Relationship between Antibody-Positive Rate against Plasmodium vivax Circumsporozoite Protein and Incidence of Malaria

The relationship between anti-Plasmodium vivax circumsporozoite protein (CSP) antibody levels and the prevalence of malaria in epidemic areas of South Korea was evaluated. Blood samples were collected from inhabitants of Gimpo-si (city), Paju-si, and Yeoncheon-gun (county) in Gyeonggi-do (province), as well as Cheorwon-gun in Gangwon-do from November to December 2004. Microscopic examinations were used to identify malaria parasites. ELISA was used to quantitate anti-circumsporozoite protein (CSP) antibodies against P. vivax. A total of 1,774 blood samples were collected. The overall CSP-ELISA-positive rate was 7.7% (n=139). The annual parasite incidences (APIs) in these areas gradually decreased from 2004 to 2005 (1.09 and 0.80, respectively). The positive rate in Gimpo (10.4%, 44/425) was the highest identified by CSP-ELISA. The highest API was found in Yeoncheon, followed by Cheorwon, Paju, and Gimpo in both years. The positive rates of CSP-ELISA were closely related to the APIs in the study areas. These results suggest that seroepidemiological studies based on CSP may be helpful in estimating the malaria prevalence in certain areas. In addition, this assay can be used to establish and evaluate malaria control and eradication programs in affected areas.     

Variation in the Circumsporozoite Protein of Plasmodium falciparum: Vaccine Development Implications

The malaria vaccine candidate RTS,S/AS01 is based on immunogenic regions of Plasmodium falciparum circumsporozoite protein (CSP) from the 3D7 reference strain and has shown modest efficacy against clinical disease in African children. It remains unclear what aspect(s) of the immune response elicited by this vaccine are protective. The goals of this study were to measure diversity in immunogenic regions of CSP, and to identify associations between polymorphism in CSP and the risk of P. falciparum infection and clinical disease. The present study includes data and samples from a prospective cohort study designed to measure incidence of malaria infection and disease in children in Bandiagara, Mali. A total of 769 parasite-positive blood samples corresponding to both acute clinical malaria episodes and asymptomatic infections experienced by 100 children were included in the study. Non-synonymous SNP data were generated by 454 sequencing for the T-cell epitopes, and repeat length data were generated for the B-cell epitopes of the cs gene. Cox proportional hazards models were used to determine the effect of sequence variation in consecutive infections occurring within individuals on the time to new infection and new clinical malaria episode. Diversity in the T-cell epitope-encoding regions Th2R and Th3R remained stable throughout seasons, between age groups and between clinical and asymptomatic infections with the exception of a higher proportion of 3D7 haplotypes found in the oldest age group. No associations between sequence variation and hazard of infection or clinical malaria were detected. The lack of association between sequence variation and hazard of infection or clinical malaria suggests that naturally acquired immunity to CSP may not be allele-specific.     

HIV infection among women undergoing abortion in Montreal.

OBJECTIVE: To determine the seroprevalence and correlates of HIV infection in a subpopulation of women of childbearing age in Montreal. DESIGN: Anonymous unlinked seroprevalence study. SETTING: Pregnancy termination unit in a teaching hospital in Montreal. PARTICIPANTS: Women presenting for abortion from July 1989 to June 1993 who resided in Quebec and were not known to have HIV infection; 12,017 (99.6%) of 12,068 eligible women were included in the study. INTERVENTION: HIV antibody testing of serum left over from samples obtained for routine Rh typing; the same algorithm as for serodiagnostic testing, namely enzyme immunoassay (EIA) followed by confirmatory testing of repeatedly EIA-reactive samples, was used. OUTCOME MEASURES: HIV serostatus by age, marital status, region of residence (metropolitan Montreal versus other), country of birth and number of living children. RESULTS: Most (84.7%) of the subjects resided in metropolitan Montreal. The median age was 27.0 (range 13 to 50) years. The serum samples of 22 women were confirmed to be HIV positive, for an overall seroprevalence rate of 1.8 per 1000 (95% confidence interval 1.1 to 2.8). The seroprevalence rate did not vary significantly by age, marital status, region of residence or study year. However, it was strongly correlated with country of birth: Canada 0.16, Haiti 23.5, HIV-endemic countries other than Haiti 5.3 and non-HIV-endemic countries other than Canada 0.0 per 1000. The seroprevalence rate among women born in Haiti was 147 times higher than that among women born in Canada (p < 0.0001). Of the women born in Haiti the rate was 3.0 times greater among those who immigrated to Canada in 1985 or later than among those who immigrated earlier (p = 0.047). CONCLUSIONS: The results of this study indicate that the HIV seroprevalence rate among women in Montreal is strongly associated with country of birth, women born in HIV-endemic countries, especially Haiti, having the highest rate. These results will help in the development of policies regarding HIV antibody testing and prevention of HIV transmission in Quebec.     

