Search

Malaria should always be ruled out in patients with fever who visited the tropics in the recent past. Even a long period of time after returning or after antimalarial treatment, malaria may be present due to relaps, recrudescence or a postponed first episode. Hypnozoites of P. vivax and P. ovale are dormant stages in the liver and not detectable in the blood, but can wake moths after inoculation. In this case, we show a patient with a mixed infection with P. falciparum and P. ovale. However, due to the absence of the erythrocytic stage of P. ovale, this species was not detected and caused symptoms weeks after treatment with artemisinin based therapy.

On 3 March 2020, the document 'Drug treatment options for patients with COVID-19 (infections with SARS-CoV-2)' was published on the website of the Dutch Working Party on Antibiotic Policy (StichtingWerkgroepAntibioticabeleid, SWAB). Based on a 7-step analysis of the literature, hydroxychloroquine (HCQ) and chloroquine (CQ) were initially included in the SWAB document as possible drug treatments for hospitalised adult COVID-19 patients. However, recent weeks have seen the publication of the results of various studies into the effectiveness of treatment with HCQ and CQ in patients with COVID-19. On the basis of these results, we conclude that there is insufficient evidence to consider HCQ and CQ as meaningful treatment options in patients with COVID-19. Clinically relevant QTc prolongation occurs in at least 1 in 10 COVID-19 patients treated with HCQ or HQ.

The new global strategy to achieve long-term malaria eradication is based on rapid treatment of individual malaria patients and blocking the spread of Plasmodium parasites in the population. In a number of countries increased funding combined with more effective control measures have resulted in a substantial decline in the incidence of malaria and in the resulting morbidity and mortality. Increasing resistance of Anopheles mosquitoes to insecticides (pyrethroids and DDT), and reduced sensitivity of Plasmodium parasites to various antimalarials increase the need for the development of new vector control strategies and medicines. Vaccine development efforts have been speeding up and a first vaccine is expected within three years.

To investigate the availability of antimalarial agents for the treatment of falciparum malaria in all Dutch hospital pharmacies, including changes in the situation over a period of two years.Descriptive.In the period October 2006 to March 2007 all Dutch hospital pharmacies were questioned about the availability of antimalarial agents, by means of a telephone survey. The survey was repeated at the end of 2008.The percentage of hospitals that had quinine in stock increased from 72 (62 of the 86 hospitals responding) to 80 (73 of 91 hospitals). In 2008 artesunate was in stock in 7 hospitals. At the end of 2008 18 Dutch hospitals had no medication available for the treatment of severe malaria tropica; 6 hospitals had no agents for the treatment of malaria at all.The ideal situation, in which every hospital in the Netherlands has a supply of adequate agents for the treatment of severe malaria, has not yet been achieved.

Er gaat ieder jaar veel geld om in de - chemische - bestrijding van malariamuggen. Maar dankzij een veelbelovende schimmel staat een heel nieuwe, duurzame aanpak voor de deur, zeggen medisch entomologen Bart Knols en Willem Takken. 'Het is toch schrijnend dat we aan het begin van de eenentwintigste eeuw nog steeds afhankelijk zijn van DDT.'

Er gaat ieder jaar veel geld om in de - chemische - bestrijding van malariamuggen. Maar dankzij een veelbelovende schimmel staat een heel nieuwe, duurzame aanpak voor de deur, zeggen medisch entomologen Bart Knols en Willem Takken. 'Het is toch schrijnend dat we aan het begin van de eenentwintigste eeuw nog steeds afhankelijk zijn van DDT.'

