In the historically high transmission region of ESP in PNG, we have observed a dramatic change in the burden and epidemiology of malaria over the period of time coinciding with the scale-up of control via nationwide LLIN distributions and strengthening of malaria diagnosis and treatment at peripheral health facilities. Overall Plasmodium prevalence as detected by LM and/or MMs has declined from 74.2% in 2005 to 12.8% in 2012/13, a substantially sharper decline than has been observed in another study area along the North Coast of Papua New Guinea (36). Alongside the reduction in prevalence and complexity of infections, we have observed a shift towards a more uniform distribution of infections and illness across age groups but greater heterogeneity in transmission across the study area and within the study villages.
Heterogeneity in malaria prevalence between villages is not a new phenomenon (3, 4, 37–39). In the 2012–2013 study, transmission in some villages had not declined as much as in others, increasing this difference between and within villages. In those areas with higher prevalence, reported use of LLINs was lower and anaemia and fever were more prevalent. While coverage of bed nets was already high in this area in 2005 (88.3%), the majority of nets at that time were untreated nets, whereas in 2012-13 most people should have had access to LLINs, and questions specified LLINs. In the village with the highest density, Sunuhu, LLIN use was lowest, which could be a major factor contributing to the high level of transmission in that village. The use of insecticide-treated nets (ITNs) has been shown in many studies to be effective in reducing mortality and morbidity from malaria (40–42). In addition, it is thought that use of ITNs leads to community-level effects, where the majority of the population (even those not using ITNs) are protected when ITN coverage in the community is high, due to reduction in the number of infected mosquitoes and mosquito survival (43–46). This effect has, however, not been well quantified and impact of LLINs varies with the coverage rate. In addition, the required coverage might be different for different areas, depending on local factors such as the anopheline density, species composition and both vector and human behaviour (47). In future studies, investigating the complex interplay of these different parasite, vector and human factors at the village level would facilitate a better understanding of the impact of bednets and other community-level interventions.
Renewed political and financial will to strengthen malaria control at the beginning of the millennium, resulted in the PNG National Department of Health launching a new campaign to quickly achieve high levels of LLIN ownership and usage. Nationwide free LLIN distribution took place between 2004 and 2009 and resulted in a significant increase in ownership of bed nets (any type 80.1%; LLINs 64.6%) (20). Despite this increase, reported LLIN use remained low (32.5%), and the majority of people not using nets reported not having access to (unoccupied) nets (20). A second round of country-wide LLIN distribution was conducted between 2010–2014 to cover the gaps in mosquito net coverage (21). LLINs in the study area in ESP were distributed 12 months prior to this 2012/13 survey (September 2011 and October 2012) and a new round of LLIN distribution occurred in 2014/2015 (personal communication, National malaria control program/Rotarians Against Malaria). Large-scale LLIN distribution campaigns were performed in ESP earlier than in many other provinces with a high malaria burden, and LLIN coverage in ESP seems to be higher than on the North Coast area in general (21, 36), likely due to a higher density of nuisance biters encouraging greater use of LLINs. The substantial impact of LLINs on transmission in this area might also be due to the fact that transmission in ESP is predominantly driven by An. punctulatus, which feeds later at night (after midnight/early morning) and equally indoors and outdoors, making it highly susceptible to LLINs. A recent study reported an increase in prevalence of An. punctulatus and a decrease of An. koliensis, another late biter, in an adjacent area in East Sepik province, as well as a shift to earlier mean biting times of An. punctulatus in addition to significantly reduced man-biting-rates and annual entomological inoculation rates after the LLIN campaign (48). Proximity to vector-breeding sites is related to the risk of malaria and can also be a main driver of heterogeneity (49–51), but was not investigated in the current study
Cultural factors, socio-economic status and education level play an additional role in risk of infection and can vary across villages and households, as well as human behavioural and genetic factors (9, 21, 28, 52–56). The time and manner of LLIN distribution in these areas can play a role in their availability, use and quality/age of the LLIN. For example, in some areas the LLINs might have been distributed directly to each household, whereas in other areas, people will have gone to their local health centres to obtain their LLINs. There are also real or perceived differences in the availability of RDTs, effective antimalarials and quality of care received at the health centres (19). In Sunuhu, for example, the population is of a different ethnic origin than surrounding villages, more closely related to the population in Gwanga local level government (LLG) than Ilahita LLG. The Sunuhu population have less material wealth, less access to nutritious food, and rates of malnutrition and generally poor health are more common than in neighbouring villages. They may also be less likely to access care at the nearby health centre (due to distance, cultural difference, perceived benefit etc.) and it’s possible their access to LLINs has been reduced as a result.
