Immunity and immunological surveillance for malaria elimination in tropical islands

Malaria remains one of the most significant global public health challenges. Nearly half of the world’s population remains at risk, largely in African Region. In the past decade, considerable progress has been made in the global fight to control and eliminate malaria. In some endemic countries, aggressive malaria control has reduced the malaria burden to a point where malaria elimination is becoming feasible. Nevertheless, sustained malaria control is crucial to prolong this downward trend for endemic countries. Understanding the contribution of local transmission, parasites movement, asymptomatic and sub-microscopic reservoirs can shape how active surveillances are used to pursue malaria elimination. Furthermore, a better understanding of the epidemiological effects of naturally acquired immunity against malaria is warranted to guide efforts to control or potentially eliminate the disease. In five cross-sectional surveys in Kenya conducted between 2012 and 2014 (N = 10,430), malaria prevalence (i.e. microscopy and PCR) and clinical assessments were evaluated to investigate the distribution and extent of malaria infections on islands (Mfangano, Takawiri, Kibuogi, and Ngodhe) and a mainland area (Ungoye) in Lake Victoria. Malaria prevalence varied significantly among setting; highest in the mainland, moderate in the large island, and lowest in small islands. More than 90% of infected populations were asymptomatic, and 50% of them were sub-microscopic with age-dependency for both proportions. These observations provide support for the inclusion of MDA in the area. Using the two surveys in 2012 (N = 4,112), antibody responses to P. falciparum PfAMA-1, PfMSP-119 and PfCSP were measured in order to describe transmission patterns and heterogeneity in Lake Victoria. The overall seroprevalence in Lake Victoria was 64% for PfAMA-1, 40% for PfMSP-119 and 13% for PfCSP. A clear relation between serological outcomes of PfAMA-1 and PfMSP-119 was observed with parasite prevalence and serology-derived EIR in heterogeneity in transmission. These observations collectively suggest that malaria serological measure could be an effective adjunct tool for assessing differences in transmission as well as for monitoring control and elimination in the high endemic area. Using msp1 and csp data from samples collected from 1996 to 2002, patterns of gene flow and population genetic structure of P. falciparum (N = 316) and P. vivax (N = 314) from seven sites on five islands (Gaua, Santo, Pentecost, Malakula, and Tanna) were analysed in order to understand the transmission and movement of Plasmodium parasites in Vanuatu. In general, genetic diversity was higher in P. vivax than P. falciparum from the same site. In P. vivax, high genetic diversity was likely maintained by a greater extent of gene flow among sites and islands. The results suggest that the current malaria control strategy in Vanuatu might need to be bolstered in order to control P. vivax movements across islands. To understand the impact of vector control interventions (i.e. ITNs) in Vanuatu, samples collected in 2003 (N = 231) and 2007 (N = 282) on Ambae Island were assessed for parasite infection (i.e. microscopy) and measured for antibody responses against three P. falciparum, three P. vivax and Anopheles-specific salivary gSG6 antigens. Decreases in seroprevalence were observed to all P. falciparum antigens but two of three P. vivax antigens, consistent with the pronounced decrease in parasite prevalence from 19% in 2003 to 3% in 2007. Seroprevalence to gSG6 also reduced significantly, suggesting that reduced exposure to vector bites was important to decrease in parasite prevalence. Together, decrease in both parasitological and seroepidemiological malaria metrics from 2003, and 2007 implied that reinforced vector control played a major role in the reduction of malaria transmission on Ambae Island

Genotyping of single nucleotide polymorphisms (SNPs) of CTLA-4 and FOXP3 genes in lymphatic filariasis and schistosomiasis.

Filariasis limfatik (LF) merupakan sejenis penyakit jangkitan parasit yang disebabkan oleh cacing halus daripada spesis Brugia dan Wuchereria yang hidup di dalam sistem limfatik manusia. Penyakit ini adalah penyumbang terbesar kepada ketidakmampuan dan perubahan kekal kepada pesakit yang tinggal di kawasan endemik. Lymphatic filariasis (LF) is a chronic parasitic disease caused by thread-like worms of Brugia and Wuchereria species that live in the human lymphatic system. It is a major cause of permanent disability and disfigurement in the endemic areas

Naturally acquired antibody response to Plasmodium falciparum describes heterogeneity in transmission on islands in Lake Victoria.

