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Background: Submicroscopic Plasmodium infections can be a source of persistent malaria transmission. The aim of this study was to assess their frequency, distribution, morbidity and associated factors in a pre-elimination malaria setting in sub-Saharan Africa, Guinea-Bissau, where the Plasmodium falciparum is the predominant Plasmodium species. Methods: Dried fingerprick whole blood samples from 601 participants in the 2017 national, household-based, cross-sectional survey to estimate malaria prevalence were subjected to DNA extraction. The DNA was used in nested end-point PCR assays targeting genus- and species-specific regions of the Plasmodium 18S rRNA genes. Statistical analysis of socio-demographic, clinical and molecular data was carried out using the Statistical Package for the Social Sciences, version 29. Factors associated with submicroscopic P. falciparum infections and their magnitude were sought using Chi-square test and multiple logistic regression models, respectively. Statistically significant level was considered at P-value < 0.05. Results: Nested PCR assays detected submicroscopic P. falciparum infections in 20.3% (95% CI = 16.8–23.8) of individuals microscopically negative for Plasmodium species in the general population and in 21.4% (95% CI = 9.9–36.5) of microscopically negative pregnant women. Submicroscopic Plasmodium malariae infections were also detected as co-infections in 3.0% individuals who were microscopically positive only for P. falciparum. Infections with other Plasmodium species were not detected. Submicroscopic P. falciparum infections were not associated with age, sex, or the presence of fever. A logistic regression model adjusted for ethnicity and health region showed that individuals from the Balanta and Bijagos ethnic groups, most of whom live in the low malaria-transmission areas of Quinara and Bissau, and the Bijagos archipelago, respectively, were less likely to have submicroscopic P. falciparum infections than individuals from the large Fula ethnic group, most of whom live in the high malaria-transmission area of Gabu. Submicroscopic P. falciparum infections were not associated with anaemia in children under 5 years of age. Conclusion: The results obtained highlight the contribution of asymptomatic and submicroscopic P. falciparum infections to malaria transmission in high malaria-transmission areas and the need for molecular-based tools to detect submicroscopic Plasmodium species. [ABSTRACT FROM AUTHOR]

Background: The RTS,S malaria vaccine has been prequalified for use in endemic settings prioritizing areas with moderate to high disease transmission. The impact of a vaccine at the population level may differ from observations during clinical trial due to programmatic, and individual-related factors, among others. The objective of this study was to assess the impact of the RTS,S malaria vaccine on uncomplicated malaria among children aged 12–59 months in the Phase IV study districts, Upper East Region, Ghana. Methods: A retrospective study was conducted using routine malaria surveillance data for the period 2020–2022. The burden of uncomplicated malaria was compared between the implementing (Kasena Nankana East and West districts) and comparator areas (Builsa North and South districts). The impact of RTS,S malaria vaccine was assessed by estimating the percentage reduction in uncomplicated malaria and incidence averted in the implementing area, accounting for the effect of confounders. Results: Over 50,000 episodes of uncomplicated malaria among children aged 12–59 months were included in the study. Uncomplicated malaria was reduced by 33% (95%CI 29–36) over the entire study period, but the malaria incidence averted declined from 324/1,000 (95% CI 298–339; p < 0.0001) in 2020 to 287/1000 (95% CI 274–299; p < 0.0001) in 2022. Conclusion: The RTS,S malaria vaccine significantly reduced the burden of uncomplicated malaria among children aged 12–59 months in the implementing area. The sequential marginal declines in malaria incidence averted over the study period might be due to waning of protective immunity and acquisition of natural immunity as children age. Strengthening uptake of the currently recommended vaccines and other malaria control interventions is required to improve public health impact. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major disease burden in Ethiopia. Migration can influence malaria transmission dynamics, with individuals relocating from malaria-free highland regions to malarious lowlands potentially facing elevated risks of contracting malaria. Migrants may find it difficult to protect themselves against malaria and have limited access to diagnosis or treatment. Settlers in gold mining sites are one type of migrant and are often neglected in malaria research yet may have particularly high malaria risk. This study was a malaria prevalence survey among settlers in a new gold mining settlement in the highly malarious Gambella Region, Ethiopia. Methods: n = 590 people were surveyed for demographic information and their knowledge and practices of malaria. Participants were tested for malaria using rapid diagnostic tests and microscopy. Using logistic regressions, the influence of demographic characteristics on malaria infections and bed net access were analysed. A sub-sample of participants was interviewed to comprehend settlement living conditions and healthcare accessibility. Results: The overall prevalence of Plasmodium falciparum was 37.5% (CI 32.4–42.3%). Young children were most likely to have malaria, with individuals aged 15–24 having 67% lower odds (aOR: 0.33; CI 0.13–0.86) of infection compared to those aged 1–4 years old. Meanwhile, those age 25-plus had 75% decreased odds of malaria infection (aOR 0.25; CI 0.10–0.65). Individuals with bed nets had ~ 50% decreased odds of testing positive for falciparum malaria than those reporting having no bed net (aOR: 0.47; CI 0.22–0.97). Individuals who relocated from low elevation with high malaria test positivity rate areas were more prone to testing positive for malaria, as were those residing in densely populated households with multiple malaria cases. Conversely, individuals from higher elevations with low malaria test positivity rates, and those living in households with 5–10 occupants and < 2 malaria infections, were more likely to possess bed nets. Conclusions: This gold mining settlement provides an example of an oft-neglected atypical community where malaria is a significant, but under-addressed, health problem. Within this community, future interventions focused on distributing bed nets, particularly to larger households and those with children, have great potential to alleviate the malaria burden. Efforts should also be made to provide affordable, and accessible, early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Malaria remains an important public health problem, particularly in sub-Saharan Africa. In Rwanda, where malaria ranks among the leading causes of mortality and morbidity, disease transmission is influenced by climatic factors. However, there is a paucity of studies investigating the link between climate change and malaria dynamics, which hinders the development of effective national malaria response strategies. Addressing this critical gap, this study analyses how climatic factors influence malaria transmission across Rwanda, thereby informing tailored interventions and enhancing disease management frameworks. Methods: The study analysed the potential impact of temperature and cumulative rainfall on malaria incidence in Rwanda from 2012 to 2021 using meteorological data from the Rwanda Meteorological Agency and malaria case records from the Rwanda Health Management and Information System. The analysis was performed in two stages. First, district-specific generalized linear models with a quasi-Poisson distribution were applied, which were enhanced by distributed lag non-linear models to explore non-linear and lagged effects. Second, random effects multivariate meta-analysis was employed to pool the estimates and to refine them through best linear unbiased predictions. Results: A 1-month lag with specific temperature and rainfall thresholds influenced malaria incidence across Rwanda. Average temperature of 18.5 °C was associated with higher malaria risk, while temperature above 23.9 °C reduced the risk. Rainfall demonstrated a dual effect on malaria risk: conditions of low (below 73 mm per month) and high (above 223 mm per month) precipitation correlated with lower risk, while moderate rainfall (87 to 223 mm per month) correlated with higher risk. Seasonal patterns showed increased malaria risk during the major rainy season, while the short dry season presented lower risk. Conclusion: The study underscores the influence of temperature and rainfall on malaria transmission in Rwanda and calls for tailored interventions that are specific to location and season. The findings are crucial for informing policy that enhance preparedness and contribute to malaria elimination efforts. Future research should explore additional ecological and socioeconomic factors and their differential contribution to malaria transmission. [ABSTRACT FROM AUTHOR]

Background: Malaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health's "Zero Malaria Plan" targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative. Methods: A cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors. Results: The survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species. Conclusions: The study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon. [ABSTRACT FROM AUTHOR]

Background: Malaria risk maps are crucial for controlling and eliminating malaria by identifying areas of varying transmission risk. In the Greater Mekong Subregion, these maps guide interventions and resource allocation. This article focuses on analysing changes in malaria transmission and developing fine-scale risk maps using five years of routine surveillance data in Laos (2017–2021). The study employed data from 1160 geolocated health facilities in Laos, along with high-resolution environmental data. Methods: A Bayesian geostatistical framework incorporating population data and treatment-seeking propensity was developed. The models incorporated static and dynamic factors and accounted for spatial heterogeneity. Results: Results showed a significant decline in malaria cases in Laos over the five-year period and a shift in transmission patterns. While the north became malaria-free, the south experienced ongoing transmission with sporadic outbreaks. Conclusion: The risk maps provided insights into changing transmission patterns and supported risk stratification. These risk maps are valuable tools for malaria control in Laos, aiding resource allocation, identifying intervention gaps, and raising public awareness. The study enhances understanding of malaria transmission dynamics and facilitates evidence-based decision-making for targeted interventions in high-risk areas. [ABSTRACT FROM AUTHOR]

Background: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3–4 years, but the 2020–2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme. Methods: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020–2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020–2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017–2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations. Results: Approximately 70% of the study population received LLINs later than scheduled in 2020–2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected. Conclusions: The model results suggest that the disruptions in the 2020–2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas. [ABSTRACT FROM AUTHOR]

