Semmelweis' discovery and its Finnish follow-up

Professor Ignác Semmelweis (1818-1865) is one of the great personalities of medical history. He insisted on washing hands with chlorine water before any obstetrical intervention, he was the first to demonstrate its importance in preventing puerperal fever. Thus, the principle of asepsis was introduced prior to the discovery of bacteria and bacterial diseases. Semmelweis carefully documented his findings and in this way pioneered the scientific analysis of clinical data Medical community of that time misinterpreted Semmelweis' great ideas, he died abandoned and forgotten. A Finnish doctor Josef Adam Joachim Pippingsk?ld was one of the first obstetricians who had realized the importance of Semmelweis' work. In 1861, in his letter to Semmelweis he reported about his own findings and favorable results in prevention of puerperal fever in Helsinki. Two decades earlier, Dr. Ehrstr?m in the University of Helsinki had submitted his thesis on pathophysiology of puerperal fever that was similar to the ideas of Semmelweis. Long before modern times in Finland, mothers traditionally had their babies delivered in smoke saunas, where heating and smoke of bactericidal phenols created a clean, rather aseptic environment. Hand washing was self-evident necessity. However, the situation was quite different in the Central European universities and departments of obstetrics, where the medical training and clinical practice took place side by side. Semmelweis' life and his contribution to medicine was appreciated even in the theatrical circles of Finland. The piece "Semmelweis" of Norwegian playwright Jens Bj?rneboe got its World Premier in the Swedish Theatre in Turku, former capital of Finland, in September 1969.     

Mosquitoes and transmission of malaria parasites – not just vectors

The regional malaria epidemics of the early 1900s provided the basis for much of our current understanding of malaria epidemiology. Colonel Gill, an eminent malariologist of that time, suggested that the explosive nature of the regional epidemics was due to a sudden increased infectiousness of the adult population. His pertinent observations underlying this suggestion have, however, gone unheeded. Here, the literature on Plasmodium seasonal behaviour is reviewed and three historical data sets, concerning seasonal transmission of Plasmodium falciparum, are examined. It is proposed that the dramatic seasonal increase in the density of uninfected mosquito bites results in an increased infectiousness of the human reservoir of infection and, therefore, plays a key role in "kick-starting" malaria parasite transmission.     

Comparison of some pollen concentrations in Finland and the Estonian SSR

Summary Pollen and spore concentrations were compared in Tartu, Estonia and in three sites in Finland (Turku, Kuopio and Oulu) during May–September 1989. The onset ofQuercus, Pinus, Poaceae,Urtica andRumex flowering started earlier in Tartu than at any site in Finland. The flowering ofJuniperus andArtemisia, on the other hand, began earlier in Turku and Kuopio than in Tartu.Pinus andJuniperus showed a significant correlation (number of pollen grains at the same date) between Tartu and Turku and between Turku and Kuopio. Poaceae andUrtica were correlated between all the sites, as wasRumex except between Tartu and Turku.Artemisia was correlated between Tartu and Turku, Turku and Oulu, and Kuopio and Oulu.Cladosporium correlated between Tartu and Turku. The pollen seasons of Poaceae,Urtica andRumex are prolonged towards the south.     

Regional,temporal, and seasonal variations in births and deaths: the effects of famines

A knowledge of the seasonal variation in births and deaths during normal years is important for analyses of the effects of wars, famines, epidemics or similar privations on these two variables. In studies of seasonality, multiple trigonometric regression models are more flexible than the simple sine curve. The seasonal variation in mortality in Iceland, 1856-1990, shows a strong secular decrease, and a connection between this and the epidemiological transition is considered. As a consequence of the severe famine in Finland in 1867-68, the mortality for the whole year 1868 was almost four times as high as during normal years, and the seasonality of the mortality was even more accentuated. The birth rate in Finland during 1868 was about 70 percent of that during normal years and showed an aberrant seasonality, with a strong trough from October 1868 to February 1869 (fewer conceptions between January and May 1868, when the food shortage was severe).     

Regional,temporal, and seasonal variations in births and deaths: The effects of famines

Abstract

A knowledge of the seasonal variation in births and deaths during normal years is important for analyses of the effects of wars, famines, epidemics or similar privations on these two variables. In studies of seasonally, multiple trigonometric regression models are more flexible than the simple sine curve. The seasonal variation in mortality in Iceland, 1856–1990, shows a strong secular decrease, and a connection between this and the epidemiological transition is considered. As a consequence of the severe famine in Finland in 1867–68, the mortality for the whole year 1868 was almost four times as high as during normal years, and the seasonality of the mortality was even more accentuated. The birth rate in Finland during 1868 was about 70 percent of that during normal years and showed an aberrant seasonality, with a strong trough from October 1868 to February 1869 (fewer conceptions between January and May 1868, when the food shortage was severe).     

