An Apicomplexan by any other name ..... is still a Protozoan

Frank E. Cox, of the London School of Hygiene and Tropical Medicine, makes the most unflattering accusation in his article "Systemics of Parasitic Protozoa". He asserts that 'parasitologists' have completely ignored the relationships revealed by 'protozoologists', between and among non-parasitic protozoan groups and that they "continue to be embedded in the classifications of the 1980s" (Cox, 2002). Ooh, ouch ! I feel that such a great wrong must soon be corrected. So, let us get right to it !

The scientific community has moved on from Whittaker's Five Kingdom classification system that you and I learnt in school. Cavalier-Smith, in 1998, proposed a "Revised Six Kingdom System" in which all botanical life was classified into Kingdoms Fungi, Plantae and Chromista, zoological species into Protozoa and Animalia, while Bacteria were awarded their own kingdom (Cavalier-Smith,1998). In an earlier paper, he proposed 18 phyla under the Kingdom Protozoa, of which Phylum Apicomplexa was but one.

Other classification styles developed before this time, rule that the three phyla Apicomplexa, Dinozoa (Dinoflagellates) and Ciliophora (Ciliates like Paramecium) must be grouped together under the monophyletic group Alveolata.  All members have a subsurface alveoli, microtubules, mitophores and mitochondria with ampulliform or tubular cristae. (Adl et al.,2005)

Cavalier-Smith proposed that the phylum Apicomplexa be further subdivided into two subphyla : Apicomonada and Gamontozon, the latter of which is divided into "infraphylum" Sporozoa (whose members have nine singelet centrioles, complete conoids and conidial rings and the general presence of oocysts and sporocysts in their life cycles) and infraphylum Hematozoa (whose members have a more primitive centriole and lack the presence of oocysts and sporocysts, instead undergoing merogony in vertebrate erythrocytes and gametogony in arthropod guts). (Cavalier-Smith,1993)

In his letter, Cox suggests that based on new analysis Apicomonada has lost its supposed relatedness to the other Apicomplexans (which certainly is true, because it had initially contained only mollusc parasites), and so Sporozoa must be restored to Phylum status (Cox, 2002). This suggestion was apparently not widely accepted, as proved by latter scientific articles that still call the phylum Apicomplexa. Textbooks including popular ones like 'Georgis' Parasitology for Veterinarians' get around this dilemma by adding 'Sporozoa' in parentheses after 'Apicomplexa'.

The traditional grouping of the Apicomplexans, on the basis of phenotype, host, tissue and vector, has been under four broad categories : Coccidians, Gregarines, Haemosporidians and Piroplasms.Each of the groups are defined below:

Coccidia : "host specific, intracellular parasites of the intestines and other organs, of vertebrates with alternating asexual and sexual phases of development resulting in the production of environmentally resistant oocysts in the feces of definitive hosts" (Barta , 2009)

Gregarines : " extra/intra cellular protozoan parasites with large mature gamonts that develop extracellularly with most exhibiting syzygy in their developmental cycles" (Barta , 2009)

Hemosporidians : "obligate heteroxenous blood parasites that undergo sexual development in Dipteran flies and asexual development in vertebrate host" (Dimitrov, 2013)

Piroplasms : Pleomorphic, heteroxenous with an incomplete apical complex; lacks an oocyst stage and flagella (Adl,2005)

Molecular phylogenetic analysis has only added to the confusion by suggesting corrections to canonical taxonomic nomenclature, that is more often not followed by others save the original authors of scientific papers. In the midst of this melee, Cryptosporidium occupies an unique phylogenetic niche. It does not exhibit the cellular vampirism exhibited by the dinoflagellates and gregarines, does not possess variant surface proteins and lacks an apicoplast (a genome- containing plastid-like organelle, homologous to chloroplasts). Analysis of the small subunit ribosomal RNA suggests that the genus is more closely related to the Archigregarines than the Coccidians, but still forms its own clade. With the Archigregarines, Cryptosporidium shares these important characters : monoxenous life cycle, oocyts with four sporozoites, a usual location in the host gastrointestinal tract and extracellular gamonts or trophozoites. (Barta , 2006)

