The changing role of village health volunteers in northeast Thailand: an ethnographic field study

Aspergillus sinusitis is an uncommon complication of advanced human immunodeficiency virus (HIV) infection. We describe 2 patients with AIDS who developed histologically proven invasive Aspergillus sinusitis. We also review the findings of 14 histologically documented and 5 probable cases of invasive Aspergillus sinusitis. The literature on the prevalence, predisposing factors, diagnosis, treatment, and prognosis of the infection is reviewed. Major risk factors for the disease are advanced AIDS, chronic sinusitis or otitis, neutropenia, use of corticosteroids and prolonged use of broad spectrum antibiotics. The most common presenting symptoms are nonspecific and include fever, local pain, and swelling. Despite the newer diagnostic and therapeutic approaches discussed herein, the infection is usually fatal in HIV-infected patients. Early diagnosis and aggressive treatment remain the only available means to improve the currently dismal prognosis of Aspergillus sinusitis.     

Invasive pulmonary aspergillosis due to Aspergillus terreus: 12-year experience and review of the literature

A 12-year retrospective analysis was done to identify and evaluate in detail cases of invasive pulmonary aspergillosis (IPA) caused by Aspergillus terreus. We identified 13 A. terreus infections among 133 total cases of confirmed invasive aspergillosis; 11 were IPA and 2 were primary peritoneal infections. Of the 11 patients with IPA, 7 developed neutropenia during hospitalization, and the remaining four were receiving immunosuppressive agents. Ten patients with IPA died; one liver transplantation patient without neutropenia survived after treatment with amphotericin B, itraconazole, and a pulmonary lobectomy. Six patients developed disseminated disease, with the heart the most common extrapulmonary site identified (four patients). These cases demonstrate that IPA caused by A. terreus rapidly progresses in immunocompromised patients receiving amphotericin B and illustrate the need for sensitive diagnostic tests and more effective antifungal agents.     

Paranasal sinus mycoses in north India

Recognizing the high incidence of paranasal sinus mycoses in north India, we analysed retrospectively the clinical, mycological and management aspects of 178 patients with proven disease attending our institute. On the basis of clinical, radiological, histopathological and mycological findings, the patients could be categorized into those with allergic (8), non-invasive (92) and invasive (78) disease types. Bony erosion without mucosal invasion by fungi was seen in 16 patients with non-invasive disease. Young men from rural areas were the most commonly affected. Rhinorrhoea with nasal polyposis (45.8%) and proptosis (46.4%) was the most common presentation. Concurrent involvement of the maxillary and ethmoid sinuses was common in these patients, whereas isolated sphenoid and frontal sinuses were involved in the invasive variety only. Orbital and intracranial extensions were detected in 100% and 13.2%, respectively, of patients with the invasive type of disease. Aspergillus flavus (79.7%) was the most common isolate. Surgical debridement and sinus ventilation were adequate for the effective management of the non-invasive disease. However, adjuvant medical therapy was included in treatment of the semi-invasive and invasive varieties of the disease. Itraconazole was found to be most useful in prevention of recurrence in the invasive type. Mortality was highest (33.3%) among patients with zygomycotic infection. Invasive fungal granuloma with orbital and intra-cranial invasion is a distinct entity in terms of its clinical course and treatment compared with non-invasive fungal sinusitis, and it needs to be treated aggressively with surgical excision and postoperative itraconazole.     

Cyclin D1 overexpression related to retinoblastoma protein expression as a prognostic marker in human oesophageal squamous cell carcinoma

Aspergillus sp. sinusitis is not uncommon in immunocompromised patients but is unusual in patients who are not immunocompromised. The disease may occur as a saprophytic condition, as an allergic sinusitis or as a potentially lethal invasive disease. The differentiation between non-invasive and invasive Aspergillus sp. sinusitis is crucial and this distinction is fully discussed. The treatment options are also considered. Invasive disease requires aggressive treatment with long-term antifungal agents in sufficient doses combined with wide surgical excision. We present a patient who presented with invasive Aspergillus fumigatus sinusitis and subsequently developed cranial neuropathies and skull base osteitis. She was initially treated with oral itraconazole (400 mg daily) for 18 months but due to lack of response this was changed to a new experimental oral azole (voriconazole) which was continued for a further 14 months. She has since remained well for the last five years.     

