HIV/AIDS, Tuberculosis, and Malaria in Pregnancy.

J Pregnancy. 2012;2012:140826

Authors: Ezechi O, Odberg Petterson K, Byamugisha J

PMID: 22593828 [PubMed - in process]

EBV Reactivation and Chromosomal Polysomies: Euphorbia tirucalli as a Possible Cofactor in Endemic Burkitt Lymphoma.

Adv Hematol. 2012;2012:149780

Authors: Mannucci S, Luzzi A, Carugi A, Gozzetti A, Lazzi S, Malagnino V, Simmonds M, Cusi MG, Leoncini L, van den Bosch CA, De Falco G

Abstract
Burkitt lymphoma is endemic in the Equatorial Belt of Africa, its molecular hallmark is an activated, MYC gene mostly due to a chromosomal translocation. Especially in its endemic clinical variant, Burkitt lymphoma is associated with the oncogenic Epstein-Barr virus (EBV), and holoendemic malaria acts as an amplifier. Environmental factors may also cooperate in Burkitt lymphomagenesis in the endemic regions, such as plants used as traditional herbal remedies. Euphorbia tirucalli, a plant known to possess EBV-activating substances, has a similar geographical distribution to endemic Burkitt's Lymphoma and is used as a hedge, herbal remedy and toy in the Lymphoma BeltI. In this study we aimed at determining if exposure to Euphorbia tirucalli could contribute to lymphomagenesis, and at which extent. Lymphoblastoid and cord blood-derived cell lines were treated with plant extracts, and the expression of EBV-coded proteins was checked, to assess EBV reactivation. The occurrence of chromosomal translocations was then investigated by FISH. Our preliminary results suggest that E. tirucalli is able to reactivate EBV and determine chromosomal alterations, which leads to c-MYC altered expression. The existence of genomic alterations might determine the accumulation of further genetic alteration, which could eventually lead to a transformed phenotype.

PMID: 22593768 [PubMed - in process]

The immune response to sand fly salivary proteins and its influence on leishmania immunity.

Front Immunol. 2012;3:110

Authors: Gomes R, Oliveira F

Abstract
Leishmaniasis is a vector-borne disease transmitted by bites of phlebotomine sand flies. During Leishmania transmission, sand fly saliva is co-inoculated with parasites into the skin of the mammalian host. Sand fly saliva consists of roughly thirty different salivary proteins, many with known roles linked to blood feeding facilitation. Apart from the anti-hemostatic capacity of saliva, several sand fly salivary proteins have been shown to be immunogenic. Immunization with a single salivary protein or exposure to uninfected bites was shown to result in a protective immune response against leishmaniasis. Antibodies to saliva were not required for this protection. A strong body of evidence points to the role for saliva-specific T cells producing IFN-γ in the form of a delayed-type hypersensitivity reaction at the bite site as the main protective response. Herein, we review the immunity to sand fly salivary proteins in the context of its vector-parasite-host combinations and their vaccine potential, as well as some recent advances to shed light on the mechanism of how an immune response to sand fly saliva protects against leishmaniasis.

PMID: 22593758 [PubMed - in process]

An alternative paradigm for the role of antimalarial plants in Africa.

ScientificWorldJournal. 2012;2012:978913

Authors: Maranz S

Abstract
Most investigations into the antimalarial activity of African plants are centered on finding an indigenous equivalent to artemisinin, the compound from which current frontline antimalarial drugs are synthesized. As a consequence, the standard practice in ethnopharmacological research is to use in vitro assays to identify compounds that inhibit parasites at nanomolar concentrations. This approach fails to take into consideration the high probability of acquisition of resistance to parasiticidal compounds since parasite populations are placed under direct selection for genetic that confers a survival advantage. Bearing in mind Africa's long exposure to malaria and extensive ethnobotanical experimentation with both therapies and diet, it is more likely that compounds not readily overcome by Plasmodium parasites would have been retained in the pharmacopeia and cuisine. Such compounds are characterized by acting primarily on the host rather than directly targeting the parasite and thus cannot be adequately explored in vitro. If Africa's long history with malaria has in fact produced effective plant therapies, their scientific elucidation will require a major emphasis on in vivo investigation.

