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Showing papers on "Malaria published in 1997"


Journal ArticleDOI
TL;DR: A recombinant vaccine based on fusion of the circumsporozoite protein and HBsAg plus a potent adjuvant can protect against experimental challenge with P. falciparum malaria.
Abstract: Background The candidate vaccines against malaria are poorly immunogenic and thus have been ineffective in preventing infection. We developed a vaccine based on the circumsporozoite protein of Plasmodium falciparum that incorporates adjuvants selected to enhance the immune response. Methods The antigen consists of a hybrid in which the circumsporozoite protein fused to hepatitis B surface antigen (HBsAg) is expressed together with unfused HBsAg. We evaluated three formulations of this antigen in an unblinded trial in 46 subjects who had never been exposed to malaria. Results Two of the vaccine formulations were highly immunogenic. Four subjects had adverse systemic reactions that may have resulted from the intensity of the immune response after the second dose, which led us to reduce the third dose. Twenty-two vaccinated subjects and six unimmunized controls underwent a challenge consisting of bites from mosquitoes infected with P. falciparum. Malaria developed in all six control subjects, seven of eight ...

933 citations


Journal ArticleDOI
TL;DR: Control of dengue at the present time is dependent on control of the principal vector mosquito, A. aegypti, and indigenous transmission in the continental United States remains a public health concern.

895 citations


Journal ArticleDOI
TL;DR: It is proposed that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate, and measures which reduce parasite transmission, and thus immunity, may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity.

705 citations


Journal ArticleDOI
TL;DR: Iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas is supported, and malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity.

384 citations


Journal ArticleDOI
TL;DR: This clinical study demonstrates that a malaria resistance gene protects against disease caused by infections other than malaria, and the mechanism of the remarkable protective effect of alpha-thalassemia against severe childhood disease remains unclear.
Abstract: In the South West Pacific region, the striking geographical correlation between the frequency of α+-thalassemia and the endemicity of Plasmodium falciparum suggests that this hemoglobinopathy provides a selective advantage against malaria. In Vanuatu, paradoxically, α+-thalassemia increases the incidence of contracting mild malaria in the first 2 years of life, but severe disease was too uncommon to assess adequately. Therefore, we undertook a prospective case-control study of children with severe malaria on the north coast of Papua New Guinea, where malaria transmission is intense and α+-thalassemia affects more than 90% of the population. Compared with normal children, the risk of having severe malaria was 0.40 (95% confidence interval 0.22–0.74) in α+-thalassemia homozygotes and 0.66 (0.37–1.20) in heterozygotes. Unexpectedly, the risk of hospital admission with infections other than malaria also was reduced to a similar degree in homozygous (0.36; 95% confidence interval 0.22–0.60) and heterozygous (0.63; 0.38–1.07) children. This clinical study demonstrates that a malaria resistance gene protects against disease caused by infections other than malaria. The mechanism of the remarkable protective effect of α+-thalassemia against severe childhood disease remains unclear but must encompass the clear interaction between this hemoglobinopathy and both malarial and nonmalarial infections.

313 citations


Journal ArticleDOI
TL;DR: The predisposing factors, clinical presentation, and outcome of severe malaria in a Karen community living on the western border of Thailand were studied over a period of 2 years, suggesting that P. vivax may attenuate the severity of P. falciparum malaria.
Abstract: The predisposing factors, clinical presentation, and outcome of severe malaria in a Karen community living on the western border of Thailand were studied over a period of 2 years. This was an area of low malaria transmission (approximately one infection per person per year), where asymptomatic malaria is unusual. In a population of 4728 persons, who had good access to facilities for malaria diagnosis and treatment, there were 2573 cases of vivax malaria, none of whom died, and there were 5776 cases of falciparum malaria, 303 (5%) of whom had severe malaria and 11 (0.2%) of whom died-a case fatality rate of 1.9 per 1000 (95% confidence interval [CI] 1.0-3.3). The risks of developing severe malaria and dying declined steadily with age. The clinical features of severe malaria differed between children and adults. Anaemia was more common in children under 5 years old than in older children and adults, whereas the incidence of cerebral involvement increased with age. Severe malaria was 3 times (95% CI 1.4-6.2) more common in pregnant than in non-pregnant women, but was 4.2 times (95% CI 2.3-7.9) less common in patients with mixed Plasmodium falciparum and P. vivax infections than in those with P. falciparum alone, suggesting that P. vivax may attenuate the severity of P. falciparum malaria.