The El Niño southern oscillation and malaria epidemics in South America

A better understanding of the relationship between the El Ni?o Southern Oscillation (ENSO), the climatic anomalies it engenders, and malaria epidemics could help mitigate the world-wide increase in incidence of this mosquito-transmitted disease. The purpose of this paper is to assess the possibility of using ENSO forecasts for improving malaria control. This paper analyses the relationship between ENSO events and malaria epidemics in a number of South American countries (Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname, and Venezuela). A statistically significant relationship was found between El Ni?o and malaria epidemics in Colombia, Guyana, Peru, and Venezuela. We demonstrate that flooding engenders malaria epidemics in the dry coastal region of northern Peru, while droughts favor the development of epidemics in Colombia and Guyana, and epidemics lag a drought by 1 year in Venezuela. In Brazil, French Guiana, and Ecuador, where we did not detect an ENSO/malaria signal, non-climatic factors such as insecticide sprayings, variation in availability of anti-malaria drugs, and population migration are likely to play a stronger role in malaria epidemics than ENSO-generated climatic anomalies. In some South American countries, El Ni?o forecasts show strong potential for informing public health efforts to control malaria.     

A dendroecological reconstruction of use by Saami of Scots Pine (Pinus sylvestris L.) inner bark over the last 350 years at Sädvajaure,N. Sweden

The historical use of Scots Pine (Pinus sylvestris L.) inner bark by the Saami near Lake Sädvajaure, N. Sweden was studied with dendro-ecological methods. Damming of the lake for hydroelectric power enabled destructive sampling of all pines with scars from bark peeling in an area of 870 ha. A total of 111 dead and live pines with 136 bark peelings were found. Stem-sections were taken for cross-dating to determine the precise peeling year and season. The oldest peeling was dated to 1618, which is the oldest reported evidence of Saami use of inner bark. No bark peelings were made after 1870 in the studied area which coincides with a shift to more extensive reindeer herding, and with colonization by Swedish farmers in the area. The regular use of inner bark over time and the absence of peeling peaks in known agrarian famine years support the hypothesis that inner bark was used regularly, and not only as an emergency food. Changes in spatial peeling activity around the lake is interpreted as temporal changes in nomadic fishing activity. We conclude that tree ring studies can provide valuable information about former mobile use of natural resources by Saami in boreal forest landscapes.     

Trimethoprim resistance in hospitals.

During November 1980 to April 1981, 1561 urinary tract pathogens were collected from Turku City Hospital, Turku University Central Hospital, and Kuopio University Central Hospital. Resistance of the strains was tested by agar-plate dilution against trimethoprim, sulphamethoxazole-trimethoprim, sulphamethoxazole, ampicillin, and nitrofurantoin. Resistance to trimethoprim (greater than 8 mg/l) occurred in 8.6-12.2% of strains from the university hospitals (Pseudomonas excluded) and 38.3% of strains from Turku City Hospital. Resistance of Escherichia coli occurred in 4.1-6.2% of strains from the university hospitals and 21% of strains from Turku City Hospital. Proteus mirabilis was the most resistant of the clinically important bacterial species with resistance to trimethoprim in 29-78%. Attention is called for in defining the type of hospital used for a particular study: bacterial resistance in different hospitals cannot be compared direct and one hospital is not necessarily representative for a whole country. After seven years'' use of plain trimethoprim the prevalence of resistance in the two university hospitals in Finland was similar to that in a London hospital just before plain trimethoprim was registered for use in Britain.     

Bark consumption of voles in relation to snow cover, population density and grazing impact

The voles Microtus agrestis and Clethrionomys glareolus consume more bark in north than in south Sweden in spite of lower availability in the former area due to snow-pressed ground. Field experiments with genetically homogeneous aspen sticks demonstrated that this pattern reflects differences in animal behaviour and not differences in plant palatability. Within a region consumption in snow-pressed areas was usually less than in subnivean spaces or runways. The amount of bark consumption was generally correlated with population density and amount of grazing impact. Great differences in bark consumption between north Swedish areas with high peak vole populations and south-central Swedish areas with moderate peak numbers imply that nutrition is of different importance at population declines in different regions. The ability of voles to move into snow-pressed areas and locate woody sticks in the snow suggests that control of ground cover will not protect tree seedlings at reforestation.     

