How advanced is the epidemiological transition in Papua New Guinea? New evidence from verbal autopsy.

BACKGROUND: Reliable cause of death (COD) data are not available for the majority of deaths in Papua New Guinea (PNG), despite their critical policy value. Automated verbal autopsy (VA) methods, involving an interview and automated analysis to diagnose causes of community deaths, have recently been trialled in PNG. Here, we report VA results from three sites and highlight the utility of these methods to generate information about the leading CODs in the country. METHODS: VA methods were introduced in one district in each of three provinces: Alotau in Milne Bay; Tambul-Nebilyer in Western Highlands; and Talasea in West New Britain. VA interviews were conducted using the Population Health Metrics Research Consortium (PHMRC) shortened questionnaire and analysed using the SmartVA automated diagnostic algorithm. RESULTS: A total of 1655 VAs were collected between June 2018 and November 2019, 87.0% of which related to deaths at age 12 years and over. Our findings suggest a continuing high proportion of deaths due to infectious diseases (27.0%) and a lower proportion of deaths due to non-communicable diseases (NCDs) (50.8%) than estimated by the Global Burden of Disease Study (GBD) 2017: 16.5% infectious diseases and 70.5% NCDs. The proportion of injury deaths was also high compared with GBD: 22.5% versus 13.0%. CONCLUSIONS: Health policy in PNG needs to address a 'triple burden' of high infectious mortality, rising NCDs and a high fraction of deaths due to injuries. This study demonstrates the potential of automated VA methods to generate timely, reliable and policy-relevant data on COD patterns in hard-to-reach populations in PNG.

Validation of SmartVA using conventional autopsy: A study of adult deaths in Brazil.

Background: Accurate cause of death data are essential to guide health policy. However, mortality surveillance is limited in many low-income countries. In such settings, verbal autopsy (VA) is increasingly used to provide population-level cause of death data. VAs are now widely interpreted using the automated algorithms SmartVA and InterVA. Here we use conventional autopsy as the gold standard to validate SmartVA methodology. Methods: This study included adult deaths from natural causes in São Paulo and Recife for which conventional autopsy was indicated. VA was conducted with a relative of the deceased using an amended version of the SmartVA instrument to suit the local context. Causes of death from VA were produced using the SmartVA-Analyze program. Physician coded verbal autopsy (PCVA), conducted on the same questionnaires, and Global Burden of Disease Study data were used as additional comparators. Cause of death data were grouped into 10 broad causes for the validation due to the real-world utility of VA lying in identifying broad population cause of death patterns. Findings: The study included 2,060 deaths in São Paulo and 1,079 in Recife. The cause specific mortality fractions (CSMFs) estimated using SmartVA were broadly similar to conventional autopsy for: cardiovascular diseases (46.8% vs 54.0%, respectively), cancers (10.6% vs 11.4%), infections (7.0% vs 10.4%) and chronic respiratory disease (4.1% vs 3.7%), causes accounting for 76.1% of the autopsy dataset. The SmartVA CSMF estimates were lower than autopsy for "Other NCDs" (7.8% vs 14.6%) and higher for diabetes (13.0% vs 6.6%). CSMF accuracy of SmartVA compared to autopsy was 84.5%. CSMF accuracy for PCVA was 93.0%. Interpretation: The results suggest that SmartVA can, with reasonable accuracy, predict the broad cause of death groups important to assess a population's epidemiological transition. VA remains a useful tool for understanding causes of death where medical certification is not possible.

Diversity of epidemiological transition in the Pacific: Findings from the application of verbal autopsy in Papua New Guinea and the Solomon Islands.

BACKGROUND: Cause of death data are essential for rational health planning yet are not routinely available in Papua New Guinea (PNG) and Solomon Islands. Indirect estimation of cause of death patterns suggests these populations are epidemiologically similar, but such assessments are not based on direct evidence. METHODS: Verbal autopsy (VA) interviews were conducted at three sites in PNG and nationwide in Solomon Islands. Training courses were also facilitated to improve data from medical certificates of cause of death (MCCODs) in both countries. Data were categorised into broad groups of endemic and emerging conditions to aid assessment of the epidemiological transition. FINDINGS: Between 2017 and 2020, VAs were collected for 1,814 adult deaths in PNG and 819 adult deaths in Solomon Islands. MCCODs were analysed for 662 deaths in PNG and 1,408 deaths in Solomon Islands. The VA data suggest lower NCD mortality (48.8% versus 70.3%); higher infectious mortality (27.0% versus 18.3%) and higher injury mortality (24.5% versus 11.4%) in PNG compared to Solomon Islands. Higher infectious mortality in PNG was evident for both endemic and emerging infections. Higher NCD mortality in Solomon Islands reflected much higher emerging NCDs (43.6% vs 21.4% in PNG). A similar pattern was evident from the MCCOD data. INTERPRETATION: The cause of death patterns suggested by VA and MCCOD indicate that PNG is earlier in its epidemiological transition than Solomon Islands, with relatively higher infectious mortality and lower NCD mortality. Injury mortality was also particularly high in PNG.This study was funded by Bloomberg Philanthropies.

