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Infectious bronchitis virus (IBV) causes a major disease problem for the poultry industry worldwide. The currently used live-attenuated vaccines have the tendency to mutate and/or recombine with circulating field strains resulting in the emergence of vaccine-derived variant viruses. In order to circumvent these issues, and to develop a vaccine that is more relevant to Egypt and its neighboring countries, a recombinant avirulent Newcastle disease virus (rNDV) strain LaSota was constructed to express the codon-optimized S glycoprotein of the Egyptian IBV variant strain IBV/Ck/EG/CU/4/2014 belonging to GI-23 lineage, that is prevalent in Egypt and in the Middle East. A wild type and two modified versions of the IBV S protein were expressed individually by rNDV. A high level of S protein expression was detected in vitro by Western blot and immunofluorescence analyses. All rNDV-vectored IBV vaccine candidates were genetically stable, slightly attenuated and showed growth patterns comparable to that of parental rLaSota virus. Single-dose vaccination of 1-day-old SPF White Leghorn chicks with the rNDVs expressing IBV S protein provided significant protection against clinical disease after IBV challenge but did not show reduction in tracheal viral shedding. Single-dose vaccination also provided complete protection against virulent NDV challenge. However, prime-boost vaccination using rNDV expressing the wild type IBV S protein provided better protection, after IBV challenge, against clinical signs and significantly reduced tracheal viral shedding. These results indicate that the NDV-vectored IBV vaccines are promising bivalent vaccine candidates to control both infectious bronchitis and Newcastle disease in Egypt. [ABSTRACT FROM AUTHOR]

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.

Background: Further reduction in malaria prevalence and its eventual elimination would be greatly facilitated by the development of biomarkers of exposure and/or acquired immunity to malaria, as well as the deployment of effective vaccines against Plasmodium falciparum and Plasmodium vivax. A better understanding of the acquisition of immunity in naturally-exposed populations is essential for the identification of antigens useful as biomarkers, as well as to inform rational vaccine development., Methods: ELISA was used to measure total IgG to a synthetic form of glycosylphosphatidylinositol from P. falciparum (PfGPI) in a cohort of 1-3 years old Papua New Guinea children with well-characterized individual differences in exposure to P. falciparum and P. vivax blood-stage infections. The relationship between IgG levels to PfGPI and measures of recent and past exposure to P. falciparum and P. vivax infections was investigated, as well as the association between antibody levels and prospective risk of clinical malaria over 16 months of follow-up., Results: Total IgG levels to PfGPI were low in the young children tested. Antibody levels were higher in the presence of P. falciparum or P. vivax infections, but short-lived. High IgG levels were associated with higher risk of P. falciparum malaria (IRR 1.33-1.66, P = 0.008-0.027), suggesting that they are biomarkers of increased exposure to P. falciparum infections. Given the cross-reactive nature of antibodies to PfGPI, high IgG levels were also associated with reduced risk of P. vivax malaria (IRR 0.65-0.67, P = 0.039-0.044), indicating that these antibodies are also markers of acquired immunity to P. vivax., Conclusions: This study highlights that in young children, IgG to PfGPI might be a useful marker of immune-status to both P. falciparum and P. vivax infections, and potentially useful to help malaria control programs to identify populations at-risk. Further functional studies are necessary to confirm the potential of PfGPI as a target for vaccine development.

Background: Papua New Guinea (PNG) is a diverse and culturally-rich country with severe infrastructural and health problems. Tuberculosis (TB) is widespread, and the number of cases with drug resistance is rising. Treatment adherence is known to be important for both effective treatment and limiting the emergence of drug resistance. The aim of this study was to construct a matrix of the factors that act as facilitators or barriers to TB treatment adherence in a remote region of PNG., Methods: The study was based in the Balimo region of the Western Province. People known to have undergone TB treatment, as well as staff involved in managing people with TB, were asked to participate in an in-depth interview about their experiences. Purposive sampling was used to identify a diverse range of participants, from different geographic locations, social backgrounds, and with successful and unsuccessful treatment outcomes. The interview data was analysed based on grounded theory methodology., Results: The study identified a range of factors that influence TB treatment adherence, with these being classified as personal, systems, and sociocultural. These factors are presented along with suggested recommendations for adaptations to DOTS-based treatment in this region. Barriers included the challenges associated with travel to treatment sites, and the difficulties of undertaking treatment alongside the daily need to maintain subsistence food production. However, facilitators were also identified, including the positive influence of religious beliefs, and high confidence in the ability of DOTS-based treatment to cure TB., Conclusions: Documenting the wide range of factors that influence treatment adherence in a severely affected remote population will assist in improving TB control. These results provide impetus for further community-based efforts aimed at improving access to TB diagnosis and treatment, and maintaining successful treatment outcomes in the face of emerging drug resistance.

Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria., Methods: Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured., Results: Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria., Conclusion: These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.

