Social Sciences and Malaria

Searching for a better willingness to pay elicitation method in rural Nigeria: the binary question with follow-up method versus the bidding game technique.

Onwujekwe O. Health Policy Research Unit, College of Medicine, University of Nigeria, Enugu, Nigeria.

OBJECTIVES: To compare the theoretical validity and predictive validity of the binary with follow-up questions technique and the bidding game, using hypothetical and actual WTP for insecticide-treated nets (ITNs) in Nigeria. METHODS: Each elicitation method was applied in one of two rural communities in Enugu state, Nigeria. A pre-tested interviewer-administered questionnaire was administered to household heads or representatives of households. WTP was elicited in each after presenting the scenario and showing a sample of the ITNs to the respondents. Then, within an interval of 1-2 months, the nets were sold to the respondents to compare hypothetical and actual WTP. FINDINGS: Consistent slightly higher mean and median WTP amounts were elicited from Mbano where the bidding game was used. The WTP technique was able to predict WTP responses correctly in 75% and 85% of cases in Orba and Mbano, respectively. Chi-square analysis did not show any statistical difference in values from both communities (p>0.05). CONCLUSION: Though the two techniques yielded similar results, the thrust should be the development of a WTP elicitation method that best mimics the bargaining process in normal market situations in rural Nigeria. Such an indigenous technique will help improve the predictive validity of the contingent valuation method. Copyright 2001 John Wiley & Sons, Ltd.

---

Past and Present 2000, 167, May, 203-237

Displacement and Disease: Epidemics and Ideas about Malaria in Matabeleland, Zimbabwe, 1945-1996

McGregor, JoAnn; Ranger, Terence. U Reading, Berkshire, UK

Four leading theories describing the history of the malaria epidemic in post-WWII southern Africa are presented, based on research conducted in northern Matabeleland. The Archives of Zimbabwe provide data about the forced resettlement campaigns that took place during the late 1940s & early 1950s. These forced resettlement operations moved people from southwestern Zimbabwe into the malaria-ridden forests of northern Matabeleland. The epidemic of 1996, the worst on record for the 20th century, is then examined. People’s response to the latter epidemic is compared to that of the earlier one: in the 1940s & 1950s, the people of Rhodesia respected biomedical interventions; by the mid-1990s they had lost faith in both science & the state. A renewed focus on custom, individuals, the land, & tradition had emerged. These new attitudes show that the history of disease is fundamentally entwined with Zimbabwean beliefs about both political & environmental history.  

PubMed

Int J Parasitol 2001 Jun;31(8):753-62DNA-based vaccines against malaria: status and promise of the Multi-Stage Malaria DNA Vaccine Operation.

Doolan DL, Hoffman SL.

Malaria Program, Naval Medical Research Center, 20910-7500, Silver Spring, MD, USA

The introduction of DNA vaccine technology has facilitated an unprecedented multi-antigen approach to developing an effective vaccine against complex pathogens such as the Plasmodium spp. parasites that cause malaria. We have established the capacity of DNA vaccines encoding Plasmodium antigens to induce CD8() cytotoxic T lymphocyte and interferon-gamma responses in mice, monkeys and humans. However, like others, we have found that the first or second generation DNA vaccines on their own are not optimal, and have demonstrated the potential of heterologous prime/boost immunisation strategies involving priming with DNA and boosting with poxvirus or recombinant protein in adjuvant. In this review, we summarise the current status and promise of our programmatic efforts to develop a DNA-based vaccine against malaria, our Multi-Stage Malaria DNA Vaccine Operation, and illustrate the transition of promising developments in the laboratory to clinical assessment in humans.

PMID: 11403765 [PubMed – in process]

---

 Infect Immun 2001 Jul;69(7):4390-7Naturally Acquired Antibody Responses to Plasmodium falciparum Merozoite Surface Protein 4 in a Population Living in an Area of Endemicity in Vietnam.

Wang L, Richie TL, Stowers A, Nhan DH, Coppel RL.

Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.