Report of the first case of invasive fungal sinusitis caused by Scopulariopsis acremonium: review of scopulariopsis infections

Scopulariopsis acremonium is a species of saprophytic fungus not previously reported to cause invasive disease in humans, although invasive infections from other species of Scopulariopsis have been reported and are reviewed. Deep infection with this fungus is associated with a high mortality rate. Invasive fungal sinusitis, in general, is a potentially fatal disease that typically affects immunocompromised patients, such as those receiving intensive chemotherapy or undergoing bone marrow transplantation. We report a case of invasive fungal sinusitis caused by Scopulariopsis acremonium in a patient with leukemia, who was successfully treated with amphotericin B, itraconazole, endoscopic sinus surgery, and granulocyte colony-stimulating factor.     

Anti-obesity drugs

In patients with hematological malignancies invasive mycoses occur frequently. In this retrospective study autopsy and histopathology material of 171 patients with hematological malignancy who had died between 1994 and 1996 at the 1st Department of Internal Medicine (Hematology), St. László Hospital, Budapest was analysed. In cases with invasive fungal infection post mortem results were compared to clinical and microbiological data. Through the three years' period an invasive mycosis could be confirmed in 33 patients by autopsy. Aspergillosis occurred in 21, candidiasis in 11, other fungal infections in 2 cases, a double infection was seen in 1 patient. The incidence was 19.2% (in invasive candidiasis: 6.4%, in aspergillosis 12.2%). Invasive aspergillosis most frequently was seen in the lung (71%), while candidiasis occurred mainly in the intestinal tract (42%). Cultures for mycology were collected from the autopsy material of 9 patients, of which 8 gave positive results. A previous fungal colonisation results was confirmed in 23 patients, but based on colonisation conclusions rarely could be driven concerning the species causing invasive infection. Sensitivity of Aspergillus antigen and antibody tests was 45 and 50%, respectively. Predisposing factors for invasive aspergillosis and candidiasis were similar, except for duration of neutropenia (24 vs. 12 days, p < 0.004). The antifungal drug most frequently used was amphotericin B. We observed a persisting infection in invasive pulmonary aspergillosis and chronic disseminated candidiasis in spite of the administration of a cumulative dosis of 1-2 g. Most frequently Aspergillus infections--primarily that of the lung--can be seen. Presence of invasive mycoses can usually be confirmed in vivo, but an early diagnosis still remains unsolved.     

The effect of prophylactic fluconazole on the clinical spectrum of fungal diseases in bone marrow transplant recipients with special attention to hepatic candidiasis. An autopsy study of 355 patients

We reviewed 355 autopsies performed between 1990 and 1994 at a major marrow transplant center to determine whether fluconazole prophylaxis prevented visceral fungal infection. Fluconazole prophylaxis was defined by a minimum of 5 prophylactic doses. Fungal infection (any site) was found in 40% of patients transplanted and autopsied at the center. Overall, the proportion of autopsies with any fungal infection was not different for those patients receiving no fluconazole prophylaxis versus those with prophylactic fluconazole. With fluconazole prophylaxis, candidal infections were less frequent, decreasing from 27% to 8%, while Aspergillus infections were more frequent, increasing from 18% to 29%. No increase in deaths related to non-albicans Candida infections was seen. Of the 329 patients with livers examined, hepatic infection caused by Candida species was significantly less common in patients who had received fluconazole. Fungal liver infection was found in 31 patients (9%), 16% of those who were not treated with fluconazole and 3% of those who were treated with fluconazole. Since patients with candidal infections died earlier after marrow transplant than patients with mold infections, we speculate that a longer length of survival may dispose toward acquisition of mold infections. Fluconazole prophylaxis in this cohort of marrow transplant patients undergoing autopsy resulted in a significant reduction in infection caused by Candida species and an increase in mold infections.     

