Recrudescence

Fish gonadal recrudescence assay effects on light and temperature sensitive sexual maturation. 

Artemisinin and its derivatives, artesunate and arthemether, kill both asexual and sexual blood stages (Fig. 2). However, artemisinins are quickly eliminated from the body, resulting in parasite recrudescence, and are therefore combined with schizontocides that have a longer biological half-life, such as amodiaquine,... 

Cidofovir 0.3%, 1%, and 3% topical agent used on a compassionate basis for acyclovir-resistant herpes lesions (3-7 days) Application site reactions, lesion recrudescence... 

Saxena, P.K. and Garg, M. Effects of insecticidal pollution on ovarian recrudescence in fresh water teleost Channapunctatus (Bl), Indian J. Exp. Biol, 16 689, 1978. 

The disadvantage of either regimen is a recrudescence of disease symptoms during the glucocorticoid-free interval. 

For uncomplicated falciparum malaria there are several options (with the major drawback in brackets) halofantrine (arrhytmia), mefloquine (neurotoxicity), quinine (vomiting, tinnitus), artemether (recrudescence), atovaquone-proguanil (possible fast development of resistance). 

Empirically it is known that effective drug concentrations are needed for at least 3 parasite-life cycles (=6 days) to obtain cure without recrudescence. By combining a drug with a fast action but short half life such as artemether and an agent with a slow action and long half life the treatment course can be short (2-3 days) which will benetit compliance, the patients condition will improve fast and resistance-development might be delayed. 

Hemandez-Rauda R., G. Rozas, P. Rey, J. Otero, and M. Aldegunde (1999). Changes in the pituitary metabolism of monoamines (dopamine, norepinephrine, and serotonin) in female and male rainbow trout (Oncorhynchus mykiss) during gonadal recrudescence. Physiological and Biochemical Zoology 72 353-359. 

In an attempt to switch the patient to the less expensive L-type CCB verapamil for discharge, she was introduced slowly to the transition on a blind basis and was also unable to maintain her previous degree of clinical improvement with carbamazepine and nimodipine (Figure 6-5C). Maximally tolerated daily doses were 320 mg of verapamil and 600 mg of carbamazepine. In light of this recrudescence of clinical symptomatology, the patient was introduced to the transition on a blind basis back to nimodipine, and substantial recapturing of her clinical responsivity was again observed. After a slowly tapered transition to the less expensive dihydropyridine CCB... 

It shows rapid schizonticidal action and brings about quick clinical improvement in falciparum malaria with low recrudescence rate. It has some gametocidal action too. 

That curious occult philosophy which constitutes the basis of alchemy in the modern sense of the term, derived from the Greek neoplatonists and transmitted mainly through Arabian disciples, was to find a recrudescence with, if possible, more extravagant manifestations of credulity, mysticism and charlatanism in the western alchemists of the fourteenth to the eighteenth centuries, a development greatly fostered also by the revolt from authority which culminated in the Protestant Reformation and was facilitated by the printing press in the latter part of the fifteenth century. 

Our study confirms the clinical effectiveness of LNIT in reducing clinical symptoms and drug intake under natural allergen exposure. Specific LNIT appears to offer considerable advantages over other hyposensitization methods. As a matter of fact parenteral therapy is in many cases unsuccessful (incomplete and temporary) regarding recrudescence of symptoms, and, from an immunological point of view, produces a systemic immune response without interesting the local one of fundamental importance in upper airway reactivity. 

The mechanism of action for such peroxidic compounds involves a reductive activation by iron in haem, released as a result of hemoglobin digestion by Plasmodium. This irreversible redox reaction affords carbon-centered free radicals causing the alkylation of haem and of proteins. One such protein (the sarcoplasmic-endoplasmic reticulum ATPase PfATP6) appears to be critical for parasite survival, and there is no indication for resistance by the parasite. However, treatment is expensive and recrudescence of malaria occurs often. Moreover, it was found that at high doses such compounds are neurotoxic. 