Seroprevalence of Plasmodium vivax in the Republic of Korea (2003-2005) using Indirect Fluorescent Antibody Test

Plasmodium vivax reemerged in the Republic of Korea (ROK) in 1993, and is likely to continue to affect public health. The purpose of this study was to measure levels of anti-P. vivax antibodies using indirect fluorescent antibody test (IFAT) in border areas of ROK, to determine the seroprevalence of malaria (2003-2005) and to plan effective control strategies. Blood samples of the inhabitants in Gimpo-si, Paju-si, and Yeoncheon-gun (Gyeonggi-do), and Cheorwon-gun (Gangwon-do) were collected and kept in Korea Centers for Disease Control and Prevention (KCDC). Out of a total of 1,774 serum samples tested, the overall seropositivity was 0.94% (n=17). The seropositivity was the highest in Paju-si (1.9%, 7/372), followed by Gimpo-si (1.4%, 6/425), Yeoncheon-gun (0.67%, 3/451), and Cheorwon-gun (0.19%, 1/526). The annual parasite incidence (API) in these areas gradually decreased from 2003 to 2005 (1.69, 1.09, and 0.80 in 2003, 2004, and 2005, respectively). The highest API was found in Yeoncheon-gun, followed by Cheorwon-gun, Paju-si, and Gimpo-si. The API ranking in these areas did not change over the 3 years. The seropositivity of Gimpo-si showed a strong linear relationship with the API of 2005 (r=0.9983, P=0.036). Seropositivity data obtained using IFAT may be useful for understanding malaria prevalence of relevant years, predicting future transmission of malaria, and for establishing and evaluating malaria control programs in affected areas.     

Cyclical Patterns of Hand,Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia

Enterovirus A71 (EV-A71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD) in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2–3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children <2 years, and decreased with age; in support of this, EV-A71 seroprevalence was significantly associated with age, indicating greater susceptibility in younger children. EV-A71 epidemics are also characterized by peaks of increased genetic diversity, often with genotype changes. Cross-sectional time series analysis was used to model the association between EV-A71 epidemic periods and EV-A71 seroprevalence adjusting for age and climatic variables (temperature, rainfall, rain days and ultraviolet radiance). A 10% increase in absolute monthly EV-A71 seroprevalence was associated with a 45% higher odds of an epidemic (adjusted odds ratio, aOR1.45; 95% CI 1.24–1.69; P<0.001). Every 10% decrease in seroprevalence between preceding and current months was associated with a 16% higher odds of an epidemic (aOR = 1.16; CI 1.01–1.34 P<0.034). In summary, the 2–3 year cyclical pattern of EV-A71 epidemics in Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs.     

