EHP LIBRARY MALARIA BULLETIN 45: SEPT 16-29, 2002 SOCIAL SCIENCES AND MALARIA

Southeast Asian J Trop Med Public Health  2002 Jun;33(2):246-54 

Knowledge and behavior relating to malaria in malaria endemic villages of

Khammouane Province, Lao PDR.

Uza M, Phommpida S, Toma T, Takakura M, Manivong K, Bounyadeth S, Kobayashi J,

Koja Y, Ozasa Y, Miyagi I.

Department of Community Health Nursing, School of Health Sciences, University of

the Ryukyus, Nishihara, Okinawa, Japan. Email: [email protected]

In order to provide basic data for evaluation of malaria control measures, a

study on the knowledge and behavior of people regarding prevention of malaria

was carried out in 8 malaria endemic villages in Khammouane Province of Lao PDR

from 1999 to 2000. The total valid questionnaire respondents were 932, with a

mean age of 32.3 +/- 14.9. 43.7% of the respondents were illiterate. About 44%

of the respondents suffered from malaria in the past. About 55% of the

illiterate group slept in mosquito nets, compared to 75.4% for the educated

group. About 29% of the illiterate respondents had knowledge of malaria

transmission by mosquito bites, compared to 48.8% for the educated groups. Out

of 167 non-impregnated mosquito nets examined in two villages, 13 were in bad

condition having holes or leaks and 39 female mosquitos including Anopheles spp

were collected in these nets by early morning catches. Knowledge of malaria and

behavior in relation to the prevention of malaria were significantly related to

educational level. Health education as well as general education must be taken

into account for communities in malaria endemic areas to become more involved in

malaria control strategies.

Am Jnl Trop Med Hyg 2002, 66(5): 481-186

Clinical and laboratory predictors of imported malaria in an

outpatient setting: An aid to medical decision making in returning

travelers with fever

D’Acremont V; Landry P; Mueller I; Pecoud A; Genton B

Univ Lausanne,Med Outpatient Clin, Travel Clin,Rue Cesar Roux 19/CH-1005

Lausanne//Switzerland/ (REPRINT); Univ Lausanne,Med Outpatient Clin,

Travel Clin,CH-1005 Lausanne//Switzerland/; Swiss Trop Inst,CH-4002

Basel//Switzerland/

No evidence-based information exists to guide clinicians for

giving presumptive treatment to returning travelers when malaria is

strongly suspected on clinical grounds but laboratory confirmation is

not immediately available or is negative. A prospective study was

conducted in travelers or migrants who sought care for fever to

identify clinical and laboratory predictors of Plasmodium parasitemia.

A total of 336 questionnaires were collected (97 malaria case patients

and 239 controls). Multivariate regression analysis showed inadequate

prophylaxis, sweating, no abdominal pain, temperature greater than or

equal to 38degreesC, poor general health, enlarged spleen, leucocytes

less than or equal to 10 x 10(3)/L, platelets < 150 x 10(3)/L,

hemoglobin < 12 g/dL, and eosinophils less than or equal to 5% to be

associated with parasitemia. Enlarged spleen had the highest positive

likelihood ratio for a diagnosis of malaria (13.6), followed by

thrombopenia (11.0). Posttest probabilities for malaria were 85% with

enlarged spleen and 82% with thrombopenia. A rapid assessment can thus

help to decide whether a presumptive treatment should be given or not,

especially when the results of the parasitological examination are not

immediately available or are uncertain.

Int Q Community Health Educ  1999;18(4):391-413 

Cognitive and behavioral factors in community-based malaria control in Malawi.

Glik DC, Rubardt M, Nwanyanwu O, Jere S, Chikoko A, Zhang W.

