Hypoendemic Areas Research Articles

Infectiousness of the human population to Anopheles arabiensis by direct skin feeding in an area hypoendemic for malaria in Senegal.

Direct skin feeding experiments are sensitive assays to determine human infectiousness to mosquitoes but are rarely used in malaria epidemiological surveys. We determined the infectiousness of inhabitants of a malaria hypoendemic area in Senegal. Gametocyte prevalence by microscopy was 13.5% (26 of 192). Of all individuals who were gametocyte positive, 44.4% (11 of 25) infected ≥ 1 Anopheles arabiensis mosquito and 10.8% (54 of 500) of mosquitoes became infected. Of all individuals who were gametocyte negative by microscopy, 4.3% (7 of 162) infected ≥ 1 mosquito and 0.4% (12 of 3240) of mosquitoes became infected. The 18.2% (12 of 66) of all mosquito infections was a result of submicroscopic gametocyte carriage and two individuals without asexual parasites or gametocytes by microscopy were infectious to mosquitoes. When infectivity and local demography was taken into account, children 5-14 years of age contributed 50.8% of the human infectious reservoir for malaria. Adults and submicroscopic gametocyte carriers may contribute considerably to onward malaria transmission in our setting.

Is the single variant form of Plasmodium vivax Duffy binding protein-II (PvDBP-II) adequate for inclusion in a PvDBP-II-based vaccine?

The binding domain of Duffy protein (DBP-II) is a leading vaccine candidate of Plasmodium vivax. In order to develop a successful vivax malaria vaccine based on DBP-II, the antigenic diversity and also naturally occurring functional antibodies to different PvDBP-II variant types in the various populations must be known. To define whether the polymorphisms in PvDBP-II influenced the nature of functional antibody responses, this investigation was designed to evaluate naturally acquired antibodies to five circulating variant forms of DBP-II antigens in infected individuals with P. vivax living in hypoendemic areas in Iran. Sequence diversity of pvdbp-II gene was performed in 63 Iranian P. vivax isolates collected during 2008-2012. The sequencing analysis showed twenty two single nucleotide polymorphisms in PvDBP-II, resulting in 16 different haplotypes among the Iranian P. vivax isolates. Five of 16 genetically distinct variants were expressed in E. coli, and anti-DBP-II responses were measured in P. vivax-infected individuals (n = 202). Also, by performing immune-depletion ELISA experiments, antibody responses to the conserved sites of all five allelic forms were evaluated using the corresponding and non-corresponding patients’ sera (n = 20). ELISA results revealed that naturally acquired anti-PvDBP-II IgG were recognized all five expressed variant forms with no statistically difference (P > 0.05, Cochran’s Q test). The antibody depletion experiments also showed presence of the cross-reactive antibody responses to heterologous variants of PvDBP-II in Iranian individuals who were infected with distinct allelic forms of the PvDBP-II. Finally, all five examined variant forms of DBP-II were expressed transiently on the surface of COS-7 cells to determine whether people exposed to vivax malaria acquire antibodies that have the ability to block erythrocyte cytoadherence to PvDBP-II. The anti-DBP-II IgG block heterologous and homologous expressed DBP-II function, indicating that the protective immunity against PvDBP-II binding is not strain specific. In conclusion, the present results indicate that the single variant of PvDBP-II is adequate to be included in a PvDBP-II-based vaccine.

Retrospective and spatial analysis tools for integrated surveillance of cystic echinococcosis and bovine cysticercosis in hypo-endemic areas.

