Risk Factors For Pneumococcal Disease Research Articles

Polymorphic Receptors of the Innate Immune System (MBL/MASP-2 and TLR2/4) and Susceptibility to Pneumococcal Bacteremia in HIV-Infected Patients: A Case-Control Study

Some deficient genetic polymorphisms of the innate immune system have been correlated to a higher susceptibility to different infections, especially in immunocompromised patients. The possible association between an increased incidence of pneumococcal bacteremia in HIV-infected patients, and deficient polymorphisms of the mannose-binding lectin (MBL), MBL-associated serine protease 2 (MASP-2), and toll-like receptors (TLR) 2 and 4 is analyzed by means of a case-control study. HIV-infected patients with pneumococcal bacteremia. HIV-infected patients without previous pneumococcal bacteremia matched with cases by sex and CD4 count in a 2:1 ratio. Fifty-seven cases and 114 controls were studied. Demographics, HIV infection status, antiretroviral therapy, risk factors for pneumococcal disease, and genotypes of MBL2, MASP2, TLR2 and TLR4 were analyzed. The prevalence of the MBL2, MASP2, TLR2 and TLR4 gene polymorphisms was similar in both groups. No statistical significance was found (OR 0.77, IC 95% 0.27 - 2.13) when analyzing the possible association of MBL2 deficient polymorphisms with pneumococcal bacteremia. In HIV infected patients, no association between the presence of deficient polymorphisms of MBL2, MASP2, TLR2 and TLR4 and the incidence of pneumococcal bacteremia was found.

Effectiveness of Polysaccharide Pneumococcal Vaccine in HIV-Infected Patients: a Case-Control Study

Polysaccharide pneumococcal vaccine (PPV) is recommended among human immunodeficiency virus (HIV)-infected patients, although its effect in reducing the incidence of pneumonia or invasive pneumococcal disease is not well established. Our objective was to determine the effectiveness of 23-valent PPV in HIV-infected adults and the risk factors for pneumococcal pneumonia or invasive pneumococcal disease. We performed a retrospective case-control study in 4 Spanish hospitals for the period from January 1995 through December 2005 using the HIV database from each hospital to identify case patients with Streptococcus pneumoniae disease and control subjects without a history of pneumococcal infection. A total of 184 case patients and 552 control subjects were identified. The factors associated with pneumococcal disease in bivariate analysis were active injection drug use (odds ratio [OR], 3.33; 95% confidence interval [CI], 2-5.55), alcoholism (OR, 3.03; 95% CI, 1.86-4.91), chronic obstructive pulmonary disease (OR, 2.58; 95% CI, 1.3-5.1), cirrhosis (OR, 6.05; 95% CI, 3.2-11.4), antiretroviral therapy (OR, 0.23; 95% CI, 0.16-0.32), trimethoprim-sulfamethoxazole prophylaxis (OR, 0.66; 95% CI, 0.45-0.97), viral load <5000 copies/mL (OR, 0.38; 95% CI, 0.26-0.54), and previous PPV (OR, 0.39; 95% CI, 0.24-0.65). Risk factors for pneumococcal disease in multivariate analysis were cirrhosis (OR, 5.64; 95% CI, 2.53-12.53), chronic obstructive pulmonary disease (OR, 2.90; 95% CI, 1.21-6.94), and alcoholism (OR, 2.15; 95% CI, 1.11-4.19), whereas protective factors were receipt of antiretroviral therapy (OR, 0.23; 95% CI, 0.14-0.36) and receipt of pneumococcal vaccine (OR, 0.44; 95% CI, 0.22-0.88), even in patients with CD4 lymphocyte counts <200 cells/microL. Antiretroviral therapy and PPV have a significant, independent protective effect against pneumococcal disease, regardless of CD4 lymphocyte count; thus, all patients with HIV infection should be vaccinated with PPV to prevent pneumococcal disease.