Monitoring of preventive health behaviors and their determinants at the level of

households is an important component in field research for malaria control

programs.  Household members in 12 rural villages in south central Malawi

participated in a study to show change over time in perceptions and behaviors in

an area undergoing multiple malaria control interventions.  Focus group

interviews were used initially to elicit the major concepts villagers used to

define and respond to the threat of malaria.  A longitudinal household survey

(T1: n = 2460; T2: n = 2149) measured biomedical or traditional knowledge about

malaria causation and control, attitudes toward mosquitoes, barriers to taking

preventive actions, and preventive behaviors defined as sanitation, traditional,

or commercial methods to control mosquitoes.  While adherence to traditional

beliefs and behaviors was found among some, the majority of respondents also had

adopted many biomedical beliefs and attitudes about malaria causation. Changes

reflected both national and local initiatives to improve health status and

control malaria.  Behaviors changed over time and were associated with a village

level intervention and with structural, situational, and cognitive attributes of

respondents.

PUBMED

Am J Clin Nutr  2002 Oct;76(4):805-812 

Effect of zinc on the treatment of Plasmodium falciparum malaria in children:

a randomized controlled trial.

BACKGROUND: Zinc supplementation in young children has been associated with

reductions in the incidence and severity of diarrheal diseases, acute

respiratory infections, and malaria. OBJECTIVE: The objective was to evaluate

the potential role of zinc as an adjunct in the treatment of acute,

uncomplicated falciparum malaria; a multicenter, double-blind, randomized

placebo-controlled clinical trial was undertaken. DESIGN: Children (n = 1087)

aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and

Zambia. Children with fever and >/=2000 asexual forms of Plasmodium falciparum/

micro L in a thick blood smear received chloroquine and were randomly assigned

to receive zinc (20 mg/d for infants, 40 mg/d for older children) or placebo for

4 d. RESULTS: There was no effect of zinc on the median time to reduction of

fever (zinc group: 24.2 h; placebo group: 24.0 h; P = 0.37), a >/=75% reduction

in parasitemia from baseline in the first 72 h in 73.4% of the zinc group and in

77.6% of the placebo group (P = 0.11), and no significant change in hemoglobin

concentration during the 3-d period of hospitalization and the 4 wk of

follow-up. Mean plasma zinc concentrations were low in all children at baseline

(zinc group: 8.54 +/- 3.93 micro mol/L; placebo group: 8.34 +/- 3.25 micro

mol/L), but children who received zinc supplementation had higher plasma zinc

concentrations at 72 h than did those who received placebo (10.95 +/- 3.63

compared with 10.16 +/- 3.25 micro mol/L, P < 0.001). CONCLUSION: Zinc does not

appear to provide a beneficial effect in the treatment of acute, uncomplicated

falciparum malaria in preschool children.

J Med Invest  2002 Aug;49(3-4):118-23 

Development of malaria vaccines that block transmission of parasites by

mosquito vectors.

Hisaeda H, Yasutomo K.

Department of Immunology and Parasitology, The University of Tokushima School of

Medicine, Japan.

Malaria is still one of the infectious diseases urgently requiring control and

causes socioeconomic burdens on people residing in developing countries. Malaria

vaccines are expected to control the disease. However, there is no effective

vaccine available despite the intense efforts of malaria scientists. One

strategy for a malaria vaccine is to prevent parasite spread by means of

interfering with parasite development in mosquito vectors, which is the

so-called transmission-blocking vaccine (TBV). We will here review the current

progress of TBV.

J Am Mosq Control Assoc  2002 Sep;18(3):202-6 

Low insecticide deposit rates detected during routine indoor residual spraying

for malaria vector control in two districts of Gokwe, Zimbabwe.

Masendu HT, Nziramasanga N, Muchechemera C.

Blair Research Institute. Ministry of Health and Child Welfare, Harare,

Zimbabwe.

Questions have been raised about the quality of indoor residual spraying for

malaria vector control after the decentralization of the national malaria

control program in Zimbabwe. Given the critical role this control method plays,

we conducted an exercise to determine the amount of insecticide (mg active

ingredient/m2 of lambda-cyhalothrin) applied during routine house spraying.

Severe insecticide underdosing was detected. Spraying efficiency ranged between

63.4 and 76.1% on walls, and 52.7 and 63.2% on roofs. Differences between 2

districts suggested the problem originates from deficient training and lack of

pump calibration. Underdosing can undermine effective residual insecticide

activity and the expected reduction in disease transmission.

J Am Mosq Control Assoc  2002 Sep;18(3):178-85 

Environmental factors associated with larval habitats of malaria vectors in

northern Kyunggi Province, Republic of Korea.

