Mycoplasma genitalium in pregnancy, including specific co-infections, is associated with lower birthweight: A prospective cohort study.

BACKGROUND: Mycoplasma genitalium infection in pregnancy is increasingly reported at similar frequencies to other sexually transmitted infections (STIs). Knowledge on its contribution to adverse pregnancy outcomes is very limited, especially relative to other STIs or bacterial vaginosis (BV). Whether M. genitalium influences birthweight remains unanswered. METHODS: Associations between birthweight and M. genitalium and other STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and BV in pregnancy were examined in 416 maternal-newborn pairs from a prospective cohort study in Papua New Guinea. FINDINGS: Compared to uninfected women, M. genitalium (-166.9 g, 95% confidence interval [CI]: -324.2 to -9.7 g, p = 0.038) and N. gonorrhoeae (-274.7 g, 95% CI: -561.9 to 12.5 g, p = 0.061) infections were associated with lower birthweight in an adjusted analysis. The association for C. trachomatis was less clear, and T. vaginalis and BV were not associated with lower birthweight. STI prevalence was high for M. genitalium (13.9%), N. gonorrhoeae (5.0%), and C. trachomatis (20.0%); co-infections were frequent. Larger effect sizes on birthweight occurred with co-infections of M. genitalium, N. gonorrhoeae, and/or C. trachomatis. CONCLUSION: M. genitalium is a potential contributor to lower birthweight, and co-infections appear to have a greater negative impact on birthweight. Trials examining the impact of early diagnosis and treatment of M. genitalium and other STIs in pregnancy and preconception are urgently needed. FUNDING: Funding was received from philanthropic grants, the National Health and Medical Research Council, and the Burnet Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Quantifying differences in iron deficiency-attributable anemia during pregnancy and postpartum.

Pregnant women in resource-limited settings are highly susceptible to anemia and iron deficiency, but the etiology of postpartum anemia remains poorly defined. To inform the optimal timing for anemia interventions, changes in iron deficiency-attributable anemia through pregnancy and postpartum need to be understood. In 699 pregnant Papua New Guinean women attending their first antenatal care appointment and following up at birth and 6 and 12 months postpartum, we undertake logistic mixed-effects modeling to determine the effect of iron deficiency on anemia and population attributable fractions, calculated from odds ratios, to quantify the contribution of iron deficiency to anemia. Anemia is highly prevalent during pregnancy and 12 months postpartum, with iron deficiency increasing the odds of anemia during pregnancy and, to a lesser extent, postpartum. Iron deficiency accounts for ≥72% of anemia during pregnancy and 20%-37% postpartum. Early iron supplementation during and between pregnancies could break the cycle of chronic anemia in women of reproductive age.

Low knowledge of newborn danger signs among pregnant women in Papua New Guinea and implications for health seeking behaviour in early infancy - findings from a longitudinal study.

BACKGROUND: Globally, 2.5 million babies die in the first 28 days of life each year with most of these deaths occurring in low- and middle-income countries. Early recognition of newborn danger signs is important in prompting timely care seeking behaviour. Little is known about women's knowledge of newborn danger signs in Papua New Guinea. This study aims to assess this knowledge gap among a cohort of women in East New Britain Province. METHODS: This study assessed knowledge of newborn danger signs (as defined by the World Health Organization) at three time points from a prospective cohort study of women in East New Britain Province, factors associated with knowledge of danger signs after childbirth were assessed using logistic regression. This study includes quantitative and qualitative interview data from 699 pregnant women enrolled at their first antenatal clinic visit, followed up after childbirth (n = 638) and again at one-month post-partum (n = 599). RESULTS: Knowledge of newborn danger signs was very low. Among the 638 women, only 9.4% knew three newborn danger signs after childbirth and only one knew all four essential danger signs defined by Johns Hopkins University 'Birth Preparedness and Complication Readiness' Index. Higher knowledge scores were associated with higher gravidity, income level, partner involvement in antenatal care, and education. CONCLUSION: Low levels of knowledge of newborn danger signs among pregnant women are a potential obstacle to timely care-seeking in rural Papua New Guinea. Antenatal and postnatal education, and policies that support enhanced education and decision-making powers for women and their families, are urgently needed.