Malaria and World War II: German malaria experiments 1939-45

The epidemiological and pharmacological fight against malaria and German malaria research during the Nazi dictatorship were completely under the spell of war. The Oberkommando des Heeres (German supreme command of the army) suffered the bitter experience of unexpected high losses caused by malaria especially at the Greek front (Metaxes line) but also in southern Russia and in the Ukraine. Hastily raised anti-malaria units tried to teach soldiers how to use the synthetic malaria drugs (Plasmochine, Atebrine) properly. Overdoses of these drugs were numerous during the first half of the war whereas in the second half it soon became clear that it would not be possible to support the army due to insufficient quantities of plasmochine and atebrine. During both running fights and troop withdrawals at all southern and southeastern fronts there was hardly any malaria prophylaxis or treatment. After war and captivity many soldiers returned home to endure heavy malaria attacks. In German industrial (Bayer, IG-Farben) and military malaria laboratories of the Heeres-Sanit?ts-Akademie (Army Medical Academy) the situation was characterised by a hasty search for proper dosages of anti-malaria drugs, adequate mechanical and chemical prophylaxis (Petroleum, DDT, and other insecticides) as well as an anti-malaria vaccine. Most importantly, large scale research for proper atebrine and plasmochine dosages was conducted in German concentration camps and mental homes. In Dachau Professor Claus Schilling tested synthetic malaria drugs and injected helpless prisoners with high and sometimes lethal doses. Since the 1920s he had been furiously looking for an anti-malaria vaccine in Italian mental homes and from 1939 he continued his experiments in Dachau. Similar experiments were also performed in Buchenwald and in a psychiatric clinic in Thuringia, where Professor Gerhard Rose tested malaria drugs with mentally ill Russian prisoners of war. Schilling was put to death for his criminal research in 1946, Rose was condemned to lifelong imprisonment in 1947, though, not for his malaria research but for his dreadful experiments with epidemic typhus sera which he also had performed in concentration camps and with prisoners of war in Russia.     

The development of Malaria Early Warning Systems for Africa

Current efforts to predict malaria epidemics focus on the role weather anomalies can play in epidemic prediction. Alongside weather monitoring and seasonal climate forecasts, epidemiological, social and environmental factors can also play a role in predicting the timing and severity of malaria epidemics. Such factors can be incorporated into a framework for malaria early warning.     

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.     

Endemic malaria: an 'indoor' disease in northern Europe. Historical data analysed

Background

Endemic northern malaria reached 68°N latitude in Europe during the 19^th century, where the summer mean temperature only irregularly exceeded 16°C, the lower limit needed for sporogony of Plasmodium vivax. Because of the available historical material and little use of quinine, Finland was suitable for an analysis of endemic malaria and temperature.

Methods

Annual malaria death frequencies during 1800–1870 extracted from parish records were analysed against long-term temperature records in Finland, Russia and Sweden. Supporting data from 1750–1799 were used in the interpretation of the results. The life cycle and behaviour of the anopheline mosquitoes were interpreted according to the literature.

Results

Malaria frequencies correlated strongly with the mean temperature of June and July of the preceding summer, corresponding to larval development of the vector. Hatching of imagoes peaks in the middle of August, when the temperature most years is too low for the sporogony of Plasmodium. After mating some of the females hibernate in human dwellings. If the female gets gametocytes from infective humans, the development of Plasmodium can only continue indoors, in heated buildings.

Conclusion

Northern malaria existed in a cold climate by means of summer dormancy of hypnozoites in humans and indoor transmission of sporozoites throughout the winter by semiactive hibernating mosquitoes. Variable climatic conditions did not affect this relationship. The epidemics, however, were regulated by the population size of the mosquitoes which, in turn, ultimately was controlled by the temperatures of the preceding summer.     

Blue mussels (Mytilus edulis) in the diet of roach (Rutilus rutilus) in outer archipelago areas of the western Gulf of Finland,Baltic Sea

The blue mussel (Mytilus edulis) is one of the key species in the Baltic Sea ecosystem and it is living at the edge of its range in the western Gulf of Finland. Roach (Rutilus rutilus) is a freshwater fish species that has benefited from recent coastal eutrophication and is at present highly abundant in the outer archipelago of the Gulf of Finland. In 2000 and 2001, a total of 516 roach were sampled for diet analysis in three study areas. Shelled molluscs formed over 95% of the diet of roach, blue mussels being the dominant single species. The proportion of this species in the food of roach in the three study areas ranged between 38–61% for smaller roach (<225 mm) and 39–85% for larger (>225 mm) roach, indicating that blue mussel is a highly important food source for roach in outer archipelago areas of the western Gulf of Finland, in contrast to reports from other parts of the northern Baltic Sea. The scarcity of large blue mussels in mussel beds in the easternmost study area was reflected in the lower proportion of blue mussels in the diet of larger roach. However, the growth of roach was not affected by the availability of blue mussels. The twofold differences observed in the annual growth of roach between warm and cold years demonstrated that temperature is an important factor controlling the growth of roach in the western Gulf of Finland.     