Seroprevalence of antibodies to hepatitis A and E viruses in pediatric age groups in Turkey

Hepatitis A and hepatitis E are enteric transmitted viral diseases occurring in epidemic and sporadic forms especially in developing countries. Previous studies in Turkey showed that most residents are infected with HAV by the second decade of life. Since HEV is generally transmitted by the same route as HAV we conducted a community-based seroprevalence study for HAV and HEV infection in Ahatli area in Antalya, Turkey where socioeconomic conditions are low. Anti-HAV total immunoglobulin was tested by using a microparticle EIA (Axsym-Abbott Lab). Anti-HEV IgG was assayed by a micro ELISA method (Genelabs-Singapore). Of the 338 sera tested, 112 (33.1%) were positive for anti-HAV total antibody. Anti-HEV IgG was detected in three (0.89%) of the serum samples. Seropositivity rates of HAV in preschool and school children were 19.9% and 43.9% respectively (p < 0.001). No antibody to HEV was detected in preschool children, while the prevalence of anti-HEV IgG was 1.6% in children attending school. Our data showed that seroprevalence of anti-HAV is high among children samples but HEV infection appears to be relatively rare in pediatric age groups.     

Comparison of immunological responses to the various types circumsporozoite proteins of Plasmodium vivax in malaria patients of Korea

We compared the seroreactivities against four synthetic peptide antigens (VK210, VK247, Korean type 1, and type 2) and a full length recombinant circumsporozoite protein (CSP) antigen of Plasmodium vivax (P. vivax ) in samples of sixty-three tertian malaria patients in Korea. Among the various CSP antigens, the full-length recombinant CSP showed the highest reactivity in malaria-exposed groups (85.7%, 54/63). No significant difference was found in the percentage of malaria patients with antibodies among four peptides examined, except a full-length recombinant CSP. Absorbance values from the peptide-based ELISA showed high correlations (r > 0.9, P < 0.05) at significant values. Five sera without the immunoaffinity against peptides were reactive towards the full-length recombinant CSP in ELISA. Sera, which were not reactive to a full length recombinant CSP antigen, were not recognized by any of peptide based ELISA. These data suggested that peptide structures included in Korean isolates, GNGAGGQAA, and VK247 peptides had immune reactivity and recognition epitopes. Among the antigens, GNGAGGQAA was less recognized by patients exposed to Korean strains of P. vivax in comparison to the VK210 structures.     

DNA Prime/Adenovirus Boost Malaria Vaccine Encoding P. falciparum CSP and AMA1 Induces Sterile Protection Associated with Cell-Mediated Immunity

Background

Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection.

Methodology/Principal Findings

The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44–817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5–102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13–408; AMA1 348, range 88–1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant.

Significance

The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection.

Trial Registration

ClinicalTrials.gov{"type":"clinical-trial","attrs":{"text":"NCT00870987","term_id":"NCT00870987"}}NCT00870987.     

Crimean-Congo hemorrhagic fever virus antibody prevalence in Mauritanian livestock (cattle,goats, sheep and camels) is stratified by the animal’s age

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most widespread zoonotic arthropod-borne viruses in many parts of Africa, Europe and Asia. It belongs to the family of Nairoviridae in the genus of Orthonairovirus. The main reservoir and vector are ticks of the genus Hyalomma. Livestock animals (such as cattle, small ruminants and camels) develop a viremias lasting up to two weeks with absence of clinical symptoms, followed by seroconversion. This study was carried out to assess risk factors that affect seroprevalence rates in different species. In total, 928 livestock animal samples (cattle = 201; sheep = 247; goats = 233; camels = 247) from 11 out of 13 regions in Mauritania were assayed for CCHFV-specific immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assays (ELISA) (including a novel indirect camel-IgG-specific CCHFV ELISA). Inconclusive results were resolved by an immunofluorescence assay (IFA). A generalized linear mixed-effects model (GLMM) was used to draw conclusions about the impact of certain factors (age, species, sex and region) which might have influenced the CCHFV antibody status of surveyed animals. In goats and sheep, about 15% of the animals were seropositive, whereas in cattle (69%) and camels (81%), the prevalence rate was significantly higher. On average, cattle and camels were up to twice to four times older than small ruminants. Interestingly, the seroprevalence in all species was directly linked to the age of the animals, i.e. older animals had significantly higher seroprevalence rates than younger animals. The highest CCHFV seroprevalence in Mauritania was found in camels and cattle, followed by small ruminants. The large proportion of positive animals in cattle and camels might be explained by the high ages of the animals. Future CCHFV prevalence studies should at least consider the age of surveyed animals in order to avoid misinterpretations.     