304 citations


Journal ArticleDOI
TL;DR: These findings vis-à-vis the present endemic areas indicate that the increase in the epidemic potential of malaria and dengue transmission may be estimated at 12–27% and 31–47%, respectively, while in contrast, schistosomiasis transmission potential may be expected to exhibit a 11–17% decrease.
Abstract: Global assessment of the potential impacts of anthropogenically-induced climate change on vector-borne diseases suggests an increase in extent of the geographical areas susceptible to transmission of malarial Plasmodium parasites, dengue Flavivirus and Schistosoma worms. The transmission potential of the three associated vector-borne diseases studied is highly sensitive to climate changes on the periphery of the currently endemic areas and at higher altitudes within such areas. Our findings vis-a-vis the present endemic areas indicate that the increase in the epidemic potential of malaria and dengue transmission may be estimated at 12–27% and 31–47%, respectively, while in contrast, schistosomiasis transmission potential may be expected to exhibit a 11–17% decrease.

273 citations


Journal ArticleDOI
TL;DR: Though the human dwellings in the study communities conferred no real protection against mosquitoes, bednet usage was low while residents combatted the nuisance of mosquitoes with insecticide sprays, burning of coils and herbs, which they largely considered as temporary measures.
Abstract: A research infrastructure was established in two ecological zones in southern Ghana to study the variables of malaria transmission and provide information to support the country's Malaria Action Plan (MAP) launched in 1992. Residents' beliefs and practices about causes, recognition, treatment and prevention of malaria were explored in two ecological zones in southern Ghana using epidemiological and social research methods. In both communities females constituted more than 80% of caretakers of children 1-9 years and the illiteracy rate was high. Fever and malaria, which are locally called Asra or Atridi, were found to represent the same thing and are used interchangeably. Caretakers were well informed about the major symptoms of malaria, which correspond to the current clinical case definition of malaria. Knowledge about malaria transmission is, however, shrouded in many misconceptions. Though the human dwellings in the study communities conferred no real protection against mosquitoes, bednet usage was low while residents combatted the nuisance of mosquitoes with insecticide sprays, burning of coils and herbs, which they largely considered as temporary measures. Home treatment of malaria combining herbs and over-the-counter drugs and inadequate doses of chloroquine was widespread. There is a need for a strong educational component to be incorporated into the MAP to correct misconceptions about malaria transmission, appropriate treatment and protection of households. Malaria control policies should recognize the role of home treatment and drug shops in the management of malaria and incorporate them into existing control strategies.

256 citations


Journal ArticleDOI
TL;DR: Genotypes at this locus from samples from a case-control study indicated an association of the polymorphism with the severity of clinical malaria such that individuals homozygous for the mutation have increased susceptibility to cerebral malaria with a relative risk of two.
Abstract: The malarial parasite Plasmodium falciparum has acted as a potent selective force on the human genome. The particular virulence of this organism is thought to be due to the adherence of parasitised red blood cells to small vessel endothelium through several receptors, including CD36, thrombospondin and intercellular adhesion molecule 1 (ICAM-1, CD54), and parasite isolates differ in their ability to bind to each. Immunohistochemical studies have implicated ICAM-1 as of potential importance in the pathogenesis of cerebral malaria, leading us to reason that if any single receptor were involved in the development of cerebral malaria, then in view of the high mortality of that complication, natural selection should have produced variants with reduced binding capacity. We therefore sequenced the N-terminal domain of ICAM-1 from a number of Africans and discovered a single mutation present at high frequency. Genotypes at this locus from samples from a case-control study indicated an association of the polymorphism with the severity of clinical malaria such that individuals homozygous for the mutation have increased susceptibility to cerebral malaria with a relative risk of two. These counterintuitive results have implications for the mechanism of malaria pathogenesis, resistance to other infectious agents and transplantation immunology.