Abstract Background Plasmodium species of non-human primates (NHP) are of great interest because they can naturally infect humans. Plasmodium simium, a parasite restricted to the Brazilian Atlantic Forest, was recently shown to cause a zoonotic outbreak in the state of Rio de Janeiro. The potential of NHP to act as reservoirs of Plasmodium infection presents a challenge for malaria elimination, as NHP will contribute to the persistence of the parasite. The aim of the current study was to identify and quantify gametocytes in NHP naturally-infected by P. simium. Methods Whole blood samples from 35 NHP were used in quantitative reverse transcription PCR (RT-qPCR) assays targeting 18S rRNA, Pss25 and Pss48/45 malaria parasite transcripts. Absolute quantification was performed in positive samples for 18S rRNA and Pss25 targets. Linear regression was used to compare the quantification cycle (Cq) and the Spearman's rank correlation coefficient was used to assess the correlation between the copy numbers of 18S rRNA and Pss25 transcripts. The number of gametocytes/µL was calculated by applying a conversion factor of 4.17 Pss25 transcript copies per gametocyte. Results Overall, 87.5% of the 26 samples, previously diagnosed as P. simium, were positive for 18S rRNA transcript amplification, of which 13 samples (62%) were positive for Pss25 transcript amplification and 7 samples (54%) were also positive for Pss48/45 transcript. A strong positive correlation was identified between the Cq of the 18S rRNA and Pss25 and between the Pss25 and Pss48/45 transcripts. The 18S rRNA and Pss25 transcripts had an average of 1665.88 and 3.07 copies/µL, respectively. A positive correlation was observed between the copy number of Pss25 and 18S rRNA transcripts. Almost all gametocyte carriers exhibited low numbers of gametocytes (

Background: Over a decade of vector control by indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) distribution on the mainland, and only LLINs on islands had a minimal impact on disease burden in Nchelenge district, northern Zambia. Anopheles funestus and Anopheles gambiae are vectors known only from the mainland. Understanding vector bionomics in the district is necessary for planning and targeting effective vector control. This study aimed to provide information on abundance, seasonality, and Plasmodium falciparum sporozoite infectivity of malaria vectors in Nchelenge, including islands. Methods: Mosquitoes were collected in 192 CDC indoor light traps set in 56 households between January 2015 and January 2016. Morphological and molecular species identifications and P. falciparum circumsporoites by ELISA were performed. Mosquito counts and relative abundances from the islands and mainland were compared, and household factors associated with vector counts were determined. Results: A total of 5888 anophelines were collected during the study. Of these, 5,704 were female Anopheles funestus sensu lato (s.l.) and 248 female An. gambiae s.l. The highest proportion of An. funestus (n = 4090) was from Chisenga Island and An. gambiae (n = 174) was from Kilwa Island. The highest estimated counts per trap for An. funestus s.l. were from Chisenga island, (89.9, p < 0.001) and from the dry season (78.6, p < 001). For An. gambiae the highest counts per trap were from Kilwa island (3.1, p < 0.001) and the rainy season (2.5, p = 0.007). The highest estimated annual entomological inoculation rate was from Chisenga Island with 91.62 ib/p/y followed by Kilwa Island with 29.77 ib/p/yr, and then Mainland with 19.97 ib/p/yr. Conclusions: There was varied species abundance and malaria transmission risk across sites and seasons. The risk of malaria transmission was perennial and higher on the islands. The minimal impact of vector control efforts on the mainland was evident, but limited overall. Vector control intervention coverage with effective tools needs to be extended to the islands to effectively control malaria transmission in Nchelenge district. [ABSTRACT FROM AUTHOR]

Background: Although Ethiopia has made great strides in recent years to reduce the threat of malaria, the disease remains a significant issue in most districts of the country. It constantly disappears in parts of the areas before reappearing in others with erratic transmission rates. Thus, developing a malaria epidemic early warning system is important to support the prevention and control of the incidence. Methods: Space-time malaria risk mapping is essential to monitor and evaluate priority zones, refocus intervention, and enable planning for future health targets. From August 2013 to May 2019, the researcher considered an aggregated count of genus Plasmodium falciparum from 149 districts in Southern Ethiopia. Afterwards, a malaria epidemic early warning system was developed using model-based geostatistics, which helped to chart the disease's spread and future management. Results: Risk factors like precipitation, temperature, humidity, and nighttime light are significantly associated with malaria with different rates across the districts. Districts in the southwest, including Selamago, Bero, and Hamer, had higher rates of malaria risk, whereas in the south and centre like Arbaminch and Hawassa had moderate rates. The distribution is inconsistent and varies across time and space with the seasons. Conclusion: Despite the importance of spatial correlation in disease risk mapping, it may occasionally be a good idea to generate epidemic early warning independently in each district to get a quick picture of disease risk. A system like this is essential for spotting numerous inconsistencies in lower administrative levels early enough to take corrective action before outbreaks arise. [ABSTRACT FROM AUTHOR]

Background: A better understanding of vector distribution and malaria transmission dynamics at a local scale is essential for implementing and evaluating effectiveness of vector control strategies. Through the data gathered in the framework of a cluster randomized controlled trial (CRT) evaluating the In2Care (Wageningen, Netherlands) Eave Tubes strategy, the distribution of the Anopheles vector, their biting behaviour and malaria transmission dynamics were investigated in Gbêkê region, central Côte d'Ivoire. Methods: From May 2017 to April 2019, adult mosquitoes were collected monthly using human landing catches (HLC) in twenty villages in Gbêkê region. Mosquito species wereidentified morphologically. Monthly entomological inoculation rates (EIR) were estimated by combining the HLC data with mosquito sporozoite infection rates measured in a subset of Anopheles vectors using PCR. Finally, biting rate and EIR fluctuations were fit to local rainfall data to investigate the seasonal determinants of mosquito abundance and malaria transmission in this region. Results: Overall, Anopheles gambiae, Anopheles funestus, and Anopheles nili were the three vector complexes found infected in the Gbêkê region, but there was a variation in Anopheles vector composition between villages. Anopheles gambiae was the predominant malaria vector responsible for 84.8% of Plasmodium parasite transmission in the area. An unprotected individual living in Gbêkê region received an average of 260 [222–298], 43.5 [35.8–51.29] and 3.02 [1.96–4] infected bites per year from An. gambiae, An. funestus and An. nili, respectively. Vector abundance and malaria transmission dynamics varied significantly between seasons and the highest biting rate and EIRs occurred in the months of heavy rainfall. However, mosquitoes infected with malaria parasites remained present in the dry season, despite the low density of mosquito populations. Conclusion: These results demonstrate that the intensity of malaria transmission is extremely high in Gbêkê region, especially during the rainy season. The study highlights the risk factors of transmission that could negatively impact current interventions that target indoor control, as well as the urgent need for additional vector control tools to target the population of malaria vectors in Gbêkê region and reduce the burden of the disease. [ABSTRACT FROM AUTHOR]

Background: Plasmodium species of non-human primates (NHP) are of great interest because they can naturally infect humans. Plasmodium simium, a parasite restricted to the Brazilian Atlantic Forest, was recently shown to cause a zoonotic outbreak in the state of Rio de Janeiro. The potential of NHP to act as reservoirs of Plasmodium infection presents a challenge for malaria elimination, as NHP will contribute to the persistence of the parasite. The aim of the current study was to identify and quantify gametocytes in NHP naturally-infected by P. simium. Methods: Whole blood samples from 35 NHP were used in quantitative reverse transcription PCR (RT-qPCR) assays targeting 18S rRNA, Pss25 and Pss48/45 malaria parasite transcripts. Absolute quantification was performed in positive samples for 18S rRNA and Pss25 targets. Linear regression was used to compare the quantification cycle (Cq) and the Spearman's rank correlation coefficient was used to assess the correlation between the copy numbers of 18S rRNA and Pss25 transcripts. The number of gametocytes/µL was calculated by applying a conversion factor of 4.17 Pss25 transcript copies per gametocyte. Results: Overall, 87.5% of the 26 samples, previously diagnosed as P. simium, were positive for 18S rRNA transcript amplification, of which 13 samples (62%) were positive for Pss25 transcript amplification and 7 samples (54%) were also positive for Pss48/45 transcript. A strong positive correlation was identified between the Cq of the 18S rRNA and Pss25 and between the Pss25 and Pss48/45 transcripts. The 18S rRNA and Pss25 transcripts had an average of 1665.88 and 3.07 copies/µL, respectively. A positive correlation was observed between the copy number of Pss25 and 18S rRNA transcripts. Almost all gametocyte carriers exhibited low numbers of gametocytes (< 1/µL), with only one howler monkey having 5.8 gametocytes/µL. Conclusions: For the first time, a molecular detection of P. simium gametocytes in the blood of naturally-infected brown howler monkeys (Alouatta guariba clamitans) was reported here, providing evidence that they are likely to be infectious and transmit P. simium infection, and, therefore, may act as a reservoir of malaria infection for humans in the Brazilian Atlantic Forest. [ABSTRACT FROM AUTHOR]