Mortality surveillance and verbal autopsy strategies: experiences, challenges and lessons learnt in Papua New Guinea.

Full notification of deaths and compilation of good quality cause of death data are core, sequential and essential components of a functional civil registration and vital statistics (CRVS) system. In collaboration with the Government of Papua New Guinea (PNG), trial mortality surveillance activities were established at sites in Alotau District in Milne Bay Province, Tambul-Nebilyer District in Western Highlands Province and Talasea District in West New Britain Province.Provincial Health Authorities trialled strategies to improve completeness of death notification and implement an automated verbal autopsy methodology, including use of different notification agents and paper or mobile phone methods. Completeness of death notification improved from virtually 0% to 20% in Talasea, 25% and 75% using mobile phone and paper notification strategies, respectively, in Alotau, and 69% in Tambul-Nebilyer. We discuss the challenges and lessons learnt with implementing these activities in PNG, including logistical considerations and incentives.Our experience indicates that strategies to maximise completeness of notification should be tailored to the local context, which in PNG includes significant geographical, cultural and political diversity. We report that health workers have great potential to improve the CRVS programme in PNG through managing the collection of notification and verbal autopsy data. In light of our findings, and in consultation with the main government CRVS stakeholders and the National CRVS Committee, we make recommendations regarding the requirements at each level of the health system to optimise mortality surveillance in order to generate the essential health intelligence required for policy and planning.

Improving medical certification of cause of death: effective strategies and approaches based on experiences from the Data for Health Initiative.

BACKGROUND: Accurate and timely cause of death (COD) data are essential for informed public health policymaking. Medical certification of COD generally provides the majority of COD data in a population and is an essential component of civil registration and vital statistics (CRVS) systems. Accurate completion of the medical certificate of cause of death (MCCOD) should be a relatively straightforward procedure for physicians, but mistakes are common. Here, we present three training strategies implemented in five countries supported by the Bloomberg Philanthropies Data for Health (D4H) Initiative at the University of Melbourne (UoM) and evaluate the impact on the quality of certification. METHODS: The three training strategies evaluated were (1) training of trainers (TOT) in the Philippines, Myanmar, and Sri Lanka; (2) direct training of physicians by the UoM D4H in Papua New Guinea (PNG); and (3) the implementation of an online and basic training strategy in Peru. The evaluation involved an assessment of MCCODs before and after training using an assessment tool developed by the University of Melbourne. RESULTS: The TOT strategy led to reductions in incorrectly completed certificates of between 28% in Sri Lanka and 40% in the Philippines. Following direct training of physicians in PNG, the reduction in incorrectly completed certificates was 30%. In Peru, the reduction in incorrect certificates was 30% after implementation and training on an online system only and 43% after training on both the online system and basic medical certification principles. CONCLUSIONS: The results of this study indicate that a variety of training strategies can produce benefits in the quality of certification, but further improvements are possible. The experiences of D4H suggest several aspects of the strategies that should be further developed to improve outcomes, particularly key stakeholder engagement from early in the intervention and local committees to oversee activities and support an improved culture in hospitals to support better diagnostic skills and practices.

A rapid triage test for active pulmonary tuberculosis in adult patients with persistent cough.

Improved tuberculosis (TB) prevention and control depend critically on the development of a simple, readily accessible rapid triage test to stratify TB risk. We hypothesized that a blood protein-based host response signature for active TB (ATB) could distinguish it from other TB-like disease (OTD) in adult patients with persistent cough, thereby providing a foundation for a point-of-care (POC) triage test for ATB. Three adult cohorts consisting of ATB suspects were recruited. A bead-based immunoassay and machine learning algorithms identified a panel of four host blood proteins, interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF), that distinguished ATB from OTD. An ultrasensitive POC-amenable single-molecule array (Simoa) panel was configured, and the ATB diagnostic algorithm underwent blind validation in an independent, multinational cohort in which ATB was distinguished from OTD with receiver operator characteristic-area under the curve (ROC-AUC) of 0.80 [95% confidence interval (CI), 0.75 to 0.85], 80% sensitivity (95% CI, 73 to 85%), and 65% specificity (95% CI, 57 to 71%). When host antibodies against TB antigen Ag85B were added to the panel, performance improved to 86% sensitivity and 69% specificity. A blood-based host response panel consisting of four proteins and antibodies to one TB antigen can help to differentiate ATB from other causes of persistent cough in patients with and without HIV infection from Africa, Asia, and South America. Performance characteristics approach World Health Organization (WHO) target product profile accuracy requirements and may provide the foundation for an urgently needed blood-based POC TB triage test.