Merozoite surface protein 4 (MSP4) of Plasmodium falciparum is a glycosylphosphatidylinositol-anchored integral membrane protein that is being developed as a component of a subunit vaccine against malaria. We report here the measurement of naturally acquired antibodies to MSP4 in a population of individuals living in the Khanh-Hoa region of Vietnam, an area where malaria is highly endemic. Antibodies to MSP4 were detected in 94% of the study population at titers of 1:5,000 or greater. Two forms of recombinant MSP4 produced in either Escherichia coli or Saccharomyces cerevisiae were compared as substrates in the enzyme-linked immunosorbent assay. There was an excellent correlation between reactivity measured to either, although the yeast substrate was recognized by a higher percentage of sera. Four different regions of MSP4 were recognized by human antibodies, demonstrating that there are at least four distinct epitopes in this protein. In the carboxyl terminus, where the single epidermal growth factor-like domain is located, the reactive epitope(s) was shown to be conformation dependent, as disruption of the disulfide bonds almost completely abolished reactivity with human antibodies. The anti-MSP4 antibodies were mainly of the immunoglobulin G1 (IgG1) and IgG3 subclasses, suggesting that such antibodies may play a role in opsonization and complement-mediated lysis of free merozoites. Individuals in the study population were drug-cured and followed up for 6 months; no significant correlation was observed between the anti-MSP4 antibodies and the absence of parasitemia during the surveillance period. As a comparison, antibodies to MSP1(19), a leading vaccine candidate, were measured, and no correlation with protection was observed in these individuals. The anti-MSP1(19) antibodies were predominantly of the IgG1 isotype, in contrast to the IgG3 predominance noted for MSP4.

PMID: 11401978 [PubMed – in process]

---

Environ Health Perspect 2001 May;109(5):489-93Coupling between Annual and ENSO Timescales in the Malaria-Climate Association in Colombia.

Poveda G, Rojas W, Quinones ML, Velez ID, Mantilla RI, Ruiz D, Zuluaga JS, Rua GL.

Postgrado en Aprovechamiento de Recursos Hidraulicos, Universidad Nacional de Colombia, Medellin, Colombia.

We present evidence that the El Nino phenomenon intensifies the annual cycle of malaria cases for Plasmodium vivax and Plasmodium falciparum in endemic areas of Colombia as a consequence of concomitant anomalies in the normal annual cycle of temperature and precipitation. We used simultaneous analyses of both variables at both timescales, as well as correlation and power spectral analyses of detailed spatial (municipal) and temporal (monthly) records. During “normal years,” endemic malaria in rural Colombia exhibits a clear-cut “normal” annual cycle, which is tightly associated with prevalent climatic conditions, mainly mean temperature, precipitation, dew point, and river discharges. During historical El Nino events (interannual time scale), the timing of malaria outbreaks does not change from the annual cycle, but the number of cases intensifies. Such anomalies are associated with a consistent pattern of hydrological and climatic anomalies: increase in mean temperature, decrease in precipitation, increase in dew point, and decrease in river discharges, all of which favor malaria transmission. Such coupling explains why the effect appears stronger and more persistent during the second half of El Nino’s year (0), and during the first half of the year. We illustrate this finding with data for diverse localities in Buenaventura (on the Pacific coast) and Caucasia (along the Cauca river floodplain), but conclusions have been found valid for multiple localities throughout endemic regions of Colombia. The identified coupling between annual and interannual timescales in the climate-malaria system shed new light toward understanding the exact linkages between environmental, entomological, and epidemiological factors conductive to malaria outbreaks, and also imposes the coupling of those timescales in public health intervention programs.

PMID: 11401760 [PubMed – in process]

---

Parassitologia 2000 Jun;42(1-2):1-182 Dealing with malaria in the last 60 years: aims, methods and results. Proceedings of a conference. May 11-14, 1998. Sleepy Hollow, New York, USA.

Publication Types:
PMID: 11400679 [PubMed – indexed for MEDLINE]

---

 Eur Cytokine Netw 2001 Apr;12(2):361Serum levels of interleukin-18 in patients with uncomplicated Plasmodium falciparum malaria.