Background: Bacterial meningitis remains an important infection globally, with the greatest burden in children in low-income settings, including Papua New Guinea (PNG). We present serotype, antimicrobial susceptibility and outcome data from paediatric meningitis patients prior to introduction of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCVs) in PNG, providing a baseline for evaluation of immunisation programs., Methods: Cerebrospinal fluid (CSF) was collected from children admitted to Goroka General Hospital with suspected meningitis between 1996 and 2005. Culture and sensitivity was conducted, and pneumococci and H. influenzae were serotyped. Laboratory findings were linked to clinical outcomes., Results: We enrolled 1884 children. A recognised pathogen was identified in 375 children (19.9%). Streptococcus pneumoniae (n = 180) and Hib (n = 153) accounted for 88.8% of pathogens isolated. 24 different pneumococcal serogroups were identified; non-PCV types 2, 24 and 46 accounted for 31.6% of pneumococcal meningitis. 10- and 13-valent PCVs would cover 44.1% and 45.4% of pneumococcal meningitis respectively. Pneumococcal isolates were commonly resistant to penicillin (21.5%) and 23% of Hib isolates were simultaneously resistant to ampicillin, co-trimoxazole and chloramphenicol. The case fatality rate in patients with a recognised bacterial pathogen was 13.4% compared to 8.5% in culture-negative patients., Conclusions: If implemented in routine expanded programme of immunisation (EPI) with high coverage, current PCVs could prevent almost half of pneumococcal meningitis cases. Given the diversity of circulating serotypes in PNG serotype replacement is of concern. Ongoing surveillance is imperative to monitor the impact of vaccines. In the longer term vaccines providing broader protection against pneumococcal meningitis will be needed.

Background: Chewing areca nut (AN), also known as betel nut, is common in Asia and the South Pacific and the habit has been linked to a number of serious health problems including oral cancer. Use of AN in pregnancy has been associated with a reduction in mean birthweight in some studies, but this association and the relationship between AN chewing and other adverse pregnancy outcomes remain poorly understood., Methods: We assessed the impact of AN chewing on adverse outcomes including stillbirth, low birthweight (LBW, <2,500 g) and anaemia at delivery (haemoglobin <11.0 g/dL) in a longitudinal cohort of 2,700 pregnant women residing in rural lowland Papua New Guinea (PNG) from November 2009 until February 2013. Chewing habits and participant characteristics were evaluated at first antenatal visit and women were followed until delivery., Results: 83.3% [2249/2700] of pregnant women used AN, and most chewed on a daily basis (86.2% [1939/2249]. Smoking and alcohol use was reported by 18.9% (511/2700) and 5.0% (135/2688) of women, respectively. AN use was not associated with pregnancy loss or congenital abnormalities amongst women with a known pregnancy outcome (n = 2215). Analysis of 1769 birthweights did not demonstrate an association between AN and LBW (chewers: 13.7% [200/1459] vs. non-chewers: 14.5% [45/310], P = 0.87) or reduced mean birthweight (2957 g vs. 2966 g; P = 0.76). Women using AN were more likely to be anaemic (haemoglobin <11 g/dL) at delivery (75.2% [998/1314] vs. 63.9% [182/285], adjusted odds ratio [95% CI]: 1.67 [1.27, 2.20], P < 0.001). Chewers more commonly had male babies than non-chewers (46.1% [670/1455] vs. 39.8% [123/309], P = 0.045)., Conclusions: AN chewing may contribute to anaemia. Although not associated with other adverse pregnancy outcome in this cohort gestational AN use should be discouraged, given the potential adverse effects on haemoglobin and well-established long-term health risk including oral cancer. Future research evaluating the potential association of AN use and anaemia may be warranted., Trial Registration: ClinicalTrials.gov NCT01136850 (06 April 2010).

Background: Fetal growth restriction (FGR) is associated with increased infant mortality rates and ill-health in adulthood. Evaluation of fetal growth requires ultrasound. As a result, ultrasound-assisted evaluations of causes of FGR in malaria-endemic developing countries are rare. We aimed to determine factors associated with indicators of abnormal fetal growth in rural lowland Papua New Guinea (PNG)., Methods: Weights and growth of 671 ultrasound-dated singleton pregnancies (<25 gestational weeks) were prospectively monitored using estimated fetal weights and birthweights. Maternal nutritional status and haemoglobin levels were assessed at enrolment, and participants were screened for malaria on several occasions. FGR was suspected upon detection of an estimated fetal weight or birthweight <10(th) centile (small-for-gestational age) and/or low fetal weight gain, defined as a change in weight z-score in the first quartile. Factors associated with fetal weight and fetal weight gain were additionally assessed by evaluating differences in weight z-scores and change in weight z-scores. Log-binomial and linear mixed effect models were used to determine factors associated with indicators of FGR., Results: SGA and low weight gain were detected in 48.3% and 37.0% of pregnancies, respectively. Of participants, 13.8%, 21.2%, and 22.8% had a low mid-upper arm circumference (MUAC, <22 cms), short stature (<150 cms) and anaemia (haemoglobin <90 g/L) at first antenatal visit. 24.0% (161/671) of women had at least one malaria infection detected in peripheral blood. A low MUAC (adjusted risk ratio [aRR] 1.51, 95% CI 1.29, 1.76, P < 0.001), short stature (aRR 1.27, 95% CI 1.04, 1.55, P = 0.009), and anaemia (aRR 1.27, 95% CI 1.06, 1.51, P = 0.009) were associated with SGA, and a low body mass index was associated with low fetal weight gain (aRR 2.10, 95% CI 1.62, 2.71, P < 0.001). Additionally, recent receipt of intermittent preventive treatment in pregnancy was associated with increased weight z-scores, and anaemia with reduced change in weight z-scores. Malaria infection was associated with SGA on crude but not adjusted analyses (aRR 1.13, 95% CI 0.95, 1.34, P = 0.172)., Conclusion: Macronutrient undernutrition and anaemia increased the risk of FGR. Antenatal nutritional interventions and malaria prevention could improve fetal growth in PNG.

