The Dutch school of malaria research

An epidemic of tertian malaria in some coastal areas of The Netherlands resulted in the setting up of official measures in 1920. A scientific and a propaganda commission were charged with control. Efforts were made to reduce mosquito populations by adult and larval spraying. After the discovery that infected mosquitoes were to be found only inside houses, control operations were focussed against adult mosquitoes. Some later discoveries resulted in a more effective control. a) Spraying ditches with Paris green did not prevent adult mosquitoes from entering the control area. b) Anopheles maculipennis turned out to be a complex of species, with A. atroparvus as the vector. The latter preferred brackish water and did not go into full hibernation. The closing of the Zuyder Sea and the expected desalinization gave hope for less suitable conditions for the vector. c) Plasmodium vivax normally had an incubation period of 8 months. d) Pyrethrum was an effective but short-lasting insecticide. e) Healthy parasite carriers could infect mosquitoes. This knowledge was applied through an extensive system of investigation, including spleen examination of schoolchildren. Suspected houses were sprayed bimonthly from August to November, during which period infected mosquitoes were likely to be present. This system worked extremely well, and during the next epidemic from 1943 to 1947 the thus treated towns remained virtually free of malaria! DDT became available and was either sprayed in suspected houses as before, or through wide-spread coverage of all houses. The epidemic subsided whatever method employed and not only due to the use of DDT. The number of cases even went down to the point of no return and the last case of Dutch malaria was recorded in 1959. The wealth of experience on house-spray control, parasite and mosquito biology and experimental malaria of the Dutch malariologists has had its impact on the international bodies engaged in the battle against malaria.     

The Rockefeller Foundation and the prevention of malaria in Corsica, 1923-1951: support given to the French parasitologist Emile Brumpt

The role of the International Health Board of the Rockefeller Foundation in campaigns for malaria control in many countries has clearly been documented extensively. In contrast, the involvement of the Rockefeller Foundation in the control of malaria in France has not been reported yet. The present paper describes the way in which the Rockefeller Foundation got involved, along with the parasitologist Emile Brumpt, in the anti-malaria campaigns in Corsica, France, between 1924 and 1951. We analyze the scientific and technological strategies used for that purpose and the manner in which the Rockefeller Foundation policy had influenced Brumpt's actions. The unusually long support of the Rockefeller Foundation to Emile Brumpt (1924-1948) and to research and teaching Parasitology in the Faculté de Médecine de Paris is also discussed.     

Internationalism and nationalism: the Rockefeller Foundation, public health, and malaria in Italy, 1923-1951

The Rockefeller Foundation's support of malaria control and public health in Italy over three decades, the 1920s, 1930s and 1940s, was one of the foundation's most successful collaborations in its history. Nearly one-sixth of the funds the Rockefeller Foundation allocated for malaria programs was spent in Italy in those years. Outstanding research, a new and important institution, and decided improvements in public health were historically-significant results. The three most important episodes of this American-Italian relationship were the operations of the Stazione Sperimentale per la Lotta Antimalarica, the founding of the Istituto Superiore di Sanità, and the campaign to eradicate mosquitoes in Sardinia. In each of these episodes there was a tension between the international aspects and national aspects of the partnership that to some degree limited its success.     

Imported Malaria in the United Kingdom

Over 2,000 cases of imported malaria have been confirmed by blood examination. Ninety percent. of cases from tropical Africa were infected with P. falciparum. Most of the patients were Caucasians and had primary infections. All developed fever within a month after arrival and most of them within two weeks of arrival. In some patients malaria parasites were seen in routine blood films.Developing forms of P. falciparum were always present in the peripheral blood of patients suffering from a primary attack which was not diagnosed or treated until a week or more after the onset of fever.All deaths investigated were caused by P. falciparum and were primary infections.In not one of the P. falciparum infections did the victim continue taking prophylactic drugs for more than a few days after leaving the endemic area. Had drugs been continued for one month probably not a single overt case of P. falciparum would have occurred.A primary attack of P. falciparum malaria is seldom, if ever, classical in that the fever is never tertian and may resemble clinically many other diseases.Children in boarding-schools returning from the tropics should be supplied with prophylactic tablets and instructions to the matron. If there is an epidemic of a fever any students who have recently returned from the tropics should have a blood film examined for malaria.The risk of contracting malaria among drug addicts is considerable, especially with P. falciparum.     