The Tree of Life Web Project has the following "hypothetical tree" for the phylum Apicomplexa showing the major branches viz. clades:

(http://tolweb.org/onlinecontributors/app?service=external/ViewImageData&sp=46943 ; Creative Commons License) 

At long last, we come to the real problem. The real question. If taxonomy is so inconstant, how will we/one study diversity and (dare I say it) evolution? There has been a clamour for a taxonomic scheme that will reflect phylogeny.

With this in mind, Morrison D. in a paper titled "Prospects for elucidating the phylogeny of Apicomplexa" lists five important changes that need to occur before any useful, directed progress can be made.

1. Taxon sampling
Anthropocentric research driven by economics and the relative veterinary-medical interest of the parasite has resulted in small, biased sample-data that do not adequately define the boundaries of taxa. Genebank is chock full of Plasmodium, Cryptosporidium, Theileria, Babesia and Toxoplasma sequences, whilst the Eimeria, Sarcocystis, Isospora and Gregarina have few to no representatives. Morrison also states that outgroups and basal taxa must be better studied to help classify already known species into clades.

The accusation of skewed sampling seems quite true. A search on NCBI revealed that as of today (6 Jan 2014), only 47 Apicomplexan species (of the many thousands that exist) have had their complete genome sequenced. All these are virulent parasites of animals/man.

2. Multiple molecular data sets
Frequently, trees are constructed on the basis of one gene (Quite simply because whole genomes are not available to play around with). Such trees, however, are not a true reflection of the relationship between species and clades. Among the Apicomplexans, the 18rRNA gene is most studied. But this gene is most prone to variation in terms of copy number. Other genes commonly studied are the HSP70, Actin, and a few mitochondrial genes. Morrison suggests that analyses be made with multiple gene sets, making sure that both nuclear and organellar genes (the latter show maternal inheritance) are included. Organellar genes can include mitochondrial genes and apicoplast (when they exist) genes.

3. Phylogentic analyses
Sequence alignment and tree building using the default parameters built into bioinformatic tools is naive, reproaches Morrison. Artifacts may arise from sequence length variation due to indel events, compositional variations like AT content and will not be resolved by multiple analyses (neighbor-joining, max-likelihood etc). Data must not violate the assumptions of the many analyses.

4. Reinterpretation of homologies
The thing about new knowledge is that it must agree or disagree completely or in degrees with old knowledge. Often reinterpretation is essential if we intend to get something worthwhile out of all our research efforts at all. A great example cited by Morrison, and which I spoke about in my previous post is the ineffectiveness of anti-coccidials on Cryptosporidium, easily explained by the genus not belonging to Coccidia.

5. Directed Data Collection
"The collection of pertinent data for the Apicomplexa can be best described as haphazard, which is unlikely to be of much practical value phylogenetically", laments Morrison. He proposes the formation of an informal group which would more likely be able to reach a consensus, over an autocratic formal group or a lackadaisical large group.(Morrison, 2008). I agree with him in that, for any progress from these mires of ignorance, directed data collection is essential.


Some, with adequate reason, have no interest at all in the systemics of taxonomy. Others are absolutely enthralled by the nuances of biological nomenclature. I, being one of the latter, have tried to understand the complexity of the system and have briefly presented the above the way I have understood it. Undoubtedly, the above is not absolute and is subject to change. But, change we will  (our understanding and even our knowledge base) when the time comes. Till then, I'll leave you here on the shores of (the land of ) Systemics. So long. Farewell !


References :

1. Adl SM, Simpson AG, Farmer MA, et al. The new higher level classification of eukaryotes with emphasis on the taxonomy of protists. J Eukaryot Microbiol 2005;52:399-451.

