Introduction

Malaria is a parasitic infection of the blood transmitted by night biting, female Anopheline mosquitoes. Around the world it kills about two million people (WHO) each year and in many countries the situation is getting worse. With 50 million people traveling from the developed to the developing world each year, it is also a great threat to travelers. In the UK alone, over two thousand travelers return each year with malaria, must of it acquired in sub-Saharan Africa. Approximately 10 returning travellers die from malaria each year in the UK alone

Avoiding malaria is probably the most time consuming and confusing health issue that the would-be traveler faces. In South Asia alone the risk varies from extremely high to zero with widespread resistance to commonly used drugs. Malaria is transmitted in some large cities; most other cities are malaria free. In some areas malaria is seasonally transmitted, in other’s it is transmitted all year round.

The risk to travelers cannot automatically be assumed to be the same as the risk that exists for the local population and the risk to more vulnerable travelers, such as pregnant women and young children must be individually assessed. In addition to this there is a bewildering array of drugs that may be used to prevent the traveler from contracting malaria and to make matters worse, doctors seem unable to agree on a particular strategy for a particular travel destination. A recent study at the CIWEC clinic discovered that the number of different regimes being used by travelers to Nepal was nine.

With such a confused picture and seemingly complete lack of consensus, quite often travelers decide to take nothing at all and leave themselves vulnerable to a potentially fatal infection. The following article is designed to help travelers to Nepal gain a better understanding of the situation that exists here in Nepal and so be in a good position to decide on what strategy they should use to avoid getting malaria.

A brief history of malaria in Nepal

For malaria transmission to take place, certain conditions need to exist. The habitat of the “transmission area” must support the lifecycle of the Anopheline mosquito. The ambient temperature must be high enough to allow the parasite to develop in the body of the infective mosquito and there must be a “pool” of infected people in the transmission area that allows the mosquito to pass the disease from an infected person to a previously non-infected person.

In Nepal, conditions for the transmission of malaria only exist in certain areas of the country, the low-lying southern belt of land known as the Terai and to a much lesser extent, the middle hills below about 1000 meters elevation. Up until 1960 the inhabitants of the Terai were almost exclusively from a single group known as the Tharu. The Tharu people of Southern Nepal are known to have developed a genetic resistance to malaria, allowing them to thrive in an area that was ill famed for being heavily infected. By 1960, after an extensive eradication campaign, the Terai was almost freed of malaria, allowing non-Tharu people to safely populate the region. Subsequently, malaria has crept back into the Terai region and the rate of malaria transmission has slowly increased to its present level. At present the "roll back malaria" campaign is attempting to control the current level of malaria transmission using pre-season spraying of mosquito habitats and education of the local population in bite avoidance. The current situation

Malaria is transmitted in all areas of Nepal except the eleven Himalayan districts and the three districts that make up the Kathmandu valley. In most of the remaining districts, which includes the middle hills and some of the districts on the Terai, the transmission rate is so low as to pose very little threat to the populations of those districts. The majority of malaria transmission in Nepal occurs in only 12 districts and these have been labeled "priority" districts. They are prioritised not only for the higher rate of malaria transmission that occurs within them, by also for the higher rate of P. Falciparum malaria transmission (except for Kavre). These districts are: Dadeldhura, Kanchanpur, Kailali and Bardia in the far western Terai; Nawalparsi in the central Terai; Sindhuli, Mahottari and Dhanusha in the east central Terai and Morang, Jhapa and Ilam in the far eastern Terai.
The twelfth priority district is Kavre, immediately east of the Kathmandu valley. In particular the Panchkal valley within Kavre sees high rates of transmission of P. Vivax malaria. (See note below on Kavre district).
About 10,000 cases of malaria are reported each year in Nepal, with over 90% being of the species Plasmodium Vivax, which causes a relatively benign form of malaria in otherwise healthy individuals. The remainder of cases Plasmodium Falciparum malaria, a potentially dangerous infection. In addition, the transmission of malaria is very seasonal, with most transmission occurring between June and August, and very little occurring in the winter months between November and March.

