Chloroquine resistance is a well established entity in South East Asia, and presents a problem of increasing importance. Strains of P. falciparum resistant to chloroquine have also been found to be resistant to amodiaquine and a combination of pyrimethamine and sulphadoxine. Knowledge of the drug sensitivity of the strains of malaria parasite in a given locality is important so that the right choice of drugs can be made in treatment of the disease. The treatment of chloroquine resistant malaria in West Malaysia is a subject of another paper but suffice it to say that increased doses of chloroquine have still been found to be effective in treating many cases of falciparum malaria from areas of chloroquine resistance.
An account is given of the first hundred consecutive proven cases of sulphone resistance in leprosy, detected in Malaysia between 1963 and 1974. Proof of resistance was clinical in eighty patients and was obtained by drug-sensitivity testing in mice in ninety-six patients; 76 cases were proved both clinically and experimentally, and there was no discrepancy between the two methods. Sulphone resistance was confined to patients with lepromatous-type leprosy--i.e., patients with a large bacterial population. Clinical evidence of relapse due to drug resistance appeared 5-24 years after the start of sulphone treatment. Low dosage favoured the appearance of resistance; therefore regular treatment of lepromatous leprosy with dapsone in full dosage is recommended. The attainment of "skin smears negative for leprosy bacilli" is no test of cure of lepromatous leprosy.
Chloroquine pressure was applied over a 22 month period on a somewhat isolated, malarious rubber estate by examination of residents at 4-week intervals and treatment of parasitaemias with chloroquine. During this time the monthly attack rate for P. falciparum rose four-fold to an average of nearly 18% per month, while that of P. vivax remained relatively constant at about 8%. Eight in vivo chloroquine resistance studies, which allowed both detection of late recrudescing R-I resistance and estimation of the risk of reinfection, showed an apparent rise in the drug resistance rate, from 12% to 20% prior to the study to the range of 40-50%. Virtually all resistance encountered was R-I in nature. There was no convincing evidence of chloroquine resistance among 148 tested P. vivax infections.
In vivo chloroquine resistance surveys, which allowed for detection of late recrudescing RI resistance, were conducted in three regions of Peninsular Malaysia, which were previously not recognized as having appreciable drug resistance. Among the 485 Plasmodium falciparum infections tested resistance rates ranged locally from 20% to 67% in those with parasitaemias over 1,000 per mm3, and 5% to 59% in all parasitaemias. The region found to have the most serious resistance was western Pahang. In one study a combination of chloroquine and pyrimethamine proved no more efficacious than chloroquine alone. Most of the resistance encountered was the late recrudescing RI type. There was no apparent correlation between drug resistance and Anopheles balabacensis as this species was not found despite intensive collections in two of the three main regions. There was no evidence of resistance among the 222 P. vivax and 35 P. malariae infections also tested.
Four strains of S. typhi isolated in Malaysia were found to show resistance to chloramphenicol and other antibiotics. In two of these strains it was possible to show that this resistance was transferable.
This problem which is widespread in neighbouring countries and undetected in Malaysia till recently has now been shown to exist in this country. Fears that the incidence of such strains will increase in the future are expressed and the need for vigilance is emphasised.
Cefotaxime [HR 756], a third generation cephalosporin with pronounced antibacterial activity
against the Enterobacteriaceae, was assessed in serious and problem antibiotic resistant infection. Good clinical success was achieved without observed untoward effects. The study suggests that due to its properties, cefotaxime could be used as a first-line antibiotic provided that the clinical situation warrants the use of a cephalosporin or aminoglycoside.
Key words - cefotaxime [HR 756], serious surgical infection, antibiotic resistant infection.
The status of P. falciparum resistance to chloroquine in Sabah, Malaysia were not know until 1971-1972. Several in-vivo and on in-vivo studies were conducted from 971-1975, and the result showed 51% out of total 57 cases studied were resistant to chloroquine. The latest in-vitro study (collaborative with WHO) started in July 1978, to continue till 1980, to cover the whole State. The preliminary result shows 65 cases (85%) out of a total 76 successful tests are resistant to chloroquine. On the basis of this preliminary result, the radical treatment for P. falciparum infection was changed from chloroquine to Fansidar from June 1979 throughout the State.
A case of Plasmodium falciparum malaria resistant to Fansidar (sulphadoxine plus pyrimethamine) at a level corresponding to R III and resistant to chloroquine is reported. The infection was most certainly acquired in Malaysia, but diagnosed and treated in a non-malarious area. Normal resorption and elimination rates of the Fansidar components excludes cure failure due to abnormal drug fate in the host. P. falciparum parasites from the patient have been maintained in vitro cultures. The patient was permanently cured with mefloquine.