Sustained Malaria Control Over an 8-Year Period in Papua New Guinea: The Challenge of Low-Density Asymptomatic Plasmodium Infections

Koepfli, Cristian; Ome-Kaius, Maria; Malau, Elisheba; Maripal, Samuel; Ginny, Jason; Timinao, Lincoln; Kattenberg, Johanna Helena; Obadia, Thomas; White, Michael T.; Rarau, Patricia; Senn, Nicolas; Barry, Alyssa E.; Kazura, James W.; Müeller, Ivo; Robinson, Leanne J.

doi:10.1093/infdis/jix507

Cited by 50 publications

(88 citation statements)

References 43 publications

(45 reference statements)

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“…In this scenario, the epidemiological differences between these demographic groups could be enhanced. Interestingly, in an area of Papua New Guinea with recent declines in transmission, reductions in parasite prevalence have been associated with an increase in the proportion of infections that are subpatent [28], indicative, perhaps of persisting immune responses that control parasitaemia in a setting where the incidence of super infection is reduced.…”

Section: Human Factors Influencing the Duration Of Infectionmentioning

confidence: 99%

Understanding the Importance of Asymptomatic and Low- Density Infections for Malaria Elimination

Drakeley¹,

Gonçalves²,

Okell³

et al. 2018

Towards Malaria Elimination - A Leap Forward

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In recent years, the use of more sensitive diagnostic techniques has demonstrated a significant number of malaria infections at densities beneath the limit of detection of conventional microscopy and rapid diagnostic tests (RDT). These low-density infections are almost always asymptomatic, found in all endemic settings, including those nearing elimination, and in all ages of the population. They typically account for a high proportion of all infections and since they have also been shown to be infectious to mosquitoes, low-density infections are thought to be important contributors to maintaining malaria transmission. However, there is currently no direct evidence that specifically targeting this low-density parasite reservoir will hasten progress towards elimination. In this chapter we review the data to date and identify knowledge gaps. We present potential scenarios for the causes of low-density infections, if and how these might drive transmission, and the likely impact of specifically targeting them.

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Section: Human Factors Influencing the Duration Of Infectionmentioning

confidence: 99%

Understanding the Importance of Asymptomatic and Low- Density Infections for Malaria Elimination

Drakeley¹,

Gonçalves²,

Okell³

et al. 2018

Towards Malaria Elimination - A Leap Forward

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“…Parasite carriers with very low-density infections in PNG were primarily found in adolescents aged 10-20 years, whereas in Thailand and Brazil most additionally gained infections were found in older individuals (>40 years of age). Therefore, the additional P. vivax infections detected by us-qPCR coincided with the age group that had presented the highest risk of infection in earlier analyses from Thailand, Brazil and PNG [19,24] [W. Monteiro, personal communication].…”

Section: Discussionmentioning

confidence: 88%

“…This study used 2252 archived DNA samples from cross-sectional blood collections in Thailand, Brazil and PNG between 2012 and 2014. A detailed description of these three study sites and results by standard qPCR were published previously [4,5,19] analysed. These cross-sectional surveys were conducted between May and July 2014 in Madang province.…”

Section: Study Sites and Archived Samplesmentioning

confidence: 99%

“…Prior to performance of us-qPCR, good quality of the stored DNA was con rmed by repeating species-speci c Pf_ and Pv_18S rRNA qPCR assays in a minimum of 150 samples from each study site. Results in these repeated subsets were compared to the rst round of Pf_ and Pv_18S rRNA assays [4,5,19]. For Thailand and Brazil complete overlap for P. falciparum-positivity and almost complete overlap for P. vivax-positivity was found.…”

Section: Study Sites and Archived Samplesmentioning

confidence: 99%

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Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities

Gruenberg

Moniz

Hofmann³

et al. 2020

Preprint

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Background The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome. Methods Plasmodium falciparum ( Pf ) and Plasmodium vivax ( Pv ) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv _18S rRNA genes or the multi-copy targets Pf _varATS and Pv _mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities. Results In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Brazil) using standard Pf _18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_ varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv _18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum , at 8.0% (66/828). Use of Pv _mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG. Conclusion The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diagnostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement. Improving sensitivity in P. vivax surveillance by us-qPCR is of particular benefit, because the additionally detected P. vivax infections signal the potential presence of hypnozoites and subsequent risk of relapse and further transmission.

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“…Sustained reduction in malaria transmission can lead to a decrease in naturally acquired immunity and consequently, a shift in the peak burden of malaria infection and illness to older age groups and change other risk factors. A declining burden of malaria illness and high-density parasite infections can also mask a substantial community burden of low-density but gametocytaemic infections that sustain transmission (25)(26)(27). In addition, the possible differential effects of these interventions on the various Plasmodium species is important to consider in co-endemic regions such as PNG, given the distinct biological differences of the two main Plasmodium species.…”

Section: Introductionmentioning

confidence: 99%

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

Kattenberg¹,

Dl²,

Ome-Kaius³

et al. 2020

Preprint

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BackgroundIn the past decade, national malaria control efforts in Papua New Guinea (PNG) have received renewed support, facilitating nationwide distribution of free long-lasting insecticidal nets (LLINs), as well as improvements in access to parasite-confirmed diagnosis and effective artemisinin-combination therapy in 2011-12. MethodsTo study the effects of these intensified control efforts on the epidemiology and transmission of P. falciparum and P. vivax infections and investigate risk factors at the individual and household level, two cross-sectional surveys were conducted in the East Sepik Province of PNG; one in 2005, before the scale-up of national campaigns and one in late 2012-early 2013, after 2 rounds of LLIN distribution (2008 and 2011-12). Differences between studies were investigated using chi-square (χ²), Fischer’s exact tests and Student’s t-test. Multivariable logistic regression models were built to investigate factors associated with infection at the individual and household level. ResultsThe prevalence of P. falciparum and P. vivax in surveyed communities decreased from 55% (2005) to 9% (2013) and 36% to 6%, respectively. The mean multiplicity of infection (MOI) decreased from 1.8 to 1.6 for P. falciparum (p=0.08) and from 2.2 to 1.4 for P. vivax (p<0.001). Alongside these reductions, a shift towards a more uniform distribution of infections and illness across age groups was observed but there was greater heterogeneity across the study area and within the study villages. Microscopy positive infections and clinical cases in the household were associated with high rate infection households (>50% of household members with Plasmodium infection).ConclusionAfter the scale-up of malaria control interventions in PNG between 2008 and 2012, there was a substantial reduction in P. falciparum and P. vivax infection rates in the studies villages in East Sepik Province. Understanding the extent of local heterogeneity in malaria transmission and the driving factors is critical to identify and implement targeted control strategies to ensure the ongoing success of malaria control in PNG and inform the development of tools required to achieve elimination. In household-based interventions, diagnostics with a sensitivity similar to (expert) microscopy could be used to identify and target high rate households.

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Sustained Malaria Control Over an 8-Year Period in Papua New Guinea: The Challenge of Low-Density Asymptomatic Plasmodium Infections

Abstract: Continuous malaria control in Papua New Guinea has resulted in a marked decline of Plasmodium falciparum and P. vivax prevalence. Yet, an increasing proportion of submicroscopic infections, many of them carrying gametocytes, demands for novel strategies to target residual transmission.

Cited by 50 publications

References 43 publications

Understanding the Importance of Asymptomatic and Low- Density Infections for Malaria Elimination

Understanding the Importance of Asymptomatic and Low- Density Infections for Malaria Elimination

Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities

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

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