Point-of-care testing and treatment of sexually transmitted and genital infections during pregnancy in Papua New Guinea (WANTAIM trial): protocol for an economic evaluation alongside a cluster-randomised trial.

INTRODUCTION: Left untreated, sexually transmitted and genital infections (henceforth STIs) in pregnancy can lead to serious adverse outcomes for mother and child. Papua New Guinea (PNG) has among the highest prevalence of curable STIs including syphilis, chlamydia, gonorrhoea, trichomoniasis and bacterial vaginosis, and high neonatal mortality rates. Diagnosis and treatment of these STIs in PNG rely on syndromic management. Advances in STI diagnostics through point-of-care (PoC) testing using GeneXpert technology hold promise for resource-constrained countries such as PNG. This paper describes the planned economic evaluation of a cluster-randomised cross-over trial comparing antenatal PoC testing and immediate treatment of curable STIs with standard antenatal care in two provinces in PNG. METHODS AND ANALYSIS: Cost-effectiveness of the PoC intervention compared with standard antenatal care will be assessed prospectively over the trial period (2017-2021) from societal and provider perspectives. Incremental cost-effectiveness ratios will be calculated for the primary health outcome, a composite measure of the proportion of either preterm birth and/or low birth weight; for life years saved; for disability-adjusted life years averted; and for non-health benefits (financial risk protection and improved health equity). Scenario analyses will be conducted to identify scale-up options, and budget impact analysis will be undertaken to understand short-term financial impacts of intervention adoption on the national budget. Deterministic and probabilistic sensitivity analysis will be conducted to account for uncertainty in key model inputs. ETHICS AND DISSEMINATION: This study has ethical approval from the Institutional Review Board of the PNG Institute of Medical Research; the Medical Research Advisory Committee of the PNG National Department of Health; the Human Research Ethics Committee of the University of New South Wales; and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine. Findings will be disseminated through national stakeholder meetings, conferences, peer-reviewed publications and policy briefs. TRIAL REGISTRATION NUMBER: ISRCTN37134032.

Spatial prediction of malaria prevalence in Papua New Guinea: a comparison of Bayesian decision network and multivariate regression modelling approaches for improved accuracy in prevalence prediction.

BACKGROUND: Considerable progress towards controlling malaria has been made in Papua New Guinea through the national malaria control programme's free distribution of long-lasting insecticidal nets, improved diagnosis with rapid diagnostic tests and improved access to artemisinin combination therapy. Predictive prevalence maps can help to inform targeted interventions and monitor changes in malaria epidemiology over time as control efforts continue. This study aims to compare the predictive performance of prevalence maps generated using Bayesian decision network (BDN) models and multilevel logistic regression models (a type of generalized linear model, GLM) in terms of malaria spatial risk prediction accuracy. METHODS: Multilevel logistic regression models and BDN models were developed using 2010/2011 malaria prevalence survey data collected from 77 randomly selected villages to determine associations of Plasmodium falciparum and Plasmodium vivax prevalence with precipitation, temperature, elevation, slope (terrain aspect), enhanced vegetation index and distance to the coast. Predictive performance of multilevel logistic regression and BDN models were compared by cross-validation methods. RESULTS: Prevalence of P. falciparum, based on results obtained from GLMs was significantly associated with precipitation during the 3 driest months of the year, June to August (ß = 0.015; 95% CI = 0.01-0.03), whereas P. vivax infection was associated with elevation (ß = - 0.26; 95% CI = - 0.38 to - 3.04), precipitation during the 3 driest months of the year (ß = 0.01; 95% CI = - 0.01-0.02) and slope (ß = 0.12; 95% CI = 0.05-0.19). Compared with GLM model performance, BDNs showed improved accuracy in prediction of the prevalence of P. falciparum (AUC = 0.49 versus 0.75, respectively) and P. vivax (AUC = 0.56 versus 0.74, respectively) on cross-validation. CONCLUSIONS: BDNs provide a more flexible modelling framework than GLMs and may have a better predictive performance when developing malaria prevalence maps due to the multiple interacting factors that drive malaria prevalence in different geographical areas. When developing malaria prevalence maps, BDNs may be particularly useful in predicting prevalence where spatial variation in climate and environmental drivers of malaria transmission exists, as is the case in Papua New Guinea.