Regarding the main tourist months of April/May and October the situation is slightly different. The number of new cases of malaria seen in local Nepalese during these months is higher than in the winter months. In October the transmission rate is about half the summer rate and falling, in April/May it is about a quarter of the summer rate and rising. For tourists this means that although the chance of acquiring malaria is slightly higher, it is still extremely low for short visits to the Terai of a week or less. The advice we give (see below) reflects our belief that the risk is still low enough to justify not taking prophylaxis in those not at special risk.

There is well-documented resistance of Falciparum malaria to Chloroquine and although less well documented, there is probably a growing problem with Fansidar resistance. Currently there have been no reported cases of Chloroquine resistant P. Vivax malaria.

The risk to tourists

The risk to tourists can be assessed in two ways. Firstly by knowing the number of tourists that actually contract malaria from a visit to Nepal. To know this we need to know the number of tourists that present with malaria in Nepal itself and also those that return to their home countries having acquired malaria in Nepal. The CIWEC Clinic has nearly 20 years of experience in treating travelers to Nepal and in that time, only two patients have presented with malaria that they may have contracted in Nepal. In addition to this, since 1985 there have been three confirmed cases of malaria in travelers returning from Nepal to the US, one of this group also traveled in south east Asia. In the UK, since 1987 there have been seven cases of malaria in travelers returning from Nepal. Detailed information as to the origin of these infections is not known and it may be that they also traveled in India. No other information regarding returning travelers to other countries is known except for Israel, where there have been no reported cases of malaria in travelers returning from Nepal.

Lastly, in 1998 a US Peace Corps volunteer developed malaria in the month of July. The volunteer was resident on the Terai and had spent some time in the far-eastern Terai just prior to being diagnosed. It is thought that this is where he contracted malaria. The case was treated as Falciparum malaria, making him the first foreigner in Nepal to have contracted P. Falciparum malaria since the CIWEC clinic first began recording cases. This was never confirmed and it is quite possible that he had P. Vivax malaria.

These very low numbers of cases should be placed in some context. In 1998-1999, about 60,000 permits were issued to visitors to the national parks on the Terai. 50,000 of these were for the Chitwan Park alone. In addition, many travelers visit Lumbini, Janakpur and other sites of cultural interest for which no permit is required. The number of travelers arriving from India via the Terai is also not included in this figure. So despite the very large numbers of visitors to the Terai each year, the number of cases of malaria acquired directly as a result of one of these visits is extremely low. It is likely that a brief visit of two or three nights to the Terai in the most popular months of the year has never resulted in a malaria infection, but the data on this is lacking. The factors contributing to this are probably many and one may be that all the visitors are using prophylaxis and so are not getting malaria. However a study done at CIWEC shows that about a third of visitors to the Terai actually take prophylaxis for their visit so it seems it is not the use of prophylaxis that is resulting in the very low number of malaria cases.

Secondly, we can guess at the risk to tourists by knowing the current risk to the local population, described above. We know that the areas of greatest risk are certain districts in the Terai. We know that malaria transmission is seasonal, occurring at a time when very few tourists visit these areas (June to August). We know that almost all the malaria that is transmitted is P.Vivax malaria and we know that the treatments currently used are effective.

Summary of malaria risk to visitors to Nepal

1. Reported cases of malaria acquired in Nepal (foreign visitors only) are extremely rare. In 20 years the CIWEC Clinic has seen just two cases that may have been acquired in Nepal. A further 10 cases have been reported in returning travelers to the US and the UK over the last 14-16 years. A peace corps volunteer contracted malaria in 1998 while residing in the eastern Terai during the monsoon.



2. The rate of transmission in Nepalese is about 10,000 cases per year.



3. Over 90% of malaria in Nepal is of the "benign" type, Plasmodium Vivax. There have been no recorded cases of P. Falciparum malaria in short-term visitors to the Terai (one week or less).