Torre D, Giola M, Speranza F, Matteelli A, Basilico C, Biondi G.

Division of Infectious Diseases, Regional Hospital, Viale Borri 57, 21100 Varese, Italy.

Interleukin (IL)-18, a newly discovered cytokine produced primarily by macrophages, has been shown to induce gamma interferon (IFN-g) production by natural killer cells, to induce the T helper type 1 response. To further elucidate the role of this cytokine in uncomplicated malaria caused by Plasmodium falciparum, serum levels of IL-18, and gamma interferon (IFN-g), determined by an immunoenzymatic assay, were analyzed in 40 adult patients, and in 15 healthy control subjects. A significant increase in serum levels of IL-18 was observed in patients with uncomplicated P. falciparum malaria on admission, whereas serum levels of IFN-g tended to increase although not significantly. Serum levels of IL-18 decreased three days later, but still remained significantly high, whereas IFN-g levels returned to normal levels compared to the controls. No significant correlation was found between parasitemia and serum levels of IL-18 and IFN-g. The increase of IL-18 levels during acute and recovery phases of uncomplicated P. falciparum malaria may reflect a proinflammatory role of IL-18 in these patients. An early and effective immune response regulated by proinflammatory Th1 cytokines, including tumor necrosis factor (TNF), interleukin (IL)-12, and possibly IFN-g may limit the progression from uncomplicated malaria to severe and life-threatening complications.

PMID: 11399527 [PubMed – in process]

---

Indian J Malariol 1999 Sep-Dec;36(3-4):75-80Malaria investigation in District Jodhpur, Rajasthan, during the summer season.

Batra CP, Mittal PK, Adak T, Sharma VP.

Malaria Research Centre, 2 Nanak Enclave, Delhi, 110 009, India.

Studies were carried out in District Jodhpur of the Thar region of Rajasthan. Epidemiological investigation revealed high slide positivity rate in the canal irrigated area (54.5 per cent), sand dunes area (67.54 per cent), stone quarry area (26.66 per cent) and in the desert plain area (41.5 per cent). Similarly, slide falciparum rates were 7.10, 4.38, 6.66 and 5.6 per cent respectively. Entomological studies showed An. stephensi and An. culicifacies as major species and their densities ranged between 2 to 14.58 and 0 to 0.9 pmh respectively. Resistance in malaria vectors to insecticides, poor surveillance and suppressive treatment of cases appear to be the factors for persistent transmission in the study area.

PMID: 11398666 [PubMed – in process]

---

 Indian J Malariol 1999 Sep-Dec;36(3-4):65-9Field studies on the sensitivity and specificity of an immunochromatographic test for the detection of Plasmodium falciparum malaria in tribal areas of Orissa.

Sharma SK, Tyagi PK, Haque MA, Padhan K.

Malaria Research Centre (Field Station), Civil Township, Rourkela-769 004, India.

A rapid immunodiagnostic test developed by an Australian Biotechnology company for the diagnosis of Plasmodium falciparum in the peripheral blood has been evaluated in the field for its sensitivity, specificity and efficacy in comparison to microscopic examination. The results showed that the tests sensitivity, specificity and efficacy were 98.2, 96.9 and 97.5 per cent respectively. The positive and negative predictive values of the test were 96.4 and 98.4 per cent respectively. The test when compared to the conventional microscopy did not show any statistically significant difference suggesting that the two diagnostic methods are equally good. The test performed did not show cross-reactions with other parasite species. It is a simple and rapid field diagnostic method, which does not require any expensive laboratory equipment or skilled personnel.

PMID: 11398664 [PubMed – in process]

---

Indian J Malariol 1999 Sep-Dec;36(3-4):53-60Breeding preferences of Anopheles culicifacies in the rice agro-ecosystem in Kheda district, Gujarat.

Kant R, Pandey SD.

Malaria Research Centre (Field Station), Civil Hospital, Nadiad, 387 001, India.