Seroepidemiologic evidence of Q fever and associated factors among workers in veterinary service laboratory in South Korea

The incidence of Q fever has rapidly increased in South Korea since 2015. This study was undertaken to investigate the seroprevalence and seroreactivity of Q fever and the risk factors associated with its seroprevalence among workers in the veterinary service laboratory (VSL) in South Korea. This seroepidemiologic study was conducted in a total of 661 human subjects out of 1,328 subjects working in 50 VSL existing in South Korea between July 15 and July 29, 2019. Data were collected by administering survey questionnaires and by analyzing collected blood samples to determine the presence of antibodies against Coxiella burnetii. The seroprevalence and seroreactivity of C. burnetii infection were determined based on serum titers as (phase II IgG ≥1:256 and/or IgM ≥1:16) and (phase II IgG ≥1:16 and/or IgM ≥1:16) as determined by indirect immunofluorescent assay. Work, work environment, behavioral risk and protective factors associated with seroprevalence of Q fever were assessed by employing multivariable logistic regression analysis. Among the 661, the seroprevalence and seroreactivity of C. burnetii infection were 7.9% and 16.0%, respectively. Multivariate logistic regression analysis showed the risk factors significantly associated with seroprevalence were the antemortem inspection of cattle, goats, or sheep (APR (adjusted prevalence ratio), 2.52; 95% CI, 1.23–4.70)), animal blood splashed into or around eyes (APR, 2.24; 95% CI, 1.04–4.41), and contact with animals having Q fever (APR, 6.58; 95% CI, 3.39–10.85) during the previous year. This study suggests the need for precautions when contact with cattle, goats, or sheep is expected, especially during the antemortem inspection, when dealing with C. burnetii infected animals, or when there is a risk of ocular contact with animal derivatives. Therefore, we recommend the consistent use of appropriate personal protective equipment and other protective measures including PPE treatment and washing of body surfaces after work to prevent C. burnetii infections among VSL staff in South Korea.     

Seroprevalence of Plasmodium vivax Circumsporozoite Protein Antibody in High-Risk Malaria Areas in Korea

The circumsporozoite protein (CSP) of Plasmodium spp. is a diagnostic antigen and useful biomarker for monitoring short-term/seasonal changes to malaria transmission. Using P. vivax CSP antibody ELISA, epidemiological characteristics were analyzed in the residents of Ganghwa, Cheorwon, Paju, and Goseong from 2017 to 2018. In Ganghwa and Cheorwon, 1.6% and 1.2% of residents, respectively, were PvCSP-antibody-positive in 2018, which indicates a decrease of 0.4% in the positive rate compared to 2017. The annual parasite incidence (API) in Ganghwa and Cheorwon was 24.9 and 10.5 in 2017 and 20.3 and 10.7 in 2018, respectively. Although the changes were not significant, the API in Ganghwa decreased slightly by 4.5 in 2018 compared to the previous year. In Paju and Goseong, 3.9% and 2.0% of residents were positive for the PvCSP antibody. The API in Paju was 13.1 in 2017 and 16.0 in 2018, although no malaria patients were reported for the 2 years. Therefore, the results suggest that PvCSP is a useful antigen for confirming initial malaria infection. Additionally, considering that the antibody is relatively transient, it can be employed for sero-epidemiological studies to determine the extent of malaria transmission in the current year.     

