Showing papers on "Malaria published in 1999"

Epidemiology and control of malaria.

Abstract: Malaria is essentially a local and focal disease since its transmission depends greatly on local eco-environmental conditions. In India, the incidence of total malaria cases has been contained to around 2–3 million cases per year. However, with the occurrence of outbreaks in different parts of the country since 1994, mortality due to malaria has increased. The challenges posed by changing epidemiological paradigms of malaria, occurrence of outbreaks, increasing trends ofP. falciparum cases, spreading resistance to available anti-malarials and development of resistance of vectors to insecticides are areas for major concern. The National Anti-Malaria Programme has made necessary modifications/adjustments in the malaria control strategy with the adoption of the Global Malaria Control Strategy.

Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant

Abstract: The contribution of malaria to morbidity and mortality among people in Africa has been a subject of academic interest, political advocacy, and speculation. National statistics for much of sub-Saharan Africa have proved to be an unreliable source of disease-specific morbidity and mortality data. Credible estimates of disease-specific burdens are required for setting global and national priorities for health in order to rationalize the use of limited resources and lobby for financial support. We have taken an empirical approach to defining the limits of Plasmodium falciparum transmission across the continent and interpolated the distributions of projected populations in 1995. By combining a review of the literature on malaria in Africa and models of acquired functional immunity, we have estimated the age-structured rates of the fatal, morbid and disabling sequelae following exposure to malaria infection under different epidemiological conditions.

Odor-mediated behavior of afrotropical malaria mosquitoes

Abstract: The African mosquito species Anopheles gambiae sensu lato s.l. and Anopheles funestus rank among the world's most efficient vectors of human malaria. Their unique bionomics, particularly their anthropophilic, endophagic and endophilic characters, guarantee a strong mosquito-host interaction, favorable to malaria transmission. Olfactory cues govern the various behaviors of female mosquitoes and here we review the role of semiochemicals in the life history of African malaria vectors. Recent evidence points towards the existence of human-specific kairomones affecting host-seeking A. gambiae s.l., and efforts are under way to identify the volatiles mediating this behavior. Based on examples from other Culicidae spp., it is argued that there is good reason to assume that mating, sugar feeding, and oviposition behavior in Afrotropical malaria vectors may also be mediated by semiochemicals. It is foreseen that increased knowledge of odor-mediated behaviors will be applied in the development of novel sampling techniques and possibly alternative methods of intervention to control malaria.

Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population.

Abstract: The contribution of malaria to morbidity and mortality among people in Africa has been a subject of academic interest, political advocacy, and speculation. National statistics for much of sub-Saharan Africa have proved to be an unreliable source of disease-specific morbidity and mortality data. Credible estimates of disease-specific burdens are required for setting global and national priorities for health in order to rationalize the use of limited resources and lobby for financial support. We have taken an empirical approach to defining the limits of Plasmodium falciparum transmission across the continent and interpolated the distributions of projected populations in 1995. By combining a review of the literature on malaria in Africa and models of acquired functional immunity, we have estimated the age-structured rates of the fatal, morbid and disabling sequelae following exposure to malaria infection under different epidemiological conditions.

Immunity to non-cerebral severe malaria is acquired after one or two infections.

Abstract: In areas of stable transmission, clinical immunity to mild malaria is acquired slowly, so it is not usually effective until early adolescence. Life-threatening disease is, however, restricted to a much younger age group, indicating that resistance to the severe clinical consequences of infection is acquired more quickly. Understanding how rapidly immunity develops to severe malaria is essential, as severe malaria should be the primary target of intervention strategies, and predicting the result of interventions that reduce host exposure will require consideration of these dynamics. Severe disease in childhood is less frequent in areas where transmission is the greatest. One explanation for this is that infants experience increased exposure to infection while they are protected from disease, possibly by maternal antibody. They therefore emerge from this period of clinical protection with considerably more immunity than those who experience lower transmission intensities. Here we use this data, assuming a period of clinical protection, to estimate the number of prior infections needed to reduce the risk of severe disease to negligible levels. Contrary to expectations, one or two successful infective bites seem to be all that is necessary across a broad range of transmission intensities.

