Malaria Transmission Potential Research Articles

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

The scale-up of effective malaria control in the last decade has resulted in a substantial decline in the incidence of clinical malaria in many countries. The effects on the proportions of asymptomatic and submicroscopic infections and on transmission potential are yet poorly understood. In Papua New Guinea, vector control has been intensified since 2008, and improved diagnosis and treatment was introduced in 2012. Cross-sectional surveys were conducted in Madang Province in 2006 (with 1280 survey participants), 2010 (with 2117 participants), and 2014 (with 2516 participants). Infections were quantified by highly sensitive quantitative polymerase chain reaction (PCR) analysis, and gametocytes were quantified by reverse-transcription qPCR analysis. Plasmodium falciparum prevalence determined by qPCR decreased from 42% in 2006 to 9% in 2014. The P. vivax prevalence decreased from 42% in 2006 to 13% in 2010 but then increased to 20% in 2014. Parasite densities decreased 5-fold from 2006 to 2010; 72% of P. falciparum and 87% of P. vivax infections were submicroscopic in 2014. Gametocyte density and positivity correlated closely with parasitemia, and population gametocyte prevalence decreased 3-fold for P. falciparum and 29% for P. vivax from 2010 to 2014. Sustained control has resulted in reduced malaria transmission potential, but an increasing proportion of gametocyte carriers are asymptomatic and submicroscopic and represent a challenge to malaria control.

Malaria suitability, urbanization and persistence: Evidence from China over more than 2000 years

We show that the climatic potential for Plasmodium falciparum malaria transmission constituted a locational fundamental that influenced the spatial distribution of urbanization since the early start of the southward expansion of the Han Chinese around 200 BCE. This effect is still detectable in today's distribution of urbanization and economic activity even though the risk of malaria falciparum has been successfully eliminated. We do not find any indication of convergence between high- and low malaria potential regions after eradication. Our identification strategy relies on a climate-based measure of Plasmodium falciparum malaria transmission intensity which is fitted to experimental data on mosquito and parasite development from laboratory studies. This measure is exogenous with respect to human population densities.

Environmental determinants of malaria transmission in African villages.

BackgroundMalaria transmission is complex, involving a range of hydroclimatological, biological, and environmental processes. The high degree of non-linearity in these processes makes it difficult to predict and intervene against malaria. This study seeks both to define a minimal number of malaria transmission determinants, and to provide a theoretical basis for sustainable environmental manipulation to prevent malaria transmission.MethodsUsing a field-tested mechanistic malaria model, HYDREMATS, a theoretical study was conducted under hypothetical conditions. Simulations were conducted with a range of hydroclimatological and environmental conditions: temperature (t), length of wet season (Twet), storm inter-arrival time (Tint), persistence of vector breeding pools (Ton), and distribution of houses from breeding pools and from each other (Xdist and Ydist, respectively). Based on the theoretical study, a malaria time scale, To, and a predictive theory of malaria transmission were introduced. The performance of the predictive theory was compared against the observational malaria transmission data in West Africa. Population density was used to estimate the scale that describes the spatial distribution of houses.ResultsThe predictive theory shows a universality in malaria endemic conditions when plotted using two newly-introduced dimension-less parameters. The projected malaria transmission potential compared well with the observation data, and the apparent differences were discussed. The results illustrate the importance of spatial aspects in malaria transmission.ConclusionsThe predictive theory is useful in measuring malaria transmission potential, and it can also provide guidelines on how to plan the layout of human habitats in order to prevent endemic malaria. Malaria-resistant villages can be designed by locating houses further than critical distances away from breeding pools or by removing pools within a critical distance from houses; the critical distance is described in the context of local climatology and hydrology.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1633-7) contains supplementary material, which is available to authorized users.