Background: Malaria remains one of the main causes of morbidity and mortality in Cameroon. To inform vector control intervention decision making, malaria vector surveillance was conducted monthly from October 2018 to September 2020 in five selected sentinel sites (Gounougou and Simatou in the North, and Bonabéri, Mangoum and Nyabessang in the South). Methods: Human landing catches (HLCs), U.S. Centers for Disease Control and Prevention (CDC) light traps, and pyrethrum spray catches (PSCs) were used to assess vector density, species composition, human biting rate (HBR), endophagic index, indoor resting density (IRD), parity, sporozoite infection rates, entomological inoculation rate (EIR), and Anopheles vectorial capacity. Results: A total of 139,322 Anopheles mosquitoes from 18 species (or 21 including identified sub-species) were collected across all sites. Out of the 18 species, 12 were malaria vectors including Anopheles gambiae sensu lato (s.l.), Anopheles funestus s.l.., Anopheles nili, Anopheles moucheti, Anopheles paludis, Anopheles demeilloni, Anopheles. pharoensis, Anopheles ziemanni, Anopheles multicinctus, Anopheles tenebrosus, Anopheles rufipes, and Anopheles marshallii. Anopheles gambiae s.l. remains the major malaria vector (71% of the total Anopheles) collected, though An. moucheti and An. paludis had the highest sporozoite rates in Nyabessang. The mean indoor HBR of Anopheles ranged from 11.0 bites/human/night (b/h/n) in Bonabéri to 104.0 b/h/n in Simatou, while outdoors, it varied from 24.2 b/h/n in Mangoum to 98.7 b/h/n in Simatou. Anopheles gambiae s.l. and An. moucheti were actively biting until at least 8:00 a.m. The mean Anopheles IRD was 17.1 females/room, and the parity rate was 68.9%. The mean EIRs for each site were 55.4 infective bites/human/month (ib/h/m) in Gounougou, 99.0 ib/h/m in Simatou, 51.2 ib/h/m in Mangoum, 24.4 ib/h/m in Nyabessang, and 18.1 ib/h/m in Bonabéri. Anopheles gambiae s.l. was confirmed as the main malaria vector with the highest vectorial capacity in all sites based on sporozoite rate, except in Nyabessang. Conclusion: These findings highlight the high malaria transmission occurring in Cameroon and will support the National Malaria Control Program to design evidence-based malaria vector control strategies, and deployment of effective and integrated vector control interventions to reduce malaria transmission and burden in Cameroon, where several Anopheles species could potentially maintain year-round transmission. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the perception and awareness of malaria vaccine policy implementation among health policy actors in Nigeria. Methods: A descriptive study was conducted to assess the opinions and perceptions of policy actors on the implementation of a vaccination programme against malaria in Nigeria. Descriptive statistics were carried out to study the characteristics of the population and the univariate analysis of the responses to questions presented to the participants. Multinomial logistic regression was conducted to evaluate the association between demographic characteristics and the responses. Results: The study revealed that malaria vaccine awareness was poor, with only 48.9% of the policy actors having previous knowledge of the malaria vaccine. The majority of participants (67.8%) declared that they were aware of the importance of vaccine policy in efforts to manage disease transmission. As the number of years of work experience of the participants increased, the odds of being more likely to be aware of the malaria vaccine increased [OR 2.491 (1.183–5.250), p value < 0.05]. Conclusion: It is recommended that policy-makers develop methods of educating populations, increase awareness of the acceptability of the vaccine and ensure that an affordable malaria vaccine programme is implemented in the population. [ABSTRACT FROM AUTHOR]

Background: Understanding Plasmodium falciparum population diversity and transmission dynamics provides information on the intensity of malaria transmission, which is needed for assessing malaria control interventions. This study aimed to determine P. falciparum allelic diversity and multiplicity of infection (MOI) among asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo (DRC). Methods: A total of 438 DNA samples (248 asymptomatic and 190 symptomatic) were characterized by nested PCR and genotyping the polymorphic regions of pfmsp1 block 2 and pfmsp2 block 3. Results: Nine allele types were observed in pfmsp1 block2. The K1-type allele was predominant with 78% (229/293) prevalence, followed by the MAD20-type allele (52%, 152/293) and RO33-type allele (44%, 129/293). Twelve alleles were detected in pfmsp2, and the 3D7-type allele was the most frequent with 84% (256/304) prevalence, followed by the FC27-type allele (66%, 201/304). Polyclonal infections were detected in 63% (95% CI 56, 69) of the samples, and the MOI (SD) was 1.99 (0.97) in P. falciparum single-species infections. MOIs significantly increased in P. falciparum isolates from symptomatic parasite carriers compared with asymptomatic carriers (2.24 versus 1.69, adjusted b: 0.36, (95% CI 0.01, 0.72), p = 0.046) and parasitaemia > 10,000 parasites/µL compared to parasitaemia < 5000 parasites/µL (2.68 versus 1.63, adjusted b: 0.89, (95% CI 0.46, 1.25), p < 0.001). Conclusion: This survey showed low allelic diversity and MOI of P. falciparum, which reflects a moderate intensity of malaria transmission in the study areas. MOIs were more likely to be common in symptomatic infections and increased with the parasitaemia level. Further studies in different transmission zones are needed to understand the epidemiology and parasite complexity in the DRC. [ABSTRACT FROM AUTHOR]

Over the past two decades, a considerable expansion of malaria interventions has occurred at the national level in Angola, together with cross-border initiatives and regional efforts in southern Africa. Currently, Angola aims to consolidate malaria control and to accelerate the transition from control to pre-elimination, along with other country members of the Elimination 8 initiative. However, the tremendous heterogeneity in malaria prevalence among Angolan provinces, as well as internal population movements and migration across borders, represent major challenges for the Angolan National Malaria Control Programme. This review aims to contribute to the understanding of factors underlying the complex malaria situation in Angola and to encourage future research studies on transmission dynamics and population structure of Plasmodium falciparum, important areas to complement host epidemiological information and to help reenergize the goal of malaria elimination in the country. [ABSTRACT FROM AUTHOR]

Background: In the last decade Plasmodium knowlesi has been detected in humans throughout South East Asia. The highest risk groups for this infection are males, adults and those performing forest-related work. Furthermore, asymptomatic cases of P. knowlesi malaria have been reported including among women and children. Methods: Pubmed, Scopus and the Web of Science databases for literature describing asymptomatic P. knowlesi malaria published between 2010 and 2020 were searched. A systematic literature review was conducted to identify studies reporting the prevalence and incidence of laboratory confirmed asymptomatic P. knowlesi cases in humans, their clinical and demographic characteristics, and methods used to diagnose these cases. Results: By analysing over 102 papers, thirteen were eligible for this review. Asymptomatic P. knowlesi infections have been detected in 0.03%–4.0% of the population depending on region, and infections have been described in children as young as 2 years old. Various different diagnostic methods were used to detect P. knowlesi cases and there were differing definitions of asymptomatic cases in these studies. The literature indicates that regionally-differing immune-related mechanisms may play a part on the prevalence of asymptomatic P. knowlesi. Conclusion: Differing epidemiological characteristics of asymptomatic P. knowlesi malaria in different regions reinforces the need to further investigate disease transmission mechanics. Effective public health responses to changes in P. knowlesi epidemiology require proactive intervention and multisectoral collaboration. [ABSTRACT FROM AUTHOR]

Background: Roraima state is the northernmost state in Brazil and the primary border-crossing point between Brazil and Venezuela. The uncontrolled surge of malaria in Venezuela, coupled with mass migration of Venezuelans to neighbouring countries and the upward trend in informal mining in the state, pose a serious threat to the broader region, especially to migrant, indigenous and mining populations, jeopardizing malaria elimination efforts. This study describes changes in the epidemiological profile of malaria in Roraima state related to time, place and populations at risk from 2016 to 2020. Methods: De-identified malaria surveillance data were obtained from the Malaria Epidemiological Surveillance System from 2016 to 2020. Pearson's chi-square tested differences between imported and autochthonous cases. Multivariable logistic regression was used to identify risk factors for imported versus autochthonous cases by demographic characteristics. Results: Odds of being an imported case were higher for Plasmodium falciparum cases (AOR = 2.08). However, as the number of cases from Venezuela decreased in 2020 following closure of the border, the proportion of P. falciparum cases increased markedly, from 6.24% in 2019 to 18.50% in 2020. Over the 5-year period, the odds of being an imported case among miners were about nine times higher than the general population (AOR = 8.99). The proportion of total malaria cases that were among indigenous people increased from 33.09% in 2016 to 54.83% in 2020. Indigenous children had a higher burden of malaria with over 40% of cases in children 0 to 9 years old, compared to 8% in non-indigenous children 0 to 9 years old. In some municipalities, place of infection differed from place of notification, with a large proportion of cases in these municipalities reporting in Boa Vista. Conclusions: Malaria remains a serious threat in Roraima state, especially among high-risk populations, such as miners, migrants, and indigenous people. As malaria cases have increased among indigenous people and miners, and the proportion of P. falciparum cases has increased, elimination efforts require understanding of these risk factors to tailor interventions appropriately. Furthermore, cross-border surveillance systems need to be urgently strengthened at formal and unofficial border points, especially since the border with Venezuela reopened in July 2021. [ABSTRACT FROM AUTHOR]

Background: The zoonotic malaria parasite Plasmodium knowlesi has emerged across Southeast Asia and is now the main cause of malaria in humans in Malaysia. A critical priority for P. knowlesi surveillance and control is understanding whether transmission is entirely zoonotic or is also occurring through human-mosquito-human transmission. Methods: A systematic literature review was performed to evaluate existing evidence which refutes or supports the occurrence of sustained human-mosquito-human transmission of P. knowlesi. Possible evidence categories and study types which would support or refute non-zoonotic transmission were identified and ranked. A literature search was conducted on Medline, EMBASE and Web of Science using a broad search strategy to identify any possible published literature. Results were synthesized using the Synthesis Without Meta-analysis (SWiM) framework, using vote counting to combine the evidence within specific categories. Results: Of an initial 7,299 studies screened, 131 studies were included within this review: 87 studies of P. knowlesi prevalence in humans, 14 studies in non-human primates, 13 studies in mosquitoes, and 29 studies with direct evidence refuting or supporting non-zoonotic transmission. Overall, the evidence showed that human-mosquito-human transmission is biologically possible, but there is limited evidence of widespread occurrence in endemic areas. Specific areas of research were identified that require further attention, notably quantitative analyses of potential transmission dynamics, epidemiological and entomological surveys, and ecological studies into the sylvatic cycle of the disease. Conclusion: There are key questions about P. knowlesi that remain within the areas of research that require more attention. These questions have significant implications for malaria elimination and eradication programs. This paper considers limited but varied research and provides a methodological framework for assessing the likelihood of different transmission patterns for emerging zoonotic diseases. [ABSTRACT FROM AUTHOR]