Malaria in Birmingham 1968-73

During the years 1968 to 1973 70 patients suffering from malaria were admitted to one hospital in England. Twenty had malignant tertian malaria while the remainder had infections caused by Plasmodium vivax, P. ovale and P. malariae. Malaria should be suspected in every febrile patient who has visited a tropical country, and the diagnosis can be confirmed only by examining blood films. Disseminated intravascular coagulation may complicate the disease, and should be considered in every case.British workers spending short periods in malarious areas and Asian immigrants returning home for a holiday are often inadequately instructed about malarial prophylaxis, particularly the need to continue this for at least a month after they return home. Companies and travel agencies should be obliged to provide such instructions.     

The antimalaria campaign in Italy between control and eradication: the Sardinian experiment]

The aim of this paper is to examine historically the alternative between control and eradication of the infectious diseases, starting with the idea of eradication itself, a result of the Pasteurian revolution. The eradication of malaria in Italy is taken as a case study. Through an extensive use of the archival sources, the alternative between control and eradication is analysed for the first years of the Sardinian Project, directed by the Rockefeller Foundation, that resulted in the eradication of malaria in Sardinia. This program is compared with the different program, grounded in the Italian malariological tradition, that in the same years carried out the eradication of malaria in the rest of Italy.     

Molecular monitoring of the Leu-164 mutation of dihydrofolate reductase in a highly sulfadoxine/pyrimethamine-resistant area in Africa

Background

Procalcitonin (PCT) is closely correlated with parasite burden and clinical outcome in falciparum malaria. The role of PCT in tertian malaria has not previously been investigated.

Patients and methods

PCT serum levels in 37 patients with tertian malaria were analysed. Clinical and laboratory parameters were assessed and statistically correlated both to the initial PCT levels and during the course of the disease.

Results

PCT levels rose for one day after commencing treatment and declined thereafter. However, there was no significant correlation with parasite burden, clinical parameters, laboratory values, or the presence of semi-immunity. Before treatment, the majority of patients showed normal or slightly elevated PCT levels (< 2.5 ng/ml), but PCT was markedly elevated (4.8 – 47 ng/ml) in one third of the population. The two groups did not differ by any other of the assessed parameters. Thus, while the post-treatment course of PCT resembles falciparum malaria, the lack of correlation between disease severity and even high PCT levels in a large proportion of patients is intriguing.

Conclusions

There is a fundamental difference in the relationship of PCT with tertian malaria not seen in other infectious diseases in which elevated PCT levels have been observed. This suggests distinct pathophysiological pathways in malaria.     

Forecasting and prevention of epidemic malaria: new perspectives on an old problem

There is a clear need for improved epidemic malaria surveillance mechanisms in areas prone to the disease. Epidemiological surveillance systems are rarely able to provide information in a sufficiently timely manner for adequate epidemic response. This is especially true in African countries where surveillance is poorly developed, and particularly so in remote regions of unstable malaria such as desert fringes. There is long standing evidence linking climatic variability and epidemic risk. The last ten years have seen significant developments in Environmental Information System (EIS) for a range of natural resource management purposes. The routine information products from these systems have been shown to be both spatially and temporally related to malaria transmission indicators across the African continent. EIS may therefore provide a useful and cost effective input to epidemic malaria control planning and response.     

Resurgence of malaria in Bombay (Mumbai) in the 1990s: a historical perspective

Bombay has achieved extraordinary success in controlling its malaria problem for nearly six decades by relying primarily on legislative measures and non-insecticidal methods of mosquito abatement. In 1992, however, malaria reemerged in Bombay with a vengeance. During 1992-1997, the city witnessed a manifold increase in the number of malaria cases diagnosed and treated by the public health system. The large number of malaria patients treated by private practitioners was not recorded by the municipal malaria surveillance system during this period. In 1995, at the peak of the resurgence, public health officials of the Municipal Corporation of Greater Bombay (MCGB) confirmed that 170 persons in the city had died due to malaria. The crisis was unprecedented in Bombay's modern public health history. In response to intense criticism from the media, the city's public health officials attributed the resurgence to the global phenomenon of mosquito-vector resistance to insecticides, and Plasmodium resistance to antimalarial chemoprophylaxis and treatment. Local scientists who investigated the problem offered no support to this explanation. So what might explain the resurgence? What factors led the problem to reach an epidemic level in a matter of two or three years? In addressing the above principal questions, this paper adopts a historical perspective and argues that in the resurgence of malaria in Bombay in the 1990s, there is an element of the 'presence of the past'. In many ways the present public health crisis in Bombay resembles the health scenario that characterized the city at the turn of the 19th century. It is possible to draw parallels between the early public health history of malaria control in Bombay, which was punctuated by events that followed the bubonic plague epidemic of 1896, and the present-day malaria epidemic punctuated by the threat of a plague epidemic in 1994. As such, the paper covers a long period, of almost 100 years. This time-depth is used to illustrate how malaria control programs in Bombay and in other parts of India have evolved through a combination of local historical forces and political expediencies in the context of technological developments. The boom in construction activities in Bombay following the liberalization of the Indian economy in 1991, and the local politics affecting administrative practices of the MCGB, are discussed as crucial factors in the crystallization of the present-day malaria resurgence in Bombay. The paper concludes by arguing that malaria in urban India is a serious problem that cannot be neglected. In the case of Bombay, the solution to the crisis can be found, in part, by reexamining the historical and political issues that have determined the nature and magnitude of the problem over the last century.     

