( SEVAMED 2001)

(Diagnosis, Diagnostics, Immunodiagnosis, Immunodiagnostics, Pathogenesis, Vaccines & Drugs)


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1326. NO Abstract

1327. Alecrim WD.  Espinosa FE.  Alecrim MG. Plasmodium falciparum infection in the pregnant patient. [Review] [77 refs] Infectious Disease Clinics of North America.  14(1):83-95, viii-ix, 2000  Mar.


Malaria should be considered a risk factor in women who are pregnant,  principally when the infection is Plasmodium falciparum. Moreover, the  risk is greater if the woman is pregnant for the first time; if she has no immunity for malaria; if the diagnosis is made late; or if P. falciparum shows resistance to antimalarial drugs. This article presents the most  significant aspects of P. falciparum malaria during pregnancy, including information about treatments and prophylaxis. [References: 77]


1328. Basco LK.  Ringwald P. Molecular epidemiology of malaria in Yaounde, Cameroon. VI. Sequence variations in the Plasmodium falciparum dihydrofolate  reductase-thymidylate synthase gene and in vitro resistance to pyrimethamine and cycloguanil. American Journal of Tropical Medicine & Hygiene.  62(2):271-6, 2000 Feb.


Pyrimethamine and cycloguanil, the major human metabolite of proguanil,  are inhibitors of dihydrofolate reductase that play a key role in the  treatment and prevention of chloroquine-resistant Plasmodium falciparum  infections in sub-Saharan Africa. Resistance to these antifolate drugs has emerged in some areas of Africa. Earlier molecular studies have  demonstrated that point mutations at key positions of the dihydrofolate  reductase-thymidylate synthase gene are strongly associated with  antifolate resistance. However, whether the same or distinct mutations are  involved in the development of resistance to both pyrimethamine and

  cycloguanil has not been well established in naturally occurring P.  falciparum isolates. In this study, the in vitro responses to both  antifolate drugs were measured in 42 Cameroonian isolates and compared  with the complete sequence of the dihydrofolate reductase domain of the  gene (from 34 of 42 isolates) to analyze the genotype that may distinguish between pyrimethamine and cycloguanil resistance. The wild-type profile (n = 11 isolates) was associated with low 50% inhibitory concentrations (IC50s) ranging from 0.32 to 21.4 nanamole for pyrimethamine and 0.60-6.40 nM for cycloguanil. Mutant isolates had at least one amino acid substitution, Asn-108. Only three mutant codons were observed among the antifolate-resistant isolates: Ile-51, Arg-59, and Asn-108. The increasing number of point mutations was associated with an increasing level of pyrimethamine IC50 and, to a much lesser extent, cycloguanil IC50. These results support a partial cross-resistance between pyrimethamine and cycloguanil that is based on similar amino acid substitutions in dihydrofolate reductase and suggest that two or three mutations, including  at least Asn-108, may be necessary for cycloguanil resistance, whereas a single Asn-108 mutation is sufficient for pyrimethamine resistance.


1329. Biswas S.  Roy A. Serology for malaria diagnosis in children. Journal of Communicable Diseases.  30(4):297-300, 1998 Dec.


1330. Bodeker G.  Willcox M. The first international meeting of the Research Initiative on Traditional Antimalarial Methods (RITAM). Journal of Alternative & Complementary Medicine.  6(2):195-207, 2000 Apr.


The first international meeting of the Research Initiative on Traditional Antimalarial Methods (RITAM) was held at the Regional Dermatology Training Centre (RDTC) of the Tumaini University of Health Sciences, Moshi, Tanzania, on December 8-11, 1999. This Inaugural Meeting of RITAM, jointly hosted by the Global Initiative for Traditional Systems of Health (GIFTS) at Oxford University and the World Health Organization (WHO), was designed to develop a strategy for more effective, evidence-based use of traditional medicines that can also inform malaria-control policy decisions. RITAM was established during 1999 as a network of researchers and other people who are active or interested in the study and use of traditional, plant-based antimalarials. RITAM is a partnership between GIFTS of Health, University of Oxford and the Tropical Disease Research (TDR) Programme of WHO. Malaria is one of the key health issues affecting developing countries, particularly in sub-Saharan Africa and Asia. With increasing drug resistance and the high cost of pharmaceutical drugs, the use of herbal antimalarials is popular. The conference was attended by biologic and social scientists, clinicians, traditional healers, and policy makers from Africa, Asia, Europe, and the Americas. The meeting was funded by the Rockefeller Foundation, the Nuffield Foundation's  Commonwealth Programme, WHO's TDR Programme, and direct support to delegates was provided by other funders. The meeting addressed the need

for research and policy on the prophylactic and therapeutic effects of

medicinal plants as well as on vector control and repellence. There were

five main outputs from the meeting: (1) targets for making a significant

contribution to the control of malaria through the use of traditional

antimalarial methods; (2) methods for achieving these targets, including

ethical guidelines; (3) an implementation strategy for moving this field

ahead quickly and soundly and for putting research findings into practice;

(4) linkages established between researchers working on traditional

antimalarial methods, based on agreed research priorities and designed to avoid unnecessary replication; and (5) strengthening the RITAM database of current knowledge on traditional herbal antimalarial methods. Four specialist groups were established to develop the above: (1) policy, advocacy, and funding; (2) preclinical studies; (3) clinical development; and (4) repellance and vector control. These will be coordinated by an executive committee managed by GIFTS. Two meetings are planned in 2000: a natural-products chemistry meeting at WHO in Geneva, Switzerland, in June; and a symposium at the World Congress on Tropical Medicine in Cartagena, Colombia, in August.


1331. Bojang KA.  Obaro S.  Morison LA.  Greenwood BM. A prospective evaluation of a clinical algorithm for the diagnosis of  malaria in Gambian children.  Tropical Medicine & International Health.  5(4):231-6, 2000 Apr.


