UNASSIGNED: Following World Health Organization (WHO) plans for thirty-five malaria-endemic countries, Indonesia will eliminate malaria by 2030. As one of the Indonesian provinces, West Java targeted subnational malaria elimination in 2022. This article aims to describe malaria surveillance data and elimination programs, including weaknesses in sustaining the program.
METHODS: This study used secondary data from malaria surveillance information system regencies/cities\' case reports for 2019-2022 and achievement data of sub-national malaria elimination certification from each regency/city from 2014-2022. The data was confirmed from the evaluation study document, analysis of reported cases, and interviews.
RESULTS: Most cases were confirmed by microscopic examination (84.1% in 2021 and 94.4% in 2022) and rapid diagnostic tests (57% in 2019 and 58.1% in 2020). Malaria is more prevalent among men (93% in 2019, 95% in 2020, 96% in 2021, and 95.9% in 2022) and productive ages of 15-64 years (98.8% in 2019, 100% in 2020, 99.2% in 2021, and 98.8% in 2022), frequently occurs in the military (56.3% in 2019, 75.7% in 2020, 45.2% in 2021) and police (40.5% in 2022), often uses passive case detection for identifying cases (97.9% in 2019 and 2020, 95.2% in 2021, and 97.6% in 2022), and the majority undergo inpatient treatment (86.4% in 2019, 81.7% in 2021, and 82.6% in 2022). Most positive cases originated from imported cases, and last indigenous cases were still found in 2019. Plasmodium vivax dominated malaria cases and and relapses were high (55.0% in 2020, and 47.3% in 2022).
UNASSIGNED: All regencies/cities have obtained sub-national malaria elimination certification in 2022. West Java has the potential to be verified for Java-Bali sub-national malaria elimination targeted in 2023, albeit cases of imported malaria still occur. It is imperative to address the issue of imported cases transitioning into locally transmitted cases (introduced) by effective coordination across all regencies/cities and inter-provincial efforts.

BACKGROUND: A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has shown extreme resilience to control measures.
OBJECTIVE: This proof-of-concept study aimed to provide evidence for implementing primaquine mass drug administration (pMDA) as a strategy for P. vivax elimination in low-endemicity settings.
METHODS: The study employed a mixed-methods trial to thoroughly evaluate the effectiveness, safety, acceptability, and community engagement of pMDA. The quantitative part was designed as a 2-period cluster-crossover randomized controlled trial. The intervention was pMDA augmented to the national prevention and control standards with directly observed treatment (DOT) by village health volunteers. The qualitative part employed in-depth interviews and brainstorming discussions. The study involved 7 clusters in 2 districts of 2 southern provinces in Thailand with persistently low P. vivax transmission. In the quantitative part, 5 cross-sectional blood surveys were conducted in both the pMDA and control groups before and 3 months after pMDA. The effectiveness of pMDA was determined by comparing the proportions of P. vivax infections per 1000 population between the 2 groups, with a multilevel zero-inflated negative binomial model adjusted for cluster and time as covariates and the interaction. The safety data comprised adverse events after drug administration. Thematic content analysis was used to assess the acceptability and engagement of stakeholders.
RESULTS: In the pre-pMDA period, the proportions of P. vivax infections in the pMDA (n=1536) and control (n=1577) groups were 13.0 (95% CI 8.2-20.4) and 12.0 (95% CI 7.5-19.1), respectively. At month 3 post-pMDA, these proportions in the pMDA (n=1430) and control (n=1420) groups were 8.4 (95% CI 4.6-15.1) and 5.6 (95% CI 2.6-11.5), respectively. No statistically significant differences were found between the groups. The number of malaria cases reduced in all clusters in both groups, and thus, the impact of pMDA was inconclusive. There were no major safety concerns. Acceptance among the study participants and public health care providers at local and national levels was high, and they believed that pMDA had boosted awareness in the community.
CONCLUSIONS: pMDA was associated with high adherence, safety, and tolerability, but it may not significantly impact P. vivax transmission. As this was a proof-of-concept study, we decided not to scale up the intervention with larger clusters and samples. An alternative approach involving a targeted primaquine treatment strategy with primaquine and DOT is currently being implemented. We experienced success regarding effective health care workforces at point-of-care centers, effective collaborations in the community, and commitment from authorities at local and national levels. Our efforts boosted the acceptability of the malaria-elimination initiative. Community engagement is recommended to achieve elimination targets.
BACKGROUND: Thai Clinical Trials Registry TCTR20190806004; https://www.thaiclinicaltrials.org/show/TCTR20190806004.