Cystic echinococcosis (CE) and bovine cysticercosis (BC) are two important parasitic zoonoses, whose prevalence varies among European countries. Few data are available on prevalence and geographic distribution of these two diseases in Veneto region in North-Eastern Italy, where they are generally perceived as minor public health problems. Available data from regional farms on cattle positive to CE and BC and slaughtered in the period 2006-2010 were analysed by spatial scan statistic using a Bernoulli probablility model. Out of 576 bovines testing positive to CE, 467 were found to be autochthonous cases. Three significant CE clusters were identified, the most likely one (P < 0.0001) located in the eastern part of the Veneto region. As for BC, two clusters were identified from 148 animals resting positive, 91 which were autochthonous. An epidemiological survey was conducted and the most likely CE cluster was centered, collecting faecal samples from 28 dogs living in the farms of the area. Out of five animals (all shepherd dogs) found positive for taenid eggs by copromicroscopy, one was confirmed positive for Echinoccus granulosus by means of polymerase chain reaction. The study demonstrates the usefulness of integration of slaughterhouse data and geographical coordinates of farms involved for effective surveillance of CE and BC. The reliability of the spatial analysis in the identification of clusters of EC cases was confirmed by the finding of one dog positive for E. granulosus.

Competition between Plasmodium falciparum strains in clinical infections during in vitro culture adaptation

We evaluated the dynamics of parasite populations during in vitro culture adaptation in 15 mixed Plasmodium falciparum infections, which were collected from a hypoendemic area near the China–Myanmar border. Allele types at the msp1 block 2 in the initial clinical samples and during subsequent culture were quantified weekly using a quantitative PCR method. All mixed infections carried two allele types based on the msp1 genotyping result. We also genotyped several polymorphic sites in the dhfr, dhps and mdr1 genes on day 0 and day 28, which showed that most of the common sites analyzed were monomorphic. Two of the three clinical samples mixed at dhps 581 remained stable while one changed to wild-type during the culture. During in vitro culture, we observed a gradual loss of parasite populations with 10 of the 15 mixed infections becoming monoclonal by day 28 based on the msp1 allele type. In most cases, the more abundant msp1 allele types in the clinical blood samples at the beginning of culture became the sole or predominant allele types on day 28. These results suggest that some parasites may have growth advantages and the loss of parasite populations during culture adaptation of mixed infections may lead to biased results when comparing the phenotypes such as drug sensitivity of the culture-adapted parasites.

The relationship between anaemia and malaria: apparently simple, yet controversial

Among many other factors, malaria plays a major causative role of anaemia globally. The mechanisms leading to anaemia in the course of malaria are extremely diverse, involving immunological factors that act differently according to age and malaria epidemiology. The malaria-attributable fraction of anaemia may then differ in different settings. While tremendous efforts are being made to control malaria, the availability of a simple and reliable biomarker of impact is of the upmost importance. Promising data are accumulating that Hb levels could be used as a proxy of malaria even in hypo-endemic areas, even if many grey areas still deserve research efforts.

Seasonal changes in the antibody responses against Plasmodium falciparum merozoite surface antigens in areas of differing malaria endemicity in Indonesia.

BackgroundThe transmission of malaria in Indonesia is highly heterogeneous spatially and seasonally. Anti-malaria antibody responses can help characterize this variation. In the present study antibody responses to Plasmodium falciparum MSP-1 and AMA-1 were measured to assess the transmission intensity in a hypo-endemic area of Purworejo and a meso-endemic area of Lampung during low and high transmission seasons.MethodsFilter-paper blood spot samples collected from Purworejo and Lampung by cross-sectional survey during high and low transmission season were stored at −20°C. Indirect ELISA assays were carried out using PfMSP1-19 and PfAMA1 antigens. A positivity threshold was determined by samples from local unexposed individuals, and the differences in seroprevalence, antibody level and correlation between antibody level and age in each site were statistically analysed.ResultsPrevalence of antibodies to either PfMSP1-19 or PfAMA1 was higher in Lampung than in Purworejo in both the low (51.3 vs 25.0%) and high transmission season (53.9 vs 37.5%). The magnitude of antibody responses was associated with increasing age in both sites and was higher in Lampung. Age-adjusted seroconversion rates showed an approximately ten-fold difference between Lampung and Purowejo. Two different seroconversion rates were estimated for Lampung suggesting behaviour-related differences in exposure. In both settings antibody responses to PfMSP1-19 were significantly lower in the low season compared to the high season.ConclusionSeasonal changes may be detectable by changes in antibody responses. This is particularly apparent in lower transmission settings and with less immunogenic antigens (in this case PfMSP1-19). Examination of antibody levels rather than seroprevalence is likely to be a more sensitive indicator of changes in transmission. These data suggest that sero-epidemiological analysis may have a role in assessing short-term changes in exposure especially in low or seasonal transmission settings.