Geographical distribution of Allium oleraceum cytotypes in Finland and Sweden

Chromosome numbers from a total number of 226 populations of Allium oleraceum were determined in Finland, Sweden and seven other countries. Two different chromosome numbers or cytotypes were found, tetraploids (2n = 32) and pentaploids (2n = 40). In Finland, samples were collected for chromosome counts from a total of 190 populations, which fairly well covers the distribution area of the species in Finland. The majority of the populations of A. oleraceum in Finland contained only one of the two cytotypes. A clear pattern in the geographical distribution of the cytotypes could be distinguished. The pentaploid cytotype predominates in the Åland Islands and in the archipelago of Regio aboënsis. The tetraploid cytotype predominates on the mainland of the Regio aboënsis and along the coast of the Nylandia. In south Häme, all studied native populations were of the tetraploid cytotype. Of all the studied populations in Finland 43.7% were tetraploid and 51.6% pentaploid. A few mixed populations with both tetraploid and pentaploid plants occurring in the same population were also found (4.7%). The chromosome numbers of 19 populations of A. oleraceum from the southern part of Sweden were pentaploids, with the exception of one tetraploid population. It seems that the pentaploid cytotype is predominant in Sweden, but no conclusions about a geographical pattern between the two cytotypes could be drawn. Based on the occurrence of the cytotypes, it is suggested that the pentaploid cytotype might have spread to Finland from the Swedish east coast via the Åland Islands to Kaland on the Finnish west coast and along the coast of Nyland to the archipelagos of Kotka and Hamina in Karelia australis. The tetraploid populations in south Häme are clearly connected to Iron Age activity and to old inland trade routes, and may be of eastern origin.     

Q & A. Philip Ingham

Philip Ingham grew up in Liverpool and graduated from Cambridge University in 1977. He did his D.Phil in Developmental Genetics at Sussex University and postdoctoral work in Strasbourg, France before joining the laboratory of David Ish-Horowicz at the ICRF Mill Hill Laboratories. Here he applied the emerging technique of tissue in situ hybridisation to the analysis of the Drosophila segmentation genes. After a short spell at the MRC Laboratory of Molecular Biology in Cambridge, he rejoined the ICRF as a Research Scientist at the Developmental Biology Unit in Oxford. His group pioneered the analysis of the Hedgehog signalling pathway in Drosophila and in collaboration with the labs of Andy McMahon and Cliff Tabin at Harvard University, discovered the Hedgehog gene family in vertebrates. In 1996 he was appointed Professor of Developmental Genetics at the University of Sheffield where he has established the Centre for Developmental Genetics.     

Control of epidemic malaria on the highlands of Madagascar

The Malagashy national malaria control programme ('Programme National de Lutte contre le Paludisme', PNLP) has been developing, since 1996, an epidemiological early warning system for malaria epidemics in the Central Highlands with the support of the Italian Development Cooperation. The system is based on the monitoring of malaria morbidity (clinical diagnosis) in 536 peripheral health centres (CSB) of the Highlands. The intervention area corresponds to 27 districts of the Antananarivo and Fianarantsoa provinces (4.7 million inhabitants) and spans around 100,000 square km. For each CSB a monthly warning threshold, defined as the 1993-1996 monthly mean number of malaria cases plus two standard deviations, was established. Three levels of epidemic alert have been defined according to the number of times the cases of presumptive malaria surpassed the threshold and according to the reported presence of severe malaria cases. The surveillance system relies also on the monitoring, in district hospitals of the Highlands, of the Plasmodium falciparum infection rate among clinically diagnosed malaria cases. A total of 185,589 presumptive malaria cases, corresponding to a 42/1000 malaria incidence, were recorded in 1997 by the surveillance system. During the same year 184 alerts of 2nd degree were reported. During 1998 173,632 presumptive malaria cases corresponding to a 38/1000 incidence were reported and 207 alerts of 2nd degree were detected; 75 of these alerts were investigated with ad hoc surveys and 3 initial malaria epidemics identified and controlled. Out of 6884 presumptive malaria cases diagnosed in the district hospitals during 1997-1998, only 835 (12.1%) have been confirmed by microscopy (P. falciparum 81.7%, P. vivax 15.0%, P. malariae 2.5%, P. ovale 0.2%, mixed infections 0.6%); 22.4% of these infections were imported cases from coastal endemic areas. The efficiency of the system in monitoring the trend of malaria morbidity and in the rapid detection and response to malaria epidemics is still being evaluated.