223 citations


Journal ArticleDOI
03 Dec 1997-JAMA
TL;DR: It is demonstrated that malaria increases by an average of about one third in the year following a Nino event; change in malaria risk can be predicted from Pacific SSTs in the previous year; therefore, the occurrence of an El Niño event may help predict malaria epidemics in this part of South America.
Abstract: Context. —Malaria has been increasing globally, and epidemics tend to occur when weather conditions favor this vector-borne disease. Long-term meteorologic forecasting using El Nino Southern Oscillation (ENSO) may assist in anticipating epidemics and targeting scarce resources. Objective. —To determine whether malaria epidemics in Venezuela are related to ENSO and rainfall and to determine whether such a relationship could be used to predict outbreaks. Design. —Retrospective analysis of national malaria morbidity (1975-1995) and mortality (1910-1935) data in the coastal zone and interior of Venezuela in relation to El Nino events and rainfall. Main Outcome Measure. —Correlation between malaria mortality and morbidity and sea surface temperatures (SSTs) in the Eastern Tropical Pacific, a parameter of ENSO. Results. —Malaria mortality and morbidity have increased by an average of 36.5% (95% confidence interval, 3.7%-69.3%;P=.004) in years following recognized El Nino events. A moderate correlation was found between Pacific tropical SST during a Nino event and malaria 1 year later (r=0.50,P Conclusions. —Historic and recent data from Venezuela demonstrate that malaria increases by an average of about one third in the year following a Nino event; change in malaria risk can be predicted from Pacific SSTs in the previous year. Therefore, the occurrence of an El Nino event may help predict malaria epidemics in this part of South America.

206 citations


Journal ArticleDOI
TL;DR: The cost of controlling malaria is lower than lost earnings or the value of output, compared with the average five days loss of output for the patient due to malaria morbidity and caretaking.

Journal ArticleDOI
TL;DR: Results show that immunization with SPf66 modulates the course of naturally occurring infections, as reflected by reduced MOIs, and provide further evidence that premunition from concurrent infections is important in immunity against clinical malaria.
Abstract: In the first phase III efficacy trial of the malaria vaccine SPf66 in Africa, MOIs in SPf66- and placebo-vaccinated children were analyzed by polymerase chain reaction-restriction fragment length polymorphism of the Plasmodium falciparum merozoite surface antigen 2 (MSA2). MOIs were significantly reduced in asymptomatic vaccine recipients compared with those in asymptomatic placebo recipients; however, no differences were observed among symptomatic children in the vaccine and control groups. These results show that immunization with SPf66 modulates the course of naturally occurring infections, as reflected by reduced MOIs. In placebo recipients, however, there was a significant negative correlation between numbers of infecting genotypes, as identified by MSA2, and morbidity. Asymptomatic placebo recipients had an average of 5 concurrent infections, whereas children with clinical cases had an average of 3.4 infections. These data provide further evidence that premunition from concurrent infections is important in immunity against clinical malaria. No such effect of multiple infections was found in the vaccinated group.