Claborn DM, Hshieh PB, Roberts DR, Klein TA, Zeichner BC, Andre RG.

Uniformed Services University of Health Sciences, Bethesda, MD 20814-4799, USA.

The larval habitats of malaria vectors near the Demilitarized Zone of the

Republic of Korea (ROK) were sampled from June through September 2000 to

determine larval abundance and to identify environmental factors associated with

high larval density. Six primary habitats were identified: rice fields,

irrigation ditches, drainage ditches, stream pools, irrigation pools, and

marshes. Most habitats harbored similar densities of larvae until August and

September, when population densities in rice fields declined and those in

irrigation pools increased. The primary vector in the ROK, Anopheles sinensis,

occurred in water with a wide range of values for environmental factors,

including pH, total dissolved solids, percent of surface covered with floating

vegetation, and nitrate and phosphate concentrations. No environmental factor or

combination of factors were found that were predictive of high larval densities.

This study suggests that larval Anopheles are capable of developing in a wide

range of stagnant, freshwater habitats in northern Kyunggi Province, ROK.

J Am Mosq Control Assoc  2002 Sep;18(3):138-51 

Mosquito vector control and biology in Latin America--a twelfth symposium.

Clark GG, Martinez HQ.

Dengue Branch, Centers for Disease Control and Prevention, San Juan, PR

00920-3860, USA.

The 12th annual Latin American symposium presented by the American Mosquito

Control Association (AMCA) was held as part of the 68th Annual Meeting in

Denver, CO, in February 2002. The principal objective, as for the previous 11

symposia, was to promote participation in the AMCA by vector control

specialists, public health workers, and academicians from Latin America. This

publication includes summaries of 35 presentations that were given orally in

Spanish or presented as posters by participants from 7 countries in Latin

America. Topics addressed in the symposium included results from chemical and

biological control programs and studies; studies of insecticide resistance; and

population genetics, molecular, ecological, and behavioral studies of vectors of

dengue (Aedes aegypti and Aedes albopictus) and other arboviruses, malaria

(Anopheles albimanus and Anopheles pseudopunctipennis), leishmaniasis

(Lutzomyia), and Chagas Disease (Triatoma). Related topics included biology and

control of Culiseta inornata, Ochlerotatus taeniorhynchus, scorpions, Chironomus

plumosus, and Musca domestica.

Malar J  2002 Aug 14;1(1):10 [epub ahead of print] 

Behavioural determinants of gene flow in malaria vector populations: Anopheles

gambiae males select large females as mates.

Okanda F, Dao A, Njiru B, Arija J, Akelo H, Toure Y, Odulaja A, Beier J, Githure

J, Yan G, Gouagna L, Knols B, Killeen G.

International Centre of Insect Physiology and Ecology, PO Box 30772, Nairobi,

Kenya. Email: [email protected]

BACKGROUND: Plasmodium-refractory mosquitoes are being rapidly developed for

malaria control but will only succeed if they can successfully compete for mates

when released into the wild. Pre-copulatory behavioural traits maintain genetic

population structure in wild mosquito populations and mating barriers have

foiled previous attempts to control malaria vectors through sterile male

release. METHODS: Varying numbers of virgin male and female Anopheles gambiae

Giles, from two strains of different innate sizes, were allowed to mate under

standardized conditions in laboratory cages, following which, the insemination

status, oviposition success and egg batch size of each female was assessed. The

influence of male and female numbers, strain combination and female size were

determined using logistic regression, correlation analysis and a simple

mechanistic model of male competition for females. RESULTS: Male An. gambiae

select females on the basis of size because of much greater fecundity among

large females. Even under conditions where large numbers of males must compete

for a smaller number of females, the largest females are more likely to become

inseminated, to successfully oviposit and to produce large egg batches.

CONCLUSIONS: Sexual selection, on the basis of size, could either promote or

limit the spread of malaria-refractory genes into wild populations and needs to

be considered in the continued development and eventual release of transgenic

vectors. Fundamental studies of behavioural ecology in malaria vectors such as

An. gambiae can have important implications for malaria control and should be

prioritised for more extensive investigation in the future.

