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ObjectiveTo examine associations between Neisseria gonorrhoeae (NG) infection during pregnancy and the risk of preterm birth, spontaneous abortion, premature rupture of membranes, perinatal mortality, low birth weight and ophthalmia neonatorum.Data sourcesWe searched Medline, EMBASE, the Cochrane Library and Cumulative Index to Nursing and Allied Health Literature for studies published between 1948 and 14 January 2020.MethodsStudies were included if they reported testing for NG during pregnancy and compared pregnancy, perinatal and/or neonatal outcomes between women with and without NG. Two reviewers independently assessed papers for inclusion and extracted data. Risk of bias was assessed using established checklists for each study design. Summary ORs with 95% CIs were generated using random effects models for both crude and, where available, adjusted associations.ResultsWe identified 2593 records and included 30 in meta-analyses. Women with NG were more likely to experience preterm birth (OR 1.55, 95% CI 1.21 to 1.99, n=18 studies); premature rupture of membranes (OR 1.41, 95% CI 1.02 to 1.92, n=9); perinatal mortality (OR 2.16, 95% CI 1.35 to 3.46, n=9); low birth weight (OR 1.66, 95% CI 1.12 to 2.48, n=8) and ophthalmia neonatorum (OR 4.21, 95% CI 1.36 to 13.04, n=6). Summary adjusted ORs were, for preterm birth 1.90 (95% CI 1.14 to 3.19, n=5) and for low birth weight 1.48 (95% CI 0.79 to 2.77, n=4). In studies with a multivariable analysis, age was the variable most commonly adjusted for. NG was more strongly associated with preterm birth in low-income and middle-income countries (OR 2.21, 95% CI 1.40 to 3.48, n=7) than in high-income countries (OR 1.38, 95% CI 1.04 to 1.83, n=11).ConclusionsNG is associated with a number of adverse pregnancy and newborn outcomes. Further research should be done to determine the role of NG in different perinatal mortality outcomes because interventions that reduce mortality will have the greatest impact on reducing the burden of disease in low-income and middle-income countries.PROSPERO registration numberCRD42016050962.

Sexually transmitted and genital infections in pregnancy are associated with adverse pregnancy and birth outcomes. Point-of-care tests for these infections facilitate testing and treatment in a single antenatal clinic visit and may reduce the risk of adverse outcomes. Successful implementation and scale-up depends on understanding comparative effectiveness of such programmes and their comparative costs and cost effectiveness. This systematic review synthesises and appraises evidence from economic evaluations of point-of-care testing and treatment for sexually transmitted and genital infections among pregnant women in low- and middle-income countries. Medline, Embase and Web of Science databases were comprehensively searched using pre-determined criteria. Additional literature was identified by searching Google Scholar and the bibliographies of all included studies. Economic evaluations were eligible if they were set in low- and middle-income countries and assessed antenatal point-of-care testing and treatment for syphilis, chlamydia, gonorrhoea, trichomoniasis, and/or bacterial vaginosis. Studies were analysed using narrative synthesis. Methodological and reporting standards were assessed using two published checklists. Sixteen economic evaluations were included in this review; ten based in Africa, three in Latin and South America and three were cross-continent comparisons. Fifteen studies assessed point-of-care testing and treatment for syphilis, while one evaluated chlamydia. Key drivers of cost and cost-effectiveness included disease prevalence; test, treatment, and staff costs; test sensitivity and specificity; and screening and treatment coverage. All studies met 75% or more of the criteria of the Drummond Checklist and 60% of the Consolidated Health Economics Evaluation Reporting Standards. Generally, point-of-care testing and treatment was cost-effective compared to no screening, syndromic management, and laboratory-based testing. Future economic evaluations should consider other common infections, and their lifetime impact on mothers and babies. Complementary affordability and equity analyses would strengthen the case for greater investment in antenatal point-of-care testing and treatment for sexually transmitted and genital infections.

