MALARIA IN THE WORLD, IN THE EASTERN MEDITERRANEAN REGION AND IN IRAN
B. Sadrizadeh MD
Communicable Disease Control (DCD), World Health Organization, Regional Office for the Eastern Mediterranean, Alexanderia, Egypt
Introduction
Malaria is an ancient disease which, in all probability, humans have inherited from their primate ancestors. This may be assumed to be true when one considers the close similarity of malaria parasites in apes and modern humans 1.
The evolutionary pressure placed upon man by malaria is one of the major factors in shaping what is today, modern man.
There is clear evidence that some of the polymorph hereditary traits, such as hemoglobin S, thalassemia, G6PD deficiency, spread and accumulated in tropical human populations due to the pressure placed by malaria.
Many more links are also thought to exist, malaria is an integral part of tropical ecosystems and therefore has made a deep impact on the behavior, socio-economic activities and pattern of distribution of human populations. It is also believed that distinctive population distribution patterns in topical mountainous areas, such as East Africa and New Guinea, in which the highest population densities are at an altitude above 2,000m, is due to the indigenous population's need to evade malaria.
Due to ecological differences, malaria as a disease behaves in different ways even in areas with comparable climates,. The fauna of the vectors (whose behavior and ability to transmit malaria varies considerably) and the genetic set-up of the human indigenous populations have a direct bearing on malarial behavior.
As noted by Wallace in 1876, geographical distribution of all animal species follows a distinct pattern of zoogeographic region, and the anopheline mosquitoes follow the same rule2.
Within zoogeographic regions, species of animals including parasites and vectors are 'grosso modo' similar and, consequently, epidemiological traits are also similar.
Seven regions are usually recognized in this regard. Most of the Northern hemisphere is occupied by the Palaeartic and Neartic regions, the former related to Eurasia (Old World) and the latter to America (New World) . In tropical areas, there is Neotropical (in America), Afrotropical, Oriental (Indian subcontinent and Indochina) and Australasian (Australia and Asia) regions.
Finally, there is an Antarctic region in the south, which is, for obvious reasons, out of our sphere of interest.
Many facts illustrate a remarkable similarity in the vector fauna within zoogeographic regions. The Anopheles maculipenis complex, to which the major palaearctic malaria vectors belong, spreadsfrom Morrocco to Eastern Siberia, but is not present outside the palaearctic region.
Exceptionally potent vectors belonging to the An.gambiae complex dominate the Afrotropical region that are unknown outside that area. Although some vectors, may to some extent, trespass regional borders, this does not upset the general rule. For example, An. culicifacies, an oriental vector, is present all along the Gulf Coast, i.e. to the west of the divide between oriental and palaearctic regions that is defined at the level of the Hormoz Strait. In spite of this, malaria to the west of this line shows a greater affinity to malaria in other neighboring palaearctic areas compared to malaria in the main area of distribution of An. culicifacies in the Indian subcontinent.
Ecological determinants of malaria are in many ways interrelated with socio-political and economical factors. These interrelations are bilateral; the ecology determines malaria and socio-economy influences ecology . Hence, malaria becomes part of a vicious cycle; it generates poverty and poverty prevents effective control measures.
Malaria control
Since antiquity, malaria has played a major role in the lives of communities and states. Ancient and medieval physicians, as early as Hippocrates, described diseases that may be identified as different types of malaria.
The presence of malaria in predynastic Egypt was recently demonstrated in mummies which dated from as early as 3,200 BC which were found to contain P.falciparum HRP-2 antigen.3
Under adverse conditions, exacerbations of malaria might have led to the disruption of the socio-economic fabric of entire civilizations, leading to their eventual downfall.1,4
Communities tried to protect themselves against malaria and some activities e.g. reclamation and proper maintenance of irrigation systems were instrumental in keeping malaria at bay despite the absence of any scientific knowledge on the causes of malaria at that time.