Low Parasitemia in Submicroscopic Infections Significantly Impacts Malaria Diagnostic Sensitivity in the Highlands of Western Kenya

Asymptomatic malaria infections represent a major challenge in malaria control and elimination in Africa. They are reservoirs of malaria parasite that can contribute to disease transmission. Therefore, identification and control of asymptomatic infections are important to make malaria elimination feasible. In this study, we investigated the extent and distribution of asymptomatic malaria in Western Kenya and examined how varying parasitemia affects performance of diagnostic methods including microscopy, conventional PCR, and quantitative PCR. In addition, we compared parasite prevalence rates and parasitemia levels with respect to topography and age in order to explore factors that influence malaria infection. Over 11,000 asymptomatic blood samples from children and adolescents up to 18 years old representing broad areas of Western Kenya were included. Quantitative PCR revealed the highest parasite positive rate among all methods and malaria prevalence in western Kenya varied widely from less than 1% to over 50%. A significantly lower parasitemia was detected in highland than in lowland samples and this contrast was also observed primarily among submicroscopic samples. Although we found no correlation between parasitemia level and age, individuals of younger age group (aged <14) showed significantly higher parasite prevalence. In the lowlands, individuals of aged 5–14 showed significantly higher prevalence than those under age 5. Our findings highlight the need for a more sensitive and time-efficient assay for asymptomatic malaria detection particularly in areas of low-transmission. Combining QPCR with microscopy can enhance the capacity of detecting submicroscopic asymptomatic malaria infections.     

Dystocia and cesarean section

We performed an anonymous seroprevalence survey of human immunodeficiency virus (HIV) type 1 infection through HIV antibody testing of blood samples from 22,512 women aged 15 to 44 years receiving prenatal care in British Columbia and the Yukon Territory from Mar. 15 to Sept. 30, 1989. Of the samples six were confirmed to be HIV positive; this yielded a crude overall seroprevalence rate of 2.7 per 10,000 pregnant women (95% confidence interval [CI] 1.0 to 5.8). All of the positive samples were from women 20 to 29 years of age; four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest seroprevalence rates were among women aged 15 to 29 years in Vancouver and Victoria (7.2 and 9.4 per 10,000 pregnant women respectively). Thus, 1 in 1300 pregnant women in that age group in the metropolitan areas of British Columbia was HIV positive. Application of seroprevalence rates to the total female population in British Columbia and the Yukon Territory revealed that as many as 401 women had HIV infection in 1989. Our estimates likely represent the minimum. As a subset of women of childbearing age pregnant women are likely at lowest risk of HIV infection, and so the true number of women 15 to 44 years of age with HIV infection is probably several times higher. Our study has provided a baseline assessment and will be repeated annually to analyse trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory.     

Serum monitoring of IgG and IgM Babesia bigemina (Haemosporidia: Babesiidae) antibodies in calves from the Mexican tropics

Antibody dynamics (IgG and IgM) against Babesia bigemina was studied on 41 under 15 days of age from three ranches (R1, R2 and R3) in Yucatan, Mexico. Blood samples were collected every 30 days, for eight months. Sera were tested by the indirect fluorescent antibody method to detect IgG and IgM. Overall IgM seroprevalence during the calves first eight months of life was 17.1% without relation to age. Overall IgG seroprevalence was 66.8%, increasing with age. Seroprevalence in R1, R2 and R3 were 87.5%, 77.1% and 31.8% respectively. Ranches 1 and 2 were in enzootic stability. In Yucatan, the modification of management factors in ranches with enzootic instability, could increase the risk of clinical babesiosis. Cattle mobilization from ranches with enzootic instability must be strictly controlled.     

Seroprevalence of Toxoplasma gondii infection in pigs, in Zhejiang Province, China

Seroprevalence of Toxoplasma gondii infection in pigs in 10 regions of Zhejiang Province, China, was obtained by enzyme-linked immunosorbent assay (ELISA). Anti- T. gondii antibodies were found in 53.4% (434/813) of pigs. Results were analyzed by a chi-square (χ(2)) test. Differences were observed according to farm size, animal age, and sampling regions. Seroprevalences in pigs raised on small farms (71.4%) were significantly higher than that (42.7%) on large farms (P < 0.05), and seroprevalence increased progressively with age. The seroprevalence ranged from 28.1% to 66.0% in different regions, with Jiaxing having the lowest level (28.1%), followed by Hangzhou (36.0%) and Taizhou (42.0%). This is the first study on seroprevalence of T. gondii infection in pigs in Zhejiang Province.     