Background: Intermittent preventive treatment in pregnancy has not been evaluated outside of Africa. Low birthweight (LBW, <2,500 g) is common in Papua New Guinea (PNG) and contributing factors include malaria and reproductive tract infections., Methods: From November 2009 to February 2013, we conducted a parallel group, randomised controlled trial in pregnant women (≤ 26 gestational weeks) in PNG. Sulphadoxine-pyrimethamine (1,500/75 mg) plus azithromycin (1 g twice daily for 2 days) (SPAZ) monthly from second trimester (intervention) was compared against sulphadoxine-pyrimethamine and chloroquine (450 to 600 mg, daily for three days) (SPCQ) given once, followed by SPCQ placebo (control). Women were assigned to treatment (1:1) using a randomisation sequence with block sizes of 32. Participants were blinded to assignments. The primary outcome was LBW. Analysis was by intention-to-treat., Results: Of 2,793 women randomised, 2,021 (72.4%) were included in the primary outcome analysis (SPCQ: 1,008; SPAZ: 1,013). The prevalence of LBW was 15.1% (305/2,021). SPAZ reduced LBW (risk ratio [RR]: 0.74, 95% CI: 0.60-0.91, P = 0.005; absolute risk reduction (ARR): 4.5%, 95% CI: 1.4-7.6; number needed to treat: 22), and preterm delivery (0.62, 95% CI: 0.43-0.89, P = 0.010), and increased mean birthweight (41.9 g, 95% CI: 0.2-83.6, P = 0.049). SPAZ reduced maternal parasitaemia (RR: 0.57, 95% CI: 0.35-0.95, P = 0.029) and active placental malaria (0.68, 95% CI: 0.47-0.98, P = 0.037), and reduced carriage of gonorrhoea (0.66, 95% CI: 0.44-0.99, P = 0.041) at second visit. There were no treatment-related serious adverse events (SAEs), and the number of SAEs (intervention 13.1% [181/1,378], control 12.7% [174/1,374], P = 0.712) and AEs (intervention 10.5% [144/1,378], control 10.8% [149/1,374], P = 0.737) was similar. A major limitation of the study was the high loss to follow-up for birthweight., Conclusions: SPAZ was efficacious and safe in reducing LBW, possibly acting through multiple mechanisms including the effect on malaria and on sexually transmitted infections. The efficacy of SPAZ in the presence of resistant parasites and the contribution of AZ to bacterial antibiotic resistance require further study. The ability of SPAZ to improve pregnancy outcomes warrants further evaluation., Trial Registration: ClinicalTrials.gov NCT01136850 (06 April 2010).

Background: Viral central nervous system (CNS) infections are common in countries where malaria is endemic but, due to limited laboratory facilities, few studies have systematically examined the prevalence and clinical consequences of the presence of viruses in cerebrospinal fluid (CSF) from children with suspected CNS infection., Methods: We performed a prospective study of Papua New Guinean children hospitalized with signs and symptoms of CNS infection. CSF samples from 300 children without proven bacterial/fungal meningitis were analyzed for human herpes viruses (HHV), picornaviruses, influenza, adenoviruses, flaviviruses and bacteria., Results: Fifty-five children (18%) had viral (42), bacterial (20) or both viral and bacterial (7) nucleic acids (NA) identified in their CSF. Human herpes viruses accounted for 91% of all viruses found. The identification of viral or bacterial NA was not associated with any characteristic clinical features. By contrast, malaria was associated with increased identification of viral and bacterial NA and with impaired consciousness, multiple convulsions and age. Malaria was also inversely associated with an adverse outcome. Amongst children with HHV infection, those with HHV-6 and -7 were younger, were more likely have impaired consciousness and had a higher proportion of adverse outcomes than children with CMV. Dengue and enteroviral infections were infrequent. Adenoviral and influenza infections were not identified., Conclusion: Infections with HHV-6, HHV-7, dengue and enterovirus have the potential to cause serious CNS disease in young PNG children. However most HHVs in this malaria-endemic setting should be considered to be the result of reactivation from a latent reservoir without clinical sequelae.