Diagnosis of clinical malaria remains difficult, especially in areas where a high proportion of the asymptomatic population have parasitaemia, for   the symptoms and signs of malaria overlap with those of other common childhood diseases, such as acute lower respiratory tract infections.   However, a study of symptoms and signs in a group of children who presented to Farafenni Health Centre, The Gambia with a history of recent fever identified a group of signs and symptoms which were strong predictors of malaria as opposed to other febrile illnesses. Using these predictors, an algorithm was developed which could be used by fieldworkers and which had a similar sensitivity and specificity for the diagnosis of malaria as that of an experienced paediatrician working without laboratory support. This algorithm has been validated prospectively on 518 children who presented to the Medical Research Council clinic at Basse, The Gambia with fever or a history of recent fever during a 10-month period. A fieldworker obtained a detailed history from the parent or guardian of each child and performed a clinical examination which included measurement of axillary temperature and respiratory rate. Packed cell volume was measured and a thick smear was examined for malaria parasites. A malaria score, based on the presence or absence of malaria-related signs and symptoms, was determined for 382 children who were seen at the clinic during the high transmission season. Using the cut-off score which was optimal during the previous retrospective study, a sensitivity of 70% and a specificity of 77% for a diagnosis of malaria was obtained. The optimal cut-off score for the Basse population was a score of 7; this gave a sensitivity of 88% and a specificity of 62%, figures comparable to those obtained by an experienced paediatrician without laboratory support.

1332. Dias RS.  Freitas AC.  Barreiro EJ.  Goins DK.  Nanayakkara D.  McChesney  JD. Synthesis and biological activity of new potential antimalarial: 1H-pyrazolo[3,4-b]pyridine derivatives. Bollettino Chimico Farmaceutico.  139(1):14-20, 2000 Jan-Feb.


The appearance of drug resistant Plasmodium falciparum malaria  necessitates the search for novel antimalarial agents. Using the classical ring-bioisosterism concept as a strategy to develop new potential drugs, 1H-pyrazolo[3,4-b]pyridine 4-aminomethanol compounds were designed and synthesized as isosteres of the classical quinoline antimalarial mefloquine. The hydrochloride form of these compounds were tested for in vitro antimalarial activity against chloroquine-sensitive (Sierra Leone D-6) and resistant (Indochina W-2) clones of P. falciparum. The results described herein indicated that 1-H-pyrazolo[3,4-b]pyridine system represents a bioisosteric framework to quinoline system in the antimalarial activity.


1333. Dobbie M.  Crawley J.  Waruiru C.  Marsh K.  Surtees R. Cerebrospinal fluid studies in children with cerebral malaria: an  excitotoxic mechanism?.  American Journal of Tropical Medicine & Hygiene.  62(2):284-90, 2000 Feb.


The pathogenesis of cerebral malaria is poorly understood. One hypothesis is that activation of microglia and astrocytes in the brain might cause the cerebral symptoms by excitotoxic mechanisms. Cerebrospinal fluid was  sampled in 97 Kenyan children with cerebral malaria, 85% within 48 hr of admission. When compared with an age-matched reference range, there were large increases in concentrations of the excitotoxin quinolinic acid (geometric mean ratio cerebral malaria/reference population [95% confidence limits] = 14.1 [9.8-20.4], P < 0.001) and total neopterin (10.9 [9.1-13.0], P < 0.001) and lesser increases in tetra-hydrobiopterin, di-hydrobiopterin, and 5-hydroxyindoleacetic acid. There was no change in tryptophan concentration. In contrast, nitrate plus nitrite concentrations

were decreased (geometric mean ratio = 0.45 [0.35-0.59], P < 0.001). There was a graded increment in quinolinic acid concentration across outcome groups of increasing severity. The increased concentration of quinolinic acid suggests that excitotoxic mechanisms may contribute to the pathogenesis of cerebral malaria.



1334. Garner P.  Gulmezoglu AM. Prevention versus treatment for malaria in pregnant women. [Review] [19 refs] Cochrane Database of Systematic Reviews [computer file].  (2):CD000169,  2000.


OBJECTIVES: Malaria contributes to antenatal anaemia and slowing of fetal growth, especially in first-time mothers. It is thought that these effects  harm the mother and baby, and interventions to prevent or mitigate the  effects of malaria are often recommended. The objective of this review was  to assess the effects of anti-malarial interventions in pregnant women  living in malarial areas on the mother and the infant. SEARCH STRATEGY: We  searched the Cochrane Infectious Diseases Group trials register, the  Cochrane Controlled Trials Register, Medline, Embase. We contacted  researchers in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials in pregnant women of interventions that aim to  mitigate the effects of malaria in pregnancy, including drugs given routinely and mosquito control measures. DATA COLLECTION AND ANALYSIS: Trial quality was assessed. Data extraction was done by two reviewers using standard criteria. MAIN RESULTS: Fifteen trials were included. Drugs given regularly and routinely were associated with fewer episodes of fever in the mother, fewer women with severe anaemia antenatally, and higher average birthweight in infants. These effects appear to be greater in primigravidae. No difference in perinatal, neonatal and infant mortality were detected in studies of prophylaxis in all parity groups, or studies confined to women of low parity. REVIEWER'S CONCLUSIONS: Drugs locally effective for malaria when given routinely for malaria during pregnancy may reduce the incidence of low birth weight and anaemia. This effect appears to be limited to low parity women. Given the costs and inputs required to effectively deliver widescale prophylaxis programmes, we believe a large simple placebo- controlled trial testing the impact of drugs given routinely on pregnancy outcome and neonatal/infant survival is warranted. [References: 19]


1335. Gosi P.  Khusmith S.  Looareesuwan S.  Sitachamroom U.  Glanarongran R. Buchachart K.  Walsh DS. Complicated malaria is associated with differential elevations in serum levels of interleukins 10, 12, and 15. Southeast Asian Journal of Tropical Medicine & Public Health.  30(3):412-7, 1999 Sep.