On the other hand, malaria often was an effective obstacle to colonization of tropical regions by outsiders. For example, malaria was the main reason why the Europeans failed to successfully colonize Sub-Saharan Africa for centuries. The breakthrough, with the ensuing rapid partition of Africa (the so called 'Scramble for Africa') became possible only after the introduction of quinine for chemoprophylaxis of malaria in circa 1805.5
The area of malaria distribution peaked at the beginning of the 20th Century6. At that time, the northernmost limit of malaria in Europe ran from Central England to Southern Norway, Central Sweden, Central Finland and Northern European Russia along the 64.N parallel.
Malaria was also prevalent in many areas of Siberia, most of the USA and some Southern Canadian states.
During the first half of the 20th Century, due mainly to ecological changes, better availability of medical care and the improvement of living standards, the malaria stricken areas effecting industrialized countries began to shrink. After the Second World War, this process accelerated due to two potent tools that became widely available, the drug chloroquine and the insecticide DDT.
These events revolutionized malaria control and led to the development of the concept that malaria could be eradicated.
A malaria eradication strategy involving indoor spraying of DDT, which was endorsed by the Eighth World Health Assembly in 1955, was a rapid success. The heavy burden of malaria was removed from Southern Italy, Greece, Southern USA and Southern USSR to name but a few.
However, malaria eradication did not touch its stronghold in Sub-Saharan Africa. In 1970, a WHO Expert Committee acknowledged that in large areas of tropical Africa, time-limited malaria eradication programs were often impractical.7
Malaria eradication was successful not only in temperate climates, but also in some tropical and subtropical countries too. However, most of them, thought successful in drastically reducing malaria, were unable to stamp it out completely.
Stagnation of malaria control programs in these countries started in the early 1970's, sometimes resulting in a serious deterioration of the malaria situation. However, re-emerging malaria did not usually reach its previous levels. In other words, sustainable malaria eradication, even when its transmission could not be completely interrupted, was to some extent successful. Only in catastrophic political situations (e.g. Afghanistan) are the achievements in the pursuit of malaria eradication completely annihilated.
At the same time, in Sub-Saharan Africa, there was no large-scale malaria control until the early 1990's. The turning point came with the African Conference on Malaria in Brazzaville in October 1991, which endorsed a strategy of malaria control in Africa. This was followed by the World Declaration on the Control of Malaria adopted at the Ministerial Conference on Malaria in October 1992. This conference committed the global community to control malaria with special emphasis being laid on the most affected countries, the bulk of which are in Sub-Saharan Africa. To date, virtually all the African countries have expressed a political commitment to control malaria and then with that aim in mind have taken practical steps towards implementing effective measures. Awareness of the magnitude of the malaria problem in Africa has become universal.
However, the malaria situation remains very preoccupying. According to the World Health Report8, the estimated toll of malaria is approximately 300 million acute cases per year, with 1.1 million deaths occurring mostly in African children. According to the same estimates, WHO African Region constitutes 85% of cases and 87% of deaths due to malaria worldwide. It has been estimated that in Africa malaria alone accounts for approximately 10% of the total disease burden.
To address this serious situation, a new initiative called 'Roll Back Malaria' (RBM) was initiated by the Director General of the World Health Organization in May 1998.
In addition to WHO, three other UN agencies participate in the fight against malaria namely the UN Children's Fund (UNICEF), the UN Development Program (UNDP) and the World Bank. The novelty of the RBM approach lies in its holistic approach, not totally relying on new methods for controlling malaria, but also strengthening existing health services in effected communities, thereby ensuring adequate access to basic health care and training of health care workers.
Partnerships between the international organizations, governments, academic institutions, the private sector and non-governmental organizations are essential in endemic and non-endemic countries if malaria is to be eradicated.
Out of the existing methods of control, emphasis is being placed on ensuring the extensive use of insecticide treated mosquito nets and encouraging the development of simpler and more effective means of administering medication. RBM will also encourage the development of more effective and new anti-malaria drugs and vaccines.
Malaria situation in the Eastern Mediterranean Region
Countries of the Eastern Mediterranean Region are situated in the three eco-epidemiological zones of malaria: Afrotropical, Oriental and Palaearctic.
Consequently, there are striking dissimilarities between the countries of the Region in relation to the malaria problem, although all of them are malaria-receptive.