Climate change and future populations at risk of malaria

Abstract: Global estimates of the potential impact of climate change on malaria transmission were calculated based on future climate scenarios produced by the HadCM2 and the more recent HadCM3 global climate models developed by the UK Hadley Centre. This assessment uses an improved version of the MIASMA malaria model, which incorporates knowledge about the current distributions and characteristics of the main mosquito species of malaria. The greatest proportional changes in potential transmission are forecast to occur in temperate zones, in areas where vectors are present but it is currently too cold for transmission. Within the current vector distribution limits, only a limited expansion of areas suitable for malaria transmission is forecast, such areas include: central Asia, North America and northern Europe. On a global level, the numbers of additional people at risk of malaria in 2080 due to climate change is estimated to be 300 and 150 million for P. falciparum and P. vivax types of malaria, respectively, under the HadCM3 climate change scenario. Under the HadCM2 ensemble projections, estimates of additional people at risk in 2080 range from 260 to 320 million for P. falciparum and from 100 to 200 million for P. vivax. Climate change will have an important impact on the length of the transmission season in many areas, and this has implications for the burden of disease. Possible decreases in rainfall indicate some areas that currently experience year-round transmission may experience only seasonal transmission in the future. Estimates of future populations at risk of malaria differ significantly between regions and between climate scenarios.

Short report: entomologic inoculation rates and Plasmodium falciparum malaria prevalence in Africa.

Abstract: Epidemiologic patterns of malaria infection are governed by environmental parameters that regulate vector populations of Anopheles mosquitoes. The intensity of malaria parasite transmission is normally expressed as the entomologic inoculation rate (EIR), the product of the vector biting rate times the proportion of mosquitoes infected with sporozoite-stage malaria parasites. Malaria transmission intensity in Africa is highly variable with annual EIRs ranging from 1,000 infective bites per person per year. Malaria control programs often seek to reduce morbidity and mortality due to malaria by reducing or eliminating malaria parasite transmission by mosquitoes. This report evaluates data from 31 sites throughout Africa to establish fundamental relationships between annual EIRs and the prevalence of Plasmodium falciparum malaria infection. The majority of sites fitted a linear relationship (r2 = 0.71) between malaria prevalence and the logarithm of the annual EIR. Some sites with EIRs 80%. The basic relationship between EIR and P. falciparum prevalence, which likely holds in east and west Africa, and across different ecologic zones, shows convincingly that substantial reductions in malaria prevalence are likely to be achieved only when EIRs are reduced to levels less than 1 infective bite per person per year. The analysis also highlights that the EIR is a more direct measure of transmission intensity than traditional measures of malaria prevalence or hospital-based measures of infection or disease incidence. As such, malaria field programs need to consider both entomologic and clinical assessments of the efficacy of transmission control measures.

A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain.

Abstract: Microvascular sequestration was assessed in the brains of 50 Thai and Vietnamese patients who died from severe malaria (Plasmodium falciparum, 49; P. vivax, 1). Malaria parasites were sequestered in 46 cases; in 3 intravascular malaria pigment but no parasites were evident; and in the P. vivax case there was no sequestration. Cerebrovascular endothelial expression of the putative cytoadherence receptors ICAM-1, VCAM-1, E-selectin, and chondroitin sulfate and also HLA class II was increased. The median (range) ratio of cerebral to peripheral blood parasitemia was 40 (1.8 to 1500). Within the same brain different vessels had discrete but different populations of parasites, indicating that the adhesion characteristics of cerebrovascular endothelium change asynchronously during malaria and also that significant recirculation of parasitized erythrocytes following sequestration is unlikely. The median (range) ratio of schizonts to trophozoites (0.15:1; 0.0 to 11.7) was significantly lower than predicted from the parasite life cycle (P < 0.001). Antimalarial treatment arrests development at the trophozoite stages which remain sequestered in the brain. There were significantly more ring form parasites (age < 26 hours) in the cerebral microvasculature (median range: 19%; 0-90%) than expected from free mixing of these cells in the systemic circulation (median range ring parasitemia: 1.8%; 0-36.2%). All developmental stages of P. falciparum are sequestered in the brain in severe malaria.