  Complicated malaria, caused by Plasmodium falciparum, is characterized by

  multiple organ dysfunction. The pathogenesis of complicated malaria

  involves complex host-parasite interactions that include polarized

  cytokine responses. Recently, correlates between Th1-like and Th2-like

  cytokines, especially interleukin-10 (IL), IL-12, and TNF-alpha, and

  specific types of organ dysfunction have been noted. Here, we measured

  IL-10, IL-12, and for the first time, IL-15, in 19 patients aged 16-55

  years old with complicated malaria on days 0 (admission), 3, 7, and 14. For analysis, patients were grouped together or sub-categorized into

hyperparasitemias or cerebral malaria (CM). For IL-10, a dramatic increase was noted on admission, followed by a reduction toward control values that closely paralleled parasite clearance. For IL-12, modest but persistent increases were noted over the entire 14 day period that did not correlate with parasitemia. In general, especially on days 0 and 3, hyperparasitemic patients had, in comparison with CM patients, higher IL-10 and IL-12 levels. In contrast, IL-15 was generally below detection in most samples. These results provide further insight into the pathogenesis of complicated malaria by strengthening the contention that cytokines such as IL-10 and IL-12 are involved in modulating the immune response to P. falciparum.


1336. Graves P.  Gelband H. Vaccines for preventing malaria. [Review] [25 refs]  Cochrane Database of Systematic Reviews [computer file].  (2):CD000129,  2000.


BACKGROUND: Despite continued efforts to control the disease, malaria remains a major health problem in many regions of the world, especially  sub-Saharan Africa, and new ways to control or eradicate the disease are  urgently needed. Two types of vaccine, SPf66 vaccine against the asexual

stages, and NANP vaccines against the sporozoite stages of the Plasmodium  parasite, have been tested in randomised clinical trials in endemic areas. OBJECTIVES: To assess the effects of malaria vaccines. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Organisations and researchers in the field were contacted. SELECTION CRITERIA: Randomised trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale, and placebo. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and conducted data extraction. MAIN RESULTS: Thirteen efficacy trials involving about 7700 people were included. There were nine trials of the Spf66 vaccine and four trials of the NANP vaccines. There was large heterogeneity between trials when investigating the effect of SPf66 in reducing incidence of the first attack of P. falciparum malaria. When trials were subcategorised by location, there was no evidence for  effect of SPf66 in reducing incidence of P. falciparum in four African  trials conducted in children under 5 years of age (Peto odds ratio [OR] =  0.96, 95% confidence interval [CI] 0.81 to 1.14). In five trials outside  Africa with participants aged 2 years to adult, there was a reduction in  incidence by SPf66 vaccine (Peto OR = 0.77, 95% CI 0.67 to 0.88, fixed effects model). Significant heterogeneity remained between trials conducted outside Africa. Using a random effects model for these five trials, the OR was 0.74 (95% CI 0.54 to 1.01). In five trials, there was no evidence for effect of the SPf66 vaccine on the incidence of the first attack of P. vivax malaria (OR 1.01, 95% CI 0.87 to 1.17). Trials to date have not indicated any severe adverse effects of SPf66 vaccine. In three trials of NANP-based vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (OR 1.12, 95% CI 0.64 to 1.93). REVIEWER'S CONCLUSIONS: There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America may be justified. Trials to date have not been of sufficient size  to evaluate the effect of malaria vaccines on mortality or on severe

  malaria requiring admission to hospital. There was not enough evidence to

  evaluate the use of NANP vaccines. [References: 25]


1337. Gurunathan S.  Klinman DM.  Seder RA. DNA vaccines: immunology, application, and optimization*. [Review] [244  refs] Annual Review of Immunology.  18:927-74, 2000.


  The development and widespread use of vaccines against infectious agents have been a great triumph of medical science. One reason for the success of currently available vaccines is that they are capable of inducing long-lived antibody responses, which are the principal agents of immune protection against most viruses and bacteria. Despite these successes, vaccination against intracellular organisms that require cell-mediated immunity, such as the agents of tuberculosis, malaria, leishmaniasis, and human immunodeficiency virus infection, are either not available or not uniformly effective. Owing to the substantial morbidity and mortality associated with these diseases worldwide, an understanding of the mechanisms involved in generating long-lived cellular immune responses has tremendous practical importance. For these reasons, a new form of vaccination, using DNA that contains the gene for the antigen of interest, is under intensive investigation, because it can engender both humoral and cellular immune responses. This review focuses on the mechanisms by which DNA vaccines elicit immune responses. In addition, a list of potential applications in a variety of preclinical models is provided. [References: 244]


1338. Hanscheid T. Diagnosis of malaria: a review of alternatives to conventional microscopy. [Review] [77 refs] Clinical & Laboratory Haematology.  21(4):235-45, 1999 Aug.


Malaria causes significant morbidity and mortality worldwide, including  countries with mainly imported malaria. In developing nations, scarce  resources lead to inadequate diagnostic procedures. In affluent countries, poor familiarity with malaria may cause clinical and laboratory misdiagnosis. Microscopy of Giemsa-stained thick and thin films remains the current standard for diagnosis. Although it has good sensitivity and allows species identification and parasite counts, it is time consuming, requires microscopical expertise and maintenance of equipment. Microscopy with fluorescent stains (QBC), dipstick antigen detection of HRP2 and pLDH (Parasight-F, ICT Malaria Pf, OptiMAL), polymerase chain reaction assays and some automated blood cell analysers offer new approaches and are reviewed here, with emphasis on clinical relevance and their potential to complement conventional microscopy, especially in countries with imported malaria. [References: 77]




2250. No abstract

2251. No abstract

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2254. No abstract


2255. Bailo Diallo A.  De Serres G.  Beavogui AH.  Lapointe C.  Viens P. Home care of malaria-infected children of less than 5 years of age in a rural area of the Republic of Guinea. Bulletin of the World Health Organization.  79(1):28-32, 2001.