Monitoring progress in reducing maternal mortality using verbal autopsy methods in vital registration systems: what can we conclude about specific causes of maternal death?

Reducing maternal mortality is a key focus of development strategies and one of the indicators used to measure progress towards achieving the Sustainable Development Goals. In the absence of medical certification of the cause of deaths that occur in the community, verbal autopsy (VA) methods are the only available means to assess levels and trends of maternal deaths that occur outside health facilities. The 2016 World Health Organization VA Instrument facilitates the identification of eight specific causes of maternal death, yet maternal deaths are often unsupervised, leading to sparse and generally poor symptom reporting to inform a reliable diagnosis using VAs. There is little research evidence to support the reliable identification of specific causes of maternal death in the context of routine VAs. We recommend that routine VAs are only used to capture the event of a maternal death and that more detailed follow-up interviews are used to identify the specific causes.

The epidemiological transition in Papua New Guinea: new evidence from verbal autopsy studies.

BACKGROUND: Recent economic growth in Papua New Guinea (PNG) would suggest that the country may be experiencing an epidemiological transition, characterized by a reduction in infectious diseases and a growing burden from non-communicable diseases (NCDs). However, data on cause-specific mortality in PNG are very sparse, and the extent of the transition within the country is poorly understood. METHODS: Mortality surveillance was established in four small populations across PNG: West Hiri in Central Province, Asaro Valley in Eastern Highlands Province, Hides in Hela Province and Karkar Island in Madang Province. Verbal autopsies (VAs) were conducted on all deaths identified, and causes of death were assigned by SmartVA and classified into five broad disease categories: endemic NCDs; emerging NCDs; endemic infections; emerging infections; and injuries. Results from previous PNG VA studies, using different VA methods and spanning the years 1970 to 2001, are also presented here. RESULTS: A total of 868 deaths among adolescents and adults were identified and assigned a cause of death. NCDs made up the majority of all deaths (40.4%), with the endemic NCD of chronic respiratory disease responsible for the largest proportion of deaths (10.5%), followed by the emerging NCD of diabetes (6.2%). Emerging infectious diseases outnumbered endemic infectious diseases (11.9% versus 9.5%). The distribution of causes of death differed across the four sites, with emerging NCDs and emerging infections highest at the site that is most socioeconomically developed, West Hiri. Comparing the 1970-2001 VA series with the present study suggests a large decrease in endemic infections. CONCLUSIONS: Our results indicate immediate priorities for health service planning and for strengthening of vital registration systems, to more usefully serve the needs of health priority setting.

New challenges for verbal autopsy: Considering the ethical and social implications of verbal autopsy methods in routine health information systems.

Verbal autopsy (VA) methods are designed to collect cause-of-death information from populations where many deaths occur outside of health facilities and where death certification is weak or absent. A VA consists of an interview with a relative or carer of a recently deceased individual in order to gather information on the signs and symptoms the decedent presented with prior to death. These details are then used to determine and assign a likely cause-of-death. At a population level this information can be invaluable to help guide prioritisation and direct health policy and services. To date VAs have largely been restricted to research contexts but many countries are now venturing to incorporate VA methods into routine civil registration and vital statistics (CRVS) systems. Given the sensitive nature of death, however, there are a number of ethical, legal and social issues that should be considered when scaling-up VAs, particularly in the cross-cultural and socio-economically disadvantaged environments in which they are typically applied. Considering each step of the VA process this paper provides a narrative review of the social context of VA methods. Harnessing the experiences of applying and rolling out VAs as part of routine CRVS systems in a number of low and middle income countries, we identify potential issues that countries and implementing institutions need to consider when incorporating VAs into CRVS systems and point to areas that could benefit from further research and deliberation.

Pneumonia research in Papua New Guinea: 1967-1986.