Sickle cell trait is not associated with endemic Burkitt lymphoma: An ethnicity and malaria endemicity‐matched case–control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer

Endemic Burkitt lymphoma (eBL) is associated with Epstein–Barr virus (EBV) and Plasmodium falciparum coinfections. Malaria appears to dysregulate immunity that would otherwise control EBV, thereby contributing to eBL etiology. Juxtaposed to human genetic variants associated with protection from malaria, it has been hypothesized that such variants could decrease eBL susceptibility, historically referred to as “the protective hypothesis.” Past studies attempting to link sickle cell trait (HbAS), which is known to be protective against malaria, with protection from eBL were contradictory and underpowered. Therefore, using a case–control study design, we examined HbAS frequency in 306 Kenyan children diagnosed with eBL compared to 537 geographically defined and ethnically matched controls. We found 23.8% HbAS for eBL patients, which was not significantly different compared to 27.0% HbAS for controls [odds ratio (OR) = 0.85; 95% confidence interval (CI) 0.61–1.17; p-value = 0.33]. Even though cellular EBV titers, indicative of the number of latently infected B cells, were significantly higher (p-value < 0.0003) in children residing in malaria holoendemic compared to hypoendemic areas, levels were not associated with HbAS genotype. Combined, this suggests that although HbAS protects against severe malaria and hyperparasitemia, it is not associated with viral control or eBL protection. However, based on receiver operating characteristic curves factors that enable the establishment of EBV persistence, in contrast to those involved in EBV lytic reactivation, may have utility as an eBL precursor biomarker. This has implications for future human genetic association studies to consider variants influencing control over EBV in addition to malaria as risk factors for eBL.What's new?Although the hypothesis dates back to 1970, studies of the “protective effect” of sickle cell trait (HbAS) on the development of endemic Burkitt lymphoma (eBL) have led to contradictory conclusions. This new study analyzed an unprecedented number of eBL cases and highlighted the importance of matching controls on ethnicity as well as malaria endemicity. The findings contribute to resolving the controversy by showing that HbAS frequency does not differ between children diagnosed with eBL and healthy children. The study also examined cellular Epstein-Barr Virus (EBV) titers, which in contrast to plasma EBV levels may serve as an informative eBL biomarker.

New tools and insights to assist with the molecular identification of Simulium guianense s.l., main Onchocerca volvulus vector within the highland areas of the Amazonia onchocerciasis focus