Pneumococcal disease is a leading cause of childhood mortality, globally. The pneumococcal conjugate vaccine (PCV) has been introduced to many countries worldwide. However there are few studies evaluating PCV impacts in low- and middle-income countries (LMIC) because measuring the impact of PCV on pneumococcal disease in LMICs is challenging. We review the role of pneumococcal carriage studies for the evaluation of PCVs in LMICs and discuss optimal methods for conducting these studies. Fifteen carriage studies from 13 LMICs quantified the effects of PCV on carriage, and identified replacement carriage serotypes in the post-PCV era. Ten studies reported on the indirect effects of PCV on carriage. Results can be used to inform cost-effectiveness evaluations, guide policy decisions on dosing and product, and monitor equity in program implementation. Critically, we highlight gaps in our understanding of serotype replacement disease in LMICs and identify priorities for research to address this gap.

Papua New Guinea (PNG) has the highest malaria transmission outside of Africa. Long-lasting insecticidal nets (LLINs) are believed to have helped to reduce average malaria prevalence in PNG from 16% in 2008 to 1% in 2014. Since 2015 malaria in PNG has resurged significantly. Here, we present observations documenting decreased bioefficacy of unused LLINs with manufacturing dates between 2013 and 2019 collected from villages and LLIN distributors in PNG. Specifically, we show that of n  = 167 tested LLINs manufactured after 2013, only 17% are fulfilling the required World Health Organisation bioefficacy standards of ≥ 80% 24 h mortality or ≥ 95% 60 min knockdown in bioassays with pyrethroid susceptible Anopheles farauti mosquitoes. In contrast, all (100%, n  = 25) LLINs with manufacturing dates prior to 2013 are meeting these bioefficacy standards. These results suggest that decreased bioefficacy of LLINs is contributing to the malaria resurgence in PNG and increased scrutiny of LLIN quality is warranted. Malaria prevalence in Papua New Guinea has risen in recent years after almost a decade of decline. In this study, the authors demonstrate that long-lasting insecticidal nets used in the country that were manufactured since 2013 have significantly reduced bioefficacy.

Background High nasopharyngeal pneumococcal carriage density is associated with severe pneumonia; however, little is known about factors that affect pneumococcal carriage density including pneumococcal vaccination. We describe pneumococcal density by clinical and demographic factors, and effect of 13-valent pneumococcal conjugate vaccine (PCV13) on density in Papua New Guinea (PNG), Lao People’s Democratic Republic (Lao PDR) and Mongolia, 3–6 years following national PCV13 introduction. Methods Three prospective pneumococcal carriage surveillance studies enrolled children aged 2–59 months with acute respiratory infections in Lao PDR (2013–2019), and pneumonia in PNG (2016–2019) and Mongolia (2015–2019). Demographic and clinical factors were collected on interview and from medical records. Nasopharyngeal swabs were tested for pneumococci using lytA real-time quantitative PCR and molecular serotyping using DNA microarray. In unvaccinated children median pneumococcal carriage density was compared across relevant clinical and demographic factors using Wilcoxon rank sum or Kruskal Wallis tests. Quantile regression models were used to determine the association between pneumococcal density, vaccination status and number of PCV doses. Results A total of 1009 (PNG), 532 (Lao PDR) and 621 (Mongolia) pneumococcal carriers were included. Of carriers with serotyping results, PCV13 serotype (VT) carriage was 36.1% (356/985) in PNG, 40.8% (189/463) in Lao PDR and 50.7% (270/532) in Mongolia. The median pneumococcal VT density was 6.25 log 10 GE/ml (genome equivalents per milliliter) (interquartile range [IQR] 5.66, 6.79) in PNG, 5.74 log 10 GE/ml (IQR 4.99, 6.40) in Lao PDR and 5.64 log 10 GE/ml (IQR 5.11, 6.32) in Mongolia. In PNG, Lao PDR and Mongolia, 54.4%, 51.1% and 34.9% pneumococcal carriers were fully vaccinated, respectively. There was no difference in VT pneumococcal density by relevant clinical and demographic factors in unvaccinated children. In PNG, VT density was slightly lower (-0.36, 95% confidence interval [CI] -0.61, -0.12; p  = 0.004) among vaccinated compared with unvaccinated children, in particular those who received three doses (-0.37 95% CI -0.63, -0.10; p  = 0.007). No differences were observed in Lao PDR and Mongolia. Conclusions We demonstrated variable results across our three sites. Indirect PCV13 effects may have resulted in limited observed reductions in VT density in unvaccinated children. In PNG, PCV13 vaccination was associated with a decline in VT density. Trial registration Not applicable.