  OBJECTIVES: To assess the ability of mothers in a rural area of the  Republic of Guinea to identify fever in their children, and to estimate  the proportion of children who received antimalarial drugs. METHODS:  Children under 5 years of age in 41 villages were selected by a two-step  cluster sampling technique. During home visits we examined the children  and questioned their mothers about the child's symptoms and treatment.  FINDINGS: Of 784 children examined, 23% were febrile and more than half of  them also had a positive smear result for Plasmodium. Mothers reported 63%  of children with a temperature > or = 37.5 degrees C as sick. Among all  children reported as feverish by their mother, 55% had a normal  temperature (< 37.5 degrees C). In contrast, a temperature > or = 37.5  degrees C was found in 38% of children identified as sick but afebrile by  their mother and in 13% of children considered healthy. Among febrile  children, 18% were given chloroquine at home or had consulted at the  health centre or a dispensary. CONCLUSION: In areas where malaria is  endemic, recognition of fever and its presumptive treatment with  antimalarial drugs is an essential part of the strategy of the World  Health Organization (WHO) to reduce the morbidity due to this disease. This population study shows that mothers often failed to identify fever in their children and to consult or to provide antimalarial treatment. Without great efforts to improve home care, it is unlikely that the  morbidity and mortality due to malaria in young children will be greatly reduced.


2256. No abstract

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2260. No abstract

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2265. No abstract


2266. Chitnis CE. Molecular insights into receptors used by malaria parasites for erythrocyte invasion. [Review] [75 refs] Current Opinion in Hematology.  8(2):85-91, 2001 Mar.


  The invasion of erythrocytes by malaria parasites is a multi-step process that requires a series of highly specific molecular interactions. Here, the authors review what has been learned about receptor-ligand interactions that mediate erythrocyte invasion. Parasite proteins involved in these interactions are promising candidates for malaria vaccines. Clear understanding of these interactions is important for the rational design of vaccines that attempt to inhibit invasion and prevent malaria. [References: 75]


2267. No abstract

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2279. No abstract


2280. Kamat VR. Private practitioners and their role in the resurgence of malaria in  Mumbai (Bombay) and Navi Mumbai (New Bombay), India: serving the affected or aiding an epidemic?. Social Science & Medicine.  52(6):885-909, 2001 Mar.


  The increased emphasis on privatization of the health care sector in many developing countries by international financial institutions and national  governments expects an expanding role for private health care  practitioners in the management of major communicable diseases such as  tuberculosis, malaria, acute respiratory infections (ARIs) and sexually  transmitted diseases (STDs). Largely unexamined in the Indian context,  however, is the socio-cultural context, the micro-level political  environment in which private practitioners carry out their activities, and  the quality of care they provide to their patients. Examining these  aspects is significant given the impressive growth of the country's  private health sector during the past decade. This paper reports the  results of an ethnographic study carried out in Mumbai (Bombay) and Nav  Mumbai (New Bombay), India on private general practitioners (GPs) and  their role in the management of malaria at a time when these two  neighboring cities were in the midst of the worst malaria epidemic in over  60 years. Described are the characteristics of a sample of 48 private  practitioners from the two cities, and their clinics. This is followed by  a discussion of the data gathered through untructured interviews with  practitioners and patients, and complemented by observational data on  doctor-patient encounters gathered at 16 clinics over a 9-month period.  The findings of the study suggest that many practitioners in Mumbai and  Navi Mumbai were poorly qualified and did not play a supportive role in  the two cities' public health departments to bring the epidemic under  control. The majority of the practitioners adopted diagnostic and  treatment practices that were not consistent with the guidelines laid down  by WHO and India's National Malaria Eradication Programme. Very few  practitioners, especially those practicing in low-income areas, relied on  a peripheral blood-smear test to make a diagnosis. Practitioners whose  clientele was mostly the poor commonly resorted to giving one-day  treatment to febrile patients that included injectable antimalarials and  broad spectrum antibiotics. Such practitioners justified their mode of  diagnosis and treatment by asserting that they were only responding to the  demands placed on them by their patients who could not afford a  blood-smear test or a full prescription. The paper argues that  practitioners who acquiesced to patient demands were at once exacerbating the health problems of their patients and jeopardizing the prospects for  the epidemic to be brought under control. Driven primarily by the need to retain the patronage of patients and maintain one's popularity in a highly competitive health arena, many providers practiced medicine that was  unethical and dangerous. The paper concludes by discussing the ramifications of this study for malaria control in Mumbai and Navi Mumbai, and highlights a few salient health policy issues concerning the growth of the private health sector in India and its regulation.


2281. Kramer MH.  Lobel HO.  Antimalarial chemoprophylaxis in infants and children. [Review] [58 refs] Paediatric Drugs.  3(2):113-21, 2001.


  The evolving patterns of drug resistance in malaria parasites and changes  in recommendations for malaria prevention present a challenge to  physicians who advise travellers on chemoprophylaxis. Because compliance  with personal protection measures is usually low, children should receive  appropriate chemoprophylaxis, including breast-fed infants who are not  protected through maternal chemoprophylaxis. For travel to areas where  chloroquine resistance has not yet been reported (i.e. parts of Central  America, the Caribbean and parts of the Middle East), chloroquine alone is  sufficient for antimalarial prophylaxis. Mefloquine is the drug of choice  for chemoprophylaxis in areas with chloroquine-resistant Plasmodium  falciparum, and can be given to infants and young children. The  combination of chloroquine and proguanil is well tolerated in children but  is much less effective against drug-resistant malaria. Further research is needed to determine the best dosage regimen for antimalarial drugs used for chemoprophylaxis in children. [References: 58]


2282. No abstract


2283. Lee CS.  Salcedo E.  Wang Q.  Wang P.  Sims PF.  Hyde JE. Characterization of three genes encoding enzymes of the folate biosynthetic pathway in Plasmodium falciparum.  Parasitology.  122 Pt 1:1-13, 2001 Jan.