Vitamin A Supplementation at Birth Delays Pneumococcal Colonization in South Indian Infants

Nasopharyngeal colonization is a risk factor for pneumococcal disease, a leading cause of complications and death in infants. We assessed the impact of vitamin A supplementation in reducing pneumococcal colonization in infants from an area with endemic vitamin A deficiency. We recruited 464 2-mo-old infants from a rural area in South India. Infants were randomly assigned to receive two 7000-microg retinol equivalent doses of vitamin A (n = 239) or placebo (n = 225) orally at birth, and nasopharyngeal specimens were collected at ages 2, 4 and 6 mo. We studied the effect of vitamin A on culture-confirmed pneumococcal colonization and on the distribution of pneumococcal serotypes. Analyses were conducted by intention-to-treat. The risk of colonization among infants aged 4 mo who were not colonized by age 2 mo was significantly reduced in the vitamin A group compared with the placebo group [odds ratio 0.51 (0.28, 0.92), P = 0.02). The odds of colonization were 27% lower in the treatment group than in the placebo group [odds ratio 0.73 (0.48, 1.1), P = 0.13]. No differences were detected in the prevalence of invasive serotypes. The risk of colonization with penicillin-resistant isolates was 74% lower in the vitamin A group than in the placebo group at 2 mo of age. However, the prevalence of penicillin-resistant isolates was only 4%. Neonatal vitamin A supplementation may play a role in lowering morbidity rates associated with pneumococcal disease by delaying the age at which colonization occurs.

Risk factors for pneumococcal disease in human immunodeficiency virus-infected patients.

To identify risk factors for pneumococcal infection among human immunodeficiency virus-infected patients, a nested case-control study was done in an urban university human immunodeficiency virus clinic. Subjects with pneumococcal illness seen between 1 January 1990 and 1 July 1994 (n=85) were randomly matched to controls from the same population. Patients with pneumococcal disease were more likely than controls to be African Americans (adjusted odds ratio [OR]=3.92), have <200 CD4 cells/mm3 (adjusted OR=3.38), have a history of any pneumonia (adjusted OR=3.28), and have an albumin level of <3.0 g/dL (adjusted OR=6.25). Use of zidovudine (adjusted OR=0.38) and pneumococcal vaccination when the subject had >200 CD4 cells/mm3 (adjusted OR=0.22) were less common in cases than in controls. Similar results were found when only cases with infections of usually sterile sites were analyzed. Pneumococcal vaccine may be most protective when it is administered before advanced immunodeficiency develops.

Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya

SummaryBackground HIV infection is a major risk factor for pneumococcal disease in industrialised countries. Although both are common infections in sub-Saharan Africa, few studies have investigated the importance of this interaction. We have followed up a cohort of female sex-workers in Nairobi and report here on the extent of invasive pneumococcal disease.Methods A well-established cohort of low-class female sex-workers, based around a community clinic, was followed up from October, 1989, to September, 1992. 587 participants were HIV positive and 132 remained HIV negative. Set protocols were used to investigate common presentations. Cases were identified clinically and radiographically. Streptococcus pneumoniae and other pathogens were diagnosed by culture.Findings Seventy-nine episodes of invasive pneumococcal disease were seen in the 587 HIV-positive women compared with one episode in the 132 seronegative women (relative risk 17·8, 95% Cl 2·5 to 126·5). In seropositive women the incidence rate was 42·5 per 1000 person-years and the recurrence rate was 264 per 1000 person-years. By serotyping, most recurrent events were re-infection. A wide spectrum of HIV-related pneumococcal disease was seen: only 56% of cases were pneumonia; sinusitis was seen in 30% of cases, and occult bacteraemia, a novel adult presentation, in 11%. Despite forty-two bacteraemic episodes, no deaths were attributable to Strep pneumoniae. At first presentation the mean CD4 cell count was 302/μL (SD 191) and was 171/μL (105) for recurrent episodes. During acute Strep pneumoniae infection the CD4 cell count was reversibly suppressed (mean fall in sixteen episodes, 105/μL [123]). The neutrophil response to acute infection was blunted and was correlated with CD4 count (r=0·50, 95% Cl 0·29 to 0·66). Strep pneumoniae caused more disease, at an earlier stage of HIV immunosuppression, than Mycobacterium tuberculosis or non-typhi salmonellae.Interpretation Our study highlights the importance of the pneumococcus as an early but readily treatable complication of HIV infection in sub-Saharan Africa.