5-Aminopyrazole-4-carboxamide analogues are selective inhibitors of Plasmodium falciparum microgametocyte exflagellation and potential malaria transmission blocking agents

Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) is essential for the exflagellation of male gametocytes. Inhibition of PfCDPK4 is an effective way of blocking the transmission of malaria by mosquitoes. A series of 5-aminopyrazole-4-carboxamide analogues are demonstrated to be potent inhibitors of PfCDPK4. The compounds are also able to block exflagellation of Plasmodium falciparum male gametocytes without observable toxicity to mammalian cells.

Phenology of malarial mosquitoes (Diptera, Culicidae) and their epidemiological significance in the south of Tomsk Province

Occurrence of malaria among the population of Tomsk Province is overviewed from 1935 till the present time. The results of phenological observations on malarial mosquitoes (Diptera, Culicidae) in the south of Tomsk Province from 2005 to 2014 are analyzed. The timing of crucial events in the mosquito life history is determined, namely, the onset of departure from overwintering sites, emergence of the first preimaginal stages, the flight of the first generation adults, and entry into diapause. The period of potential transmission of malaria in the south of Tomsk Province is calculated retrospectively.

Human-biting activities of Anopheles species in south-central Ethiopia.

BackgroundIndoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are the key malaria vector control interventions in Ethiopia. The success of these interventions rely on their efficacy to repel or kill indoor feeding and resting mosquitoes. This study was undertaken to monitor human-biting patterns of Anopheles species in south-central Ethiopia.MethodsHuman-biting patterns of anophelines were monitored for 40 nights in three houses using human landing catches (HLC) both indoors and outdoors between July and November 2014, in Edo Kontola village, south-central Ethiopia. This time coincides with the major malaria transmission season in Ethiopia, which is usually between September and November. Adult mosquitoes were collected from 19:00 to 06:00 h and identified to species. Comparisons of HLC data were done using incidence rate ratio (IRR) calculated by negative binomial regression. The nocturnal biting activities of each Anopheles species was expressed as mean number of mosquitoes landing per person per hour. To assess malaria infections in Anopheles mosquitoes the presence of Plasmodium falciparum and P. vivax circumsporozoite proteins (CSP) were determined by enzyme-linked immunosorbent assay (ELISA).ResultsAltogether 3,408 adult female anophelines were collected, 2,610 (76.6 %) outdoors and 798 (23.4 %) indoors. Anopheles zeimanni was the predominant species (66.5 %) followed by An. arabiensis (24.8 %), An. pharoensis (6.8 %) and An. funestus (s.l.) (1.8 %).The overall mean anopheline density was 3.3 times higher outdoors than indoors (65.3 vs 19.9/person/night, IRR: 3.3, 95 % CI: 1.1–5.1, P = 0.001). The mean density of An. zeimanni, An. pharoensis and An. funestus (s.l.) collected outdoors was significantly higher than indoors for each species (P < 0.05). However, the mean An. arabiensis density outdoors was similar to that indoors (11.8 vs 9.4/person/night, IRR: 1.3, 95 % CI: 0.8–1.9, P = 0.335). The mean hourly human-biting density of An. arabiensis was greater outdoors than indoors and peaked between 21:00 and 22:00 h. However, An. arabiensis parous population showed high indoor man biting activities during bedtimes (22:00 to 05:00 h) when the local people were indoor and potentially protected by IRS and LLINs. All mosquito samples tested for CSP antigen were found negative to malaria parasites.ConclusionsResults show much greater mosquito human-biting activities occurring outdoors than indoors and during early parts of the night, implying higher outdoor malaria transmission potential in the area. However, high bedtime (22:00 to 05:00 h) indoor biting activities of parous An. arabiensis suggest high potential intervention impact of IRS and LLINs on indoor malaria transmission.