Otomastoiditis caused by Aspergillus in AIDS

BACKGROUND: Aspergillus otomastoiditis is an infrequent infection that occurs in most cases in immunocompromised hosts. Although fungal infections are common in AIDS patients, few cases of Aspergillus otomastoiditis have been reported. METHODS: Two clinical cases of AIDS patients with Aspergillus otomastoiditis are reported, and a review of the literature is performed. RESULTS: Clinical presentation in both cases was similar to those of other diseases involving middle and internal ear. Infection was linked to severe immunosuppression (C3 group). CONCLUSIONS: Aspergillus otomastoiditis is an infrequent infection in AIDS patients. Different routes by which Aspergillus obtains access to the middle ear have been proposed (tympanogenic, meningogenic, hematogenous and direct spread from paranasal sinuses or external auditory canal). Otorrhea, otalgia, hearing loss and facial nerve involvement are common findings. Bone destruction and invasion of brain or skull base may occur. CT or MRI are necessary to evaluate the extent of the disease. Etiologic diagnosis requires histopathologic confirmation on deep tissue biopsy or isolation from blood cultures or fistula exudates, because Aspergillus is a common saprophytic fungus in external auditory canal. Concurrent infections (i.e. Pseudomonas aeruginosa) frequently delay the correct diagnosis. Aggressive surgical resection and intravenous antifungal chemotherapy (amphotericin B or itraconazole) are the main therapeutic options. Outcome is poor as a consequence of severity, delay of etiologic diagnosis and difficulty of aggressive surgical approach in compromised patients. In patients with AIDS a low CD4 cell count would favour invasive Aspergillus infection, implying a worse outcome.     

N-acetylcysteine prevents development of the hyperdynamic circulation in the portal hypertensive rat

Infective endocarditis, defined as pathologically or clinically definite by the Duke criteria, was observed in 14 transplant recipients at our institutions. In addition, we reviewed 32 previously reported cases in solid organ transplant recipients. The spectrum of organisms causing infective endocarditis was clearly different in transplant recipients than in the general population; 50% of the infections were due to Aspergillus fumigatus or Staphylococcus aureus, but only 4% were due to viridans streptococci. Fungal infections predominated early (accounting for six of 10 cases of endocarditis within 30 days of transplantation), while bacterial infections caused most cases (80%) after this time. In 80% (37) of the 46 cases in transplant recipients, there was no underlying valvular disease. Seventy-four percent (34) of the 46 cases were associated with previous hospital-acquired infection, notably venous access device and wound infections. Three patients with S. aureus endocarditis had had an episode of S. aureus bacteremia > 3 weeks prior to the diagnosis of endocarditis and had received treatment for the initial bacteremia of < 14 days' duration. The overall mortality rate was 57% (26 of 46 patients died), with 58% (15) of the 26 fatal cases not being suspected during life. Endocarditis is an underappreciated sequela of hospital-acquired infection in transplant recipients.     

Association of class I HLA antigens with invasive meningococcal disease

BACKGROUND: The majority of meningococcal infections are characterized by nasopharyngeal carriership. In some patients invasive disease with a mild course develops, while some cases have a lethal outcome. The reasons of this wide variation range are not clear. The objective of the present work was to assess whether the development of invasive meningococcal disease or its prognosis are associated with HLA class I. METHODS AND RESULTS: The group of patients was formed by 40 patients (29 females, 11 males, mean age 16 years, range 8 months to 52 years). In 28 patients the disease was caused by N. meningitidis group C, in 9 cases group B, in three cases the serotype was not assessed. The etiology was confirmed by cultivation or latex agglutination. Twenty-three patients had a mild course of the disease, 8 a medium severe one, 9 patients a severe clinical course (score according to Stiehme, Damrosch and Rosenblat). The patients were compared with 227 non-related blood donors (114 women, 113 men, 18 to 50 years old). In patients and controls 24 lymphocytic HLA antigens class I were identified as to type. Typing was done using the standard microlymphocytotoxic test in the NIH modification. The results were processed by statistical methods using Fisher's exact test and the 2 x 2 test with Yates correction. In patients with a mild course HLA antigens B7 and B12 predominate (p = 0.03; p = 0.02), in medium severe cases antigen A11 (p = 0.03), in patients with the most severe course antigen A9 (p = 0.04). In invasive infections caused by N. meningitidis serotype B antigen B17 predominates (p = 0.05). CONCLUSIONS: The severity of meningococcal invasive infections is associated with HLA class I. Invasive disease caused by N. meningitidis serotype B are more likely to occur in carriers of HLA B17. No relationship was found between HLA class I and invasive disease caused by N. meningitidis regardless of serotype and with serotype C.     