Background: To understand the Plasmodium vivax malaria transmission intensity and to assess the effectiveness of prevention and control measures taken along the China–Myanmar border, a catalytic model was used to calculate the seroconversion rate, an important indicator of malaria transmission intensity with high sensitivity, which is particularly useful in areas of low transmission. Methods: Five counties in Yunnan Province bordering Myanmar were selected as survey sites, and subjects were obtained in each county by stratified random sampling in 2013–2014. Fingerstick blood was collected from each subject and tested for antibodies to P. vivax Merozoite Surface Protein 1-19 (PvMSP1-19) using indirect ELISA. A catalytic conversion model was used to assess the transmission intensity of P. vivax malaria based on the maximum likelihood of generating a community seroconversion rate. Results: A total of 3064 valid blood samples were collected. Antibody levels were positively correlated with age. The seroconversion rate (SCR) values for each village were Luoping (0.0054), Jingqiao (0.0061), Longpen (0.0087), Eluo (0.0079), Banwang (0.0042) and Banbie (0.0046), respectively. Conclusion: Overall, the intensity of P. vivax malaria transmission in the border areas of Yunnan Province is low and not entirely consistent across counties. Consecutive serological surveys are needed to provide a sensitive evaluation of transmission dynamics and can help to confirm areas where infection is no longer present. [ABSTRACT FROM AUTHOR]

Background: Achieving malaria elimination requires the targeting of the human reservoir of infection, including those patients with asymptomatic infection. The objective was to synthesise evidence on the accuracy of the rapid-onsite diagnostic tests (RDTs) and microscopy for the detection of asymptomatic malaria as part of the surveillance activities in Asian countries. Methods: This was a meta-analysis of diagnostic test accuracy. Relevant studies that evaluated the diagnostic performance of RDTs and microscopy for detection of asymptomatic malaria were searched in health-related electronic databases. The methodological quality of the studies included was assessed using the QUADAS-2 tool. Results: Ten studies assessing RDT and/or microscopy were identified. The diagnostic accuracies in all these studies were verified by PCR. Overall, the pooled sensitivities of RDT, as well as microscopy for detection of any malaria parasites in asymptomatic participants, were low, while their pooled specificities were almost ideal. For the detection of Plasmodium falciparum, pooled sensitivity by RDT (59%, 95%CI:16–91%) or microscopy (55%, 95%CI: 25–82%) were almost comparable. For detection of Plasmodium vivax, pooled sensitivity of RDT (51%, 95% CI:7–94%) had also the comparable accuracy of microscopy (54%, 95%CI,11–92%). Of note are the wide range of sensitivity and specificity. Conclusion: The findings of this meta-analysis suggest that RDTs and microscopy have limited sensitivity and are inappropriate for the detection of asymptomatic Plasmodium infections. Other methods including a combination of PCR-based strategies, Loop-Mediated Isothermal Amplification (LAMP) technique must be considered to target these infections, in order to achieve malaria elimination. However, more data is needed for the wide acceptance and feasibility of these approaches. Studies to explore the role of asymptomatic and sub-patent infections in the transmission of malaria are of critical importance and are recommended. [ABSTRACT FROM AUTHOR]

Background: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission. Methods: In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa–Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals. Results: The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11–15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR. Conclusions: This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission. [ABSTRACT FROM AUTHOR]

Sub-Saharan Africa is registering one of the highest urban population growth across the world. It is estimated that over 75% of the population in this region will be living in urban settings by 2050. However, it is not known how this rapid urbanization will affect vector populations and disease transmission. The present study summarizes findings from studies conducted in urban settings between the 1970s and 2020 to assess the effects of urbanization on the entomological inoculation rate pattern and anopheline species distribution. Different online databases such as PubMed, ResearchGate, Google Scholar, Google were screened. A total of 90 publications were selected out of 1527. Besides, over 200 additional publications were consulted to collate information on anopheline breeding habitats and species distribution in urban settings. The study confirms high malaria transmission in rural compared to urban settings. The study also suggests that there had been an increase in malaria transmission in most cities after 2003, which could also be associated with an increase in sampling, resources and reporting. Species of the Anopheles gambiae complex were the predominant vectors in most urban settings. Anopheline larvae were reported to have adapted to different aquatic habitats. The study provides updated information on the distribution of the vector population and the dynamic of malaria transmission in urban settings. The study also highlights the need for implementing integrated control strategies in urban settings. [ABSTRACT FROM AUTHOR]

Background: Malaria blood-stage infection length and intensity are important drivers of disease and transmission; however, the underlying mechanisms of parasite growth and the host's immune response during infection remain largely unknown. Over the last 30 years, several mechanistic mathematical models of malaria parasite within-host dynamics have been published and used in malaria transmission models. Methods: Mechanistic within-host models of parasite dynamics were identified through a review of published literature. For a subset of these, model code was reproduced and descriptive statistics compared between the models using fitted data. Through simulation and model analysis, key features of the models were compared, including assumptions on growth, immune response components, variant switching mechanisms, and inter-individual variability. Results: The assessed within-host malaria models generally replicate infection dynamics in malaria-naïve individuals. However, there are substantial differences between the model dynamics after disease onset, and models do not always reproduce late infection parasitaemia data used for calibration of the within host infections. Models have attempted to capture the considerable variability in parasite dynamics between individuals by including stochastic parasite multiplication rates; variant switching dynamics leading to immune escape; variable effects of the host immune responses; or via probabilistic events. For models that capture realistic length of infections, model representations of innate immunity explain early peaks in infection density that cause clinical symptoms, and model representations of antibody immune responses control the length of infection. Models differed in their assumptions concerning variant switching dynamics, reflecting uncertainty in the underlying mechanisms of variant switching revealed by recent clinical data during early infection. Overall, given the scarce availability of the biological evidence there is limited support for complex models. Conclusions: This study suggests that much of the inter-individual variability observed in clinical malaria infections has traditionally been attributed in models to random variability, rather than mechanistic disease dynamics. Thus, it is proposed that newly developed models should assume simple immune dynamics that minimally capture mechanistic understandings and avoid over-parameterization and large stochasticity which inaccurately represent unknown disease mechanisms. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission-blocking vaccines (TBVs) could help break the cycle of malaria transmission by conferring community rather than individual protection. When introducing new intervention strategies, uptake is dependent on acceptability, not just efficacy. In this exploratory study on acceptability of TBVs in Sierra Leone, it was hypothesized that TBVs would be largely acceptable to adults and health workers in areas with relatively few ongoing malaria interventions, and that (i) knowledge of malaria and vaccines, (ii) health behaviours associated with malaria and vaccines, and (iii) attitudes towards different vaccines types could lead to greater TBV acceptability. Methods: This study used a mixed methods approach in Bo, Sierra Leone, to understand community knowledge, attitudes, and practices related to malaria and vaccination in general. This included: (i) a population-based cross-sectional survey (n=615 adults), (ii) 6 focus group discussions with parents, and (iii) 20 key informant interviews. The concept of a TBV was explained to participants before they were asked about their willingness to accept this vaccine modality as part of an integrated malaria elimination programme. Results: This study found that most adults would be willing to receive a TBV vaccine. Respondents noted mostly positive past experiences with adult and childhood vaccinations for other infectious diseases and high levels of engagement in other malaria prevention behaviors such as bed nets. Perceived barriers to TBV acceptance were largely focused on general community-level distribution of a vaccine, including personal fears of vaccination and possible costs. After an explanation of the TBV mechanism, nearly all focus group and interview participants believed that community members would accept the vaccine as part of an integrated malaria control approach. Both parents and health workers offered insight on how to successfully roll-out a future TBV vaccination programme. Conclusions: The willingness of community members in Bo, Sierra Leone to accept a TBV as part of an integrated anti-malarial strategy suggests that the atypical mechanism of TBV action might not be an obstacle to future clinical trials. This study's findings suggests that perceived general barriers to vaccination implementation, such as perceived personal fears and vaccine cost, must be addressed in future clinical and implementation research studies. [ABSTRACT FROM AUTHOR]

Abstract Background Much of the extensive research regarding transmission of malaria is underpinned by mathematical modelling. Compartmental models, which focus on interactions and transitions between population strata, have been a mainstay of such modelling for more than a century. However, modellers are increasingly adopting agent-based approaches, which model hosts, vectors and/or their interactions on an individual level. One reason for the increasing popularity of such models is their potential to provide enhanced realism by allowing system-level behaviours to emerge as a consequence of accumulated individual-level interactions, as occurs in real populations. Methods A systematic review of 90 articles published between 1998 and May 2018 was performed, characterizing agent-based models (ABMs) relevant to malaria transmission. The review provides an overview of approaches used to date, determines the advantages of these approaches, and proposes ideas for progressing the field. Results The rationale for ABM use over other modelling approaches centres around three points: the need to accurately represent increased stochasticity in low-transmission settings; the benefits of high-resolution spatial simulations; and heterogeneities in drug and vaccine efficacies due to individual patient characteristics. The success of these approaches provides avenues for further exploration of agent-based techniques for modelling malaria transmission. Potential extensions include varying elimination strategies across spatial landscapes, extending the size of spatial models, incorporating human movement dynamics, and developing increasingly comprehensive parameter estimation and optimization techniques. Conclusion Collectively, the literature covers an extensive array of topics, including the full spectrum of transmission and intervention regimes. Bringing these elements together under a common framework may enhance knowledge of, and guide policies towards, malaria elimination. However, because of the diversity of available models, endorsing a standardized approach to ABM implementation may not be possible. Instead it is recommended that model frameworks be contextually appropriate and sufficiently described. One key recommendation is to develop enhanced parameter estimation and optimization techniques. Extensions of current techniques will provide the robust results required to enhance current elimination efforts.