  Although the folate metabolic pathway in malaria parasites is a major  chemotherapeutic target, resistance to currently available antifolate  drugs is an increasing problem. This pathway, however, includes a number  of enzymes that, to date, have not been characterized despite their  potential for clinical exploitation. As a step towards evaluation of  additional targets in this pathway, we report the isolation and  characterization of 3 new genes that encode homologues of GTP  cyclohydrolase I (GTP-CH), dihydrofolate synthase/folylpolyglutamate synthase (DHFS/FPGS) and serine hydroxymethyltransferase (SHMT). The genes encoding GTP-CH and SHMT are unambiguously assigned to chromosome 12, while that for DHFS/FPGS is tentatively assigned to chromosome 13. All 3 genes are expressed in blood-stage parasites, yielding transcripts of which only ca 60-70% is accounted for by coding sequence. All 3 of the proteins predicted to be encoded by these genes display sequence differences compared to the human host homologues that may be of functional significance. These data bring the complement of cloned genes that encode activities in the pathway to seven, leaving only the gene encoding dihydroneopterin aldolase (DHNA) to be identified in the route from GTP to folate synthesis and folate turnover in the thymidylate cycle.



2284. Lee HK.  Lim J.  Kim M.  Lee S.  Oh EJ.  Lee J.  Oh J.  Kim Y.  Han K.  Lee EJ.  Kang CS.  Kim BK. Immunological alterations associated with Plasmodium vivax malaria in South Korea. Annals of Tropical Medicine & Parasitology.  95(1):31-9, 2001 Jan.


  Various haematological and immunological studies on patients infected with  Plasmodium vivax were undertaken, at diagnosis (day 0), after treatment with chloroquine but during primaquine treatment (day 10) and after all treatment (day 59), in South Korea (where there has been a recent and abrupt increase in the incidence of such infection). The main aims were to gain an understanding of the haemto-immunological alterations of this malarial infection, both before and after treatment, and to identify at least one useful marker for the diagnosis and post-treatment monitoring of P. vivax malaria. Thirty-eight patients with P. vivax malaria were compared with 20, apparently healthy controls. At diagnosis, the patients had lymphopenia, marked eosinopenia (the eosinophil count being correlated with the platelet count) and thrombopenia. Cells of most of the lymphocyte subsets investigated [i.e. CD3+, CD8+, CD19+, CD56+, CD3-/CD56+ and CD8+/CD56+ but not CD4+, CD3+/CD56+ or CD25+] were significantly less common among the lymphocytes of patients at diagnosis than among those of the controls. After initiating treatment, the numbers of CD19+ lymphocytes gradually increased (to normal values by day 59), whereas those of CD3+/56+ lymphocytes remained abnormally low throughout the follow-up period. The proportions of lymphocytes identified as CD4+ appeared to be unaffected by treatment. Although serum concentrations of IgE (and, to a lesser extent, IgM) were elevated in the patients at diagnosis, they were subnormal on day 10 post-treatment and normal at the day-59 follow-up. Serum concentrations of IgG and IgA in the patients were always found to be similar to those in the controls. At diagnosis the serum concentrations of complements C3 and C4 were significantly elevated in the patients. C3 remained at the same high concentration during follow-up but the  concentration of C4, like that of IgE, was found to be subnormal on day 10 and normal 7 weeks later. The level of parasitaemia (%) was only found to be significantly correlated with haemoglobin concentration. The observation of eosinopenia with elevated IgE and C4 could be a useful indicator of P. vivax malaria, and treatment response could be followed by serial monitoring of serum concentrations of IgE and C4.


2285. No abstract


2286. Letvin NL.  Bloom BR.  Hoffman SL. Prospects for vaccines to protect against AIDS, tuberculosis, and malaria. JAMA.  285(5):606-11, 2001 Feb 7.


  Given the scope of the worldwide health problems caused by the acquired immunodeficiency syndrome, tuberculosis, and malaria, it is imperative that vaccines be developed to prevent these infections. Recent advances in the understanding of these diseases suggest that T-lymphocyte-mediated immunity is important in containing these infections. The application of novel vaccine technologies for eliciting this type of immunity promises to provide successful vaccines for controlling the spread of these deadly infections.


2287. No abstract

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2293. No abstract


2294. Nacher M.  Singhasivanon P.  Vannaphan S.  Treeprasertsuk S.  Phanumaphorn

  M.  Traore B.  Looareesuwan S.  Gay F. Socio-economic and environmental protective/risk factors for severe malaria in Thailand. Acta Tropica.  78(2):139-46, 2001 Feb 23.


  We conducted a cross-sectional study to identify the socio-economic and  environmental protective/risk factors for severe malaria in Thailand. Forty-six cases of severe malaria, 72 cases of non-severe malaria with high parasite biomass and 40 mild malaria cases were included. When comparing severe malaria and non-severe malaria with high parasite biomass, specific logistic regression models showed a significant protective effect for helminths, adjusted odds ratio 0.24 (0.07-0.78) for low body mass index (BMI), adjusted odds ratio 0.11 (0.02-0.58). When comparing severe and mild malaria, a longer residence duration, adjusted odds ratio 0.36 (0.09-0.83) and the use of antimalarial self-medication,  adjusted odds ratio 0.08 (0.009-0.84) were associated with protection from  severe malaria. Using stepwise logistic regression with all the variables  inserted in the model yielded similar results. These findings suggest  specific immunity and self-medication control parasite multiplication whereas helminths and malnutrition more specifically affect the pathogenesis of severe malaria.


2295. Nardin EH.  Calvo-Calle JM.  Oliveira GA.  Nussenzweig RS.  Schneider M. Tiercy JM.  Loutan L.  Hochstrasser D.  Rose K. A totally synthetic polyoxime malaria vaccine containing Plasmodium falciparum B cell and universal T cell epitopes elicits immune responses in volunteers of diverse HLA types.  Journal of Immunology.  166(1):481-9, 2001 Jan 1.


