114

We do agree, however, with the conclusion that biological variability may in practice work against a selective approach to chemotherapy. This is not a novel conclusion, but it has not previously been supported by such extensive epidemiological data. A selective approach may also be unsatisfactory because of the costs of diagnosis in relation to treatment, because of resistance in the community to selective treatment, and because of the ethical issues of diagnosis without treatment. For these reasons the suggestion that an effective means of controlling helminth infections is mass treatment targeted at age groups with high average worm loads8,9 is gaining increasing support. Wellcome Trust Research Centre for Parasitic Infections, West Beit, Imperial College, London SW7 2BB, UK

ANDREW HALL D. A. P. BUNDY R. M. ANDERSON

Centre for International Child Health, Institute for Child Health, London WC1

A. M. TOMKINS

1. Bensted-Smith R, Anderson RM, Butterworth AE, et al. Evidence for predisposition of individual patients to reinfection with Schistosoma haematobium after treatment, Trans R Soc Trop Med Hyg 1987; 81: 651-54. 2. Holland CV, Asaolu SO, Crompton DWT, et al. The epidemiology of Ascaris lumbricoides and other soil-transmitted helminths in primary school from Ife-Ife, Nigeria. Parasitology 1989; 99: 275-85. 3. Chan LS, Kan SP, Bundy DAP. The effect of repeated chemotherapy on age-related predisposition to Ascaris lumbricoides and Trichuris trichiura. Parasitology 1992; 104: 371-77. 4. Forrester JE, Scott ME, Bundy DAP, Golden MHN. Predisposition of individuals and families in Mexico to heavy infection with Ascaris lumbricoides and Trichuris trichiura Trans R Soc Trop Med Hyg 1990; 84: 272-76. 5. Keymer A, Pagel M. Predisposition to helminth infection. In: Schad GA, Warren KS, eds. Hookworm disease: current status and new directions. London: Taylor and Francis, 1990: 177-209. 6. McCallum HI. Covariance in parasite burdens: the effect of predisposition to infection. Parasitology 1990; 100: 153-59 7. Bundy DAP, Medley GF. Immune-epidemiology of human geohelminthiasis: ecological and immunological determinants of worm burden. Parasitology 1992; 104: 105-19. 8. Butterworth AE, Sturrock RF, Ouma JH, et al. Comparison of different chemotherapy strategies against Schistosoma mansoni in Machakos District, Kenya: effects on human infection and morbidity. Parasitology 1991; 103: 339-55. 9. Bundy DAP, Wong MS, Lewis LL, Horton J. Control of geohelminths by delivery of targeted chemotherapy through schools. Trans R Soc Trop Med Hyg 1990; 84: 115-20.

Artificial

breeding grounds for mosquito control

SIR,-Mosquitoes transmit some of mankind’s most troubling diseases but vector control measures are difficult and expensive. Mosquito densities fluctuate over time, and analysis of the causes of such fluctuations may provide new ideas for control. One such observation in a Colombo suburb suggests a promising line. A large municipal drain carries waste water from houses to the sea. The flow is sluggish, and stagnant puddles and decaying organic matter provide good breeding grounds for certain species. When there is no rain the houses in the area teem with mosquitoes. However, the drain also serves as a conduit for rainwater, and whenever it rains the number of mosquitoes falls. If occasional showers persist over several weeks the mosquito density builds up again, this time unaffected by the continuing rain. This indicates that alternative grounds are available for laying eggs, although they were ignored during spells when the municipal drain is a more attractive site. By drawing mosquitoes to lay their eggs in the drain so that all the larvae are washed out to sea with the first rains, this drain offers a lesson worth emulating. Unfortunately, the drain cannot produce a lasting benefit because the rains clear not just the larvae but also the ingredients that attract mosquitoes to lay eggs there. If the drain continued to attract gravid females, while periodically flushing out the larvae, the impact would be much

greater. Artificial breeding grounds more attractive to mosquitoes than sites available naturally could overcome this difficulty. The provision of controlled breeding grounds from which the larvae can regularly be eliminated should not be difficult and could even be undertaken as a community health venture by householders. Faculty of Medicine, Colombo 8, Sri Lanka

