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Documents at the Australian Academy of Science and the United States National Academy of Sciences reveal that wartime research by the Australian Army at Cairns had a significant impact on United States malaria research programs, as well as providing a scientific basis for drug control of malaria.
OBJECTIVES: Mefloquine has now largely replaced earlier malaria prophylaxis drugs which are no longer considered to be effective against all Plasmodium species, due to parasite resistance. However mefloquine may be associated with neuropsychological harmful effects. The objective of this review was to assess the effects of mefloquine in adult travellers. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, Medline, Embase, Lilacs, Science Citation Index and reference lists of articles. We contacted researchers in the subject of malaria chemoprophylaxis, and drug companies. SELECTION CRITERIA: Randomised trials comparing mefloquine with other standard prophylaxis or placebo in non-immune adult travellers. DATA COLLECTION AND ANALYSIS: The two reviewers independently assessed trial quality and extracted data. Study authors were also contacted. MAIN RESULTS: Ten trials involving 2750 non-immune adult travellers were included. One trial comparing mefloquine with placebo showed mefloquine prevented malaria episodes in an area of drug resistance (odds ratio 0.04, 95% confidence interval 0.02 to 0.08). Withdrawals in the mefloquine group were consistently higher in four placebo controlled trials (odds ratio 3. 56, 95% confidence interval 1.67 to 7.60). In five trials comparing mefloquine with other chemoprophylaxis, no difference in tolerability was detected. REVIEWER'S CONCLUSIONS: Mefloquine prevents malaria, but there is not enough evidence to evaluate its tolerability and toxicity, particularly for general travellers.
The incidence of severe malaria and malaria-specific mortality were investigated in a hospital, for miners and their families, at Tensa in the Sundergarh district of Orissa state in India. Tensa lies in area where malaria (predominantly caused by Plasmodium falciparum) is hyper-endemic. The hospital records for 1995--1999 showed that, although annual admissions for malaria increased over the study period, there were very few admissions for severe, complicated malaria and no reports of malaria-specific deaths. Most of the patients who had been admitted with cerebral malaria either came from areas around but not within the town of Tensa or were recent arrivals in the town. It appears that the outcome of malaria is influenced not only by the intensity of local transmission (which affects the immunological status of the human hosts) but also by social factors such as the education and health-seeking behaviour of the local population and the health-care facilities available. The low incidence of severe malaria observed in Tensa was probably the result of patients presenting early in the course of their illness and taking antimalarial treatment, iron supplementation and supportive therapy at the appropriate times.
Serum samples from 95 patients with acute uncomplicated falciparum malaria (AM) and 95 patients with cerebral malaria (CM) were tested by the indirect immunofluorescent assay (IFA) for IgG and IgM antibodies against Plasmodium falciparum and P. vivax sporozoites. Forty-six (48%) CM patients were positive for antibodies against P. falciparum sporozoites whereas only 23 (24%) were positive for antibodies against P. vivax sporozoites (P less than 0.002). A similar result was obtained in AM patients. However, CM patients had significantly lower mean IgG anti-sporozoite titer for P. falciparum than did AM patients (P less than 0.05), especially when only anti-sporozoite antibody-positive CM and AM patients were compared (P less than 0.0005), suggesting that CM patients had relatively less exposure and were probably less immune to malaria than were AM patients. The persistence of anti-sporozoite antibodies also was investigated in paired sera taken 63 days apart from 108 patients with acute falciparum malaria. There were significant decreases in the mean antibody titers in the follow-up sera during the period of stay in the malaria-free area. It was proposed that determination of anti-sporozoite antibody be made as a substitute for, or in addition to, anti-blood stage antibody for seroepidemiological study of malaria, especially in the monitoring of the success of the malaria control program.
A battery of sixty-six blood samples from Senegal was analysed by the ParaSight F test, the ICT Malaria PF and the Malaria IgG CELISA. These three assays detect the histidine rich protein 2 antigen of Plasmodium falciparum. Thick smear microscopy was used as the reference method. Sensitivity, specificity, predictive positive and negative values were respectively 89%, 100%, 100%, 88% for the ICT; 86%, 93%, 94%, 85% for the paraSight and 88%, 87%, 88%, 87% for the Malaria IgG CELISA. The three assays failed to detect two positive samples with P. ovale and P. malariae. Assays were also compared with regard to the expense of equipment and reagents and speed and ease of use. The rapid ICT and ParaSight F test can be performed with minimal training and may be specially useful in areas where P. falciparum is the predominant malaria species, in epidemic malaria regions, and where skilled microscopy is not readily available.
