International Strategies for Tropical Disease Treatments - Experiences with Praziquantel - EDM Research Series No. 026
(1998; 113 pages) View the PDF document
Table of Contents
View the documentAbstract
View the documentAcknowledgments
View the documentInformation on authors
View the documentExchange rates used in the report
Open this folder and view contentsChapter 1: Policies for praziquantel*
Open this folder and view contentsChapter 2: Bayer & E. Merck: Discovery and development of praziquantel*
Open this folder and view contentsChapter 3: Shin Poong Pharmaceutical Co.: Process development in the Republic of Korea*
Open this folder and view contentsChapter 4: The Egyptian International Pharmaceutical Industries Co.: Praziquantel formulation*
Open this folder and view contentsChapter 5: The international supply of praziquantel*
Close this folderChapter 6: Demand for praziquantel and national distribution*
View the documentThe demand for praziquantel
View the documentNational distribution of praziquantel
View the documentReferences
Open this folder and view contentsChapter 7: Prices and production costs of praziquantel*
View the documentOther documents in the DAP Research Series
View the documentDAP Research Series No. 26
 

The demand for praziquantel

Non-schistosomiasis demand

The non-schistosomiasis demand for praziquantel can be considered along several dimensions, as noted below: human versus veterinary use; developed country versus developing country markets; and within the human market, use for treatment of schistosomiasis versus treatment of other helminthic infections.

• First, the veterinary market may be smaller in terms of volume, but is probably comparable in terms of sales value to the human market, because of the higher prices of veterinary products. In 1993, the total value of global veterinary sales of praziquantel were about US$ 90 million. This compares favourably with our approximate estimation of the global value of sales of human praziquantel formulations in the same year. Assuming an average price per tablet (based on the prices and relative sales in developed and developing countries) of the human formulations of about US$ 1,** our estimate of global supply in 1993 of 89 million tablets (see Chapter 5) would suggest that a global sales value of human praziquantel formulations is about US$ 89 million. The veterinary market probably also offers higher profit margins to producers of praziquantel than the human market.

** The estimate of an average price per tablet of about US$ 1 should be taken as very rough, based on three main assumptions: very small market share in developed countries at full price; relatively small private market share in developing countries (perhaps 20%); and predominantly tender market for developing countries (perhaps 80%) at deeply discounted prices. See Chapter 7 for more data on prices.

• Second, veterinary sales of praziquantel are dominated by the developed world, although China does use the drug for the treatment of schistosomiasis infections in cattle (World Bank, 1991) as a means of reducing disease transmission. Given that the veterinary market is comparable to the human market and is located primarily in developed countries, developed country praziquantel sales (veterinary plus human) may well exceed sales in developing countries.

• Third, the demand (both potential and realized) for praziquantel for schistosomiasis treatment dominates that for other helminthic infections, although the potential demand for praziquantel for treatment of these other diseases is significant and increasing. WHO’s global estimates of prevalence of these other helminthic diseases in 1993 are shown below:

Table 6.1: Estimated global prevalences for selected helminthic diseases

Helminthic diseases

Estimated global prevalence

Clonorchiasis

7.0 million

Opisthorchiasis

10.3 million

Paragonimiasis

20.7 million

Various intestinal fluke infections

1.3 million

Schistosomiasis

200.0 million

Source: Schistosomiasis Control Unit, WHO, 1994.

These estimates would suggest that praziquantel may have other potential markets in the future. For this report, however, the non-schistosomiasis market and the veterinary market are not discussed further, due to the limited availability of data and the study’s focus on schistosomiasis.

Potential demand for praziquantel for schistosomiasis treatment

In 1989, WHO compiled an estimate of the global “need” for praziquantel, based on country by country estimates of the prevalence of schistosomiasis and assumed treatment of all infected people (Utroska et al., 1989). This represents the only public effort to calculate the potential demand for praziquantel. The analysis compiled studies from developing countries to estimate the global prevalence of schistosomiasis. Estimates of the population at risk (population in endemic areas of the country) and the average prevalence of schistosomiasis in the country were used to estimate the total number of people infected. The infected people were then separated into two groups, persons below 15 years and those above 15 years. Then, using standard national weight charts for these two groups, estimates of the total body weight of each group were made. Finally, the total weight for each group was divided by the standard dosage of praziquantel of 40 mg/kg body weight, to arrive at the total number of 600 mg praziquantel tablets needed. The analysis calculated that about 424 million tablets were needed annually to treat all people estimated to be infected with schistosomiasis in endemic countries.