Mycoplasma genitalium and Other Reproductive Tract Infections in Pregnant Women, Papua New Guinea, 2015-2017.

Much about the range of pathogens, frequency of coinfection, and clinical effects of reproductive tract infections (RTIs) among pregnant women remains unknown. We report on RTIs (Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Treponema pallidum subspecies pallidum, bacterial vaginosis, and vulvovaginal candidiasis) and other reproductive health indicators in 699 pregnant women in Papua New Guinea during 2015-2017. We found M. genitalium, an emerging pathogen in Papua New Guinea, in 12.5% of participants. These infections showed no evidence of macrolide resistance. In total, 74.1% of pregnant women had >1 RTI; most of these infections were treatable. We detected sexually transmitted infections (excluding syphilis) in 37.7% of women. Our findings showed that syndromic management of infections is greatly inadequate. In total, 98.4% of women had never used barrier contraception. These findings will inform efforts to improve reproductive healthcare in Papua New Guinea.

Risk factors and knowledge associated with high unintended pregnancy rates and low family planning use among pregnant women in Papua New Guinea.

Unintended pregnancy is a major driver of poor maternal and child health in resource-limited settings. Data on pregnancy intention and use of family planning (FP) is scarce in Papua New Guinea (PNG), but are needed to inform public health strategies to improve FP accessibility and uptake. Data from a facility-based cross-sectional sample of 699 pregnant women assessed prevalence and predictors of unintended pregnancy and modern FP use among pregnant women in East New Britain Province, PNG. More than half (55%) the women reported their pregnancy as unintended. Few (18%) reported ever having used a modern FP method, and knowledge of different methods was low. Being single, separated or divorced (AOR 9.66; 95% CI 3.27-28.54), educated to a tertiary or vocational level (AOR 1.78 CI 1.15-2.73), and gravidity > 1 (AOR 1.43 for each additional pregnancy CI 1.29-1.59) were associated with unintended pregnancy; being accompanied by a male partner to ANC was associated with a reduced unintended pregnancy (0.46 CI 0.30-0.73). Factors associated with modern FP use included male partner involvement (AOR 2.26 CI 1.39-3.67) and gravidity > 1 (AOR 1.54 for each additional pregnancy CI 1.36-1.74). FP use also varied by the facility women attended. Findings highlight an urgent need for targeted interventions to improve FP knowledge, uptake and access, and male partner involvement, to reduce unintended pregnancies and their complications.

Diarrhoeal disease surveillance in Papua New Guinea: findings and challenges.

Diarrhoeal diseases are among the leading causes of morbidity and mortality in the Western Pacific Region. However, data on the major causes of infectious diarrhoea are limited in many countries within the Region, including Papua New Guinea. In 2013-2014, we conducted surveillance for acute diarrhoeal illness in four provinces in Papua New Guinea. One rural health clinic from each province participated in the surveillance activity. Samples were sent to central laboratories and batch analysed for bacterial and viral gastrointestinal pathogens that are commonly associated with diarrhoea. Across the four sites, the most commonly detected pathogens were Shigella spp., Campylobacter spp. and rotavirus. In this paper, we report the results of the surveillance activity and the challenges that we faced. The lessons learnt may be applicable to other parts of the Region with a similar socioeconomic status.

The epidemiology of Plasmodium falciparum and Plasmodium vivax in East Sepik Province, Papua New Guinea, pre- and post-implementation of national malaria control efforts.