Breeding preferences of Anopheles culicifacies, a principle malaria vector, in the plains of India was studied in the rice agro-ecosystem of Kheda district in central Gujarat. Extensive breeding of this species was found in the rice field channels (20.83 per cent) and in rice fields (5.32 per cent). However, rice nurseries (0.91 per cent) and post-harvested rice fields (2.51 per cent) were less preferred. The species was found in abundance in newly transplanted rice fields and during early months of rice cultivation with a peak prevalence in the non-monsoon (Rabi) season. The breeding of An. culicifacies was inversely proportional and negatively correlated (r = -0.868; p < 0.05) with the height of the plants, whereas it showed a positive correlation (r = 0.779; p < 0.05) with the distance between plants. Rice fields near the villages supported maximum breeding of An. culicifacies (48 per cent) followed by the rice fields, 0.5 to one km away from the human habitation. Co-efficient of association (C8 index) revealed a positive association of the species with An. annularis, An. pallidus, An. subpictus and Cx. quinquefasciatus. However, it was negatively associated with An. nigerrimus, Cx. tritaeniorhynchus and Cx. vishnui sub groups.

PMID: 11398662 [PubMed – in process]

---

J Infect Dis 2001 Jul 1;184(1):107-11Fcgamma Receptor IIa (CD32) Polymorphism Is Associated with Protection of Infants against High-Density Plasmodium falciparum Infection. VII. Asembo Bay Cohort Project.

Shi YP, Nahlen BL, Kariuki S, Urdahl KB, McElroy PD, Roberts JM, Lal AA.

Division of Parasitic Diseases, National Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia and Vector Biology and Control Research Center, Kenya Medical Research Institute, Kisumu. [email protected]

In vitro studies have shown that inhibition of Plasmodium falciparum blood-stage parasite growth by antibody-dependent cellular inhibition is mediated by cooperation between malaria-specific IgG1 and IgG3, but not IgG2, and monocytes via the Fcgamma receptor II (FcgammaRII). A single amino acid substitution at position 131 in FcgammaRIIa is critical in the binding of human IgG subclasses. The hypothesis that the FcgammaRIIa-Arg/Arg131 genotype, which does not bind to IgG2, is a host genetic factor for protection against high-density P. falciparum infection was tested. One hundred eighty-two infants from a large community-based birth cohort study in western Kenya were selected for an unmatched case-control study. Results showed that the infants with the FcgammaRIIa-Arg/Arg131 genotype were significantly less likely to be at risk for high-density falciparum infection, compared with infants with the FcgammaRIIa-His/Arg131 genotype (adjusted odds ratio, 0.278; 95% confidence interval, 0.123-0.627; P=.0021). This finding supports the hypothesis.

PMID: 11398118 [PubMed – in process]

---

: Parasitology 2001 May;122(Pt 5):507-13Landscape features associated with infection by a malaria parasite (Plasmodium mexicanum) and the importance of multiple scale studies.

Eisen RJ, Wright NM.

Department of Biology, University of Vermont, Burlington 05405, USA. [email protected]

In a 3-year study, we examined landscape features (aspect, slope, sun exposure, canopy cover, type of ground cover, and nearest water source) that were potentially related to prevalence of infection with Plasmodium mexicanum in fence lizards (Sceloporus occidentalis) within a 4.5 ha study area in northern California, USA. Logistic regression analysis showed that ground cover type was the primary mediator of the probability of P. mexicanum infection. Infected lizards were captured more often in rock and/or leaf litter locations than in grassy ones. In another experiment, the study area was divided into 9 sites (0.07-0.33 ha), and infection prevalence was calculated for each. Three sites with high (> 30%) infection prevalence had significantly more rocky outcrops and leaf litter than those with low (< 20%) or moderate (20-30%) infection prevalence (N = 3 sites each). We conclude that lizard site selection may influence the probability of exposure to infected vectors and thus the likelihood of P. mexicanum infection. We also demonstrate that studies at different spatial scales may be required to understand fully the relationship between landscape features and parasite distribution.

PMID: 11393823 [PubMed – in process]

---

Parasitology 2001 May;122(Pt 5):491-6The influence of host haematocrit on the blood feeding success of Anopheles stephensi: implications for enhanced malaria transmission.

Taylor PJ, Hurd H.