As markers of exposure anti-malaria antibody responses can help characterise heterogeneity in malaria transmission. In the present study antibody responses to Plasmodium falciparum AMA-1, MSP-119 and CSP were measured with the aim to describe transmission patterns in meso-endemic settings in Lake Victoria. Two cross-sectional surveys were conducted in Lake Victoria in January and August 2012. The study area comprised of three settings: mainland (Ungoye), large island (Mfangano) and small islands (Takawiri, Kibuogi, Ngodhe). Individuals provided a finger-blood sample to assess malaria infection by microscopy and PCR. Antibody response to P. falciparum was determined in 4,112 individuals by ELISA using eluted dried blood from filter paper. The overall seroprevalence was 64.0% for AMA-1, 39.5% for MSP-119, and 12.9% for CSP. Between settings, seroprevalences for merozoite antigens were similar between Ungoye and Mfangano, but higher when compared to the small islands. For AMA-1, the seroconversion rates (SCRs) ranged from 0.121 (Ngodhe) to 0.202 (Ungoye), and were strongly correlated to parasite prevalence. We observed heterogeneity in serological indices across study sites in Lake Victoria. These data suggest that AMA-1 and MSP-119 sero-epidemiological analysis may provide further evidence in assessing variation in malaria exposure and evaluating malaria control efforts in high endemic area

Serological measures to assess the efficacy of malaria control programme on Ambae Island, Vanuatu.

BACKGROUND: Seroepidemiology can provide evidence for temporal changes in malaria transmission and is an important tool to evaluate the effectiveness of control interventions. During the early 2000s, Vanuatu experienced an acute increase in malaria incidence due to a lapse in funding for vector control. After the distribution of subsidised insecticide-treated nets (ITNs) resumed in 2003, malaria incidence decreased in the subsequent years. This study was conducted to find the serological evidence supporting the impact of ITN on exposure to Anopheles vector bites and parasite prevalence. METHODS: On Ambae Island, blood samples were collected from 231 and 282 individuals in 2003 and 2007, respectively. Parasite prevalence was determined by microscopy. Antibodies to three Plasmodium falciparum (PfSE, PfMSP-119, and PfAMA-1) and three Plasmodium vivax (PvSE, PvMSP-119, and PvAMA-1) antigens, as well as the Anopheles-specific salivary antigen gSG6, were detected by ELISA. Age-specific seroprevalence was analysed using a reverse catalytic modelling approach to estimate seroconversion rates (SCRs). RESULTS: Parasite rate decreased significantly (P < 0.001) from 19.0% in 2003 to 3.2% in 2007, with a shift from P. falciparum predominance to P. falciparum-P. vivax co-dominance. Significant (P < 0.001) decreases were observed in seroprevalence to all three P. falciparum antigens but only two of three P. vivax antigens (except PvAMA-1; P = 0.153), consistent with the more pronounced decrease in P. falciparum prevalence. Seroprevalence to gSG6 also decreased significantly (P < 0.001), suggesting that reduced exposure to vector bites was important to the decrease in parasite prevalence between 2003 and 2007. Analyses of age-specific seroprevalence showed a three-fold decrease in P. falciparum transmission, but the evidence for the decrease in P. vivax transmission was less clear. CONCLUSIONS: Serological markers pointed to the effectiveness of ITNs in reducing malaria prevalence on Ambae Island between 2003 and 2007. The recombinant gSG6 antigen originally developed to indicate exposure to the Afrotropical vector An. gambiae may be used in the Pacific to complement the traditional measure of entomological inoculation rate (EIR)

Malaria resurgence after significant reduction by mass drug administration on Ngodhe Island, Kenya