  This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine  in volunteers of diverse HLA types. The polyoxime, designated  (T1BT(*))(4)-P3C, was constructed by chemoselective ligation, via oxime  bonds, of a tetrabranched core with a peptide module containing B cell  epitopes and a universal T cell epitope of the Plasmodium falciparum  circumsporozoite protein. The triepitope polyoxime malaria vaccine was  immunogenic in the absence of any exogenous adjuvant, using instead a core modified with the lipopeptide P3C as an endogenous adjuvant. This totally  synthetic vaccine formulation can be characterized by mass spectroscopy,  thus enabling the reproducible production of precisely defined vaccines  for human use. The majority of the polyoxime-immunized volunteers (7/10)  developed high levels of anti-repeat Abs that reacted with the native  circumsporozoite on P. falciparum sporozoites. In addition, these seven  volunteers all developed T cells specific for the universal epitope,  termed T(*), which was originally defined using CD4(+) T cells from  protected volunteers immunized with irradiated P. falciparum sporozoites. The excellent correlation of T(*)-specific cellular responses with high anti-repeat Ab titers suggests that the T(*) epitope functioned as a universal Th cell epitope, as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes. The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic, multicomponent synthetic vaccines for malaria, as well as for other pathogens.


2296. No abstract


2297. Oliveira-Ferreira J.  Daniel-Ribeiro C. Protective CD8+ T cell responses against the pre-erythrocytic stages of malaria parasites: an overview. [Review] [56 refs] Memorias do Instituto Oswaldo Cruz.  96(2):221-7, 2001 Feb.


  CD8+ T cells have been implicated as critical effector cells in protection against the pre-erythrocytic stage of malaria in mice and humans following  irradiated sporozoite immunization. Immunization experiments in animal  models by several investigators have suggested different strategies for  vaccination against malaria and many of the targets from liver stage  malaria antigens have been shown to be immunogenic and to protect mice  from the sporozoite challenge. Several prime/boost protocols with  replicating vectors, such as vaccinia/influenza, with non-replicating  vectors, such as recombinant particles derived from yeast transposon  (Ty-particles) and modified vaccinia virus Ankara, and DNA, significantly  enhanced CD8+ T cell immunogenicity and also the protective efficacy  against the circumsporosoite protein of Plasmodium berghei and P. yeti.  Based on these experimental results the development of a CD8+ T cell  inducing vaccine has moved forward from epitope identification to planning  stages of safety and immunogenicity trials of candidate vaccines.  [References: 56]


2298. No abstract

2299. No abstract

2300. No abstract

2301. No abstract


2302. Proux S.  Hkirijareon L.  Ngamngonkiri C.  McConnell S.  Nosten F. Paracheck-Pf: a new, inexpensive and reliable rapid test for P. falciparum malaria. Tropical Medicine & International Health.  6(2):99-101, 2001 Feb.


  We compared the performance of Paracheck-Pf, a new and cheap rapid malaria  test, with ICT-Pf/PvR and microscopy in two malaria surveys in Thai villages on the Thai-Burmese border. The specificity, sensitivity, predictive positive and negative values of the Paracheck-PfR and ICT-PfR tests were calculated taking microscopy results as the gold standard. The 294 ICT-Pf/Pv tests resulted in two invalid (no control line) and 11 doubtful results. Both the ICT-Pf/PvR and Paracheck-PfR tests reliably detected P. falciparum infections. However, Paracheck-PfR failed to detect three P. falciparum cases and likewise, ICT-Pf/PvR failed to detect the same three cases and an additional four cases. These seven cases were detected by microscopy and had a parasitaemia under 150 parasites/microl. At a cost of c. US $1.00, the Paracheck-PfR test, based on the detection of the P. falciparum specific HRP-2 protein, is a reliable, easy to use and affordable tool for the diagnosis of P. falciparum malaria.


2303. No abstract


2304. Schluesener HJ.  Kremsner PG.  Meyermann R. Heme oxygenase-1 in lesions of human cerebral malaria. Acta Neuropathologica.  101(1):65-8, 2001 Jan.


  Human cerebral malaria is a life threatening complication of Plasmodium falciparum infection. The cascades of signaling events resulting in tissue  trauma, lesion formation, coma or resolution of lesions are only slowly  becoming unraveled. Understanding the generation of local tissue  protective cellular reactions might pave the way for generation of novel  drugs limiting the formation of cerebral malaria lesions. Heme oxygenase-1  (HO-1) is an inducible enzyme degrading heme into the gaseous mediator  carbon monoxide (CO) and biliverdin, a local antioxidant. Expression of  HO-1 is considered a protective reaction against inflammatory and other  insults to the brain. We have localized HO-1 to Durck's granulomas,  typical lesions of advanced cerebral malaria. Here, activated monocytic  cells and ramified microglia in direct vicinity to the lesions express  HO-1. The striking association of HO-1 expression with areas of bleedings  suggests that released hemoglobin and heme-- known inducers of HO-1--are  mainly responsible for induction of monocytic HO-1 expression. HO-1 is  expressed rather late to play a protective role in lesion formation and  appears to have only a major role in Durck's granulomas. Further,  generation of the gaseous mediator CO might contribute to the neurological derangements of advanced cerebral malaria.


2305. Sharma P.  Sharma JD. A review of plant species assessed in vitro for antiamoebic activity or both antiamoebic and antiplasmodial properties. [Review] [60 refs] Phytotherapy Research.  15(1):1-17, 2001 Feb.