Delayed mortality effects cut the malaria transmission potential of insecticide-resistant mosquitoes

Malaria transmission has been substantially reduced across Africa through the distribution of long-lasting insecticidal nets (LLINs). However, the emergence of insecticide resistance within mosquito vectors risks jeopardizing the future efficacy of this control strategy. The severity of this threat is uncertain because the consequences of resistance for mosquito fitness are poorly understood: while resistant mosquitoes are no longer immediately killed upon contact with LLINs, their transmission potential may be curtailed because of longer-term fitness costs that persist beyond the first 24 h after exposure. Here, we used a Bayesian state-space model to quantify the immediate (within 24 h of exposure) and delayed (>24 h after exposure) impact of insecticides on daily survival and malaria transmission potential of moderately and highly resistant laboratory populations of the major African malaria vector Anopheles gambiae Contact with LLINs reduced the immediate survival of moderately and highly resistant An. gambiae strains by 60-100% and 3-61%, respectively, and delayed mortality impacts occurring beyond the first 24 h after exposure further reduced their overall life spans by nearly one-half. In total, insecticide exposure was predicted to reduce the lifetime malaria transmission potential of insecticide-resistant vectors by two-thirds, with delayed effects accounting for at least one-half of this reduction. The existence of substantial, previously unreported, delayed mortality effects within highly resistant malaria vectors following exposure to insecticides does not diminish the threat of growing resistance, but posits an explanation for the apparent paradox of continued LLIN effectiveness in the presence of high insecticide resistance.

Malaria transmission potential could be reduced with current and future climate change.

Several studies suggest the potential for climate change to increase malaria incidence in cooler, marginal transmission environments. However, the effect of increasing temperature in warmer regions where conditions currently support endemic transmission has received less attention. We investigate how increases in temperature from optimal conditions (27 °C to 30 °C and 33 °C) interact with realistic diurnal temperature ranges (DTR: ± 0 °C, 3 °C, and 4.5 °C) to affect the ability of key vector species from Africa and Asia (Anopheles gambiae and An. stephensi) to transmit the human malaria parasite, Plasmodium falciparum. The effects of increasing temperature and DTR on parasite prevalence, parasite intensity, and mosquito mortality decreased overall vectorial capacity for both mosquito species. Increases of 3 °C from 27 °C reduced vectorial capacity by 51–89% depending on species and DTR, with increases in DTR alone potentially halving transmission. At 33 °C, transmission potential was further reduced for An. stephensi and blocked completely in An. gambiae. These results suggest that small shifts in temperature could play a substantial role in malaria transmission dynamics, yet few empirical or modeling studies consider such effects. They further suggest that rather than increase risk, current and future warming could reduce transmission potential in existing high transmission settings.

Immune response and insulin signalling alter mosquito feeding behaviour to enhance malaria transmission potential.

Malaria parasites alter mosquito feeding behaviour in a way that enhances parasite transmission. This is widely considered a prime example of manipulation of host behaviour to increase onward transmission, but transient immune challenge in the absence of parasites can induce the same behavioural phenotype. Here, we show that alterations in feeding behaviour depend on the timing and dose of immune challenge relative to blood ingestion and that these changes are functionally linked to changes in insulin signalling in the mosquito gut. These results suggest that altered phenotypes derive from insulin signalling-dependent host resource allocation among immunity, blood feeding, and reproduction in a manner that is not specific to malaria parasite infection. We measured large increases in mosquito survival and subsequent transmission potential when feeding patterns are altered. Leveraging these changes in physiology, behaviour and life history could promote effective and sustainable control of female mosquitoes responsible for transmission.

Species Composition and Diversity of Malaria Vector Breeding Habitats in Trincomalee District of Sri Lanka.