The validity of the WHO global estimate is difficult to assess, because the figure is based on variable data and several assumptions. A potential for bias exists at each step of the analysis, and, therefore, in the overall results, although it is difficult to know what the extent and overall direction of the bias might be. For example, the quality of the prevalence estimate differs by country, depending on whether a scientific study was undertaken or the country simply provided its own assessment. Some countries have reassessed WHO’s point estimate of prevalence, and found it either too high or too low. Cameroon’s estimates, for example, were found to be too high (Ratard et al., 1992). One factor that could contribute to under-estimates is that schistosomiasis is not a reportable disease-except in a few countries-which would reduce the level of reliable reporting. On the other hand, some countries calculated national figures based on projections from pilot studies in endemic areas; this method would tend to generate over-estimates of prevalence. To deal with these problems, future estimates of schistosomiasis prevalence by WHO could include ranges.

While WHO’s estimates for specific countries may have wide margins of error, the ordering of countries is probably reliable. Table 6.2 lists the top countries according to WHO’s global estimate of praziquantel need, along with each country’s share of global need, and the overall global need. Table 6.2 also includes the limited data that we could collect on the estimated availability of praziquantel in the national markets of the top 30 countries, plus data for the Republic of Korea. It should be stressed that these estimates of national supply are very rough, based on incomplete data. Also, substitutes for praziquantel are used in some countries. Brazil, for example, makes its own oxamniquine, and therefore does not use much praziquantel.

Market data for praziquantel in developing countries are extremely difficult to obtain. For example, WHO does not have figures on praziquantel procurement by the 24 national schistosomiasis control programmes that it supports (WHO, 1993). And estimates of private market sales are limited and spotty at best. In seeking these data, we mailed questionnaires to MOHs and government offices in the top 30 endemic countries, to experts in schistosomiasis, and to others involved in national schistosomiasis control programme operations. Few responses were received, however, with even fewer reliable estimates of public procurement or private market sales for praziquantel. The responses included partially completed questionnaires from three schistosomiasis experts, and from seven countries (Botswana, Brazil, Egypt, Ghana, Nigeria, South Africa, and Zambia). In addition, information was received that eleven questionnaires had been forwarded to the proper authorities, although no response was received from these sources by April 1995. A few additional questionnaires were returned with suggestions that other people be contacted; these leads, however, did not produce usable data. As shown in Table 6.2, we were able to collect very limited market data on only 8 of the top 30 countries (plus the Republic of Korea), accounting for about 40% of the global supply of praziquantel (36 million tablets out of the estimated total supply of 89 million).

Table 6.2: Estimated need and availability for praziquantel in the top 30 countries

Country

Tablets needed

% of global need

Cumulative % of global needa

Availability in 1993

% of need metb

1. Nigeria

61,827,176

14.6%

14.6%

negligible

negligible

2. Tanzania

31,409,269

7.4%

22.0%

160,000

0.5%

3. Ghana

27,611,179

6.5%

28.5%

200,000

0.7%

4. Mozambique

27,311,159

6.4%

35.0%

n/a


5. Egypt

26,316,941

6.2%

41.2%

10 million

38.0%

6. Zaire

23,945,287

5.7%

46.8%

n/a


7. Brazil

19,680,000

4.6%

51.5%

negligiblec

negligible

8. Madagascar

15,413,514

3.6%

55.1%

n/a


9. Mali

13,962,618

3.3%

58.4%

607,000d

4.3%

10. Uganda

13,900,410

3.3%

61.7%

125-200,000

1.4%

Nos. 11-20

99,642,543

23.5%

85.2%



21-30 (inc. China)

43,035,263

10.1%

95.4%



of which China

2,826,355

0.7%


24 millione

850%

Availability in the Republic of Koreaf



1-1.2 million


Total estimates (for top 30)

404,124,000 need



(36,367,000 accounted for)