Chronic mycoses of the paranasal sinuses--value of endonasal paranasal sinus surgery

BACKGROUND: Many host factors even in immunocompetent patients may have an influence on development of a fungal diseases within the paranasal sinuses. Fungal sinusitis can occur in an acute form or more often to a chronic type of the disease. These mainly relatively asymptomatic chronic forms and further divided into a chronic noninvasive, chronic allergic, and chronic invasive disease. Endonasal microsurgery has significantly changed the management of chronic fungal sinusitis and allows adequate removal of pathologic tissue even in advanced situations. The aim of this study was to analyze the efficacy of endonasal surgery in chronic fungal sinusitis. MATERIAL AND METHODS: In a retrospective study we assessed a group of 40 patients who had endonasal surgery for chronic fungal sinusitis. Patient records, CT and MRI scans, microbiology and histology as well as the postoperative clinical follow-up including endoscopic photo documentation were evaluated over a period of 5 years. All patients underwent endonasal surgery using endoscopic techniques. The microscopic was of additional help in a few cases with extended disease and multiple dehiscences of the skull base. RESULTS: Twenty-four patients had a chronic noninvasive of fungal sinusitis and 16 patients had a chronic invasive form. All these patients underwent endonasal surgery without external incision. The fungal disease was erradicated in 39 cases, and revision surgery was required in only one case in which involvement of the contralateral side was not initially detected. in two cases scar tissue in the middle meatus was later excised but without evidence of residual fungal disease. Only in 6 cases was antifungal chemotherapy required, where the disease had spread into surrounding tissue or the patient had severe symptoms. CONCLUSIONS: Endonasal microsurgical techniques are today the appropriate approach for managing chronic fungal sinus disease even in severe cases with radiologic evidence of expansion or invasion of surrounding tissue. Additional antifungal chemotherapy is only rarely indicated, specifically when the fungal disease invades surrounding tissue.     

Evaluation of PCR for detection of DNA specific for Aspergillus species in sera of patients with various forms of pulmonary aspergillosis

Pulmonary aspergillosis is classified into invasive, saprophytic, and allergic forms. In this study, we evaluated the usefulness of PCR for differentiating between different forms of aspergillosis or in monitoring disease activity during treatment by detecting DNA specific for Aspergillus species in the serum. Nested PCR was used to detect Aspergillus DNA in the sera of 30 patients with various forms of pulmonary aspergillosis. The results were compared with those of latex agglutination tests for detecting galactomannan antigen. We also examined the serial changes in the results of nested PCR during and after treatment of a subgroup of patients with invasive pulmonary aspergillosis with amphotericin B. The highest proportion of positive nested PCR results were in patients with invasive aspergillosis (10 of 12; 83%), while patients with pulmonary aspergilloma had the lowest frequency of positive tests (1 of 9; 11%). These results suggested that the sensitivity of the nested PCR depends on the extent of invasion by Aspergillus species. Serial assays showed that the results of nested PCR became negative shortly after commencement of antifungal treatment and that such changes did not correlate with clinical responsiveness to treatment. Our results indicate the potential usefulness of nested PCR with serum samples for the diagnosis of invasive aspergillosis and the detection of a shift in the status of infection from a noninvasive type to invasive aspergillosis. However, the results of the nested PCR did not correlate with the response to antifungal treatment.     