About 45% of the population of the Eastern Mediterranean Region live under the risk of both falciparum and vivax malaria, and additional 15% under the risk of P. vivax alone. The estimated number of malaria cases is about 14 millions annually, out of which 95% are generated by just four countries: Afghanistan, Somalia, Sudan and Yemen.
Malariogenic conditions are most favorable in the areas of Afrotropical malaria that encompass sub-Saharan Africa (including Djibouti, Somali and Sudan), Yemen, with the exception of Sokorta island, and the adjoining south-western part of Saudi Arabia.
The main feature of Afrotropical malaria is the predominance of P. falciparum, which is highly endemic and refractory to control measures, this is mostly due to the presence of vectors belonging to the An. gambiae complex, primarily An. gambiae s. s. and An. arabiensis. These vectors in particular are extremely effective because of their very high susceptibility to human Plasmodia, very long life span and their close association with human beings (predilection to human blood and to man-made habitats).9
Elimination of malaria from the Afrotropical areas is unrealistic in the foreseeable future, except in fringe areas in Southern Africa and ocean islands. Attempts to decrease malaria transmission may be risky if not sustained, because this leads to a decrease in population immunity. A decrease in the force of infection of falciparum malaria from very high to high and even moderate levels may increase incidence of cerebral malaria in children.10
This in turn may shift the incidence of severe malaria from young children to adolescents and even young adults, which is perceived by the communities concerned as an outright deterioration of the malaria situation.
There are many examples of man-made epidemics occurring after haphazard unsustained indoor residual spraying campaigns in Africa.
That is why malaria control strategies in these areas concentrate on diminishing the severity of the disease and the elimination of its inherent mortality, which is a technically feasible goal, even in the presence of drug resistance.
Prevention of malaria epidemics is one of the ways leading to this goal.
In North Africa that belongs to a Palaearctic region, many areas were highly endemic and heavily affected by P. falciparum in the pre-eradication era, but transmission was always comparatively low, seasonal and maintained by relatively weak vectors. Malaria transmission was severely reduced by the end of the 1980s under the impact of control/eradication activities. At present, malaria transmission, although at a very low level and in a very limited number of villages, continues in two foci in Morocco, one focus in Algeria (P.vivax only) and in one focus in Egypt (p. falciparum an P. vivax). The total number of cases in these areas was less than 100 cases annually in 1996-98.
The malaria situation in these countries was reviewed at an EMRO/AFRO meeting held in Tunis in May 1997 that recognized the feasibility of a complete interruption of malaria transmission within 5 years in the whole of the North Africa and requested WHO to provide support in this endeavor.
A similar situation is observed in the Palaearctic portion of Asia that occupies, within the Eastern Mediterranean Region, areas from the Mediterranean coast to the Hindukush, excluding the southern part of the Arabian peninsula and south-eastern corner of Iran. P falciparum disappeared from these areas except along its eastern fringes.
However, transmission of P. vivax is continuing in a number of areas reaching epidemic proportion in times of political upheaval, as happened in Iraq in the wake of the Gulf war of 1991.
The oriental type of malaria is present in Pakistan, Afghanistan south from the Hindukush, south-eastern Iran, Oman and adjoining areas of the United Arab Emirates. It is characterised by the presence of both P. falciparum and P. vivax in roughly equal proportions and the involvement of rather effective vectors, primarily those belonging to the complexes of An. culicifacies, An. fluvialis and An. stephensi. Oriental malaria is more difficult to control compared to Palaearctic malaria.
However, with systematic applications of antimalaria measures, its transmission may be interrupted anywhere, in contrast with Afrotropical malaria in its heartland, where this is impossible.
By malaria control status, countries of the Region are classified as shown in Table 1, and main events that lead to this situation are summarized in Table 2.
To date, the situation is quite serious in the countries with Afrotropical malaria, especially if health systems are disrupted. On the other hand, past experience shows that in the rest of the region, a rapid decline of malaria is achievable provided that a normal political situation prevails.
Therefore, normalization of the political situation in Afghanistan and north Iraq are likely to lead to a rapid improvement in the malaria situation, including the neighboring countries that suffer from malaria importation.