Following the success of the Onchocerciasis Elimination Programme for the Americas (OEPA), there is now just one Latin American onchocerciasis focus where onchocerciasis transmission is described as ‘on-going:’ the Amazonia Onchocerciasis focus. In the hyperendemic highland areas of the Amazonia focus, Simulium guianense s.l. Wise are the most important vectors of the disease. Populations of S. guianense s.l. are, however, known to vary in their cytogenetics and in a range of behaviours, including in their biting habits. In the hypoendemic lowland areas of the Amazonia focus, for example, S. guianense s.l. are generally regarded as zoophilic and consequently unimportant to disease transmission. Robust tools, to discriminate among various populations of S. guianense s.l. have, however, not yet been developed. In the work reported here, we have assessed the utility of a ribosomal DNA sequence fragment spanning the nuclear ribosomal ITS-1, ITS-2 and 5.8S sequence regions and a ∼850 nucleotide portion of the mitochondrial cytochrome oxidase gene (CO1) for species-level identification and for resolving the within species substructuring. We report here how we have generated 78 CO1 sequences from a rich set of both zoophilic and anthropophilic populations of S. guianense s.l. that were collected from eight sites that are broadly distributed across Brazil. Consistent with previous findings, our analysis supports the genetic isolation of Simulium litobranchium from S. guianense s.l. In contrast with previous findings, however, our results did not provide support for the divergence of the two species prior to the radiation of S. guianense s.l. In our analysis of the S. guianense s.l. ribosomal DNA sequence trace files we generated, we provide clear evidence of multiple within-specimen single nucleotide polymorphisms and indels suggesting that S. guianense s.l. ribosomal DNA is not a good target for conventional DNA barcoding. This is the first report of S. guianense s.l. within individual ribosomal DNA variation and thus the first evidence that the species is not subject to the normal effects of concerted evolution. Collectively, these data illustrate the need for diverse sampling in the development of robust molecular tools for vector identification and suggest that ribosomal DNA might be able to assist with resolving S. guianense s.l. species substructuring that C01 barcoding has hitherto failed to.

Impact of Eighteen-Year Varied Compliance to Onchocerciasis Treatment with Ivermectin in Sentinel Savannah Agrarian Communities in Kaduna State of Nigeria.

Baseline and impact assessment data were generated in 1994 (n = 532) and 2011 (n = 593) from 6 sentinel villages with generalized onchocerciasis. Only volunteers and a cohort (n = 445, 75%) were screened at both visits. Each village had received 11 (64.7%) annual treatments and 92.6%, range 88.7–100%, treatment compliance. Overall mean number of treatment was 2.9 ± 1.6 with a range 2.0 ± 1.2–3.3 ± 0.6. Significant decreases in skin microfilaria prevalence from 201 (38%) to 0 (0%), palpable nodule from 77 (15%) to 4 (0.7%), dermal changes from 51 (9.6%) to 2 (0.04%), optic nerve disease from 24 (4.5%) to 4 (2.0%), and onchocercal inducible ocular lesions from 31 (5.8%) to 12 (2.0%) were recorded, P < 0.05, (t-test of unpaired data). Cases of glaucoma, 8 (1.4%), and blindness, 6 (1.05%), remained unchanged. Visual acuity ≥6/24 in one or both eyes, 198 (33.45%); cataract, 169 (28.5%); pterygium 157 (26.5%); and acute senilis, 165 (27.9%), were significantly increased and positively correlated with increase in age (R 2 = 0.898 − 0.949). Dissected parous Simulium damnosum caught (n = 222) were without infective third stage larva. Active onchocerciasis transmission seems halted despite varied compliance to long-term ivermectin treatment. We recommend continued surveillance and targeted treatment of controlled and hypoendemic areas.

Distribution of erythrocyte binding antigen 175 (EBA-175) alleles and ABO blood groups in a hypoendemic area in Senegal

The study was conducted to determine for the first time the association between the erythrocyte binding antigen 175 (EBA-175) alleles and ABO blood groups in malaria patients living in Thies, a hypoendemic area in Senegal. In 2007, the EBA-175 alleles and blood group types were determined by nested PCR and the Simonin test respectively in blood samples obtained from uncomplicated Plasmodium falciparum malaria positive patients. In total, 129 patients were enrolled in the study. The EBA-175 genotyping showed a prevalence of 67.45% for the F-allele, 27.90% for the C-allele and 4.65% of mixed C+F infection. The distribution of the ABO blood group type showed 59.8% for the O group, 19.7% for the A group, 17.2% for the B group, and 3.3% for the AB group. No correlation was noted between the EBA-175 alleles and either the blood group type or parasitemia.