  The resurgence of the protozoal diseases amoebiasis and malaria has been known to occur, from time to time, in endemic and epidemic proportions all  over the world. Furthermore, the import of these individual pathogens to  other areas from tropical regions encourages these protozoal diseases to  occur on a global scale with considerable associated mortality and  morbidity. From time immemorial, the cure of these diseases has been  attempted with the use of traditional plant products, derived from such  species as are available within local habitats and ecosystems, and  dependent on their host community for their conservation. Scientific  validation and in vitro investigation, continues to be an important  requirement for drug development, particularly with the emergence of  resistance and cross resistance to some standard drugs used in such  protozoal diseases. This paper provides a comparative compilation of the  various studies reported between 1982 and 1999, on plants with antiamoebic  activities and those which possess both antiamoebic and antiplasmodial  activities. The results suggest that it is advisable to increase efforts  towards the conservation of such plants, in order to retain their economic  and therapeutic significance. Copyright 2001 John Wiley & Sons, Ltd.  [References: 60]


2306. No abstract

2307. No abstract

2308. No abstract

2309. No abstract

2310. No abstract

2311. No abstract

2312. No abstract

2313. No abstract

2314. No abstract

2315. No abstract


2316. Watanabe J.  Sasaki M.  Suzuki Y.  Sugano S. FULL-malaria: a database for a full-length enriched cDNA library from human malaria parasite, Plasmodium falciparum. Nucleic Acids Research.  29(1):70-1, 2001 Jan 1.


  FULL-malaria is a database for a full-length-enriched cDNA library from the human malaria parasite Plasmodium falciparum (http://133.11. 149.55/). Because of its medical importance, this organism is the first target for genome sequencing of a eukaryotic pathogen; the sequences of two of its 14 chromosomes have already been determined. However, for the full exploitation of this rapidly accumulating information, correct identification of the genes and study of their expression are essential. Using the oligo-capping method, we have produced a full-length-enriched cDNA library from erythrocytic stage parasites and performed one-pass reading. The database consists of nucleotide sequences of 2490 random clones that include 390 (16%) known malaria genes according to BLASTN analysis of the nr-nt database in GenBank; these represent 98 genes, and  the clones for 48 of these genes contain the complete protein-coding sequence (49%). On the other hand, comparisons with the complete chromosome 2 sequence revealed that 35 of 210 predicted genes are expressed, and in addition led to detection of three new gene candidates that were not previously known. In total, 19 of these 38 clones (50%) were full-length. From these observations, it is expected that the database contains approximately 1000 genes, including 500 full-length clones. It should be an invaluable resource for the development of vaccines and novel drugs.


2317. No abstract

2318. No abstract

2319. No abstract




2830.    Avila SL.  Goldberg AC.  Arruk VG.  Marin ML.  Guilherme L.  Kalil J.  Ferreira AW.  Immune responses to multiple antigen peptides containing T and B epitopes from Plasmodium falciparum circumsporozoite protein of Brazilian individuals naturally exposed to malaria. Parasite Immunology.  23(2):103-8, 2001 Feb.


2831.    Bashwari LA.  Mandil AM.  Bahnassy AA.  Al-Shamsi MA.  Bukhari HA. Epidemiological profile of malaria in a university hospital in the eastern region of Saudi Arabia.  Saudi Med J.  22(2):133-8, 2001 Feb.


  OBJECTIVE: To study the epidemiological, clinical and hematological profile of laboratory-diagnosed malaria cases at King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, during the period from January 1990 to December 1999, and to provide suitable recommendations accordingly. METHODS: This was a clinical case series study of confirmed cases presenting to King Fahd Hospital of the University during the period from January 1990 to December 1999. A specially designed form was used for data collection and 602, laboratory-confirmed cases of malaria were retrospectively analyzed. RESULTS: There were 602 cases with a mean age of 25.8 + 14.3 and a male to female ratio of 2.9:1. Less than half the cases were Saudis (42%), most of whom (93%) reported a history of travel to the Southwestern part of the Kingdom. The highest frequency of cases was observed in the years 1992, 1994 and 1998 and 40% of the cases were diagnosed during the months of February, March and September. Plasmodium falciparum was the most common species among Saudi (83%), Sudanese (72%) and Yemeni (64%) patients, while Plasmodium vivax was predominant among others. Most of these cases (75%) had a history of travel to their home countries (endemic areas). The most common clinical presentation was fever (97%), while the most common clinical signs were splenomegaly (9%) and jaundice (8%). Anemia (60%) and thrombocytopenia (53%) were the most common hematological findings. CONCLUSION: Although it appears that the Eastern Province is still free of indigenous malaria transmission, this could not be confirmed by the data. Imported cases, however represent a continuous threat due to the existence of such vectors as Anopheles stephensi, Anopheles fluviatilis, Anopheles sergentii and Anopheles superpictus and a large number of non-immune persons. It is recommended that malaria be always considered in the differential diagnosis of all acute fevers, especially among those with a history of travel to an endemic area. Prompt diagnosis and treatment is necessary. Chemoprophylaxis, when traveling to endemic areas is mandatory, as well as the use of other primary preventive measures to protect against mosquito bites.


2838.    Biswas S.  Karmarkar MG.  Sharma YD. Antibodies detected against Plasmodium falciparum haemozoin with inhibitory properties to cytokine production.  FEMS Microbiology Letters.  194(2):175-9, 2001 Jan 15.

2839.    Coleman MD. Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention. [Review] [51 refs]  Toxicology.  162(1):53-60, 2001 Apr 12.

2840.    Crispo A.  Tamburini M.  De Marco MR.  Ascierto P.  Silvestro P.  Ronga D.  Tridente V.  Desicato S.  Carbone S.  Fabbrocini G.  Spiteri D.  Montella M. HHV-8 prevalence, immunosuppression and Kaposi's sarcoma in South Italy.  International Journal of Molecular Medicine.  7(5):535-8, 2001 May.

2841.    Efferth T.  Dunstan H.  Sauerbrey A.  Miyachi H.  Chitambar CR. The anti-malarial artesunate is also active against cancer. International Journal of Oncology.  18(4):767-73, 2001 Apr.

2842.    Hensmann M.  Kwiatkowski D.  Cellular basis of early cytokine response to Plasmodium falciparum.  Infection & Immunity.  69(4):2364-71, 2001 Apr.

