55 (3.8%) chronic, and 160 (11.0%) were past infections. Risk factors for PM included residing in rural areas (adjusted odds ratio (AOR) 3.65, 95% CI 1.76-7.51; p </= 0.001), being primigravid (AOR 2.45, 95% CI 1.26-4.77; p = 0.008) and having symptomatic malaria during pregnancy (AOR 2.05, 95% CI 1.16-3.62; p = 0.013). After adjustment for covariates, compared to uninfected women, acute infections (AOR 1.97, 95% CI 0.98-3.95; p = 0.056) were associated with low birth weight babies, whereas chronic infections were associated with preterm delivery (AOR 3.92, 95% CI 1.64-9.38; p = 0.002) and anaemia (AOR 2.22, 95% CI 1.02-4.84; p = 0.045). CONCLUSIONS: Among pregnant PNG women receiving at least one dose of intermittent preventive treatment in pregnancy and using insecticide-treated bed nets, active PM infections were associated with adverse outcomes. Improved malaria prevention is required to optimize pregnancy outcomes

Risk factors and pregnancy outcomes associated with placental malaria in a prospective cohort of Papua New Guinean women

BACKGROUND: Plasmodium falciparum in pregnancy results in substantial poor health outcomes for both mother and child, particularly in young, primigravid mothers who are at greatest risk of placental malaria (PM) infection. Complications of PM include maternal anaemia, low birth weight and preterm delivery, which contribute to maternal and infant morbidity and mortality in coastal Papua New Guinea (PNG). METHODS: Placental biopsies were examined from 1451 pregnant women who were enrolled in a malaria prevention study at 14-26 weeks gestation. Clinical and demographic information were collected at first antenatal clinic visits and women were followed until delivery. Placental biopsies were collected and examined for PM using histology. The presence of infected erythrocytes and/or the malaria pigment in monocytes or fibrin was used to determine the type of placental infection. RESULTS: Of 1451 placentas examined, PM infection was detected in 269 (18.5%), of which 54 (3.7%) were acute, 55 (3.8%) chronic, and 160 (11.0%) were past infections. Risk factors for PM included residing in rural areas (adjusted odds ratio (AOR) 3.65, 95% CI 1.76-7.51; p </= 0.001), being primigravid (AOR 2.45, 95% CI 1.26-4.77; p = 0.008) and having symptomatic malaria during pregnancy (AOR 2.05, 95% CI 1.16-3.62; p = 0.013). After adjustment for covariates, compared to uninfected women, acute infections (AOR 1.97, 95% CI 0.98-3.95; p = 0.056) were associated with low birth weight babies, whereas chronic infections were associated with preterm delivery (AOR 3.92, 95% CI 1.64-9.38; p = 0.002) and anaemia (AOR 2.22, 95% CI 1.02-4.84; p = 0.045). CONCLUSIONS: Among pregnant PNG women receiving at least one dose of intermittent preventive treatment in pregnancy and using insecticide-treated bed nets, active PM infections were associated with adverse outcomes. Improved malaria prevention is required to optimize pregnancy outcomes

Data from: Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model

Background: The undetectable hypnozoite reservoir for relapsing Plasmodium vivax and P. ovale malarias presents a major challenge for malaria control and elimination in endemic countries. This study aims to directly determine the contribution of relapses to the burden of P. vivax and P. ovale infection, illness, and transmission in Papua New Guinean children. Methods and Findings: From 17 August 2009 to 20 May 2010, 524 children aged 5–10 y from East Sepik Province in Papua New Guinea (PNG) participated in a randomised double-blind placebo-controlled trial of blood- plus liver-stage drugs (chloroquine [CQ], 3 d; artemether-lumefantrine [AL], 3 d; and primaquine [PQ], 20 d, 10 mg/kg total dose) (261 children) or blood-stage drugs only (CQ, 3 d; AL, 3 d; and placebo [PL], 20 d) (263 children). Participants, study staff, and investigators were blinded to the treatment allocation. Twenty children were excluded during the treatment phase (PQ arm: 14, PL arm: 6), and 504 were followed actively for 9 mo. During the follow-up time, 18 children (PQ arm: 7, PL arm: 11) were lost to follow-up. Main primary and secondary outcome measures were time to first P. vivax infection (by qPCR), time to first clinical episode, force of infection, gametocyte positivity, and time to first P. ovale infection (by PCR). A basic stochastic transmission model was developed to estimate the potential effect of mass drug administration (MDA) for the prevention of recurrent P. vivax infections. Targeting hypnozoites through PQ treatment reduced the risk of having at least one qPCR-detectable P. vivax or P. ovale infection during 8 mo of follow-up (P. vivax: PQ arm 0.63/y versus PL arm 2.62/y, HR = 0.18 [95% CI 0.14, 0.25], p < 0.001; P. ovale: 0.06 versus 0.14, HR = 0.31 [95% CI 0.13, 0.77], p = 0.011) and the risk of having at least one clinical P. vivax episode (HR = 0.25 [95% CI 0.11, 0.61], p = 0.002). PQ also reduced the molecular force of P. vivax blood-stage infection in the first 3 mo of follow-up (PQ arm 1.90/y versus PL arm 7.75/y, incidence rate ratio [IRR] = 0.21 [95% CI 0.15, 0.28], p < 0.001). Children who received PQ were less likely to carry P. vivax gametocytes (IRR = 0.27 [95% CI 0.19, 0.38], p < 0.001). PQ had a comparable effect irrespective of the presence of P. vivax blood-stage infection at the time of treatment (p = 0.14). Modelling revealed that mass screening and treatment with highly sensitive quantitative real-time PCR, or MDA with blood-stage treatment alone, would have only a transient effect on P. vivax transmission levels, while MDA that includes liver-stage treatment is predicted to be a highly effective strategy for P. vivax elimination. The inclusion of a directly observed 20-d treatment regime maximises the efficiency of hypnozoite clearance but limits the generalisability of results to real-world MDA programmes. Conclusions: These results suggest that relapses cause approximately four of every five P. vivax infections and at least three of every five P. ovale infections in PNG children and are important in sustaining transmission. MDA campaigns combining blood- and liver-stage treatment are predicted to be a highly efficacious intervention for reducing P. vivax and P. ovale transmission