The control strategies usually recommended in Africa south of the Sahara have not been followed by a lasting decline in the endemic level of the disease in the rural environment. The set-backs of the eradication period have revealed the need to redefine control objectives and strategies adapted to each type of malaria. Systematic chemotherapy for attacks of fever is a strategy that can be proposed in all circumstances; it avoids mortality from malaria; it can be carried out in the field on a country scale. The other means of control, directed against the parasites and the vectors, may be used depending of the specific situation in each country and on each type of malaria. Malaria control has to be integrated into the basic health system of each country, and we need to improve health education and develop primary health care. We must continue with our efforts to develop new antimalarial drugs, insecticides and vaccines; urgent steps must be taken to train malariologists capable of adapting the new techniques to the actual situation in the field. It is by associating socioeconomic development with the control means as a whole that we shall be able to control the various types of malaria and to reach out towards the objective of health for all by the year 2000.
The article analyses the evolution of knowledge and rationale of control of a special case of malaria transmission based on Bromelia-Kerteszia complex. Since bromeliaceae function as a 'host of the carrier' and were previously associated with natural forests, the elucidation of bromeliad malaria historically elicited controversies concerning the imputation of Kertesziae as transmitters as well as over control strategies directed to bromelia eradication (manual removal, herbicides and deforestation), use of insecticides and chemoprophylaxis. Established authority, disciplinary traditions, conceptual premises and contemporary criteria for validating knowledge in the field partly explain the long time gap since Adolpho Lutz announced at the beginning of the century the existence of a new mosquito and breeding site as responsible for a 'forest malaria' epidemic occurring at a high altitude. The article brings attention to how economic, political and institutional determinants played an important role in redefining studies that led both in Trinidad and Brazil to the recognition of the importance of kerteszia transmission, including urban areas, and establishing new approaches to its study, most relevant of all the concurrence of broad ecological research. The article then describes the Brazilian campaign strategies which showed significant short-term results but had to wait four decades to achieve the goal of eradication due to the peculiar characteristics of this pathogenic complex. Finally, it brings attention to the importance of encompassing social values and discourses, in this case, environmental preservation, to understanding historical trends of malaria control programs.
The IgG and IgM antibody responses to the C-terminal 783 amino acids of the P. falciparum glutamate-rich protein, GLURP489-1271, expressed as an E. coli fusion protein, the IgG response to a 18-mer synthetic peptide EDKNEKGQHEIVEVEEIL (GLURP899-916) representing the C-terminal repeats of GLURP, and a synthetic peptide (EENV)6 representing the C-terminal repeats from Pf155/RESA, were investigated longitudinally in 13 children and 7 adults living under conditions of continuous, intense malaria transmission. Some subjects did not recognize the antigens after malaria infection, and in subjects recognizing the antigens, the responses were often short-lived. In adults, the antibody responses to the GLURP489-1271 fusion protein and the (EENV)6 peptide peaked after 2 weeks, and not all individuals responded to all antigens. The antibody response, even against large fragments of conserved antigens, is not uniformly elicited by natural malaria infection in previously primed donors.
Serum taken from mice immune to malaria as a result of infection and drug cure, or from mice immunized with a recombinant form of the merozoite surface protein, MSP1, can provide passive protection of recipient mice against the lethal parasite, Plasmodium yoelii YM. However, recipients of MSP1-immune serum go on to develop long-term immunity, whereas recipients of serum from mice naturally immune to malaria rapidly lose their resistance to infection. We demonstrate that 'infection/cure' serum suppresses the development of both antibody and cell-mediated parasite-specific responses in recipients, whereas these develop in recipients of MSP1-specific antibodies. These data have profound implications for our understanding of the development of malaria immunity in babies who passively acquire antibodies from their mothers.