Background Malaria in pregnancy (MIP) is a major public health problem due to the vulnerability of pregnant women to infections, resulting in adverse maternal/foetal outcomes in endemic areas. Methods We did a field-based study to assess the burden of MIP (prevalence at the time of enrolment and follow-up) and to identify risk factors for MIP in the Birsa and Baihar blocks of district Balaghat in Madhya Pradesh, which have perennial malaria transmission. Malaria screening (during 2015-2017) was done by microscopy and bivalent rapid diagnostic test (SD Bioline RDT, malaria antigen Plasmodium falciparum/Plasmodium vivax Pf/Pv). Dried blood spots were used for haemoglobin estimation. Sociodemographic details with past and present pregnancy status were obtained. A subset of pregnant women were followed up for malaria during pregnancy. Women were also screened for malaria post delivery. Malaria treatment was given as per the National Guidelines of 2013. Multivariate analysis was done to assess independent risk factors for malaria. Results A total of 1728 pregnant women were screened, of which 1651 were included in the final analysis. Malaria prevalence at first screening was 23.4% (Pf 88%). Prevalence and Pf parasitaemia both were significantly higher among primigravid (G1) compared to multigravid (G>2; p value 0.012 and 0.019, respectively). Pregnant women of the Baiga ethnic group were more likely to have malaria compared to those belonging to the Gond group (OR [95% CI]; 2.4 [1.7-3.4]; p<0.00001) and non-indigenous group (OR [95% CI]; 8.3 [3.9-19.7]; p<0.00001). Primigravid status of women, first and second trimester of pregnancy, women belonging to indigenous ethnic tribal group and cash crop insufficiency for whole year (a socioeconomic indicator) in the family were the independent risk factors for malaria. Conclusion MIP is a major public health problem in forested tribal settlements of Birsa and Baihar blocks of Balaghat district in Madhya Pradesh and requires immediate intervention.

BACKGROUND: Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria.
METHODS: Data on imported malaria cases reported in Sri Lanka from 2013 to 2023 were extracted from the national malaria database maintained by the Anti Malaria Campaign (AMC) of Sri Lanka. Case data of severe malaria as defined by the World Health Organization were analysed with regard to patients\' general characteristics and their health-seeking behaviour, and the latter compared with that of uncomplicated malaria patients. Details of the last three cases of severe malaria in 2023 are presented.
RESULTS: 532 imported malaria cases were diagnosed over 11 years (2013-2023); 46 (8.6%) were severe malaria, of which 45 were Plasmodium falciparum and one Plasmodium vivax. Most severe malaria infections were acquired in Africa. All but one were males, and a majority (87%) were 26-60 years of age. They were mainly Sri Lankan nationals (82.6%). Just over half (56.5%) were treated at government hospitals. The average time between arrival of the person in Sri Lanka and onset of illness was 4 days. 29 cases of severe malaria were compared with 165 uncomplicated malaria cases reported from 2015 to 2023. On average both severe and uncomplicated malaria patients consulted a physician equally early (mean = 1 day) with 93.3% of severe malaria doing so within 3 days. However, the time from the point of consulting a physician to diagnosis of malaria was significantly longer (median 4 days) in severe malaria patients compared to uncomplicated patients (median 1 day) (p = 0.012) as was the time from onset of illness to diagnosis (p = 0.042). All severe patients recovered without sequelae except for one who died.
CONCLUSIONS: The risk of severe malaria among imported cases increases significantly beyond 5 days from the onset of symptoms. Although patients consult a physician early, malaria diagnosis tends to be delayed by physicians because it is now a rare disease. Good access to expert clinical care has maintained case fatality rates of severe malaria at par with those reported elsewhere.