Centre for Applied Entomology and Parasitology, School of Life Sciences, Keele University, Staffs, UK. [email protected]

Two studies were carried out to determine the effect of the rodent malaria Plasmodium yoelii nigeriensis on the blood feeding success of Anopheles stephensi. Initially, pairs of mice with similar packed cell volume (PCV) (measured by haematocrit) were selected. Following infection of one of the pair its PCV gradually fell. At various times post-infection, a comparison was made of the bloodmeal size (haemoglobin content) of mosquitoes feeding on these mice. The bloodmeal sizes increased with parasite-induced fall in PCV down to a haematocrit of 43-44%, which occurred approximately 48 h post-infection. Bloodmeals were significantly reduced, however, when mosquitoes fed on mice with higher parasitaemias and a haematocrit of 15-35%. Thus, at early stages of infection, mosquitoes ingested a bloodmeal significantly greater than did the mosquitoes feeding on the control mice. However, mosquitoes were not able to compensate for severe infection-associated anaemia. To compensate for variation due to innate differences in the mice, a second experiment was performed. Mosquitoes were fed on the same mice before (control) and after infection. Again, the bloodmeal size increased with decreasing PCV down to haematocrits of 42-45%, but declined thereafter. In this host-parasite-vector system, haematocrits that maximized erythrocyte intake were produced when gametocytes, capable of exflagellation, were present.

PMID: 11393821 [PubMed – in process]

---

West Afr J Med 2000 Oct-Dec;19(4):293-7Treatment of malaria in north-eastern and south-eastern Nigeria: a population study of mefloquine, sulphadoxine, pyrimethamine combination (MSP) vs chloroquine (CQ).

Ekanem OJ, Ezedinachi EN, Molta NB, Watila IM, Chukwuani CM, Meremikwu MM, Akpede G, Ojar EA.

Consultant Malarialogist, Lanex International Agency, Lagos, Nigeria.

In a population-based study involving 4019 patients in 20 peripheral health facilities in Nigeria, the outcome of presumptive malaria treatment with MSP was compared to that of CQ. The study was conducted between January 1995 and January 1996. Patients aged 6 months or more with a clinical diagnosis of malaria based on history of fever and axillary temperature > 37.5 degrees C were either treated with MSP (250 mg mefloquine, 500 mg sulphadoxine, and 25 mg pyrimethamine per tablet) or CQ (150 mg chloroquine base per tablet). The clinical cure rate was assessed by the disappearance of clinical signs and symptoms over a 7-day period. Tolerability was assessed by the incidence of adverse events (adverse drug reaction and intercurrent illness). The result shows that the clinical care rate of suspected malaria was 97.6% with MSP and 85.6% with CQ. The incidence of adverse event was 9.5% with MSP and 9.2% with CQ. The withdrawal rate was 2.0% with MSP and 5.0% with CQ; 3.5% of the patients in the CQ group withdrew due to adverse events compared to 0.47% with MSP. In conclusion it was observed that in addition to superior efficacy of MSP over CQ, fever clearance rate with MSP was comparable to that of CQ. The study also demonstrated that two tablets maximum dose of MSP is safe and effective in a large population of Nigeria malaria patients.

PMID: 11391844 [PubMed – in process]

---

J Biol Chem 2001 Jun 4;[epub ahead of print]

full-text article at: http://www.jbc.orgThe Plasmodium falciparum bifunctional ornithine decarboxylase, S-adenosylmethionine decarboxylase enables a well balanced polyamine synthesis without domain-domain interaction.

Wrenger C, Luersen K, Krause T, Muller S, Walter RD.

Biochemistry, Bernhard Nocht Institute for Tropical Medicine, Hamburg 20359.