DIYANATH SAMARASINGHE

Corynebacterium pseudodiphtheriticum pulmonary infection in AIDS patients SiR,—Infectious pneumonia remains a leading cause of morbidity and mortality among HIV patients. Although most cases are due to opportunistic agents, common bacterial pathogens and less pathogenic bacteria, especially the coryneform bacterium Rhodoccus equi, have been increasingly implicated.i We present two cases of pneumonia due to Corynebacterium pseudodiphtheriticum, a rare human pathogen, in two HIV seropositive men. Case 1-43, AIDS with tuberculosis adenitis, 6 months earlier admitted to our intensive care unit with 15 day history of high temperature, rigors, non-productive cough and progressive dyspnoea; on zidovudine and co-trimoxazole prophylaxis. Temperature was 39°C, regular heart rate 120/min, arterial blood pressure 100/50 mm Hg, respiratory rate 50/min, and he had pulmonary crackles over both lung fields. Pa02 was 51 mm Hg while breathing room air, CD4 count was 172/ [11, and HIV serology was positive. Radiography showed confluent alveolar opacities in the middle and lower left lung. Bronchoalveolar lavage fluid, blood, and cerebrospinal fluid cultures remained sterile, whereas culture of a protected brush specimen (PBS) obtained under fibreoptic bronchoscopy yielded 4 x 103 coryneform bacteria colony-forming units (CFU) per ml, resistant to macrolides, co-trimoxazole, and teicoplanin. Vancomycin was started to ensure activity against a possible R equi. These coryneform bacteria had rapid urease activity (5 min) that strongly suggested C pseudodiphtheriticum, which was confirmed by the Institut Pasteur, Paris. Clinical and radiographic findings rapidly became normal. After 4 weeks, there was no evidence of recurrent pneumonia. Case 2-34, AIDS with 2 week history of progressive dyspnoea, high temperature, productive cough, mucopurulent sputum, vomiting, and rigors; 5 months earlier, admitted for Pneumocystis carinii pneumonia (PCP) treated by co-trimoxazole, changed to dapsone because of adverse reactions; after discharge he received zidovudine and inhaled pentamidine once a month. Temperature was 38°C, heart rate 100/min, arterial blood pressure 120/70 mm Hg, and he had pulmonary crackles over both lung fields. Pa02 was 70 mm Hg while breathing room air, CD4 count was 130/ul, and HIV serology was positive. Radiography showed alveolar opacities in the right lung. Examination of bronchoalveolar lavage fluid revealed P carinii. Bronchial secretions (fibreoptic bronchoscopy) showed numerous polynuclear cells and gram-positive bacilli with morphological features suggestive of coryneform bacteria. Culture grew IOS CFU per ml of an organism that was identified as C pseudodiphtheriticum. Resistance was confined to fluoroquinolones. The patient was treated with dapsone and inhaled pentamidine (300 mg once a day) for PCP, and vancomycin. Clinical and radiographic findings quickly became normal. 4 weeks later, physical findings were unremarkable and the chest radiograph was

normal.

Cpseudodiphtheriticum can cause endocarditis and pneumonia,3-7 especially in apparently immunocompetent patients with previous pulmonary disease. Another case occurred in a young man on steroids for systemic lupus erythematosus.11 There has been only one report in a patient with a disease clinically compatible with HIV infection, although no serological confirmation for HIV was obtained. This patient had a lung abscess from which only C pseudodiphtherriticum was isolated and subsequently required lobectomy.9 Our two cases had documented HIV infection. They are the only cases from about 200 HIV-positive patients who underwent diagnostic fibreoptic bronchoscopy during the past year in our two institutions. Case 2 had relapsing PCP and concomitant infection by C pseudodiphtheriticum. It is difficult to delineate the role of each organism, but C pseudodiphtheritfczan as pure culture and abundant mucopurulent sputum suggest that this organism was at least in part responsible. Infection with C pseudodiphtheriticum is combined with other pathogens in many instances,IO although it was the sole causative agent in some reports.6 By contrast with R equi, which is susceptible to macrolides,’" one of our isolates

was

resistant

to

these

compounds. This

may have

115

clinical relevance in HIV-positive patients with pneumonia when bacteria are found in sputum. Failure to suspect infection with C pseudodiphtheriticum may lead to treatment delay if macrolides are administered before culture. In addition, one of our isolates was resistant to co-trimoxazole given for PCP prophylaxis.

coryneform

We thank Dr Martine Kimedjian, Laboratoire des Identifications, Institut Pasteur, Paris, for identifying C pseudodiphtheriticum. Medical Resuscitation, Microbiology, and Internal Medicine Units,