2. Barta JR, Thompson RC. What is Cryptosporidium? Reappraising its biology and phylogenetic affinities. Trends Parasitol 2006;22:463-468.

3. Cavalier-Smith T. Kingdom protozoa and its 18 phyla. Microbiol Rev 1993;57:953-994.

4. Cavalier-Smith T. A revised six-kingdom system of life. Biol Rev Camb Philos Soc1998;73:203-266.

5. Cox FE. Systematics of the parasitic Protozoa. Trends Parasitol 2002;18:108.

6. Moore RB, Oborník M, Janouskovec J, et al. A photosynthetic alveolate closely related to apicomplexan parasites. Nature 2008;451:959-963.

7. Dimitrov, D., Valkiunas, G., Zehtindjiev, P., Ilieva, M., & Bensch, S. (2013). Molecular characterization of haemosporidian parasites (Haemosporida) in yellow wagtail (Motacilla flava), with description of in vitro ookinetes of Haemoproteus motacillae. Zootaxa, 3666(3), 369–381.

8. Morrison DA. Prospects for elucidating the phylogeny of the Apicomplexa.Parasite. 2008;15(3):191-6.

9. Šlapeta, Jan and Victoria Morin-Adeline. 2011. Apicomplexa Levine 1970. Sporozoa Leucart 1879. Version 18 May 2011. http://tolweb.org/Apicomplexa/2446/2011.05.18 in The Tree of Life Web Project

Cryptosporidiosis in dogs : Add another agent to the differential diagnosis list, why don't you?

I started my research for this post under the assumption that I was soon going to be buried under a ton of clinical articles and good-practice reviews about Cryptosporidium infections in dogs. I came away bitterly disappointed at the utter lack of clinical pointers.I had fully expected a well defined, pathognomonic diagnostic finding , to have been developed and published under the aegis of one Veterinary Association or the other. Unfortunately, that does not seem to be the case.

Ordinarily, when a case presents with diarrhea, a vet would try to narrow down the possible causes, . A list called the "Differential Diagnosis List" is (mentally) made which is conveniently divided into infectious and non infectious etiological agents that could have caused the clinical sign(s). Agents are eliminated based on clinical evidence and the results of the tests at the clinician's disposal. 'Cryptosporidiosis' is listed among the glorified ranks of Tritrichomonas foetus, Giardia sps, Balantidium coli and metazoans under the broad category of 'Parasites that cause diarrhea' in that definitive guide of lists, called "Differential Diagnosis in Small Animal Medicine"(edited by Gough A.). Listing the disease and not the agent is still a thing of great curiosity to me. On the list that runs six pages, Cryptosporidium has scored a spot. If Cryptosporidium caused diarrhea in dogs frequently, it would earn a firm place on the DD list of  every veterinarian.

However, allow me make a statement that seems to defy all clinical logic, but is firmly within the grasp of commonly understood parasitology knowledge : Cryptosporidium canis, C. parvum and C. meleagridis  (all of which have been found in dogs) do not always seem to produce "clinical" disease in dogs. They are typical parasites, carried along for the journey, which do not really harm the host. They seem to favour featuring in multiple etiology dramas, playing the roles of supporting parasites, neither sufficient nor necessary, over the role of protogonist parasites that direct the ebb and flow of the disease.

To treat this "disease" in dogs with the commonly available coccidiostats would be utterly silly and would cast a clinician in poor light , because the parasite is technically not a Coccidian to begin with. The taxonomy tempests have not been stilled on the displacement of Cryptosporidium from the Coccidian Apicomplexans.