Although WHO recommends mass drug administration (MDA) for malaria elimination, further evidence is required for understanding the obstacles for the optimum implementation of MDA. Just before the long rain in 2016, two rounds of MDA with artemisinin/piperaquine (Artequick) and low-dose primaquine were conducted with a 35-day interval for the entire population of Ngodhe Island (~500 inhabitants) in Lake Victoria, Kenya, which is surrounded by areas with moderate and high transmission. With approximately 90% compliance, Plasmodium prevalence decreased from 3% to 0% by microscopy and from 10% to 2% by PCR. However, prevalence rebounded to 9% by PCR two months after conclusion of MDA. Besides the remained local transmission, parasite importation caused by human movement likely contributed to the resurgence. Analyses of 419 arrivals to Ngodhe between July 2016 and September 2017 revealed Plasmodium prevalence of 4.6% and 16.0% by microscopy and PCR, respectively. Risk factors for infection among arrivals included age (0 to 5 and 11 to 15 years), and travelers from Siaya County, located to the north of Ngodhe Island. Parasite importation caused by human movement is one of major obstacles to sustain malaria elimination, suggesting the importance of cross-regional initiatives together with local vector control

A fatal case of cerebral malaria complicated with Gemella bergeri bacteremia: role of Plasmodium mitochondrial cox3 gene and MALDI-TOF mass spectrometry for species identification

Here, we described a fatal case of a 37-year-old returning traveller from Burkina Faso, West Africa, who presented with an acute fitting episode later diagnosed as cerebral malaria induced by Plasmodium falciparum based on microscopic examination and Plasmodium mitochondrial cytochrome c oxidase III (cox3) gene PCR target. Unfortunately, the patient passed away due to severe malaria with multi organ failure complicated with Gemella bergeri bacteremia. G. bergeri was identified using MALDI-TOF mass spectrometry

Seroepidemiological surveillance, community perceptions and associated risk factors of malaria exposure among forest-goers in Northeastern Thailand.

Malaria remains a major public health challenge in Thailand. Continuous assessment and understanding of the behavior and perceptions related to malaria exposure in the high-risk group are necessary to achieve the elimination goal. This study aimed to investigate the parasite prevalence, seroprevalence rate, knowledge, attitudes, and practices (KAP), and malaria risk factors in rural communities living close to a forested area in the northeastern part of Thailand. A community-based cross-sectional survey was conducted in three forest-goer communities (i.e., Ban Khok, Ban Koh, and Dong Yang) located in Khamcha-i district, Mukdahan Province, Thailand, from July to August 2019. Demographic, socioeconomic information and KAP data were collected using a structured questionnaire. Parasite prevalence was determined by microscopy. Seroprevalence was determined via ELISA using two Plasmodium falciparum (PfAMA-1 and PfMSP-119) and two Plasmodium vivax (PvAMA-1 and PvMSP-119) antigens. Age-adjusted antibody responses were analyzed using a reversible catalytic model to calculate seroconversion rate (SCR). Malaria parasite was not detected in any of the 345 participants. The overall malaria seroprevalence was 72.2% for PfAMA-1, 18.8% for PfMSP-119, 32.5% for PvAMA-1, and 4.4% for PvMSP-119. The proportion of seroprevalence for P. falciparum and P. vivax antigens was significantly highest in Ban Koh (35.1%, P < 0.001) and Don Yang (18.8%, P < 0.001), respectively. For all parasite antigens except PvMSP-119, the proportion of seropositive individuals significantly increased with age (P < 0.001). Based on the SCRs, there was a higher level of P. falciparum transmission than P. vivax. Regarding KAP, almost all respondents showed adequate knowledge and awareness about malaria. Nevertheless, significant effort is needed to improve positive attitudes and practices concerning malaria prevention measures. Multivariate regression analyses showed that living in Ban Koh was associated with both P. falciparum (adjusted odds ratio [aOR] 12.87, P < 0.001) and P. vivax (aOR 9.78, P < 0.001) seropositivities. We also found significant associations between age and seropositivity against P. falciparum and P. vivax antigens. The data suggest that seroepidemiological surveillance using AMA-1 and MSP-119 antigens may provide further evidence to reconstruct malaria exposure history. The absence of weak evidence of recent malaria transmission in Mukdahan Province is promising in the context of the disease elimination program

The presence of Plasmodium malariae and Plasmodium knowlesi in near malaria elimination setting in western Indonesia