To describe the outcome of 21 successive patients with falciparum malaria treated with artemether-lumefantrine in 6 oral doses of 80-480 mg in 96 hrs (5-day schedule).Retrospective cohort study.The data on all successive patients with falciparum malaria that were treated with artemether-lumefantrine in the Leiden University Medical Centre (n = 15) and the Bronovo Hospital (n = 6), the Netherlands, during the period from August 2003 to February 2006 were evaluated.Ten patients with uncomplicated falciparum malaria were treated exclusively with artemether-lumefantrine; time to parasitological clearance was less than 48 hrs in 5 out of 6 tested patients. The mean admission time was 1.3 days (95% CI: 0.7-1.9). 6 patients with non-severe falciparum malaria were initially treated with intravenous quinine because of vomiting; artemether-lumefantrine was started after an average of 0.9 days. Parasite clearance required more than 48 hrs in all patients. The mean admission time was 3.8 days (95% CI: 2.7-4.9). 5 patients had severe falciparum malaria. They received artemether-lumefantrine 4-24 hrs after starting quinine therapy. The parasite count was0.1% after an average of 1.5 days (95% CI: 0.3-2.7). The mean admission time was 4.2 days (95% CI: 2.2-5.2). The serum level of lumefantrine wasor = 500 microg/l (target value) in 9 out of 10 tested patients.Treatment of falciparum malaria with artemether-lumefantrine according to a 5-day schedule resulted in a swift recovery and short admissions. No relapses were reported.

Only a few drugs are available for the treatment of malaria. Artemisinin combination treatment is advocated because of its efficacy and to prevent the development of resistance. In the Netherlands, falciparum malaria is treated with atovaquone-proguanil or artemether-lumefantrine, both registered as 3-day treatments. In a recent study, 21 patients were treated with artemether-lumefantrine for 5 days. There are arguments in favour of a 5-day course: absorption of lumefantrine is dependent on food intake and the serum levels of lumefantrine are higher on day 7 after a 5-day course than after a 3-day course. As shown by studies in Thailand, the serum level is related to the relapse rate, although these studies revealed no difference in relapse rate between the 3- and 5-day courses. In endemic countries, short courses of treatment are favoured to further patient compliance. Artesunate for i.v. administration is urgently needed.

A 28-year-old patient had suffered from fever, headache, abdominal pains and vomiting for the past three weeks. She had visited a region in the Dominican Republic where the risk of malaria is considered to be low. The complaints were initially regarded as a viral infection. Later, however, she was found to have severe falciparum malaria. She recovered completely following antibiotic therapy. Since November 2004, 17 cases of falciparum malaria have been reported world-wide among travellers to non-endemic regions in the Dominican Republic. Physicians should always consider the possibility of malaria in travellers because a timely diagnosis of falciparum malaria can be of vital importance.

A 39-year-old man, who had made a cycling tour from Tibet to Nepal, visited the outpatients' clinic one month later because of prolonged diarrhoea, abdominal complaints and serious weight loss. Parasitological examination of the stool revealed oocysts of Cyclospora cayetanensis and the patient was treated with trimethoprim-sulfamethoxazole (co-trimoxazole) with good result. C. cayetanensis has only recently been discovered as a protozoal cause of diarrhoea. Infections are primarily reported from areas with a low hygienic standard e.g. Central and South America, the Indian subcontinent (Nepal), Indonesia and South-East Asia. Clinical symptoms of infection are diarrhoea (usually watery), abdominal cramps and discomfort. The infection can have a prolonged course. Diagnosis is made by parasitological examination of the stool (one should be cautious not to confuse with cryptosporidia) and treatment with trimethoprim-sulfamethoxazole is effective.

During a flight to Kenya, a 42-year-old man took a therapeutic dose of chloroquine because of fever. He regularly travelled to Africa and always took chloroquine and proguanil for malaria prophylaxis. The fever disappeared but he did not fully recover. He complained of malaise and weight loss. Fourteen years previously he had suffered from amoebic dysentery. One month after the onset of the patient's complaints, an amoebic liver abscess was suspected on the basis of his medical history, an elevated ESR and a slight leukocytosis. The diagnosis was confirmed by ultrasonography and serology.

In November 1999 nine European cases of malaria caused by Plasmodium falciparum reportedly were imported by tourists from the Dominican Republic. The incidence of malaria has increased since the hurricane George and since building activities for tourist centres have favoured growth of the mosquito population. Travellers to the Dominican Republic are advised to take precautions against mosquitoes and to take proguanil prophylaxis also malaria should be considered in patients with fever who have visited the area, if only as tourists.