Background: The accuracy of the World Health Organization method of estimating malaria parasite density from thick blood smears by assuming a white blood cell (WBC) count of 8,000/μL has been questioned in several studies. Since epidemiological investigations, anti-malarial efficacy trials and routine laboratory reporting in Papua New Guinea (PNG) have all relied on this approach, its validity was assessed as part of a trial of artemisinin-based combination therapy, which included blood smear microscopy and automated measurement of leucocyte densities on Days 0, 3 and 7., Results: 168 children with uncomplicated malaria (median (inter-quartile range) age 44 (39-47) months) were enrolled, 80.3% with Plasmodium falciparum monoinfection, 14.9% with Plasmodium vivax monoinfection, and 4.8% with mixed P. falciparum/P. vivax infection. All responded to allocated therapy and none had a malaria-positive slide on Day 3. Consistent with a median baseline WBC density of 7.3 (6.5-7.8) × 10(9)/L, there was no significant difference in baseline parasite density between the two methods regardless of Plasmodium species. Bland Altman plots showed that, for both species, the mean difference between paired parasite densities calculated from assumed and measured WBC densities was close to zero. At parasite densities <10,000/μL by measured WBC, almost all between-method differences were within the 95% limits of agreement. Above this range, there was increasing scatter but no systematic bias., Conclusions: Diagnostic thresholds and parasite clearance assessment in most PNG children with uncomplicated malaria are relatively robust, but accurate estimates of a higher parasitaemia, as a prognostic index, requires formal WBC measurement.

Background: The incidence and characteristics of tuberculosis (TB) in remote areas of Papua New Guinea (PNG) are largely unknown. The purpose of our study was to determine the incidence of TB in the Gulf Province of PNG and describe disease characteristics, co-morbidities and drug resistance profiles that could impact on disease outcomes and transmission., Methods: Between March 2012 and June 2012, we prospectively collected data on 274 patients presenting to Kikori Hospital with a presumptive diagnosis of TB, and on hospital inpatients receiving TB treatment during the study period. Sputum was collected for microscopy, GeneXpert analysis, culture and genotyping of isolates., Results: We estimate the incidence of TB in Kikori to be 1290 per 100,000 people (95% CI 1140 to 1460) in 2012. The proportion of TB patients co-infected with HIV was 1.9%. Three of 32 TB cases tested were rifampicin resistant. Typing of nine isolates demonstrated allelic diversity and most were related to Beijing strains., Conclusions: The incidence of TB in Kikori is one of the highest in the world and it is not driven by HIV co-infection. The high incidence and the presence of rifampicin resistant warrant urgent attention to mitigate substantial morbidity in the region.

Background: The success of health programs is influenced not only by their acceptability but also their ability to meet and respond to community expectations of service delivery. The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have recommended medical male circumcision (MC) as an essential component of comprehensive HIV prevention programs in high burden settings. This study investigated community-level perceptions of MC for HIV prevention in Papua New Guinea (PNG), a setting where diverse traditional and contemporary forms of penile foreskin cutting practices have been described., Methods: A multi-method qualitative study was undertaken in four provinces in two stages from 2009 to 2011. A total of 82 in-depth interviews, and 45 focus group discussions were completed during Stage 1. Stage 2 incorporated eight participatory workshops that were an integral part of the research dissemination process to communities. The workshops also provided opportunity to review key themes and consolidate earlier findings as part of the research process. Qualitative data analysis used a grounded theory approach and was facilitated using qualitative data management software., Results: A number of diverse considerations for the delivery of MC for HIV prevention in PNG were described, with conflicting views both between and within communities. Key issues included: location of the service, service provider, age eligibility, type of cut, community awareness and potential shame amongst youth. Key to developing appropriate health service delivery models was an appreciation of the differences in expectations and traditions of unique cultural groups in PNG. Establishing strong community coalitions, raising awareness and building trust were seen as integral to success., Conclusions: Difficulties exist in the implementation of new programs in a pluralistic society such as PNG, particularly if tensions arise between biomedical knowledge and medico-legal requirements, compared to existing socio-cultural interests. Community participatory approaches offer important opportunities to explore and design culturally safe, specific and accessible programs.

Background: In resource-limited settings where healthcare services are limited and poverty is common, it is difficult to ethically conduct clinical research without providing patient-care. Therefore, integration of patient-care with clinical research appears as an attractive way of conducting research while providing patient-care. In this article, we discuss the ethical implications of such approach with perspectives from Papua New Guinea., Discussion: Considering the difficulties of providing basic healthcare services in developing countries, it may be argued that integration of clinical research with patient-care is an effective, rational and ethical way of conducting research. However, blending patient-care with clinical research may increase the risk of subordinating patient-care in favour of scientific gains; therapeutic misconception and inappropriate inducement; and the risk of causing health system failures due to limited capacity in developing countries to sustain the level of healthcare services sponsored by the research. Nevertheless, these ethical and administrative implications can be minimised if patient-care takes precedence over research; the input of local ethics committees and institutions are considered; and funding agencies acknowledge their ethical obligation when sponsoring research in resource-limited settings., Summary: Although integration of patient-care with clinical research in developing countries appears as an attractive way of conducting research when resources are limited, careful planning and consideration on the ethical implications of such approach must be considered.

