INTOX Home Page
  CBD for Leishmaniasis

Can CBD help with leishmaniasis, and if so, how?

The Centers for Disease Control and Prevention (CDC) describes leishmaniasis as a disease caused by infection with leishmania parasites, which are spread by the bite of a phlebotomine sand fly. 

Leishmaniasis belongs to the category of neglected tropical diseases (NTDs) (1). 

According to the World Health Organization (WHO), NTDs are communicable diseases that prevail in tropical and subtropical conditions, affecting more than a billion people and costing economies billions of dollars every year (2).

When Sand Flies Bite

Phlebotomine sand flies are known for their ability to transmit several viral, bacterial, and protozoal disease-causing organisms on humans and other animals (3.

Infection is transmitted through the bite of infected female phlebotomine sand flies. Sand flies become infected by sucking blood from an infected animal or person.

Sand flies live in a wide range of habitats, and individual species often have precise habitat requirements. They are distributed from Argentina to the United States, including Brazil, Columbia, Panama and Costa Rica (4).
Common Types of Leishmaniasis 
There are several types of leishmaniasis in people. The most common types are cutaneous leishmaniasis and visceral leishmaniasis.

Cutaneous leishmaniasis causes skin lesions that can persist for months or years. The skin lesions develop within several weeks or months after the exposure but first appear years later, as in trauma or immunosuppression (5).

Visceral leishmaniasis affects internal organs (mainly, spleen, liver, and bone marrow) and encompasses a wide range of severity and manifestations. 

Although the incubation period ranges from weeks to months, an asymptomatic infection can manifest decades after the exposure. This delayed presentation is particularly true in people who become immunocompromised, such as those with HIV/AIDS.

Unfortunately, there are no vaccines or drugs to prevent leishmaniasis infection. The best way for people to avoid infection is to protect themselves from sand fly bites (6). 

Minimizing nocturnal outdoor activities, wearing protective clothing, and applying insect repellent to exposed skin may also help.

How CBD May Help With Leishmaniasis: A Close Look at Pinene

Full-spectrum CBD oil contains a complete range of cannabinoids, terpenes, and flavonoids naturally present in cannabis, including a variety of fatty acids and beneficial fiber. 

Terpenes are the compounds in cannabis that give it distinctive aromas and flavors, while flavonoids are responsible for the vivid colors in most plants.

The combination of all these components creates a synergy known as “entourage effect,” where all of the constituents working together are more efficient than their isolated elements (7).

One of the essential terpenes found in cannabis plants is pinene, an aromatic compound that smells similar to a forest of pine trees. Pinene can also be found in orange peels, turpentine, pine needles, rosemary, dill, basil, parsley, and conifer trees.

Alpha-pinene and beta-pinene are the two types of pinene. The alpha type is typically abundant in cannabis.

In a 2014 study, which was published in the Journal of Ethnopharmacology, the authors examined the effects of Syzygium cumini essential oil (ScEO) and its major component, α-pinene, on leishmania (8).

Syzygium cumini is widely used in folk medicine against leishmaniasis, inflammation, chronic diarrhea, and ulcers. It is also one of the most commonly used plants for the treatment of diabetes worldwide. 

The researchers concluded that ScEO and its principal constituent, α-pinene, have significant anti-Leishmania activity.

A recent study published in Biomolecules examined the therapeutic potential of pinene (9). 

    The researchers found that these terpenes had antimicrobial, anticancer, anti-inflammatory, and antiallergic properties. 

These results parallel those from a previous study published in the British Journal of Pharmacology (10). 

The authors of the said study noted that alpha-pinene acts as a bronchodilator when working with tetrahydrocannabinol (THC), opening up airways to help inflammatory disorders, like asthma. 

Also, a 2015 study published in PLoS ONE showed pinene’s antibiotic benefits (11). 

Working with cannabidiol (CBD) and cannabinol (CBN), alpha-pinene demonstrated a broad spectrum of antibiotic properties that worked against infections, like MRSA (12).

The studies mentioned above highlight the therapeutic benefits of pinene, which may help alleviate symptoms of leishmaniasis, such as inflammation and bacterial infection.