Now, for a brief review of clinical research.
In 2000, the "Dog genotype" was validated by phylogenetic analysis of 18S and HSP70 as the new species, Cryptosporidium canis . (Morgan et al., 2000). Publications have implicated C.canis as the causal agent in both canine and human patients, including a case of a HIV infected human patient who harboured the canine genotype. (Pieniazek et al., 1999) But, how clinically relevant these are, is highly debatable

In the first infection report of Cryptosporidiosis in a week old pup, published in 1983, the authors include this disclaimer, "Cryptosporidia may have played a role in the enteritis seen in this pup, but further studies are needed to establish its pathogenecity". That is, the fact that they saw organisms that resembled Cryptosporidium could have been a happy coincidence, or in strict Pathology terms, "an incidental finding" that masked an insidious underlying cause. (Wilson et al., 1983) It has been established since that "Morphology is not a reliable tool for delineating species within Cryptosporidium" (Fall et al., 2003). Thus, it is impossible to know, which species of Cryptosporidium had infected the pup or if there had been another agent , say CPV that had coinfected it.

In a paper published in the Journal of American Animal Hospital Association in 1999, Willard and Bouley describe the fatal case of an immunocompromised 8 wk old dog that was coinfected with Cryptosporidium and other Coccidia. Which came first - the immunocompromise or the infection - is unknown.

Titilincu et al., in a paper titled "Prevalence of Cryptosporidium Spp. in asymptomatic dogs by ELISA and risk factors associated with infection" , published in Lucrari Stiiniifice Medicina Veterinara Vol XLIII (I) , in 2010 maintain that 53% of the 374 sampled dogs were positive on the ELISA, but were clinically asymptomatic. The positive animals when serotyped, were found to be infected with C.canis.

In a longitudinal study (from birth to 1 year of age) published in Acta Veterinaria Scandinavica in 2007 by Hamnes et al., Cryptosproridium was found by immunofluorescent staining in 44.1% of the 290 sampled animals from Norway. Since they used a direct FITC conjugated MAb against C.parvum, the samples identified were of course exclusively C.parvum. Again, the glaringly obvious point in the study is the complete lack of clinical data to support a clinical infection.

Despite the above mentioned studies, the jury is still out on the importance of Cryptosporidium sps. as a pathogenic agent in dog diarrhea, and we are left to ponder on these questions that will still haunt us:
1. Does Cryptosporidium canis actually cause disease in dogs?
2. What percentage of the cases harbour other enteric pathogens?
3. Do detection methods matter? Is it better to perform a PCR on a clinical sample than to perform a ZN staining on it ?
4. Should all cases that are positive using PCR be prescribed coccidiostats irrespective of clinical status ?
5. Should we add the agent to our DD list just to be safe ?

While some answers are obvious, others require a fair bit of clinical and lab research. To assume that answers will be obtained without both working together is obviously foolish.

References :
Morgan UM, Xiao L, Monis P, et al. Cryptosporidium spp. in domestic dogs: the "dog" genotype. Appl Environ Microbiol 2000;66:2220-2223.

 Pieniazek NJ, Bornay-Llinares FJ, Slemenda SB, et al. New cryptosporidium genotypes in HIV-infected persons. Emerg Infect Dis 1999;5:444-449.

Fall A, Thompson RC, Hobbs RP, et al. Morphology is not a reliable tool for delineating species within Cryptosporidium. J Parasitol 2003;89:399-402.
Wilson RB, Holscher MA, Lyle SJ. Cryptosporidiosis in a pup. J Am Vet Med Assoc1983;183:1005-1006.

A change of direction

The end of the semester is in sight. I had maintained this blog for the MICR756 class and had focused my attention on the 'Public Health Aspects of a complex Apicomplexan disease', viz. Malaria. Over the course of the semester, I found that I liked maintaining a blog and that I actually liked this sort of unofficial scientific writing.

So, from January, the blog will move to a new URL : apicomplexity.blogspot.com and will include topics starring other less known (and according to me, more interesting) apicomplexans such as Cryptosporidium, Isospora etc.

Thank you, all, for your patience. A special thanks to Dr.Nathan Fisher for the idea of a blog . 