Background: Prune belly syndrome is a rare congenital malformation of unknown aetiology and is characterised by abnormalities of the urinary tract, a deficiency of abdominal musculature and bilateral cryptorchidism in males. We report a case of prune belly syndrome from Papua New Guinea, which was suspected on pregnancy ultrasound scan and confirmed upon delivery., Case Presentation: A 26-year-old married woman, Gravida 3 Para 2, presented to antenatal clinic in Madang, Papua New Guinea, at 21(+5) weeks' gestation by dates. She was well with no past medical or family history of note. She gave consent to participate in a clinical trial on prevention of malaria in pregnancy and underwent repeated ultrasound examinations which revealed a live fetus with persistent megacystis and anhydramnios. Both mother and clinicians agreed on conservative management of the congenital abnormality. The mother spontaneously delivered a male fetus weighing 2010 grams at 34 weeks' gestation with grossly abnormal genitalia including cryptorchidism, penile aplasia and an absent urethral meatus, absent abdominal muscles and hypoplastic lungs. The infant passed away two hours after delivery. This report discusses the implications of prenatal detection of severe congenital abnormalities in PNG., Conclusion: This first, formally reported, case of prune belly syndrome from a resource-limited setting in the Oceania region highlights the importance of identifying and documenting congenital abnormalities. Women undergoing antenatal ultrasound examinations must be carefully counseled on the purpose and the limitations of the scan. The increasing use of obstetric ultrasound in PNG will inevitably result in a rise in prenatal detection of congenital abnormalities. This will need to be met with adequate training, referral mechanisms and better knowledge of women's attitudes and beliefs on birth defects and ultrasound. National medicolegal guidance regarding induced abortion and resuscitation of a fetus with severe congenital abnormalities may be required.

Background: Plasmodium vivax and Plasmodium falciparum malaria remain highly endemic in the Pacific Islands including Lihir Island, Papua New Guinea. Lihir Gold Limited is conducting mining activities and funded an integrated vector control intervention within the villages surrounding the mine. The aim of this study was to assess the impact of such programme by comparing the epidemiological trends of malaria in different parts of the island., Methods: Two cross-sectional surveys were conducted before and after the intervention (2006-2010) to determine malaria prevalence in mine-impact (MI) and non-MI areas. Incidence of malaria was estimated for the Lihir Medical Centre catchment area using island population denominators and a health-centre passive case detection ongoing from 2006-2011., Results: A total of 2,264 and 1,653 children < 15 were surveyed in the cross-sectional studies. The prevalence of any malaria parasitaemia initially was 31.5% in MI areas and, 34.9% in non-MI (POR 1.17; 95 CI 0.97 - 1.39). After four years there was a significant reduction in prevalence in the MI areas (5.8%; POR 0.13, 95 CI 0.09-0.20), but reduction was less marked in non-MI areas (26.9%; POR 0.69, 95 CI 0.58-0.81).28,747 patients were included in the evaluation of incidence trends and overall malaria in local Lihirian population in MI areas declined over time, while it remained at similar high levels among migrants. The age-incidence analysis showed that for each higher age range the malaria incidence declines compared to that of the previous stratum., Conclusions: There was a substantial reduction in prevalence and incidence rates of both P. vivax and P. falciparum in the mining area following implementation of a malaria control intervention, which was not seen in the area outside the mining activities.

Background: The motivation of health workers (HWs) to deliver services in developing countries has been described as a critical factor in the success of health systems in implementing programmes. How the sociocultural context of Papua New Guinea (PNG) affects the values, motivation and actions of HWs involved in sexual and reproductive health services is important for policy development and programme planning. With interest in male circumcision (MC) as an HIV prevention option in PNG, this study explored the perceptions and motivations of HWs involved in sexual and reproductive health services in PNG, examining their implications for the possible future roll out of a national MC programme., Methods: A multi-method qualitative study was conducted with HWs across a range of health care professions working in sexual health facilities. A total of 29 in-depth interviews and one focus group discussion were completed. Qualitative thematic analysis of the transcripts and field notes was undertaken using a social constructivist approach and complemented by documentary organizational, programme and policy analysis., Results and Discussions: Introduction of new health programmes, such as a MC programme for HIV prevention, are likely to impact upon one or more of the many motivational determinants. Social-cultural and individual factors influencing HW motivation to be involved in sexual and reproductive health services in PNG included community expectation and concern, sense of accomplishment and religious conviction. Strong links to community responsibility outweighed organizational ties. Faced with an often dysfunctional work environment, HWs perceived themselves as responsible to compensate for the failed health system. The impact of community influence and expectation needs to be considered when introducing a MC programme, particularly to communities in PNG where penile foreskin cutting is a common and accepted practice., Conclusions: The potential contribution to the success of a MC programme that HWs may have means that taking into account the differing needs of communities as well as the motivational influences on HWs that exist within the sociocultural environment is important. These findings will assist not only in programme planning for MC, but also in the expansion of other existing sexual and reproductive health services.