Background: Plasmodium knowlesi and Plasmodium vivax are the predominant Plasmodium species that cause malaria in Malaysia and play a role in asymptomatic malaria disease transmission in Malaysia. The diagnostic tools available to diagnose malaria, such as microscopy and rapid diagnostic test (RDT), are less sensitive at detecting lower parasite density. Droplet digital polymerase chain reaction (ddPCR), which has been shown to have higher sensitivity at diagnosing malaria, allows direct quantification without the need for a standard curve. The aim of this study is to develop and use a duplex ddPCR assay for the detection of P. knowlesi and P. vivax, and compare this method to nested PCR and qPCR. Methods: The concordance rate, sensitivity and specificity of the duplex ddPCR assay were determined and compared to nested PCR and duplex qPCR. Results: The duplex ddPCR assay had higher analytical sensitivity (P. vivax = 10 copies/µL and P. knowlesi = 0.01 copies/µL) compared to qPCR (P. vivax = 100 copies/µL and P. knowlesi = 10 copies/µL). Moreover, the ddPCR assay had acceptable clinical sensitivity (P. vivax = 80% and P. knowlesi = 90%) and clinical specificity (P. vivax = 87.84% and P. knowlesi = 81.08%) when compared to nested PCR. Both ddPCR and qPCR detected more double infections in the samples. Conclusions: Overall, the ddPCR assay demonstrated acceptable efficiency in detection of P. knowlesi and P. vivax, and was more sensitive than nested PCR in detecting mixed infections. However, the duplex ddPCR assay still needs optimization to improve the assay's clinical sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background: Although mixed infection by two Plasmodium species has been recognized, mixed infection by three different Plasmodium species within one individual has not been clarified. This study sought to determine the pooled prevalence and proportion of triple mixed Plasmodium spp. infection compared with double mixed infection. Methods: Articles from PubMed, Scopus, and Web of Science were searched for cross-sectional studies of triple mixed infection by Plasmodium species and then were retrieved and extracted. The pooled proportion and prevalence of triple mixed infection by Plasmodium species were subjected to random-effects analysis. The secondary outcomes were differences in the pooled proportion between triple mixed infection and double mixed infection by Plasmodium species reported in the included studies. Results: Of 5621 identified studies, triple mixed infection data were available for 35 records, including 601 patients from 22 countries. The overall pooled prevalence of triple mixed infection was 4% (95% Confidence Interval (CI) 3–5%; I2 = 92.5%). The pooled proportion of triple mixed infection compared with double mixed infection was 12% (95% CI 9–18; I2 = 91%). Most of the included studies (29/35; 82.9%) presented a lower proportion of triple mixed infection than double mixed infection. Subgroup analysis demonstrated that the proportion of triple mixed infection was the highest in Oceania (23%; 95% CI 15–36%) and Europe (21%; 95% CI 5–86%), but the lowest in the USA (3%; 95% CI 2–4%). Moreover, the proportion of triple mixed infection was higher in residents (20%; 95% CI 14–29%) than in febrile patients (7%; 95% CI 4–13%), when compared with the proportion of double mixed infection. Subgroup analysis of the age groups demonstrated that, compared with the proportion of double mixed infection, triple mixed infection was lower in patients aged ≤ 5 years (OR = 0.27; 95% CI 0.13–0.56; I2 = 31%) and > 5 years (OR = 0.09; 95% CI 0.04–0.25, I2 = 78%). Conclusions: The present study suggested that, in areas where triple mixed infection were endemic, PCR or molecular diagnosis for all residents in communities where malaria is submicroscopic can provide prevalence data and intervention measures, as well as prevent disease transmission and enhance malaria elimination efforts. [ABSTRACT FROM AUTHOR]

Background: Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal. Methods: Clustering of infection was defined by the percent of persons with positive slides for asexual P. falciparum sleeping in a house which had been geopositioned. Data from each site were then tested for spatial, temporal and spatio-temporal clustering in relation to the prevalence of infection from smear surveys. Results: These studies suggest that clustering of P. falciparum infection also affects the effectiveness of control interventions. For example, the clustering of infection in Madina Fall disappeared in 2014–2016 after vector control eliminated the only breeding site in 2013. In contrast, the temporal clustering of infection in Dioro (rainy season of 2014, dry season of 2015) was consistent with the loss of funding for Dioro in the second quarter of 2014 and disappeared when funds again became available in late 2015. The clustering of infection in rural (western) areas of Gambissara was consistent with known rural–urban differences in the prevalence of infection and with the thatched roofs, open eaves and mud walls of houses in rural Gambissara. In contrast, the most intense transmission was in Dangassa, where the only encouraging observation was a lower prevalence of infection in the dry season. Taken together, these results suggest: (a) the transmission of infection was stopped in Madina Fall by eliminating the only known breeding site, (b) the prevalence of infection was reduced in Dioro after financial support became available again for malaria control in the second half of 2015, (c) improvements in housing should improve malaria control by reducing the number of vectors in rural communities such as western Gambissara, and (d) beginning malaria control during the dry season may reduce transmission in hyperendemic areas such as Dangassa. Conclusions: From a conceptual perspective, testing for spatial, temporal and spatio-temporal clustering based on epidemiologic data permits the generation of hypotheses for the clustering observed and the testing of candidate interventions to confirm or refute those hypotheses. [ABSTRACT FROM AUTHOR]

Background: A major health burden in Cameroon is malaria, a disease that is sensitive to climate, environment and socio-economic conditions, but whose precise relationship with these drivers is still uncertain. An improved understanding of the relationship between the disease and its drivers, and the ability to represent these relationships in dynamic disease models, would allow such models to contribute to health mitigation and adaptation planning. This work collects surveys of malaria parasite ratio and entomological inoculation rate and examines their relationship with temperature, rainfall, population density in Cameroon and uses this analysis to evaluate a climate sensitive mathematical model of malaria transmission. Methods: Co-located, climate and population data is compared to the results of 103 surveys of parasite ratio (PR) covering 18,011 people in Cameroon. A limited set of campaigns which collected year-long field-surveys of the entomological inoculation rate (EIR) are examined to determine the seasonality of disease transmission, three of the study locations are close to the Sanaga and Mefou rivers while others are not close to any permanent water feature. Climate-driven simulations of the VECTRI malaria model are evaluated with this analysis. Results: The analysis of the model results shows the PR peaking at temperatures of approximately 22 °C to 26 °C, in line with recent work that has suggested a cooler peak temperature relative to the established literature, and at precipitation rates at 7 mm day−1, somewhat higher than earlier estimates. The malaria model is able to reproduce this broad behaviour, although the peak occurs at slightly higher temperatures than observed, while the PR peaks at a much lower rainfall rate of 2 mm day−1. Transmission tends to be high in rural and peri-urban relative to urban centres in both model and observations, although the model is oversensitive to population which could be due to the neglect of population movements, and differences in hydrological conditions, housing quality and access to healthcare. The EIR follows the seasonal rainfall with a lag of 1 to 2 months, and is well reproduced by the model, while in three locations near permanent rivers the annual cycle of malaria transmission is out of phase with rainfall and the model fails. Conclusion: Malaria prevalence is maximum at temperatures of 24 to 26 °C in Cameroon and rainfall rates of approximately 4 to 6 mm day−1. The broad relationships are reproduced in a malaria model although prevalence is highest at a lower rainfall maximum of 2 mm day−1. In locations far from water bodies malaria transmission seasonality closely follows that of rainfall with a lag of 1 to 2 months, also reproduced by the model, but in locations close to a seasonal river the seasonality of malaria transmission is reversed due to pooling in the transmission to the dry season, which the model fails to capture. [ABSTRACT FROM AUTHOR]

Background: Malaria cases among mobile and migrant populations (MMPs) represent a large and important reservoir for transmission, if undetected or untreated. The objectives of this review were to identify which intersectoral actions have been taken and how they are applied to interventions targeted at the MMPs and also to assess the effect of interventions targeted to these special groups of population. Results: A total of 36 studies met the inclusion criteria for this review. Numerous stakeholders were identified as involved in the intersectoral actions to defeat malaria amongst MMPs. Almost all studies discussed the involvement of Ministry of Health/Public Health (MOH/MOPH). The most frequently assessed intervention among the studies that were included was the coverage and utilization of insecticide-treated nets as personal protective measures (40.5%), followed by the intervention of early diagnoses and treatment of malaria (33.3%), the surveillance and response activities (13.9%) and the behaviour change communication (8.3%). There is a dearth of information on how these stakeholders shared roles and responsibilities for implementation, and about the channels of communication between-and-within the partners and with the MOH/MOPH. Despite limited details in the studies, the intermediate outcomes showed some evidence that the intersectoral collaborations contributed to improvement in knowledge about malaria, initiation and promotion of bed nets utilization, increased access to diagnosis and treatment in a surveillance context and contributed towards a reduction in malaria transmission. Overall, a high proportion of the targeted MMPs was equipped with correct knowledge about malaria transmission (70%, 95% CI 57–83%). Interventions targeting the use of bed nets utilization were two times more likely to reduce malaria incidence amongst the targeted MMPs (summary OR 2.01, 95% CI 1.43–2.6) than the non-users. The various intersectoral actions were often more vertically organized and not fully integrated in a systemic way within a given country or sub-national administrative setting. Conclusion: Findings suggest that interventions supported by the multiple stakeholders had a significant impact on the reduction of malaria transmission amongst the targeted MMPs. Well-designed studies from different countries are recommended to robustly assess the role of intersectoral interventions targeted to MMPs and their impact on the reduction of transmission. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission is driven by multiple factors, including complex and multifaceted connections between malaria transmission, socioeconomic conditions, climate and interventions. Forecasting models should account for all significant drivers of malaria incidence although it is first necessary to understand the relationship between malaria burden and the various determinants of risk to inform the development of forecasting models. In this study, the associations between malaria risk, environmental factors, and interventions were evaluated through a systematic review. Methods: Five electronic databases (CAB Abstracts, EMBASE, Global Health, MEDLINE and ProQuest Dissertations & Theses) were searched for studies that included both the effects of the environment and interventions on malaria within the same statistical model. Studies were restricted to quantitative analyses and health outcomes of malaria mortality or morbidity, outbreaks, or transmission suitability. Meta-analyses were conducted on a subset of results using random-effects models. Results: Eleven studies of 2248 potentially relevant articles that met inclusion criteria were identified for the systematic review and two meta-analyses based upon five results each were performed. Normalized Difference Vegetation Index was not found to be statistically significant associated with malaria with a pooled OR of 1.10 (95% CI 0.07, 1.71). Bed net ownership was statistically associated with decreasing risk of malaria, when controlling for the effects of environment with a pooled OR of 0.75 (95% CI 0.60, 0.95). In general, environmental effects on malaria, while controlling for the effect of interventions, were variable and showed no particular pattern. Bed nets ownership, use and distribution, have a significant protective effect while controlling for environmental variables. Conclusions: There are a limited number of studies which have simultaneously evaluated both environmental and interventional effects on malaria risk. Poor statistical reporting and a lack of common metrics were important challenges for this review, which must be addressed to ensure reproducibility and quality research. A comprehensive or inclusive approach to identifying malaria determinants using standardized indicators would allow for a better understanding of its epidemiology, which is crucial to improve future malaria risk estimations. [ABSTRACT FROM AUTHOR]