BACKGROUND: In the past decade, national malaria control efforts in Papua New Guinea (PNG) have received renewed support, facilitating nationwide distribution of free long-lasting insecticidal nets (LLINs), as well as improvements in access to parasite-confirmed diagnosis and effective artemisinin-combination therapy in 2011-2012. METHODS: To study the effects of these intensified control efforts on the epidemiology and transmission of Plasmodium falciparum and Plasmodium vivax infections and investigate risk factors at the individual and household level, two cross-sectional surveys were conducted in the East Sepik Province of PNG; one in 2005, before the scale-up of national campaigns and one in late 2012-early 2013, after 2 rounds of LLIN distribution (2008 and 2011-2012). Differences between studies were investigated using Chi square (χ2), Fischer's exact tests and Student's t-test. Multivariable logistic regression models were built to investigate factors associated with infection at the individual and household level. RESULTS: The prevalence of P. falciparum and P. vivax in surveyed communities decreased from 55% (2005) to 9% (2013) and 36% to 6%, respectively. The mean multiplicity of infection (MOI) decreased from 1.8 to 1.6 for P. falciparum (p = 0.08) and from 2.2 to 1.4 for P. vivax (p < 0.001). Alongside these reductions, a shift towards a more uniform distribution of infections and illness across age groups was observed but there was greater heterogeneity across the study area and within the study villages. Microscopy positive infections and clinical cases in the household were associated with high rate infection households (> 50% of household members with Plasmodium infection). CONCLUSION: After the scale-up of malaria control interventions in PNG between 2008 and 2012, there was a substantial reduction in P. falciparum and P. vivax infection rates in the studies villages in East Sepik Province. Understanding the extent of local heterogeneity in malaria transmission and the driving factors is critical to identify and implement targeted control strategies to ensure the ongoing success of malaria control in PNG and inform the development of tools required to achieve elimination. In household-based interventions, diagnostics with a sensitivity similar to (expert) microscopy could be used to identify and target high rate households.

Mapping routine malaria incidence at village level for targeted control in Papua New Guinea.

Malaria surveillance and response-systems are essential for identifying the areas most affected by malaria and for targeting interventions and optimising resources. This study aimed to assess whether the visualisation of routinely collected health facility data linked to village of residence provides evidence for targeting control interventions in four sentinel health facilities in Papua New Guinea. A video format was used to visualise the dynamics in case incidence over time and space alongside photographs illustrating the context of the data collection in the study sites. Incidence changes overtime were illustrated in animated maps. Despite limitations, this approach appeared useful in sites with very few remaining cases or with increasingly marked heterogeneity. Villages that could benefit from targeted interventions or investigations were identified.

Repeated mosquito net distributions, improved treatment, and trends in malaria cases in sentinel health facilities in Papua New Guinea.

BACKGROUND: Long-lasting insecticidal nets (LLIN), improved diagnosis and artemisinin-based combination therapy (ACT) have reduced malaria prevalence in Papua New Guinea since 2008. Yet, national incidence trends are inconclusive due to confounding effects of the scale-up of rapid diagnostic tests, and inconsistencies in routine reporting. METHODS: Malaria trends and their association with LLIN and ACT roll-out between 2010 and 2014 in seven sentinel health facilities were analysed. The analysis included 35,329 fever patients. Intervention effects were estimated using regression models. RESULTS: Malaria incidence initially ranged from 20 to 115/1000 population; subsequent trends varied by site. Overall, LLIN distributions had a cumulative effect, reducing the number of malaria cases with each round (incidence rate ratio ranging from 0.12 to 0.53 in five sites). No significant reduction was associated with ACT introduction. Plasmodium falciparum remained the dominant parasite in all sentinel health facilities. Resurgence occurred in one site in which a shift to early and outdoor biting of anophelines had previously been documented. CONCLUSIONS: LLINs, but not ACT, were associated with reductions of malaria cases in a range of settings, but sustainability of the gains appear to depend on local factors. Malaria programmes covering diverse transmission settings such as Papua New Guinea must consider local heterogeneity when choosing interventions and ensure continuous monitoring of trends.

Targets of complement-fixing antibodies in protective immunity against malaria in children.

Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.

Does test-based prescription of evidence-based treatment for malaria improve treatment seeking and satisfaction? Findings of repeated cross-sectional surveys in Papua New Guinea.

