523
CORRESPONDENCE
baseper kg. of body weight and did not reappearduring a further 28 daysin hospital. In vitro drug sensitivity testing was not performed on any isolatesfrom these 10 personstreated with amodiaquine. It has been reported that the drug-resistantVietnam (Marks) strain is more susceptibleto amodiaquine than chloroquine (RIECKMAUN, 1971). We detected no differencesin clinical responseor parasiteclearance between Ethiopian patients treated with amodiaquineor chloroquine in equivalent, small, dosage.Some Ethiopians with falciparum malaria experienced a delayed recrudescencefollowing treatment with 10 mg. baseper keg. of body weight of either drug. We are, etc., DAVID T. DENNIS* EDWARD
B. DOBERSTYN~
20 January, 1975. A. SISSAY. U.S. Naval Medical Research Unit No. 5, Addis Ababa, Ethiopia. *Present address : NAMR U-2, Djakarta Detachment, APO San Francisco 96356. fPresent address : SEA TO Medical Research Laboratory, APO San Francisco 96346.
This work was supported by the Bureau of Medicine and Surgery, Work Unit No. MF12.524.0093016BF61.The opinionsand assertionsherein are those of the authors and are not to be construedasofficial or asreflecting the views of the United StatesNavy Department or naval service at large. REFERENCES DENNIS, D. RIECKIMANN,
E. B., & SISSAY, A. (1974). Trans. R. Sot. trap. Med. Hyg., 68, 241. K. H. (1971).J. Am. med. Ass., 217, 573.
T.,
DOBERSTYN,
CI-IL,OROQuINEJ
PSYCHOSIS
SIR,-Toxic psychosisdue to chloroquine is unusualand very few reports are availablein the literature. The purposeof this communicationis to report a further caseof acute psychosisdue to chloroquine, in which the symptomsappearedon the very fist day after 1 grammedose. Our patient was a 45years-old female, who was prescribed chloroquine phosphatefor malaria. Two hours after taking the first doseof 1 grammethe patient becameagitated, confusedand developedauditory hallucinations.On examinationshewasapyrexial, and there wasno neurologicalabnormality except deranged mental functions. She respondedto withdrawal of chloroquine and administrationof chlorpromazine. The first caseof chloroquine psychosiswasreported by BKJRREL and MARINEZ (1958). Since that time 7 more caseshave beenadded,all of them rapidly reversibleupon cessationof drug (MUSTAKALLIO et al., 1962; DORNHORST and ROBINSON, 1963;RAB, 1963;NEFF,1964; SAPP,1964;BROOKES, 1966).Thepsychosisappeared in thesecasesafter between 2.4 to 4 grammeof chloroquine had been taken over a period of time between 4 and 40 days. The actual mechanismof how chloroquine may causepsychosisis unknown. The evidence seemsto point toward an idiosyncratic reaction in sensitiveindividual. We are etc., B. S. BOMB, Lecturer H. K. BEDI,Prof. and Head L. K. BHATNAGAR, Registrar Department of Medicine, R.N.T. Medical College,Udaipur (Raj.), India. 15 May, 1975. NOTE: A consultingpsychiatrist writes : “I agreethat it is confusingto namea whole seriesof syndromes to describewhat are really Toxic Confusional States.” We accept the term “Psychosis” only becauseit has becomeacceptedusagein respectof similar syndromescausedby various drugs. Editor. REFERENCES BROOKES, D B. (1966). Brit. med. J., i, 983. BURRELL, Z. L. & MARINEZ, A. C. (1958). New EngZandJ. Med., 258, 798. DORNHORST, A. C. & ROBINSON, B. F. (1963). Lancet, i, 108. MUSTAKALLIO, K. K., PUTKONEN, T. & PIHAKANEN, T. A. (1962). Ibid., ii, NEFF, L. (1964).J. Amer. med. Assoc.,204, 867.
1387.