BACKGROUND: Malaria remains a severe parasitic disease, posing a significant threat to public health and hindering economic development in sub-Saharan Africa. Ethiopia, a malaria endemic country, is facing a resurgence of the disease with a steadily rising incidence. Conventional diagnostic methods, such as microscopy, have become less effective due to low parasite density, particularly among Duffy-negative human populations in Africa. To develop comprehensive control strategies, it is crucial to generate data on the distribution and clinical occurrence of Plasmodium vivax and Plasmodium falciparum infections in regions where the disease is prevalent. This study assessed Plasmodium infections and Duffy antigen genotypes in febrile patients in Ethiopia.
METHODS: Three hundred febrile patients visiting four health facilities in Jimma town of southwestern Ethiopia were randomly selected during the malaria transmission season (Apr-Oct). Sociodemographic information was collected, and microscopic examination was performed for all study participants. Plasmodium species and parasitaemia as well as the Duffy genotype were assessed by quantitative polymerase chain reaction (qPCR) for all samples. Data were analysed using Fisher\'s exact test and kappa statistics.
RESULTS: The Plasmodium infection rate by qPCR was 16% (48/300) among febrile patients, of which 19 (39.6%) were P. vivax, 25 (52.1%) were P. falciparum, and 4 (8.3%) were mixed (P. vivax and P. falciparum) infections. Among the 48 qPCR-positive samples, 39 (13%) were negative by microscopy. The results of bivariate logistic regression analysis showed that agriculture-related occupation, relapse and recurrence were significantly associated with Plasmodium infection (P < 0.001). Of the 300 febrile patients, 85 (28.3%) were Duffy negative, of whom two had P. vivax, six had P. falciparum, and one had mixed infections. Except for one patient with P. falciparum infection, Plasmodium infections in Duffy-negative individuals were all submicroscopic with low parasitaemia.
CONCLUSIONS: The present study revealed a high prevalence of submicroscopic malaria infections. Plasmodium vivax infections in Duffy-negative individuals were not detected due to low parasitaemia. In this study, an improved molecular diagnostic tool was used to detect and characterize Plasmodium infections, with the goal of quantifying P. vivax infection in Duffy-negative individuals. Advanced molecular diagnostic techniques, such as multiplex real-time PCR, loop-mediated isothermal amplification (LAMP), and CRISPR-based diagnostic methods. These techniques offer increased sensitivity, specificity, and the ability to detect low-parasite-density infections compared to the employed methodologies.

UNASSIGNED: Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations of Plasmodium falciparum-infected erythrocytes in the placenta. However, the pathomechanism of placental Plasmodium vivax infection has not been thoroughly investigated. Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator of the response to hypoxic conditions, which interacts with the change and imbalances of many chemical mediators, including angiogenic factors, leading to fetal growth abnormality.
UNASSIGNED: This study was conducted cross-sectionally in Maumere, Sikka Regency, East Nusa Tenggara Province, previously known as one of the malaria endemic areas with a high incidence of low birth weight (LBW) cases. This study collected peripheral and umbilical blood samples and placental tissues from mothers who delivered their babies with LBW at the TC Hiller Regional Hospital. All of the blood samples were examined for parasites by microscopic and PCR techniques, while the plasma levels of VEGF, PlGF, VEGFR-1, VEGFR-2, and HIF-1α were determined using ELISA. The sequestration of infected erythrocytes and hemozoin was determined from placental histological slides, and the expression of placenta angiogenic factors was observed using the immunofluorescent technique.
UNASSIGNED: In this study, 33 cases had complete data to be analyzed. Of them, 19 samples were diagnosed as vivax malaria and none of falciparum malaria. There were significant differences in Δ 10th percentile growth curve of baby\'s body weights and also all angiogenic factors in placental tissues {VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α} between those infected and not infected cases (p<0.05), but not for VEGF and VEGFR-2 in the plasma.
UNASSIGNED: This study indicated that Plasmodium vivax sequestration may promote LBW through alterations and imbalances in angiogenic factors led by HIF-1α.

BACKGROUND: Malaria, a prominent vector borne disease causing over a million annual cases worldwide, predominantly affects vulnerable populations in the least developed regions. Despite their preventable and treatable nature, malaria remains a global public health concern. In the last decade, India has faced a significant decline in malaria morbidity and mortality. As India pledged to eliminate malaria by 2030, this study examined a decade of surveillance data to uncover space-time clustering and seasonal trends of Plasmodium vivax and Plasmodium falciparum malaria cases in West Bengal.
METHODS: Seasonal and trend decomposition using Loess (STL) was applied to detect seasonal trend and anomaly of the time series. Univariate and multivariate space-time cluster analysis of both malaria cases were performed at block level using Kulldorff\'s space-time scan statistics from April 2011 to March 2021 to detect statistically significant space-time clusters.
RESULTS: From the time series decomposition, a clear seasonal pattern is visible for both malaria cases. Statistical analysis indicated considerable high-risk P. vivax clusters, particularly in the northern, central, and lower Gangetic areas. Whereas, P. falciparum was concentrated in the western region with a significant recent transmission towards the lower Gangetic plain. From the multivariate space-time scan statistics, the co-occurrence of both cases were detected with four significant clusters, which signifies the regions experiencing a greater burden of malaria cases.
CONCLUSIONS: Seasonal trends from the time series decomposition analysis show a gradual decline for both P. vivax and P. falciparum cases in West Bengal. The space-time scan statistics identified high-risk blocks for P. vivax and P. falciparum malaria and its co-occurrence. Both malaria types exhibit significant spatiotemporal variations over the study area. Identifying emerging high-risk areas of P. falciparum malaria over the Gangetic belt indicates the need for more research for its spatial shifting. Addressing the drivers of malaria transmission in these diverse clusters demands regional cooperation and strategic strategies, crucial steps towards overcoming the final obstacles in malaria eradication.

