Background: Malaria in North-East sector is the most important cause of morbidity and if not treated in time, leads to mortality. Troops are engaged in counter insurgency Ops in this area & deployed all over in the known hyper endemic malaria Zone; notified chloroquine resistant areas both by National Anti Malaria Programme (NAMP) & State Health Depts.
Presently chloroquine is the only drug used for chemoprophylaxis in Army for malarious zones even in chloroquine resistant pockets. It is argued that continuation of chloroquine as suppressive is not justified and as an alternative, more acceptable drugs need to be used
A study with chloroquine & proguanil has been carried out in other areas in the sector but compliance of taking proguanil daily was very poor due to its frequency.
Therefore two groups were taken, one large gp in area A which was on Tab chloroquine 300 mg/ weekly as per” forces Policy “ and other small group in area B placed on Cap Doxycycline 100 mg daily as a pilot project, keeping in view the same frequency, easy availability and easy compliance.
AIM: To find out the comparative efficacy differential in suppressive treatment with Tab chloroquine and Doxycycline
Material & Method: The adequate amount of tablets were demanded & distributed to troops. All troops were subjected to consumption of Tab Chloroquine (300 mg) once a week under supervision without fail after meals. They were given enough dose of Tab Chloroquine, when proceeding on leave. Diagnostic facility was improved by provisioning of MT malaria detection Para check kit.
Incoming new troops were placed on suppressive treatment at least 2 weeks prior to arrival in area (Though policy is 4 weeks).
Results: There is definite reduction in the incidence of malaria during 2010 (0.20/1000) as compared to 2008 (0.52/1000) & 2009 (0.59/1000) with chloroquine 300 mg, provided the compliance is strictly ensured with the active participation of supiriors. The results of the pilot study in area B indicated that suppressive treatment with Doxycycline is effective in prevention of malaria. There was significant difference in the incidence rate of malaria compared to chloroquine. It is therefore recommended as a food for thought that a study on a larger scale with a greater statistically significant sample size over a prolonged duration of time be carried out to substantiate the findings of this pilot study. The collateral advantage of the Doxycycline will also provide Chemoprophylaxis against Leptospirosis, plague, Scrub typhus.
Malaria in North East sector of India is the most important cause of morbidity and if not treated in time, leads to mortality. Troops are engaged in counter insurgency operations in area A & deployed all over in the known hyper endemic malaria Zone. The area includes Karbi Anglong, Silchar (Assam), Bishanpur, Kakching (Nagaland) and Agartala etc, which are heavily forested & situated along international borders. These are notified chloroquine resistant areas both by National Anti Malaria Programme (NAMP) & State Health Depts.
Presently chloroquine is the only drug used for chemoprophylaxis for malarious zones even in chloroquine resistant pockets. Chloroquine may be used where the parasite is still sensitive.  However due to resistance one of three medications: mefloquine (Lariam),doxycycline (available generically), and the combination of atovaquone and proguanil hydrochloride (Malarone) is frequently needed. It is argued that continuation of chloroquine as chemoprophylaxis is not justified and as an alternative, more acceptable drugs need to be used. Specific regimens are recommended by the WHO, UK HPA and CDC for prevention of P. falciparum infection. HPA and WHO advice are broadly in line with each other (although there are some differences). CDC guidance frequently contradicts HPA and WHO guidance.
These regiments include:
* doxycycline 100 mg once daily (started one day before travel, and continued for four weeks after returning);
* mefloquine 228 to 250 mg once weekly (started two-and-a-half weeks before travel, and continued for four weeks after returning);
* atovaquone/proguanil (Malarone) 1 tablet daily (started one day before travel, and continued for 1 week after returning).
In areas where chloroquine remains effective:
* chloroquine 300 to 310 mg once weekly, and proguanil 200 mg once daily (started one week before travel, and continued for four weeks after returning);
A study with chloroquine & proguanil has been carried out in this area, but compliance of taking proguanil daily was very poor due to its frequency.
Therefore two groups were taken one large gp in area A which was on Tab chloroquine 300 mg/ weekly as per” Forces Policy” and other small group in area B placed on Cap Doxycycline 100 mg daily as a pilot project, keeping in view the frequency, easy availability and easy compliance .
To find out the comparative efficacy differential in chemoprophylaxis with Tab chloroquine and Doxycycline.
1. To compare incidence of malaria among groups of troops on chloroquine 300 mg weekly and Doxycycline 100 mg daily as chemoprophylaxis.
2. To analyze decrease if any in the incidence of malaria among troops with Doxycycline as chemoprophylaxis against chloroquine.
Material & Method
All troops in the area A (approx 15000 plus) are considered as study population. The compliance of chloroquine 300 mg as suppressive treatment commenced from top to bottom ranks among troops. It was ensured that all troops in the area take suppressive treatment once a week. The troops were counseled before the start of chemoprophylaxis.Strict compliance of suppressive treatment was the criteria as it was made compulsory for all troops, under strict supervision.
The adequate amount of tablets were demanded & distributed.
* All troops were subjected to consumption of Tab Chloroquine (300 mg) once a week under supervision without fail after meals.
* They were given enough dose of Tab Chloroquine, when proceeding on leave.
* Diagnostic facility was improved by provisioning of Malaria detection Para check kit.
* Incoming new troops were placed on chemoprophylaxis at least 2 weeks prior to arrival in area (Though policy is 4 weeks).
* Anyone who suffered from malaria was treated & given radical treatment prior to discharge.