    Given that pinene is found in cannabis, a full-spectrum CBD oil is most likely to contain this terpene as well. Thus, CBD oil may also have the potential to help with leishmaniasis.

Conclusion

Studies have shown that terpenes work with some cannabinoids, like THC, CBD, and CBN, to provide therapeutic effects. 
Through this synergy, a full-spectrum CBD oil may be able to deliver maximum benefits to those looking to alleviate symptoms and conditions linked to leishmaniasis. 

However, while the opportunities for the medicinal applications of the entourage effect are extensive, scientific research in this area is still lacking. Also, long-term side effects of CBD use are still unknown.

Thus, before using CBD for leishmaniasis symptoms or related conditions, consult with and seek advice from a doctor experienced in cannabis use.  

References
  1. CDC. (2018, July 24). Parasites - Leishmaniasis. Retrieved from https://www.cdc.gov/parasites/leishmaniasis/index.html.
  2. WHO. Neglected tropical diseases. Retrieved from https://www.who.int/neglected_diseases/diseases/en/.
  3. UF-IFAS. (2018, April). A Sand Fly. Retrieved from http://entnemdept.ufl.edu/creatures/misc/flies/lutzomyia_shannoni.htm.
  4. Ibid..
  5. CDC. (2018, Oct 15). Parasites - Leishmaniasis. Retrieved from https://www.cdc.gov/parasites/leishmaniasis/health_professionals/index.html.
  6. Ibid.
  7. Russo EB. The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No "Strain," No Gain. Front Plant Sci. 2019;9:1969. Published 2019 Jan 9. DOI:10.3389/fpls.2018.01969.
  8. Rodrigues et al. Syzygium cumini (L.) Skeels essential oil and its major constituent α-pinene exhibit anti-Leishmania activity through immunomodulation in vitro. https://doi.org/10.1016/j.jep.2014.11.024.
  9. Salehi B, Upadhyay S, Erdogan Orhan I, et al. Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature. Biomolecules. 2019;9(11):738. Published 2019 Nov 14. DOI:10.3390/biom9110738.
  10. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344–1364. DOI:10.1111/j.1476-5381.2011.01238.x.
  11. Kovač J, Šimunović K, Wu Z, et al. Antibiotic resistance modulation and modes of action of (-)-α-pinene in Campylobacter jejuni. PLoS One. 2015;10(4):e0122871. Published 2015 Apr 1. DOI:10.1371/journal.pone.0122871.
  12. CDC. (2019, Feb 5). Methicillin-resistant Staphylococcus aureus (MRSA). Retrieved from https://www.cdc.gov/mrsa/index.html.



    UKPID MONOGRAPH









    SODIUM STIBOGLUCONATE









    WN Harrison PhD CChem MRSC

    SM Bradberry BSc MB MRCP

    JA Vale MD FRCP FRCPE FRCPG FFOM



    National Poisons Information Service

    (Birmingham Centre),

    West Midlands Poisons Unit,

    City Hospital NHS Trust,

    Dudley Road,

    Birmingham

    B18 7QH





    This monograph has been produced by staff of a National Poisons

    Information Service Centre in the United Kingdom.  The work was

    commissioned and funded by the UK Departments of Health, and was

    designed as a source of detailed information for use by poisons

    information centres.



    Peer review group: Directors of the UK National Poisons Information

    Service.





    SODIUM STIBOGLUCONATE



    Toxbase summary



    Type of product



    Used in the treatment of visceral, cutaneous and mucocutaneous

    leishmaniasis.



    Toxicity



    Toxic effects have been reported following parenteral administration

    of antimony pharmaceuticals.



    Features



    There are no reports of ingestion, inhalation or topical exposure.

    However, effects similar to those reported for other antimony

    compounds may be expected (see antimony Toxbase entry).