Status of pyrethroid resistance in Anopheles gambiae sensu lato

Abstract: The present study confirms the presence of pyrethroid resistance among Anopheles gambiae s.l mosquitos in Cote d'Ivoire and reports the observation of such resistance in two other countries in West Africa (Benin and Burkina Faso). Malaria vector populations from Cameroon (Central Africa), Senegal (West Africa) and Botswana (southern Africa) were found to be susceptible to pyrethroids. In the most resistant mosquito populations, resistance to permethrin was associated with reduced mortality, not only with respect to this compound but also towards deltamethrin. Moreover, a significant increase in knockdown time was observed in some mosquito populations before any decrease in mortality, suggesting that knockdown time could be a good indicator for the early detection of pyrethroid resistance. In view of the current extension of such resistance, there is an urgent need to set up a network in Africa to evaluate its development. It is also vital that the impact of this resistance on pyrethroid-impregnated bednets be assessed.

A Low Interleukin-10 Tumor Necrosis Factor-α Ratio Is Associated with Malaria Anemia in Children Residing in a Holoendemic Malaria Region in Western Kenya

Abstract: The balance between Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma) and Th2 cytokines (interleukin [IL]-10, -4) may be critical in the development of severe falciparum malaria. Therefore, plasma concentrations of these cytokines were determined in children with various manifestations of malaria. Plasma levels of IFN-gamma and IL-4 were undetectable in most children. However, TNF-alpha and IL-10 were significantly elevated in children with high-density parasitemia and malaria anemia compared with children in control groups. In children with mild malaria, IL-10, but not TNF-alpha, was significantly elevated. While the highest concentrations of TNF-alpha were found in children with malaria anemia, IL-10 levels were highest in children with high-density uncomplicated malaria. The mean ratio of IL-10 to TNF-alpha was significantly higher in children with mild and high-density parasitemia (4.64, P<.005) than in children with malaria anemia (1.77). Thus, higher levels of IL-10 over TNF-alpha may prevent development of malaria anemia by controlling the excessive inflammatory activities of TNF-alpha.

Incidence of malaria among children living near dams in northern Ethiopia: community based incidence survey

Abstract: Objective: To assess the impact of construction of microdams on the incidence of malaria in nearby communities in terms of possibly increasing peak incidence and prolonging transmission. Design: Four quarterly cycles of malaria incidence surveys, each taking 30 days, undertaken in eight at risk communities close to dams paired with eight control villages at similar altitudes but beyond flight range of mosquitoes. Setting: Tigray region in northern Ethiopia at altitudes of 1800 to 2225 m. Subjects: About 7000 children under 10 years living in villages within 3 km of microdams and in control villages 8-10 km distant. Main outcome measures: Incidence of malaria in both communities. Results: Overall incidence of malaria for the villages close to dams was 14.0 episodes/1000 child months at risk compared with 1.9 in the control villages—a sevenfold ratio. Incidence was significantly higher in both communities at altitudes below 1900 m. Conclusions: There is a need for attention to be given to health issues in the implementation of ecological and environmental development programmes, specifically for appropriate malaria control measures to counteract the increased risks near these dams. Key messages Environmental development may have important effects on the epidemiology of vector borne diseases such as malaria This may be particularly important where disease transmission is unstable—for example, in highland areas Children in villages near recently constructed microdams in northern Ethiopia had a significantly increased risk of malaria It seems that this irrigation development programme is leading to increased malaria transmission across a range of altitudes and seasons Intersectoral collaboration is necessary in development projects that may affect communities both positively and negatively