RAB, S. M. (1963). Brit. med.J., i, 1275. SAPP, 0. L. (1964).J. Amer. med. Assoc., 187, 373. Leishmania
FROM
A HYRAX
IN SOUTH
WEST AFRICA
SIR,~FOUT casesof cutaneousleishmaniasis (C.L.) i? white womenin South WesgAfrica were described GROVE (1970), and C.L. in a black Ovambo by GROVE and VAN DYK (1973). GROVE et al. (1971) listed the
by sandflies(Phlebotominae)then known from the northern parts of the territory, and reported negativeresults for a number of wild animalsexaminedfor infection with Leishmania. ASHFORD et al. (1973) proved that the hyraxes Procavia habessinica and Heterohyrax brucei are the natural reservoirsof C.L. in highland Ethiopia. In late 1973and early 19745 further casesof C.L. were diagnozedin South West Africa by finding amastigotes
524
CORRESPONDENCE
in sections of excised lesions. All 5 cases occurred in the southern part of the country, which at the time was the focus of a population explosion of the hyrax P. cupensis (J. LENSING, personal communication). The fauna1 similarities between the arid south-west and north-east parts of Africa that have been noted by many authors led us to examine hyraxes in southern South West Africa for the presence of Leishmania, using the techniques describedby ASHFORD et al. (1973). In May 1974we worked on farms in the Bethanie and Keetmanshoop districts, and examined37 P. cape&s. None of our tissueculturesin NNN medium yielded promastigotes,but a singlespecimenof an apparently new Phlebotomus (D. J. LEWIS,personalcommunication)wascollectedin a hyrax hole. In April 1975work was continued on two farms approximately 100km south-eastof Keetmanshoop.Numbers of the undescribed Phlebotomus were collected from hyrax holes.A sampleof 30 P. cupensis was made, and a culture of tissue from the tip of the noseof one animalin diphasicblood-agarmedium showedactive promastigotes14 days after inoculation. We are preparing further reports to provide more detailsof our work. We are, etc., S. S. GROVE!, RegionalDirector, South African Institute for Medical Research,Windhoek, South West 27 June, 1975 Africa. JOHNA. LEDGER, Department of Entomology, South African Institute for Medical Research,Johannesburg, South Africa. REFERENCES ASI-IPORD,~~ 5X’; BRAY,M. A., HUTCHINSON, M. P. & BRAY, R. S. (1973). Trans. R. Sot. trop. Med. Hyg., GROVE,S. s’. (1670). S. Afr. med.J., 44,206. -, DOWNES,R. G. & ZIELKE,E. (1971). Ibid., 45, 293. & VAN DYK, J. H. (1973).Ibid., 47, 516. We thank the Director of the South African Institute for Medical Research.,ProfessorJ. F. Murray, for supporting our project, and the Department of Nature Conservationand Tourism, South West Africa, and especiallyMr. J. Lensmgof the Department, for help in numerousways. ONCHOCERCIASIS ANDSTREPTOCERCIASIS IN PATIENTS WITHLEPROSY. ALTERED MAZZOTTIREACTIONS SIR,-ln 1948 Mazzotti describedthe early onsetof severeitching, cutaneousoedema,and frequently systemic symptoms in Mexicans with onchocerciasis,following the administration of diethylcarbamazine (DEC). In Upper Volta MONJUSIAUet al. (1964) observedthat DEC provoked Mazzotti reactionsin 114 of 120 (95%) patients with onchocerciasis.The high frequency of Mazzotti reactionsin onchocerciasishasled to its useby someasa presumptivediagnosticprocedure.MEYERSet al. (1972)in Zaire noted responses similar to Mazzotti reactionsin 29 of 35 patients (71%) with streptocerciasistreated with DEC. During the period 1967-1973we studied 49 Zai’reanswith both leprosy and dermal microfilariasis.We treated 32 of thesepatients (31 adults, 1 child; 20 male, 12 female)with DEC under careful