A study of risk factors for pneumococcal disease among children in a rural area of west Africa.

Pneumoccal infection is one of the leading causes of pneumonia, meningitis and septicaemia in developing countries. We have investigated possible risk factors for pneumococcal disease among children living in a rural area of The Gambia. A prospective case-control study was conducted in which children with pneumococcal infection were identified from among children attending out-patient and under-fives clinics and matched according to age with healthy children selected randomly from the local community. A questionnaire was used to investigate possible nutritional, medical, socioeconomic and environmental risk factors for pneumococcal disease. An increased risk of pneumococcal disease was associated with poor weight gain, a history of serious illness in the previous 6 months, exposure to cigarette smoke or being carried on mother's back while cooking. The risk of pneumococcal disease was reduced among children whose mothers had a personal source of income. The incidence of pneumococcal disease could be reduced by improving nutrition and taking steps to identify and rehabilitate those children whose weight is faltering or falling. Encouraging mothers to develop greater financial independence may also be beneficial. Reduced exposure to smoke should be promoted by improving ventilation in kitchens, introducing more efficient and less polluting stoves, keeping children away from smoky environments and discouraging parental smoking.

Preventing bacterial respiratory tract infections among persons infected with human immunodeficiency virus.

Bacterial respiratory tract infections occur frequently in persons infected with human immunodeficiency virus (HIV) and may be caused by a wide variety of pathogens. Pneumonia is the most commonly diagnosed respiratory infection in HIV-infected persons and is more common in those persons than in non-HIV-infected ones. HIV-infected persons have a much higher risk of pneumococcal disease than do noninfected controls, and disease may occur relatively early in the course of HIV infection. While mortality associated with the disease does not seem to be high among HIV-infected persons, there is a higher rate of recurrence of the disease in that population. Risk factors for pneumococcal disease in HIV-infected persons are not well characterized. Though efficacy data are limited, the 23-valent polysaccharide pneumococcal vaccine is recommended for use early in the course of HIV infection. There are no data suggesting that HIV-infected persons should be revaccinated routinely. Antiretroviral agents may enhance the immunologic response to the polysaccharide vaccine. Prophylactic antibiotics may have a role in preventing recurrences of severe bacterial respiratory infections, and intravenous immunoglobulin may be useful in preventing serious bacterial infections in HIV-infected children. HIV-infected persons are also at greater risk for serious infections with Haemophilus influenzae than are non-HIV-infected persons. Vaccination against H. influenzae type b (Hib) is recommended for HIV-infected children but not for adults. Antimicrobial drug-resistant strains of Streptococcus pneumoniae and H. influenzae have become more prevalent recently and consequently have impacted on strategies for prevention and treatment of those infections.

Invasive pneumococcal disease in central Australia.

Invasive pneumococcal disease remains a major problem in certain groups of people. We undertook a hospital-based review of all cases of invasive pneumococcal disease in central Australia over a 2-year period. We observed 79 cases of invasive disease in 78 patients. The incidence of invasive pneumococcal disease was highest in Aborigines under 5 years of age (1,025 cases per 100,000 population per year). The relative risk for Aborigines compared with non-Aborigines was 31.6 (95% CI, 12.8-78.1). Pneumonia was the commonest disease observed (82% of patients). Eight patients died (10.1%), and all of these patients had identifiable risk factors for pneumococcal disease. Serotyping showed that all except two isolates were covered by the existing 23-valent pneumococcal vaccine. These data reveal that Aborigines in central Australia have the highest reported rate of invasive pneumococcal disease in the world. A vaccination program in central Australia should decrease admissions and deaths due to pneumococcal disease.