Hairs are produced in hair follicles that have a cyclic activity. The cycles that normal hair follicles go through are the metabolically active anagen phase, the catagen transitional phase and the resting telogen phase. Loss of more than 120 hairs daily is called alopecia. Drugs typically cause a diffuse, reversible alopecia by influencing one of the cycles that hair follicles go through. Because hair loss can have many causes, a causal relationship between a suspected drug and hair loss may be hard to prove. The principal categories of drugs that may cause alopecia listed in the literature are cytostatics, anticoagulants, interferons, tretinoid derivatives and lithium carbonate. The Netherlands Pharmacovigilance Foundation LAREB has received reports of alopecia as side effect of antimalarials, beta-receptor blocking agents, sex hormones, ACE inhibitors, angiotensin II antagonists and anticoagulants.

In 1996 and 1997 the Dutch Pharmacovigilance Foundation LAREB received 6 reports of patients with convulsions that were attributed to prophylactic use of mefloquine. Five patients had no neurological history; one patient had a history of epilepsy but had not had any convulsion during the preceding 5-year period. The convulsions took place 1 to 23 days after start of the treatment with mefloquine. Because of the convulsions, the treatment was discontinued. The 4 patients with known follow-up showed full recovery with regard to the convulsions. The practising physician should be aware of the possible occurrence of rare neuropsychiatric adverse events like convulsions during the prophylactic use of mefloquine.

Recently, the Dutch Working Group on Malaria Prophylaxis produced new national guidelines. The new approach takes the risk of malaria and of serious morbidity or mortality for the individual traveller as its point of departure. In large areas in the tropics, there is no malaria risk. In some areas with limited risk, proguanil is still an effective chemoprophylactic (mainly in Central America, the Near East, Central Asia and parts of Indonesia). However, multiple-drug resistant Plasmodium falciparum necessitates the use of mefloquine, despite disturbing side effects in some people, in Sub-Saharan Africa, major parts of South East Asia and the Amazone basin of South America. If mefloquine is contraindicated, alternatives advised are the combination of proguanil and chloroquine or (in South East Asia) doxycycline. For visits to transmission areas lasting 7 days or less, alternative prophylactic measures may be acceptable, but only if the traveller after the visit has easy access to adequate medical facilities. When exposure lasts not more than two nights, use of a mosquito net, repellents and protective clothing without chemoprophylaxis is acceptable, provided the traveller is well informed. To take along pocket treatment is only advised for some journeys lasting more than one month to areas with multiple-drug resistant falciparum malaria. When mefloquine prophylaxis is used, such stand-by treatment is only advocated for a few countries in South East Asia; when mefloquine cannot be given, also for other areas. The type of pocket treatment recommended depends on the chemoprophylaxis used and on whether contraindications exist. Drugs that can be used are: halofantrine (if no contraindications exist and an ECG shows no prolongation of the QT interval) or quinine, either alone (in pregnancy) or combined with doxycycline or clindamycine (the latter for children8 years). With the new individual approach advice may differ for different persons visiting similar tropical areas. It is the physician's task to explain the risks of a particular journey and the measures advised.

Two patients, a 25-year-old woman and a 62-year-old man, with Plasmodium vivax infection, suffered repeated attacks of malaria despite standard treatment with chloroquine and subsequently primaquine. The relapses were due to a combination of decreased primaquine sensitivity and incorrect prescription of primaquine. Primaquine is administered as diphosphate (salt), but the required amount has to be prescribed as base (26.3 mg diphosphate corresponds to 15 mg base).

The diagnosis of malaria should include the species involved and in case of P. falciparum infection the parasitaemia index: the percentage of the infected red cells. P. vivax, ovale and malariae infection are treated with chloroquine, in case of P. vivax and ovale malaria followed by primaquine. Mefloquine and halofantrine are indicated for chloroquine-resistant vivax infections. Advice on management and treatment is different for mild and severe (or = 5% infected erythrocytes or presence of complications) P. falciparum infections. Mild infections may be treated on an outpatient basis. In severe infections quinine has to be started immediately, while frequent checks of vital functions and blood parameters are indicated. New treatment options are the use of artemisinine (preparations) or atovaquone, both efficacious and low in adverse effects and toxicity.