Mol Ecol  2002 Oct;11(10):2183-2187 

Genetic structure of Anopheles gambiae (Diptera: Culicidae) in Sao Tome 

and Principe (West Africa): implications for malaria control.

Pinto J, Donnelly MJ, Sousa CA, Gil V, Ferreira C, Elissa N, Do Rosario VE,

Charlwood JD.

Centro de Malaria e outras Doencas Tropicais, Instituto de Higiene e Medicina

Tropical, Universidade Nova de Lisboa. Rua da Junqueira 96 1349-008 Lisbon,

Portugal, Division of Parasite and Vector Biology, Liverpool School of Tropical

Medicine. Pembroke Place, Liverpool L3 5QA, UK, Division of Parasitic Diseases,

Centers for Disease Control and Prevention. MS; F22, 4770, Buford Highway,

Chamblee GA, USA, Unidade de Entomologia Medica, Instituto de Higiene e Medicina

Tropical, Universidade Nova de Lisboa. Rua da Junqueira 96 1349-008 Lisbon,

Portugal, Centro Nacional de Endemias, Ministerio de Saude. Caixa Postal 218 Sao

Tome, Democratic Republic of Sao Tome e Principe, Centre International de

Recherche Medicale de Franceville. BP 769 Franceville, Gabon.

The impact of a vector eradication programme, conducted in the 1980s, on

Anopheles gambiae populations from the islands of Sao Tome and Principe, was

evaluated by microsatellite DNA analysis. Significant genetic differentiation

was observed within and between the two islands and between the islands and a

population from Gabon, suggesting a degree of isolation between them. Large

estimates of long-term Ne suggested that the control programme did not affect

the effective population size of the vector. Heterozygosity tests were also not

consistent with a recent bottleneck.

Natl Med J India  2002 Jul-Aug;15(4):199-201 

Passive malaria surveillance in a low endemic area of India: validation of a

clinical case definition.

Anand K, Kant S, Samantaray JC, Kapoor SK.

All India Institute of Medical Sciences, Ansari Nagar, New Delhi.

BACKGROUND: In India, 2.55 million cases of malaria were reported during 1997;

roughly one-third were due to Plasmodium falciparum. Malaria cases are

identified by passive and active surveillance and all patients with fever are

treated with chloroquine (10 mg/kg body weight). Since all fevers are not

malaria, this results in overtreatment and has a bearing in terms of the

parasites developing resistance. We aimed to test the validity of a clinical

algorithm for passive malaria surveillance by primary care doctors (fever with

pallor or splenomegaly) in a low endemic, Plasmodium vivax-predominant area of

Ballabgarh block in Faridabad District, Haryana. METHODS: Passive surveillance

was carried out at the general and paediatric outpatient departments (OPDs) of

Ballabgarh hospital. All persons with fever attending the OPD were examined for

the presence of fever, pallor and splenomegaly by the treating doctor. A blood

smear was prepared and examined in all these cases. RESULTS: A total of 3119

slides for malaria were made at Ballabgarh hospital but clinical details in the

requisition form were available for only 2616 patients who form the subjects of

this analysis. A total of 59 malaria cases (30 P. vivax cases and 29 P.

falciparum) were diagnosed. The presence of fever with pallor or splenomegaly

had a sensitivity of 28.8% (95% CI: 18.1-42.3); specificity of 88.6% (95% CI:

87.3-89.8), positive predictive value of 5.5% (95% CI: 3.3-8.8) and negative

predictive value of 98.2% (95% CI: 97.5-98.7). CONCLUSION: The algorithm did not

have sufficient sensitivity to detect malaria cases by passive surveillance.

Mol Biochem Parasitol  2002 Aug 28;123(2):85 

Functional characterization of the acyl carrier protein (PfACP) and

beta-ketoacyl ACP synthase III (PfKASIII) from Plasmodium falciparum.

Waters N, Kopydlowski K, Guszczynski T, Wei L, Sellers P, Ferlan J, Lee P, Li Z,

Woodard C, Shallom S, Gardner M, Prigge S.