Invasive pneumococcal disease in central Australia.

To document the incidence, case fatality, clinical and demographic features of invasive pneumococcal disease in central Australia. Invasive isolates from the regional central laboratory were prospectively recorded over five years and case notes retrospectively reviewed. Population denominators were calculated from national Census data from 1986 and 1991. The population estimates for the region were 14,568 for Aboriginals and 28,680 for non-Aboriginals. There were 185 episodes of invasive pneumococcal disease over the five years, 162 (87.5%) in Aboriginals and 23 (12.5%), in non-Aboriginals. The incidence in Aboriginal children under two years of age was 2052.7 per 100,000 and for those 20-59 years was 178.2 per 100,000. The relative risk in Aboriginals compared with non-Aboriginals was 10.8 (95% CI, 5.6-20.7; P < 0.0001) for those aged 0-4 years and 20.4 (95% CI, 9.7-42.5; P < 0.0001) for those 15-59 years. Forty-one Aboriginal adults aged over 14 (62%) had at least one conventional risk factor for pneumococcal disease; alcohol abuse was present in 27 (41%). There were 13 Aboriginal deaths and the case fatality rose from 2% in those under four years to 40% for those over 59 years. Central Australian Aboriginals have the highest incidence of invasive pneumococcal disease reported. The rate for children under two years is 59 to 80 times the rates for children in the United States and Sweden. These data have implications for improving vaccine use, health service delivery and environmental health in Aboriginal communities.

An epidemic of pneumococcal disease in an overcrowded, inadequately ventilated jail.

In the United States many correctional facilities now operate at far over capacity, with the potential for living conditions that permit outbreaks of respiratory infections. We investigated an outbreak that was identified in an overcrowded Houston jail after two inmates died of pneumococcal sepsis on the same day. Outbreaks of pneumococcal disease have been rare in the era of antibiotics. We assessed risk factors for pneumococcal disease in both a case-control and a cohort study. Ventilation was evaluated by measuring carbon dioxide levels and air flow to the living areas of the jail. The extent of asymptomatic infection was determined by culturing pharyngeal specimens from a random sample of inmates. Type-specific immunity was determined with an enzyme immunoassay. Over a four-week period, 46 inmates had either acute pneumonia or invasive pneumococcal disease due to Streptococcus pneumoniae serotype 12F. The jail's capacity had been set at 3500 inmates, but it housed 6700 at the time of the outbreak; the inmates had a median living area of only 34 ft2 (3.2 m2) (interquartile range, 28 to 56 ft2 [2.6 to 5.2 m2]) per person. There were significantly fewer cases of disease among inmates with 80 ft2 (7.4 m2) per person or more (P = 0.030). Carbon dioxide levels ranged from 1100 to 2500 ppm (acceptable, < 1000), and the ventilation system delivered a median of only 6.1 ft3 of outside air per minute per person (interquartile range, 4.4 to 8.5 ft3; recommended, > or = 20 ft3). The attack rate was highest among inmates in cells with the highest carbon dioxide levels and the lowest volume of outside air delivered by the ventilation system (relative risk, 1.94; 95 percent confidence interval, 1.08 to 3.48). Of underlying medical conditions, intravenous drug use was most strongly associated with disease (odds ratio, 4.50). The epidemic strain (serotype 12F) was cultured from 7 percent of the asymptomatic inmates. Of 11 case patients tested with the enzyme immunoassay, 9 (82 percent) lacked preexisting immunity to this strain. Severe overcrowding, inadequate ventilation, and altered host susceptibility all contributed to this outbreak of pneumococcal disease in a large urban jail.