INTRODUCTION: The presumptive treatment of febrile illness with antimalarial medication is becoming less common in low-income and middle-income countries as access to reliable diagnostic tests improves. We explore whether the shift towards test-based antimalarial prescription, and the introduction of highly efficacious artemisinin combination therapies (ACTs), reduces critical delays in seeking treatment for febrile illness or increases patient satisfaction. METHODS: We conducted countrywide repeat, cross-sectional surveys in 118 randomly selected primary healthcare services in Papua New Guinea. The clinical case management of 1765 consecutively presenting febrile patients was observed and exit interviews were completed at discharge. This was done prior to implementation of test-based ACT prescription (2011) and at 12 (2012) and 60 months (2016) postimplementation. We conducted multiple logistic regressions. Treatment response time was dichotomised as <24 hours from symptom onset vs 24+ hours. Satisfaction was dichotomised as a 'high' vs 'low' rating based on participant response to a visual, 7-point Likert-type scale. RESULTS: 62% (322/517) of febrile patients reported seeking treatment within 24 hours of symptom onset in 2011 compared with 53% (230/434) in 2012 and 42% (339/814) in 2016. Adjusted ORs for reporting a treatment response time <24 hours in the postimplementation surveys were 0.77 (95% CI 0.48 to 1.26) and 0.45 (95% CI 0.31 to 0.65), respectively when compared with the preimplementation period. 53% (230/533) of febrile patients reported 'high' satisfaction with the service received in 2011 compared with 32% (143/449) in 2012 and 35% (278/803) in 2016. Adjusted ORs for reporting high satisfaction in the postimplementation surveys were 0.52 (95% CI 0.32 to 0.85) and 0.65 (95% CI 0.39 to 1.10), respectively when compared with the preimplementation period. CONCLUSION: Nationwide implementation of test-based ACT prescription in Papua New Guinea has increased the likelihood of critical treatment seeking delays and decreased patient satisfaction with the service received.

A Trial of a Triple-Drug Treatment for Lymphatic Filariasis.

BACKGROUND: The World Health Organization has targeted lymphatic filariasis for global elimination by 2020 with a strategy of mass drug administration. This trial tested whether a single dose of a three-drug regimen of ivermectin plus diethylcarbamazine plus albendazole results in a greater sustained clearance of microfilariae than a single dose of a two-drug regimen of diethylcarbamazine plus albendazole and is noninferior to the two-drug regimen administered once a year for 3 years. METHODS: In a randomized, controlled trial involving adults from Papua New Guinea with Wuchereria bancrofti microfilaremia, we assigned 182 participants to receive a single dose of the three-drug regimen (60 participants), a single dose of the two-drug regimen (61 participants), or the two-drug regimen once a year for 3 years (61 participants). Clearance of microfilariae from the blood was measured at 12, 24, and 36 months after trial initiation. RESULTS: The three-drug regimen cleared microfilaremia in 55 of 57 participants (96%) at 12 months, in 52 of 54 participants (96%) at 24 months, and in 55 of 57 participants (96%) at 36 months. A single dose of the two-drug regimen cleared microfilaremia in 18 of 56 participants (32%) at 12 months, in 31 of 55 participants (56%) at 24 months, and in 43 of 52 participants (83%) at 36 months (P=0.02 for the three-drug regimen vs. a single dose of the two-drug regimen at 36 months). The two-drug regimen administered once a year for 3 years cleared microfilaremia in 20 of 59 participants (34%) at 12 months, in 42 of 56 participants (75%) at 24 months, and in 51 of 52 participants (98%) at 36 months (P=0.004 for noninferiority of the three-drug regimen vs. the two-drug regimen administered once a year for 3 years at 36 months). Moderate adverse events were more common in the group that received the three-drug regimen than in the combined two-drug-regimen groups (27% vs. 5%, P<0.001). There were no serious adverse events. CONCLUSIONS: The three-drug regimen induced clearance of microfilariae from the blood for 3 years in almost all participants who received the treatment and was superior to the two-drug regimen administered once and noninferior to the two-drug regimen administered once a year for 3 years. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01975441 .).

Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria in Papua New Guinea.