CTRP is essential for mosquito infection by malaria ookinetes

Abstract: The malaria parasite suffers severe population losses as it passes through its mosquito vector. Contributing factors are the essential but highly constrained developmental transitions that the parasite undergoes in the mosquito midgut, combined with the invasion of the midgut epithelium by the malaria ookinete (recently described as a principal elicitor of the innate immune response in the Plasmodium-infected insect). Little is known about the molecular organization of these midgut-stage parasites and their critical interactions with the blood meal and the mosquito vector. Elucidation of these molecules and interactions will open up new avenues for chemotherapeutic and immunological attack of parasite development. Here, using the rodent malaria parasite Plasmodium berghei, we identify and characterize the first microneme protein of the ookinete: circumsporozoite- and TRAP-related protein (CTRP). We show that transgenic parasites in which the CTRP gene is disrupted form ookinetes that have reduced motility, fail to invade the midgut epithelium, do not trigger the mosquito immune response, and do not develop further into oocysts. Thus, CTRP is the first molecule shown to be essential for ookinete infectivity and, consequently, mosquito transmission of malaria.

The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration

Abstract: Objectives: This study was undertaken to determine the relative effect of malaria infection on HIV concentration in blood plasma, and prospectively to monitor viral concentrations after antimalarial therapy. Design: A prospective, double cohort study was designed to compare the blood HIV-1 RNA concentrations of HIV-positive individuals with and without acute malaria illness. Subjects were followed for 4 weeks after successful malaria therapy, or for 4 weeks from enrollment (controls). Methods: Malawian adults with symptomatic Plasmodium falciparum parasitemia (malaria group) and asymptomatic, aparasitemic blood donors (control group) were tested for HIV-1 antibodies to identify appropriate study groups. The malaria group received antimalarial chemotherapy only and were followed with sequential blood films. In both groups, blood plasma HIV-1 RNA viral concentrations were determined at enrollment and again at 1, 2 and 4 weeks. Results: Forty-seven malaria patients and 42 blood donors were enrolled. At enrollment blood plasma HIV-1 RNA concentrations were approximately sevenfold higher in patients with malaria than in blood donors (medians 15.1 × 10 4 and 2.24 × 10 4 copies/ml, respectively, P = 0.0001). No significant changes in median HIV-1 concentrations occurred in the 21 blood donors followed to week 4 (P = 0.68). In the 27 subjects successfully treated for malaria who were followed to week 4, a reduction in plasma HIV-1 RNA was observed from a median of 19.1 × 10 4 RNA copies/ml at enrollment, to 12.0 × 10 4 copies/ml at week 4, (P = 0.02). Plasma HIV-1 concentrations remained higher in malaria patients than controls (median 12.0 × 10 4 compared with 4.17 × 10 4 copies/ml, P = 0.086). Conclusions: HIV-1 blood viral burden is higher in patients with P. falciparum malaria than in controls and this viral burden can, in some patients, be partly reduced with antimalarial therapy.

Interferon-γ Responses Are Associated with Resistance to Reinfection with Plasmodium falciparum in Young African Children

Abstract: The contribution of T cell-mediated responses was studied with regard to resistance to reinfection in groups of Gabonese children participating in a prospective study of severe and mild malaria due to infection with Plasmodium falciparum. In those admitted with mild malaria, but not in those with severe malaria, production of IFN-gamma by peripheral blood mononuclear cells (PBMC) in response to either liver-stage or merozoite antigen peptides was associated with significantly delayed first reinfections and with significantly lower rates of reinfection. Proliferative or tumor necrosis factor responses to the same peptides showed no such associations. Production of interferon-gamma by PBMC in response to sporozoite and merozoite antigen peptides was observed in a higher proportion of those presenting with mild malaria. Differences in the Th1/Th2 cytokine balance may be linked to the ability to control parasite multiplication in these young children, helping to explain the marked differences observed in both susceptibility to infection as well as in clinical presentation.

Epidemiology of visceral leishmaniasis in India.