Background: There is evidence that suggests that undernutrition has a detrimental effect on malarial immunity in children. The aim of the study was to discover whether nutrient supplementation improved development of malarial antibody immunity in children up to 18 months of age. Methods: The study was conducted with a subset of 432 Malawian children from a randomized controlled trial of nutritional supplements. The arms included pre- and postnatal small-quantity lipid-based nutrient supplements for both mother and child; prenatal supplementation with iron and folic acid; and pre- and postnatal supplementation with multiple micronutrients. Paired plasma samples were collected at 6 and 18 months of age. The levels of antibodies against merozoite surface protein 1 (MSP1 19kD) and MSP2, erythrocyte binding antigen 175 (EBA175), reticulocyte binding protein homologue 2A (Rh2A9), schizont extract and variant antigens expressed on the surface of infected erythrocytes were measured. Results: At 18 months of age, 5.4% of children were parasitaemic by microscopy and 49.1% were anaemic. Antibodies to the tested merozoite antigens and schizont extract increased between 6 and 18 months and this increase was statistically significant for MSP1, MSP2 and EBA175 (p < 0.0001) whereas IgG to variant surface antigens decreased with increasing age (p < 0.0001). However, the supplementation type did not have any impact on the prevalence or levels of antibodies at either 6 or 18 months of age to any of the tested malaria antigens in either univariate analysis or multivariate analysis after adjusting for covariates. Conclusions: Pre- and postnatal lipid-based nutrient supplementation did not alter malaria antibody acquisition during infancy, compared to prenatal supplementation with iron and folic acid or pre- and postnatal supplementation with multiple micronutrients. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional surveys of chimpanzee (Pan troglodytes) communities across sub-Saharan Africa show large geographical variation in malaria parasite (Plasmodium spp.) prevalence. The drivers leading to this apparent spatial heterogeneity may also be temporally dynamic but data on prevalence variation over time are missing for wild great apes. This study aims to fill this fundamental gap. Methods: Some 681 faecal samples were collected from 48 individuals of a group of habituated chimpanzees (Taï National Park, Côte d'Ivoire) across four non-consecutive sampling periods between 2005 and 2015. Results: Overall, 89 samples (13%) were PCR-positive for malaria parasite DNA. The proportion of positive samples ranged from 0 to 43% per month and 4 to 27% per sampling period. Generalized Linear Mixed Models detected significant seasonal and inter-annual variation, with seasonal increases during the wet seasons and apparently stochastic inter-annual variation. Younger individuals were also significantly more likely to test positive. Conclusions: These results highlight strong temporal fluctuations of malaria parasite detection rates in wild chimpanzees. They suggest that the identification of other drivers of malaria parasite prevalence will require longitudinal approaches and caution against purely cross-sectional studies, which may oversimplify the dynamics of this hostparasite system. [ABSTRACT FROM AUTHOR]

Malaria is the leading public health problem in Ethiopia where over 75% of the land surface is at risk with varying intensities depending on altitude and season. Although the mortality because of malaria infection has declined much during the last 15-20 years, some researchers worry that this success story may not be sustainable. Past notable achievements in the reduction of malaria disease burden could be reversed in the future. To interrupt, or even to eliminate malaria transmission in Ethiopia, there is a need to implement a wide range of interventions that include insecticide-treated bed nets, indoor residual spraying, improved control of residual malaria transmission, and improved diagnostics, enhanced surveillance, and methods to deal with the emergence of resistance both to drugs and to insecticides. Developments during the past years with increasing awareness about the role of very low levels of malaria prevalence can sustain infections, may also demand that tools not used in the routine control efforts to reduce or eliminate malaria, should now be made available in places where malaria transmission occurs. [ABSTRACT FROM AUTHOR]

Background: Transmission of Plasmodium greatly depends on the foraging behaviour of its mosquito vector (Anopheles spp.). The accessibility of blood hosts and availability of plant sugar (i.e., nectar) sources, together with mosquito energy state, have been shown to modulate blood feeding (and thus biting rates) of anopheline mosquitoes. In this study, the influence of mosquito starvation status and availability of nectar on the decision of female Anopheles gambiae mosquitoes to leave a bed net-protected blood host was examined. Methods: Two small-scale mesocosm experiments were conducted using female mosquitoes starved for 0, 24 or 48 h, that were released inside a specially constructed hut with mesh-sealed exits and containing a bed net-protected human volunteer. Floral cues were positioned on one side of the hut or the other. Several biologically plausible exponential decay models were developed that characterized the emigration rates of mosquitoes from the huts. These varied from simple random loss to leaving rates dependent upon energy state and time. These model fits were evaluated by examining their fitted parameter estimates and comparing Akaike information criterion. Results: Starved mosquitoes left domiciles at a higher rate than recently fed individuals however, there was no difference between 1- and 2-day-starved mosquitoes. There was also no effect of floral cue placement. The best fitting emigration model was one based on both mosquito energy state and time whereas the worst fitting model was one based on the assumption of constant leaving rates, independent of time and energy state. Conclusions: The results confirm that mosquito-leaving behaviour is energy-state dependent, and provide some of the first evidence of state-dependent domicile emigration in An. gambiae, which may play a role in malarial transmission dynamics. Employment of simple, first-principle, mechanistic models can be very useful to our understanding of why and how mosquitoes leave domiciles. [ABSTRACT FROM AUTHOR]

Background: As the prevalence of the malaria has been decreasing in many endemic countries including Myanmar, malaria elimination in Greater Mekong Region was targeted not later than 2030. The relevance of molecular and serological tools to identify residual transmission remains to be established in this setting. Methods: One-year cohort study was conducted and sera samples were collected in every 3 months with active and passive case detection for clinical malaria episodes by RDT, microscopy and molecular method. The sera were used to detect the malaria antibody against PfMSP1-19, PvAMA1, PvDBPII and PvMSP1-19 by protein microarray. Results: Among the recruited 1182 participants, there was no RDT positive case for malaria infection although two vivax infections were detected by microscopy in initial collection. Molecular methods detected the asymptomatic cases of 28/1182 (2.37%) in first, 5/894 (0.42%) in second, 12/944 (1.02%) in third, 6/889 (0.51%) in fourth collection, respectively. Seropositivity rates against the PfMSP1-19, PvMSP1-19, PvAMA1 and PvDBPII were 73/270 (27.0%), 85/270 (31.5%), 65/270 (24.1%) and 160/270 (59.3%), respectively. PfMSP1-19 and PvMSP1-19 showed high and stable antigenicity in acute and subacute samples but declining in 1-year history samples. No cross reactivity of PfMSP1-19 and PvMSP1-19 between the two species and higher seropositivity among the asymptomatic carriers were observed. Mapping data indicated serological surveillance can detect the geographical pattern of malaria infection under low transmission setting. Conclusions: These findings support that PfMSP1-19 and PvMSP1-19 are suggested for serosurveillance of the malaria especially in low transmission setting for further necessary actions have to be carried out to eliminate the malaria. [ABSTRACT FROM AUTHOR]

Background: A vaccine that targets multiple developmental stages of malaria parasites would be an effective tool for malaria control and elimination. Methods: A conserved gene in Plasmodium, the Plasmodium berghei gene (PBANKA_020570) encoding a 51 kDa protein (pb51 gene), was identified through search of the PlasmoDB database using a combination of expression and protein localization criteria. A partial domain of the Pb51 protein was expressed in a prokaryotic expression system (rPb51) and used for immunization in mice. The protein expression profile and localization were studied by Western blot and indirect immunofluorescence assay (IFA), respectively. The inhibitory effect of the anti-rPb51 antibodies on parasite proliferation was evaluated in erythrocytes in vivo. The transmission-blocking activity of the immune sera was determined by in vitro ookinete conversion assay and by direct mosquito feeding assay (DFA). Results: The rPb51 elicited specific antibodies in mice. Western blot confirmed Pb51 expression in schizonts, gametocytes and ookinetes. IFA showed localization of Pb51 on the outer membranes of schizonts, gametocytes, zygotes, retorts, ookinetes and sporozoites of P. berghei. Mice immunized with the rPb51 protein significantly reduced parasite proliferation and gametocyte conversion in vivo. Moreover, the rPb51 antisera also significantly reduced the in vitro ookinete conversion when added into the ookinete culture medium. In DFA, mice immunized with the rPb51 reduced the prevalence of mosquito infection by 21.3% and oocyst density by 54.8%. Conclusions: In P. berghei, P51 was expressed in both asexual erythrocytic and sexual stages and localized on the surface of these stages with the exception of the ring stage. The anti-rPb51 antibodies inhibited both P. berghei proliferation in mice and transmission of the parasite to mosquitoes. [ABSTRACT FROM AUTHOR]