Total global estimates

423,609,839 need



89,000,000g availability

21.0%

Source: Estimated need is for use of praziquantel in treatment of schistosomiasis, based on a case treatment strategy, from Utroska et al., 1989; estimates of praziquantel availability are mostly for 1993, and are based on various sources, including a survey distributed to governments and schistosomiasis experts, as part of this study.

a The cumulative % of global need refers to the percentage of total global need accounted for by that country and all countries above.

b The % need met is based on the highest estimate of availability as a percentage of the estimated need.

c Brazil has wide availability of oxamniquine, which is produced in Brazil and is used for treatment of S. mansoni.

d The data for Mali are for 1995 and include purchases for projects and for the Ministry of Health.

e This figure for China is based on import and production estimates; the high volume is partly explained by China’s strategy of mass treatment for schistosomiasis in endemic areas, not only for infected cases, and by China’s treatment of cattle (which require large dosages of praziquantel).

f the Republic of Korea is included because praziquantel is widely available (for treatment of schistosomiasis and liver fluke).

g This figure of 89 million probably overestimates the global supply of praziquantel for human usage, since it includes the quantity used in China for both human and veterinary treatment.


Figure 6.1: Current global availability of praziquantel compared to total need

Total need = 424 million tablets
Current availability = 89 million tablets

Gap between need and supply of praziquantel

Table 6.2 and Figure 6.1 show a striking disparity between WHO’s estimated need for praziquantel, and our estimate of the supply of the drug in developing countries. As noted above, WHO estimated that the total global need for praziquantel is approximately 424 million tablets annually. This figure contrasts with our best estimate of the current annual supply of praziquantel, of about 89 million tablets (based on production data)-representing only 21.0% of the WHO’s estimate of global need. If WHO over-estimated the global need for praziquantel by a factor of two (about 210 million tablets), then the current global supply of praziquantel would still meet only about 40% of the revised global need. The gap is even more marked within certain individual countries.

The situation in six countries is reviewed next (in the order of estimated national “need” for praziquantel), to illustrate the gap that exists between the demand for praziquantel and its supply in developing countries with endemic schistosomiasis.

Nigeria (#1): According to WHO’s estimates, Nigeria has the greatest national need for praziquantel, about 62 million tablets annually, which is almost 15% of the total global need. However, according to a report received from the Nigerian MOH, and other informed sources, very little praziquantel is available in Nigeria-in either public or private sectors (Nigeria MOH, 1995). The high cost of praziquantel, and Nigeria’s huge requirement for the drug, has limited the country’s ability to procure the drug from Bayer and from international agencies (despite the concessional prices offered by these agencies). The same holds true for a number of other Sub-Saharan countries, such as Mozambique, Tanzania and Zaire.

Ghana (#3): According to WHO’s estimates, Ghana requires approximately 28 million tablets of praziquantel annually, which is about 6.5% of the estimated global need, ranking Ghana in third place in terms of need for praziquantel. The government has procured praziquantel through UNICEF and WHO, though the procurement has been irregular, and the annual supply has never exceeded 100,000 tablets. In 1993, however, the Ghana Partnership for Child Development project in the Volta region procured 200,000 tablets of praziquantel. Reportedly, praziquantel is available in the private market in Ghana (along with metrifonate, and Ambilhar (niridazole), a drug not officially recommended for schistosomiasis), although the volume of private sales is unknown.

Egypt (#5): Egypt is the world’s second largest single-country consumer of praziquantel, according to our estimates (approximately 10 million tablets in 1992), and ranks fifth in the world in its need for praziquantel, according to WHO’s estimates. But even the current level of praziquantel supply in Egypt provides only 38% of WHO’s estimate of national need (26 million tablets per year). It is difficult to gauge whether this gap reflects an over-estimation of need in Egypt by WHO, or a shortfall in supply. Starting in 1988, Egypt’s MOH procured praziquantel from Bayer, and later from EIPICO. Since 1990, however, the MOH has obtained almost all of its praziquantel from EIPICO. Praziquantel is distributed by the MOH to the local health units. Cases of schistosomiasis identified through field tests are treated with the drug in primary health care and endemic disease units. A follow-up is undertaken after three months through a re-examination and testing of the treated patients.

