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Inhaled frusemide and asthma
1539
Distribution of ivermectin by health workers SIR,-In 1987 the international health community was heartened to learn of the generous promise by Merck & Co, the developers of ivermectin (’Mectizan’), to supply the drug free to organisations interested in using it to combat river blindness. Merck set up the Mectizan Expert Committee (MEC) to screen applications for the
drug. MEC’s guidelines reflect Merck’s concern about product liability and diversion of the drug to the lucrative veterinary market, and access to the drug is restricted to organisations capable of delivering it responsibly and of preventing misappropriation. Governments and other organisations which receive the medicine free of charge are in turn encouraged to restrict access. These concerns, though understandable, have unfortunately created a climate in which most organisations, including ministries of health, are reluctant to permit village health workers to distribute the drug. Village health workers form the foundation of many successful primary health care programmes. They have proved themselves capable, when properly trained and supervised, of safely and effectively delivering a variety of health services (including oral contraception) and managing malaria, diarrhoea, and childbirth. No-one claims that they should work alone: a cornerstone of their training is the recognition of cases requiring referral. After listening to the concerns of some of the experts planning ivermectin distribution programmes one might think that the task is complex and that those who take the drug are at risk of life-threatening side-effects. Neither assertion is valid. Ivermectin is an oral medication, the dose of which depends upon body weight. Inexpensive "bathroom" scales are accurate enough for this purpose. In communities where onchocerciasis is a serious public health concern the drug should be dispensed to everyone except children weighing less than 15 kg, women who think they may be pregnant or who have been delivered of a baby in the previous week, and people who cannot walk or who otherwise appear seriously ill. The screening process thus comes down to a weighing, a quick visual assessment of general fitness, and, for women of childbearing age, two questions. In theory, the only record keeping essential to the distribution process is a tally of the people treated and the tablets dispensed. If village health workers distribute the drug house-to-house they can record the house number and the name and dose for every recipient. This permits supervisors to verify the accuracy of the records by visiting a sample of houses. Is ivermectin safe enough to be distributed by village health workers? The answer is "yes". Experts from the World Health Organisation and various research institutions have monitored community trials of the drug in West Africa in which over 100 000 people have been treated. Their conclusion was: "There are few, if any, drugs at present in use for the treatment of tropical diseases that have undergone the scrutiny that ivermectin has had. The drug is extremely safe, and is without known pharmacological side-effects in humans".1 Serious reactions to ivermectin have occurred to fewer than 1 in 1000 recipients (which is approximately a woman’s risk of stroke or thromboembolism while on oral contraceptives). These reactions have consisted of postural hypotension or of wheezing in people with a history of asthma.. All reactions seen thus far have evolved slowly over several hours and, according to a member of the MEC appointed to advise WHO: "It is probable that none of the reactions were life-threatening".2 The few serious reactions to ivermectin were easy to recognise (dizziness or shortness of breath) and evolved so slowly that a village health worker on a bicycle or motorcycle would have had plenty of time to seek help from a clinic within 20 km of the village. Merck has, in effect, set up a vertical hierarchy for distributing its drug. Every level in the hierarchy is reluctant to relinquish control over access to ivermectin. At the bottom are people living in villages hyperendemic for onchocerciasis. Such communities typically are tiny settlements of fewer than 500 people and are the very ones that seldom receive even the most basic of health and development services. The centralised hierarchies do not reach out that far, except piecemeal with shortlived pilot programmes. If ivermectin is to reach every one of the 50 000 or so mesoendemic or
hyperendemic communities in the world on a sustained annual basis, the controlling agencies (Merck, MEC, government health services, non-governmental organisations) must accept that tight control of the distribution process is unnecessary and impracticable. MEC has shown a commendable flexibility in its approval of alternative strategies of distribution and has permitted some programmes to hand over certain responsibilities to village health workers-but the perception remains amongst governments and other agencies that tight control is essential and is a prerequisite for receipt of the drug from Merck. More must be done to convince planners and administrators of a fundamental principle of the primary health care movement-namely, that Health for All depends upon community participation and community participation comes at the expense of tight central control. Kwara State Blindness Prevention Program, PO Box 52839, Falomo, Ikoyi, SW.