Within the region, there are countries with residual malaria where an interruption of transmission is deemed feasible and sustainable (Morocco, Egypt, Oman and United Arab Emirates). Some of these countries have already expressed their commitment to malaria eradication. In other countries, the maintenance of their malaria-free status is the main objective, this requires the development of a common approach through updating the malaria eradication strategy.
It is expected that RBM would not only concentrate on the countries with a very serious malaria problem (which is the priority), but also help countries with a less acute malaria problem.
Problem of malaria in the Islamic Republic of Iran
In the past, malaria was highly endemic in most parts of Iran. In 1924, it was estimated that out of a population of 13 million, 4-5 million people had contracted malaria. Organized malaria control started before the Second World War and in 1957, the strategy of malaria eradication was endorsed by the Government.
A vertical malaria eradication program operated up to 1988, when it became integrated into the general health program, and that program became a Malaria Control Program.
The Islamic Republic of Iran belongs to the EMR and sustains a strong malaria control program. There has been a decreasing trend in the malaria incidence in recent years. According to Iran's report to the EMRO in 1997, 10,000,000 (16%) out of the total population of 61,000,000 lived in initially non-malarious areas. In addition, 40,000,000 (66%) lived in areas freed from malaria, 7,500,000 (12%) in areas with sporadic transmission, mostly P.vivax, and only 3.500,000 (6%) in areas of continuous transmission with a high proportion of P.falciparum.
During 1997, 3,244,334 blood slides were examined and of them 38,766 were found to be positive (Slide Positivity Rate 1.19%). Out of the positive cases, 8,698 (22%) were due to P. falciparum of which 434 cases were hospitalized, which may serve as an approximate indicator of the number of severe cases. Twenty-two fatalities were reported.
From an operational point of view, three regions are recognized in the country:
1.Regions to the north of the Zargros range with a population of approximately 43 million. Annual Parasite Incidence (API) in this area was 0.14 per 1,000 in 1997. About 77% of the malaria cases were imported from abroad or the south eastern part of the country.
2.Regions to the south of the Zargros range with a population of approximately 15 million. API in 1997 was reported to be 0.18 per 1,000 of which 48% were classified as imported.
3.The south eastern corner of Iran which consists of Sistan and Buluchistan Province, Hormozgan Province and the tropical part of Kerman Province with a combined population of approximately 3 million is considered to be a 'refractory malaria region'. API was reported to be 8.74 per 1,000 population in 1997. In this part of the country, malaria belongs to the oriental type; hence it is more difficult to control than elsewhere in Iran. The inherent problems being the drug resistance of P.falciparum, and vector resistance to insecticides with the additional complication of the importation of malaria, mostly P.falciparum, from Afghanistan and, to a lesser extent, Pakistan.
A new threat of malaria importation recently emerged from the Republic of Azerbaijan in the north-west of the country, which was affected by a serious epidemic of P. Vivax malaria. Malaria has been seen on the Iranian side of the border, first reports indicating its emergence in the most receptive areas along the lowland Aras river basin, which is at an altitude of 150m. Along this particular valley, the villages on both sides of the border are within the flying range of Anopheles. Geographically, the area around Parsabad is a westward extension of the Mughan Steppe most of which lies within the Republic of Azerbaijan. In the past, the Mughan Steppe was notorious for devastating epidemics of malaria, this fact even resulted in the failure of a resettlement project initiated by the Tsarist Government of Russia in the early part of the 20th Century.
Another risk of importation of malaria into Iran is provided by long haul truck drivers that regularly travel between Bilaswar along the Aras valley up to Julfa in order to supply the Azerbaijan enclave of Nikhichevan. In addition, there is always the strong possibility of smugglers crossing the Aras valley at various sites.
Although this area along the Aras is highly receptive, a further spread of malaria to the south into East Azerbijan and Ardebil Provinces is unlikely due to the existence of a relatively high mountain range, which would prohibit malaria transmission. More favorable conditions lie along the Karusu Valley, an area that should be closely monitored.
Another receptive area is Gilan, starting from Astara where local transmission of malaria already exists. Disturbingly, there is no geographical barrier to the south, unlike Ardebil, and without the implementation of stringent preventive measures, it is possible that malaria could spread up to the Sefid Rud delta where the main centers of the province are situated and where the receptivity must be very high.