The natural products quinine and artemisinine have been effective antimalarials for centuries. Most synthetic antimalarials were developed because of pressure of war; against all some degree of resistance has developed. The newer drugs are too expensive for large-scale use. Development of new antimalarials is financially too risky for the pharmaceutical industry. Co-operation among industries, research institutes, governments and international organizations is coming off the ground. Dutch researchers should contribute to international malaria research for humanitarian reasons and out of self-interest, for the benefit of public health.

To investigate the prevalence of health problems and compliance with respect to malaria prophylaxis of travellers to the (sub)tropics.Travel department of the Public Health Care Centre Groningen, the Netherlands.Retrospective follow-up study.A questionnaire was sent out to 450 visitors to the Public Health Care Centre. They had stayed in the (sub)tropics for at most three months. Two subgroups used malaria prophylaxis (mefloquine or proguanil/proguanil-chloroquine): the control group used no prophylaxis.40% of the 321 responders reported health problems during their stay in the (sub)tropics. Users of proguanil (with or without concurrent chloroquine prophylaxis) reported significantly more health problems (55%). Symptoms reported most frequently were vomiting and diarrhoea. Insomnia and neuropsychiatric disorders were reported only rarely (1%) and these complaints were equally distributed over the prophylaxis subgroups. The reported compliance with chemoprophylaxis was 77%.The frequently reported psychiatric complaints during use of mefloquine were not confirmed by this study. The compliance with malaria prophylaxis in this study was similar to that in other studies.

A 58-year-old man and his 60-year-old wife returned from a journey through Indonesia with complaints of persisting diarrhoea. In the stools of both patients we found oocysts of the parasite Cyclospora cayetanensis. We treated them with co-trimoxazole which resulted in fast clinical improvement. An infection with the parasite C. cayetanensis should be considered in travellers returning from tropical countries with persisting diarrhoea. Despite the self-limiting nature of the infection treatment with co-trimoxazole 960 mg 2 dd for 7 days may be considered in cases with a protracted course.

After her holiday in South Africa, a 50-year-old woman was admitted because of fever and pain in the upper abdomen. The laboratory tests showed moderately increased serum liver enzyme activities. The liver biopsy showed a granulomatous hepatitis. Further investigations revealed no evidence for sarcoidosis, tuberculosis or infectious hepatitis, nor for other granulomatous diseases or infectious diseases relevant to South Africa. Upon discontinuation of the malaria prophylaxis with Daraclor (pyrimethamine and chloroquine (sulphate)) the symptoms disappeared and the liver function tests returned to normal. It was concluded that Daraclor was the probable cause of granulomatous hepatitis in this patient. This adverse effect was not published before.

Drug resistance is a major problem in malaria. The resistance mechanism remains unresolved but contributing factors are probably heavy drug use, parasite selection, cross resistance and genetic influences of drugs. Plasmodium ovale en P. malariae are sensitive to the current antimalarial drugs. P. vivax has some chloroquine resistant strains, notably on Papua New Guinea, Irian Jaya and other islands in the Pacific. The geographical distribution of P. falciparum strains resistant to proguanil and pyrimethamine is not well known. Chloroquine-resistant strains are found in South East Asia, the Amazon region (almost 100% resistance in both regions) and in Africa south of the Sahara (resistance not everywhere 100%). Sulfadoxine-pyrimethamine is not an effective treatment in South East Asia and the Amazon region; it is useful in tropical Africa. Mefloquine resistance is a problem mainly confined to Thailand. There is cross resistance between halofantrine and mefloquine. Decreased sensitivity to quinine was reported from Thailand, but it remains an effective drug, notably when given in combination with tetracycline or doxycycline. In cases of severe or complicated malaria intravenous quinine is still the preferred therapy. Resistance to artemisinine has not yet been reported. Pharmaceutical companies show little interest in antimalarial drug development, which in view of the increasing drug resistance is a matter of great concern.