4. Malaria transmission is highest between June and August, outside the tourist season. Transmission rates during the winter months are very low.



5. The majority of malaria in Nepal is transmitted in "priority" districts; all of these are on the Terai except Kavre (see below).



6. Most visitors to the Terai visit non-priority districts with low malaria risk.



7. All Vivax malaria is sensitive to Chloroquine.



8. Malaria is acquired between dusk and dawn, mostly in rural areas. This means you have to sleep in a malarious area (sleeping tourist) to have any hope of catching it.



9. The priority district that sees most "sleeping" tourists is Bardia, in the western Terai. Bardia is very rarely visited between June and September.



10. Effective treatment for malaria is available in the CIWEC Clinic, Kathmandu.

So what should you do?

Irrespective of what pills anybody tells you to swallow, you must take measures to avoid being bitten by mosquitoes. This is most important in the prevention of all mosquito borne diseases, not just malaria and is something that should be deeply imprinted in the minds of all travelers, wherever they happen to be. Bite avoidance (personal protective measures or "ppm's") is most important between dusk and dawn, when most mosquitoes are active and searching for blood meals. It may sound obvious but here it is again:

1. Cover up. Use light, long legged trousers and long sleeves. Some experienced travelers even impregnate their evening clothes with insecticide.



2. Use insect repellants. DEET containing repellents are very effective.



3. Bed nets, especially if impregnated with insecticide, are very effective at protecting you while you sleep.



4. Burn coils or use vaporizing mats in your room at night.



5. Ceiling or pedestal fans will deter mosquitoes if you are not using a bed net.

Malaria prophylaxis - should you take it?

Malaria prophylaxis (pronounced pro-fee-lak-sis) refers to the drugs that are taken to prevent malaria and is somewhere between a vaccine and a treatment. Like all vaccines, it is a balance of risks. In this case it is the risk of contracting malaria versus the risk of side effects from the prophylaxis. Like all treatments, there are various options depending on the needs and condition of the traveler. The above ten points summarise the risk to visitors in Nepal and it is clear that the risk of contracting malaria while on a brief visit is extremely low. If you fall into one of the special risk categories below and you are unsure as to how to proceed we suggest that you contact the clinic for advice.

Travelers at special risk from malaria and those with other medical conditions

1. Pregnant women: pregnant women are at great risk from severe malaria and should avoid visiting areas of malaria transmission if at all possible. If a visit to a high-risk area (e.g. a priority rural area during the early monsoon period) is absolutely necessary, prophylaxis should be taken. (See below). Chloroquine and Proguanil have a long safety record in pregnancy but Proguanil use should be supplemented with Folic acid 5mgs daily. Mefloquine should not be used in the first three months of pregnancy and Fansidar is also not to be used by pregnant women.



2. Young children: young children are not necessarily at greater risk of contracting malaria, but they have a habit of getting sick rapidly. Looking after a sick child can be a nerve racking experience, especially if they have a potentially dangerous illness. Making a diagnosis can also be difficult, especially in babies and infants. We would advise having a low threshold for giving a young child prophylaxis if visiting a high-risk area were essential. Chloroquine is safe to give young children and comes in a liquid suspension (the only prophylactic that does) but its taste is incredibly bitter. Mefloquine can also be used if the child weighs more than 5kgs. This is a convenient once weekly dose that can be crushed and added to food. Doxycycline must not be given to children under the age of 12 years. Bednets, mosquito coils and insect repellents are essential items when traveling with children.



3. Anybody without a spleen: the spleen is situated under your ribcage in the left side of your chest, just beneath the diaphragm. Its job is essentially to clean the circulating blood, removing old or damaged cells as it does so. As a result it has an important job to do when the red cells are infected by malaria parasites. Without it, malaria infections can progress rapidly so those who have no spleen (it is removed usually as a result of trauma) should have a low threshold for taking prophylaxis and be meticulous in avoiding mosquito bites.