Need for a reorientation of malaria control in the Islamic Republic of Iran
The Islamic Republic of Iran has eradicated P.falciparum from most of its territory, which, in itself, is a major achievement. The underlying reason for the continued transmission of this species in the south-east is probably due to the fact that P.falciparum belongs to the oriental ecological system. However, in the rest of the country, small pockets of transmission still exist.
These pockets are not specifically monitored nor is priority given to selecting appropriate control measures, as is the case in areas where P. vivax alone is present.
Therefore, if special efforts are made to eliminate all residual foci of P.falciparum outside its main range in the south east, it is feasible to make the majority of Iran a sustainable falciparum-free zone. Previous experience gained from other countries with a palaearctic type of malaria has shown that this is possible.
Therefore, a different approach to the goals of malaria control and eradication should be adopted.
Autochthonous cases of P. falciparum outside of south east Iran should be given emergency status; cases of infection should be promptly investigated and vector control measures implemented. Cases of P. vivax are a lesser priority.
In areas where interruption of malaria has already been achieved, that is to say in most of the Iranian territory, the objective is to maintain a malaria-free status. In the endemic areas of the south east, efforts should be concentrated on the limitation of the nefarious effects of malaria with special emphasis being placed on P. falciparum.
The information system needs to be adapted to more effectively meet the needs of differing epidemiological situations, emphasis should be placed on monitoring the effects of intervention with priority accorded to P.falciparum. In reference to the areas of residual transmission and malaria-free zones, the time-honored principles developed in previous eradication programs should be applied.
In practice, this means that instead of monitoring the incidence in terms of cases over a large territory, the monitoring of foci should be adopted. The malaria status of each focus (village by village) should be recorded. Information collected on the focus should include the name, population, altitude (as an indicator of malariogenic potential), spraying history, number of local and imported cases of malaria, paying particular attention to cases of P. falciparum.
This information should be updated on a monthly basis and each focus reclassified according to present status, when necessary. For example, a residual non-active focus should be reclassified as active as soon as evidence is obtained that a local transmission has occurred.
The epidemiological classification of the focus should be used as a yardstick for decision making regarding control measures. In this regard, WHO has sponsored a small research project to establish a computerized surveillance system working along these lines. It is hoped that this project, which is currently underway, will fulfill the above criteria for improved surveillance.
Epidemic preparedness should be enhanced in highly receptive areas, especially those bordering the Republic of Azerbaijan. Co-ordination with Azerbaijan is essential and WHO has organized a meeting to take place in August 1999 between the countries of the EMR and European Regions where these matters are on the agenda for discussion.
Malariological stratification of the country is a high priority, this will serve as a means of identification of problem areas, their vulnerability and receptivity, especially in relation to P. falciparum. In the initial stage, a good indicator of malariogenic potential will be the altitude above sea level, the contributions of specialists in physio and biogeography will be essential in this exercise.
Retrospective and prospective monitoring of meteorological data should be initiated in order to study the possible correlation between meteorological events and the exacerbation of malaria, this would enable the development of mechanisms to help forecast epidemics.
There is a need to streamline quality assurance systems in relation to microscopic diagnosis in order to make routine crosschecking of examined slides more efficient. In this regard, the following modifications are proposed: standardized reporting on diagnosis, including parasite densities; blind re-examination by the control laboratory; feedback to peripheral laboratories regarding the quality of staining; continued monitoring of individual laboratory’s quality control in order to detect changes in their performance; periodic spot-check visits to all laboratories by senior laboratory technicians.
Monitoring of drug resistance should be undertaken on a continuous basis using the sentinel network as set out by the WHO protocol. In the immediate future, chloroquine should be retained as a first line drug treatment for falciparum malaria, sulfa-pyrimethamine combination as a second line drug and mefloquine as a third line drug. Quinine should be reserved in the treatment of severe cases only. If the result of the laboratory investigation cannot be obtained within the same working day, presumptive treatment should be given in areas where P. falciparum is present.
It is hoped that the government of the Islamic Republic of Iran makes a commitment to malaria control along the principles of the Roll Back Malaria program at the forthcoming meeting of regional countries in Cairo 1999.
Reference