Abstract: Kala-azar has re-emerged from near eradication. The annual estimate for the incidence and prevalence of kala-azar cases worldwide is 0.5 million and 2.5 million, respectively. Of these, 90% of the confirmed cases occur in India, Nepal, Bangladesh and Sudan. In India, it is a serious problem in Bihar, West Bengal and eastern Uttar Pradesh where there is under-reporting of kala-azar and post kala-azar dermal leishmaniasis in women and children 0-9 years of age. Untreated cases of kala-azar are associated with up to 90% mortality, which with treatment reduces to 15% and is 3.4% even in specialized hospitals. It is also associated with up to 20% subclinical infection. Spraying of DDT helped control kala-azar; however, there are reports of the vector Phlebotomus argentipes developing resistance. Also lymphadenopathy, a major presenting feature in India raises the possibility of a new vector or a variant of the disease. The widespread co-existence of malaria and kala-azar in Bihar may lead to a difficulty in diagnosis and inappropriate treatment. In addition, reports of the organism developing resistance to sodium antimony gluconate--the main drug for treatment--would make its eradication difficult. Clinical trials in India have reported encouraging results with amphotericin B (recommended as a third-line drug by the National Malaria Eradication Programme). Phase III Trials with a first-generation vaccine (killed Leishmania organism mixed with a low concentration of BCG as an adjuvant) have also yielded promising results. Preliminary studies using autoclaved Leishmania major mixed with BCG have been successful in preventing infection with Leishmania donovani. Until a safe and effective vaccine is developed, a combination of sandfly control, detection and treatment of patients and prevention of drug resistance is the best approach for controlling kala-azar.

Increased prevalence of malaria in HIV-infected pregnant women and its implications for malaria control.

Abstract: Findings are presented from an assessment of the relationship between HIV infection and malaria prevalence in pregnant women and the effectiveness of sulphadoxine-pyrimethamine (SP) in clearing Plasmodium falciparum infection in the context of HIV infection. HIV status was assessed in 621 women who attended for antenatal care and delivery at 2 rural hospitals in southern Malawi during 1993-94. The prevalence of P. falciparum was measured at first antenatal visit and delivery. The overall prevalence of HIV infection was 25.6% of which all infections were of HIV type 1. Malaria prevalence among primigravidae at recruitment was 56.3% among those HIV-infected and 36.5% among those not infected. Corresponding figures for multigravidae were 23.8% and 11.0% respectively. HIV-infected primigravidae had increased malaria prevalence at all gestational ages with peak parasite prevalence occurring earlier in gestation among HIV-infected primigravidae. HIV infection is therefore associated with a significant increase in malaria prevalence in pregnant women of all parities with the effect apparent from early in gestation. 2 routine treatment doses of SP 1 at first antenatal visit and the second between 28 and 34 weeks gestation were inadequate to clear parasitemia in many women by the time of delivery independent of HIV status and despite high sensitivity to SP in this area.

Anaemia of acute malaria infections in non-immune patients primarily results from destruction of uninfected erythrocytes.

Abstract: While anaemia has long been recognized as a consequence of acute infections with malaria, the relative contributions of direct erythrocyte destruction by parasites, destruction of uninfected erythrocytes and changes in erythropoiesis have been unclear. Fitting of parasitaemia and anaemia data from neurosyphilis patients undergoing malaria therapy to a mathematical model shows that in these patients, an average of 8.5 erythrocytes were destroyed in addition to each erythrocyte observed to become parasitized. The model also showed that dyserythropoiesis plays an insignificant role in the resulting anaemia. The anaemia occurs before a substantial antibody response to parasites or erythrocytes could be generated. We postulate that uninfected erythrocyte destruction occurs through phagocytosis of erythrocytes bound to merozoites killed as a result of the accompanying malaria paroxysms.