South Africa (#16): According to WHO estimates, South Africa has a need of almost 10 million tablets, placing it 16th among the countries needing praziquantel. Though exact figures were not available, South Africa’s procurement of praziquantel for schistosomiasis is probably considerably lower than its need, although the procurement might increase in the future with the expanded implementation of the government’s mass parasitic treatment projects. Praziquantel is used in South Africa for a number of parasitic infections, including schistosomiasis, cysticercosis, and various other cestode infections. Although the Bayer patent has expired in South Africa, it still holds a trademark registration, and evidently is, to date, the sole supplier to South Africa of praziquantel for treatment of schistosomiasis (although Merck, South Africa, produces a praziquantel-containing drug for treatment of cysticercosis). Praziquantel is sourced from Bayer, Germany, as a finished product and is then packaged locally in Bayer’s South African subsidiary and distributed through its own distribution company. Bayer supplies praziquantel to the South African government at a tender price, and also supplies the private sector, offering discounts based on the volume of purchases.

Zambia (#23): Zambia, according to WHO, has an annual need of about 5 million tablets, placing it 23rd in the list of countries needing praziquantel. Zambia, however, purchases hardly any praziquantel. The small quantities purchased are used for research purposes in Zambia’s attempts to find the best strategy for community-based control of schistosomiasis. Annually, about 1,000 tablets have been purchased for the last several years from Bayer, IDA, and WHO. Oxamniquine and metrifonate are reportedly available in the private market. Praziquantel is distributed by Medical Stores, Ltd., a pharmaceutical company run by the Ministry of Health.

China (#29): In China, the Schistosomiasis Control Programme in the MOH’s Department of Endemic Disease Control is responsible for the distribution of praziquantel to the provinces, through a special provincial office for schistosomiasis control. In 1993, China was the largest single-country consumer of praziquantel, with approximately 24 million tablets, according to our estimates of imports (10 tons of raw material) plus domestic production (5 tons of raw material), although this figure includes veterinary uses (for cattle) as well as human uses. We were unable to obtain any estimates of human versus veterinary consumption of praziquantel in China (or number of cases treated), despite numerous attempts with Chinese authorities and international agencies.

Several factors help explain the large gap between WHO’s estimate of the theoretical “need” and our estimate of the current supply of praziquantel:

• First, the relatively low profile of schistosomiasis as a disease priority has helped to constrain demand in many countries. Though it affects about 4% of the world’s population (with three times that number at risk), schistosomiasis is often perceived as a relatively low public health priority, because of the insidious nature of the disease and its tendency to affect morbidity without dramatically increasing mortality.

• Second, the availability of praziquantel may not reduce incidence rates of schistosomiasis, despite the drug’s high cure rates, because reinfection remains a major problem. If praziquantel availability does not affect the transmission of schistosomiasis, then the need for praziquantel would not decline and could even increase over time. Consequently, the gap between need and supply would persist in the foreseeable future at current production levels.

• Third, the high cost of praziquantel has created an irregular and uncertain supply in many countries. The problems of high cost are compounded by the low purchasing power (and limited foreign exchange) of most developing countries with endemic schistosomiasis. We explore price problems and cost issues in more detail in the next section.

• Finally, even when praziquantel is “available,” the public and private distribution systems may not work effectively in countries with endemic schistosomiasis. Major obstacles exist in the delivery of praziquantel to infected populations in rural areas.

The cost of praziquantel within schistosomiasis control programmes

The high procurement cost of praziquantel is commonly identified as the biggest obstacle to implementation of a successful schistosomiasis control programme. Table 6.3 summarizes information from the limited number of studies that have estimated the costs of praziquantel as a proportion of the total costs of schistosomiasis control programmes using different control strategies.

Table 6.3 demonstrates the paucity of good studies on the costs of schistosomiasis control programmes. Undertaking such studies in different country settings could help explain the role of praziquantel costs in national control programmes for schistosomiasis. Some studies suggest that the structures and strategies of control programmes affect the total cost of praziquantel as well as the proportion of total programme costs devoted to praziquantel. If the schistosomiasis programme is decentralized and integrated with local health delivery systems, in a horizontal approach, then the delivery costs are often reduced, while the proportion of praziquantel cost to total programme costs increases (Gryseels, forthcoming). A vertical programme, on the other hand, is more efficient at providing mass screening and preliminary sample surveys in a developing country, while the proportion of praziquantel cost to total programme costs decreases, because of the high cost of other inputs, such as vehicles and personnel (Gryseels, forthcoming).