Introduction. Mosquito larval ecology is important in determining larval densities and species assemblage. This in turn influences malaria transmission in an area. Therefore, understanding larval habitat ecology is important in designing malaria control programs. Method. Larval surveys were conducted in 20 localities under five sentinel sites (Padavisiripura, Gomarankadawala, Thoppur, Mollipothana, and Ichchallampaththu) in Trincomalee District, Eastern Province of Sri Lanka, between June 2010 and July 2013. The relationship between seven abiotic variables (temperature, pH, conductivity, Total Dissolved Solid (TDS), turbidity, Dissolved Oxygen (DO), and salinity) was measured. Results. A total of 21,347 anophelines were recorded representing 15 species. Anopheles subpictus 24.72% (5,278/21,347) was the predominant species, followed by 24.67% (5,267/21,347) of An. nigerrimus and 14.56% (3,109/21,347) of An. peditaeniatus. A total of 9,430 breeding habitats under twenty-one categories were identified. An. culcicifacies was noted to be highest from built wells (20.5%) with high salinity (1102.3 ± 81.8 mg/L), followed by waste water collections (20.2%) having low DO levels (2.85 ± 0.03 mg/L) and high TDS (1,654 ± 140 mg/L). Conclusion. This study opens an avenue to explore new breeding habitats of malaria vectors in the country and reemphasizes the requirement of conducting entomological surveillance to detect potential transmission of malaria in Sri Lanka under the current malaria elimination programme.

Efficacy and safety of the mosquitocidal drug ivermectin to prevent malaria transmission after treatment: a double-blind, randomized, clinical trial.

Artemisinin combination therapy effectively clears asexual malaria parasites and immature gametocytes but does not prevent posttreatment malaria transmission. Ivermectin (IVM) may reduce malaria transmission by killing mosquitoes that take blood meals from IVM-treated humans. In this double-blind, placebo-controlled trial, 120 asymptomatic Plasmodium falciparum parasite carriers were randomized to receive artemether-lumefantrine (AL) plus placebo or AL plus a single or repeated dose (200 µg/kg) of ivermectin (AL-IVM1 and AL-IVM2, respectively). Mosquito membrane feeding was performed 1, 3, and 7 days after initiation of treatment to determine Anopheles gambiae and Anopheles funestus survival and infection rates. The AL-IVM combination was well tolerated. IVM resulted in a 4- to 7-fold increased mortality in mosquitoes feeding 1 day after IVM (P < .001). Day 7 IVM plasma levels were positively associated with body mass index (r = 0.57, P < .001) and were higher in female participants (P = .003), for whom An. gambiae mosquito mortality was increased until 7 days after a single dose of IVM (hazard rate ratio, 1.34 [95% confidence interval, 1.07-1.69]; P = .012). Although we found no evidence that IVM reduced Plasmodium infection rates among surviving mosquitoes, the mosquitocidal effect of AL-IVM1 and AL-IVM2 resulted in 27% and 35% reductions, respectively, in estimated malaria transmission potential during the first week after initiation of treatment. We conclude that IVM can be safely given in combination with AL and can reduce the likelihood of malaria transmission by reducing the life span of feeding mosquitoes. NCT0160325.

Seasonal genetic partitioning in the neotropical malaria vector, Anopheles darlingi.

BackgroundAnopheles darlingi is the main malaria mosquito vector in the Amazonia region. In spite of being considered a riverine, forest-dwelling species, this mosquito is becoming more abundant in peri-urban areas, increasing malaria risk. This has been associated with human-driven environmental changes such as deforestation.MethodsMicrosatellites were used to characterize A. darlingi from seven localities along the Madeira River, Rondônia (Brazil), collected in the early and late periods of the rainy season.ResultsTwo genetically distinct subpopulations were detected: one (subpopulation A) was associated with the late rainfall period and seems to be ecologically closer to the typical forest A. darlingi; the other (subpopulation B) was associated with the early rainfall period and is probably more adapted to drier conditions by exploiting permanent anthropogenic breeding sites. Results suggest also a pattern of asymmetric introgression, with more subpopulation A alleles introgressed into subpopulation B. Both subpopulations (and admixed mosquitoes) presented similar malaria infection rates, highlighting the potential for perennial malaria transmission in the region.ConclusionsThe co-occurrence of two genetically distinct subpopulations of A. darlingi adapted to different periods of rainfall may promote a more perennial transmission of malaria throughout the year. These findings, in a context of strong environmental impact due to deforestation and dam construction, have serious implications for malaria epidemiology and control in the Amazonian region.

