Friday, 5 July 2013

MALARIA: additional questions about Chloroquin

:William Brieger

Date:Fri, Jul 5, 2013 6:37 am
1)      There has been some report also of CQ-antihistamine effectiveness in Southern Nigeria. Could it be that administration of CQ is done in combination with antihistamines that are now known to reverse CQ resistance (at least in vitro)?

There was a study published 5 years ago that addressed this question, but since the advent of widespread use of ACTs, the issue was never taken any further:
Ann Trop Med Parasitol. 2008 Jan;102(1):3-9. doi: 10.1179/136485908X252179.

Comparative study of interactions between chloroquine and chlorpheniramine or promethazine in healthy volunteers: a potential combination-therapy phenomenon for resuscitating chloroquine for malaria treatment in Africa.


Malaria Research Laboratories, Institute of Advanced Medical Research and Training, College of Medicine, University College Hospital, Ibadan, Nigeria.


Although, in in-vitro and limited in-vivo studies, chlorpheniramine (CP) and promethazine (PR) have each been shown to reverse chloroquine (CQ) resistance, the pharmacokinetic basis of this reversal has not been fully elucidated. In the present study, 15 healthy volunteers were randomly allotted to receive standard doses of CQ alone or in combination with CP or PR. Blood samples were collected from each volunteer at 21 time-points, from immediately before to 168 h after the initial dose. These samples were used to follow the changes in the plasma and erythrocytic concentrations of CQ. The ratio between the mean maximum CQ concentration in the erythrocytes and that in the plasma was 4.2 for the volunteers given CQ alone, 7.3 in those given CQ-CP, and 3.2 in those given CQ-PR. CP significantly enhanced the erythrocytic accumulation of CQ, increasing the maximum CQ concentration observed in the erythrocytes by 24% (P = 0.02). The bio-availability of CQ was also significantly increased in the presence of CP, with the mean value for the area under the curve, of erythrocytic concentration v. time, increasing from 99,921 to 214,516 ng/ml.h (P=0.001). The mean half-life of CQ in the erythrocytes also increased when CP was used, from 51 to 100 h, but this change was not statistically significant (P=0.83). In contrast to CP, PR had no statistically significant effect on the disposition of CQ. As CP clearly enhances disposition of CQ, a combination of CQ with CP may be useful in the management of CQ-resistant infections. Detailed toxicological studies are required to understand the full clinical implications of CP's elevation of erythrocytic CQ concentrations.

2)      "Given that Nigeria has a 'talking culture' (as opposed to a writing one),..' Tarry Asoka page 1,  Which means that many of the actions taken by government and her agencies in Nigeria are not evidenced based or at best slanted. The recent experience with polymer bank notes is a case in point. A few years ago we were told it would be the best thing that would happen to our currency. Now, we know better. Yet, the proponents have assumed A SIDDON LOOK posture.  Please, before chloroquine disappears from the scene, let us be VERY SURE the alternatives are AFFORDABLE, BETTER and readily available in rural Nigeria.

Basically CQ no longer work/clears the parasitess in most of Nigeria, although in the far northwest it may be better than nothing. In the southeast I have seen almost dead children who were given the full dose of CQ to no avail.  True the alternative and officially recognized ACTs are more expensive, but from the consumer’s point of view child treatment in public clinics with ACTs should be free – emphasis on should.  ACT is now standard practice, but as the authors in the abstract shown above have said elsewhere, we are not helping people if ACTs are used with the same non-compliance to standard regimens as was CQ.

No comments:

Post a Comment