    Injection



         -    Parenteral sodium stibogluconate administration has been

              associated with anorexia, nausea, vomiting, abdominal pain,

              a metallic taste, diarrhoea, pancreatitis, reversible

              elevations of liver enzyme activities, myalgia, arthralgia,

              proteinuria, ECG changes (T wave inversion, Q-T interval

              prolongation, S-T segment abnormalities), phlebitis,

              uveitis, optic atrophy and rarely anaphylactic shock, acute

              renal failure, hepatic necrosis and bone marrow hypoplasia.



    Management



    Injection



    1.   Discontinue therapy if significant adverse effects occur.

    2.   Symptomatic and supportive measures as dictated by the patient's

         condition.

    3.   Monitor the ECG, biochemical and haematological profiles.

    4.   Collect urine and blood for antimony concentration measurements.

    5.   Chelation therapy with dimercaprol, DMSA or DMPS may be

         considered, but discussion with a NPIS physician is recommended.



    References



    Bailly R, Lauwerys R, Buchet JP, Mahieu P, Konings J.

    Experimental and human studies on antimony metabolism: their relevance

    for the biological monitoring of workers exposed to inorganic

    antimony.

    Br J Ind Med 1991;48: 93-7.



    Hepburn NC, Siddique I, Howie AF, Beckett GJ, Hayes PC.

    Hepatotoxicity of sodium stibogluconate in leishmaniasis.

    Lancet 1993; 342: 238-9.



    Hepburn NC, Nolan J, Fenn L, Herd RM, Neilson JM, Sutherland GR,

    Fox KA.

    Cardiac effects of sodium stibogluconate: myocardial,

    electrophysiological and biochemical studies.

    QJM 1994; 87: 465-72.



    Lauwers LF, Roelants A, Rosseel M, Heyndrickx B, Baute L.

    Oral antimony intoxications in man.

    Crit Care Med 1990; 18: 324-6.



    Winship KA.

    Toxicity of antimony and its compounds.

    Adverse Drug React Acute Poisoning Rev 1987; 2: 67-90.



    Substance name



         Sodium stibogluconate



    Origin of substance



         NIF



    Synonyms



         Antimony sodium gluconate

         Myostibin

         Pentostam

         Solustibosan

         Solustin

         Solusurmin

         Solyusurmin

         Stibanate

         Stibanose

         Stibatin

         Stibinol                                (RTECS, 1997)



    Chemical group



         A pentavalent compound of antimony, a group V A element.



    Reference numbers



         CAS            16037-91-5               (RTECS, 1997)

                        12001-86-4               (RTECS, 1997)

         RTECS          CC7930000                (RTECS, 1997)

         UN             NIF

         HAZCHEM CODE   NIF



    Physicochemical properties



    Chemical structure

         C6H9Na2O6Sb                             (MARTINDALE, 1996)



    Molecular weight

         1048.91                                 (RTECS, 1997)



    Physical state at room temperature

         Solid                                   (MARTINDALE, 1996)



    Colour

         Colourless                              (MARTINDALE, 1996)



    Odour

         Odourless                               (MARTINDALE, 1996)



    Viscosity

         NA



    pH

         NIF



    Solubility

         Very soluble in water.

         Practically insoluble in alcohol and ether.

                                                 (MARTINDALE, 1996)



    Autoignition temperature

         NIF



    Chemical interactions

         NIF



    Major products of combustion

         Antimony and sodium oxides.             (SAX'S 1996)



    Explosive limits

         NIF



    Flammability

         NIF



    Boiling point

         NIF



    Density

         NIF



    Vapour pressure

         NIF



    Relative vapour density

         NIF



    Flash point

         NIF



    Reactivity

         NIF



    Uses



         In the treatment of visceral, cutaneous and mucocutaneous

         leishmaniasis.                          (MARTINDALE, 1996)



    Hazard/risk classification



    Index no. (Antimony compounds) 051-003-00-9

    Risk phrases

         Xn; R20/22

         Harmful by inhalation and if swallowed.

    Safety phrases

         S(2-) 22* (*If appropriate)

         Keep out of reach of children. Do not breathe dust*.

