Probable mother to infant transmission of Pneumocystis jiroveci from an HIV-infected woman to her HIV-uninfected infant

Pneumocystis jiroveci pneumonia (PCP) was first identified as a clinical entity in malnourished children in European orphanages during the Second World War [1]. The transmission and immunology of PCP is complex and many questions remain unanswered. The majority of children will have had subclinical infection before the age of 4 years [2], but clinical disease is rare outside of patients with immunodeficiency, respiratory disease or malnutrition. We report on a presumed case of PCP transmission from an HIV-infected mother to her HIV-uninfected infant. Case report A 43-day-old female infant presented in January 2002 with a 7-day history of cough and difficulty breathing. The mother was known to be HIV infected and both mother and infant had received single-dose nevirapine at delivery. The child had not received trimethoprim–sulphamethoxazole prophylaxis. On examination she was well nourished, weighing 4.5 kg (64th centile) and was 61 cm long (99th centile). The child had a respiratory rate of 72 breaths/min, a heart rate of 178 beats/min and was afebrile. She was not clinically cyanosed but her oxygen saturation was 89% on pulse oximetry. Clinical markers of HIV disease included cervical and axillary lymphadenopathy, hepatosplenomegaly and oral candida. On chest auscultation she had left-sided bronchial breathing. Her chest radiograph revealed diffuse interstitial infiltrates suggestive of PCP. She was commenced on our standard antimicrobial regimen of benzylpenicllin (120 000 iu/kg per day), gentamicin (7.5 mg/kg per day) and high-dose trimethoprim–sulphamethoxazole (120 mg/kg per day). Forty-eight hours after admission her respiratory signs worsened and she had a non-bronchoscopic bronchoalveolar lavage with maternal consent. Direct immunofluorescence of the non-bronchoscopic bronchoalveolar lavage fluid diagnosed PCP, and she was commenced on dexamethasone 0.15 mg/kg four times a day for a week, which was tailed off over the second week. The infant had a positive HIV enzyme-linked immunosorbent assay test but HIV-DNA polymerase chain reaction was negative and quantitative RNA polymerase chain reaction was below the level of detection. Both assays are 100% sensitive by 7 weeks of age [3] and use different amplification methods, primers and probes. As the diagnosis of PCP in HIV-infected infants under 2 months old is unusual, the mother was interviewed about her own respiratory symptoms. She reported that she had been coughing for 2 weeks before delivery and also described exertional dyspnoea. An exercise test was performed on the mother and her oxygen saturations dropped from 93 to 84% after 10 min exercise breathing room air. Her chest radiograph showed diffuse ground-glass opacification suggestive of PCP, and she was referred to the adult respiratory unit. Samples obtained during flexible bronchoscopy the next day confirmed a diagnosis of PCP. The mother was treated with high-dose trimethoprim–sulphamethoxazole and adjuvant steroids and was admitted to hospital with her daughter. Both mother and daughter did well and were discharged a month later. We do not have molecular facilities available to genotype PCP, and have not been able to confirm whether the strains of PCP in the mother and infant were identical. However, we feel that the circumstantial evidence of the presence of maternal symptoms before the infant's delivery and the unusually young age of the infant suggests that in this case there was mother-to-infant transmission of PCP. HIV in the infant has been excluded and the infant was well nourished and had no other co-morbidity to explain the diagnosis of clinical PCP. There have been previous reports of the transmission of PCP from mothers to their infants [4,5], including two HIV infected infants. Cell-mediated immunity is particularly important in PCP infection. CD4 cell counts of pregnant women fall throughout their pregnancy [6], and HIV-exposed but uninfected infants have different CD4 cell counts from the infants of HIV-uninfected mothers [7]. IgG antibodies are known to rise in PCP infection but are lower in HIV-infected adults than HIV-uninfected peers [8]. It is not known whether maternal IgG antibodies against PCP are important in protecting HIV-exposed infants. However, the reported decreased transplacental transfer of protective antibodies against Streptococcus pneumoniae from HIV-infected mothers to their infants suggests that this may also be the case in PCP [8,9]. There is no published work on the transfer of anti-PCP antibodies from HIV-infected mothers to their infants. We hypothesize that in this case the HIV-uninfected infant was exposed to PCP through close contact with her mother, and that because of the reduced placental passage of immunoglobulins and altered cell-mediated immunity the infant developed clinical PCP. Sponsorship: The Durban Paediatric Pneumonia Pathogen Study and L.McN.'s salary are funded though a Wellcome Trust Clinical Tropical Medicine Fellowship: grant no. GR056609MA.