By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.

Invasive Pneumococcal Disease in HIV

Flannery B, et al. Changes in Invasive Pneumococcal Disease Among HIV-Infected Adults Living in the Era of Childhood Pneumococcal Immunization. Ann Intern Med. 2006;144:1-9.

Following the introduction of more highly active antiretroviral therapy in ~1995, epidemiologists observed a 50% decrease in rates of invasive pneumococcal disease in persons with HIV/AIDS. By 1997, the incidence of invasive pneumococcal disease had leveled off, but still remained significantly higher (~35 x) in persons with HIV-infection compared with non-HIV-infected adults. Since then, there has been a gradual decline in the rates of invasive pneumococcal infection in adults, which has been attributed to the introduction of pediatric pneumococcal conjugate vaccine.

Flannery and colleagues examined the frequency of invasive pneumococcal infection in HIV-infected adults living in 7 core surveillance areas in the United States, before and after the introduction of the pediatric pneumococcal conjugate vaccine. A total of 8582 cases of invasive pneumococcal infection occurred in adults, including 2013 (24%) cases in persons with HIV/AIDS. Between 1998 and 2003, the rate of pneumococcal disease decreased 19% in persons with HIV/AIDS (from 1127 to 919 cases per 100,000 AIDS population). Excluding persons with AIDS, the rate in HIV steadily declined to ~9 cases per100,000 by 2003. The most common presentations of infection among HIV-infected adults were pneumonia (81%), followed by bacteremia without a recognized focus (15%), and meningitis (4%). The case fatality rate was 8%.

Before the introduction of the pediatric conjugate vaccine, serotypes contained in the vaccine accounted for the majority (58%) of invasive pneumococcal infections in adults. Data on serotypes in this study, which were available for 91% of the isolates, indicated a 62% decrease in disease caused by serotypes contained in the vaccine, although the ratio of disease caused by non-vaccine serotypes increased by 44%. Interestingly, this observation was limited to black men and women with HIV or AIDS, and was not observed in whites. This is consistent with other data demonstrating that close contact with children is more common for black persons with HIV/AIDS than whites.

Trends in antibiotic susceptibility were similar in patients with or without HIV/AIDS. The percentage of isolates resistant to trimethoprim-sulfamethoxazole (27%) and penicillin (20%) remained fairly stable throughout the study.

Penile Elephantiasis and LGV

Kumaran MS, et al. Saxophone Penis Revisited. Int J STD AIDS. 2006:17:65-66.

Lymphogranuloma Venereum (LGV) has been making a comeback in parts of the developing worlds, especially in gay men in Europe and in the United States. LGV is caused by L1-L3 serovars of Chlamydia trachomatis. It was previously uncommon outside of Southeastern Asia, India, and Africa, where it is responsible for about < 1% to 9% of sexually transmitted infections.

Kumaran and colleagues from Chandigarh, India, report a 24-year-old male with an unusual clinical finding, only rarely encountered but typical for chronic LGV infection. The man had numerous male and female sexual partners. He presented with mildly tender inguinal lymphadenopathy, multiple draining sinuses around the perianal area, narrowing of the anal canal, and a firm, twisted penis with edema of the prepuce, which "accented the dorsal curvature." Serologies for HIV, syphilis, and chlamydia were negative. Computed tomography of the pelvis demonstrated asymmetric thickening of the rectal mucosa, diffuse stranding of the perirectal fat, and distortion of the fascial planes. He was diagnosed with chronic LGV and received treatment with doxycycline.

About 25% of LGV infections result in chronic changes such as these. Progressive lymphatic inflammation and obstruction eventually leads to suppurative regional lymphangitis and sclerosis of connective tissue. While some patients present with genital or rectal ulcers and draining sinuses, others may present with more chronic gastrointestinal complaints such as constipation, painful bowel movements, and what appears to be an irritable bowel syndrome. Penoscrotal edema, or elephantiasis, occurs in 4% of cases, and may develop over 1 to 20 years. Sclerosis of subcutaneous tissue in the penis eventually leads to a twisting deformity of the shaft, with edema of the prepuce, variously called a "ram horn penis" or "saxophone penis."

Since the CDC alert concerning the resurgence of LGV was raised last year, only 27 cases of LGV have thus far been reported in the United States, but most experts assume this is only the tip of the iceberg. The infection can be difficult to recognize, existing serologic studies may lack sensitivity and specificity, and many laboratories do not offer these types of tests. Because the symptoms can be difficult to recognize, may remain indolent for months to years, and early initiation of antibacterial treatment is important, some HIV experts are calling for screening of all sexually active gay men. While 3 weeks of doxycycline is effective for active infection, antibiotic treatment may not remedy its chronic manifestations.

Malaria in Returning Soldiers

Kotwal RS, et al. An Outbreak of Malaria in US Army Rangers Returning From Afghanistan. JAMA. 2005;293:212-216. Erratum in: JAMA. 2005;293:678.

These authors warn that both military and civilian health care personnel may encounter delayed presentations of malaria in soldiers returning from Iraq and Afghanistan, even in those perceived to be at lower risk. P. vivax accounts for 80%to 90% of malaria in Afghanistan and about 95% of cases in Iraq, but the risk of infection varies considerably depending on the geography and the season. P. falciparum makes up the other fraction of cases.

Depending on the perceived risk, United States Army soldiers deployed in these areas are directed to take antimalarial prophylaxis and to use personal protective measures, such as mosquito netting, permethrin impregnated uniforms and gear, and frequent use of DEET. Soldiers doing nighttime patrol remain at particular risk, especially at dawn and dusk.

This provides a partial explanation as to how 38 cases of P. vivax malaria occurred in a group of 725 US Army Rangers deployed to combat zones in Eastern Afghanistan in the summer/fall of 2002. All of the rangers received weekly mefloquine prophylaxis during their tour in Afghanistan, as well as terminal prophylaxis for 4 weeks. A diagnosis of malaria was made largely on the basis of fever, although headache, myalgias, and gastrointestinal symptoms were common.

However, there is an interesting twist to this story, as the diagnosis of malaria was complicated by an intervening tour of duty in Iraq 169 days after returning from Afghanistan, where they were perceived to be at low risk for malaria. While in Iraq, the men received daily doxycycline (due to the added risk of a biological attack), but they did not receive terminal antimalarial prophylaxis because the season and locale was considered such low risk for malaria. No doubt the doxycycline effectively prevented the emergence of active bloodstream infection during their tour of duty in Iraq, but did little to eliminate the hypnozoites. As a result, three-fourths (76%) of the malaria cases were diagnosed 4 months after the men returned from Iraq. The median time to diagnosis was 233 days (range, 1-339 days) after returning from the Afghan arena. Two cases relapsed within one year. One case was complicated by ARDS. All personnel received chloroquine for 3 days, followed by a 2 week course of primaquine. Although there was certain disagreement as to where the malaria was acquired, consultants from the Army and the CDC were brought in and, based on epidemiologic risk, determined the cases were most likely acquired during the first tour in Afghanistan.

Anonymous questioning revealed that only about one-half of the men actually took their weekly antimalarial prophylaxis, and 41% took terminal treatment. Only one-third were compliant with both, and fewer than one-third admitted to using DEET. Both perceived lack of a threat from malaria, a lack of a significant mosquito problem, and a tumultuous schedule where "too many other things were happening" as hampering compliance. Malaria should be considered in the differential of febrile or gastrointestinal illness in returning military personnel, even if the risk may not be proximate or immediately apparent.