    EEC No:

         NIF                                     (CHIP2, 1994)



    INTRODUCTION AND EPIDEMIOLOGY



    Sodium stibogluconate is a pentavalent antimony compound. It is used

    in the treatment of visceral, cutaneous and mucocutaneous

    leishmaniasis. Adverse effects from pentavalent antimony drugs are

    reportedly less frequent and less severe than from trivalent antimony

    preparations (Reynolds, 1996). Pentostam, an aqueous solution of

    sodium stibogluconate, is the treatment of choice for visceral

    leishmaniasis. Most reports of adverse effects occur during

    therapeutic use.



    MECHANISM OF TOXICITY



    The mechanism of toxicity of antimony compounds is unclear but may

    involve disruption of thiol proteins via binding to sulphydryl groups

    (de Wolff, 1995).



    TOXICOKINETICS



    Absorption



    Antimony compounds may be absorbed by inhalation and ingestion, though

    gastrointestinal absorption in man is poor necessitating parenteral

    administration of antimony pharmaceuticals.



    Distribution and Excretion



    Following intravenous or intramuscular sodium stibogluconate

    administration, antimony is excreted rapidly via the kidneys. Rees et

    al (1980) demonstrated that some 80-90 per cent of an intramuscular

    dose of sodium stibogluconate was recovered in the urine within six

    hours of administration. Rapid renal elimination is reflected by a

    marked fall in the serum or whole blood antimony concentration to

    approximately one to four per cent of the peak concentration eight

    hours after an intravenous dose. However, even some 6-24 months after

    parenteral antimony therapy, Mansour et al (1967) reported increased

    urine antimony concentrations (range 5.8-145.3 µg/L) compared to

    untreated controls (range 2.9-9.1 µg/L). During daily administration

    there is slow distribution to the central compartment so that tissue

    concentrations reach a theoretical maximum after some seven days

    (ABPI, 1996).



    Small amounts of antimony appear in faeces via bile after conjugation

    with glutathione. A significant amount of antimony excreted in bile

    undergoes enterohepatic circulation (Bailly et al, 1991).



    CLINICAL FEATURES: ACUTE EXPOSURE



    There are no reports of acute ingestion, inhalation or topical

    exposure to sodium stibogluconate. However, effects similar to those

    reported for other antimony compounds may be expected (see antimony

    monograph).



    Injection



    Hepatotoxicity



    A 27 year-old woman with cutaneous leishmaniasis developed a transient

    rise in alanine aminotransferase activity (to 2.4 times the upper

    limit of normal) when she was inadvertently given ten times the

    intended dose of parenteral pentavalent sodium stibogluconate

    (Herwaldt et al, 1992). However, more typically hepatotoxicity is

    observed during prolonged therapy with antimony pharmaceuticals.



    Cardiovascular toxicity



    No cardiovascular complications arose in a patient who accidentally

    was given ten times the intended intravenous dose of sodium

    stibogluconate (Herwaldt et al, 1992).



    Gastrointestinal and pulmonary toxicity



    Coughing, nausea, vomiting, diarrhoea or substernal pain may occur

    rarely during intravenous injection (ABPI, 1996).



    CLINICAL FEATURES: CHRONIC EXPOSURE



    There are no reports of chronic ingestion, inhalation or topical

    exposure to sodium stibogluconate. However, effects similar to other

    antimony compounds may be expected (see antimony monograph).



    Injection



    Dermal toxicity



    Davis (1968) reported antimony dermatitis in some four per cent of 160

    patients treated with antimony-containing drugs.



    Gastrointestinal toxicity



    Patients treated for some one to two weeks with parenteral antimony

    compounds frequently reported anorexia, nausea and vomiting with some

    complaints of abdominal pain, a metallic taste and diarrhoea (Davis,

    1968).



    Pancreatitis also has been reported as a complication of parenteral

    therapy with stibogluconate or meglumine antimonate (de Lalla et al,

    1993; McCarthy et al, 1993; Gasser et al, 1994; Domingo et al, 1996).



    Hepatotoxicity



    Parenteral treatment with antimony compounds has caused hepatic

    necrosis although reversible elevations of liver enzyme activities are

    more typical (Winship, 1987; Saenz et al, 1991; Hepburn et al, 1993).



