[A return of endemic malaria to the Netherlands is highly unlikely]. / Terugkeer van endemische malaria in Nederland uiterst onwaarschijnlijk.

The Netherlands has been free from malaria since the early 1960, due to a combination of factors: active search and treatment of patients and parasite carriers, targeted use of insecticides, changes in farming and in housing of man and cattle, pollution of surface water with phosphates and the fact that surface waters became fresher. These factors reduced the mosquito population that is dependent on brackish water. The Dutch malaria mosquito cannot transmit the parasite of tropical malaria. The mosquito population could possibly increase due to measures to 'develop nature' but the number of parasite carriers, the acute disease manifestations, the quality and organization of the health care system make it extremely unlikely that local transmission will occur. Fears that malaria may become endemic and that the population in the western parts of the country will have to apply malaria chemoprophylaxis in the near future, are unfounded.

Parasitological and haematological responses to treatment of Plasmodium falciparum malaria with sulphadoxine-pyrimethamine in southern Malawi.

In 1993, Malawi introduced sulphadoxine-pyrimethamine (SP) for the treatment of uncomplicated, Plasmodium falciparum malaria and became the first country in Africa to abandon chloroquine for first-time therapy. This decision produced an urgent need to monitor local P. falciparum for resistance to SP and to establish both clinical and parasitological criteria for drug failure. The parasitological and haematological responses to treatment of malaria in southern Malawi with SP have now been investigated. Children, aged 6-59 months, who attended health-care facilities with uncomplicated infections of P. falciparum alone were enrolled in the study. Each received standard treatment with SP and paracetamol and was followed-up on days 3, 7, 14, 21 and 28 post-treatment. Haemoglobin (Hb) was measured on days 0, 14 and 28. Zinc erythroprotoporphyrin (ZP) was estimated once during follow-up, as an indicator of iron status. Of 107 children enrolled, 84 children (78.5%) were followed for 14 days or until clinical failure. The parasitological success rate amongst the latter was 90.5% (76/84). One child showed poor parasite clearance (with a parasitaemia at day 3 > 25% of that at day 0), one had a low level of persistent parasitemia, and six were parasitaemic on day 14 after being parasite free on day 7. A 14-day follow-up increased the detection of parasitological failure by 7.2%. Haematological recovery on day 14 was not significantly different for parasitological successes or failures. The geometric mean parasite density (GMPD) was significantly lower in children classified as iron deficient (ZP > or = 3.0 micrograms/g Hb) and these children were significantly more likely to be severely anaemic (Hb < 8 g/dl) at day 0. Parasitological responses and haemoglobin levels 28 days after SP treatment were independent of ZP levels. These results show that, 2 years after the introduction of SP in Malawi for the treatment of uncomplicated, P. falciparum malaria, the drug combination remains effective in 90.5% of cases. Iron status did not affect parasitological recovery. Although iron-deficient children were at greater risk of severe anaemia they did not show significantly reduced recovery from malarial anaemia.

Falciparum malaria and climate change in the northwest frontier province of Pakistan.

Following a striking increase in the severity of autumnal outbreaks of Plasmodium falciparum during the last decade in the Northwest Frontier Province (NWFP) of Pakistan, the role of climatologic variables was investigated. A multivariate analysis showed that during the transmission season of P. falciparum, the amount of rainfall in September and October, the temperature in November and December, and the humidity in December were all correlated (r2 = 0.82) with two measures of P. falciparum, the falciparum rate (percent of slides examined positive for P. falciparum) since 1981 and the annual P. falciparum proportion (percent of all malaria infections diagnosed as P. falciparum) since 1978. Climatologic records since 1876 show an increase in mean November and December temperatures by 2 degrees C and 1.5 degrees C, respectively, and in October rainfall. Mean humidity in December has also been increasing since 1950. These climatologic changes in the area appear to have made conditions for transmission of P. falciparum more favorable, and may account for the increase in incidence observed in the NWFP in recent years.

The El Niño Southern Oscillation and the historic malaria epidemics on the Indian subcontinent and Sri Lanka: an early warning system for future epidemics?