Epidemiology and control of malaria in Colombia

Malaria is currently one of the most serious public health problems in Colombia with an endemic/epidemic transmission pattern that has maintained endemic levels and an average of 105,000 annual clinical cases being reported over the last five years. Plasmodium vivax accounts for approximately 70% of reported cases with the remainder attributed almost exclusively to Plasmodium falciparum. A limited number of severe and complicated cases have resulted in mortality, which is a downward trend that has been maintained over the last few years. More than 90% of the malaria cases in Colombia are confined to 70 municipalities (about 7% of the total municipalities of Colombia), with high predominance (85%) in rural areas. The purpose of this paper is to review the progress of malaria-eradication activities and control measures over the past century within the eco-epidemiologic context of malaria transmission together with official consolidated morbidity and mortality reports. This review may contribute to the formulation of new antimalarial strategies and policies intended to achieve malaria elimination/eradication in Colombia and in the region.     

Eurycoma属植物之化学成分与药理活性研究概况

Eurycoma属植物于东南亚各地广泛地供作药用及食用,主要用于增强性功能,于东南亚各地被视为万应仙丹。本文将概述Eurycoma属植物的化学成分与药理活性的研究进展。     

Observations on the Spores of Pleistophora gigantea (Thélohan, 1895) Swellengrebel, 1911, a Microsporidan Parasite of the Fish Crenilabrus melops*

SYNOPSIS. After 1914 protozoologists have generally agreed that Pleistophora gigantea (Thélohan, 1895) Swellengrebel, 1911, Ichthyosporidium giganteum (Thélohan, 1895) Swarczewsky, 1914, and I. phymogenes Caullery and Mesnil, 1905, are identical. Because no polar filament was found in the spores, however, some authors have followed Swarczewsky in considering this species to be a haplosporidan, while others have persisted in thinking it a microsporidan. Using preserved material that Swellengrebel saved from a tumor on which he based his studies, we have found a polar filament in the spores both with the PAS reaction and with the electron microscpe. This new information removes the only basis for the doubt which some authors have entertained, that Thélohan and Sweliengrebel correctly considered the parasite to belong to the Microsporida. Since Pleistophora gigantea is believed to be identical with I. phymogenes, recently selected by Sprague as type species of genus Ichthyosporidium Caullery and Mesnil, 1905, then Ichthyosporidium, originally assigned to the Haplosporida, must be regarded as a microsporidan genus. Whether it is distinct from all other microsporidan genera is a matter needing further consideration.     

Understanding and improving access to prompt and effective malaria treatment and care in rural Tanzania: the ACCESS Programme

Background

Malaria is a significant public health problem in Tanzania. Approximately 16 million malaria cases are reported every year and 100,000 to 125,000 deaths occur. Although most of Tanzania is endemic to malaria, epidemics occur in the highlands, notably in Kagera, a region that was subject to widespread malaria epidemics in 1997 and 1998. This study examined the relationship between climate and malaria incidence in Kagera with the aim of determining whether seasonal forecasts may assist in predicting malaria epidemics.

Methods

A regression analysis was performed on retrospective malaria and climatic data during each of the two annual malaria seasons to determine the climatic factors influencing malaria incidence. The ability of the DEMETER seasonal forecasting system in predicting the climatic anomalies associated with malaria epidemics was then assessed for each malaria season.