    Nephrotoxicity



    Sodium stibogluconate therapy has caused acute tubular necrosis

    (Balzan and Fenech, 1992; Rai et al, 1994a; Rai et al, 1994b).



    Renal tubular acidosis has also been described (Horber et al, 1991).



    In a review of 92 patients with visceral leishmaniasis (kala-azar)

    treated with sodium stibogluconate, two showed evidence of renal

    toxicity with casts and proteinuria although these patients also were

    receiving intramuscular pentamidine, another recognized renal toxin

    (Chunge et al, 1984).



    Cardiovascular and peripheral vascular toxicity



    ECG changes following exposure to antimony compounds are seen

    typically in patients with leishmaniasis or schistosomiasis who have

    been treated with parenteral antimony compounds. Typical features

    include T wave inversion or amplitude reduction, Q-T interval

    prolongation and S-T segment abnormalities (Davis, 1968; Chulay et al,

    1985; Henderson and Jolliffe, 1985). These effects usually reverse

    when treatment is discontinued.



    In 12 soldiers with cutaneous leishmaniasis treated with sodium

    stibogluconate Hepburn et al (1994) found that although a reversible

    decrease in T-wave amplitude occurred during treatment there were no

    significant changes in echocardiographic indices of left ventricular

    function, arrhythmia frequency or heart-rate variability. The authors

    concluded that 20 mg/kg/day sodium stibogluconate for 20 days had no

    cardiac side-effects in most fit, young patients.



    Gupta (1990) similarly noted that T-wave changes induced by antimony

    therapy were not associated with a deterioration in cardiac function.



    In a review of 160 patients with schistosomiasis treated with

    antimony-containing drugs (Davis, 1968) retrosternal chest pain was

    reported by 27 individuals. In three cases this was associated with

    acute vascular collapse immediately after intravenous drug

    administration (after the first dose in one case) suggesting an

    anaphylactic-type response.



    Phlebitis occurred in 31 patients receiving intravenous sodium

    stibogluconate in the treatment of visceral leishmaniasis (Chunge et

    al, 1984) and in one patient administered antimony sodium tartrate in

    the treatment of urinary schistosomiasis (Davis, 1968).



    Neurotoxicity



    Rai et al (1994b) described combined ninth and tenth cranial nerve

    palsies in a patient with kala-azar treated with parenteral

    stibogluconate. There was significant improvement within two weeks of

    cessation of treatment.



    Reversible peripheral neuropathy associated with sodium stibogluconate

    therapy has been reported also (Brummitt et al, 1996).



    Acute hydrocephalus in association with significant ocular toxicity

    (see below) occurred in a child following 23 antimony potassium

    tartrate injections (Grant and Schuman, 1993).



    Haemotoxicity



    Mallick (1990) described bone marrow hypoplasia as a complication of

    sodium stibogluconate administration. Haematological indices improved

    significantly following treatment withdrawal and steroid therapy.

    Other authors have described leucopenia (Hiçsönmez et al, 1988; Saenz

    et al, 1991) or recurrent episodes of thrombocytopenia (Braconier and

    Miörner, 1993) during parenteral antimonial therapy though no bone

    marrow biopsies were performed.



    Chunge et al (1984) reported epistaxis in 13 patients receiving

    parenteral antimony-containing drugs, in three cases associated with

    pancytopenia.



    Musculoskeletal toxicity



    Myalgia and arthralgia are reported frequently by patients with

    leishmaniasis or schistosomiasis treated with parenteral antimony

    compounds (Davis, 1968; Winship, 1987; Castro et al, 1990; Saenz et

    al, 1991). This effect is not necessarily dose-related (Gastro et al,

    1990).



    Ocular toxicity



    In a review of 92 patients with visceral leishmaniasis treated with

    parenteral stibogluconate, six developed uveitis and two retinal

    haemorrhages after completion of treatment and apparent cure (Chunge

    et al, 1984).



    In an early case report cited by Grant and Schuman (1993) a child

    developed acute onset bilateral blindness with fixed dilated pupils

    following 23 antimony tartrate injections. There was clinical evidence

    of optic neuritis with papilloedema and subsequent permanent optic

    atrophy.