4. Those with epilepsy: those with epilepsy or other seizure disorders should avoid both Chloroquine and Mefloquine. Alternatives are to use Proguanil alone or Doxycycline at a higher dose if anti-convulsant medications are being taken. Fansidar is safe as standby treatment but should not be used as prophylaxis.



5. Those with liver or kidney disease: Proguanil may not be used by those with kidney disease. Chloroquine, Mefloquine and Doxycycline are safe. Those with mild liver dysfunction may use Chloroquine and Proguanil, Mefloquine and Doxycycline should be avoided. Those with severe liver dysfunction may only take Proguanil and so should avoid travel to transmission areas if at all possible.

CIWEC Clinic guidelines on malaria prophylaxis in Nepal

1. Situations for which prophylaxis is NOT routinely recommended at any time of year:
   1. Visitors to Kathmandu arriving by air and remaining in the Kathmandu valley or trekking in the hills above Kathmandu.
   
   
   
   2. Visitors to Pokhara, traveling overland from Kathmandu having arrived by air and trekking in the hills above Pokhara.
   
   
   
   3. All other trekkers and mountaineers arriving in Kathmandu by air who reach their start point without visiting the Terai.
   
   
   
   4. Visitors rafting high altitude rivers e.g. the Bhote Khosi.
   
   
   
2. Situations for which prophylaxis IS routinely recommended:
   1. Visitors to the "priority" districts during the summer months (June to September) intending to sleep in rural areas for longer than one week. This includes visitors to Bardia and Suklaphanta national parks and the rural areas surrounding Janakpur and Nepalgunj during the summer months.
   
   
   
3. Situations where the risk of contracting malaria is extremely low but for which prophylaxis is NOT routinely recommended:
   1. Healthy individuals not at special risk (see 'Travelers at special risk') visiting either Bardia or Chitwan national parks between October and May and returning immediately to within quick access to competent medical help (Kathmandu or home country).
   
   
   
   2. Healthy individuals not at special risk (see 'Travelers at special risk) visiting urban areas of the Terai between October and May who are then returning directly to within quick access to competent medical help (Kathmandu or home country).
   
   
   
   3. Healthy individuals not at special risk (see 'Travelers at special risk'), rafting rivers in the middle hills between October and May, where the pull out point is on the Terai, and returning directly to within quick access to competent medical help (Kathmandu or to your home country). This includes those going on to visit one of the national parks during the winter months, having completed a river-rafting trip.
   
   
   
4. Situations for which the risk is extremely low and prophylaxis should be considered:
   1. Visitors to the western Terai who are then traveling on to remote areas for longer than a week. Typically this includes visitors to Humla (including Mt Kailash trekkers), Jumla or Dolpa regions who are sleeping overnight on the edge of Bardia district (Nepalgunj), especially during the summer months (June to September) when these high treks are most popular.
   
   
   
   2. Visitors to the eastern Terai who are then traveling on to remote areas for longer than a week. Typically this includes visitors to Kanchenjunga region (especially during the summer months (June to September) that overnight in Biratnagar, Dharan or Dankuta before starting a long trek. This also applies to visitors traveling down to the trek start point from Kathmandu by road, especially those staying overnight on the Terai during the journey.
   
   
   

Kavre District: Kavre is the district immediately east of the Kathmandu valley and within this district is a relatively low-lying valley named the Panchkhal valley. Within this valley there is a fairly high transmission rate of P. Vivax malaria. For this reason and because of its proximity to Kathmandu it has been labeled a "malaria priority district". Tourists very rarely stay in this district and there are no tourist lodges in the Panchkhal valley. Travelers to Tibet or the resorts near the Tibetan border ("The Last resort", "Borderlands" etc) and those rafting the Bhote Khosi river will pass through this valley during their journey. Transiting Kavre does not constitute a risk of acquiring malaria, nor does staying in the town of Dhulikhel situated immediately west of the Panchkhal valley. Dhulikhel is on the ridge between Panchkhal and Kathmandu and at considerably higher altitude than both places.