PMID: 22593717 [PubMed - in process]

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen.

J Immunol. 2012 May 16;

Authors: Dreyer AM, Matile H, Papastogiannidis P, Kamber J, Favuzza P, Voss TS, Wittlin S, Pluschke G

Abstract
An effective malaria vaccine could prove to be the most cost-effective and efficacious means of preventing severe disease and death from malaria. In an endeavor to identify novel vaccine targets, we tested predicted Plasmodium falciparum open reading frames for proteins that elicit parasite-inhibitory Abs. This has led to the identification of the cysteine-rich protective Ag (CyRPA). CyRPA is a cysteine-rich protein harboring a predicted signal sequence. The stage-specific expression of CyRPA in late schizonts resembles that of proteins known to be involved in merozoite invasion. Immunofluorescence staining localized CyRPA at the apex of merozoites. The entire protein is conserved as shown by sequencing of the CyRPA encoding gene from a diverse range of P. falciparum isolates. CyRPA-specific mAbs substantially inhibited parasite growth in vitro as well as in a P. falciparum animal model based on NOD-scid IL2Rγ(null) mice engrafted with human erythrocytes. In contrast to other P. falciparum mouse models, this system generated very consistent results and evinced a dose-response relationship and therefore represents an unprecedented in vivo model for quantitative comparison of the functional potencies of malaria-specific Abs. Our data suggest a role for CyRPA in erythrocyte invasion by the merozoite. Inhibition of merozoite invasion by CyRPA-specific mAbs in vitro and in vivo renders this protein a promising malaria asexual blood-stage vaccine candidate Ag.

PMID: 22593616 [PubMed - as supplied by publisher]

Limited Usefulness of Microsatellite Markers From the Malaria Vector Anopheles gambiae When Applied to the Closely Related Species Anopheles melas.

J Hered. 2012 May 16;

Authors: Deitz KC, Reddy VP, Reddy MR, Satyanarayanah N, Lindsey MW, Overgaard HJ, Jawara M, Caccone A, Slotman MA

Abstract
Anopheles melas is a brackish water mosquito found in coastal West Africa where it is a dominant malaria vector locally. In order to facilitate genetic studies of this species, 45 microsatellite loci originally developed for Anopheles gambiae were sequenced in An. melas. Those that were suitable based on repeat number and flanking regions were examined in 2 natural populations from Equatorial Guinea. Only 15 loci were eventually deemed suitable as polymorphic markers in An. melas populations. These loci were screened in 4 populations from a wider geographic range. Heterozygosity estimates ranged from 0.18 to 0.79, and 2.5-15 average alleles were observed per locus, yielding 13 highly polymorphic markers and 2 loci with lower variability. To examine the usefulness of microsatellite markers when applied in a sibling species, the original An. gambiae specific markers were used to amplify 5 loci in An. melas. Null alleles were found for 1 An. gambiae marker. We discuss the pitfalls of using microsatellite loci across closely related species and conclude that in addition to the problem of null alleles associated with this practice, many loci may prove to be of very limited use as polymorphic markers even when used in a sibling species.

PMID: 22593601 [PubMed - as supplied by publisher]

Complex effects of temperature on mosquito immune function.

Proc Biol Sci. 2012 May 16;

Authors: Murdock CC, Paaijmans KP, Bell AS, King JG, Hillyer JF, Read AF, Thomas MB

Abstract
Over the last 20 years, ecological immunology has provided much insight into how environmental factors shape host immunity and host-parasite interactions. Currently, the application of this thinking to the study of mosquito immunology has been limited. Mechanistic investigations are nearly always conducted under one set of conditions, yet vectors and parasites associate in a variable world. We highlight how environmental temperature shapes cellular and humoral immune responses (melanization, phagocytosis and transcription of immune genes) in the malaria vector, Anopheles stephensi. Nitric oxide synthase expression peaked at 30°C, cecropin expression showed no main effect of temperature and humoral melanization, and phagocytosis and defensin expression peaked around 18°C. Further, immune responses did not simply scale with temperature, but showed complex interactions between temperature, time and nature of immune challenge. Thus, immune patterns observed under one set of conditions provide little basis for predicting patterns under even marginally different conditions. These quantitative and qualitative effects of temperature have largely been overlooked in vector biology but have significant implications for extrapolating natural/transgenic resistance mechanisms from laboratory to field and for the efficacy of various vector control tools.