The recurrent great malaria epidemics which occurred in the Punjab province of former British India and Ceylon before the introduction of residual insecticides have been related to excessive and failing monsoon rains respectively. In the arid Punjab, rainfall facilitated breeding and increased the lifespan of the mosquito vector and, in the wet part of Ceylon, failing monsoon rains caused rivers to pool, creating more favourable breeding conditions. The periodic fluctuations in monsoon rainfall and epidemic malaria are here explained in relation to the El Niño Southern Oscillation. In the Punjab, epidemic malaria between 1868 and 1943 correlates significantly (r = 0.34, P < 0.005) with the sea surface temperature anomalies in the Eastern Equatorial Pacific, a parameter of the oscillation, and epidemics were significantly more prevalent in a year with a wet monsoon following a dry El Niño year than in other years. In Ceylon, epidemics were significantly more prevalent during El Niño years, when the same south-west monsoon tends to fail. With the reduced reliance on residual insecticides and the recurrence of epidemic malaria on the Indian subcontinent, advances made in predicting El Niño events may be used to forecast high and low risk years for future malaria epidemics.

A comparison of amodiaquine and chloroquine in the treatment therapy of falciparum malaria in Kenya.

During June to August 1989, 158 symptomatic outpatients with P. falciparum malaria were randomly treated with either amodiaquine or chloroquine 25 mg/kg, divided over three days. Amodiaquine (Camoquin, Parke-Davis) was significantly more effective in terms of the rate of parasite clearance, 2.4 versus 3.1 days; parasite clearance day 7; 87% versus 41%; and clinical amelioration, 98% versus 68%. Moreover, this study demonstrates the lack of therapeutic toxicity of amodiaquine. Globally, tolerance was better with amodiaquine than with chloroquine; in particular, cutaneous side effects were less frequent with amodiaquine. There was no evidence of granulocyte or gross hepatic toxicity. These results suggest that WHO recommendations concerning amodiaquine should be questioned. In view of its low cost, demonstrated efficacy and lack of proven therapeutic toxicity, amodiaquine should be considered as a viable replacement for chloroquine in areas with high levels of clinical chloroquine failure.

The consequences of malaria infection in pregnant women and their infants.

Preliminary results are presented from this study which indicate that 84.8% of pregnant women present at first antenatal visit with anemia (Hb 11g/dl) an 8.7% of their infants (n = 230) have a hemoglobin at birth below 14g/dl. There is an association between pregnancy anemia and malaria. A case control study in pregnant women and an infant cohort study to 18 months of age, are employed to study the cause and effects of anemia and malaria on women and their infants health.

A study of the consequences of malarial infection in pregnant women and their infants.

An outline is given of a field research study to be undertaken in Malawi to investigate the pattern and consequences of malaria in pregnancy and infants. The central question to be investigated is whether babies born to anaemic mothers in malarious areas are at increased risk of developing anaemia or altered risk for morbidity from malaria or develop anaemia in the first year of life. The framework for the case control and cohort study to be undertaken is outlined.

PIP: Outlined is the protocol for field research in Malawi aimed at ascertaining whether infants born to anemic mothers in areas where malaria is prevalent are at increased risk of morbidity. Specifically, the research seeks to: 1) quantify the prevalence and pattern of anemia in infants living in areas where malaria is endemic; 2) investigate whether birth hemoglobin is associated with clinical risk in infancy; 3) measure the associations between fetal anemia, maternal iron status, and malaria in pregnancy; and 4) quantify the contribution of maternal anemia and iron status to fetal growth retardation. Anemia incidence and malaria prevalence will be assessed through a larger cohort study of infants enrolled at birth and followed for up to 18 months. Also planned is a case-control study that will compare infants born with and without fetal anemia. Odds ratios for maternal anemia, iron deficiency, and parasitemia will be computed for cases and controls to determine the relative contribution of each to fetal hemoglobin status. Finally, the risk of maternal parasitemia, iron deficiency, and anemia will be measured in low-birth-weight, growth-retarded infants and those with normal birth weights. The findings will be used to develop a strategy for anemia control among high risk mothers and infants. This is of particular concern in developing countries, where blood transfusions for anemia can lead to human immunodeficiency virus infection.

Reappearance of Plasmodium malariae in Suriname?