High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG

Occult hepatitis B virus (HBV) infection is a well-recognized clinical entity characterized by the detection of HBV DNA in serum and/or liver in the absence of detectable hepatitis B surface antigen (HBsAg). The frequency of the diagnosis depends on the relative sensitivity of both HBsAg and HBV DNA assays. We aimed at determining the prevalence of occult HBV infection in a high risk group of children who developed HBV infection despite immunoprophylaxis. The sera of 75 children born to HBsAg-positive mothers previously immunized by HBIG and prophylaxic vaccine regimen were assayed for HBV DNA by real-time PCR. Subsequently, the samples were tested using a sensitive standard PCR, with an independent set of primers for all HBV genes, and analyzed by direct sequencing. HBV DNA was detected in 21/75 (28%) children, and ranged between 77 and 9240 copies/ml. All were positive for anti-HBs. Five (24%) children were found to be positive for anti-HBc, while anti-HBc-only positive individuals were not observed. Eight isolates (38%) did not carry any mutation. Thirteen infected children (62%) had at least one mutation in regions known to be involved in functional and/or immune epitope activity. Ten had G145R mutations. HBV occult infection seems to be relatively frequent in immunized children born to HBsAg-positive mothers. HBsAg negativity is not sufficient to completely exclude HBV DNA presence. These findings emphasize the importance of considering occult HBV infection in hypo-endemic areas.

Age-dependent sex bias in clinical malarial disease in hypoendemic regions.

Background and ObjectivesExperimental models show a male bias in murine malaria; however, extant literature on biases in human clinical malaria is inconclusive. Studies in hyperendemic areas document an absence of sexual dimorphism in clinical malaria. Data on sex bias in clinical malaria in hypoendemic areas is ambiguous—some reports note a male bias but do not investigate the role of differential mosquito exposure in that bias. Moreover, these studies do not examine whether the bias is age related. This study investigates whether clinical malaria in hypoendemic regions exhibits a sex bias and whether this bias is age-dependent. We also consider the role of vector exposure in this bias.MethodsRetrospective passive clinical malaria datasets (2002–2007) and active surveillance datasets (2000–2009) were captured for the hypoendemic Mumbai region in Western India. To validate findings, passive retrospective data was captured from a primary malaria clinic (2006–2007) in hypoendemic Rourkela (Eastern India). Data was normalized by determining percent slide-positivity rates (SPRs) for males and females, and parasite-positivity distributions were established across age groups. The Mann–Whitney test, Wilcoxon Signed Rank test, and Chi-square analysis were used to determine statistical significances.ResultsIn both the Mumbai and Rourkela regions, clinical malaria exhibited an adult male bias (p<0.01). A sex bias was not observed in children aged ≤10. Post-puberty, male SPRs were significantly greater than females SPRs (p<0.01). This adult male bias was observed for both vivax and falciparum clinical disease. Analysis of active surveillance data did not reveal an age or sex bias in the frequency of parasite positivity.ConclusionThis study demonstrates an age-dependent sex bias in clinical malaria in hypoendemic regions and enhanced incidence of clinical malaria in males following puberty. Possible roles of sex hormones, vector exposure, co-infections, and other factors in this enhanced susceptibility are discussed.

Assessing the validity of an ELISA test for the serological diagnosis of human fascioliasis in different epidemiological situations

To improve the diagnosis of human fascioliasis caused by Fasciola hepatica and Fasciola gigantica, we evaluated the diagnostic accuracy of an enzyme-linked immunosorbent assay (ELISA), with Fasciola antigen from the adult liver fluke, for the detection of IgG against fascioliasis in human sera. The sera of 54 fascioliasis cases, originating from three endemic areas, were used in this evaluation: (i) a hyperendemic F. hepatica area where humans usually shed a great number of parasite eggs in faeces (11 sera); (ii) an epidemic F. hepatica area where humans usually shed small amounts of parasite eggs (24 sera) and (iii) an overlap area of both Fasciola species and where human shedding of parasite eggs in faeces is usually scarce or non-existent (19 sera). One hundred and sixty-eight patients with other parasitic infections and 89 healthy controls were also analysed. The respective sensitivity and specificity of this assay were 95.3% (95% confidence intervals, 82.9-99.2%) and 95.7% (95% confidence intervals, 92.3-97.5%). No correlation between egg output and the OD450 values of the F. hepatica IgG ELISA test was observed. This test could be used both as an individual serodiagnostic test for human fascioliasis when backed up by a compatible clinical history together with a second diagnostic technique for other cross-reactive helminth infections, and in large-scale epidemiological studies of human fascioliasis worldwide.