The impact of insecticide treated nets on malaria transmission potential in Kamuli district, Uganda

The impact of insecticide treated nets on malaria transmission potential in Kamuli district, Uganda

Malaria Transmission Potential in the Three Gorges Reservoir of the Yangtze River, China

ObjectiveTo define and evaluate the malaria transmission potential in the Yangtze River, following construction of the Three Gorges Reservoir. MethodsSix villages, namely, Kaixian, Fengjie, Wanzhou, Fuling, Yubei, and Zigui were selected for investigating the malaria transmission potential in the reservoir. Transmission potential was estimated by mathematical modeling and evaluation of the local malaria situation. Factors that influenced the transmission potential were analyzed using Poisson regression analysis in combination with Grey Systematic Theory (based on evaluation by the Delphi method). ResultsIndirect fluorescent antibody data and the incidence of malaria in the local population were consistent with the malaria transmission potential calculated for the area. Multivariate Poisson regression analysis showed a statistically significant association between the riparian zone and the man-biting rate. ConclusionThe risk of a malaria epidemic can be forecasted using the malaria transmission potential parameters investigated here which was closely correlated with the riparian zone.

A sticky situation: the unexpected stability of malaria elimination.

Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination's ‘stickiness’ must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system's increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination's stickiness at moderate-to-low transmission in areas with well-developed health systems, it is not yet clear if such patterns will hold in all areas. The sticky endpoint changes the projected costs of maintaining elimination and makes it substantially more attractive for countries acting alone, and it makes spatially progressive elimination a sensible strategy for a malaria eradication endgame.

Anopheles species associations in Southeast Asia: indicator species and environmental influences

BackgroundSoutheast Asia presents a high diversity of Anopheles. Environmental requirements differ for each species and should be clarified because of their influence on malaria transmission potential. Monitoring projects collect vast quantities of entomological data over the whole region and could bring valuable information to malaria control staff but collections are not always standardized and are thus difficult to analyze. In this context studying species associations and their relation to the environment offer some opportunities as they are less subject to sampling error than individual species.MethodsUsing asymmetrical similarity coefficients, indirect clustering and the search of indicator species, this paper identified species associations. Environmental influences were then analysed through canonical and discriminant analysis using climatic and topographic data, land cover in a 3 km buffer around villages and vegetation indices.ResultsSix groups of sites characterized the structure of the species assemblage. Temperature, rainfall and vegetation factors all play a role. Four out of the six groups of sites based on species similarities could be discriminated using environmental information only.ConclusionsVegetation indices derived from satellite imagery proved very valuable with one variable explaining more variance of the species dataset than any other variable. The analysis could be improved by integrating seasonality in the sampling and collecting at least 4 consecutive days.

A protocol for membrane feeding assays to determine the infectiousness of P. falciparum naturally infected individuals to Anopheles gambiae.

Mosquito feeding assays play an important role in quantifying malaria transmission potential in epidemiological and clinical studies. At present, membrane feeding assays are incompletely standardised. This affects our understanding of the precision of the assay and its suitability for evaluating transmission-blocking interventions. Here, we present a detailed protocol for membrane feeding using Anopheles gambiae mosquitoes and naturally P. falciparum infected individuals.

Mosquitoes in degraded and preserved areas of the Atlantic Forest and potential for vector-borne disease risk in the municipality of São Paulo, Brazil

In order to assess the epidemiological potential of the Culicidae species in remaining areas of the Brazilian Atlantic Forest, specimens of this family were collected in wild and anthropic environments. A total of 9,403 adult mosquitoes was collected from May, 2009 to June, 2010. The most prevalent among species collected in the wild environment were Anopheles (Kerteszia) cruzii, the Melanoconion section of Culex (Melanoconion), and Aedes serratus, while the most common in the anthropic site were Coquillettidia chrysonotum/albifera, Culex (Culex) Coronator group, and An. (Ker.) cruzii. Mosquito richness was similar between environments, although the abundance of individuals from different species varied. When comparing diversity patterns between environments, anthropic sites exhibited higher richness and evenness, suggesting that environmental stress increased the number of favorable niches for culicids, promoting diversity. Increased abundance of opportunistic species in the anthropic environment enhances contact with culicids that transmit vector-borne diseases.