One Health - Policy

A determinant by another name is a problem that must be overcome
Many of the determinants involved in the spread of malaria can be controlled by policy. For example, in areas of Africa where malaria  transmission is unstable (seasonal transmission, low intensity, low immunity among the population, affecting all ages), irrigation patterns affect transmission by affecting (increasing) the number of vectors available at a particular location. Mosquitoes breed well in the water logged soil of rice fields, increasing malaria transmission, although the very purpose of irrigation is to increase food productivity. (Ijumba, 2001) The authors have elegantly called this the 'paddy paradox'. Issues like this are at the very core of the dilemma of achieving all the goals of the One Health Initiative. Because all life is linked in an intricate network, a policy that affects one area inevitably affects another, in a veritable 'circle of life'.

Collaborative efforts and critical areas
One of the Manhattan principles on 'One World, One Health' really caught my eye. It states that "Forming collaborative relationships among governments, local people, and the private and  public (i.e. non-profit) sectors" will "meet the challenges of global health and biodiversity conservation." (CDC,2004). To discuss the need for collaboration is great, but the only thing that will sustain the collaboration is (mandatory) policy that will hold collaborators to their promises.

In a manner similar to the one adopted for HPAI (UNDG,2008)., a coordinated global response policy for malaria must focus on critical areas that include :
a. Preventing a epidemic by controlling malaria transmission and preparing for future epidemics by improving malaria surveillance.
b. Rapidly detecting the disease, treating it and preventing its sustained spread from the index case to others

c. Ensuring that all essential services are continually available in  the event of an outbreak

Whose responsibility is it anyway?

Policies must be put in place for the things discussed above. But, who is responsible for drafting such policies? Will these policies form a basis for laws that could be legislated by different governments? Will the local government that holds executive powers enforce such laws created by a Legislature? Will such laws/policies be upheld by local branches of the Judiciary? Or will the policies only be convention among the involved parties?

For such diseases that have a marked impact on both veterinary and medical fields (like psittacosis, cysticercosis etc), the approach that was taken in the reading for the week in New South Wales (Adamson, 2011) works really well. There can be effective collaboration between vets and physicians for prevention and preparedness, detection , analysis and response. However, it should not escape our notice that malaria is not listed as a notifiable disease by both the human and animal sectors, because many still strictly consider it an obligate human-mosquito pathogen.

With malaria caused by Plasmodium knowlesi however the NSW setup would work perfectly with physicians and wildlife experts filling in their expertise. This framework can be effective in P.knowlesi endemic areas , not so much in others because of differences in the niche occupied by the other Plasmodia.

Stakeholders in the One Health theory

Physicians, who are at the top of the 'health care access pyramid', should work together with researchers, epidemiologists and other stake holders (governmental and nongovernmental) . One example of a non governmental stake holder is the Bill and Melinda Gates Foundation, who support R&D financially by funding research grants (2 billion USD so far) for drug development, diagnostics, vector control methods and vaccines. They are partners with organizations such as the Global fund to Fight AIDS, tuberculosis and Malaria, Roll back Malaria, PATH Malaria Vaccine Initiative, Medicines for Malaria Venture, Malaria No more and Nothing but Nets. Such broad partnerships lay a broad resource network that can well be used to eradicate malaria soon. Although these private investors work on their own time frame and donate money for research, at the present time, there are no laws/ policies according to which they are expected to act. 

This must be rectified and policy frameworks established to moderate everyone's role, without infringing on anyone's freedom to help, because financial gifts cannot be demanded. 

The following pyramid from the Maternal and Child Health Program of the US Dept of Health and Human Services shows the essential features that must be covered by One Health policies for the eradication and management of disease. They can be adopted for malaria. 

(MCH,2013)

References :

1. Adamson S, Marich A, Roth I. One Health in NSW: coordination of human and animal health sector management of zoonoses of public health significance. N S W Public Health Bull 2011;22:105-112.

2. Ijumba JN, Lindsay SW. Impact of irrigation on malaria in Africa: paddies paradox. Med Vet Entomol 2001;15:1-11.

3. "Bill & Melinda Gates Foundation." Malaria. Gates Foundation, Seattle, 2013. Web. 18 Nov. 2013.