PMID: 22593107 [PubMed - as supplied by publisher]

Effects of educational intervention on long-lasting insecticidal nets use in a malarious area, southeast iran.

Acta Med Iran. 2012 Apr;50(4):279-87

Authors: Soleimani Ahmadi M, Vatandoost H, Shaeghi M, Raeisi A, Abedi F, Eshraghian MR, Aghamolaei T, Madani AH, Safari R, Jamshidi M, Alimorad A

Abstract
Long-lasting insecticidal nets (LLINs) have been advocated as an effective tool against malaria transmission. However, success of this community based intervention largely depends on the knowledge and practice regarding malaria and its prevention. According to the national strategy plan on evaluation of LLINs (Olyset nets), this study was conducted to determine the perceptions and practices about malaria and to improve use of LLINs in Bashagard district, one of the important foci of malaria in southeast Iran. The study area comprised 14 villages that were randomized in two clusters and designated as LLINs and untreated nets. Each of households in both clusters received two bed nets by the free distribution and delivery. After one month quantitative data collection method was used to collect information regarding the objectives of the study. On the basis of this information, an educational program was carried out in both areas to increase motivation for use of bed nets. Community knowledge and practice regarding malaria and LLIN use assessed pre- and post-educational program. The data were analyzed using SPSS ver.16 software. At baseline, 77.5% of respondents in intervention and 69.4 % in control area mentioned mosquito bite as the cause of malaria, this awareness increased significantly in intervention (90.3%) and control areas (87.9%), following the educational program. A significant increase also was seen in the proportion of households who used LLINs the previous night (92.5%) compared with untreated nets (87.1%). Educational status was an important predictor of LLINs use. Regular use of LLIN was considerably higher than the targeted coverage (80%) which recommended by World Heaths Organization. About 81.1% and 85.3% of respondents from LLIN and control areas reported that mosquito nuisance and subsequent malaria transmission were the main determinants of bed net use. These findings highlight a need for educational intervention in implementation of long-lasting insecticidal nets; this should be considered in planning and decision-making in the national malaria control program during the next campaigns of LLINs in Iran.

PMID: 22592579 [PubMed - in process]

Heterologous expression of the C-terminal antigenic domain of the malaria vaccine candidate Pfs48/45 in the green algae Chlamydomonas reinhardtii.

Appl Microbiol Biotechnol. 2012 May 18;

Authors: Jones CS, Luong T, Hannon M, Tran M, Gregory JA, Shen Z, Briggs SP, Mayfield SP

Abstract
Malaria is a widespread and infectious disease that is a leading cause of death in many parts of the world. Eradication of malaria has been a major world health goal for decades, but one that still remains elusive. Other diseases have been eradicated using vaccination, but traditional vaccination methods have thus far been unsuccessful for malaria. Infection by Plasmodium species, the causative agent of malaria, is currently treated with drug-based therapies, but an increase in drug resistance has led to the need for new methods of treatment. A promising strategy for malaria treatment is to combine transmission blocking vaccines (TBVs) that prevent spread of disease with drug-based therapies to treat infected individuals. TBVs can be developed against surface protein antigens that are expressed during parasite reproduction in the mosquito. When the mosquito ingests blood from a vaccinated individual harboring the Plasmodium parasite, the antibodies generated by vaccination prevent completion of the parasites life-cycle. Animal studies have shown that immunization with Pfs48/45 results in the production of malaria transmission blocking antibodies; however, the development of this vaccine candidate has been hindered by poor expression in both prokaryotic and eukaryotic hosts. Recently, the chloroplast of Chlamydomonas reinhardtii has been used to express complex recombinant proteins. In this study, we show that the C-terminal antigenic region of the Pfs48/45 antigen can be expressed in the chloroplast of the green algae C. reinhardtii and that this recombinant protein has a conformation recognized by known transmission blocking antibodies. Production of this protein in algae has the potential to scale to the very large volumes required to meet the needs of millions at risk for contracting malaria.