In the human malaria parasite Plasmodium falciparum polyamines are synthesised by a bifunctional enzyme which possesses both ODC and AdoMetDC activities. The mature enzyme consists of the heterotetrameric N-terminal AdoMetDC and the C-terminal dimeric ODC, which results in the formation of a heterotetrameric complex. For the native bifunctional protein a half-life longer than two hours was determined, which is in contrast to the extreme short half-life of its mammalian monofunctional counterparts. The biological advantage of the plasmodial bifunctional ODC/AdoMetDC might be that the control of polyamine synthesis is achieved by only having to regulate the abundance and activity of one protein. An interesting feature in the regulation of the bifunctional protein is that putrescine inhibits PfODC activity about 10 fold more efficiently than the mammalian ODC activity, and in contrast to the mammalian AdoMetDC, the activity of the PfAdoMetDC domain is not stimulated by the diamine. In order to analyse posttranslational processing, polymerisation and domain-domain interactions, several mutant proteins were generated which have single mutations in either the PfODC or PfAdoMetDC domains. The exchange of amino acids essential for the activity of one domain had no effect on the enzyme activity of the other domain. Even prevention of the postranslational cleavage of the AdoMetDC domain or ODC dimerisation and thus the interference with the folding of the protein hardly affected the activity of the partner domain.In addition, inhibition of the activity of the PfODC domain had no effect on the activity of the PfAdoMetDC domain and vice versa. These results demonstrate that no domain-domain interactions occur between the two enzymes of the bifunctional PfODC/AdoMetDC and both enzymatic activities are operating as independent catalytical sites which do not affect each other.

PMID: 11390378 [PubMed – as supplied by publisher]

---

 Blood 2001 Jun 15;97(12):3966-71Inhibition of Plasmodium yoelii blood-stage malaria by interferon alpha through the inhibition of the production of its target cell, the reticulocyte.

Vigario AM, Belnoue E, Cumano A, Marussig M, Miltgen F, Landau I, Mazier D, Gresser I, Renia L.

INSERM Unite 445, ICGM, Universite Rene Descartes, Hopital Cochin, Batiment Gustave Roussy, 27, rue du Fbg Saint Jacques, 75014 Paris, France.

The effect of a recombinant hybrid human interferon alpha (IFN-alpha) (which cross-reacts with murine cells) on C57BL/6 mice infected with Plasmodium yoelii sporozoites or parasitized erythrocytes was determined. IFN-alpha did not inhibit the development of the parasite in the liver, but it did reduce the blood parasite load and the hepatosplenomegaly induced by the infection in mice injected with blood-stage parasites. The extent of anemia in IFN-alpha-treated and control mice was similar, despite the lower parasite load in the IFN-alpha-treated mice. The reduced blood parasite load in IFN-alpha-treated mice was associated with reduced erythropoiesis and reticulocytosis. As reticulocytes are the preferred target cells for the strain of P yoelii used (P yoelii yoelii 265 BY), it was postulated that the inhibition of reticulocytosis in IFN-alpha-treated mice was causally related to the observed decreased blood parasite load. This was supported by the finding that IFN-alpha inhibited a different strain of P yoelii (17X clone A), which also displays a tropism for reticulocytes, but not a line of Plasmodium vinckei petteri, which infects only mature red blood cells. As human malaria species also display different tropism for reticulocytes, these findings could be relevant for people coinfected with multiple Plasmodium species or strains or coinfected with Plasmodium and virus. (Blood. 2001;97:3966-3971)

PMID: 11389041 [PubMed – in process]

---

Am J Trop Med Hyg 2000 Sep-Oct;63(3-4):199-203Dynamics of P. falciparum gametocytemia in symptomatic patients in an area of intense perennial transmission in Tanzania.

Akim NI, Drakeley C, Kingo T, Simon B, Senkoro K, Sauerwein RW.

Ifakara Health Research and Development Centre, Tanzania.

We investigated the dynamics of Plasmodium falciparum gametocytemia in symptomatic patients attending a local dispensary in the Kilombero district, Tanzania. Consenting individuals aged one and above, with varying asexual and sexual parasitemias were treated appropriately and asked to return weekly for 28 days. Gametocyte prevalence was highest on Day 7 of follow-up in all age groups (overall 30.5%). Multifactorial analysis showed that young age (chi2 = 18.4; P = 0.004), high asexual parasitemia on presentation (chi2 = 19.4; P = 0.0007) and gametocyte positivity on presentation (chi2 = 29.4; P = 0.001) were all significantly associated with the presence of gametocytes on Days 7 and 14 of follow-up. High presentation of asexual parasitemia alone was positively correlated with higher gametocyte densities on both days of follow-up (F4, 297 = 2.0; P = 0.049). Gametocyte incidence rates decreased significantly with age (chi2 = 7.6, P < 0.005). In summary, in this group of chloroquine-treated individuals, gametocyte prevalence and incidence rates decreased with age, while densities remained relatively constant.