Background: The acceptability of female-controlled biomedical prevention technologies has not been established in Papua New Guinea, the only country in the Pacific region experiencing a generalised, moderate-prevalence HIV epidemic. Socio-cultural factors likely to impact on future product uptake and effectiveness, such as women's ability to negotiate safer sexual choices, and intravaginal hygiene and menstrual practices (IVP), remain unclear in this setting., Methods: A mixed-method qualitative study was conducted among women and men attending a sexual health clinic in Port Moresby. During in-depth interviews, participants used copies of a hand-drawn template to indicate how they wash/clean the vulva and/or vagina. Interviewers pre-filled commercially available vaginal applicators with 2-3mL KY Jelly® to create a surrogate vaginal microbicide product, which was demonstrated to study participants., Results: A total of 28 IDIs were conducted (women=16; men=12). A diverse range of IVP were reported. The majority of women described washing the vulva only with soap and water as part of their daily routine; in preparation for sex; and following sexual intercourse. Several women described cleaning inside the vagina using fingers and soap at these same times. Others reported cleaning inside the vagina using a hose connected to a tap; using vaginal inserts, such as crushed garlic; customary menstrual 'steaming' practices; and the use of material fragments, cloth and newspaper to absorb menstrual blood. Unprotected sex during menstruation was common. The majority of both women and men said that they would use a vaginal microbicide gel for HIV/STI protection, should a safe and effective product become available. Microbicide use was considered most appropriate in 'high-risk' situations, such as sex with non-regular, transactional or commercial partners. Most women felt confident that they would be able to negotiate vaginal microbicide use with male sexual partners but if necessary would be prepared to use product covertly., Conclusions: Notional acceptability of a vaginal microbicide gel for HIV/STI prevention was high among both women and men. IVP were diverse in nature, socio-cultural dimensions and motivators. These factors are likely to impact on the future acceptability and uptake of vaginal microbicides and other biomedical HIV prevention technologies in this setting.

Background: Male circumcision (MC) has been shown to reduce the risk of HIV acquisition among heterosexual men, with WHO recommending MC as an essential component of comprehensive HIV prevention programs in high prevalence settings since 2007. While Papua New Guinea (PNG) has a current prevalence of only 1%, the high rates of sexually transmissible diseases and the extensive, but unregulated, practice of penile cutting in PNG have led the National Department of Health (NDoH) to consider introducing a MC program. Given public interest in circumcision even without active promotion by the NDoH, examining the potential health systems implications for MC without raising unrealistic expectations presents a number of methodological issues. In this study we examined health systems lessons learned from a national no-scalpel vasectomy (NSV) program, and their implications for a future MC program in PNG., Methods: Fourteen in-depth interviews were conducted with frontline health workers and key government officials involved in NSV programs in PNG over a 3-week period in February and March 2011. Documentary, organizational and policy analysis of HIV and vasectomy services was conducted and triangulated with the interviews. All interviews were digitally recorded and later transcribed. Application of the WHO six building blocks of a health system was applied and further thematic analysis was conducted on the data with assistance from the analysis software MAXQDA., Results: Obstacles in funding pathways, inconsistent support by government departments, difficulties with staff retention and erratic delivery of training programs have resulted in mixed success of the national NSV program., Conclusions: In an already vulnerable health system significant investment in training, resources and negotiation of clinical space will be required for an effective MC program. Focused leadership and open communication between provincial and national government, NGOs and community is necessary to assist in service sustainability. Ensuring clear policy and guidance across the entire sexual and reproductive health sector will provide opportunities to strengthen key areas of the health system.

Background: Monitoring drug resistance in Mycobacterium tuberculosis is essential to curb the spread of tuberculosis (TB). Unfortunately, drug susceptibility testing is currently not available in Papua New Guinea (PNG) and that impairs TB control in this country. We report for the first time M. tuberculosis mutations associated with resistance to first and second-line anti-TB drugs in Madang, PNG. A molecular cluster analysis was performed to identify M. tuberculosis transmission in that region., Results: Phenotypic drug susceptibility tests showed 15.7% resistance to at least one drug and 5.2% multidrug resistant (MDR) TB. Rifampicin resistant strains had the rpoB mutations D516F, D516Y or S531L; Isoniazid resistant strains had the mutations katG S315T or inhA promoter C15T; Streptomycin resistant strains had the mutations rpsL K43R, K88Q, K88R), rrs A514C or gidB V77G. The molecular cluster analysis indicated evidence for transmission of resistant strain., Conclusions: We observed a substantial rate of MDR-TB in the Madang area of PNG associated with mutations in specific genes. A close monitoring of drug resistance is therefore urgently required, particularly in the presence of drug-resistant M. tuberculosis transmission. In the absence of phenotypic drug susceptibility testing in PNG, molecular assays for drug resistance monitoring would be of advantage.