Journal ArticleDOI
TL;DR: Plasmodium falciparum malaria does not present with a characteristic clinical or haematological picture, but is a major cause of the morbidity and mortality in children with severe anaemia who live on the Kenyan coast, a malaria endemic area.
Abstract: Severe anaemia is an important cause of morbidity and mortality in African children, but the causes, particularly falciparum malaria, are difficult to determine. We assessed the contribution of falciparum malaria to anaemia in Kenyan children by clinical examination and measurement of parasitaemia and haemoglobin (Hb) concentration in 559 children in the community and in 2412 children admitted to Kilifi district hospital during a 2-year period. We also attempted to characterize severe malarial anaemia by examining the causes and pathophysiology of anaemia in 101 children admitted with Hb concentration < or = 50 g/l during a 1-year period. Plasmodium falciparum infection was associated with reduced Hb concentration in children in the community and in those admitted to hospital irrespective of diagnosis. Falciparum malaria was the primary cause in 46 cases (46%) of severe anaemia admitted to hospital. There was no difference in the frequency of haemolysis or dyserythropoiesis in the children with malarial anaemia and those with anaemia from other causes, such as iron deficiency or sickle cell disease. The mortality rate in the children with severe malarial anaemia was 8.6% compared with 3.6% in children with severe anaemia due to other causes. Falciparum malaria does not present with a characteristic clinical or haematological picture, but is a major cause of the morbidity and mortality in children with severe anaemia who live on the Kenyan coast, a malaria endemic area.

Book
22 Dec 1997
TL;DR: Watt as discussed by the authors investigates the relationship between violent environmental changes and disease, and between disease and society, both in the material sphere and in the minds and spirit of rulers and those who where ruled.
Abstract: A wide ranging study of the great epidemic scourges of humanity - plague, leprosy. smallpox, syphilis, cholera and yellow fever/malaria - over the last six centuries. Sheldon Watts, applies his perspective to the study of global disease, exploring the connections between the movement of epidemics and the manifestations of imperial power in the Americas, Asia, Africa and in European homelands. He shows how the perceptions of whom a disease targeted changed over time and effected various political and medical responses. He argues that not only did western medicine fail to cure the diseases that its own expansion engendered, but that imperial medicine was in fact an agent and tool of empire. Watts examines the relationship between the pre-modern medical profession and such epidemic disasters as the plague in western Europe and the Middle East; leprosy in the medieval west and in the 19th-century tropical world; the spread of smallpox to the new world in the age of exploration; syphilis and nonsexual diseases in Europe's connection with Asia; cholera in India during British rule; and malaria in the Atlantic basin during the eras of slavery and social Darwinism. He investigates in detail the relation between violent environmental changes and disease, and between disease and society, both in the material sphere and in the minds and spirit of rulers and those who where ruled. This book is an account of the way diseases - arising through chance, through reckless environmental change engineered by man, or through a combination of each - were interpreted in western Europe and in the colonized world.

Journal ArticleDOI
18 Apr 1997-Science
TL;DR: Genetic mapping revealed one major and two minor quantitative trait loci for this encapsulation reaction in Anopheles gambiae that can encapsulate and kill the malaria parasites within a melanin-rich capsule in the mosquito midgut.
Abstract: The severity of the malaria pandemic in the tropics is aggravated by the ongoing spread of parasite resistance to antimalarial drugs and mosquito resistance to insecticides. A strain of Anopheles gambiae, normally a major vector for human malaria in Africa, can encapsulate and kill the malaria parasites within a melanin-rich capsule in the mosquito midgut. Genetic mapping revealed one major and two minor quantitative trait loci (QTLs) for this encapsulation reaction. Understanding such antiparasite mechanisms in mosquitoes may lead to new strategies for malaria control.