Hôpital Louis Mourier, Colombes,

and 22 months of the first episode of pancytopenia. A third patient, the infant with CMV-B19 co-infection, died at 9 months. On the basis of our findings, B19 can be regarded as a cause of pancytopenia in children with HIV infection, independently of the haemophagocytic syndrome. Like other children with an impaired immune system HIV-infected children may not be able to produce neutralising antibodies, and thus develop persistently active B19

infection.4 On the other hand, as suggested for herpesviruses,s,6 a reciprocal activation between HIV and B19, and a possible role of B19 in the progression of HIV disease, cannot be ruled out.4

INSERM U 82, Faculty of Medicine Xavier Bichat, Université Paris VII,

YVES COHEN GILLES FORCE ISABELLE GROS

We thank Dr Pasquale Pisano, Dr Andreas Krzysztofiak, and Dr Elsa Bevivino for their collaboration. This work has been supported by funds from Ministry of Scientific Research (Ateneo projects) and National Council of

75018 Paris, and Internal Medicine and Microbiology Units, Hôpital Notre Dame du Perpétuel Secours, Lavallois-Perret, France

ANNE-MARIE CANZI LAURENCE LECLEACH DIDIER DREYFUSS

Research

GU, Stein DS. Pulmonary manifestations of acquired immunodeficiency syndrome, Clin Infect Dis 1992; 14: 98-113. 2. Emmons W, Reichwein B, Winslow DL. Rhodococcus equi infection m the patient with AIDS: literature review and report of an unusual case. Rev Infect Dis 1991; 13: 1. Meduri

91-96. 3. Rikitomi N, Nagatake T, Matsumoto K, Watanabe K, Mbaki N. Lower respiratory tract infections due to non-diphtheria corynebacteria m 8 patients with underlying lung diseases. Tohoku J Exp Med 1987; 153: 313-25. 4. Williams EA, Green JD, Salazar S, Berk SL. Pneumonia caused by Corynebacterium pseudodiphtheriticum. J Tenn Med Assoc 1991; 84: 223-24. 5. Morris A, Guild I. Endocarditis due to Corynebacterium pseudodiphtheriticum: five case reports, review, and antibiotic susceptibilities of nine strains. Rev Infect Dis

1991; 13: 887-92. 6. Rubler S, Harvey L, Avitabile A, Abenavoli T. Mitral valve obstruction in a case of bacterial endocarditis due to Corynebacterium hofmanii: echocardiographic diagnosis. NY State J Med 1982; 82: 1590-94. 7 Coyle MB, Lipsky BA. Coryneform bacteria in infectious diseases: clinical and laboratory aspects. Clin Microbiol Rev 1990; 3: 227-46. 8. Donaghy M, Cohen J. Pulmonary infection with Corynebacterium hofmanni complicating systemic lupus erythematosus. J Infect Dis 1983; 147: 962. 9. Andavolu RH, Jagadha V, Lue Y, McLean T. Lung abscess involving Corynebacterium pseudodiphtheriticum in a patient with AIDS-related complex. N Y State J 1986; 86: 594-96. 10. Brown AE. Other corynebacteria. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. 8th ed. 1990; 1581-86.

Parvovirus-B19-related pancytopenia in children with HIV infection SIR,-Dr Muir and colleagues (May 9, p 1139) report parvovirus-BI9-related pancytopenia and haemophagocytosis in patients with hereditary spherocytosis, suggesting that haemophagocytosis could account for the leucopenia and thrombocytopenia associated with parvovirus B19 infection. We have examined serum samples from four children with vertically-transmitted HIV infection and pancytopenia for IgM and IgG antibodies against parvovirus B19, by means of two enzyme immunoassays with synthetic peptide or recombinant protein and subsequent detection of serum B19-DNA with polymerase chain reaction.1-3 The patients (two boys, two girls) were, respectively, aged 1, 8, 14, and 26 months, and were in Centers for Disease Control disease stages P2ABD(two) and P2A (two). All were on zidovudine (600 mg daily). The 1-month-old infant also received ganciclovir (10 mg/kg daily for 2 weeks), since she had congenital cytomegalovirus (CMV) infection, as shown by culture and specific IgM at birth. The main clinical features were: hepatosplenomegaly with raised aminotransferase activities (3 patients), encephalopathy (3), interstitial pneumonitis (2), and cardiomyopathy (2). Pancytopenia was shown by a drop in mean values of haemoglobin (Hb), total while cell count (WCC), and platelets from 9-6 gdl, 54xx 109/1, and 198 x 109/1 to 5-6 g/dl, 3d x 109/1, and 68 x z1, respectively. Reticulocyte count ranged between 0-016% and 1% (mean 041%). Three patients also had fever and two had two