BOB POND
Lagos, Nigeria
Organisation. Report of a meeting of the TDR/OCP/OCT Subcommittee for Monitoring of Community Trials of Ivermectin (Ouagadougou, Burkina Faso, Jan 25-27, 1989). 2. Green B. Information and opinions to be conveyed by Dr Bruce Greene to the independent Mectizan Committee following the meeting of the Monitoring Sub-Group for Ivermectin Trials in Onchocerciasis (March 20, 1988). 1. World Health
Inhaled frusemide and asthma SIR,-We agree with your April 21 editorial that studies with frusemide may shed further light on the pathophysiology of asthma. We have evidence that one of the sites of action of frusemide is airway nerves. Investigations in healthy subjects show that inhaled frusemide inhibits cough responses induced by low chloride content solutions and prostaglandin F2, but not by capsaicin.1,2 We interpret these effects as probably being inhibition of the afferent limb of the cough reflex. In-vitro investigations with guineapig airways demonstrate that frusemide inhibits in a dose-dependent manner airway smooth-muscle contraction induced by stimulation of cholinergic and non-cholinergic, non-adrenergic nerves in tracheal and bronchial tissues, respectively.3 This effect was independent of airway epithelium and of cyclo-oxygenase production. Frusemide had no effect against direct activation of cholinergic or peptidergic receptors, and so clearly was inhibiting neural excitation. Bumetanide, another loop diuretic, was more potent than frusemide in these studies,3 which supports the view that such diuretics may + + act through inhibition of the Na /K 12Cl- co-transporter on airway nerves. National Heart & Lung Institute, London SW3 6LY, UK
K. F. CHUNG P. J. BARNES
P, Nichol GM, Barnes PJ, Chung KF. Inhaled frusemide inhibits cough induced by low chloride content solutions and not by capsaicin. Am Rev Respir Dis
1. Ventresca
(in press). P, Nichol GM, Barnes PJ, Chung KF. Inhibitory effects of inhaled frusemide against the induction and potentiation of cough responses in normal subjects. Am Rev Respir Dis 1990; 141: A361. 3. Elwood W, Barnes PJ, Chung KF. Frusemide and bumetanide loop diuretics inhibit neurally-mediated airway smooth muscle contraction in guinea-pig. Br J Pharmacol (in press). 2. Ventresca
Intrauterine devices and removal times SIR,-The advice given by manufacturers/distributors of intrauterine devices (IUDs) is that removal at the recommended time limit is to be preferred because of the possible increase in the likelihood of pregnancy and side-effects if the device is used for longer. Data collected in studies by the UK Family Planning Research Network suggest that this view may be incorrect. Pregnancy rates in a use-effectiveness study of 433 users of the ’Short Multiload’ IUD (recommended period of use 3 years) are
Distribution of ivermectin by health workers SIR,-In 1987 the international health community was heartened to learn of the generous promise by Merck & Co, the developers of ivermectin (’Mectizan’), to supply the drug free to organisations interested in using it to combat river blindness. Merck set up the Mectizan Expert Committee (MEC) to screen applications for the
drug. MEC’s guidelines reflect Merck’s concern about product liability and diversion of the drug to the lucrative veterinary market, and access to the drug is restricted to organisations capable of delivering it responsibly and of preventing misappropriation. Governments and other organisations which receive the medicine free of charge are in turn encouraged to restrict access. These concerns, though understandable, have unfortunately created a climate in which most organisations, including ministries of health, are reluctant to permit village health workers to distribute the drug. Village health workers form the foundation of many successful primary health care programmes. They have proved themselves capable, when properly trained and supervised, of safely and effectively delivering a variety of health services (including oral contraception) and managing malaria, diarrhoea, and childbirth. No-one claims that they should work alone: a cornerstone of their training is the recognition of cases requiring referral. After listening to the concerns of some of the experts planning ivermectin distribution programmes one might think that the task is complex and that those who take the drug are at risk of life-threatening side-effects. Neither assertion is valid. Ivermectin is an oral medication, the dose of which depends upon body weight. Inexpensive "bathroom" scales are accurate enough for this purpose. In communities where onchocerciasis is a serious public health concern the drug should be dispensed to everyone except children weighing less than 15 kg, women who think they may be pregnant or who have been delivered of a baby in the previous week, and people who cannot walk or who otherwise appear seriously ill. The screening process thus comes down to a weighing, a quick visual assessment of general fitness, and, for women of childbearing age, two questions. In theory, the only record keeping essential to the distribution process is a tally of the people treated and the tablets dispensed. If village health workers distribute the drug house-to-house they can record the house number and the name and dose for every recipient. This permits supervisors to verify the accuracy of the records by visiting a sample of houses. Is ivermectin safe enough to be distributed by village health workers? The answer is "yes". Experts