Journal ArticleDOI
TL;DR: Data show that even in areas of intense and perennial transmission, there exist large longitudinal variations and strong heterogeneity in entomologic parameters of malaria transmission, and it is important to take these into account for the study of the variations in clinical and biological parameters of human malaria.
Abstract: We conducted a three-year entomologic study in Dielmo, a village of 250 inhabitants in a holoendemic area for malaria in Senegal. Anophelines were captured on human bait and by pyrethrum spray collections. The mosquitoes belonging to the Anopheles gambiae complex were identified using the polymerase chain reaction. Malaria vectors captured were An. funestus, An. arabiensis, and An. gambiae. Anopheles funestus was the most abundant mosquito captured the first year, An. arabiensis in the following years. The annual entomologic inoculation rates calculated by enzyme-linked immunosorbent assay were 238, 89, and 150 for the first, second, and third years, respectively. Each year there was a peak of transmission at the end of the rainy season, but transmission occurred year round. The heterogeneity of transmission was found at four different levels: 1) the relative vector proportion according to the place and method of capture, 2) the human biting rate and relative proportion of vectors by month and year, 3) the infection rate of each vector by year, and 4) the number of infected bites for all vectors, and for each species, for the year. Our data show that even in areas of intense and perennial transmission, there exist large longitudinal variations and strong heterogeneity in entomologic parameters of malaria transmission. It is important to take these into account for the study of the variations in clinical and biological parameters of human malaria, and to evaluate this relationship, a very thorough investigation of transmission is necessary.

Journal ArticleDOI
TL;DR: Pfs28 and Pfs25 are immunogenic, have limited antigenic diversity, and are structurally similar and genetically linked on chromosome 10, and may prove a useful addition to PFS25 in an effective transmission-blocking vaccine.
Abstract: Antibodies to Pfs28 block Plasmodium falciparum transmission and when combined with antibodies to Pfs25 provide synergy in blocking transmission. Pfs28 and Pfs25 are immunogenic, have limited antigenic diversity, and are structurally similar and genetically linked on chromosome 10. Pfs28 may prove a useful addition to Pfs25 in an effective transmission-blocking vaccine.

Journal ArticleDOI
TL;DR: Malarial infection of the placenta seems to result in a higher susceptibility of infants to the parasite, and a better understanding of the involved mechanisms may have important implications for the development of malaria control strategies.
Abstract: In areas endemic for malaria, pregnant women frequently present with a placenta that has been parasitized by Plasmodium falciparum, an infection associated with a reduction in the birth weight of the offspring. However, the impact of placental infection on malaria-related morbidity during the infant's first years of life has not been investigated. Between 1993 and 1995, 197 children in southern Cameroon were followed weekly clinically and monthly parasitologically. The dates of first positive blood smear and the evolution of the parasite prevalence rates were compared between infants born to mothers presenting with (n = 42) and without (n = 155) P. falciparum infection of the placenta. Infants born to placenta-infected mothers were more likely to develop a malaria infection between 4 and 6 months of age; then the difference progressively disappeared. Similarly, parasite prevalence rates were higher in placenta-infected infants from 5 to 8 months of age. Thus, malarial infection of the placenta seems to result in a higher susceptibility of infants to the parasite. This was not related to maternally transmitted antibodies, as specific antibody levels were similar in both groups of infants. A better understanding of the involved mechanisms may have important implications for the development of malaria control strategies.

Journal ArticleDOI
TL;DR: Mannitol controlled the ICP in children with intermediate intracranial hypertension, but it did not prevent the development of intractable intrac cranial hypertension in childrenWith cerebral malaria, severe intrusion hypertension is a feature of Kenyan children with cerebral malaria and severe intrac Cranial hypertension is associated with a poor outcome.
Abstract: The causes of death and neurological sequelae in African children with cerebral malaria are obscure. Intracranial pressure (ICP) was monitored and cerebral perfusion pressure (CPP) calculated in 23 Kenyan children with cerebral malaria. Four children had severe intracranial hypertension (ICP >40 mm Hg, CPP 20 mm Hg, CPP