inpatient supervision. Of this group, the speciesof microfilariae were identified by skin snips and biopsy in 20 patients (onchocerciasis,14 patients; streptocerciasis,8 patients) and by skin biopsy alonein 12 patients. In the latter group of patientswe did not distinguishthe microfilariae of Onchocerca volvulus from those of Dipetalonema streptocerca. Two patients had both onchocerciasis and streptocerciasis;hencethe total of 34 filarial infections in the 32 patients.The leprosy patientswere classifiedaccordingto the criteria of RIDLEYand JOPLING(1966), and their distribution was as follows: lepromatous (LL) and borderline lepromatous(BL), 15 patients; borderline (BB), 6 patients; borderline tuberculoid (BT) and tuberculoid (TT), 11 patients. Microfilarial density in 20 patients wasdeterminedon 2 dermalsnips(2 mm. in diameter)taken from the scapulararea. The snipswere teasedapart in physiologicalsalineand severalmicroscopicobservationsmade over a 30 minute period. Total microfilarial counts in the 2 snipsrangedfrom 1 to 15. The doseof DEC on the first daywas25 mg. in 7 patients,50 mg. in 2 patients,and 100mg. in 23 patients. The lower dosesweregiven to patientswho weremore seriouslyill. On days2 to 21 eachpatient receivedDEC 50 mg. 3 times daily. None of the patients was receiving steroidsor antihistaminesjust prior to or during DEC therapy. All but 2 patients were on long term diaminodiphenylsulphfone(DDS) therapy for leprosy. Dosesof DDS rangedfrom 25 mg. twice weekly to 50 mg. 3 times weekly. Mazzotti reactionsoccurred in 9 patients and not inthe remaining 23 patients: a reaction rate of 28%. Reactionsin the 9 patientswere all mild, and nonerequired specifictreatment nor suspension of DEC therapy. The distribution of reaction rates among the various classesof leprosy patients was as follows: LL+BL, 12%: BB. 50%: and BT+TT. 33%. Onchocercomatawere excisedfrom 9 patients 24 to 72 hours after the initial doseof DEC and examined histopathologically.There was a significant eosinophilicresponseabout the adult filariae and in the fibrous tissueof the nodule. A few degeneratingmicrofilariae were observedin the skin. We cannot explain the low frequency and reduced severity of the Mazzotti reaction in these leprosy patients but offer the following possibilities: IIS
CORRESPONDENCE
baseper kg. of body weight and did not reappearduring a further 28 daysin hospital. In vitro drug sensitivity testing was not performed on any isolatesfrom these 10 personstreated with amodiaquine. It has been reported that the drug-resistantVietnam (Marks) strain is more susceptibleto amodiaquine than chloroquine (RIECKMAUN, 1971). We detected no differencesin clinical responseor parasiteclearance between Ethiopian patients treated with amodiaquineor chloroquine in equivalent, small, dosage.Some Ethiopians with falciparum malaria experienced a delayed recrudescencefollowing treatment with 10 mg. baseper keg. of body weight of either drug. We are, etc., DAVID T. DENNIS* EDWARD
B. DOBERSTYN~
20 January, 1975. A. SISSAY. U.S. Naval Medical Research Unit No. 5, Addis Ababa, Ethiopia. *Present address : NAMR U-2, Djakarta Detachment, APO San Francisco 96356. fPresent address : SEA TO Medical Research Laboratory, APO San Francisco 96346.
This work was supported by the Bureau of Medicine and Surgery, Work Unit No. MF12.524.0093016BF61.The opinionsand assertionsherein are those of the authors and are not to be construedasofficial or asreflecting the views of the United StatesNavy Department or naval service at large. REFERENCES DENNIS, D. RIECKIMANN,