Severe Malarial Anemia and Cerebral Malaria Are Associated with Different Tumor Necrosis Factor Promoter Alleles

Abstract: Experimental evidence implicates tumor necrosis factor (TNF) in the pathogenesis of malarial anemia, but there are few data relating to this hypothesis. This study found that severely anemic children with Plasmodium falciparum infection have low plasma TNF levels, in contrast to the high levels found in cerebral malaria. A previous case-control study in The Gambia found cerebral malaria, but not severe malarial anemia, was associated with the TNF-308 A allele. This study found that in the same population, severe malarial anemia was associated with the TNF-238 A allele, with an odds ratio of 2.5 (P<.001) after stratification for HLA type. These findings suggest that severe malarial anemia and cerebral malaria are influenced by separate genetic factors situated near the TNF gene.

African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death.

Abstract: Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] = 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was independently found in all children with hypoglycemia (odds ratio [OR] = 6.7, 95% confidence interval [CI] = 3.9-11.7), in children 1-7 months of age with tachypnea (OR = 8.8, 95% CI = 2.6-30.5) and dehydration (OR = 5.0, 95% CI = 1.9-14.2), and in children 8 months to 4 years of age with chest indrawing (OR = 4.7, 95% CI = 2.0-11.2) and inability to localize a painful stimulus (OR = 6.9, 95% CI = 2.9-16.5). Children in the bottom quartile of weight-for-age were more likely to die (OR = 2.1, 95% CI = 1.3-3.5). Eight percent of the malaria cases had severe anemia (packed cell volume < 15%) but 24% received a blood transfusion. The epidemiology of malaria disease may be more complex than previously thought. Improved case management in a wide variety of health facilities may result from adequate identification and treatment of dehydration and hypoglycemia. Transfusion-requiring anemia is a major problem and sustainable, effective preventive measures are urgently needed.

Bacteraemia complicating severe malaria in children

Abstract: Bacteraemia associated with severe malaria in childhood is a sporadically reported phenomenon but its incidence and clinical importance are unknown. We have reviewed clinical and laboratory data from 783 Kenyan children sequentially admitted with a primary diagnosis of severe malaria. The overall incidence of bacteraemia in children with severe malaria was 7.8% (95% CI 5.5-10.0); however, in children under 30 months of age the incidence was 12.0% (95% CI 8.3-15.7). The presence of bacteraemia was associated with a 3-fold increase in mortality (33.3% vs. 10.4%, P < 0.001). We conclude that invasive bacterial disease may contribute to the pathophysiology of the clinical syndrome of severe malaria in an important subgroup of children. We recommend that young children with severe malaria be treated with broad-spectrum antibiotics in addition to antimalarial drugs.

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children.

Abstract: A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. Between June 1992 and July 1994, 1,848 children less than 15 years of age were monitored prospectively for a mean of 236 days. During this period, 12,035 blood smears were examined for malaria and only 34% were found to be negative. Parasite prevalence (all species) decreased with age (from a high of 83% among children 1-4 years old to 60% among children 10-14 years old). Even more dramatic decreases were noted in the prevalence of high density falciparum infection (from 37% among children 12-23 months old to < 1% among 10-14-year-old children) and in clinical malaria (20% to 0.3% in the same age groups). Children < 1 year of age accounted for 55% of all cases of anemia detected. Anemia was consistently associated with high density infection in children < 10 years of age (20% to 210% increased risk relative to aparasitemic children). These results demonstrate the relationship between high-density malaria infection and two clinical manifestations of malarial illness.

Malaria vaccines

Abstract: Malaria remains one of the most important vector-borne human diseases. Control of malaria caused by Plasmodium falciparum is a major goal, particularly for populations in sub-Saharan Africa. An effective vaccine against malaria that would protect nonimmune individuals from the disease has long been a dream. But will it be a reality? The concept that vaccination may be a useful tool to control the disease is based on a number of observations. Individuals continually exposed to infection by the parasitic protozoan responsible do eventually develop immunity to the disease, and passive immunization with antibody from immune donors can have a dramatic effect on blood stage parasitemia (1). Furthermore, inoculation of live attenuated parasites can protect naive volunteers against infection (2), and immunization with whole killed organisms can protect in animal models (3). Intensive studies of the immune response to the malaria parasite in humans and in models, particularly rodent malaria parasites in laboratory mice, have provided a wealth of information on potential protective mechanisms. Twenty years of antigen identification and gene cloning and expression, have produced many candidates for subunit vaccines (for a comprehensive recent review see ref. 4). Single proteins or peptides have been shown to be at least partially protective when used in vaccination studies in humans or in animal models (see, for example ref. 5). Within these antigens important epitopes have been identified, such as those recognized by neutralizing antibodies (6). All of these findings may suggest that an effective vaccine is “just around the corner,” but what is reality, and what are the scientific obstacles? By its very nature malaria vaccine research is a mix of empirical and rational approaches. It is hampered by the complexity of the parasite life cycle, imperfect tools to assess the efficacy of immune responses, and limited knowledge and understanding of the …