Journal ArticleDOI
TL;DR: There has been no decline in the efficacy of the 3 d artesunate plus mefloquine regimen since it was introduced in 1992 and this regimen is safe, well tolerated, and highly effective in the treatment of multi-drug resistant falciparum malaria.
Abstract: On the western border of Thailand, in an area endemic for multi-drug resistant Plasmodium falciparum malaria, therapeutic responses were assessed in 1967 patients with uncomplicated falciparum malaria treated with 3 d of artesunate (total dose 12 mg/kg) plus mefloquine (total dose 25 mg/kg). The regimen was well tolerated and resulted in a rapid clinical response; within 48 h, 96% of patients were aparasitaemic and 94% were afebrile. After correcting for reinfections, the cure rate by day 42 was 89% (95% confidence interval [95% CI] 87-91%). Three independent factors were found to predict recrudescence: age 40,000/microL (AHR = 1.6, 95%, CI 1.2-2.2), and pure P. falciparum infections (AHR = 1.8, 95% CI 1.3-2.7). These 3 factors combined accounted for 62% of all treatment failures. Patients who received mefloquine on admission with a high admission parasitaemia (> 40,000/microL) had a three-fold (95% CI 1.3-7) risk of subsequent recrudescence compared with those who received their mefloquine on the second or third day (P = 0.01). There has been no decline in the efficacy of the 3 d artesunate plus mefloquine regimen since it was introduced in 1992. This regimen is safe, well tolerated, and highly effective in the treatment of multi-drug resistant falciparum malaria.

Journal ArticleDOI
TL;DR: The recent actions to ban DDT, the health costs of such a ban, perspectives on DDT use in agriculture versus malaria control, and costs versus benefits of DDT and alternative insecticides are discussed.
Abstract: Malaria is reemerging in endemic-disease countries of South America. We examined the rate of real growth in annual parasite indexes (API) by adjusting APIs for all years to the annual blood examination rate of 1965 for each country. The standardized APIs calculated for Brazil, Peru, Guyana, and for 18 other malariaendemic countries of the Americas presented a consistent pattern of low rates up through the late 1970s, followed by geometric growth in malaria incidence in subsequent years. True growth in malaria incidence corresponds temporally with changes in global strategies for malaria control. Underlying the concordance of these events is a causal link between decreased spraying of homes with DDT and increased malaria; two regression models defining this link showed statistically significant negative relationships between APIs and house-spray rates. Separate analyses of data from 1993 to 1995 showed that countries that have recently discontinued their spray programs are reporting large increases in malaria incidence. Ecuador, which has increased use of DDT since 1993, is the only country reporting a large reduction (61%) in malaria rates since 1993. DDT use for malaria control and application of the Global Malaria Control Strategy to the Americas should be subjects of urgent national and international debate. We discuss the recent actions to ban DDT, the health costs of such a ban, perspectives on DDT use in agriculture versus malaria control, and costs versus benefits of DDT and alternative insecticides.

Journal ArticleDOI
TL;DR: The article by Warhurst et al' raised interesting practical issues regarding the laboratory diagnosis of malaria, which are often missed by many inexperienced parasitologists and technical staff and needs careful consideration before making a diagnosis.
Abstract: The article by Warhurst et al' raised interesting practical issues regarding the laboratory diagnosis of malaria, which are often missed by many inexperienced parasitologists and technical staff. Aspects of storage in relation to time, type of anticoagulant, and subsequent interpretation certainly needs careful consideration before making a diagnosis. Further to Warhurst et al's article, we briefly discuss our experience of the detection of malaria parasite in routine diagnosis. In an ongoing prospective study, we are evaluating the sensitivity of acridine orange staining compared to techniques such as quantitative buffy coat, Giemsa stain, Zenner stain, Field's stain, and HRP-II antigen detection. Diagnosis of malaria using acridine orange staining has been performed since initial studies reported lower sensitivity and specificity than Giemsa.2 Recently, however, acridine orange staining using interference filter in a light microscope has shown four times more sensitivity than the conventional Giemsa stain.' All of the test smears (244) and control smears (50) in our study have been examined by both acridine orange and Giemsa staining. All slides were coded in a blind manner and were examined separately by two groups of observers, and confirmed by a senior parasitologist. All the developmental stages of parasite were easily identified at a magnification of x900 under special oil immersion lens (Paralens, Becton Dickinson, USA). The time required to find the first parasite in these smears ranged from five seconds to five minutes. We also evaluated acridine orange and Giemsa in relation to stages and density of parasite found. Parasite count was 1.5 times higher using acridine orange than using Giemsa. In only two test samples asexual stages of Plasmodium falciparum were found using acridine orange staining with parasite count less than 1 00/pl ofblood that could not be detected by Giemsa. Acridine orange staining is also cheaper and faster than quantitative buffy coat examination. Morphological findings were much clearer using acridine orange compared with quantitative buffy coat examination (as the concentration of parasite is very high in buffy layer). We strongly support the continued use of Giemsa stain in laboratory diagnosis of malaria; however, we find acridine orange staining more reliable and consistent. It can show positivity with much lower parasitaemia compared with other stains. One question which we are not yet able to answer is how long acridine orange stained slides can be kept for referral or review.