Between 1967 and 1985 research on pneumonia in Papua New Guinea (PNG) was fundamental not only to standard treatments of disease in PNG, but also to the establishment of the World Health Organization's global Program for Control of Acute Respiratory Infections. Pneumonia was the leading cause of death in both population-based and hospital studies. Research that began in 1967 revealed a pattern of disease in adults reminiscent of that seen in industrialized countries in the early 20th century. Streptococcus pneumoniae (pneumococcus) was the predominant causative organism. Pneumococci were commensals of the upper respiratory tract that invaded first the lungs and then the blood stream. Some serotypes were more invasive than others and case fatality increased with deeper levels of invasion. The pandemic of Hong Kong (H3N2) influenza spread to the Southern Highlands in 1969 resulting in 2000 deaths. The conclusion that pneumococcal pneumonia had been the principal cause of death led to the establishment of a pneumonia research unit in Tari. A field trial of pneumococcal polysaccharide vaccine showed the vaccine to be most effective in preventing invasive disease. Vaccination reduced pneumonia mortality by 44% in previously healthy adults. The epidemiological situation was more complex in children than in adults because many different species and serotypes of bacteria could be isolated from lung aspirate. Although many of these organisms would normally have been regarded as non-pathogenic, S. pneumoniae and Haemophilus influenzae, recognized pathogens, were the principal causes of severe morbidity and mortality. The same principles of carriage of and invasion by upper respiratory commensals applied as much to children as they did to adults, and the rank order of invasive serotypes of S. pneumoniae and H. influenzae was the same in different age groups. Slow maturation of a child's immune system meant, however, that children could be susceptible to invasion by particular serotypes. Infants were frequently colonized by pathogenic bacteria within days of birth. Nasal discharge, which was extremely common, was most probably a result of domestic smoke pollution and low standards of hygiene. Aspiration of infected secretions was a likely explanation for the variety of organisms isolated from lung aspirate. A trial of pneumococcal polysaccharide vaccine showed the vaccine to be effective in preventing death from pneumonia in children 6-9 months of age provided pneumonia was not associated with other causes of death; this result was shown to be consistent with the principles of infection and invasion described above. Principles of antibiotic therapy for child pneumonia were also established at this time.

Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and X-ray defined pneumonia in children less than two years of age.

BACKGROUND: Pneumonia, caused by Streptococcus pneumoniae, is a major cause of morbidity and mortality among children in low-income countries. The effectiveness of pneumococcal conjugate vaccines (PCVs) against invasive pneumococcal disease (IPD), pneumonia, and mortality needs to be evaluated. OBJECTIVES: To update the 2004 review on the efficacy of PCVs in preventing vaccine-serotypes IPD (VT-IPD) , X-ray defined pneumonia among HIV-1 negative children, and other new outcomes. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1990 to Week 4 February 2009); and EMBASE (1974 to March 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, in children under two with IPD and clinical / radiographic pneumonia as outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies, extracted data, and evaluated their corresponding risks of bias. Differences were resolved by discussion. Meta-analysis used the inverse variance method. MAIN RESULTS: We identified 11 publications from six RCTs conducted in Africa, US, Philippines and Finland where 57,015 children received PCV; while 56,029 received placebo or another vaccine. Seven publications provided high quality evidence on PCV efficacy against IPD and four provided moderate quality evidence against pneumonia. None of the five trials with all-cause mortality data were powered to investigate this outcome. Only two trials have data on all-cause admissions.The main analysis for this review involved HIV-1 negative children and used the pooled results of random-effects model, intent-to-treat analysis (ITT).Pooled vaccine efficacy (VE) for VT-IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes-IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X-ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all-cause mortality, 11% (95% CI -1% to 21%, P = 0.08). Analysis involving HIV-1 positive children had similar findings. AUTHORS' CONCLUSIONS: PCV is effective in preventing IPD, X-ray defined pneumonia, and clinical pneumonia among HIV-1 negative and HIV-1 positive children under two years. The impact was greater for VT-IPD than for all serotypes-IPD, and for X-ray defined pneumonia than for clinical pneumonia. An 11% reduction with a 95% CI of -1% to 21% and a P = 0.08 is compatible with reduction in all-cause mortality.

The epidemiology of malaria in the Papua New Guinea highlands: 3. Simbu Province.