•Pneumococcal carriage and antimicrobial non-susceptibility in the first PCV10-PCV13 trial in children in a high-risk setting.•Pneumococcal carriage rates remain high in PCV10 and PCV13 recipients.•Children carry a broad range of vaccine and non-vaccine serotypes.•Ongoing carriage of highly non-susceptible vaccine serotypes 14 and 19A and non-serotypeable pneumococci was evident. Children in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13). Infants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC). S. pneumoniae was isolated from 883/1063 NPS collected at 1–23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6–97.6%) of PCV10 recipients and 88.6% (95%CI 80.1–94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2–29.5) than PCV13 recipients (9.3%, 95%CI 4.1–17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC ≥ 0.12 µg/mL), but resistance was rare (1.1%) using the non-meningitis cut-off (MIC ≥ 8 µg/mL). Non-susceptibility to trimethoprim-sulfamethoxazole (SXT) was common: 23.2% of isolates showed intermediate resistance (MIC 1/19–2/38 µg/mL) and 16.9% full resistance (MIC ≥ 4/76 µg/mL). PCV serotypes 14 and 19A were commonly non-susceptible to both penicillin (14, 97%; 19A, 70%) and SXT (14, 97%; 19A, 87%). Even after PCV10 or PCV13 vaccination, children living in a high-risk setting such as PNG continue to experience high levels of pneumococcal colonization, including carriage of highly antimicrobial-resistant PCV serotypes. The study is registered with ClinicalTrials.gov (CTN NCT01619462).

Background Although global poverty rates have declined in the last decade, the fall in the Asia-Pacific region has been slow relative to the rest of the world. Poverty continues to be a major cause of poor maternal and newborn health, and a barrier to accessing timely antenatal care. Papua New Guinea has one of the highest poverty rates and some of the worst maternal and neonatal outcomes in the Asia-Pacific region. Few studies have investigated equity in antenatal care utilization in this setting. We explored equity in antenatal care utilization and the determinants of service utilization, which include a measure of multidimensional poverty in Papua New Guinea. Methods To explore the association between poverty and antenatal care utilization this study uses data from a ten-cluster randomized controlled trial. The poverty headcount, average poverty gap, adjusted poverty headcount, and multidimensional poverty index of antenatal clinic attendees are derived using the Alkire-Foster method. The distribution of service utilization is explored using the multidimensional poverty index, followed by multivariate regression analyses to evaluate the determinants of service utilization. Results The poverty headcount was 61.06%, the average poverty gap 47.71%, the adjusted poverty headcount 29.13% and the average multidimensional poverty index was 0.363. Further, antenatal care utilization was regressive with respect to poverty. The regression analyses indicated that older women; being a widow (small number of widows ( n  = 3) asserts interpreting result with caution); or formally employed increase the likelihood of accessing antenatal care more often in pregnancy. Travelling for over an hour to receive care was negatively associated with utilization. Conclusion This study indicated high levels of multidimensional poverty in PNG and that ANC utilization was regressive; highlighting the need to encourage pregnant women, especially those who are economically more vulnerable to visit clinics regularly throughout pregnancy.

The human-infecting parasite Strongyloides fuelleborni subspecies kellyi has been reported from the island of New Guinea. We analyzed fecal DNA extracts (n = 164) from 19 infants in Papua New Guinea by using Strongyloides real-time PCR and undertook metabarcoding of cox1 and 18S rRNA hypervariable regions I and IV loci. Eight infants were infected with Strongyloides spp.; 7 were infected with S. fuelleborni subsp. fuelleborni and 1 with a Strongyloides sp. previously misattributed to S. fuelleborni subsp. kellyi. Phylogenetic and haplotyping analyses indicated S. fuelleborni in Papua New Guinea belongs to the Indochina subclade of S. fuelleborni subsp. fuelleborni and is not a unique subspecies. We report molecular evidence of S. fuelleborni subsp. fuelleborni infection in humans in the Pacific. Our findings also demonstrate the potential co-existence of an undescribed human-infecting Strongyloides sp. on the island of New Guinea, indicating a need for renewed clinical and epidemiologic investigations into infant strongyloidiasis.