Results

It was found that malaria incidence is positively correlated with rainfall during the first season (Oct-Mar) (R-squared = 0.73, p < 0.01). For the second season (Apr-Sep), high malaria incidence was associated with increased rainfall, but also with high maximum temperature during the first rainy season (multiple R-squared = 0.79, p < 0.01). The robustness of these statistical models was tested by excluding the two epidemic years from the regression analysis. DEMETER would have been unable to predict the heavy El Niño rains associated with the 1998 epidemic. Nevertheless, this epidemic could still have been predicted using the temperature forecasts alone. The 1997 epidemic could have been predicted from observed temperatures in the preceding season, but the consideration of the rainfall forecasts would have improved the temperature-only forecasts over the remaining years.

Conclusion

These results demonstrate the potential of a seasonal forecasting system in the development of a malaria early warning system in Kagera region.     

New Concepts in Treatment of Malaria with Malignant Tertian Cerebral Involvement

Of 140 patients with malignant tertian malaria seen during 1956 to 1967 10 died. Death was caused by cerebral malaria in all cases. Since 1968 more intensified treatment has resulted in the complete recovery of three patients and the partial recovery of one, all of whom had been in a cerebral malaria coma for various periods of time before admission and in whom a fatal outcome was expected. In these cases a polypragmatic therapeutic approach using intravenous low molecular weight dextran, besides the usual quinine and fluids, corticosteroids, heparin and urea, separately or combined, was adopted.     

Transmission dynamics of Plasmodium falciparum

Recent models of malaria have been developed by Gupta and her co-workers. A frequent assumption used to illustrate these models is that levels of malaria are controlled by lifelong strain-specific immunity. In this article, Allan Saul examines the predictions this model makes about the equilibrium values of parasite prevalence and the dynamics of an epidemic following the introduction of a new strain. He reaches the conclusion that the stability of malaria makes long-term strain-specific immunity highly improbable, thus rendering models requiring lifelong strain-specific immunity unlikely to be of relevance in most epidemiological contexts.     

Latent Infections with Plasmodium ovale Malaria

Two cases of Plasmodium ovale malaria acquired in West Africa appeared as primary delayed attacks after one year''s continuous residence in Canada. Both patients took full prophylactic doses of chloroquine before, during, and for several weeks after exposure. The inadequacy of the 4-aminoquinolines for protection against latent benign tertian malaria is noted, and the use of primaquine is recommended. Paroxysms occurred in the evening and were accompanied by severe muscle pain, features considered typical of ovale malaria. One patient showed electrocardiographic changes and clinical signs of cardiac malfunction; these disappeared following specific treatment for malaria. In this age of accelerated travel and international movements of people it is important that physicians in temperate regions be aware of the exotic infections of the tropics, as well as of the need for protective measures for travellers to areas where these diseases are endemic.     

Malaria vaccine development: current status

The development of an effective malaria vaccine represents one of the most important approaches that would provide a cost-effective intervention for addition to currently available malaria control strategies. Here, Howard Engers and Tore Godal review recent advances. Over the past decade there has been considerable progress in the understanding of immune mechanisms involved in conferring protection to malaria and in the identification of vaccine candidate antigens and their genes. Several new vaccines have entered Phase I/II trials recently, new adjuvants have been developed for human use and new approaches, such as DNA vaccines and structural modification of antigens to circumvent some of the strategies the parasite uses to avoid the immune response, are being applied. Thus, from the TDR perspective, global malaria vaccine development is entering a crucial period with unprecedented opportunities.     

Malaria outbreaks in new foci in Sri Lanka

During its Malaria Eradication Programme (1958-1964) Sri Lanka spectacularly reduced its malaria incidence from around half a million per year to 17. Regrettably, this magnificent achievement could not be maintained, and malaria once again reached epidemic proportions in some areas. Of particular concern however, has been the emergence of new foci of malaria around the hill capital, Kandy, discussed here by Manel Wijesundera. The new outbreaks seem intimately related to hydrological changes brought about by major irrigation and hydroelectric schemes on the Mahaweli river. The priority for such schemes is not, of course, to flush out the pools where mosquito larvae thrive, but to divert water for irrigation and power generation. In parallel, human migration between malaria endemic and non-endemic areas - stimulated by the resettlement required by the dam reservoirs - has contributed to increased malaria transmission. In a sense therefore, this story is a classic of health impact overlooked in favour of agricultural and industrial development. But whereas most documented cases relate to extensive flooding causing an increase in vector breeding sites and so exacerbating disease transmission, this story is just the opposite. Here, it is reduction in water flow that has promoted an increase in vector breeding.