2843.    Hoffmann EH.  da Silveira LA.  Tonhosolo R.  Pereira FJ.  Ribeiro WL.  Tonon AP.  Kawamoto F.  Ferreira MU. Geographical patterns of allelic diversity in the Plasmodium falciparum malaria-vaccine candidate, merozoite surface protein-2. Annals of Tropical Medicine & Parasitology.  95(2):117-32, 2001 Mar.

2844.    Hviid L.  Kurtzhals JA.  Adabayeri V.  Loizon S.  Kemp K.  Goka BQ.  Lim A.  Mercereau-Puijalon O.  Akanmori BD.  Behr C. Perturbation and proinflammatory type activation of V delta 1(+) gamma delta T cells in African children with Plasmodium falciparum malaria. Infection & Immunity.  69(5):3190-6, 2001 May.

2845.    Kenyon G. GSK renews malaria efforts. GlaxoSmithKline Biologicals. Nature Medicine.  7(4):389, 2001 Apr.

2846.    Khattab A.  Kun J.  Deloron P.  Kremsner PG.  Klinkert MQ. Variants of Plasmodium falciparum erythrocyte membrane protein 1 expressed by different placental parasites are closely related and adhere to chondroitin sulfate A.  Journal of Infectious Diseases.  183(7):1165-9, 2001 Apr 1.

2847.    Lal AA.  Patterson PS.  Sacci JB.  Vaughan JA.  Paul C.  Collins WE.  Wirtz RA.  Azad AF. Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship.  Proceedings of the National Academy of Sciences of the United States of America.  98(9):5228-33, 2001 Apr 24.

2848.    Magnussen P.  Ndawi B.  Sheshe AK.  Byskov J.  Mbwana K. Malaria diagnosis and treatment administered by teachers in primary schools in Tanzania.  Tropical Medicine & International Health.  6(4):273-9, 2001 Apr.


  A school health programme in Mwera Division, Pangani District included treatment of malaria attacks occurring in children during school time. A combination of symptoms (headache, muscle/joint pains, feeling feverish) and oral temperature > or = 37.5 degrees C was used for the diagnosis of malaria. Chloroquine (25 mg/kg given over 3 days) was used for treatment. Malariometric surveys on children aged 7-15 years (mean 10 years) were conducted once a year (1995-1997). Plasmodium falciparum accounted for 100% of infections and the parasite prevalence varied between 32.7 and 35.3% from 1995 to 1997. The number of malaria cases (cases/1000 registered school children) diagnosed and treated by school teachers was 159 (67) in 1995, 324 (124) in 1996, 348 (128) in 1997 and 339 (108) in 1998. Children in grades 1-4 (age 7-13) accounted for 64.6% of cases. Symptoms and oral temperature were recorded for 1258 children. Of those, 992 (78.9%) complained of fever and at least one other symptom when presenting to teachers, 98 (7.8%) had fever as their only complaint and 168 (13.5%) presented without a perception of fever, but with other symptoms. Of these children, 36 (21.4%) had a temperature > or =37.5 degrees C. The sensitivity of "feeling feverish" was 96.5% with a specificity of 54.5%. The positive predictive value of feeling feverish was 89.9% and the negative predictive value 78.6%. Blood slides were prepared from 55.3 and 37.2% of children diagnosed by teachers during 1995 and 1996, respectively, and 71.4% were found positive. Among children who fulfilled the algorithm criteria 75.0% had a positive blood slide. With little training and regular supervision it was feasible for school teachers to make a presumptive diagnosis of malaria. We conclude that teachers can play a major role in school health programmes and are willing to be involved in health matters as long as they are supported by health and educational authorities.


2849.    Muniz-Junqueira MI.  dos Santos-Neto LL.  Tosta CE. Influence of tumor necrosis factor-alpha on the ability of monocytes and lymphocytes to destroy intraerythrocytic Plasmodium falciparum in vitro. Cellular Immunology.  208(2):73-9, 2001 Mar 15.

2850.    Nuwaha F. The challenge of chloroquine-resistant malaria in sub-Saharan Africa. [Review] [127 refs] Health Policy & Planning.  16(1):1-12, 2001 Mar.

2851.    Ockenhouse CF.  Barbosa A.  Blackall DP.  Murphy CI.  Kashala O.  Dutta S.  Lanar DE.  Daugherty JR. Sialic acid-dependent binding of baculovirus-expressed recombinant antigens from Plasmodium falciparum EBA-175 to Glycophorin A.  Molecular & Biochemical Parasitology.  113(1):9-21, 2001 Mar.

2852.    Ohnishi K.  Kimura K.  Serum levels of vascular cell adhesion molecule 1 in the early post-treatment defervescent phase of falciparum malaria.  Parasitology Research.  87(1):67-9, 2001 Jan.

2853.    Phillips RS. Current status of malaria and potential for control. [Review] [212 refs] Clinical Microbiology Reviews.  14(1):208-26, 2001 Jan.

2854.    Schellenberg D.  Menendez C.  Kahigwa E.  Aponte J.  Vidal J.  Tanner M.  Mshinda H.  Alonso P. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet.  357(9267):1471-7, 2001 May 12.

2855.    Stead AM.  Bray PG.  Edwards IG.  DeKoning HP.  Elford BC.  Stocks PA.  Ward SA.  Diamidine compounds: selective uptake and targeting in Plasmodium falciparum. Molecular Pharmacology.  59(5):1298-306, 2001 May.

2856.    Toteja R.  Nair L.  Bhasin V. Genome comparison of progressively drug resistant Plasmodium falciparum lines derived from drug sensitive clone.  Memorias do Instituto Oswaldo Cruz.  96(3):427-33, 2001 Apr.

2857. Webster G.  Barnes E.  Dusheiko G.  Franklin I.  Protecting travellers from hepatitis A. BMJ.  322(7296):1194-5, 2001 May 19.




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