Table 6.3: Studies on the cost of praziquantel compared to overall costs of schistosomiasis control programme

Study location

Year

Authors

Praziquantel as % of total costs

Comments

Mali

1988

Brinkmann et al.

8.5 to 17.3%

Range based on whether programme involved targeted or mass chemotherapy.

Global

1983

WHO study

10 to 30%

Estimate of costs not based on data collected in a specific setting.

Madagascar/Mali

1989

Rohde

39 to 47%

Estimated costs of alternative scenarios for control programmes, for a hypothetical population, assuming various expenses and using data collected in Madagascar and Mali.

Kilombero, Tanzania

1994

Guyatt et al.

30.9%
58.1%
83.5%

Lower estimate is for reagent strip testing of schoolchildren. Middle estimate is for passive testing & treatment at PHCs. Higher estimate is for mass treatment of schoolchildren using mobile teams.

Pemba, Tanzania

1986-87

Savioli et al.

80 to 89%

Estimate of total costs calculated with only drugs and urinary reagent strips included.

Congo

1986

Korte et al.

Not calculated

Model-based cost estimates for metrifonate and praziquantel.

Table 6.3 highlights the great variability across studies of the relative costs for praziquantel. While part of this variation can be explained by different control strategies (e.g., mass chemotherapy versus targeted strategies), as explained above, the variation also results from inconsistency in the cost categories. The two most widely cited, and probably more reliable, studies (Brinkmann et al., 1988; and WHO, 1983) show that the costs of praziquantel as a proportion of overall programme costs are significant (8.5 to 17.3%; and 10 to 30%).

The cost of praziquantel within government health budgets

Can countries with endemic schistosomiasis afford to pay for praziquantel from the government health budget? Below we briefly consider this question for the countries of Sub-Saharan Africa.

In 1990, average per capita expenditure on health in all of Africa was about US$ 23 (Murray, Govindaraj, and Musgrove, 1994). Of this, spending in the entire public sector (including social insurance and spending by parastatal agencies) was just over US$ 10 per capita. If only the Ministry of Health expenditures are considered, then the average annual per capita expenditure would be about US$ 5-7 per capita. If one were to disregard countries like Botswana, the Seychelles and South Africa, which are significant outliers in terms of health spending, then the annual spending on health by the Ministries of Health would be under US$ 4 per capita. For several countries, like Mozambique, the level of spending is even less.

If about 20% of the MOH health budget is spent on drugs and medical products (Murray, Govindaraj, and Chellaraj, 1994), then the average spending on drugs in Africa by Ministries of Health would be about US$ 0.80 per capita. If, for example, Nigeria were to procure as much praziquantel as it needs annually to treat all schistosomiasis cases (62 million tablets, according to the WHO estimate), at the UNICEF price of about US$ 0.22 per tablet, then the MOH would require an annual expenditure of US$ 13.6 million, or a per capita spending of almost US$ 0.14-about 17.5% of all MOH spending on drugs and medical supplies. This rough calculation demonstrates why it would be difficult to expect Nigeria’s MOH to pay for the praziquantel “need” out of the government’s health budget.

The study in Tanzania by Guyatt et al. (1994) provides roughly similar figures for the cost of praziquantel compared to total government per capita health spending. The cost per capita of praziquantel in the three types of programmes evaluated by the authors can be calculated at approximately US$ 0.02-0.07 (from 30.9% of US$ 0.05, to 58.1% of US$ 0.11). Per capita government expenditure on drugs would be US$ 0.24, based on the estimate from Guyatt et al. of per capita government health spending of US$ 1.20, and assuming (as in the previous example) 20% expenditure of this amount on drugs. Once again, expenditure on praziquantel alone would constitute a substantial proportion (8-29%) of the government’s total spending on drugs, probably putting it beyond the means of the Tanzanian government.

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