Diagnosis of malaria: a review of alternatives to conventional microscopy.

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

Malaria reemergence in the Peruvian Amazon region.

Abstract: Epidemic malaria has rapidly emerged in Loreto Department, in the Peruvian Amazon region. Peru reports the second highest number of malaria cases in South America (after Brazil), most from Loreto. From 1992 to 1997, malaria increased 50-fold in Loreto but only fourfold in Peru. Plasmodium falciparum infection, which has increased at a faster rate than P. vivax infection in the last 3 years, became the dominant Plasmodium infection in the highest transmission areas in the 1997 rainy season. The vector Anopheles darlingi has also increased during this epidemic in Loreto. Moreover, chloroquine and pyrimethamine-sulfadoxine drug-resistant P. falciparum strains have emerged, which require development of efficacious focal drug treatment schemes.

Highland malaria in Uganda: prospective analysis of an epidemic associated with El Niño.

Abstract: Malaria epidemics in African highlands cause serious morbidity and mortality and are being reported more frequently. Weather is likely to play an important role in initiating epidemics but limited analysis of the association between weather conditions and epidemic transmission parameters has been undertaken. We measured entomological variables before and during an epidemic of malaria (which began in February 1998) in a highland region of south-western Uganda and analysed temporal variation in weather data against malaria incidence (estimated from clinic records), mosquito density and entomological inoculation rates (EIR). Indoor resting density of Anopheles gambiae s.l. was positively correlated with malaria incidence (r = 0.68, P < 0.05) despite extremely low vector densities. EIR totalled only 0.41 infectious bites per person during the entire 8-month study period. Rainfall during and following the El Nino event in 1997 was much higher than normal, and rainfall anomaly (difference from the mean) was positively correlated with vector density 1 month later (r = 0.55, P < 0.05). Heavier than normal rainfall associated with El Nino may have initiated the epidemic; the relationship between temperature and transmission parameters remains to be defined. The results from this study indicate that, in this highland population, epidemic malaria may occur at extremely low inoculation rates.

Imported malaria (1985-95): trends and perspectives.

Abstract: Malaria is frequently imported into nonendemic industrialized areas. In this study we collated data on the reported malaria cases in industrialized countries during the period 1985-95, with the object of identifying trends and promising strategies. The main outcome measures were incidence, case-fatality rates (CFRs), and attack rates in tourists returning from Kenya. Our survey showed gross underreporting and marked heterogeneity in the type and availability of national data. The total incidence or reported numbers of malaria infections in Europe increased from 6840 in 1985 to 7244 in 1995, with a peak of 8438 in 1989. The principal importing countries were France, Germany, Italy, and the United Kingdom. In the former USSR, the reported annual incidence dropped from 1145 in 1989 to 356 in 1990 after cessation of activities in Afghanistan. Among the imported species of malaria parasite, Plasmodium falciparum was identified in an increasing proportion, the CFR ranging from 0% to 3.6%, with consistently high rates in Germany. The attack rates among travellers to Kenya in 1990-95 were high, ranging from 18 to 207 per 100,000 travellers. Our findings indicate that in industrialized countries malaria is associated with a high CFR and remains a public health problem. Irregular surveillance and lack of homogeneity in the collected data hinder the assessment of incidences, risk groups, and the efficacy of chemoprophylaxis.