Pilot project with doxycycline
Another study was carried out in area B with Cap Doxycycline 100 mg daily in place of Tab Chloroquine. The study population was divided in two groups. Experimental group of 151 individuals (X location) and control group 137 individuals (Y location) both were in malarious & notified chloroquine resistant area as per NMAP. Duration of study was wef 01 May 10 to Oct 10 & follow up was carried out till 15 Nov 10 for outcome variables in terms of cases of fresh local malaria from 15th May to Nov 10.The longest incubation period of 14 days was covered before and after the study period. Diagnostic criteria were taken as malaria positive by paracheck test.
Inclusion Criteria: Troops on chemoprophylaxis for 122 day or more and between 31 Oct to 15 Nov 10 was included in outcome criteria.
Exclusion Criteria: Troops not on chemoprophylaxis and away for 63 days or more & troops developing malaria between 01 May to 15 May.
Conduct of Study: All troops present on 01 May 10 in both control & experiment group were made part of study. Troops on leave/Temporary duty were given suppressive treatment for entire duration of absence, all fever cases were subjected to Para check test. At the end, all individuals completing 122 days with chemoprophylaxis. (¾ of entire duration of 184 days) were compiled.
Observations & Results
Total number of malaria cases admitted in the year 2008 & 2009 to various hospitals in sector have been compared with total number of cases in the year 2010 till 10 oct 10.
Results indicate that there is definite reduction in the incidence of malaria cases admitted to hospitals in 2010 (0.20/1000) as compared to 2008 (0.52/1000) & 2009 (0.59/1000). This can be attributed to strict compliance of suppressive treatment policy.
Result of pilot project: - Total strength of subjects considered for this study as per inclusion & exclusion criteria were as under:-
Exp Group &nbs p; - 91
Control Group - 111
Comparative incidence of malaria per 1000 troops in control & Experimental Group for the year 2008- 2010
In the year 2008 & 2009, Chloroquine as suppressive treatment was used in both the Exp and Control groups. There is no significant difference in the incidence rate of malaria in the 2008-2009. In the year 2010, Chloroquine as suppressive treatment was used in the Control Group ( Y location ) and Doxycycline as suppressive treatment used in the Exp group ( X location ), a significant difference was observed in the rate of incidence of malaria in Control & Exp Groups.
Comparative efficacy of Doxycycline and Chloroquine (Table 3)
Incidence in Exp Group &nbs p; - 0
Incidence in Control Group - 63 per 1000
Efficacy of Doxycycline - 100 % in prevention of malaria
The efficacy of Doxycycline chemoprophylaxis is 100%. In other words, Doxycycline chemoprophylaxis reduced the occurrence of malaria by 100% in this pilot study in very small group in malarious area.
As per the analysis of the results of cases admitted in hospitals in area A it is evident that suppressive treatment with chloroquine 300 mg is effective, provided the compliance is strictly ensured with the active participation from the top level downward, which needs combined & coordinated effort & suitable appropriate advise for sustained results.
Cases occurred even after the strict compliance of suppressive treatment, this could be due to
(a) Non compliance by certain individuals.
(b) Irregularity in compliance by certain individuals (left for 2 or 3 Weeks).
(c) Not consuming suppressive treatment during leave.
(d) 60% of cases admitted in hospitals gave history of irregularity in taking suppressive treatment during operations in jungles.
(e) Chloroquine resistance among these cases.
As per the analysis of the results of this pilot study in area B and observation with chloroquine with large sample in area A, it is evident that suppressive treatment with Doxycycline is effective in prevention of malaria. There is significant difference in the incidence rate of malaria in 2010 in the Exp and the control groups as compared to 2008 & 2009 against chloroquine. No side effects/ adverse reactions were noticed in any of the troops. It was well tolerated.
The efficacy of Doxycycline chemoprophylaxis is 100%. In other words, Doxycycline chemoprophylaxis reduced the occurrence of malaria by 100%. Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. (5)
This being a pilot study, there are certain inherent lacunae’s. The sample size was very small and may not be statistically significant to draw any firm conclusions. The duration of the study was for only 6 months, therefore the significant difference observed in this study needs to be further verified.
It is therefore recommended that a study on a larger scale with a greater statistically significant sample size among civil population over a prolonged duration of time may be carried out to substantiate the findings of this pilot study for general population.
The collateral advantage of the Doxycycline will also provide prevention against Leptospirosis, plague, Scrub typhus and other diseases which are prone to occur in North East sector. Hence if recommended, in place of chloroquine, then Doxycycline only will be able to cover other diseases also as Chemoprophylaxis.
1. Jacquerioz FA, Croft AM (2009). "Drugs for preventing malaria in travellers". Cochrane Database Syst Rev (4): 006491.doi:10.1002/14651858.CD006491.pub2. PMID 19821371
2. The World Health Organisation provides country-specific advice on malaria prevention.
3. 2007 guidelines are available from the UK Health Protection Agency website as a PDF file and includes detailed country-specific information for UK travellers.
4. The Centers for Disease Control and Prevention website hosts constantly updated country-specific information on malaria. The advice on this website is less detailed, is very cautious and may not be appropriate for all areas within a given country. This is the preferred site for travellers from the US.
5. Kathrine R. Tan, Alan J. Magill, Monica E. Parise, and Paul M. Arguin. Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis. Am J Trop Med Hyg. 2011 April 5; 84(4): 517–531.
Source(s) of Funding
This article has been downloaded from WebmedCentral. With our unique author driven post publication peer
review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is
completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript
but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before
submitting any information that requires obtaining a consent or approval from a third party. Authors should also
ensure not to submit any information which they do not have the copyright of or of which they have transferred
the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to
the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor
replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the
WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm
that you may suffer or inflict on a third person by following the contents of this website.