Aqueous and lipophilic extracts of Neurolaena lobata (Asteraceae), obtained from Guatemala, were tested against Plasmodium falciparum in vitro. Moreover, sesquiterpene lactones, of the germacranolide and furanoheliangolide type, isolated from N. lobata, were shown to be active against P. falciparum in vitro. In addition to their antiplasmodial activity, their cytotoxic effects on human carcinoma cell lines were evaluated. Structure-activity relationships are discussed.

To determine how and where malaria was diagnosed in a forestry area in South-Vietnam and how it was treated.Descriptive.Hieu Liem, Dong Nai province, Vietnam.In the government hospital and health posts malaria diagnosis and treatment were free of charge while treatment had to be paid for in four private clinics. A population survey was carried out in the forestry area and outside this area: the people were examined for splenic enlargement and a blood sample was analysed.Most patients went to private clinics and it was here that malaria was most frequently diagnosed. In 7.5% of the population in the forest area parasites were found while 1.8% of those living outside the forest appeared to have parasites in the blood. None of the persons with parasitaemia had splenomegaly. Splenomegaly was found in 2.9% of the population, 6.7% in and 0.9% outside the forest area.Recent changes in the health sector in Vietnam have liberalized malaria treatment, possibly control. The wide distribution and extensive use of effective drugs like artesunate and mefloquine have probably contributed to reduction of (severe) malaria, but development of resistance to these drugs is to be feared. Control of drug distribution and of prescription practices is urgently needed.

To gain insight into the changes concerning diagnosis and treatment of malaria since 1984.Retrospective.University Medical Centre, Amsterdam.From October 1991 to October 1992, 74 patients with malaria were diagnosed and treated. Country of origin, plasmodium strain involved, country of infection, interval between return to the Netherlands and onset of symptoms, prophylaxis and therapy, were recorded in every case.Of these patients 46 (62%) were of European origin; 28 were born in endemic malarial areas. Plasmodium falciparum was diagnosed in 49 of the 74 patients; 88% of these infections were acquired in subsaharan Africa, mainly West Africa. In falciparum malaria, the first symptoms were noticed I-30 days after returning home. P. vivax infections occurred up to 2 years after return. Five of the 49 patients developed severe complications; 2 died. Twenty-six (53%) of the 49 patients had not taken any chemoprophylaxis. The patients with falciparum malaria were treated with sulfadoxine-pyrimethamine or halofantrine, often combined with quinine; the cure rate was 90%.Quinine remains the mainstay in the treatment of complicated falciparum malaria, but is also often used in the initial treatment of uncomplicated malaria. Compliance in malaria prophylaxis still remains a problem.

From 1986 to 1990 we have treated 215 patients with falciparum malaria. In 8 patients (4%) who had not returned to any malarial area, malaria attacks recurred after 6-20 weeks. Curiously these were now caused by different species: Plasmodium vivax (4 patients) and P. ovale (4 patients). After proper management of malignant tertian malaria caused by P. falciparum, patients are considered cured, provided the treatment has been in accordance with the resistance pattern of the parasite in the country of origin. Yet, in a small number of patients attacks of malaria recur after different time intervals. The explanation of this seemingly paradoxical phenomenon is that these were delayed primary attacks of benign tertian malaria rather than recrudescences of malignant tertian malaria. Consequently the patients must have been infected by two different species of malaria at a time. In P. vivax and P. ovale hypnozoites occur (notably absent in P. falciparum), dormant stages in the liver that are not susceptible to the antimalarials in use for the eradication or prophylaxis of the blood stages which cause the acute attacks of malaria. After a variable amount of time the blood is then (re)invaded and the patient suffers a delayed primary attack or a relapse. Physicians should be aware that definite cure of malignant tertian malaria does not prevent future attacks of benign tertian malaria. They should inform their patients accordingly.