Division of Experimental Therapeutics, Walter Reed Army Institute of Research,

20910-5100, Silver Spring, MD, USA

The genome of the malaria parasite, Plasmodium falciparum, appears to contain

the proteins necessary for a Type II dissociated fatty acid biosynthetic system.

Here we report the functional characterization of two proteins from this system.

Purified recombinant acyl carrier protein (ACP) and beta-ketoacyl-ACP synthase

III (KASIII) from P. falciparum are soluble and active in a truncated form.

Malarial ACP is activated by the addition of a 4'-phosphopantetheine prosthetic

group derived from coenzyme A, generating holo-PfACP. Holo-PfACP is an effective

substrate for the transacylase activity of PfKASIII, but substitution of a key

active site cysteine in PfKASIII to alanine or serine abolishes enzymatic

activity. During the schizont stage of parasite development, there is a

significant up-regulation of the mRNAs corresponding to these proteins,

indicating an important metabolic requirement for fatty acids during this stage.

Immunol Lett  2002 Nov 1;84(2):133 

Novel Plasmodium falciparum malaria vaccines: evidence-based searching

for variant surface antigens as candidates for vaccination against

pregnancy-associated malaria.

Staalsoe T, Jensen A, Theander T, Hviid L.

Centre for Medical Parasitology, Department of Infectious Diseases, Department

of Clinical Microbiology, Copenhagen University Hospital, M7641 Rigshospitalet,

Institute for Medical Microbiology and Immunology, University of Copenhagen,

Blegdamsvej 9, 2100, Copenhagen, Denmark

Malaria vaccine development has traditionally concentrated on careful molecular,

biochemical, and immunological characterisation of candidate antigens. In

contrast, evidence of the importance of identified antigens in immunity to human

infection and disease has generally been limited to statistically significant

co-variation with protection rather than on demonstration of causal

relationships. We have studied the relationship between variant surface

antigen-specific antibodies and clinical protection from Plasmodium falciparum

malaria in general, and from pregnancy-associated malaria (PAM) in particular,

to provide robust evidence of a causal link between the two in order to allow

efficient and evidence-based identification of candidate antigens for malaria

vaccine development.

Mol Cells  2002 Aug 31;14(1):158-62 

Intragenomic length variation of the ribosomal DNA intergenic spacer in a

malaria vector, Anopheles sinensis.

Whang IJ, Jung J, Park JK, Min GS, Kim W.

School of Biological Sciences, Seoul National University, Korea.

We determined the complete sequences of six size variants of intergenic spacer

(IGS) region from one individual of the malaria vector mosquito species,

Anopheles sinensis. All six size variants observed in this study show almost the

same basic primary structure in which three repeat regions (A, B, and C) are

interspersed by highly conserved nonrepeating sections. In contrast to the

well-ordered subrepeating patterns found in A and C, the repeat region B

displays extremely variable and complicated profiles in the number and

arrangement of subrepeat units among different size classes. It is apparent that

the prominent level of length difference in the repeat regions B and C is

responsible for the intragenomic length variations of the IGS molecule observed

in the present study. High level of sequence homology and regularly arranged

repeating pattern of 11 to 14 bp motif sequences harbored within the B repeat

region allow us to consider that these motif sequences may be associated with

their potential role as a recombination site. Compared to those previously

published in other mosquito species, the IGS of A. sinensis showed a very unique

structural format in subrepeat patterns of the IGS region. This result suggests

that the structure and sequence profiles of the IGS region would provide useful

information for the exploitation of a convenient molecular marker to identify

morphologically complicated species complex and to characterize the genetic

variation of population. This suggestion is far from being conclusive at

present, but a further genetic study will bring more compelling evidences for

this pending issue.

Med Vet Entomol  2002 Sep;16(3):329-34 

Presence of Anopheles culicifacies B in Cambodia established by the PCR-RFLP

assay developed for the identification of Anopheles minimus species A and C

and four related species.

Van Bortel W, Sochanta T, Harbach RE, Socheat D, Roelants P, Backeljau T,

Coosemans M.