Two very distinct malaria zones can be found within Simbu Province. The north of the province is characterized by the absence or very low level of local malaria transmission, but there is a considerable risk of epidemics prevalent in the lower-lying parts. During non-epidemic periods, parasite prevalence was usually under 5%, with similar frequencies for Plasmodium falciparum and P. vivax (47% each), and malaria was an only minor source of febrile illness. During epidemics, however, 13-36% of people were infected, predominantly with P. falciparum (64%), and high levels of severe morbidity were present. In south Simbu malaria is clearly endemic with an overall prevalence of 35%, combined with a strong age-dependence of infections, low haemoglobin levels, high rates of enlarged spleen and moderate to severe anaemia (haemoglobin level < 7.5 g/dl) in children. The malaria epidemiology in south Simbu is thus more similar to the lowlands than to other highlands areas. Epidemic prevention, surveillance and response in the north, and bednet distribution and strengthening of curative services in the south, are therefore the priorities for malaria control in Simbu Province.

Studies of maternal immunisation with pneumococcal polysaccharide vaccine in Papua New Guinea.

In two studies, pneumococcal polysaccharide (Pnc PS) vaccine was given to more than 400 pregnant Papua New Guinean women. No deleterious effects were found. The vaccine prevented acute lower respiratory infection (ALRI) among offspring in utero or aged 1-17 months at the time of maternal immunisation, suggesting protection through breast feeding. Serum IgG antibody titres were higher in vaccinated than unvaccinated groups for 2-4 months after delivery and no immune suppression, evaluated by the response to subsequent Pnc PS vaccination, was detected. Breast milk IgA to four serotypes was 1.1-1.8 times higher in immunised than unimmunised women for 6 months postpartum. Given results from several developing countries, large-scale safety and efficacy trials are now justified. Postpartum maternal immunisation is another intervention under consideration.

The epidemiology of malaria in the Papua New Guinea highlands: 1. Western Highlands Province.

Despite a resurgence of malaria in many Papua New Guinea highlands and highlands fringe areas after the cessation of control activities in the early 1980s the malaria situation in these areas has received little attention. A series of cross-sectional surveys were therefore carried out to provide accurate and up-to-date information on the prevalence of malaria and the risk of epidemics and to propose adequate malaria control strategies. Studies in 24 villages in Western Highlands Province found the prevalence of malarial infections to be strongly correlated with altitude, ranging from 1.6% at altitudes of 1500-1800 m to over 30% in villages below 900 m. Malaria outbreaks were observed at the end of the rainy season. All four human malaria species were present with P. falciparum infections clearly dominating. The relative importance of P. vivax increased with altitude, while both P. malariae and P. ovale were rare. Many infections were of low density. While malaria is an important source of febrile illness in endemic areas below 1500 m altitude, only few observed or reported fevers are due to malarial infections in higher, nonendemic areas. Rates of enlarged spleens, mean haemoglobin levels and the prevalence of anaemia (Hb <7.5 g/dl) were strongly linked to the level of malaria found in each community and were associated with both altitude and concurrent malarial infection. Based on the survey results, areas of different malaria epidemiology are delineated and options for control in each area are discussed.

The epidemiology of malaria in the Papua New Guinea highlands: 2. Eastern Highlands Province.

The epidemiology of malaria in Eastern Highlands Province (EHP) is characterized by generally very low-level or no local malaria transmission but a considerable risk of epidemics. In non-epidemic situations, parasite prevalence was under 5% in all but one area, Lufa Valley, where P. vivax was the most common parasite (prevalence rate of 58%). During epidemics, however, 23% (range 8-63%) of people were infected, with P. falciparum the predominant parasite. Mixed infections were very common (12%) but P. malariae and P. ovale were rare. Outside epidemics, malaria was only a minor source of febrile illness and enlarged spleens and anaemia (haemoglobin level < 7.5 g/dl) were virtually absent. However, epidemics were associated with a high incidence of relatively severe morbidity, both in terms of fevers and moderate to severe anaemia. Epidemic prevention, surveillance and response therefore are priorities in malaria control in EHP.

Pneumonia vaccine trials at Tari.

Pneumonia is the commonest cause of death of children in Papua New Guinea (PNG). At Tari pneumonia is most commonly caused by Streptococcus pneumoniae and Haemophilus influenzae, which set up rapid severe infections in the lungs that require urgent treatment. In rural PNG, however, treatment is often delayed. Penicillin-resistant forms of these bacteria are on the increase. It is therefore important to have another means of protection against this serious disease. This paper describes three field trials of a vaccine against the commonest serotypes of S. pneumoniae found in PNG. The trials show that a pneumococcal vaccine can prevent deaths from uncomplicated acute lower respiratory tract infection in small children and adults. It is likely that the vaccine does this by limiting the replication of bacteria in the lungs and thus limiting their spread to other parts of the body.