Use of doxycycline

Editor, – In Australian Prescriber Vol. 16 No. 4, there are two letters by A.W. Hartwig ('Letters' Aust Prescr 1993;16:76). In a reply to one of these, regarding malaria prophylaxis, Drs I. Riley and A. Cooper state that `... doxycycline is sufficient to suppress P. falciparum but not other species'. In the very next letter, Dr A. Broomhead, after apparently confirming that 'Doxycycline is indicated ... as chemoprophylaxis for malaria caused by P. falciparum', then states that 'Doxycycline is only able to suppress malaria caused by P. vivax'.

Are those not contradictory statements, or is it just that we are suffering from an epidemic of the 'miller's beautiful daughter/beautiful miller's daughter' syndrome of A.W. Hartwig's first letter?

It is quite possible to use words to express unambiguously exactly what is meant. What are the word 'suppress' and the placing of the word 'only' meant to indicate?

In 'suppressing' the malarial parasites, does doxycycline actually kill P. falciparum as opposed to 'only' inhibiting the growth of P. vivax? Or does it suppress 'only' P. vivax and not P. falciparum?

Could I please ask for clarification?

A.G. Moskwa
Senior Lecturer
School of Pharmacy and Medical Sciences
University of South Australia
Adelaide, S.A.

Editor, – In reply to the letter from Dr Hartwig (Aust Prescr 1993;16:76), it has been mentioned that doxycycline 50 mg daily is sufficient to suppress P. falciparum but not other species, whereas in the letter from Dr A. Broomhead the last line says 'Doxycycline is only able to suppress malaria caused by P. vivax.'

Dr A.S. Deshpande
Ahmedabad, India

The following response has been prepared by the Editor after consultation with Professor K. Rieckmann, Army Malaria Research Unit, Professor I. Riley and Dr A. Broomhead:

Certain terms have acquired specific meanings and are well established in the literature of antimalarial chemotherapy and chemoprophylaxis.¹

- Suppressive prophylaxis is the effective prevention of acute attacks of malaria by the action of drugs against the asexual blood forms only.

- Causal prophylaxis is the effective prevention of acute attacks of malaria by the action of drugs against the sporozoite or against the preerythrocytic stages.

Parasites can be present in the bloodstream, but not be detectable on light microscopy (subpatent infection) and not cause clinical malaria. A suppressive prophylactic can be effective but permit subpatent infection. Without the aid of more sensitive tests, evidence of subpatent infection can only be obtained when subjects experience 'breakthrough' while still taking the drug or recrudescence after ceasing the drug.

Doxycycline acts against the asexual erythrocytic stages of P. falciparum and P. vivax. It has only slight activity against the preerythrocytic stages of P. vivax and has recently been shown not to be uniformly effective against the preerythrocytic stages of P. falciparum. As the drug is not active against the dormant tissue forms (hypnozoites) of P. vivax, relapse may occur after cessation of doxycycline prophylaxis.

A dose of 100 mg doxycycline daily can be expected to suppress both P. falciparum and P. vivax malaria by acting against asexual blood, but not tissue, forms. At a dose of 50 mg, P. falciparum is suppressed, but breakthroughs of P. vivax are known to occur.² As chloroquine resistance in P. vivax is still rare, the combination of doxycycline and chloroquine is logical for travellers to areas where P. falciparum and P. vivax co-exist.

Hypnozoites are not affected by either drug so relapses of P. vivax may occur after therapy has been stopped. P. vivax relapse can only be prevented by an 8-aminoquinoline such as primaquine. This drug can be taken by travellers after return from overseas if there has been a heavy exposure to malaria.