4. "MCH Programs Overview." MCH Programs Overview. Washington, 2013. Web. 19 Nov. 2013.

5. "The Manhattan Principles." cdc.gov. CDC, Atlanta, 2004. Web. 19 Nov. 2013.

6. "Contributing to One World, One Health.*" Undg.org. United Nation Development Group, 2008. Web. 19 Nov. 2013.

One Health - Sociology

The sociology of the one heath concept for malaria is built around human social behavior in the context of the disease's zoonotic nature. Of the five species of Plasmodium that can infect man (P.malariae, P.ovale, P.falciparum, P.vivax and P. knowlesi), P.knowlesi is a natural pathogen of long tailed and pig tailed macaques in South East Asia and hence considered a zoonosis. (CDC, 2013).  There are numerous reports of the other Plasmodium species arising in the great apes and engulfing an ecological niche created by the movement of humans.

(Singh, 2013)

 Although wild macaques are the original hosts of P.knowlesi, increased human depredations in forest areas has led to human infections. Some scientists theorize that in such an ecological mosaic such as the one that exists in SouthEast Asia, an increase in human interference could force a pathogenic species such as P.knowlesi to switch to humans as its preferred host. (Lee et al.,2011)

Since P.knowlesi multiplies every 24 hrs, cases of infection progress rapidly, often being fatal. The parasite resembles P.malariae (more benign) and is misdiagnosed as such, when diagnosis is based on microscopy. (Cox-Singh et al., 2008) Visitors entering endemic zones are at the highest risks.

 Spread of the disease is influenced by many cultural factors as well. Due to population booms, much more of the forest land has been cleared for agricultural use, driving people and their animals to the edges of forests. People living in such close proximity to the jungle tend to enter it to forage for food, to gather firewood etc, where they encounter the infected mosquitoes.

There are two transmission cycles that ought to be addressed : (1) between macaques and (2) between humans and macaques. The latter occurs in the ecological mosaic where a vector that can bite both primates exists, which can transmit the parasite (Singh,2013; Thrusfield, 2007). Studies of this sort have involved entomologists, landscape epidemiologists, veterinarians etc. The conclusion that was reached was that the disease is transmitted to humans by mosquitoes that normally feed on animals and that human to human transmission does not seem to occur with the same vectors. It is exceedingly interesting to note that no urban outbreaks of P.knowlesi has occurred.

Management of such a zoonotic pathogen requires coordinated, consistent action from health professionals, scientists and the government, which is the basis of One Health. Further epidemiological studies are warranted. These must look at infection rates, describe intrinsic and extrinsic determinants,  notify nosogenic territories, predict persistence and patterns of the disease. Surveillance must be undertaken by governmental agencies and health organizations. Trips into deep jungles by tourists, naturalists intent on discovering new species, military personnel undergoing jungle training and others must be kept to a minimum.

References :

1. Cox-Singh J, Davis TM, Lee KS, et al. Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis2008;46:165-171.

2. Lee KS, Divis PC, Zakaria SK, et al. Plasmodium knowlesi: reservoir hosts and tracking the emergence in humans and macaques. PLoS Pathog2011;7:e1002015.

3. Singh B, Daneshvar C. Human infections and detection of Plasmodium knowlesi. Clin Microbiol Rev 2013;26:165-184.

4. Thrusfield, M. V. "7 : The Ecology of Disease." Veterinary Epidemiology. 3rd ed. N.p.: Blackwell, 2007. 116-36. Print.

5.  Day MJ. One health: the importance of companion animal vector-borne diseases. Parasit Vectors 2011;4:49.

6. http://www.cdc.gov/malaria/about/biology/parasites.html

Policy for anti-malarial chemotherapy

I was under the impression that the WHO and other international health organizations laid down (non-mandatory) policy guidelines for the treatment of malaria and that endemic countries did not really care about those guidelines. After all, doctors prescribe the medication and are trained to tailor it to the needs of their patient, right ? As I read on the subject though, I quickly found that the Medical Association and Health Department of every malaria-endemic country has it's own mandatory policy based on the WHO's guidelines.