Background: Malaria remains a worldwide public health concern and, in Colombia, despite the efforts to stop malaria transmission, the incidence of cases has increased over the last few years. In this context, it is necessary to evaluate vector diversity, infection rates, and spatial distribution, to better understand disease transmission dynamics. This information may contribute to the planning and development of vector control strategies. Results: A total of 778 Anopheles mosquitoes were collected in fifteen localities of Córdoba from August 2015 to October 2016. Six species were identified and overall, Anopheles albimanus was the most widespread and abundant species (83%). Other species of the Nyssorhynchus subgenus were collected, including Anopheles triannulatus (13%), Anopheles nuneztovari (1%), Anopheles argyritarsis (< 1%) and two species belonging to the Anopheles subgenus: Anopheles pseudopunctipennis (3%) and Anopheles neomaculipalpus (< 1%). Four species were found naturally infected with two Plasmodium species: Anopheles nuneztovari was detected naturally infected with Plasmodium falciparum and Anopheles pseudopunctipennis with Plasmodium vivax, whereas An. albimanus and An. triannulatus were found infected with both parasite species and confirmed by nested PCR. Conclusions: In general, the obtained results were contrasting with previous studies in terms of the most abundant and widespread collected species, and regarding infection rates, which were higher than those previously reported. A positive relationship between mosquito local abundance at the locality level and human infection at the municipality level was found. Mosquito local abundance and the number of houses with mosquitoes in each village are factors explaining malaria human cases in these villages. The obtained results suggest that other factors related to the apparent variation in malaria eco-epidemiology in northern Colombia, must be identified, to provide health authorities with better decision tools aiming to design control and prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Insect vectors, namely mosquitoes (Diptera: Culicidae), are compulsory for malaria parasites (Plasmodium spp.) to complete their life cycle. Despite this, little is known about vector competence of different mosquito species for the transmission of avian malaria parasites. Methods: In this study, nested PCR was used to determine Plasmodium spp. occurrence in pools of whole individuals, as well as the diversity of mitochondrial cytochrome b gene sequences in wild-caught mosquitoes sampled across Eastern Austria in 2013-2015. Results: A total of 45,749 mosquitoes in 2628 pools were collected, of which 169 pools (6.43%) comprising 9 mosquito species were positive for avian Plasmodium, with the majority of positives in mosquitoes of Culex pipiens s.l./Culex torrentium. Six different avian Plasmodium lineages were found, the most common were Plasmodium vaughani SYAT05, Plasmodium sp. Linn1 and Plasmodium relictum SGS1. In 2014, mosquitoes of the Culex pipiens complex were genetically identified and Culex pipiens f. pipiens presented with the highest number of avian Plasmodium positives (n = 37; 16.74%). Despite this, the minimum infection rate (MIR) was highest in Culex torrentium (5.36%) and Culex pipiens f. pipiens/f. molestus hybrids (5.26%). During 2014 and 2015, seasonal and annual changes in Plasmodium lineage distribution were also observed. In both years P. vaughani SYAT05 dominated at the beginning of the sampling period to be replaced later in the year by P. relictum SGS1 (2014) and Plasmodium sp. Linn1 (2015). Conclusions: This is the first large-scale study of avian Plasmodium parasites in Austrian mosquitoes. These results are of special interest, because molecular identification of the taxa of the Cx. pipiens complex and Cx. torrentium enabled the determination of Plasmodium prevalence in the different mosquito taxa and hybrids of this complex. Since pools of whole insects were used, it is not possible to assert any vector competence in any of the examined mosquitoes, but the results are nonetheless valuable in providing an overview of avian Plasmodium species and lineages present in Austria. [ABSTRACT FROM AUTHOR]

Background: As Swaziland progresses towards national malaria elimination, the importation of parasites into receptive areas becomes increasingly important. Imported infections have the potential to instigate local transmission and sustain local parasite reservoirs. Methods: Travel histories from Swaziland's routine surveillance data from January 2010 to June 2014 were extracted and analysed. The travel patterns and demographics of rapid diagnostic test (RDT)-confirmed positive cases identified through passive and reactive case detection (RACD) were analysed and compared to those found to be negative through RACD. Results: Of 1517 confirmed cases identified through passive surveillance, 67% reported travel history. A large proportion of positive cases reported domestic or international travel history (65%) compared to negative cases (10%). The primary risk factor for malaria infection in Swaziland was shown to be travel, more specifically international travel to Mozambique by 25- to 44-year old males, who spent on average 28 nights away. Maputo City, Inhambane and Gaza districts were the most likely travel destinations in Mozambique, and 96% of RDT-positive international travellers were either Swazi (52%) or Mozambican (44%) nationals, with Swazis being more likely to test negative. All international travellers were unlikely to have a bed net at home or use protection of any type while travelling. Additionally, paths of transmission, important border crossings and means of transport were identified. Conclusion: Results from this analysis can be used to direct national and well as cross-border targeting of interventions, over space, time and by sub-population. The results also highlight that collaboration between neighbouring countries is needed to tackle the importation of malaria at the regional level. [ABSTRACT FROM AUTHOR]

Background: Small islands serve as potential malaria reservoirs through which new infections might come to the mainland and may be important targets in malaria elimination efforts. This study investigated malaria vector species diversity, blood-meal hosts, Plasmodium infection rates, and long-lasting insecticidal net (LLIN) coverage on Mageta, Magare and Ngodhe Islands of Lake Victoria in western Kenya, a region where extensive vector control is implemented on the mainland. Results: From trapping for six consecutive nights per month (November 2012 to March 2015) using CDC light traps, pyrethrum spray catches and backpack aspiration, 1868 Anopheles mosquitoes were collected. Based on their cytochrome oxidase I (COI) and intergenic spacer region PCR and sequencing, Anopheles gambiae s.l. (68.52%), Anopheles coustani (19.81%) and Anopheles funestus s.l. (11.67%) mosquitoes were differentiated. The mean abundance of Anopheles mosquitoes per building per trap was significantly higher (p < 0.001) in Mageta than in Magare and Ngodhe. Mageta was also the most populated island (n = 6487) with low LLIN coverage of 62.35% compared to Ngodhe (n = 484; 88.31%) and Magare (n = 250; 98.59%). Overall, 416 (22.27%) engorged Anopheles mosquitoes were analysed, of which 41 tested positive for Plasmodium falciparum infection by high-resolution melting (HRM) analysis of 18S rRNA and cytochrome b PCR products. Plasmodium falciparum infection rates were 10.00, 11.76, 0, and 18.75% among blood-fed An. gambiae s.s. (n = 320), Anopheles arabiensis (n = 51), An. funestus s.s. (n = 29), and An. coustani (n = 16), respectively. Based on HRM analysis of vertebrate cytochrome b, 16S rRNA and COI PCR products, humans (72.36%) were the prominent blood-meal hosts of malaria vectors, but 20.91% of blood-meals were from non-human vertebrate hosts. Conclusions: These findings demonstrate high Plasmodium infection rates among the primary malaria vectors An. gambiae s.s. and An. arabiensis, as well as in An. coustani for the first time in the region, and that non-human bloodmeal sources play an important role in their ecology. Further, the higher Anopheles mosquito abundances on the only low LLIN coverage island of Mageta suggests that high LLIN coverage has been effective in reducing malaria vector populations on Magare and Ngodhe Islands. [ABSTRACT FROM AUTHOR]

Background: Anti-malarial drugs are an important tool for malaria control and elimination. Alongside their direct benefit in the treatment of disease, drug use has a community-level effect, clearing the reservoir of infection and reducing onward transmission of the parasite. Different compounds potentially have different impacts on transmission-with some providing periods of prolonged chemoprophylaxis whilst others have greater transmission-blocking potential. The aim was to quantify the relative benefit of such properties for transmission reduction to inform target product profiles in the drug development process and choice of first-line anti-malarial treatment in different endemic settings. Methods: A mathematical model of Plasmodium falciparum epidemiology was used to estimate the transmission reduction that can be achieved by using drugs of varying chemoprophylactic (protection for 3, 30 or 60 days) or transmission-blocking activity (blocking 79, 92 or 100% of total onward transmission). Simulations were conducted at low, medium or high transmission intensity (slide-prevalence in 2-10 year olds being 1, 10 or 40%, respectively), with drugs administered either via case management or mass drug administration (MDA). Results: Transmission reductions depend strongly on deployment strategy, treatment coverage and endemicity level. Transmission-blocking was most effective at low endemicity, whereas chemoprophylaxis was most useful at high endemicity levels. Increasing the duration of protection as much as possible was beneficial. Increasing transmission-blocking activity from the level of ACT to a 100% transmission-blocking drug (close to the effect estimated for ACT combined with primaquine) produced moderate impact but was not as effective as increasing the duration of protection in medium-to-high transmission settings (slide prevalence 10-40%). Combining both good transmission-blocking activity (e.g. as achieved by ACT or ACT + primaquine) and a long duration of protection (30 days or more, such as provided by piperaquine or mefloquine) within a drug regimen can substantially increase impact compared with drug regimens with only one of these properties in medium to high transmission areas (slide-prevalence in 2-10 year olds ~10 to 40%). These results applied whether the anti-malarials were used for case management or for MDA. Discussion: These results emphasise the importance of increasing access to treatment for routine case management, and the potential value of choosing first-line anti-malarial treatment policies according to local malaria epidemiology to maximise impact on transmission. There is no indication that the optimal drug choice should differ between delivery via case management or MDA. [ABSTRACT FROM AUTHOR]