Falciparum malaria parasitemia index for predicting severe malaria

While hyperparasitemia is considered an important indicator for the development of severe malaria, there is currently no consensus on the quantitative definition of hyperparasitemia. This study was conducted to establish a cutoff point for peripheral parasitemia among patients with Plasmodium falciparum malaria, to define severe malaria. The clinical presentations of 200 uncomplicated P. falciparum malaria, and 189 severe P. falciparum malaria, patients, admitted to the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, were analyzed. A peripheral parasitemia of 0.5% was found to be the optimal cutoff point for defining severe malaria, demonstrating highest sensitivity (85.1%), specificity (62.0%), and accuracy (73.2%). Symptoms of severe falciparum malaria depend on many factors. For the definition of hyperparasitemia in areas of low or seasonal transmission, peripheral parasitemia of 0.5% might be considered a cutoff point for discrimination between severity levels. This value might be useful for the clinical management of malaria, particularly in hypo-endemic areas, unstable transmission areas, and other areas with similar transmission patterns.

Stable allele frequency distribution of the polymorphic region of SURFIN4.2 in Plasmodium falciparum isolates from Thailand

Plasmodium falciparum SURFIN4.2 (PFD1160w) is a polymorphic protein expressed on the surface of parasite-infected erythrocytes. Such molecules are expected to be under strong host immune pressure, thus we analyzed the nucleotide diversity of the N-terminal extracellular region of SURFIN4.2 using P. falciparum isolates obtained from a malaria hypoendemic area of Thailand. The extracellular region of SURFIN4.2 was divided into four regions based on the amino acid sequence conservation among SURFIN members and the level of polymorphism among SURFIN4.2 sequences; N-terminal segment (Nter), a cysteine-rich domain (CRD), a variable region 1 (Var1), and a variable region 2 (Var2). Comparison between synonymous and non-synonymous substitutions, Tajima's D test, and Fu and Li's D* and F* tests detected signatures of positive selection on Var2 and to a lesser extent Var1, suggesting that these regions were likely under host immune pressure. Strong linkage disequilibrium was detected for nucleotide pairs separated by a distance of more than 1.5kb, and 7 alleles among 19 alleles detected in 1988–1989 still circulated 14years later, suggesting low recombination of the analyzed surf4.2 sequence region in Thailand. The allele frequency distribution of polymorphic areas in Var2 did not differ between two groups collected in different time points, suggesting the allele frequency distribution of this region was stable for 14years. The observed allele frequency distribution of SURFIN4.2 Var2 may be fixed in Thai P. falciparum population as similar to the observation for P. falciparum merozoite surface protein 1, for which a stable allele frequency distribution was reported.

Differential kinetics of plasma procalcitonin levels in cerebral malaria in urban Senegalese patients according to disease outcome

&lt;em&gt;P. falciparum&lt;/em&gt; malaria continues as the serial killer of over a million lives yearly, mainly for children in sub-Saharan Africa. For severe malaria, we are still on the quest for a prognostic marker of fatal outcome. We analysed the association between serum levels of Procalcitonin (PCT), a marker of septic inflammation, and clinical outcome in Senegalese patients admitted with confirmed cerebral malaria in the intensive care facility of Hopital Principal. A total of 98 patients living in the hypoendemic urban area of Dakar, Senegal, were enrolled during transmission seasons. Levels of PCT were compared between surviving vs the 26.5 % fatal cases in blood samples of the 3 days following hospitalisation. Mean PCT levels were elevated in patients with active infection, with a large range of values (0.1 to 280 nanog per mL), significantly higher on day 0 in fatal cases than in surviving (53.6 vs 27.3; P=0.01). No exact individual threshold level could indicate occurrence of fatality, however mortality could be most accurately predicted by PCT level above 69 nanog per ML and there was a very clear different profile of evolution of PCT levels on the 3 days of observation decreasing early from day 1 in surviving patients (P&amp;lt;10–3), contrary to fatal cases. These results indicate that PCT kinetic rather than intrinsic level could be of use to predict a reduced risk of fatality in patient with cerebral malaria and could serve as potential predicting marker for severe malaria.