Prophylaxis choice for travelers "at risk" in Nepal

Having established that you are a traveler "at risk" by either the timing and duration of your visit or by the type of traveler you are, you need to choose a malaria prophylactic to use in addition to bite avoidance. The vast majority of malaria in Nepal is P.Vivax malaria and is sensitive to Chloroquine. There is a tiny chance that a brief visit to the Terai while in transit will result in infection with P.Falciparum malaria, even though to our knowledge it has not yet happened. But it is for this small chance when going into a remote area for which precautions need to be taken. Here are your choices:

1. Mefloquine (Lariam) 250mgs once weekly, taken at least two weeks before entering a transmission area and continued for four weeks after leaving a transmission area. Mefloquine is more effective against resistant P.Falciparum malaria than Chloroquine alone, but has a slightly higher rate of side effects, especially neuropsychological side effects, even though these are rare (about one in ten thousand users). It is safe for use by young children and in pregnancy after the first three months. Women of childbearing age are advised not to take Mefloquine without using adequate contraception methods. Mefloquine is not suitable for those with a history of epilepsy or convulsions and those with neuropsychiatric disorders. It should be stopped if anyone using it experiences nightmares or panic attacks.



2. Doxycycline (Vibramycin) 100mgs once daily, taken at least a week before entering a transmission area and continued for four weeks after leaving the transmission area. This is a tetracycline antibiotic should not be taken used by pregnant women or children under the age of 12 years. It should be taken with plenty of water and not just before retiring to bed. In about 3% of users, doxycycline causes a photosensitivity rash. This is a sore, red rash that appears on sun-exposed areas and resembles sunburn. If it appears then this drug should be discontinued. Women of child bearing age should take adequate contraception and also note that doxycycline may cause vaginal yeast infections (thrush). It is particularly useful in mefloquine resistant areas of Asia e.g. along Thai-Burmese and Thai-Cambodia borders.



3. Atovaquone (250mgs) and Proguanil (100mgs) (Malarone): a new, relatively safe, effective malaria prophylactic medication. It is especially useful in areas where Mefloquine resistance has developed (not the case in Nepal) or in travelers who are unable to tolerate other prophylactic drugs. As a "causal" prophylactic it kills malaria parasites in the early stages of infection as they are entering the liver. This means that it only needs to be taken for a week following exposure and not for four weeks as do the other drugs. This makes it cost effective for short exposures or repeated exposures. It is taken daily at the above dose (one tablet) with food or a milky drink starting a day or two before entering a malaria endemic area and continued for seven days after leaving an endemic area. Its use in pregnant women is not licensed but there is a paediatric formulation available. No dose adjustment is required for elderly travelers, even those with mild liver or kidney disease.

Standby treatment following potential malaria exposure.

Standby treatment is a drug treatment effective against malaria infection that is carried by a traveler to a remote area (usually defined as being more than 24 hours from competent medical help) for the purpose of treating a presumed malaria infection. Evidence has shown that standby treatment is often misused or used inappropriately due to the subjective difficulty in diagnosing malaria. For this reason and the fact that P.Falciparum malaria is a very rare (as yet unknown) entity in short term foreign visitors to Nepal, we do not advocate the use of standby treatment. If you wish to know more about standby treatment, especially if you fall into one of the "Travelers at special risk" categories, please contact us.

Advice for returning travelers

The golden rule for travelers returning home from an area where malaria is transmitted is to seek help immediately if you develop a fever within a year of you return, especially within the first three months. P. Falciparum malaria is rarely a cause of fever after three months have elapsed, P.Vivax however can lie dormant in the liver for up to several years following infection. If you develop a fever having visited an area where malaria is transmitted, seek medical advice promptly and specifically mention your exposure to malaria.

If you have any questions regarding malaria in Nepal you can contact one of the CIWEC physicians by e-mailing us at ciwecclinic@mail.com.np