Despite the decrease in prevalence and significant geographic heterogeneity, the genetic diversity of both P. falciparum and P. vivax appears to have been maintained at relatively high levels. Multiplicity of infection and especially the proportion of multiple clone infections has decreased. The proportion of multiple clone infections correlated well with prevalence and might be a suitable indicator of hotspot areas and areas of high transmission. Further investigation of markers that are not under selective pressure is required for a more detailed analysis of the impact of malaria control on genetic diversity, differentiation and population structure in this area (57, 58).
Although the prevalence of malaria has decreased across all age groups and there is no marked shift in the peak age of infections (compared to the 2005 survey and others (5)), there is a relatively higher proportion of symptomatic infections in the 2012/13 survey). This, together with a 5- to 9-fold increase in the proportion of symptomatic infections in adults is an indication that there might be reduced or delayed acquisition of immunity. More detailed investigations on the effect of the decreased transmission intensity on the incidence (and complexity) of malaria infections and clinical malaria episodes, and age/exposure related acquisition of clinical immunity are being conducted in several longitudinal child cohorts in East Sepik and Madang Province.
The impact on the prevalence of P. vivax was similar or higher as on P. falciparum, in 10 of 12 villages surveyed in both years. Based on the biology of relapsing P. vivax infections from hypnozoites and the fact that neither LLINs nor ACTs act to prevent these relapsing infections it is generally thought that P. vivax burden is more resilient to these tools and that an equivalent impact may not be observed in the same timeframe as for P. falciparum. In the same area as this study, a series of cohort studies showed that while P. vivax clinical episodes declined at rates comparable to P. falciparum, force of blood stage infections and prevalence took longer to decline (59). The data presented here suggest that 8 years post-scale-up of LLINs appears to be a sufficient length of time for the hypnozoite burden to have been exhausted in most villages.
A limitation of the study was that the MM used to detect infections in the two time periods was not the same. However, a previous study directly comparing qPCR and LDR-FMA reported substantial agreement between the two methods (32). While the LDR-FMA detected slightly higher numbers of P. falciparum infections in that study (47% vs 41%) (32), this is not sufficient to be responsible for the observed difference in prevalence between the two studies, which mirrors the drop in prevalence by LM. The decreased prevalence of sub-microscopic P. falciparum and P. vivax infections in the 2012/13 study is potentially influenced by the difference between qPCR and LDR-FMA and thus the data from this earlier survey will appear to have a slightly higher proportion of sub-microscopic infections than when qPCR was used. In addition, 2nd reads of microscopy slides in 2012-13 were performed based on qPCR results, potentially resulting in a lower proportion of sub-microscopic infection.
This study was not a formal component of the monitoring and evaluation of the national malaria control program, with the primary aim to delve into the impact that reduced transmission is having on the epidemiology of malaria rather than assess the program itself. Prevalence reported in this study is much higher than provincial averages from the national reports (22, 60), which to a large extent can be explained by the higher sensitivity of the MM that were used in these studies as compared to microscopy and RDTs. Molecular tools are much more sensitive at detecting low levels of parasitaemia and are therefore crucial to get a detailed insight on the prevalence of not only clinical disease, but also asymptomatic reservoirs of infection. Microscopic infections in the household, as well as gametocyte carriers were associated with high rate infection households in both years and in 2012-13 many high rate households contained clinical cases, highlighting the utility of clinical and microscopy-based surveillance to identify transmission foci that could be specifically targeted with interventions aimed at reducing not only clinical cases, but the asymptomatic reservoir as well. Although the national program is very effective in determining the impact on a national level, this study facilitates the investigation at a different level of sensitivity, geographical scale and subsequent detection of fine-scale heterogeneity in transmission.
Identifying and targeting focal points and hotspots of malaria is highly relevant for malaria control, since these are likely to be the areas where residual malaria transmission will persist, and can become an obstacle in efforts to eliminate malaria (28, 61, 62). In addition they can play a catalysing role: hotspots fuel transmission within transmission foci, and interventions targeted at transmission hotspots therefore have the potential to reduce community-wide malaria transmission (28, 62). Many of the high burden villages found in 2012/13 were also areas of the highest prevalence in 2005, and it remains to be seen if these same areas are still high in prevalence in future. If these hot spots are consistently at the same location, implementation of control tools to target them will be much easier. In other regions in the world, it has been observed that hotspots are remarkably stable even when transmission intensity declines, although clinical incidence might vary with time (28, 63–65). In addition to scaling up conventional vector control tools such as LLINs and indoor residual spraying in these hotspot areas, other tools could be implemented that might prove more useful in these particular areas. Ongoing entomological studies in East Sepik and Madang provinces may advise on the suitability of additional vector control tools. Alternatively targeting the parasite via interventions to reduce the infectious reservoir in these communities, such as mass screening and treatment (MSAT) and mass drug administration (MDA). Modelling has shown that MDA targeting blood and liver stage drugs might be more effective in reducing P. falciparum and P. vivax prevalence than MSAT (66) and implementation of such strategies may be feasible to achieve in these relatively small communities.