Background Indonesia is progressing towards malaria elimination. To achieve this goal, intervention measures must be addressed to cover all Plasmodium species. Comprehensive control measures and surveillance programmes must be intensified. This study aims to determine the prevalence of microscopic and submicroscopic malaria in Langkat district, North Sumatera Province, Indonesia. Methods A cross-sectional survey was conducted in six villages in Langkat district, North Sumatera Province in June 2019. Data were recorded using a standardized questionnaire. Finger pricked blood samples were obtained for malaria examination using rapid diagnostic test, thick and thin blood smears, and polymerase chain reaction. Results A total of 342 individuals were included in the study. Of them, one (0.3%) had a microscopic Plasmodium malariae infection, no positive RDT examination, and three (0.9%) were positive for P. malariae (n = 1) and Plasmodium knowlesi (n = 2). The distribution of bed net ownership was owned by 40% of the study participants. The participants had a house within a radius of 100–500 m from the forest (86.3%) and had the housing material of cement floor (56.1%), a tin roof (82.2%), wooden wall (35.7%), bamboo wall (28.1%), and brick wall (21.6%). Conclusion Malaria incidence has substantially decreased in Langkat, North Sumatera, Indonesia. However, submicroscopic infection remains in the population and may contribute to further transmission. Surveillance should include the detection of microscopic undetected parasites, to enable the achievement of malaria elimination

The presence of Plasmodium malariae and Plasmodium knowlesi in near malaria elimination setting in western Indonesia

Background Indonesia is progressing towards malaria elimination. To achieve this goal, intervention measures must be addressed to cover all Plasmodium species. Comprehensive control measures and surveillance programmes must be intensified. This study aims to determine the prevalence of microscopic and submicroscopic malaria in Langkat district, North Sumatera Province, Indonesia. Methods A cross-sectional survey was conducted in six villages in Langkat district, North Sumatera Province in June 2019. Data were recorded using a standardized questionnaire. Finger pricked blood samples were obtained for malaria examination using rapid diagnostic test, thick and thin blood smears, and polymerase chain reaction. Results A total of 342 individuals were included in the study. Of them, one (0.3%) had a microscopic Plasmodium malariae infection, no positive RDT examination, and three (0.9%) were positive for P. malariae (n = 1) and Plasmodium knowlesi (n = 2). The distribution of bed net ownership was owned by 40% of the study participants. The participants had a house within a radius of 100–500 m from the forest (86.3%) and had the housing material of cement floor (56.1%), a tin roof (82.2%), wooden wall (35.7%), bamboo wall (28.1%), and brick wall (21.6%). Conclusion Malaria incidence has substantially decreased in Langkat, North Sumatera, Indonesia. However, submicroscopic infection remains in the population and may contribute to further transmission. Surveillance should include the detection of microscopic undetected parasites, to enable the achievement of malaria elimination

Perceptions and prevention practices on malaria among the indigenous Orang Asli community in Kelantan, Peninsular Malaysia

Background Malaysia is on track towards malaria elimination. However, several cases of malaria still occur in the country. Contributing factors and communal aspects have noteworthy effects on any malaria elimination activities. Thus, assessing the community’s knowledge, attitudes and practices (KAP) towards malaria is essential. This study was performed to evaluate KAP regarding malaria among the indigenous people (i.e. Orang Asli) in Peninsular Malaysia. Methods A household-based cross-sectional study was conducted in five remote villages (clusters) of Orang Asli located in the State of Kelantan, a central region of the country. Community members aged six years and above were interviewed. Demographic, socio-economic and KAP data on malaria were collected using a structured questionnaire and analysed using descriptive statistics. Results Overall, 536 individuals from 208 households were interviewed. Household indoor residual spraying (IRS) coverage and bed net ownership were 100% and 89.2%, respectively. A majority of respondents used mosquito bed nets every night (95.1%), but only 50.2% were aware that bed nets were used to prevent malaria. Nevertheless, almost all of the respondents (97.9%) were aware that malaria is transmitted by mosquitoes. Regarding practice for managing malaria, the most common practice adopted by the respondents was seeking treatment at the health facilities (70.9%), followed by self-purchase of medication from a local shop (12.7%), seeking treatment from a traditional healer (10.5%) and self-healing (5.9%). Concerning potential zoonotic malaria, about half of the respondents (47.2%) reported seeing monkeys from their houses and 20.1% reported entering nearby forests within the last 6 months. Conclusion This study found that most populations living in the villages have an acceptable level of knowledge and awareness about malaria. However, positive attitudes and practices concerning managing malaria require marked improvement