Updates By Carol A. Kemper, MD, FACP
A New Flu Peptide with a Purpose?
Source: Chen W, et al. Nat Med. 2001;7:1306-1312.
A novel peptide found in certain influenza viruses, which may be derived from strains of avian influenza, may explain the significant morbidity associated with certain outbreaks of influenza. For years, influenza was thought to have just 8 genes, which encoded 10 different proteins. Chen and associates discovered that the translation of an alternate reading frame for one of these genes, PB-1, resulted in a completely different 87-residue protein, PB1-F2. This new peptide is uniquely capable of being recognized by CD8+T cells, and induces apoptosis of human monocytes. Interestingly, the gene product could not be isolated from certain animal influenza viruses (eg, swine), but could be found in certain avian viruses. Chen et al theorize that PB1-F2 may function to promote killing of influenza virus-infected host immune cells, resulting in a rapid inability to fight off infection and higher frequency of morbidity and mortality.
D4T and Neuromuscular Weakness
Source: Stevens MR. Drug Warning, BMS Virology, February 2002.
The long-term administration of nucleoside analogue therapy, especially the agents zidovudine (AZT), didanosine (ddI), and stavudine (d4T), has been linked to the development of lactic acidosis and mitochondrial toxicity in patients with HIV (Kemper CA. Infectious Disease Alert. 2001;20(8)59-60). While some patients receiving NRTIs develop asymptomatic elevations of lactic acid, the significance of which is not known, such patients may rarely develop a rapidly progressive and sometimes fatal syndrome of lactic acidosis, often associated with pancreatitis, hepatic steatosis, and myopathy.
In addition, several cases of rapidly progressive neuromuscular weakness, resembling Guillain Barré syndrome, have been described in patients receiving d4T in combination with other antiretrovirals. Progression to frank paralysis and respiratory failure has occurred. Most of the cases occurred in patients with symptomatic elevations in lactic acid or more severe lactic acidosis. The manufacturer recommends immediate discontinuation of d4T in any patient with motor weakness, sudden neurologic symptoms, or lactic acidosis. Immediate hospitalization with close observation, administration of fluids, bicarbonate, and carnitine may be of benefit.
Source: MMWR Morb Mortal Wkly Rep. 2002;51:164-165.
Congenitally acquired malaria is unusual, but vertical transmission of Plasmodium malariae is almost unheard of. In September 2000, a 10-week-old infant presented with fever, anemia, and thrombocytopenia. The child had been born in North Carolina and had never been out of the country, although both parents were from the Democratic Republic of Congo (the mother in 1996). Multiple cultures of blood, urine, and CSF were negative, but blood smears obtained 2 days after admission were positive for P malariae. The mother reported a history of malaria and received chloroquine shortly before immigrating to the United States. However, multiple specimens from the mother, including smears and PCR for all 4 malaria species were negative, although anti-malarial antibody titers were high.
Unlike P vivax and P ovale, which may remain dormant in the liver for years, P malariae has no dormant hepatic phase and can only persist in erythrocytes. Cases of asymptomatic, low-level parasitemia have been described, and recrudescence of infection has occurred as many as 70 years after primary infection! Vertical transmission in this case can only have resulted from inadequate treatment with residual low-level parasitemia in the mother prior to delivery, despite her negative studies at the later date.
This case is a reminder of the single case of congenital transmission of malaria that I’ve seen, which occurred many years ago at the county hospital.1 A 4-week-old infant presented with fever and irritability to the Pediatric Clinic. Fortunately, while doing a manual differential, the laboratory detected ring forms of P vivax—a finding that would have been missed with an automated differential. Mom was newly immigrated to California from Mexico, and was unaware of any history of malaria, was asymptomatic, and had negative smears. Although unusual, clinicians should consider congenital malaria in any infant with persistent fever, anemia, and unremarkable cultures whose mother has risk factors for malaria.
1. Kemper CA, et al. Efficiency of diagnosis and adequacy of antimalarial therapy in patients hospitalized with malaria. In: Lobel H, Steffen R, Kozarsky P, eds. Travel Medicine 2: Proceedings of the Second Conference on International Travel Medicine. 1991; 109-111.