Background: The sexual stages (gametocytes) of Plasmodium falciparum do not directly contribute to the pathology of malaria but are essential for transmission of the parasite from the human host to the mosquito. Mature gametocytes circulate in infected human blood for several days and their circulation time has been modelled mathematically from data of previous in vivo studies. This is the first time that longevity of gametocytes is studied experimentally in vitro. Methods: The in vitro longevity of P. falciparum gametocytes of 1 clinical isolate and 2 laboratory strains was assessed by three different methods: microscopy, flow cytometry and reverse transcription quantitative real-time PCR (RTqPCR). Additionally, the rate of gametocytogenesis of the used P. falciparum strains was compared. Results: The maximum in vitro lifespan of P. falciparum gametocytes reached almost 2 months (49 days by flow cytometry, 46 days by microscopy, and at least 52 days by RT-qPCR) from the starting day of gametocyte culture to death of last parasite in the tested strains with an average 50% survival rate of 6.5, 2.6 and 3.5 days, respectively. Peak gametocytaemia was observed on average 19 days after initiation of gametocyte culture followed by a steady decline due to natural decay of the parasites. The rate of gametocytogenesis was highest in the NF54 strain. Conclusions: Plasmodium falciparum mature gametocytes can survive up to 16-32 days (at least 14 days for mature male gametocytes) in vitro in absence of the influence of host factors. This confirms experimentally a previous modelling estimate that used molecular tools for gametocyte detection in treated patients. The survival time might reflect the time the parasite can be transmitted to the mosquito after clearance of asexual parasites. These results underline the importance of efficient transmission blocking agents in the fight against malaria. [ABSTRACT FROM AUTHOR]

Background: Cross-border malaria transmission in China is a major component of Chinese imported malaria cases. Such cases mostly are travellers returning from malaria endemic countries in Africa. By investigating malaria infectious status among Chinese worker in Africa, this study analysed the malaria risk factors, in order to establish infectious forecast model. Methods: Chinese returnees data from Africa were collected at Guangzhou Baiyun International Airport, Guangzhou, China between August 2015 and March 2016 and were included in the cross-sectional and retrospective survey. Results: A total of 1492 respondents were included in the study with the majority consisting of junior middle school educated male. Most of them are manual and technical workers hired by companies, with average of 37.04 years of age. Overall malaria incidence rate of the population was 8.98% (134/1492), and there were no significant differences regarding age, gender, occupation, or team. Forecast model was developed on the basis of malaria risk factors including working country, local ecological environment type, work duration and intensity of mosquito bite prevention. Conclusions: The survey suggested that malaria incidence was high among Chinese travellers who had worked in Africa countries of heavy malaria burden. Further research on the frequency and severity of clinical episodes among Chinese travellers having worked in Africa is needed. [ABSTRACT FROM AUTHOR]

Background: Cross-border malaria transmission is an important problem for national malaria control programmes. The epidemiology of cross-border malaria is further complicated in areas where Plasmodium falciparum and Plasmodium vivax are both endemic. By combining passive case detection data with entomological data, a transmission scenario on the northwestern Thai-Myanmar border where P. falciparum is likely driven by importation was described, whereas P. vivax is also locally transmitted. This study highlights the differences in the level of control required to eliminate P. falciparum and P. vivax from the same region. Methods: Malaria case data were collected from malaria clinics in Suan Oi village, Tak Province, Thailand between 2011 and 2014. Infections were diagnosed by light microscopy. Demographic data, including migrant status, were correlated with concomitantly collected entomology data from 1330 mosquito trap nights using logistic regression. Malaria infection in the captured mosquitoes was detected by ELISA. Results: Recent migrants were almost four times more likely to be infected with P. falciparum compared with Thai patients (OR 3.84, p < 0.001) and cases were significantly associated with seasonal migration. However, P. falciparum infection was not associated with the Anopheles mosquito capture rates, suggesting predominantly imported infections. In contrast, recent migrants were equally likely to present with P. vivax as mid-term migrants. Both migrant groups were twice as likely to be infected with P. vivax in comparison to the resident Thai population (OR 1.96, p < 0.001 and OR 1.94, p < 0.001, respectively). Plasmodium vivax cases were strongly correlated with age and local capture rates of two major vector species Anopheles minimus and Anopheles maculatus (OR 1.23, p = 0.020 and OR 1.33, p = 0.046, respectively), suggesting that a high level of local transmission might be causing these infections. Conclusions: On the Thai-Myanmar border, P. falciparum infections occur mostly in the recent migrant population with a seasonality reflecting that of agricultural activity, rather than that of the local mosquito population. This suggests that P. falciparum was mostly imported. In contrast, P. vivax cases were significantly associated with mosquito capture rates and less with migrant status, indicating local transmission. This highlights the different timelines and requirements for P. falciparum and P. vivax elimination in the same region and underlines the importance of multinational, cross-border malaria control. [ABSTRACT FROM AUTHOR]

Background: An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vector. However, in initial clinical trials the limited immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge. Methods: Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime boost vaccination strategies to augment the immune response against Pfs25. Specifically, an Ad5 vector that directs expression of full-length, membrane-bound Pfs25 was used as a priming immunization followed by a boost with Ad5 viral particles displaying only the Pfs25 epitope targeted by transmission-blocking antibodies 4B7 and 1D2 (Pfs25 aa 122-134) in hypervariable region 5 of the hexon capsid protein. Results: This heterologous prime-boost vaccine strategy induced antibodies that significantly inhibit P. falciparum transmission to mosquitoes in a standard membrane-feeding assay. Further, immunized mice generated a robust anti- Pfs25 antibody response characterized by higher titer, higher relative avidity and a broader IgG subclass profile than observed with a homologous prime-boost with recombinant Pfs25/alum. Conclusion: The data suggest that focusing the immune response against defined epitopes displayed on the viral capsid is an effective strategy for transmission-blocking vaccine development. [ABSTRACT FROM AUTHOR]

Background: The current trend of Plasmodium vivax cases imported from Southeast Asia into China has sharply increased recently, especially from the China-Myanmar border (CMB) area. High recombination rates of P. vivax populations associated with varied transmission intensity might cause distinct local selective pressures. The information on the genetic variability of P. vivax in this area is scant. Hence, this study assessed the genetic diversity of P. vivax genome sequence in CMB area and aimed to provide information on the positive selection of new gene loci. Results: This study reports a genome-wide survey of P. vivax in CMB area, using blood samples from local patients to identify population-specific selective processes. The result showed that considerable genetic diversity and mean pair-wise divergence among the sequenced P. vivax isolates were higher in some important gene families. Using the standardized integrated haplotype score (|iHS|) for all SNPs in chromosomal regions with SNPs above the top 1% distribution, it was observed that the top score locus involved 356 genes and most of them are associated with red blood cell invasion and immune evasion. The XP-EHH test was also applied and some important genes associated with anti-malarial drug resistance were observed in high positive scores list. This result suggests that P. vivax in CMB area is facing more pressure to survive than any other region and this has led to the strong positive selection of genes that are associated with host-parasite interactions. Conclusions: This study suggests that greater genetic diversity in P. vivax from CMB area and positive selection signals in invasion and drug resistance genes are consistent with the history of drug use during malaria elimination programme in CMB area. Furthermore, this result also demonstrates that haplotype-based detecting selection can assist the genome-wide methods to identify the determinants of P. vivax diversity. [ABSTRACT FROM AUTHOR]

Background: Myanmar has the heaviest burden of malaria in the Greater Mekong Sub-region. Asymptomatic Plasmodium spp. infections are common in this region and may represent an important reservoir of transmission that must be targeted for malaria elimination. Methods: A mass blood survey was conducted among 485 individuals from six villages in Kayah State, an area of endemic but low transmission malaria in eastern Myanmar. Malaria infection was screened by rapid diagnostic test (RDT), light microscopy and real-time polymerase chain reaction (PCR), and its association with demographic factors was explored. Results: The prevalence of asymptomatic Plasmodium spp. infection was 2.3% (11/485) by real-time PCR. Plasmodium vivax accounted for 72.7% (8/11) and Plasmodium falciparum for 27.3% (3/11) of infections. Men were at greater risk of infection by Plasmodium spp. than women. Individuals who worked as farmers or wood and bamboo cutters had an increased risk of infection. Conclusion: A combination of RDT, light microscopy and PCR diagnostics were used to identify asymptomatic malaria infection, providing additional information on asymptomatic cases in addition to the routine statistics on symptomatic cases, so as to determine the true burden of disease in the area. Such information and risk factors can improve malaria risk stratification and guide decision-makers towards better design and delivery of targeted interventions in small villages, representative of Kayah State. [ABSTRACT FROM AUTHOR]

Background: Transmission-blocking interventions (TBIs) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. TBIs include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. Accurate methodologies are key to assess TBI efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials. Measuring intervention efficacy can be problematic because there is substantial variation in the number of parasites in both the host and vector populations, which can impact transmission even in laboratory settings. Methods: A statistically robust empirical method is introduced for estimating intervention efficacy from standardised population assay experiments. This method will be more reliable than simple summary statistics as it captures changes in parasite density in different life-stages. It also allows efficacy estimates at a finer resolution than previous methods enabling the impact of the intervention over successive generations to be tracked. A major advantage of the new methodology is that it makes no assumptions on the population dynamics of infection. This enables both host-to-vector and vector-to-host transmission to be density-dependent (or other) processes and generates easy-tounderstand estimates of intervention efficacy. Results: This method increases the precision of intervention efficacy estimates and demonstrates that relying on changes in infection prevalence (the proportion of infected hosts) alone may be insufficient to capture the impact of TBIs, which also suppress parasite density in secondarily infected hosts. Conclusions: The method indicates that potentially useful, partially effective TBIs may require multiple infection cycles before substantial reductions in prevalence are observed, despite more rapidly suppressing parasite density. Accurate models to quantify efficacy will have important implications for understanding how TBI candidates might perform in field situations and how they should be evaluated in clinical trials. [ABSTRACT FROM AUTHOR]