Population cytogenetic and molecular evidence for existence of a new species in Anopheles fluviatilis complex (Diptera: Culicidae)

Anopheles fluviatilis James, an important malaria vector in the Oriental region has been established as a complex of at least three cryptic species which vary in their biological characteristics and malaria transmission potential. The sibling species S, T and U of Fluviatilis Complex can be identified by examination of species-specific fixed inversions in the polytene chromosomes and can also be differentiated by an allele-specific PCR assay based on differences in the D3 region of 28S ribosomal DNA (rDNA) of these species. Here we report a new An. fluviatilis population from villages under Laksar Community Health Centre, District Haridwar (Uttarakhand state), India which differs from the three sibling species of Fluviatilis Complex by two fixed paracentric inversions, s1 and S in polytene chromosome arms 2 and 3 respectively. Longitudinal study carried out in study villages showed that the new cytotype was sympatric with species T and U in all the collections and no inversion heterozygotes were observed between them. Thus presence of two fixed paracentric inversions in polytene chromosomes with total absence of inversion heterozygotes demonstrates reproductive isolation which unequivocally establishes this cytological variant as a new species, provisionally designated as species V in the Fluviatilis Complex. Analysis of DNA sequences of D3 domain of 28S rDNA and ITS 2 region has also shown that species V is distinctly different from species S, T and U. With the discovery of new species in the Fluviatilis Complex, in-depth studies are required to know its distribution pattern and biological characteristics and to ascertain its role in malaria transmission.

Extended malaria parasite clearance time in African children following artemisinin-combination therapy enhances transmission to Anopheles mosquitoes

Artemisinin resistance was recently shown to have spread or emerged on the Thailand/Myanmar border. Evidence is accumulating that the parasite clearance time after artemisinin-based combination therapy (ACT) is increasing in settings in Asia and Africa. It is currently unknown if an extended parasite clearance time after ACTs has consequences for the individual patient or confers a higher malaria transmission potential. 298 children in Mbita, Western Kenya, with uncomplicated falciparum malaria were randomized to artemether-lumefantrine (AL, n = 153) ordihydroartemisinin-piperaquine (DP, n = 145). Parasite carriage post-treatment was determined by microscopy and qPCR, gametocyte carriage by quantitative nucleic acid sequence based amplication. Infectiousness to mosquitoes was determined by mosquito membrane feeding assays. Both drugs were efficacious as judged by standard trial outcomes. Sub-patent residual parasitaemia on day 3 was detected by qPCR in 36.11% (95% CI 25.11 - 48.29) of children treated with AL, and in 30.16% (95% CI 19.23 - 43.02) of children treated with DP. After adjustment for age, treatment arm and enrolment parasite density, children with an extended parasite clearance time were significantly more likely to have microscopically detected recurrent parasitaemia during follow-up (Odds Ratio: 19.51, 95% CI 5.24 - 72.71, p < 0.001). Children with an extended parasite clearance time were also more likely to be infectious to mosquitoes (Odds Ratio 2.76; 95% CI 1.14 - 6.67, p = 0.02) and gave rise to a higher oocyst load in mosquitoes (Incidence Rate Ratio 2.80, 95% CI 1.49 - 5.24, p = 0.001). Our findings indicate that an extended parasite clearance time after ACTs has consequences for the individual patient and for the population at large due to higher transmission potential. The high prevalence of residual subpatent parasitaemia after treatment may be due to novel parasite genotypes with reduced drug sensitivity, inadequate population-level immunity, or the higher sensitivity of qPCR for detection of persisting parasites.