Background: Male circumcision (MC) has been shown to reduce vaginal transmission of HIV to men. While community acceptability is important in a countries preparedness to introduce MC, it is equally important to map contemporary MC and other penile cutting practices, and the socio-cultural dimensions underpinning these practices., Methods: A total of 482 men and women (n = 276 and n = 210, respectively) participated in 82 semi-structured and 45 focus group discussions from four different provinces of Papua New Guinea (PNG), each representing one of the four socially and geographically diverse regions of the country., Results: Of the men interviewed 131 self-reported that they had undergone a penile alteration with some reporting multiple types. Practices were diverse and could be grouped into five broad categories: traditional (customary) penile cutting; contemporary penile cutting; medical circumcision; penile inserts; and penile bloodletting practices in which sharp objects are used to incise the glans and or inserted and withdrawn from the male urethra or in order to induce bleeding. Socio-cultural traditions, enhanced sexual pleasure and improved genital hygiene were key motivators for all forms of penile practices., Conclusions: The findings from this study highlight the complex and diverse nature of penile practices in PNG and their association with notions of masculinity, sexuality and contagion. Contemporary penile practices are critical to a community's acceptance of MC and of a country's ability to successfully implement MC in the context of a rich and dynamic culture of penile practices. If a MC program were to be successfully rolled out in PNG to prevent HIV it would need to work within and build upon these diverse cultural meanings and motivators for penile practices already commonly performed in PNG by men.

Background: Papua New Guinea (PNG) is one of the nutritionally vulnerable countries with a high rate of children death without showing a sign of improvement in last two decades. Current study investigated the prevalences of stunting and wasting among a cohort of children in PNG and described the spatial features of these outcomes at the province and district-levels., Objective: To determine the prevalences of stunting and wasting among a cohort of children in PNG and to describe the spatial features of these outcomes at the province and district-levels. We also described the spatial features of these outcomes at province and district-levels., Methods: The health and nutritional status of 683 children aged less than five years was assessed using a cross-sectional multi-stage household survey conducted in the Eastern Highlands and Madang Provinces of PNG during the period of 2003-2004. Growth z-scores such as height-for-age and weight-for-age were generated using World Health Organization classifications., Results: The prevalences of stunting (height-for-age z-score less than -2.0) were 59% and 49% in the Eastern Highlands and Madang respectively (P = 0.019). The prevalences of wasting (weight-for-height z-score less than -2.0) were 14% and 22% in Eastern Highlands and Madang respectively, (P = 0.039); overall, only 21% of the children had completed all their scheduled vaccines and 95% of the caregivers had less than primary school education. Our statistical maps showed considerable spatial variations (province- and district-levels) with regard to the stunting, wasting and other key factors within a relatively small geographical region., Conclusions: Current study determined one of the highest prevalence of stunting among children in PNG. The impact of geographical locations on the risk factors must be recognized as it affects epidemiology and intervention coverage.

Microvascular sequestration of Plasmodium falciparum underlies cerebral malaria. Despite suggestive ex vivo evidence, this phenomenon has not been convincingly demonstrated in coma complicating Plasmodium vivax malaria. Severely-ill Papua New Guinean children with mixed P. falciparum/P. vivax infections are more likely to develop cerebral malaria and die than those with P. falciparum alone, possibly reflecting P. vivax sequestration. Nested PCR was performed on post mortem brain tissue from three such children dying from cerebral malaria due to mixed-species infections. No P. vivax DNA was detected. These findings do not support the hypothesis that P. vivax sequestration occurs in human brain.

Introduction: Interleukin-22 (IL-22) is a cytokine of IL-10 family with significant proliferative effect on different cell lines. Immunopathological role of IL-22 has been studied in rheumatoid arthritis (RA) and psoriasis. Here we are reporting the functional role of IL-22 in the inflammatory and proliferative cascades of psoriatic arthritis (PsA)., Method: From peripheral blood and synovial fluid (SF) of PsA (n = 15), RA (n = 15) and osteoarthritis (OA, n = 15) patients, mononuclear cells were obtained and magnetically sorted for CD3+ T cells. Fibroblast like synoviocytes (FLS) were isolated from the synovial tissue of PsA (n = 5), RA (n = 5) and OA (n = 5) patients. IL-22 levels in SF and serum were measured by enzyme linked immunosorbent assay (ELISA). Proliferative effect of human recombinant IL-22 (rIL-22) on FLS was assessed by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole) and CFSE dilution (Carboxyfluorescein succinimidyl ester) assays. Expression of IL-22Rα1 in FLS was determined by western blot., Results: IL-22 levels were significantly elevated in SF of PsA patients (17.75 ± 3.46 pg/ml) compared to SF of OA (5.03 ± 0.39 pg/ml), p < 0.001. In MTT and CFSE dilution assays, rIL-22 (MTT, OD: 1.27 ± 0.06) induced significant proliferation of FLS derived from PsA patients compared to media (OD: 0.53 ± 0.02), p < 0.001. In addition, rIL-22 induced significantly more proliferation of FLS in presence of TNF-α. IL-22Rα1 was expressed in FLS of PsA, RA and OA patients. Anti IL-22R antibody significantly inhibited the proliferative effect of rIL-22. Further we demonstrated that activated synovial T cells of PsA and RA patients produced significantly more IL-22 than those of OA patients., Conclusion: SF of PsA patients have higher concentration of IL-22 and rIL-22 induced marked proliferation of PsA derived FLS. Moreover combination of rIL-22 and TNF-α showed significantly more proliferative effect on FLS. IL-22Rα1 was expressed in FLS. Successful inhibition of IL-22 induced FLS proliferation by anti IL-22R antibody suggests that blocking of IL-22/IL-22R interaction may be considered as a novel therapeutic target for PsA.