PMID: 22592550 [PubMed - as supplied by publisher]

A multidisciplinary approach to engage VFR migrants in Madrid, Spain.

Travel Med Infect Dis. 2012 May 14;

Authors: Navarro M, Navaza B, Guionnet A, López-Vélez R

Abstract
VFRs are at a greater risk of contracting travel-related illnesses such as malaria, and their knowledge about travel health tends to be poor. Since 2009, community-based activities targeting potential and impending VFRs were performed by a multidisciplinary team in Madrid, Spain. The design and distribution of multilingual and culturally-sensitive material following a qualitative research, and intercultural mediators were key tools of the health education programme.

PMID: 22592114 [PubMed - as supplied by publisher]

Systems immunology of human malaria.

Trends Parasitol. 2012 May 15;

Authors: Tran TM, Samal B, Kirkness E, Crompton PD

Abstract
Plasmodium falciparum malaria remains a global public health threat. Optimism that a highly effective malaria vaccine can be developed stems in part from the observation that humans can acquire immunity to malaria through experimental and natural P. falciparum infection. Recent advances in systems immunology could accelerate efforts to unravel the mechanisms of acquired immunity to malaria. Here, we review the tools of systems immunology, their current limitations in the context of human malaria research, and the human 'models' of malaria immunity to which these tools can be applied.

PMID: 22592005 [PubMed - as supplied by publisher]

Disulfide Prodrugs of Albitiazolium (T3/SAR97276): Synthesis and Biological Activities.

J Med Chem. 2012 May 16;

Authors: Caldarelli SA, Hamel M, Duckert JF, Ouattara M, Calas M, Maynadier M, Wein S, Périgaud C, Pellet A, Vial HJ, Peyrottes S

Abstract
We report herein the design, synthesis, and biological screening of a series of 15 disulfide prodrugs as precursors of albitiazolium bromide (T3/SAR97276, compound 1), a choline analogue which is currently being evaluated in clinical trials (phase II) for severe malaria. The corresponding prodrugs are expected to revert back to the active bis-thiazolium salt through an enzymatic reduction of the disulfide bond. To enhance aqueous solubility of these prodrugs, an amino acid residue (valine or lysine) or a phosphate group was introduced on the thiazolium side chain. Most of the novel derivatives exhibited potent in vitro antimalarial activity against P. falciparum. After oral administration, the cyclic disulfide prodrug 8 showed the best improvement of oral efficacy in comparison to the parent drug.

PMID: 22591034 [PubMed - as supplied by publisher]

[Effects of integrated malaria control measures in Shandong Province, 2010].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2012 Feb;24(1):116, 118

Authors: Bu XQ, Wang YB, Zhao CL, Chen XX, Kong XL, Zhang BG

Abstract
A total of 117 malaria patients were reported in Shandong Province, 2010 and the annual incidence was 0.13 per hundred thousand. Totally 23 cases of malaria were reported in Shanxian County, which was the most; and 6 patients who came back from Africa were reported in Daiyue County, which was the second. A total of 296 230 fever patients were examined with blood tests, and the positive rate was 0.03%. Totally 101 diapause patients were administered with medicine, and the administered rate was 95.28% and the regular administered rate was 100%. For the present patients, the regular administered rate was 100%. There were 73 malaria epidemic foci and they were all treated, and the area of residual spraying was 51.98 hm2. The malaria epidemic was steady declined in Shandong Province. Although the prevention and control work achieved desired results, the monitor for mobile population and mosquitoes still should be strengthened to prevent the malaria epidemic increasing or outbreak.