    Forsyth (1958) reported one patient who developed transient retinal

    haemorrhages and exudates and another in whom the fundus was described

    as 'granular' following parenteral sodium antimony tartrate therapy

    for schistosomiasis. Visual acuity was diminished in both cases but

    returned to normal within six months.



    Three children who received repeated courses of parenteral tartar

    emetic in the treatment of schistosomiasis developed optic atrophy

    (Kassem et al, 1976).



    MANAGEMENT



    Management following ingestion or inhalation of antimony compounds are

    discussed in the antimony monograph.



    Injection



    If serious adverse effects develop discontinuation of antimony therapy

    is a priority.



    Treatment is symptomatic and supportive. Monitor cardiac rhythm and

    biochemical and haematological profiles.



    In cases of overdose, if an increased antimony body burden is

    suspected antidotal therapy may be considered following analytical

    confirmation of antimony concentrations (see antimony monograph).



    MEDICAL SURVEILLANCE



    Sodium stibogluconate should not be administered to patients with

    significantly impaired renal function and used with caution in

    patients with heart or liver disease (ABPI, 1996).



    OCCUPATIONAL DATA



    Maximum exposure limit



    Antimony and compounds: Long-term exposure limit (8 hour TWA reference

    period) 0.5 mg/m3 (Health and Safety Executive, 1997).



    OTHER TOXICOLOGICAL DATA



    Carcinogenicity



    There are no data regarding the carcinogenicity of sodium

    stibogluconate.



    There is some evidence that occupational antimony exposure is

    associated with an increased risk of lung cancer although frequent

    concomitant exposure to arsenic and other heavy metals precludes a

    definitive conclusion about its carcinogenic potential (Gerhardsson et

    al, 1982; McCallum, 1989; Gerhardsson and Nordberg, 1993; Jones, 1994;

    Schnorr et al, 1995).



    Antimony also has been implicated in the aetiology of bladder tumours

    in patients with schistosomiasis who have been treated with antimony

    compounds (Winship, 1987).



    Reprotoxicity



    There are no data regarding the reprotoxicity of sodium

    stibogluconate.



    Women occupationally exposed to antimony aerosols were reported to

    have a higher incidence of spontaneous abortion, premature births and

    menstrual disorders. Antimony was present in the blood, urine,

    placenta, amniotic fluid and breast milk of these women (Belyaeva,

    1967).



    Genotoxicity



    NIF



    Fish toxicity



    NIF



    EC Directive on Drinking Water Quality 80/778/EEC



    Antimony: Maximum admissible concentration 10 µg/L (DOSE, 1992).



    WHO Guidelines for Drinking Water Quality



    Antimony: Provisional guideline value 0.005 mg/L (WHO, 1993).



    AUTHORS



    WN Harrison PhD CChem MRSC

    SM Bradberry BSc MB MRCP

    JA Vale MD FRCP FRCPE FRCPG FFOM



    National Poisons Information Service (Birmingham Centre),

    West Midlands Poisons Unit,

    City Hospital NHS Trust,

    Dudley Road,

    Birmingham

    B18 7QH

    UK



    This monograph was produced by the staff of the Birmingham Centre of

    the National Poisons Information Service in the United Kingdom. The

    work was commissioned and funded by the UK Departments of Health, and

    was designed as a source of detailed information for use by poisons

    information centres.



    Date of last revision

    28/1/98



    REFERENCES



    ABPI/The Association of the British Pharmaceutical Industry.

    ABPI Compendium of Data Sheets and Summaries of Product

    Characteristics 1996-97.

    London: Datapharm Publications Ltd, 1996.



    Bailly R, Lauwerys R, Buchet JP, Mahieu P, Konings J.

    Experimental and human studies on antimony metabolism: their relevance

    for the biological monitoring of workers exposed to inorganic

    antimony.

    Br J Ind Med 1991;48: 93-7.



    Balzan M, Fenech F.

    Acute renal failure in visceral leishmaniasis treated with sodium

    stibogluconate.