Background: Adult male surgical circumcision (MC) has been shown to reduce HIV acquisition in men and is recommended by the WHO for inclusion in comprehensive national HIV prevention programs in high prevalence settings. Only limited research to date has been conducted in countries experiencing moderate burden epidemics, where the acceptability, operational feasibility and potential epidemiological impact of MC remain unclear., Methods: A multi-method qualitative research study was conducted at four sites in Papua New Guinea (PNG), with 24 focus group discussions and 65 in-depth interviews carried out among 276 men., Results: The majority of men were in favour of MC being introduced for HIV prevention in PNG and considered improved genital hygiene, enhanced sexual pleasure and culturally appropriateness key factors in the acceptability of a future intervention. A minority of men were against the introduction of MC, primarily due to concerns regarding sexual risk compensation and that the intervention went against prevailing cultural and religious beliefs., Conclusion: This is one of the first community-based MC acceptability studies conducted in a moderate prevalence setting outside of Africa. Research findings from this study suggest that a future MC program for HIV prevention would be widely accepted by men in PNG.

Background: Reports of severe cases and increasing levels of drug resistance highlight the importance of improved Plasmodium vivax case management. Whereas monitoring P. vivax resistance to anti-malarial drug by in vivo and in vitro tests remain challenging, molecular markers of resistance represent a valuable tool for high-scale analysis and surveillance studies. A new high-throughput assay for detecting the most relevant markers related to P. vivax drug resistance was developed and assessed on Papua New Guinea (PNG) patient isolates., Methods: Pvdhfr, pvdhps and pvmdr1 fragments were amplified by multiplex nested PCR. Then, PCR products were processed through an LDR-FMA (ligase detection reaction - fluorescent microsphere assay). 23 SNPs, including pvdhfr 57-58-61 and 173, pvdhps 382-383, 553, 647 and pvmdr1 976, were simultaneously screened in 366 PNG P. vivax samples., Results: Genotyping was successful in 95.4% of the samples for at least one gene. The coexistence of multiple distinct haplotypes in the parasite population necessitated the introduction of a computer-assisted approach to data analysis. Whereas 73.1% of patients were infected with at least one wild-type genotype at codons 57, 58 and 61 of pvdhfr, a triple mutant genotype was detected in 65.6% of the patients, often associated with the 117T mutation. Only one patient carried the 173L mutation. The mutant 647P pvdhps genotype allele was approaching genetic fixation (99.3%), whereas 35.1% of patients were infected with parasites carrying the pvmdr1 976F mutant allele., Conclusions: The LDR-FMA described here allows a discriminant genotyping of resistance alleles in the pvdhfr, pvdhps, and pvmdr1 genes and can be used in large-scale surveillance studies.

Background: Building on previous acceptability research undertaken in sub-Saharan Africa this article aims to investigate the acceptability of intermittent preventive treatment of malaria in infants (IPTi) in Papua New Guinea (PNG)., Methods: A questionnaire was administered to mothers whose infants participated in the randomised placebo controlled trial of IPTi. Mothers whose infants participated and who refused to participate in the trial, health workers, community reporters and opinion leaders were interviewed. Men and women from the local community also participated in focus group discussions., Results: Respondents viewed IPTi as acceptable in light of wider concern for infant health and the advantages of trial participation. Mothers reported complying with at-home administration of IPTi due to perceived benefits of IPTi and pressure from health workers. In spite of patchy knowledge, respondents also demonstrated a demand for infant vaccinations and considered non-vaccination to be neglect. There is little evidence that IPTi has negative impacts on attitudes to EPI, EPI adherence or existing malaria prevention practices., Conclusion: The degree of similarity between findings from the acceptability studies undertaken in sub-Saharan Africa and PNG allows some generalization relating to the implementation of IPTi outside of Africa: IPTi fits well with local health cultures, appears to be accepted easily and has little impact on attitudes towards EPI or malaria prevention. The study adds to the evidence indicating that IPTi could be rolled out in a range of social and cultural contexts.