Department of Parasitology, Prince Leopold Institute of Tropical Medicine,

Antwerpen, Belgium. Email: [email protected]

A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)

assay developed for identification of five species of the Anopheles minimus

Theobald group and a related mosquito species of the Myzomyia Series (Diptera:

Culicidae) was applied to morphologically identified adult female specimens

collected in Ratanakiri Province, north-eastern Cambodia. In addition to finding

An. aconitus Donitz, An. minimus species A and An. pampanai Buttiker & Beales,

some specimens showed a new restriction banding pattern. Siblings of specimens

that exhibited this new PCR-RFLP pattern were morphologically identified as An.

culicifacies James sensu lato. Based on nucleotide sequences of the ribonuclear

DNA internal transcribed spacer 2 region (ITS2) and the mitochondrial cytochrome

oxidase I gene (COI), these specimens were recognized as An. culicifacies

species B (sensu Green & Miles, 1980), the first confirmed record of the An.

culicifacies complex from Cambodia. This study shows that the PCR-RFLP assay can

detect species not included in the initial set-up and is capable of identifying

at least seven species of the Myzomyia Series, allowing better definition of

those malaria vector and non-vector anophelines in South-east Asia.

Med Vet Entomol  2002 Sep;16(3):321-7 

Extensive multiple test centre evaluation of the VecTest malaria antigen

panel assay.

Ryan JR, Dave K, Collins KM, Hochberg L, Sattabongkot J, Coleman RE, Dunton RF,

Bangs MJ, Mbogo CM, Cooper RD, Schoeler GB, Rubio-Palis Y, Magris M, Romer LI,

Padilla N, Quakyi IA, Bigoga J, Leke RG, Akinpelu O, Evans B, Walsey M,

Patterson P, Wirtz RA, Chan AS.

Department of Entomology, Walter Reed Army Institute of Research, Silver Spring,

MD 20910-7500, USA. Email: [email protected]

To determine which species and populations of Anopheles transmit malaria in any

given situation, immunological assays for malaria sporozoite antigen can replace

traditional microscopical examination of freshly dissected Anopheles. We

developed a wicking assay for use with mosquitoes that identifies the presence

or absence of specific peptide epitopes of circumsporozoite (CS) protein of

Plasmodium falciparum and two strains of Plasmodium vivax (variants 210 and

247). The resulting assay (VecTest Malaria) is a rapid, one-step procedure using

a 'dipstick' test strip capable of detecting and distinguishing between P.

falciparum and P. vivax infections in mosquitoes. The objective of the present

study was to test the efficacy, sensitivity, stability and field-user

acceptability of this wicking dipstick assay. In collaboration with 16 test

centres world-wide, we evaluated more than 40 000 units of this assay, comparing

it to the standard CS ELISA. The 'VecTest Malaria' was found to show 92%

sensitivity and 98.1% specificity, with 97.8% accuracy overall. In accelerated

storage tests, the dipsticks remained stable for > 15 weeks in dry conditions up

to 45 degrees C and in humid conditions up to 37 degrees C. Evidently, this

quick and easy dipstick test performs at an acceptable level of reliability and

offers practical advantages for field workers needing to make rapid surveys of

malaria vectors.

Med Vet Entomol  2002 Sep;16(3):316-20 

Effect of adult nutrition on the melanization immune response of the malaria

vector Anopheles stephensi.

Koella JC, Sorense FL.

Laboratoire de Parasitologie Evolutive, UMR 7103, Universite Pierre & Marie

Curie, Paris, France. Email: [email protected]

Two dietary resources - blood and sugar - were assessed for effects on the

melanization immune response of the mosquito Anopheles stephensi Liston

(Diptera: Culicidae) towards inoculated Sephadex beads (negatively charged

C-25). This melanization is conferred by genetic factors capable of making the

mosquito refractory to malaria parasites. If An. stephensi females had obtained

a bloodmeal one day before inoculation with a bead, the efficacy of their immune

response increased with the concentration of sugar ingested. At the highest

sugar concentration (6%) tested, 38% of the mosquitoes completely melanized

their bead, whereas at the lowest sugar concentration (2%), none of the

mosquitoes were able to melanize their bead completely. Among mosquitoes not

having a bloodmeal, the immuno-competence was low (c. 9% of the mosquitoes

completely melanized their bead) and independent of sugar concentration. The

observed interaction between these two resources indicates that both resources

are required for the Anopheles female to develop an effective melanization

immune response.