Plasmodium malariae has not been reported from Suriname since 1979. In 1989 an increasing number of P. vivax infections among Bush-negroes returning from the eastern part of the interior was reported in Paramaribo. A microscopical re-examination of all malaria cases in the eastern part of the country failed to confirm any P. vivax infections, but instead P. malariae infections were diagnosed. A study followed to determine the Duffy blood group antigens of 4 Bush-negroes allegedly with a P. vivax infection in their medical history and of 28 and 32 unselected Bush-negroes and Amerindians respectively. Three of the 4 former Bush-negroes had the FyB antigen, while only 7% of the unselected Bush-negroes had this antigen. This low frequency of the genotype is incompatible with reports of high P. vivax prevalences in Bush-negro populations. The Amerindians tested showed a low proportion of Fy0 genotype, which is compatible with the frequent diagnosis of P. vivax among this ethnic group. Reports of P. vivax infections among Bush-negroes are due to misdiagnosis of P. malariae, emphasizing the need to include all 4 species of human Plasmodium when (re)training microscopists. The question whether P. malariae reappeared in Suriname due to increased contact with the simian reservoir, or was simply missed, is discussed.

Flow cytometric screening of blood samples for malaria parasites.

An automated method for the detection and estimation of malaria parasites in blood samples using flow cytometry is presented. In a single-step procedure 50 microliters of blood sample was collected in 1 ml of lysis solution containing formaldehyde, causing red blood cells to lyse while parasites and white blood cells are preserved. Thus prepared, samples could be transported and remained stored in lysis solution until flow cytometric analysis was performed. The cells were stained for DNA with the fluorescent dye Hoechst 33258 and subsequently analyzed by a FACStar flow cytometer. Parasites and white blood cells were distinguished and counted based on blue Hoechst fluorescence and forward scattering. Since red blood cells were lysed, parasite numbers were given related to the number of white blood cells similar to what is done in microscopic examination of thick blood smears. In dilution experiments with animal and human material, parasite counts by flow cytometry correlated very well with the theoretically calculated numbers (regression coefficients of > 0.94). In human material parasitemias of approximately 0.005% were detected. In a pilot study, 700 samples were collected in Thailand and screened by microscopic examination of thick smears and by flow cytometry; 29 were found positive by combining both methods, 2 were missed by flow cytometry, and 20 were missed by microscopists in the field. After microscopic reexamination in the central laboratory, 15 of these 20 were found positive, 5 remained unconfirmed.

[Cutaneous leishmaniasis in 49 patients in The Netherlands]. / Cutane leishmaniasis bij 49 patiënten in Nederland.

In a retrospective study the data concerning 49 patients with cutaneous leishmaniasis were analysed. The group included 39 patients seen in Amsterdam in the period 1979-1988 in the Royal Institute for the Tropics and the University Medical Centre and 10 patients seen in the University Hospital of Leiden in the period 1970-1982. Mediterranean countries, especially Spain, were important sources of infection. In 26 patients, one skin lesion was found. All but one of the patients had (papulo)nodules, nodules with central scab formation and/or ulcerative skin lesions. In most cases the lesions were localized on the face and extremities, one patient had a mucosal lesion of the nose, three had sporotrichoid extension and six, lymphadenitis. For demonstration of the parasite, aspiration, smear, biopsy and culture were used with varying frequencies. The biopsy and culture methods contributed most to the diagnosis. The treatment in 22 patients consisted in parenteral administration of sodium stibogluconate while 13 received primary cryotherapy. In addition, four patients were subjected to cryotherapy because of a recurrence after, or side effects of the treatment with sodium stibogluconate. In three patients, spontaneous healing was awaited. Owing to incomplete follow-up, the ultimate condition was not known of all patients; the skin lesions treated with cryotherapy all healed. In case of nodular and ulcerative skin lesions in a person who has lived in the (sub)tropics, cutaneous leishmaniasis should be considered; the geographical anamnesis is of great importance in this respect.

Automated flow cytometric analysis of drug susceptibility of malaria parasites.

A method is described for the fully automated reading of Plasmodium falciparum drug susceptibility tests. Cultured material was fixed and could be stored for greater than or equal to 6 months until analysis. The parasites were stained for DNA with the fluorescent dye Hoechst 33258 and analyzed by flow cytometry. The procedure was done in 96-well microtiter plates, after which the material was directed through the sensing region in the flow cytometer. The data resulting from the analysis were stored by microcomputer and processed by a program developed for this purpose. Using this method, a number of different parameters describing the growth in culture can be assessed.