An overview of the chemotherapy policies for different regions are listed on the WHO's website here. (WHO, 2013)

Even as early as 1990, the WHO had some "General considerations for the development of  a malaria treatment policy". I have briefly discussed some of them here, but the considerations are not restricted to the ones listed below.

 The seasonality of the disease and the level of acquired immunity in the population are epidemiological factors that must be accounted for in Rx policies. Severity of illness is severely influenced by the species of Plasmodium that has infected the person. Drug resistance too depends on the species, with P.falciparum being the most prone to develop drug resistance. So, prevalance and drug sensitivity studies are essential before polices are drafted.

Availability of malaria services in a region heavily influences the success of chemotherapeutic intervention policies. Malaria services are best implemented in association with general health services, than as stand alone programs. Such an integration, if necessary, must be spelled out clearly.

It is also essential to identify and define high risk groups/individuals, who would need prophylaxis. This would help in triage in outbreak settings and also in delivering radical curative treatment in unstable malaria areas.
Treatment regimens are also usually available in the policies , for different age groups and physiological conditions (pregnancy etc). However, these must be tailored to suit each individual patient's needs as many of the regimens are based on clinical trials and are not validated for field conditions. Regimens must take into account the medical supervision available for the treatment, that is, different forms of the drugs can/must be used for outpatients and some other forms are better suited for in-hospital administration.

Sociological aspects such as self medication must be taken into account too.

Unit cost of the drug and number of doses needed form the basis of the economy of chemotherapy Subsidies play a huge role in adherence to therapy regimens, by giving a pseudo-increase in buying power. But, even with subsidies and free medication, adherence is not 100%, which on a side note is one of the driving forces for resistance development.

Here is an example , from India, of the national drug policy against malaria :

The chemotherapy recommendations are given by the National Vector Borne Disease Control Programme, operating under the Ministry of Health & Family Welfare, Govt of India. The policy statement, in the 2013 edition, declares that one of the aims is "to minimize the risk of spread of drug resistant parasites by use of effective drugs in appropriate doses for everyone". With that goal in mind, the drug policy is intended to be "Appropriate for today and safe for tomorrow".

The ultimate goals of these policies are to provide complete clinical and parasitological cure of all malaria cases, prevent the progression of uncomplicated malaria into severe malaria and thereby reduce mortality, prevent relapse by administration of chemotherapeutic agents, interrupt transmission by the use of gametocytocidal drugs and prevent the development of drug resistant malaria .

References:
 Neave PE, Taylor S, Behrens RH. Does public subsidy of the cost of malaria chemoprophylaxis reduce imported malaria? A comparative policy analysis. Malar J 2013;12:238.

Country antimalarial drug policies: by region. (n.d.). WHO. Retrieved October 22, 2013, from http://www.who.int/malaria/am_drug_policies_by_region_afro/en/index.html

National Vector Borne Disease Control Programme (NVBDCP). (n.d.). National Vector Borne Disease Control Programme (NVBDCP). Retrieved October 22, 2013, from http://nvbdcp.gov.in/

Antimalarial drug resistance - Who is to blame?

Malaria treatment failure can arise either due to true antimalarial drug resistance or due to failure to clear malarial parasites from the circulation. The latter is due to incorrect dosing, non-compliance with the duration of dosing, poor drug quality , drug interactions, poor or erratic absorption and misdiagnosis. (Sosa, 2010)

The problem of misdiagnosis is essentially one of overdiagnosis. In many endemic countries, many febrile cases are prescribed antimalarial medication. A prospective observational study conducted in Afghanistan noted that 99% of the bloodsmear-negative patients received antimalarial medication when the diagnosis was based solely on clinical diagnosis. But even when blood smears were used for diagnosis, 50% of smear-negative patients received the medication. (Leslie, 2012). Many patients were thus unnecessarily exposed to the drugs and if they had had low parasitemia, there would have been enough selection pressure to cause drug resistance development.