Med Vet Entomol  2002 Sep;16(3):253-65 

Molecular and morphological studies on the Anopheles minimus group of

mosquitoes in southern China: taxonomic review, distribution and malaria

vector status.

Chen B, Harbach RE, Butlin RK.

School of Biology, The University of Leeds, UK. Email: [email protected]

Mosquitoes of the Anopheles minimus group (Diptera: Culicidae) from nine

Provinces of southern China were identified morphologically and by molecular

characterization, using single-strand conformation polymorphisms (SSCPs) and

sequence data for the D3 region of the 28S ribosomal DNA and the mitochondrial

COII locus. Species A and C (sensu Green et al., 1990) of the An. minimus

complex were found to be sympatric in Yunnan Province. Species A occurs eastward

from Yunnan through southern Guangxi, Hainan, Guangdong and Taiwan Provinces,

whereas species C occurs northward to northern Guangxi, Guizhou and Sichuan

Provinces. Morphological and molecular evidence (based on specimens from the

field and four isofemale lines) shows that An. minimus forms A and B (sensu Yu &

Li, 1984) are morphological variants of species A, which is accepted as An.

minimus Theobald sensu stricto (type-locality: Pokfulam, Hong Kong). The

so-called subspecies x of An. minimus (sensu Baba, 1950) is reinterpreted as An.

aconitus Donitz. The distribution and vector status of members of the An.

minimus group are discussed in relation to the historical and current

transmission of malaria and filariasis in China. Both An. minimus A and C have

been implicated as widespread vectors of malaria, whereas only species A has

been found in Hainan, where An. minimus s.l. was a vector of Bancroftian

filariasis. The presence of An. aconitus in Hainan and Yunnan Provinces is

confirmed, but the occurrence of An. varuna Iyengar and An. fluviatilis James,

which were previously recorded in China, could not be verified.

Lancet  2002 Aug 24;360(9333):610 

Immunity to malaria after administration of ultra-low doses of red cells

infected with Plasmodium falciparum.

Pombo D, Lawrence G, Hirunpetcharat C, Rzepczyk C, Bryden M, Cloonan N, Anderson K, Mahakunkijcharoen Y, Martin L, Wilson D, Elliott S, Elliott S, Eisen D,

Weinberg J, Saul A, Good M.

Queensland Institute of Medical Research, Australian Centre for International

and Tropical Health and Nutrition, and Cooperative Research Centre for Vaccine

Technology, PO Royal Brisbane Hospital, Australia

Background The ability of T cells, acting independently of antibodies, to

control malaria parasite growth in people has not been defined. If such was

shown to be effective, an additional vaccine strategy could be pursued. Our aim

was to ascertain whether or not development of cell-mediated immunity to

Plasmodium falciparum blood-stage infection could be induced in human beings by

exposure to malaria parasites in very low density.Methods We enrolled five

volunteers from the staff at our research institute who had never had malaria.

We used a cryopreserved inoculum of red cells infected with P falciparum strain

3D7 to give them repeated subclinical infections of malaria that we then cured

early with drugs, to induce cell-mediated immune responses. We tested for

development of immunity by measurement of parasite concentrations in the blood

of volunteers by PCR of the multicopy gene STEVOR and by following up the

volunteers clinically, and by measuring antibody and cellular immune responses

to the parasite.Findings After challenge and a extended period without drug

cure, volunteers were protected against malaria as indicated by absence of

parasites or parasite DNA in the blood, and absence of clinical symptoms.

Immunity was characterised by absence of detectable antibodies that bind the

parasite or infected red cells, but by the presence of a proliferative T-cell

response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of

interferon gamma but not interleukin 4 or interleukin 10, induction of high

concentrations of nitric oxide synthase activity in peripheral blood mononuclear

cells, and a drop in the number of peripheral natural killer T

cells.Interpretation People can be protected against the erythrocytic stage of

malaria by a strong cell-mediated immune response, in the absence of detectable

parasite-specific antibodies, suggesting an additional strategy for development

of a malaria vaccine

Arch Med Res  2002 Jul-Aug;33(4):416 

The future outlook of antimalarial drugs and recent work on the treatment

of malaria.