BACKGROUND AND OBJECTIVES: Blood donations are often wasted for lack of a satisfactory procedure to evaluate donors potentially exposed to malaria. MATERIALS AND METHODS: We evaluated a commercial ELISA for the detection of antibodies to malaria and compared it with an immunofluorescent antibody test (IFAT). RESULTS: When 5,311 sera from routine non-exposed donors were tested, 24 (0.45%) were positive by the ELISA, using a Plasmodium falciparum antigen. Seventeen were subjected to confirmatory testing but none were positive by IFAT. Of 1,000 donors potentially exposed in endemic areas 15 (1.5%) were repeatably reactive by ELISA. 10 of these were tested by IFAT and 2 were positive. When 150 patients attending the Hospital for Tropical Diseases in London with acute malaria were tested, 73% of those infected with P. falciparum were repeatably reactive for malarial antibodies by ELISA and 56% with Plasmodium vivax. Of 88 stored clinical sera tested by both IFAT and ELISA 56 were positive by IFAT and of these 52 (93 degrees/0) were positive by ELISA. CONCLUSION: The ELISA is sufficiently sensitive and specific to screen at-risk donors. Its use could safely retrieve 40,000 red cell units currently discarded each year in Great Britain.
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.
In 1997, the information was collected in collaboration with WHO on the actual status of malaria in large ports of Africa, Asia, and America, on the level of endemicity, prevailing Plasmodium species and the resistance to antimalarial drugs. The factors determining the risk of infection in seafarers were discussed. The risk is different than it is for other groups of travellers. The strategy of malaria prevention in crews of ships should be based on balancing the actual risk of infection in the visited ports of the tropics with the risk of side effects of antimalarials used for prophylaxis. Five schemes for malaria prevention in seafarers may be recommended, depending on the geographical areas of the ship's voyage.
BACKGROUND: Despite continued efforts to control the disease, malaria remains a major health problem in many regions of the world, especially sub-Saharan Africa, and new ways to control or eradicate the disease are urgently needed. Two types of vaccine, SPf66 vaccine against the asexual stages, and NANP vaccines against the sporozoite stages of the Plasmodium parasite, have been tested in randomised clinical trials in endemic areas. OBJECTIVES: To assess the effects of malaria vaccines. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Organisations and researchers in the field were contacted. SELECTION CRITERIA: Randomised trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale, and placebo. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and conducted data extraction. MAIN RESULTS: Thirteen efficacy trials involving about 7700 people were included. There were nine trials of the Spf66 vaccine and four trials of the NANP vaccines. There was large heterogeneity between trials when investigating the effect of SPf66 in reducing incidence of the first attack of P. falciparum malaria. When trials were subcategorised by location, there was no evidence for effect of SPf66 in reducing incidence of P. falciparum in four African trials conducted in children under 5 years of age (Peto odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.81 to 1.14). In five trials outside Africa with participants aged 2 years to adult, there was a reduction in incidence by SPf66 vaccine (Peto OR = 0.77, 95% CI 0.67 to 0.88, fixed effects model). Significant heterogeneity remained between trials conducted outside Africa. Using a random effects model for these five trials, the OR was 0.74 (95% CI 0.54 to 1.01). In five trials, there was no evidence for effect of the SPf66 vaccine on the incidence of the first attack of P. vivax malaria (OR 1.01, 95% CI 0.87 to 1.17). Trials to date have not indicated any severe adverse effects of SPf66 vaccine. In three trials of NANP-based vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (OR 1.12, 95% CI 0.64 to 1.93). REVIEWER'S CONCLUSIONS: There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America may be justified. Trials to date have not been of sufficient size to evaluate the effect of malaria vaccines on mortality or on severe malaria requiring admission to hospital. There was not enough evidence to evaluate the use of NANP vaccines.
Intraleucocytic malaria pigment has been suggested as a measure of disease severity in malaria. We have tested this hypothesis by studying 146 children aged 6 months to 14 years in 4 categories--cerebral malaria, mild malaria, asymptomatic malaria and 'no malaria'--in Ibadan, Nigeria, an area of intense malaria transmission in Africa. Children with cerebral malaria were studied at the university hospital, those with mild malaria at 2 primary health centres and the other 2 groups were studied in a primary school. The proportion of pigment-containing neutrophils showed a clear rise across the spectrum no malaria--asymptomatic malaria--mild malaria--cerebral malaria (median values 2.0%, 6.5%, 9.0% and 27.0%, respectively; P < 0.0001). The proportion of pigment-containing monocytes did not differ significantly between the mild malaria, asymptomatic malaria and no malaria groups but the cerebral malaria group had a higher median value than the other 3 groups. The ratio of pigment-containing neutrophils to pigment-containing monocytes showed the same trend across the groups of subjects as was observed with the number of pigment-containing neutrophils. It is concluded that the pigment-containing neutrophil count is a simple marker of disease severity in childhood malaria in addition to the parasite count.