Persons with lymphatic filariasis (LF) are often co-infected with soil-transmitted helminths. A single co-administered dose of ivermectin/diethylcarbamazine/albendazole (IDA) is recommended by WHO for mass drug administration (MDA) for LF instead of diethylcarbamazine/albendazole (DA) in Papua New Guinea (PNG). We compared the effectiveness of a single round of MDA with IDA or DA on hookworm and strongyloidiasis in PNG. This study was conducted as part of a cluster randomized trial of MDA with IDA versus DA for LF in individuals willing to provide stool and blood samples at baseline and 12 months after MDA. Participants from 23 villages were included in the clinical trial. Primary outcomes were changes in hookworm prevalence and infection intensity assessed by Kato Katz and Strongyloides prevalence by serology. Hookworm prevalence at baseline was 78% (91/117) and 80% (119/149) in villages assigned to DA and IDA treatment, respectively. Twelve months post-MDA, hookworm prevalence decreased to 56.5% in DA- and 34.4% in IDA-treated villages, respectively (p<0.001, both comparisons). The proportion of individuals with moderate to heavy infection (>2000 egg per gram (EPG)) similarly decreased from 8.7% to 1.5% after DA (p = 0.001) and from 5.7% to 1.0% after IDA (p = 0.002). Using a logistic regression model adjusting for age, gender, baseline hookworm prevalence, and village drug coverage, IDA resulted in a 45% greater reduction in hookworm prevalence than DA (Odds ratio 0.55, 95% CI [0.31,0.99], p = 0.049). MDA also reduced hookworm transmission. Strongyloides seroprevalence at baseline was 68% (192/283) and 62% (180/290) in IDA and DA villages, respectively, with 49% becoming seronegative in the IDA versus 23% in DA villages at 12 months (p = 0.0001). MDA with IDA was more effective than DA for reducing hookworm and Strongyloides infections in PNG, extending the benefit of MDA with IDA beyond its effect on LF.

Background Papua New Guinea (PNG) has one of the highest burdens of HIV and syphilis in pregnancy in the Asia-Pacific region. Timely and effective diagnosis can alleviate the burden of HIV and syphilis and improve maternal and newborn health. Supply-side factors related to implementation and scale up remain problematic, yet few studies have considered their impact on antenatal testing and treatment for HIV and syphilis. This study explores health service availability and readiness for antenatal HIV and/or syphilis testing and treatment in PNG. Methods Using data from two sources, we demonstrate health service availability and readiness. Service availability is measured at a province level as the average of three indicators: infrastructure, workforce, and antenatal clinic utilization. The readiness score comprises 28 equally weighted indicators across four domains; and is estimated for 73 health facilities. Bivariate and multivariate robust linear regressions explore associations between health facility readiness and the proportion of antenatal clinic attendees tested and treated for HIV and/or syphilis. Results Most provinces had fewer than one health facility per 10 000 population. On average, health worker density was 11 health workers per 10 000 population per province, and approximately 22% of pregnant women attended four or more antenatal clinics. Most health facilities had a composite readiness score between 51% and 75%, with urban health facilities faring better than rural ones. The multivariate regression analysis, when controlling for managing authority, catchment population, the number of clinicians employed, health facility type and residence (urban/rural) indicated a weak positive relationship between health facility readiness and the proportion of antenatal clinic attendees tested and treated for HIV and/or syphilis. Conclusion This study adds to the limited evidence base for the Asia-Pacific region. There is a need to improve antenatal testing and treatment coverage for HIV and syphilis and reduce healthcare inequalities faced by rural and urban communities. Shortages of skilled health workers, tests, and medicines impede the provision of quality antenatal care. Improving service availability and health facility readiness are key to ensuring the effective provision of antenatal care interventions.