Strategies for Understanding and Reducing the Plasmodium vivax and Plasmodium ovale Hypnozoite Reservoir in Papua New Guinean Children: A Randomised Placebo-Controlled Trial and Mathematical Model

BACKGROUND: The undetectable hypnozoite reservoir for relapsing Plasmodium vivax and P. ovale malarias presents a major challenge for malaria control and elimination in endemic countries. This study aims to directly determine the contribution of relapses to the burden of P. vivax and P. ovale infection, illness, and transmission in Papua New Guinean children. METHODS AND FINDINGS: From 17 August 2009 to 20 May 2010, 524 children aged 5-10 y from East Sepik Province in Papua New Guinea (PNG) participated in a randomised double-blind placebo-controlled trial of blood- plus liver-stage drugs (chloroquine [CQ], 3 d; artemether-lumefantrine [AL], 3 d; and primaquine [PQ], 20 d, 10 mg/kg total dose) (261 children) or blood-stage drugs only (CQ, 3 d; AL, 3 d; and placebo [PL], 20 d) (263 children). Participants, study staff, and investigators were blinded to the treatment allocation. Twenty children were excluded during the treatment phase (PQ arm: 14, PL arm: 6), and 504 were followed actively for 9 mo. During the follow-up time, 18 children (PQ arm: 7, PL arm: 11) were lost to follow-up. Main primary and secondary outcome measures were time to first P. vivax infection (by qPCR), time to first clinical episode, force of infection, gametocyte positivity, and time to first P. ovale infection (by PCR). A basic stochastic transmission model was developed to estimate the potential effect of mass drug administration (MDA) for the prevention of recurrent P. vivax infections. Targeting hypnozoites through PQ treatment reduced the risk of having at least one qPCR-detectable P. vivax or P. ovale infection during 8 mo of follow-up (P. vivax: PQ arm 0.63/y versus PL arm 2.62/y, HR = 0.18 [95% CI 0.14, 0.25], p < 0.001; P. ovale: 0.06 versus 0.14, HR = 0.31 [95% CI 0.13, 0.77], p = 0.011) and the risk of having at least one clinical P. vivax episode (HR = 0.25 [95% CI 0.11, 0.61], p = 0.002). PQ also reduced the molecular force of P. vivax blood-stage infection in the first 3 mo of follow-up (PQ arm 1.90/y versus PL arm 7.75/y, incidence rate ratio [IRR] = 0.21 [95% CI 0.15, 0.28], p < 0.001). Children who received PQ were less likely to carry P. vivax gametocytes (IRR = 0.27 [95% CI 0.19, 0.38], p < 0.001). PQ had a comparable effect irrespective of the presence of P. vivax blood-stage infection at the time of treatment (p = 0.14). Modelling revealed that mass screening and treatment with highly sensitive quantitative real-time PCR, or MDA with blood-stage treatment alone, would have only a transient effect on P. vivax transmission levels, while MDA that includes liver-stage treatment is predicted to be a highly effective strategy for P. vivax elimination. The inclusion of a directly observed 20-d treatment regime maximises the efficiency of hypnozoite clearance but limits the generalisability of results to real-world MDA programmes. CONCLUSIONS: These results suggest that relapses cause approximately four of every five P. vivax infections and at least three of every five P. ovale infections in PNG children and are important in sustaining transmission. MDA campaigns combining blood- and liver-stage treatment are predicted to be a highly efficacious intervention for reducing P. vivax and P. ovale transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT02143934