While malaria pigment or haemozoin is known to be an end product of haemoglobin digestion by the malaria parasite, its clinical significance is just beginning to be elucidated. We have studied the distribution of intraleucocyte malaria pigment in 92 children, consisting of 32 children with asymptomatic malaria, 32 children with mild or uncomplicated malaria and 28 children with no malaria. Over 90% of children in each of the three groups had pigment-containing monocytes and the numbers of pigment-containing monocytes were not significantly different between the three groups. While over 90% of children in both the asymptomatic malaria and uncomplicated malaria groups had pigment-containing neutrophils, 71.4% of the no malaria group had such neutrophils. The numbers of pigment containing neutrophils was highest in the uncomplicated malaria group, followed by the asymptomatic malaria group with the no malaria group having the least numbers. The pigmented neutrophil: monocyte ratio followed the same pattern. It was concluded that the number of pigment-containing neutrophils and the pigmented neutrophil:monocyte ratio may be a marker of the severity of malaria infection when one considers the conditions: no malaria, asymptomatic malaria and mild malaria. Further work to verify this hypothesis across the full spectrum of the manifestations of malaria infection is needed.
A mother's ability to suspect malaria in the presence of fever has important consequences for child survival in malaria-endemic areas. This paper presents results of a clinic-based study of mothers' abilities to suspect malaria in the event of recognizing fever and other physiological and behavioral changes associated with the disease. The study population consisted of all (439) women or mothers who had accompanied children 5 years and below to the Old Mulago Hospital, Kampala, Uganda over a 10 day period during the malaria season of 1992. The children were those who had fever as a major complaint at the time of the visit or those who had fever in the last 7 days and were visiting the clinic for the first time for the current illness. The children were physically examined and their blood tested for malaria parasites. Mothers' diagnosis was compared with clinical and laboratory diagnosis of malaria. Mothers associated the presence of fever with several types of illness and malaria was often not suspected. Only 40% of the mothers suspected malaria in their children. The mothers were poor at recognizing malaria when, in fact, it was present. The sensitivity of the mothers' diagnosis of malaria was found to be 37%; 63% of malaria cases were misclassified as other conditions. The doctors classified most (92%) of the cases presenting with fever as having malaria, but laboratory tests indicated that only 64% of the children really had malaria. The sensitivity of clinical diagnosis was 98%, but the specificity was only 18%. Ninety percent of the mothers gave some medicines before visiting the health centre; and, of these, 76% gave modern drugs exclusively, including antimalarials, antipyretics, antibiotics and other drugs. Among the modern drugs given to children suspected of having malaria, 50% were antimalarials. The most commonly used antimalarial was chloroquine tablets. Mothers indiscriminately administered antimalarials to children irrespective of the perceived cause of the fever. There is need to educate mothers to suspect malaria first in every case of febrile illness, just like the doctors do, and about the first line drugs for the treatment of malaria.
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Even now 50% of the world population are still living in malaria endemic areas and every year 200 million new cases with 2 million deaths are reported. Most of the malaria deaths are children under 5 years old. Although malaria endemicity currently exists mainly in tropics, before the human started its efforts to eradicate malaria in large scale in 1950s, malaria was more widely distributed in the world. At this time Japan and malaria together with North America and European countries. However some areas were precluded from malaria endemicity: i.e., high mountains and deserts. Also Polynesian islands in the Pacific have never been malarious, even though Melanesian Papua New Guinea, Solomon, and Vanuatu are highly malarious even now. Human disease malaria is caused by Plasmodium parasites and transmitted by Anopheles mosquitoes. Human is classified into the malaria donor and recipient. The environment is supporting this system: for example, temperature and rainfall are important factors together with vegetation, or housing, health infrastructure, war situation, and poverty status. In 1950s, the WHO malaria eradication program focused its efforts on vector control, using DDT-residual spraying. But the program completely failed with mainly operational reasons and we already learned it is almost impossible to control malaria only killing mosquitoes. In 1992 the new Global Malaria Control Strategy adopted by Malaria Summit at Amsterdam says the primary objective is early diagnosis and treatment to prevent malaria death. In this context malaria chemotherapy is a key issue. Also we understand more and more the environmental management is very important. Malaria vaccine may be a conceptually important tool, but may be available soon.