Journal ArticleDOI
TL;DR: Several testable hypotheses are proposed that might explain why natural selection has not favoured variants producing more transmission stages of malaria parasites.

Journal ArticleDOI
TL;DR: The experience shows that a low-cost, community-based intervention aimed at providing children with prompt and adequate treatment of presumptive episodes of clinical malaria is feasible, and suggests that it may lead to a reduction in the morbidity from severe malaria.
Abstract: A community-based programme to ensure prompt and adequate treatment of presumptive episodes of clinical malaria in children has been established in a rural province of Burkina Faso. The implementation strategy was based on training a core group of mothers in every village and supplying community health workers with essential antimalarial drugs specially packed in age-specific bags containing a full course of treatment. Drugs were sold under a cost-recovery scheme. The programme was run in 1994 by the national malaria control centre (CNLP), and in 1995 it was developed to the provincial health team (PHT). Knowledge and awareness of malaria increased with the intervention. Drug consumption by age group was compatible with the distribution of disease, and no major problem of misuse emerged. The actual implementation costs of the intervention were US$ 0.06 per child living in the province. An evaluation of the impact of the intervention on the severity of malaria, using routine data from the health information system and taking as an indicator the proportion of malaria cases which were recorded as severe in health centres, was performed. In 1994, when the intervention was implemented on a provincial scale by CNLP, this proportion was lower than the average of the 4 preceding years (3.7% vs. 4.9%). In 1995, when the programme was implemented by the PHT, the proportion of severe cases was lower in health centres achieving a programme coverage of > or = 50% in their catchment area compared with the others (4.2% vs. 6.1%). Our experience shows that a low-cost, community-based intervention aimed at providing children with prompt and adequate treatment of presumptive episodes of clinical malaria is feasible, and suggests that it may lead to a reduction in the morbidity from severe malaria.

Journal ArticleDOI
TL;DR: It is suggested that it is feasible to directly measure the anti-parasite efficacy of a prototype malaria vaccine in human volunteers without subjecting them to the risk of disease.
Abstract: Several prototype vaccines against the asexual blood stage of malaria are undergoing preclinical and phase I testing. Although these vaccines have been chosen for their ability to elicit an anti-parasite response, no practical and sensitive clinical trial procedure has been available for measuring their impact on parasite growth. We describe a system that allows parasite growth rates to be measured in volunteers through the incubation period. Two necessary elements of this system are developed: suitable blood-stage Plasmodium falciparum inocula, and a highly sensitive and quantitative assay to measure parasite growth during the incubation period. We infected five nonimmune volunteers with an inoculum as small as 300 parasites and demonstrated that the resultant in vivo asexual parasite growth rates were reproducible at 12-15-fold per cycle. The system allowed the infection to be followed for eight days before treatment without symptoms developing. These findings suggest that it is feasible to directly measure the anti-parasite efficacy of a prototype malaria vaccine in human volunteers without subjecting them to the risk of disease.