PMID: 11388515 [PubMed – indexed for MEDLINE]

---

Am J Trop Med Hyg 2000 Sep-Oct;63(3-4):158-73Placental changes associated with fetal outcome in the Plasmodium coatneyi/rhesus monkey model of malaria in pregnancy.

Davison BB, Cogswell FB, Baskin GB, Falkenstein KP, Henson EW, Krogstad DJ.

Department of Pathology, Tulane Regional Primate Research Center, Covington, Louisiana 70433, USA.

Term placentas collected surgically from seven Plasmodium coatneyi-infected rhesus monkeys, one abortion, and five controls were evaluated histopathologically. The placentas from Plasmodium-infected dams had more significant pathologic changes than those from controls for six parameters (P < 0.05) and higher numbers of activated (LN5 Zymed) macrophages in the intervillous space (IVS) (P = 0.0173). Total parasite load (TPL) was defined as the sum of all weekly peripheral infected red blood cell counts for each trimester and for the entire pregnancy. High first trimester PLs were more likely to result in fetal demise (P = 0.0476) or increased placental damage in surviving infants. As trimester 2-3 TPL increased, so did the number of activated macrophages (P < 0.05) and the total malaria pigment scores (P < 0.05). Low birth weight (LBW) and intrauterine growth retardation (IUGR) were associated with high pigment scores and high numbers of activated macrophages in the IVS. High placental damage scores were not associated with IUGR, LBW, or early infant mortality.

PMID: 11388509 [PubMed – indexed for MEDLINE]

---

Am J Trop Med Hyg 2000 Sep-Oct;63(3-4):150-2Diagnosis of malaria in non-endemic countries by the ParaSight-F test.

Brenier-Pinchart MP, Pinel C, Croisonnier A, Brion JP, Faure O, Ponard D, Ambroise-Thomas P.

Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire, Grenoble, France.

QBC, examination of thin blood smears, and Parasight-F were performed for every case of malaria suspected between May 1997 and December 1998. Data from 310 patients were reported. Fifty had malaria infection diagnosed by QBC and thin blood film, among whom 39 had Plasmodium falciparum infection. Three of these 39 were negative with the Parasight-F test. Eleven patients had a positive ParaSight-F test but microscopic diagnosis methods were negative. Interpretation of these 11 positive ParaSight-F results is proposed to depend on clinical criteria.

PMID: 11388507 [PubMed – indexed for MEDLINE]

---

 Am J Trop Med Hyg 2000 Sep-Oct;63(3-4):139-45Performance of the OptiMAL assay for detection and identification of malaria infections in asymptomatic residents of Irian Jaya, Indonesia.

Fryauff DJ, Purnomo, Sutamihardja MA, Elyazar IR, Susanti I, Krisin, Subianto B, Marwoto H.

United States Naval Medical Research Unit Number Two, Jakarta, Indonesia. 
[email protected]