Among the factors affecting the effectiveness of malaria control is poor knowledge of the entomologic drivers of the disease. We investigated anopheline populations as part of a baseline study to implement house screening of windows and doors as a supplementary malaria control tool towards elimination in Jabi Tehnan district, Amhara Regional State of Ethiopia. The samples were surveyed monthly using CDC light traps between June 2020 and May 2021. Mosquito trap density (< 3 mosquitoes/trap) was low, however, with a high overall Plasmodium sporozoite rate (9%; indoor = 4.3%, outdoor = 13.1%) comprising P. falciparum (88.9%) and P. vivax (11.1%). Anopheles gambiae s.l., mostly An. arabiensis, comprised > 80% of total anopheline captures and contributed ~ 42% of Plasmodium-infected mosquitoes. On the other hand, morphologically scored Anopheles funestus s.l., constituting about 6% of anopheline collections, accounted for 50% of sporozoite-infected mosquitoes. Most of the infected An. funestus s.l. specimens (86.7%) were grouped with previously unknown or undescribed Anopheles species previously implicated as a cryptic malaria vector in the western Kenyan highlands, confirming its wider geographic distribution in eastern Africa. Other species with Plasmodium infection included An. longipalpis C, An. theileri, An. demillioni, and An. nili. Cumulatively, 77.8% of the infected mosquitoes occurred outdoors. These results suggest efficient malaria parasite transmission despite the low vector densities, which has implications for effective endpoint indicators to monitor malaria control progress. Additionally, the largely outdoor infection and discovery of previously unknown and cryptic vectors suggest an increased risk of residual malaria transmission and, thus, a constraint on effective malaria prevention and control.

BACKGROUND: Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The putative-secreted ookinete protein 25 (PSOP25), highly conserved in Plasmodium spp., is a promising TBV target. Here, we investigated PvPSOP25 from P. vivax as a TBV candidate using transgenic murine parasite P. berghei and clinical P. vivax isolates.
RESULTS: A transgenic P. berghei line expressing PvPSOP25 (TrPvPSOP25Pb) was generated. Full-length PvPSOP25 was expressed in the yeast Pichia pastoris and used to immunize mice to obtain anti-rPvPSOP25 sera. The transmission-blocking activity of the anti-rPvPSOP25 sera was evaluated through in vitro assays and mosquito-feeding experiments. The antisera generated by immunization with rPvPSOP25 specifically recognized the native PvPSOP25 antigen expressed in TrPvPSOP25Pb ookinetes. In vitro assays showed that the immune sera significantly inhibited exflagellation and ookinete formation of the TrPvPSOP25Pb parasite. Mosquitoes feeding on mice infected with the transgenic parasite and passively transferred with the anti-rPvPSOP25 sera showed a 70.7% reduction in oocyst density compared to the control group. In a direct membrane feeding assay conducted with five clinical P. vivax isolates, the mouse anti-rPvPSOP25 antibodies significantly reduced the oocyst density while showing a negligible influence on mosquito infection prevalence.
CONCLUSIONS: This study supported the feasibility of transgenic murine malaria parasites expressing P. vivax antigens as a useful tool for evaluating P. vivax TBV candidates. Meanwhile, the moderate transmission-reducing activity of the generated anti-rPvPSOP25 sera necessitates further research to optimize its efficacy.

BACKGROUND: Malaria elimination strategies in the Republic of Korea (ROK) have decreased malaria incidence but face challenges due to delayed case detection and response. To improve this, machine learning models for predicting malaria, focusing on high-risk areas, have been developed.
METHODS: The study targeted the northern region of ROK, near the demilitarized zone, using a 1-km grid to identify areas for prediction. Grid cells without residential buildings were excluded, leaving 8,425 cells. The prediction was based on whether at least one malaria case was reported in each grid cell per month, using spatial data of patient locations. Four algorithms were used: gradient boosted (GBM), generalized linear (GLM), extreme gradient boosted (XGB), and ensemble models, incorporating environmental, sociodemographic, and meteorological data as predictors. The models were trained with data from May to October (2019-2021) and tested with data from May to October 2022. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC).
RESULTS: The AUROC of the prediction models performed excellently (GBM = 0.9243, GLM = 0.9060, XGB = 0.9180, and ensemble model = 0.9301). Previous malaria risk, population size, and meteorological factors influenced the model most in GBM and XGB.
CONCLUSIONS: Machine-learning models with properly preprocessed malaria case data can provide reliable predictions. Additional predictors, such as mosquito density, should be included in future studies to improve the performance of models.