Journal Article
TL;DR: In this paper, Mefloquine and doxycycline are the two drugs recommended for prophylaxis of malaria for visitors to areas where Plasmodium falciparum is resistant to chloroquine.
Abstract: Background: Mefloquine and doxycycline are the two drugs recommended for prophylaxis of malaria for visitors to areas where Plasmodium falciparum is resistant to chloroquine. Objective: To compare ...

Journal ArticleDOI
TL;DR: Predicting malaria risk associated with ENSO and related climate variables may also serve as a short‐term analogue for predicting longer‐term effects posed by global climate change.
Abstract: The interannual variation in malaria cases in Colombia between 1960 and 1992 shows a close association with a periodic climatic phenomenon known as El Nino Southern Oscillation (ENSO). Compared with other years, malaria cases increased by 17.3% during a Nino year and by 35.1% in the post-Nino year. The annual total number of malaria cases is also strongly correlated (r = 0.62, P < 0.001) with sea surface temperature (SST) anomalies in the eastern equatorial Pacific, a principal parameter of ENSO. The strong relation between malaria and ENSO in Colombia can be used to predict high and low-risk years for malaria with sufficient time to mobilize resources to reduce the impact of epidemics. In view of the current El Nino conditions, we anticipate an increase in malaria cases in Colombia in 1998. Further studies to elucidate the mechanisms which underlie the association are required. As Colombia has a wide range of climatic conditions, regional studies relating climate and vector ecology to malaria incidence may further improve an ENSO-based early warning system. Predicting malaria risk associated with ENSO and related climate variables may also serve as a short-term analogue for predicting longer-term effects posed by global climate change.

Journal ArticleDOI
TL;DR: The high mean number of clones in Michenga is associated with a very high frequency of out-crossing compared with that estimated in Asar, where malaria is mesoendemic and transmission is markedly seasonal.
Abstract: We have compared allelic polymorphism of two merozoite surface protein genes, MSP-1 and MSP-2, of Plasmodium falciparum and the parasite load in infected individuals in two villages in east Africa. In Michenga village in Tanzania, malaria is holoendemic and transmission is perennial; in Asar village in Sudan, malaria is mesoendemic and transmission is markedly seasonal. The numbers of alleles of both genes were found to be much greater in Michenga than in Asar. More parasite clones exhibiting higher allelic polymorphisms of the genes studied were carried by infected inhabitants in Michenga than those in Asar. The high mean number of clones in Michenga is associated with a very high frequency of out-crossing compared with that estimated in Asar.

Journal ArticleDOI
TL;DR: The RBC-D, measured by ektacytometry, was significantly reduced in severe malaria and was particularly low in all fatal cases, and appeared to result mainly from changes in unparasitized erythrocytes.
Abstract: Severe falciparum malaria is associated with microvascular obstruction resulting from sequestration of erythrocytes containing mature stages of the parasite. Since reduced red blood cell deformability (RBC-D) can contribute to impaired microcirculatory flow, RBC-D was measured in 23 patients with severe falciparum malaria (seven of whom subsequently died), 30 patients with uncomplicated malaria, and 17 healthy controls. The RBC-D, measured by ektacytometry, was significantly reduced in severe malaria and was particularly low in all fatal cases. At a low shear stress of 1.7 Pascal (Pa), a red blood cell elongation index less than 0.21 on admission to the hospital predicted fatal outcome with a sensitivity of 100% (confidence interval [CI] = 59–100%) and a specificity of 88% (CI = 61–98%). The reduction in the RBC-D appeared to result mainly from changes in unparasitized erythrocytes. Reduced deformability of unparasitized red blood cells in severe malaria may contribute to impaired microcirculatory flow and a fatal outcome in severe falciparum malaria.

Journal ArticleDOI
TL;DR: A well-designed and carefully conducted direct comparison of the efficacy and tolerability of these two compounds was necessary because mefloquine and doxycycline are the agents currently recommended for prophylaxis of malaria.
Abstract: Background: Mefloquine and doxycycline are the two drugs recommended for prophylaxis of malaria for visitors to areas where Plasmodium falciparum is resistant to chloroquine.