Patients not at risk of reinfection should be reexamined several weeks after treatment for signs of recrudescence which may result from inadequate chemotherapy or survival of persistent hepatic forms. 

All three Artemisia derivatives are quickly hydrolysed to the active substance dihydroartemisinin. They produce a more rapid clinical and parasitological response than other antimalarial drugs. There are no reports of significant toxicity, and as late as 1994 there was no convincing evidence of specific resistance, but chloroquine-resistant Plasmodium berghei is resistant to artemisinin as well. The recrudescence rate is fairly high (1). 

The artemisinin derivatives are limited by an unacceptable incidence of recrudescence with monotherapy, and they therefore need to be used in combination. A summary of prospective trials that looked specifically for adverse effects showed that artemisinins alone are very well tolerated (10). The same study showed no evidence of adverse interactions of artesunate with mefloquine, with an incidence of adverse effects similar to that expected from malaria and mefloquine (25 mg/kg) together. Reducing doses of mefloquine increases recrudescence rates to unacceptable levels (11). Combinations of artemisinins with quinine, co-trimoxazole, and doxycycUne are well tolerated. 

In a double-blind, randomized study in Vietnam (n — 227), extending the duration of oral artemisinin monotherapy 500 mg/day from 5 to 7 days did not reduce recrudescence rates (total 23%) (20). 

Artemisinin derivatives (artesunate and artemether) for the treatment of multidrug-resistant Plasmodium falciparum malaria have been evaluated in 83 Karen pregnant women in Thailand 55 women were treated for recrudescent infection after quinine or mefloquine, 12 for uncomplicated hyperparasitemic episodes, and 16 had not declared their pregnancy when treated (32). 

Boudreau EF, Fleckenstein L, Pang LW, Childs GE, Schroeder AC, Ratnaratorn B, Phintuyothin P. Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria and in healthy volunteers. Clin Pharmacol Ther 1990 48(4) 399-t09. 

In humans pefloxacin was tested in a dosage of 400 mg every 12 hours for 3 days against chloroquine-resistant P. falciparum infections in Madagascar, and proved successful in 9 out of 22 cases seven further cases responded at first but recrudescence followed. The investigators suggested that pefloxacin should be used as a complementary drug rather than as a primary antimalarial drug. 

The novel combination (Artekin ) of dihydroartemisinin and piperaquine has been assessed in 106 patients (76 children and 30 adults) with uncomplicated P. falciparum malaria in Cambodia (1). The respective doses of dihydroartemisinin and piperaquine, which were given at 0, 8, 24, and 32 hours, were 9.1 and 74 mg/kg in children and 6.6 and 53 mg/kg in adults. All the patients became apar-asitemic within 72 hours. Excluding the results in one child who died on day 4, there was a 97% 28-day cure rate (99% in children and 92% in adults). Patients who had recrudescent infections used low doses of Artekin. Adverse effects, most commonly gastrointestinal complaints, were reported by 22 patients (21%) but did not necessitate premature withdrawal. 

Adverse effects of quinine are common at plasma concentrations over 10 pg/ml. The dose often recommended, 10 mg/kg intravenously over 10-20 minutes, may be too high in patients with cerebral malaria (SEDA-14, 240). In the USA, intravenous quinine has been discontinued in favor of quinidine (SEDA-17, 329). In some areas, a high rate of recrudescence is seen after short-term treatment with quinine. The addition of specific antibiotics may improve the cure rate. 

Topical corticosteroids usually result in some clinical improvement in putative viral keratitis in the horse. However, subsequent recrudescence and worsening of the clinical signs can be a problem, and their use during the acute stages of the disease is not recommended. They can be used with caution in conjunction with the antiviral agent once epithelial repair is complete, when they may promote stromal clearing. There is anecdotal evidence that topical ciclosporin has some therapeutic benefit in type 2 keratitis in the horse (see p. 239). 

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