    Trans R Soc Trop Med Hyg 1992; 86: 515-6.



    Belyaeva AP.

    [The effect produced by antimony on the generative function.]

    Gig Tr Prof Zabol 1967; 11: 32-7.



    Braconier JH, Miörner H.

    Recurrent episodes of thrombocytopenia during treatment with sodium

    stibogluconate (letter).

    J Antimicrob Chemother 1993; 31: 187-8.



    Brummitt CF, Porter JA, Herwaldt BL.

    Reversible peripheral neuropathy associated with sodium stibogluconate

    therapy for American cutaneous leishmaniasis.

    Clin Infect Dis 1996; 22: 878-9.



    Castro C, Sampaio RN, Marsden PD.

    Severe arthralgia, not related to dose, associated with pentavalent

    antimonial therapy for mucosal leishmaniasis.

    Trans R Soc Trop Med Hyg 1990; 84: 362.



    CHIP2/Chemicals (Hazard Information and Packaging for Supply)

    Regulations 1994.

    Health and Safety Commission.

    Sudbury: Health and Safety Executive, 1994.



    Chulay JD, Spencer HC, Mugambi M.

    Electrocardiographic changes during treatment of leishmaniasis with

    pentavalent antimony (sodium stibogluconate).

    Am J Trop Med Hyg 1985; 34: 702-9.



    Chunge CN, Gachihi G, Chulay JD, Spencer HC.

    Complications of kala azar and its treatment in Kenya.

    East Afr Med J 1984; 61: 120-7.



    Davis A.

    Comparative trials of antimonial drugs in urinary schistosomiasis.

    Bull WHO 1968; 38: 197-227.



    de Lalla F, Pellizzer G, Gradoni L, Vespignani M, Franzetti M, Stecca

    C.

    Acute pancreatitis associated with the administration of meglumine

    antimonate for the treatment of visceral leishmaniasis (letter).

    Clin Infect Dis 1993; 16: 730-1.



    de Wolff FA.

    Antimony and health.

    Br Med J 1995; 310: 1216-7.



    Domingo P, Ferrer S, Kolle L, Muñoz C, Rodriquez P.

    Acute pancreatitis associated with sodium stibogluconate treatment in

    a patient with human immunodeficiency virus.

    Arch Intern Med 1996; 156: 1029-30.



    DOSE/Dictionary of substances and their effects. Vol 1.

    Cambridge: Royal Society of Chemistry, 1992.



    Forsyth DM.

    Visual disturbances associated with trivalent antimony salts. A report

    of two cases.

    Br Med J 1958; 2: 1272-3.



    Gasser RA Jr, Magill AJ, Oster CN, Franke ED, Grögl M, Berman JD.

    Pancreatitis induced by pentavalent antimonial agents during treatment

    of leishmaniasis.

    Clin Infect Dis 1994; 18: 83-90.



    Gerhardsson L, Brune D, Nordberg GF, Wester PO.

    Antimony in lung, liver and kidney tissue from deceased smelter

    workers.

    Scand J Work Environ Health 1982; 8: 201-8.



    Gerhardsson L, Nordberg GF.

    Lung cancer in smelter workers-interactions of metals as indicated by

    tissue levels.

    Scand J Work Environ Health 1993; 19: 90-4.



    Grant WM, Schuman JS.

    Toxicology of the eye. 4th ed.

    Illinois: Charles C Thomas, 1993.



    Gupta P.

    Electrocardiographic changes occurring after brief antimony

    administration in the presence of dilated cardiomyopathy.

    Postgrad Med J 1990; 66: 1089.



    Health and Safety Executive.

    EH40/97. Occupational exposure limits 1997.

    Sudbury: Health and Safety Executive, 1997.



    Henderson A, Jolliffe D.

    Cardiac effects of sodium stibogluconate.

    Br J Clin Pharmacol 1985; 19: 73-7.



    Hepburn NC, Siddique I, Howie AF, Beckett GJ, Hayes PC.

    Hepatotoxicity of sodium stibogluconate in leishmaniasis.