from the World Health Organisation and various research institutions have monitored community trials of the drug in West Africa in which over 100 000 people have been treated. Their conclusion was: "There are few, if any, drugs at present in use for the treatment of tropical diseases that have undergone the scrutiny that ivermectin has had. The drug is extremely safe, and is without known pharmacological side-effects in humans".1 Serious reactions to ivermectin have occurred to fewer than 1 in 1000 recipients (which is approximately a woman’s risk of stroke or thromboembolism while on oral contraceptives). These reactions have consisted of postural hypotension or of wheezing in people with a history of asthma.. All reactions seen thus far have evolved slowly over several hours and, according to a member of the MEC appointed to advise WHO: "It is probable that none of the reactions were life-threatening".2 The few serious reactions to ivermectin were easy to recognise (dizziness or shortness of breath) and evolved so slowly that a village health worker on a bicycle or motorcycle would have had plenty of time to seek help from a clinic within 20 km of the village. Merck has, in effect, set up a vertical hierarchy for distributing its drug. Every level in the hierarchy is reluctant to relinquish control over access to ivermectin. At the bottom are people living in villages hyperendemic for onchocerciasis. Such communities typically are tiny settlements of fewer than 500 people and are the very ones that seldom receive even the most basic of health and development services. The centralised hierarchies do not reach out that far, except piecemeal with shortlived pilot programmes. If ivermectin is to reach every one of the 50 000 or so mesoendemic or
hyperendemic communities in the world on a sustained annual basis, the controlling agencies (Merck, MEC, government health services, non-governmental organisations) must accept that tight control of the distribution process is unnecessary and impracticable. MEC has shown a commendable flexibility in its approval of alternative strategies of distribution and has permitted some programmes to hand over certain responsibilities to village health workers-but the perception remains amongst governments and other agencies that tight control is essential and is a prerequisite for receipt of the drug from Merck. More must be done to convince planners and administrators of a fundamental principle of the primary health care movement-namely, that Health for All depends upon community participation and community participation comes at the expense of tight central control. Kwara State Blindness Prevention Program, PO Box 52839, Falomo, Ikoyi, SW.
BOB POND
Lagos, Nigeria
Organisation. Report of a meeting of the TDR/OCP/OCT Subcommittee for Monitoring of Community Trials of Ivermectin (Ouagadougou, Burkina Faso, Jan 25-27, 1989). 2. Green B. Information and opinions to be conveyed by Dr Bruce Greene to the independent Mectizan Committee following the meeting of the Monitoring Sub-Group for Ivermectin Trials in Onchocerciasis (March 20, 1988). 1. World Health
Inhaled frusemide and asthma SIR,-We agree with your April 21 editorial that studies with frusemide may shed further light on the pathophysiology of asthma. We have evidence that one of the sites of action of frusemide is airway nerves. Investigations in healthy subjects show that inhaled frusemide inhibits cough responses induced by low chloride content solutions and prostaglandin F2, but not by capsaicin.1,2 We interpret these effects as probably being inhibition of the afferent limb of the cough reflex. In-vitro investigations with guineapig airways demonstrate that frusemide inhibits in a dose-dependent manner airway smooth-muscle contraction induced by stimulation of cholinergic and non-cholinergic, non-adrenergic nerves in tracheal and bronchial tissues, respectively.3 This effect was independent of airway epithelium and of cyclo-oxygenase production. Frusemide had no effect against direct activation of cholinergic or peptidergic receptors, and so clearly was inhibiting neural excitation. Bumetanide, another loop diuretic, was more potent than frusemide in these studies,3 which supports the view that such diuretics may + + act through inhibition of the Na /K 12Cl- co-transporter on airway nerves. National Heart & Lung Institute, London SW3 6LY, UK
K. F. CHUNG P. J. BARNES
P, Nichol GM, Barnes PJ, Chung KF. Inhaled frusemide inhibits cough induced by low chloride content solutions and not by capsaicin. Am Rev Respir Dis
1. Ventresca
(in press). P, Nichol GM, Barnes PJ, Chung KF. Inhibitory effects of inhaled frusemide against the induction and potentiation of cough responses in normal subjects. Am Rev Respir Dis 1990; 141: A361. 3. Elwood W, Barnes PJ, Chung KF. Frusemide and bumetanide loop diuretics inhibit neurally-mediated airway smooth muscle contraction in guinea-pig. Br J Pharmacol (in press). 2. Ventresca
Intrauterine devices and removal times SIR,-The advice given by manufacturers/distributors of intrauterine devices (IUDs) is that removal at the recommended time limit is to be preferred because of the possible increase in the likelihood of pregnancy and side-effects if the device is used for longer. Data collected in studies by the UK Family Planning Research Network suggest that this view may be incorrect. Pregnancy rates in a use-effectiveness study of 433 users of the ’Short Multiload’ IUD (recommended period of use 3 years) are