BACKGROUND: In 2009, the Papua New Guinea (PNG) Department of Health adopted artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) as the first- and second-line treatments for uncomplicated malaria, respectively. This study was conducted to assess the efficacy of both drugs following adoption of the new policy. METHODS: Between June 2012 and September 2014, a therapeutic efficacy study was conducted in East Sepik and Milne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillance of anti-malarial drug efficacy. Patients ≥ 6 months of age with microscopy confirmed Plasmodium falciparum or Plasmodium vivax mono-infections were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Study endpoints were adequate clinical and parasitological response (ACPR) on days 28 and 42. The in vitro efficacy of anti-malarials and the prevalence of selected molecular markers of resistance were also determined. RESULTS: A total of 274 P. falciparum and 70 P. vivax cases were enrolled. The day-42 PCR-corrected ACPR for P. falciparum was 98.1% (104/106) for AL and 100% (135/135) for DHA-PPQ. The day-42 PCR-corrected ACPR for P. vivax was 79.0% (15/19) for AL and 92.3% (36/39) for DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2% with AL and 100% with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to chloroquine (34% of samples above IC50 threshold) but not to lumefantrine (0%). Molecular markers assessed in a sub-set of the study population indicated high rates of chloroquine resistance in P. falciparum (pfcrt SVMNT: 94.2%, n = 104) and in P. vivax (pvmdr1 Y976F: 64.8%, n = 54). CONCLUSIONS: AL and DHA-PPQ were efficacious as first- and second-line treatments for uncomplicated malaria in PNG. Continued in vivo efficacy monitoring is warranted considering the threat of resistance to artemisinin and partner drugs in the region and scale-up of artemisinin-based combination therapy in PNG.

Iron deficiency during pregnancy is associated with a reduced risk of adverse birth outcomes in a malaria-endemic area in a longitudinal cohort study.

BACKGROUND: Low birth weight (LBW) and preterm birth (PTB) are major contributors to infant mortality and chronic childhood morbidity. Understanding factors that contribute to or protect against these adverse birth outcomes is an important global health priority. Anaemia and iron deficiency are common in malaria-endemic regions, but there are concerns regarding the value of iron supplementation among pregnant women in malaria-endemic areas due to reports that iron supplementation may increase the risk of malaria. There is a lack of evidence on the impact of iron deficiency on pregnancy outcomes in malaria-endemic regions. METHODS: We determined iron deficiency in a cohort of 279 pregnant women in a malaria-endemic area of Papua New Guinea. Associations with birth weight, LBW and PTB were estimated using linear and logistic regression. A causal model using sequential mediation analyses was constructed to assess the association between iron deficiency and LBW, either independently or mediated through malaria and/or anaemia. RESULTS: Iron deficiency in pregnant women was common (71% at enrolment) and associated with higher mean birth weights (230 g; 95% confidence interval, CI 118, 514; p < 0.001), and reduced odds of LBW (adjusted odds ratio, aOR = 0.32; 95% CI 0.16, 0.64; p = 0.001) and PTB (aOR = 0.57; 95% CI 0.30, 1.09; p = 0.089). Magnitudes of effect were greatest in primigravidae (birth weight 351 g; 95% CI 188, 514; p < 0.001; LBW aOR 0.26; 95% CI 0.10, 0.66; p = 0.005; PTB aOR = 0.39, 95% CI 0.16, 0.97; p = 0.042). Sequential mediation analyses indicated that the protective association of iron deficiency on LBW was mainly mediated through mechanisms independent of malaria or anaemia. CONCLUSIONS: Iron deficiency was associated with substantially reduced odds of LBW predominantly through malaria-independent protective mechanisms, which has substantial implications for understanding risks for poor pregnancy outcomes and evaluating the benefit of iron supplementation in pregnancy. This study is the first longitudinal study to demonstrate a temporal relationship between antenatal iron deficiency and improved birth outcomes. These findings suggest that iron supplementation needs to be integrated with other strategies to prevent or treat infections and undernutrition in pregnancy to achieve substantial improvements in birth outcomes.