    Lancet 1993; 342: 238-9.



    Hepburn NC, Nolan J, Fenn L, Herd RM, Neilson JM, Sutherland GR,

    Fox KA.

    Cardiac effects of sodium stibogluconate: myocardial,

    electrophysiological and biochemical studies.

    QJM 1994; 87: 465-72.



    Herwaldt BL, Kaye ET, Lepore TJ, Berman JD, Baden HP.

    Sodium stibogluconate (Pentostam) overdose during treatment of

    American cutaneous leishmaniasis.

    J Infect Dis 1992; 165: 968-71.



    Hiçsönmez G, Jama H, Özsoylu S.

    Severe leucopenia during treatment of visceral leishmaniasis.

    Trans R Soc Trop Med Hyg 1988; 82: 417.



    Horber FF, Lerut J, Jaeger P.

    Renal tubular acidosis, a side effect of treatment with pentavalent

    antimony (letter).

    Clin Nephrol 1991; 36: 213.



    Jones RD.

    Survey of antimony workers: mortality 1961-1992.

    Occup Environ Med 1994; 51: 772-6.



    Kassem A, Hussein HA, Abaza H, Sabry N.

    Optic atrophy following repeated courses of tartar emetic for the

    treatment of bilharziasis.

    Bull Ophthalmol Soc Egypt 1976; 69: 459-63.



    Mallick BK.

    Hypoplasia of bone marrow secondary to sodium antimony gluconate

    (letter).

    J Assoc Physicians India 1990; 38: 310-1.



    Mansour MM, Rassoul AAA, Schulert AR.

    Anti-bilharzial antimony drugs.

    Nature 1967; 214: 819-20.



    MARTINDALE.

    The Extra Pharmacopoeia. 31st ed. Reynolds JEF, ed.

    London: The Pharmaceutical Society, 1996.



    McCallum RI.

    The industrial toxicology of antimony. The Ernestine Henry lecture

    1987.

    J R Coll Physicians Lond 1989; 23: 28-32.



    McCarthy AE, Keystone JS, Kain KC.

    Pancreatitis occurring during therapy with stibogluconate: two case

    reports (letter; comment).

    Clin Infect Dis 1993; 17: 952-3.



    Rai US, Kumar H, Kumar U.

    Renal dysfunction in patients of kala azar treated with sodium

    antimony gluconate.

    J Assoc Physicians India 1994a; 42: 383.



    Rai US, Kumar H, Kumar U, Amitabh V.

    Acute renal failure and 9th, 10th nerve palsy in patient of kala-azar

    treated with stibanate.

    J Assoc Physicians India 1994b; 42: 338.



    Rees PH, Keating MI, Kager PA, Hockmeyer WT.

    Renal clearance of pentavalent antimony (sodium stibogluconate).

    Lancet 1980; 2: 226-9.



    Reynolds JEF, ed.

    Martindale: The Extra Pharmacopoeia. 31st ed.

    London: The Pharmaceutical Society, 1996.



    RTECS/Registry of Toxic Effects of Chemical Substances.

    In: Tomes plus. Environmental Health and Safety Series I. Vol 32.

    National Institute for Occupational Safety and Health (NIOSH), 1997.



    Saenz RE, De Rodriguez CG, Johnson CM, Berman JD.

    Efficacy and toxicity of pentostam against panamanian mucosal

    leishmaniasis.

    Am J Trop Med Hyg 1991; 44: 394-8.



    SAX'S/Lewis RJ.

    Sax's dangerous properties of industrial materials. 9th ed. Vol 2.

    New York: Van Nostrand Reinhold, 1996.



    Schnorr TM, Steenland K, Thun MJ, Rinsky RA.

    Mortality in a cohort of antimony smelter workers.

    Am J Ind Med 1995; 27: 759-70.



    Winship KA.

    Toxicity of antimony and its compounds.

    Adverse Drug React Acute Poisoning Rev 1987; 2: 67-90.



    WHO.

    Guidelines for drinking-water quality. 2nd ed. Vol 1. Recommendations.

    Geneva: World Health Organization, 1993.