Unregulated dispensing of drugs is another common problem and is frequently associated with the self-medication. In many developing countries, prescription medication can commonly be purchased over the counter. These include antibiotics and antimalarial drugs. Although there are laws to prevent such practices, these are almost always ignored. The ethics of pharmaceutical personnel are also questionable in these cases and may arise out of sheer ignorance of both pharmaceutical ethics and sound science.

 (Dernavich)

Poverty driven practices are explored in the paper by Planta, M. , titled "The role of poverty in Antimicrobial resistance" , published in the Journal of American Board of Family Medicine, in Nov 2007. The author compares the practices in developing and developed nations. Noncompliance takes different forms in these cohorts, with the factors in developing countries being inadequate access to effective drugs, unregulated manufacture and dispensation of antimicrobials and lack of money to pay for appropriate, high quality medication. In contrast, the practices in developed countries mainly are sharing of antimicrobials and self medication using leftovers from unfinished drug regimens . (Planta MB, 2007). This was also explored at length in the reading for the day (McNulty,2007). Although both the articles explored antibacterial resistance, the same principles apply to sociology of antimalarial resistance.

Other factors that affect drug compliance include age, sex, martial status,educational level, ability to read and household monthly income. A demographical study of arteminisin combination therapy compliance conducted in rural Kenya revealed that only upto 47% of all malaria patients adhered to therapy, in terms of duration and dosage. Of these, 58% were <13 years of age. Adherence was higher among females (55.7%) than males (50.3%). Underaged patients (children) were the most adherent (57.1%), when compared to the married (21.4%), widowed (7.9%), single (2.9%), and separated (0.7%).  (Onyango EO,2012) . This was probably because of higher concern among parents when the children are affected. Busyness and forgetfulness may be contributing factors among the older age groups, because no one intentionally wants to die of malaria, when they have access to medicines.Curiously, adherence increased as household size increased , with households with >6 people being more compliant than others. Undoubtedly, the statistics from this study cannot be extrapolated to wide regions across the globe. But, it gives a glimpse of the various factors that ought to be addressed when policies are laid down to overcome antimalarial resistance.

Increasing the awareness of people everywhere to antimicrobial resistance is an essential next step. Targeted education, information and communication activities are the need of the hour to reduce the risk of contributing to antimalarial resistance. Extension strategies used for doctors and health care workers, pharmaceutical personnel, policy makers and ordinary people residing in endemic areas must be specially designed to adequately cater to each group. Together, we can achieve our goal of overcoming antimalarial resistance.

References :

Leslie T, Mikhail A, Mayan I, et al. Overdiagnosis and mistreatment of malaria among febrile patients at primary healthcare level in Afghanistan: observational study. BMJ 2012;345:e4389.

Sosa AbdJ. Antimicrobial resistance in developing countries. New York: Springer, 2010.

Planta MB. The role of poverty in antimicrobial resistance. J Am Board Fam Med 2007;20:533-539.

McNulty CA, Boyle P, Nichols T, et al. The public's attitudes to and compliance with antibiotics. J Antimicrob Chemother 2007;60 Suppl 1:i63-68

Onyango EO, Ayodo G, Watsierah CA, et al. Factors associated with non-adherence to Artemisinin-based combination therapy (ACT) to malaria in a rural population from holoendemic region of western Kenya.BMC Infect Dis 2012;12:143.

Cartoons :

Dernavich, D. http://www.condenaststore.com/-sp/Woman-looking-at-pharmacy-shelves-labelled-Classics-Best-Sellers-and-New-Yorker-Cartoon-Prints_i8479870_.htm

Glasbergen, R. http://www.glasbergen.com/pharmacy-cartoons/