Malaria transmission in a central area of Futa Djalon (Guinea): results of a parasitological survey during the 1989 rainy season.

A malaria survey based on household surveys and dispensary visits without notice was carried out during the rainy season of 1989 in three selected areas of central Futa Djalon (Republic of Guinea). Preliminary entomological evidence showed that Anopheles gambiae was the main vector in the area with a CS positive rate of 7.6% and a human blood index of 78% in August 1989. Indoor resting densities were highest in the rural village, lowest in Labé and intermediate in the town of Timbi Madina (median density per room of 18, 2 and 4.5, respectively). The household survey showed different parasite rates in the three areas: 78.2% of children had parasitaemia in Sombili, 45.8% in Timbi Madina and 16.7% in the urban sector of Labé. Prevalence and levels of P. falciparum antisporozoite antibodies were lowest in the urban area (seroprevalence of 51.9% and median titre of 2.4 arbitrary units), intermediate in the town (70.1% and 5.2) and highest in the rural village (78.9% and 5.8). Serological findings produced by dispensary visits were similar to those obtained with the household surveys except in the rural area, while parasitological data obtained with the two sampling methods were different both in rural and in urban areas. Routine malaria diagnosis made on a presumptive basis in the health services in the survey period was able to detect 30.1% of cases with parasitaemia and 53.2% of cases with hyperparasitaemia (sensitivity) and malaria was correctly not suspected in 82.8% of non parasitized people (specificity).     

Estimating the malaria transmission of Plasmodium vivax based on serodiagnosis

ABSTRACT: BACKGROUND: Plasmodium vivax re-emerged in 1993 and has now become a major public health problem during the summer season in South Korea. The aim of this study was to interpret and understand the meaning of seroepidemiological studies for developing the best malaria control programme in South Korea. METHODS: Blood samples were collected in Gimpo city, Paju city, Yeoncheon County, Cheorwon County and Goseong County of high risk area in South Korea. Microscopy was performed to identify patients infected with P. vivax. Antibody detection for P. vivax was performed using indirect fluorescent antibody test (IFAT). RESULTS: A total of 1,574 blood samples was collected from participants in the study areas and evaluated against three parameters: IFAT positive rate, annual antibody positive index (AAPI), and annual parasite index (API). The IFAT positive rate was 7.24% (n = 114). Of the five study areas, Gimpo had the highest IFAT positive rate (13.68%) and AAPI (4.63). Yeongcheon had the highest API in 2005 (2.06) while Gimpo had the highest API in 2006 (5.00). No correlation was observed between any of the three parameters and study sites' distance from the demilitarized zone (DMZ). CONCLUSIONS: These results showed that P. vivax antibody levels could provide useful information about the prevalence of malaria in endemic areas. Furthermore, AAPI results for each year showed a closer relationship to API the following year than the API of the same year and thus could be helpful in predicting malaria transmission risks.     

Variation in exposure to Anopheles gambiae salivary gland peptide (gSG6-P1) across different malaria transmission settings in the western Kenya highlands