Wilairatana P, Krudsood S, Treeprasertsuk S, Chalermrut K, Looareesuwan S.

Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol

University, Bangkok, Thailand

With the emergence of multidrug-resistant falciparum malaria, new drugs and

drugs in combination are urgently needed.New antimalarial drugs investigated at

the Hospital for Tropical Diseases of the Faculty of Tropical Medicine at

Mahidol University in Bangkok, Thailand in recent years for treatment of

uncomplicated and severe falciparum malaria are as follows: atovaquone, and

artemisinin derivatives (artesunate, artemether, arteether, and

dihydroartemisinin) combined with other antimalarials.Malarone((R)), artemisinin

derivatives combined with lumefantrine or doxycycline, and mefloquine combined

with tetracycline or doxycycline have been evaluated with improvement of the

cure rate in uncomplicated malaria. Artemisinin derivatives intravenously or

intrarectally combined with mefloquine may be alternatives to intravenous

quinine for treatment of severe malaria.In Thailand, drug treatment for

uncomplicated malaria consists of the combinations or artesunate plus mefloquine

or artemether plus lumefantrine or quinine plus tetracycline. In treatment of

severe malaria, antimalarial drugs of choice are intravenous quinine or

artemisinin derivatives.

J Infect Dis  2002 Oct 1;186(7):1007-12 

Profound Bias in Interferon-gamma and Interleukin-6 Allele Frequencies in

Western Kenya, Where Severe Malarial Anemia Is Common in Children.

Gourley IS, Kurtis JD, Kamoun M, Amon JJ, Duffy PE.

Department of Pathology and Laboratory Medicine, Hospital of the University of

Pennsylvania, Philadelphia, Pennsylvania, USA.

The intensity of malaria transmission is related to the pattern of malarial

disease observed in different regions, but populations may also differ in their

underlying predispositions to severe malarial anemia or cerebral malaria. In

western Kenya, where severe malarial anemia is much more common than cerebral

malaria, the distributions of tumor necrosis factor (TNF)-alpha, interleukin

(IL)-10, transforming growth factor (TGF)-beta, IL-6, and interferon (IFN)-gamma

alleles were examined in a cohort of young men. The cohort displayed a marked

bias toward genotypes associated with low expression of IFN-gamma and IL-6,

cytokines that, at high levels, have been implicated in malarial anemia and poor

malaria outcomes. By contrast, the frequency of the TNF-alpha -238A allele,

which has been associated with severe malarial anemia, was found to be similar

to the frequency previously reported in comparison populations in Africa and

elsewhere. IFN-gamma and IL-6 genotypes may play roles in the development of

severe malaria and could contribute to the relative frequency of severe malarial

anemia or cerebral malaria in exposed populations.

J Infect Dis  2002 Oct 1;186(7):999-1006 

Origin and Dissemination of Plasmodium falciparum Drug-Resistance Mutations

in South America.

Cortese JF, Caraballo A, Contreras CE, Plowe CV.

Malaria Section, Center for Vaccine Development, University of Maryland School

of Medicine, Baltimore, Maryland, USA.

Multidrug resistance is a major obstacle to the control of Plasmodium falciparum

malaria, and its origins and modes of dissemination are imperfectly understood.

In this study, haplotyping and microsatellite analysis of malaria from 5 regions

of the South American Amazon support the conclusion that the parasite mutations

conferring mid- and high-level resistance to the antifolate combination

sulfadoxine-pyrimethamine have a common origin. Parasites harboring these

mutations are also found to share drug-resistance alleles that confer a unique

chloroquine resistance phenotype and to be similar at loci not linked to drug

resistance, although not genetically identical. Since the 1980s,

multidrug-resistant P. falciparum has spread in a north-northwest manner across

the continent, from an origin likely in the lower Amazon. This study highlights

the importance of continent-wide malaria-control policies and suggests that the

containment of resistance to the next generation of therapies may be feasible.