PMID: 22590888 [PubMed - in process]

[Improvement of fully automatically microscopic scanning system based on the oil-lens and its application in reading of malaria blood smears].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2012 Feb;24(1):67-71

Authors: Gao Y, Zhong ZM, Yang PC, Zhang HY, Wei DH, Li YQ, Huang JZ, Zhou XN

Abstract
OBJECTIVE: To improve the automatically microscopic scanning system based on the oil-lens and apply it in reading of malaria blood smears.
METHODS: The software of the system was modified and optimized. A total of 115 blood films from Tengchong City of Yunnan Province were examined by the automatically systematic method or read by blood smear examination staff of Tengchong City and the accuracy, sensitivity and specificity were determined and compared between the two methods.
RESULTS: The scanning of the system was speedier and the actual operation was more simple and convenient. The accuracy, sensitivity and specificity of the system were better than those of the professional staff. There was a significant difference of accuracy between the two methods (P = 0.002) and there was a significant difference of comprehensive sensitivity and specificity between the two methods (P < 0.01). Moreover, the system had the function of automatically saving scanning pictures which could be read again by everyone through the Internet.
CONCLUSIONS: The fully automatically microscopic scanning system based on the oil-lens has many functions and the operation is simple. It can improve the speed, accuracy, sensitivity and specificity of malaria blood smears and those indices are much better than those of the reading smears under a microscope by the professional staff. Therefore, it is easier to be applied at the grassroots level.

PMID: 22590868 [PubMed - in process]

[Cross-section study on co-infection of HIV and Cryptosporidium].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2012 Feb;24(1):54-7, 61

Authors: Tian LG, Wang TP, Cheng GJ, Wang FF, Tong XM, Guo J, Cai YC, Chen JX, Zhou XN

Abstract
OBJECTIVE: To investigate the co-infection status of HIV and Cryptosporidium, and explore the influencing factors associated with the co-infection.
METHODS: A total of 309 people with HIV positive in Fuyang City of Anhui Province were recruited and their fecal and blood samples were collected for examinations of Cryptosporidium spp. infection and the levels of hemoglobin, cytokines and CD4+/CD8+ T-lymphocytes. Meanwhile, the questionnaire survey was conducted.
RESULTS: Among 302 people involved in fecal examinations, the infection rate of Cryptosporidium spp. was 8.28%, and the difference between infection rates of the male (13.49%) and the female (2.92%) was statistically significant (P < 0.05). The multivariate logistic regression model showed that 4 factors were significantly associated with the coinfection of HIV and Cryptosporidium spp, including male (OR = 6.700, 95% CI: 2.030, 22.114), younger than 42 years old (OR = 4.148, 95% CI: 1.348, 12.761), level of IL-2 below 77 pg/ml (OR = 0.226, 95%CI: 0.076, 0.674) and personal hygiene habits (OR = 0.324, 95% CI: 0.105, 0.994).
CONCLUSION: The co-infection rate of Cryptosporidium spp. and HIV is high, the key targets of control are the people who are male, younger than 42 years old, with high level of IL2 and poor personal hygiene habits.

PMID: 22590865 [PubMed - in process]

[Burden of disease in Schistosomiasis japonica. IV. Community socioeconomic determinants of chronic schistosomiasis].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2012 Feb;24(1):10-3, 20

Authors: Jia TW, Sun LP, Hong QB, Deng Y, Zhang GH, Yi P, Guo JG, Zhou XN

Abstract
OBJECTIVE: To explore the socioeconomic determinants of chronic schistosomiasis japonica at a community (village) level.
METHODS: The socioeconomic and epidemiological data (Years lived with disability, YLDs) came from the thematic research carried out in two schistosome-endemic counties, Dangtu and Hanshou, in lake areas between 2004 and 2005. A concentration index was calculated and used to assess the health inequalities between socioeconomic statuses. The community risk factors relating to chronic schistosomiasis were explored by the multiple regression model.
RESULTS: The concentration index was -0.12 of Dangtu County and 0.03 of Hanshou County which indicated that there were no health inequalities due to schistosomiasis between communities with different socioeconomic statuses. There was no linear relationship between the economic levels and YLDs of chronic schistosomiasis. The results of multiple regression model showed that the distance from village to schistosome-infested water (P < 0.01) and wet land area per capita (P < 0.05) were significantly related to YLDs of chronic schistosomiasis.
CONCLUSION: There is non-linear relationship between socioeconomic levels and YLDs of chronic schistosomiasis, but the distance from village to schistosome-infested water and wet land area per capita are significantly related to the latter.

PMID: 22590855 [PubMed - in process]