E. B., & SISSAY, A. (1974). Trans. R. Sot. trap. Med. Hyg., 68, 241. K. H. (1971).J. Am. med. Ass., 217, 573.
T.,
DOBERSTYN,
CI-IL,OROQuINEJ
PSYCHOSIS
SIR,-Toxic psychosisdue to chloroquine is unusualand very few reports are availablein the literature. The purposeof this communicationis to report a further caseof acute psychosisdue to chloroquine, in which the symptomsappearedon the very fist day after 1 grammedose. Our patient was a 45years-old female, who was prescribed chloroquine phosphatefor malaria. Two hours after taking the first doseof 1 grammethe patient becameagitated, confusedand developedauditory hallucinations.On examinationshewasapyrexial, and there wasno neurologicalabnormality except deranged mental functions. She respondedto withdrawal of chloroquine and administrationof chlorpromazine. The first caseof chloroquine psychosiswasreported by BKJRREL and MARINEZ (1958). Since that time 7 more caseshave beenadded,all of them rapidly reversibleupon cessationof drug (MUSTAKALLIO et al., 1962; DORNHORST and ROBINSON, 1963;RAB, 1963;NEFF,1964; SAPP,1964;BROOKES, 1966).Thepsychosisappeared in thesecasesafter between 2.4 to 4 grammeof chloroquine had been taken over a period of time between 4 and 40 days. The actual mechanismof how chloroquine may causepsychosisis unknown. The evidence seemsto point toward an idiosyncratic reaction in sensitiveindividual. We are etc., B. S. BOMB, Lecturer H. K. BEDI,Prof. and Head L. K. BHATNAGAR, Registrar Department of Medicine, R.N.T. Medical College,Udaipur (Raj.), India. 15 May, 1975. NOTE: A consultingpsychiatrist writes : “I agreethat it is confusingto namea whole seriesof syndromes to describewhat are really Toxic Confusional States.” We accept the term “Psychosis” only becauseit has becomeacceptedusagein respectof similar syndromescausedby various drugs. Editor. REFERENCES BROOKES, D B. (1966). Brit. med. J., i, 983. BURRELL, Z. L. & MARINEZ, A. C. (1958). New EngZandJ. Med., 258, 798. DORNHORST, A. C. & ROBINSON, B. F. (1963). Lancet, i, 108. MUSTAKALLIO, K. K., PUTKONEN, T. & PIHAKANEN, T. A. (1962). Ibid., ii, NEFF, L. (1964).J. Amer. med. Assoc.,204, 867.
1387.
RAB, S. M. (1963). Brit. med.J., i, 1275. SAPP, 0. L. (1964).J. Amer. med. Assoc., 187, 373. Leishmania
FROM
A HYRAX
IN SOUTH
WEST AFRICA
SIR,~FOUT casesof cutaneousleishmaniasis (C.L.) i? white womenin South WesgAfrica were described GROVE (1970), and C.L. in a black Ovambo by GROVE and VAN DYK (1973). GROVE et al. (1971) listed the
by sandflies(Phlebotominae)then known from the northern parts of the territory, and reported negativeresults for a number of wild animalsexaminedfor infection with Leishmania. ASHFORD et al. (1973) proved that the hyraxes Procavia habessinica and Heterohyrax brucei are the natural reservoirsof C.L. in highland Ethiopia. In late 1973and early 19745 further casesof C.L. were diagnozedin South West Africa by finding amastigotes
524
CORRESPONDENCE
in sections of excised lesions. All 5 cases occurred in the southern part of the country, which at the time was the focus of a population explosion of the hyrax P. cupensis (J. LENSING, personal communication). The fauna1 similarities between the arid south-west and north-east parts of Africa that have been noted by many authors led us to examine hyraxes in southern South West Africa for the presence of Leishmania, using the techniques describedby ASHFORD et al. (1973). In May 1974we worked on farms in the Bethanie and Keetmanshoop districts, and examined37 P. cape&s. None of our tissueculturesin NNN medium yielded promastigotes,but a singlespecimenof an apparently new Phlebotomus (D. J. LEWIS,personalcommunication)wascollectedin a hyrax hole. In April 1975work was continued on two farms approximately 100km south-eastof Keetmanshoop.Numbers of the undescribed Phlebotomus were collected from hyrax holes.A sampleof 30 P. cupensis was made, and a culture of tissue from the tip of the noseof one animalin diphasicblood-agarmedium showedactive promastigotes14 days after