Influence du traitement présomptif intermittent par la sulfadoxinepyriméthamine sur l’acquisition d’anticorps anti-VAR2CSA chez la femme enceinte vivant en zone hypoendémique au Sénégal

The impact of intermittent presumptive treatment (IPT) on the immunity of pregnant women in Senegal is still not very well known. We conducted a prospective study at the Roi-Baudouin maternity of Guediawaye in Senegal to assess IgG antibodies production against MSP1, GLURP and DBL5 in pregnant women under IPT. Blood samples were collected from the participating women at inclusion and delivery. Samples were analyzed after centrifugation for the detection of IgG antibodies in sera by Elisa. Informed consent was given by each study participant prior to their inclusion. A total of 101 eligible women aged from 18 to 44 were included in this study. Multigravidae women represented 70.3% of the study population, whereas primigravidae accounted for 29.7%. The IgG level decreased slightly from inclusion to delivery for the women with regard to anti-MSP1 (83.1at inclusion versus 79.5 at delivery, p = 0.52) as well as anti-GLURP-R2 (84.1 at inclusion versus 75.9 at delivery, p = 0.16). After adjustment for number of pregnancies, there was a significant decrease in the production of anti-VAR2CSA between inclusion and delivery (p < 0.05). By reducing the incidence of malaria during pregnancy, IPT reduced the acquisition of placental parasites antibodies suppressors which could delay the development of protective immunity against malaria. The application of IPT in pregnant women would thus be more appropriate in hypoendemic areas where malaria exposure is lower.

Integrated monitoring and evaluation and environmental risk factors for urogenital schistosomiasis and active trachoma in Burkina Faso before preventative chemotherapy using sentinel sites

BackgroundOver 1 billion of the world's poorest inhabitants are afflicted by neglected tropical diseases (NTDs). Integrated control programmes aimed at tackling these debilitating NTDs have been recently initiated, mainly using preventative chemotherapy. Monitoring and evaluation (M&E) of these integrated programs presents particular challenges over and above those required for single disease vertical programmes. We used baseline data from the National NTD Control Programme in Burkina Faso in order to assess the feasibility of an integrated survey design, as well as to elucidate the contribution of environmental variables to the risk of either Schistosoma haematobium, trachoma, or both among school-aged children.MethodsS. haematobium infection was diagnosed by detecting eggs in urine. A trachoma case was defined by the presence of Trachomatous inflammation-Follicular (TF) and/or Trachomatous inflammation-Intense (TI) in either eye. Baseline data collected from 3,324 children aged 7-11 years in 21 sentinel sites across 11 regions of Burkina Faso were analyzed using simple and multivariable hierarchical binomial logistic regression models fitted by Markov Chain Monte Carlo estimation methods. Probabilities of the risk of belonging to each infection/disease category were estimated as a function of age, gender (individual level), and environmental variables (at sentinel site level, interpolated from national meteorological stations).ResultsOverall prevalence at the sentinel sites was 11.79% (95% CI: 10.70-12.89) for S. haematobium; 13.30% (12.14-14.45) for trachoma and 0.84% (0.53-1.15) for co-infections. The only significant predictor of S. haematobium infection was altitude. There were significant negative associations between the prevalence of active trachoma signs and minimum temperature, and air pressure. Conditional upon these predictors, these data are consistent with the two pathogens being independent.ConclusionsUrogenital schistosomiasis and trachoma constitute public health problems in Burkina Faso. Sentinel site (at school level) surveys for these two NTDs can be implemented simultaneously. However, to support MDA treatment decisions in Burkina Faso, the protocol used in this study would only be applicable to hypoendemic trachoma areas. More research is needed to confirm if these findings can be generalized to West Africa and beyond.