The impact of the scale-up of malaria rapid diagnostic tests on the routine clinical diagnosis procedures for febrile illness: a series of repeated cross-sectional studies in Papua New Guinea.

BACKGROUND: This paper examines the impact of the scale-up of malaria rapid diagnostic tests (RDT) on routine clinical diagnosis procedures for febrile illness in primary healthcare settings in Papua New Guinea. METHODS: Repeat, cross-sectional surveys in randomly selected primary healthcare services were conducted. Surveys included passive observation of consecutive febrile case management cases and were completed immediately prior to RDT scale-up (2011) and at 12- (2012) and 60-months (2016) post scale-up. The frequency with which specified diagnostic questions and procedures were observed to occur, with corresponding 95% CIs, was calculated for febrile patients prescribed anti-malarials pre- and post-RDT scale-up and between febrile patients who tested either negative or positive for malaria infection by RDT (post scale-up only). RESULTS: A total of 1809 observations from 120 health facilities were completed across the three survey periods of which 915 (51%) were prescribed an anti-malarial. The mean number of diagnostic questions and procedures asked or performed, leading to anti-malarial prescription, remained consistent pre- and post-RDT scale-up (range 7.4-7.7). However, alterations in diagnostic content were evident with the RDT replacing body temperature as the primary diagnostic procedure performed (observed in 5.3 and 84.4% of cases, respectively, in 2011 vs. 77.9 and 58.2% of cases in 2016). Verbal questioning, especially experience of fever, cough and duration of symptoms, remained the most common feature of a diagnostic examination leading to anti-malarial prescription irrespective of RDT use (observed in 96.1, 86.8 and 84.8% of cases, respectively, in 2011 vs. 97.5, 76.6 and 85.7% of cases in 2016). Diagnostic content did not vary substantially by RDT result. CONCLUSIONS: Rapid diagnostic tests scale-up has led to a reduction in body temperature measurement. Investigations are very limited when malaria infection is ruled out as a cause of febrile illness by RDT.

Performance of syndromic management for the detection and treatment of genital Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis among women attending antenatal, well woman and sexual health clinics in Papua New Guinea: a cross-sectional study.

OBJECTIVE: Papua New Guinea (PNG) has among the highest estimated prevalences of genital Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) of any country in the Asia-Pacific region. Diagnosis and treatment of these infections have relied on the WHO-endorsed syndromic management strategy that uses clinical presentation without laboratory confirmation to make treatment decisions. We evaluated the performance of this strategy in clinical settings in PNG. DESIGN: Women attending antenatal (ANC), well woman (WWC) and sexual health (SHC) clinics in four provinces were invited to participate, completed a face-to-face interview and clinical examination, and provided genital specimens for laboratory testing. We estimated the performance characteristics of syndromic diagnoses against combined laboratory diagnoses. RESULTS: 1764 women were enrolled (ANC=765; WWC=614; SHC=385). The prevalences of CT, NG and TV were highest among women attending ANC and SHC. Among antenatal women, syndromic diagnosis of sexually transmitted infection had low sensitivity (9%-21%) and positive predictive value (PPV) (7%-37%), but high specificity (76%-89%) and moderate negative predictive value (NPV) (55%-86%) for the combined endpoint of laboratory-confirmed CT, NG or TV. Among women attending WWC and SHC, 'vaginal discharge syndrome' had moderate to high sensitivity (72%-78%) and NPV (62%-94%), but low specificity (26%-33%) and PPV (8%-38%). 'Lower abdominal pain syndrome' had low sensitivity (26%-41%) and PPV (8%-23%) but moderate specificity (66%-68%) and high NPV (74%-93%) among women attending WWC, and moderate-high sensitivity (67%-79%) and NPV (62%-86%) but low specificity (26%-28%) and PPV (14%-33%) among SHC attendees. CONCLUSION: The performance of syndromic management for the detection and treatment of genital chlamydia, gonorrhoea and trichomonas was poor among women in different clinical settings in PNG. New diagnostic strategies are needed to control these infections and to prevent their adverse health outcomes in PNG and other high-burden countries.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.