ABSTRACT: BACKGROUND: The existing metrics of malaria transmission are limited in sensitivity under low transmission intensity. Robust surveillance systems are needed as interventions to monitor reduced transmission and prevention of rapid reintroduction. Serological tools based on antibody responses to parasite and vector antigens are potential tools for transmission measurements. The current study sought to evaluate antibody responses to Anopheles gambiae salivary gland peptide (gSG6- P1), as a biomarker of human exposure to Anopheles bites, in different transmission settings and seasons. The comparison between anti-MSP-119 IgG immune responders and non-responders allowed exploring the robustness of the gSG6-P1 peptide as a surveillance tool in an area of decreasing malaria transmission. METHODS: Total IgG levels to gSG6-P1 were measured in an age-stratified cohort (< 5, 5-14 and [greater than or equal to] 15 years) in a total of 1,366 participants from three localities in western Kenya [Kisii (hypoendemic), Kakamega (mesoendemic), and Kombewa (hyperendemic)] including 607 sera that were additionally tested for MSP-119 specific responses during a low and a high malaria transmission seasons. Antibody prevalence and levels were compared between localities with different transmission intensities. Regression analysis was performed to examine the association between gSG6-P1 and MSP-119 seroprevalence and parasite prevalence. Result Seroprevalence of gSG6-P1 in the uphill population was 36 % while it was 50 % valley bottom (chi2 = 13.2, df = 1, p < 0.001). Median gSG6-P1 antibody levels in the Valley bottom were twice as high as that observed in the uphill population [4.50 vs. 2.05, p < 0.001] and showed seasonal variation. The odds of gSG6-P1 seropositives having MSP-119 antibodies were almost three times higher than the odds of seronegatives (OR = 2.87, 95 % CI [1.977, 4.176]). The observed parasite prevalence for Kisii, Kakamega and Kombewa were 4 %, 19.7 % and 44.6 % whilst the equivalent gSG6-P1 seroprevalence were 28 %, 34 % and 54 %, respectively. CONCLUSION: The seroprevalence of IgG to gSG6-P1 was sensitive and robust in distinguishing between hypo, meso and hyper transmission settings and seasonal fluctuations.     

Probability of Antibody Formation against Circumsporozoite Protein of Plasmodium vivax among Korean Malaria Patients

To evaluate the seroprevalence against circumsporozoite protein (CSP) of Plasmodium vivax in sera of Korean patients, the central repeating domain (CRD) of CSP was cloned and analyzed. From the genomic DNA of patient''s blood, 2 kinds of CSPs were identified to belong to a VK210 type, which is the dominant repeating of GDRA(D/A)GQPA, and named as PvCSPA and PvCSPB. Recombinantly expressed his-tagged PvCSPA or PvCSPB in Escherichia coli reacted well against sera of patients in western blot, with the detecting rate of 47.9% (58/121), which included 15 cases positive for PvCSPA, 6 cases positive for PvCSPB, and 37 cases for both. The mixture of PvCSPA and PvCSPB was loaded to a rapid diagnostic test kit (RDT) and applied with the same set of patient sera, which resulted in detection rates of 57.0% (69/121). When the protein sequences of PvCSPA were compared with those of P. vivax in endemic regions of India and Uganda, they were compatibly homologous to PvCSPA with minor mutations. These results suggested that the recombinant PvCSPA and PvCSPB loaded RDT may be a milestone in latent diagnosis which has been a hot issue of domestic malaria and important for radical therapy in overlapped infections with P. falciparum in tropical and subtropical areas. During the biological process of malarial infection, exposure of CSP to antigen-antibody reaction up to 57.0% is the first report in Korea.     

Structure of the gene encoding the circumsporozoite protein of Plasmodium yoelii. A rodent model for examining antimalarial sporozoite vaccines

The gene encoding the circumsporozoite protein (CSP) from the rodent malaria parasite, Plasmodium yoelii, has been cloned and the nucleotide sequence has been determined. The gene encodes a protein of 367 amino acids as deduced from the nucleotide sequence. This gene is structurally similar to other Plasmodium spp. CSP genes in that it contains putative hydrophobic signal and anchor sequences at the NH2 and COOH termini, respectively, two small regions (Regions I and II) that are conserved in all CSP genes analyzed to date, and a central region containing the immunodominant repeating peptide sequence. Unlike other CSP genes, however, the immunodominant repeat region of the gene is composed of two distinctly different types of tandem repeats. One repeating unit is six amino acids (Gln-Gly-Pro-Gly-Ala-Pro) in length while the other is only four (Gln-Gln-Pro-Pro) residues long. A synthetic peptide, Gln-Gly-Pro-Gly-Ala-Pro X 3, strongly inhibits the binding of anti-CSP monoclonal antibody to sporozoite antigens while another peptide, Gln-Gln-Pro-Pro X 4, weakly inhibits the binding of this same antibody to sporozoite antigens. This work should allow the construction of a mouse model system to parallel human vaccine trials.