Antibody Responses and Avidity of Naturally Acquired Anti-Plasmodium vivax Duffy Binding Protein (PvDBP) Antibodies in Individuals from an Area with Unstable Malaria Transmission

Plasmodium vivax remains an important cause of morbidity outside Africa, and no effective vaccine is available against this parasite. The P. vivax Duffy binding protein (PvDBP) is essential during merozoite invasion into erythrocytes, and it is a target for protective immunity against malaria. This investigation was designed to evaluate naturally acquired antibodies to two variant forms of PvDBP-II antigen (DBP-I and -VI) in malaria individuals (N = 85; median = 22 years) who were living in hypoendemic areas in Iran. The two PvDBP-II variants were expressed in Escherichia coli, and immunoglobulin G (IgG) isotype composition and avidity of naturally acquired antibodies to these antigens were measured using enzyme-linked immunosorbent assay (ELISA). Results showed that almost 32% of the studied individuals had positive antibody responses to the two PvDBP-II variants, and the prevalence of responders did not differ significantly (P > 0.05; χ(2) test). The IgG-positive samples exhibited 37.03% and 40.8% high-avidity antibodies for PvDBP-I and PvDBP-VI variants, respectively. Furthermore, high-avidity IgG1 antibody was found in 39.1% of positive sera for each examined variant antigen. The avidity of antibodies for both PvDBP variant antigens and the prevalence of responders with high- and intermediate-avidity IgG, IgG1, and IgG3 antibodies were similar in patients (P > 0.05; χ(2) test). Moreover, the prevalence of IgG antibody responses to the two variants significantly increased with exposure and host age. To sum up, the results provided additional data in our understanding of blood-stage immunity to PvDBP, supporting the rational development of an effective blood-stage vaccine based on this antigen.

IgG subclass antibodies to three variants of Plasmodium falciparum merozoite surface protein-1 (PfMSP-119) in an area with unstable malaria transmission in Iran

Plasmodium falciparum remains globally an important cause of mortality and morbidity and despite decades of research, no effective vaccine is available against this deadly parasite. The 19-kDa C-terminal fragment of P. falciparum merozoite surface protein 1 (PfMSP-119) is a target for protective immunity against malaria and the major concern in development of vaccine based on this antigen is the presence of polymorphisms. This investigation was designed to evaluate naturally acquired antibodies and antigen-binding avidity of IgG antibodies to three variant forms of PfMSP-119 antigen (E/TSG/L, E/KNG/F and Q/KNG/L) in malaria individuals who are living in hypoendemic areas in Iran (n=92, 4–75years old). The three variant forms of PfMSP-119 were expressed in Escherichia coli and IgG isotype composition and avidity of naturally acquired antibodies to the 19-kDa antigen were measured by ELISA assay. Results showed that almost 72% of the studied individuals had positive antibody responses to three PfMSP-119 variants and the prevalence of responders did not differ significantly (P>0.05). High-avidity IgG (62.7%, 65.7% and 47.76%) and IgG1 (64.2%, 50.75%, and 50.75%) were found in positive sera for E/TSG/L, E/KNG/F and Q/KNG/L variants, respectively. Moreover, the prevalence and titers of IgG1 antibody responses to the three variants increased with age (P<0.05). In summary, individuals in low transmission areas in Iran can develop and maintain equal immune responses with high avidity to the PfMSP-119 variants (E/TSG/L, E/KNG/F and Q/KNG/L); however, the precise role of the total IgG and its isotypes in protection requires further investigation. These results could support the design of a universal PfMSP-119-based vaccine.