inoculation. We are preparing further reports to provide more detailsof our work. We are, etc., S. S. GROVE!, RegionalDirector, South African Institute for Medical Research,Windhoek, South West 27 June, 1975 Africa. JOHNA. LEDGER, Department of Entomology, South African Institute for Medical Research,Johannesburg, South Africa. REFERENCES ASI-IPORD,~~ 5X’; BRAY,M. A., HUTCHINSON, M. P. & BRAY, R. S. (1973). Trans. R. Sot. trop. Med. Hyg., GROVE,S. s’. (1670). S. Afr. med.J., 44,206. -, DOWNES,R. G. & ZIELKE,E. (1971). Ibid., 45, 293. & VAN DYK, J. H. (1973).Ibid., 47, 516. We thank the Director of the South African Institute for Medical Research.,ProfessorJ. F. Murray, for supporting our project, and the Department of Nature Conservationand Tourism, South West Africa, and especiallyMr. J. Lensmgof the Department, for help in numerousways. ONCHOCERCIASIS ANDSTREPTOCERCIASIS IN PATIENTS WITHLEPROSY. ALTERED MAZZOTTIREACTIONS SIR,-ln 1948 Mazzotti describedthe early onsetof severeitching, cutaneousoedema,and frequently systemic symptoms in Mexicans with onchocerciasis,following the administration of diethylcarbamazine (DEC). In Upper Volta MONJUSIAUet al. (1964) observedthat DEC provoked Mazzotti reactionsin 114 of 120 (95%) patients with onchocerciasis.The high frequency of Mazzotti reactionsin onchocerciasishasled to its useby someasa presumptivediagnosticprocedure.MEYERSet al. (1972)in Zaire noted responses similar to Mazzotti reactionsin 29 of 35 patients (71%) with streptocerciasistreated with DEC. During the period 1967-1973we studied 49 Zai’reanswith both leprosy and dermal microfilariasis.We treated 32 of thesepatients (31 adults, 1 child; 20 male, 12 female)with DEC under careful inpatient supervision. Of this group, the speciesof microfilariae were identified by skin snips and biopsy in 20 patients (onchocerciasis,14 patients; streptocerciasis,8 patients) and by skin biopsy alonein 12 patients. In the latter group of patientswe did not distinguishthe microfilariae of Onchocerca volvulus from those of Dipetalonema streptocerca. Two patients had both onchocerciasis and streptocerciasis;hencethe total of 34 filarial infections in the 32 patients.The leprosy patientswere classifiedaccordingto the criteria of RIDLEYand JOPLING(1966), and their distribution was as follows: lepromatous (LL) and borderline lepromatous(BL), 15 patients; borderline (BB), 6 patients; borderline tuberculoid (BT) and tuberculoid (TT), 11 patients. Microfilarial density in 20 patients wasdeterminedon 2 dermalsnips(2 mm. in diameter)taken from the scapulararea. The snipswere teasedapart in physiologicalsalineand severalmicroscopicobservationsmade over a 30 minute period. Total microfilarial counts in the 2 snipsrangedfrom 1 to 15. The doseof DEC on the first daywas25 mg. in 7 patients,50 mg. in 2 patients,and 100mg. in 23 patients. The lower dosesweregiven to patientswho weremore seriouslyill. On days2 to 21 eachpatient receivedDEC 50 mg. 3 times daily. None of the patients was receiving steroidsor antihistaminesjust prior to or during DEC therapy. All but 2 patients were on long term diaminodiphenylsulphfone(DDS) therapy for leprosy. Dosesof DDS rangedfrom 25 mg. twice weekly to 50 mg. 3 times weekly. Mazzotti reactionsoccurred in 9 patients and not inthe remaining 23 patients: a reaction rate of 28%. Reactionsin the 9 patientswere all mild, and nonerequired specifictreatment nor suspension of DEC therapy. The distribution of reaction rates among the various classesof leprosy patients was as follows: LL+BL, 12%: BB. 50%: and BT+TT. 33%. Onchocercomatawere excisedfrom 9 patients 24 to 72 hours after the initial doseof DEC and examined histopathologically.There was a significant eosinophilicresponseabout the adult filariae and in the fibrous tissueof the nodule. A few degeneratingmicrofilariae were observedin the skin. We cannot explain the low frequency and reduced severity of the Mazzotti reaction in these leprosy patients but offer the following possibilities: IIS