The OptiMAL assay, a new immunochromatographic “dipstick” test for malaria based on detection of Plasmodium lactate dehydrogenase (pLDH), is purported to detect infections of approximately 200 parasites/microL of blood and to differentiate between Plasmodium falciparum and non-P. falciparum. We evaluated OptiMAL performance by comparing the test strip interpretations of two independent readers with consensus results obtained independently by expert malaria microscopists. Unbiased measures of sensitivity were derived by applying the OptiMAL test for detection and differentiation of light, asymptomatic infections by P. falciparum and Plasmodium vivax. OptiMAL readings were separated in time to determine whether the reaction signal was stable. Microscopy identified infections in 225 of 505 individuals screened; those with P. falciparum (n = 170) averaged 354 asexual forms/microL and P. vivax/Plasmodium malariae (n = 112) averaged 216 asexual forms/microL of blood. Concordance between OptiMAL and microscopy was 81% and 78% by the two independent readings. The assay’s sensitivity for detection of any malaria species was 60.4% and 70.2% respectively and specificity was 97% and 89%. Most cases identified by microscopy as P. falciparum were graded as negative or non-falciparum by both OptiMAL readers. OptiMAL false negatives as well as misidentifications were related to low parasitemias (Y 500/microL). The OptiMAL assay demonstrated 88-92% sensitivity for detecting infections of 500-1,000 parasites/microL, a range covering the mean parasitemia of primary symptomatic P. falciparum infections in malaria-naive Indonesian transmigrants. This device was markedly less sensitive than expert microscopy for discriminating between malaria species and is presently unsuited for use as an epidemiological screening tool. The OptiMAL assay is not approved for diagnostic use but is commercially available for research purposes only.

PMID: 11388505 [PubMed – indexed for MEDLINE]

---

Am J Trop Med Hyg 2000 Sep-Oct;63(3-4):128-32IgE deposition in brain microvessels and on parasitized erythrocytes from cerebral malaria patients.

Maeno Y, Perlmann P, PerlmannH, Kusuhara Y, Taniguchi K, Nakabayashi T, Win K, Looareesuwan S, Aikawa M.

Department of Virology and Parasitology, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan.

Postmortem brain tissues of 21 cerebral malaria cases were obtained in Myanmar and Vietnam. The tissues were examined by light microscopy and by an immunohistochemical method. Brain microvessels (capillaries and venules) were examined for the presence of immunoglobulins IgE and IgG, Plasmodium falciparum antigen, and parasitized erythrocytes (PRBC). Deposition of IgE, IgG, and P. falciparum antigen was observed in the microvessels from all specimens examined. Sequestered PRBC in the microvessels were positive for IgG in all 21 cases and for IgE in six cases. In the latter cases, the percentage of microvessels with sequestered PRBC was > 50%, with the frequency of IgE-positive cells ranging from 42% to 52%. In contrast, in five cases that were only weakly positive for IgE, the percentage of microvessels with sequestered PRBC was remarkably low (< 1%). These data indicate that the degree of deposition of IgE in microvessels and on PRBC from cerebral malaria patients correlated with that of PRBC sequestration. As IgE-containing immune complexes are known to induce local overproduction of tumor necrosis factor-alpha (TNF-alpha), a major pathogenic factor in cerebral malaria, IgE may contribute to the pathogenesis of this severe disease.

PMID: 11388503 [PubMed – indexed for MEDLINE]

---

Am J Trop Med Hyg 2000 Sep-Oct;63(3-4):119-20Short report: failure to select for chloroquine- or mefloquine-resistant Plasmodium berghei through drug pressure in Anopheles stephensi mosquitoes.

Coleman RE, Song GH, Wirtz RA.

Department of Entomology, United States Army Medical Component-Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

We investigated whether chloroquine- or mefloquine-resistant Plasmodium berghei could be selected through drug pressure applied during continuous cyclical transmission in Anopheles stephensi mosquitoes. Mosquitoes were infected by feeding them on mice previously inoculated with a drug-sensitive clone of P. berghei ANKA. Mosquitoes ingested mefloquine or chloroquine with the infectious blood-meal, or by feeding on a drug-treated (uninfected) mouse 4 or 10 days after the infectious blood-meal. Twenty-two days after being infected, mosquitoes transmitted sporozoites to uninfected mice. Blood from these animals was used to infect naive mice that were then used to reinitiate the mouse/mosquito/mouse cycle. A total of 20 passages through mosquitoes were completed while under drug pressure. Drug-resistance levels were assessed in the initial clone and after 20 passages through mosquitoes. None of 18 “sub-clones” of parasites showed significant increases in chloroquine or mefloquine resistance, suggesting that exposure of sporogonic stage Plasmodium to chloroquine or mefloquine will not result in the development of drug resistance.