erythema. No haemophagocytosis could be

seen in either bonein bone marrow from another patient. At first the children showed strongly positive B19 IgM and IgG, which persisted for 8, 16, and 22 months in the three with recurrent pancytopenia. In addition, the 1-month-old infant showed B19 DNA. All children needed frequent blood transfusions for 2-4 months and one required repeated transfusions of platelets. However, two patients with persistent B 19 infection died within 5

marrow aspirate from two patients or

(CNR), project FATMA, no 9103613.

Paediatric Institute of "La Sapienza" University, 00137 Rome, Italy, Bambino Gesú Hospital, Rome; and Department of Virology, National Bacteriological Laboratory and Karolinska Institute, Stockholm, Sweden

GIOVANNI NIGRO GUIDO CASTELLI GATTINARA SILVIA MATTIA MAURIZIO CANIGLIA EVA FRIDELL

1. Fridell E, Cohen BJ, Wahren B. Evaluation of a synthetic peptide enzyme-linked immunosorbent assay for immunoglobulin M to human parvovirus B19. J Clin Microbiol 1991; 29: 1376-81. 2. Soderlund M, Brown KE, Meurman O, Hedman K. Prokaryotic expression of a VP1 polypeptide antigen for diagnosis by a human parvovirus B19 antibody enzyme immunoassay. J Clin Microbiol 1992; 30: 305-11. 3. Sahamans MMM, Holsappel S, van de Rijke FH, et al. Rapid detection of human parvovirus infection by dot-blot hybridization and the polymerase chain reaction. J Virol Methods 1989; 23: 19-28. 4. Nigro G, Luzi G, Fridell E, et al. Parvovirus infection in children with AIDS: high prevalence of B19-specific immunoglobulin M and G antibodies. AIDS 1992; 6: 679-84. 5. Rando RE, Pellett PE, Luciw PA, Bohan CA, Srinivasan A. Transactivation of human immunodeficiency virus by herpesviruses. Oncogene 1987; 1: 13-18. 6. Ho W-Z, Harouse JM, Rando RF, Gonczol E, Srinivasan A, Plotkin SA. Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. J Gen Virol 1990; 71: 97-103.

Erbium YAG laser for micromanipulation of oocytes and spermatozoa SIR,-Dr Tadir and colleagues (June 6, p 1424) express concern about potential thermal damage caused by our erbium-YAG laser (March 28, p 811) in the infrared range and potential mechanical damage. An erbium-YAG laser is usually guided by an optical mirror system like a "light scalpel" in non-contact mode. In usual applications (eg, in orthopaedic surgery), full energy is provided by this system. Guiding an erbium-YAG laser through a quartz-fibre means that most of its energy is being absorbed. Only a negligible amount of its original energy is released from the distal end of the fibre without any thermal effect and the cutting energy is limited to a thin layer (3 um). Therefore, the fibreoptic system of the erbium-YAG laser is ideally suited for micromanipulation of human oocytes and spermatozoa. Because of the high absorption coefficient in water and the low ablation threshold there is no mechanical damage due to shock waves or a cavitation effect. Previous investigations have shown that the erbium-YAG laser is better than the laser system proposed by Tadir et al-a 308 nm ultraviolet (UV) excimer laser-for avoidance of thermal tissue injury.’ Furthermore, there are indications of a certain risk of mutagenesis caused by excimer radiation in the UVA region in

therapeutic applications.2 Micromanipulation of spermatozoa (subzonal insemination) with our system is not based on the principle of an optical trap. Three to four spermatozoa are pushed by laser energy through a lasergenerated opening in the zona pellucida. Further clinical experience has shown that our laser-guided micromanipulation technique offers good results with the technique of assisted hatching.33 Recently, healthy twins have been delivered after transfer of laser-manipulated embryos. Assisted hatching, with the use of erbium-YAG laser, in patients with previously failed in-vitro fertilisation (IVF) attempts, has resulted in a pregnancy rate higher than that obtained with common IVF techniques: ten of fifteen patients became pregnant (seven singleton, three twin pregnancies;