耐碳青霉烯鲍曼不动杆菌医院内播散和感染患者预后分析

目的:分析2007年1月至2008年3月北京大学第三医院临床分离的耐碳青霉烯鲍曼不动杆菌的同源性,调查其定植或感染的危险因素,评价该菌所致医疗相关性感染的抗菌药物治疗.方法:通过复习病历收集耐碳青霉烯鲍曼不动杆菌定植或感染患者的临床资料.菌株的药敏试验采用纸片法,通过脉冲场凝胶电泳分析菌株的同源性.结果:研究期间共分离到49株耐碳青霉烯鲍曼不动杆菌菌株,其脉冲场凝胶电泳分型为7型,共45株(91.8%)具有同源性.分离到菌株前患者最常见的暴露因素为住ICU、侵入性操作和低白蛋白血症,最常见的合并症是慢性阻塞性肺疾病(12例)和脑血管病(10例).在这49株菌中,定植者28株,导致感染者21株,感染患者的死亡率为38.1%.Logistic回归分析发现APACHEⅡ评分是导致死亡的独立危险因素(P=0.02,OR=1.7,95%CI1.1～2.5).抗菌药物联合治疗的成功率高于单药治疗(11/13例,84.6%vs.3/17例,17.6%),尤其是头孢哌酮/舒巴坦联合左氧氟沙星联合治疗.结论:我院自2007年出现了耐碳青霉烯鲍曼不动杆菌菌株的院内播散,导致播散的危险因素为住ICU、侵入性操作、低白蛋白血症、慢性阻塞性肺疾病和脑血管病,对耐碳青霉烯鲍曼不动杆菌感染,抗菌药物联合治疗可能优于单药治疗.     

Allergic fungal sinusitis: clinicopathological characteristics

Allergic fungal sinusitis is a comparatively new disease entity in paranasal sinus mycoses. It is not a very rare condition, but diagnosis is difficult to establish. Of 28 consecutive cases of allergic nasal polyposis during a 2-year period, 11 patients had allergic fungal sinusitis and the diagnosis was based on the presence of type I hypersensitivity, eosinophilic mucus without tissue invasion of fungi on histopathology and detection of septate hyphae on direct microscopy. On culture, Aspergillus flavus was isolated from nine patients and A. fumigatus and A. niger from one patient each. Among patients with allergic fungal sinusitis, five had asthma, four had proptosis, of whom two had impaired vision, and all 11 patients had nasal obstruction. Eight patients described a history of recurrence. All patients underwent surgical clearance of the diseased sinuses and were given post-operative topical steroids to prevent recurrence.     

Microbiology of sinusitis in patients undergoing bone marrow transplantation

As a result of increasing use of bone marrow transplantation and new cytotoxic chemotherapy, more patients have become susceptible to sinus disease caused by unusual organisms. Sinusitis caused by fungi and gram-negative bacteria can be difficult to treat, may lead to severe complications, and should be managed promptly in the bone marrow transplant patient. Here we present the results of 41 cultures of the paranasal sinuses obtained from 18 bone marrow transplant patients in whom sinusitis developed. The most common agents were gram-negative bacteria (56.7%), followed by gram-positive bacteria (26.7%) and fungi (16.6%). In 13 samples the cultures were negative. Nasal cultures were performed ipsilateral to the sinus drained in 28 cases. Concordance was obtained in only 5 (17.8%) samples. The antibiogram of the isolated agents from the maxillary sinuses in this series revealed that the most efficient antibiotics were those that covered gram-negative bacteria. Treatment was usually prolonged in these patients, and different antibiotics were necessary to clear infections from the sinuses. In conclusion, treating sinusitis in bone marrow transplant patients may be challenging. Considerations about the microbiology and antibiogram susceptibilities of this specific population should be kept in mind when dealing with such cases.     

The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-1993: results of population-based laboratory active surveillance

Population-based active laboratory surveillance for invasive mycotic infections was conducted during 1992 and 1993 in three California counties: Alameda, Contra Costa, and San Francisco (population, 2.94 million). The cumulative incidence of invasive mycotic infections was 178.3 per million per year. Invasive mycoses were most commonly caused by Candida (72.8 per million per year), Cryptococcus (65.5), Coccidioides (15.3), Aspergillus (12.4), and Histoplasma (7.1). The clinical significance of other, less common fungi was determined by detailed chart review. The cumulative incidence was determined for zygomycosis (1.7 per million per year), hyalohyphomycosis (1.2), and phaeohyphomycosis (1.0). The most common underlying conditions were human immunodeficiency virus infection (47.4%), nonhematologic malignancy (14.7%), diabetes mellitus (9.9%), and chronic lung disease (9.3%). This represents the first population-based epidemiological assessment of invasive mycoses in the United States.     

Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis

BACKGROUND: Few cases of allergic fungal sinusitis have been systematically evaluated to conclusively confirm working clinical, histopathologic, and serologic diagnostic criteria. OBJECTIVES: The objective of this study was to describe 67 consecutive cases of allergic fungal sinusitis, the largest number of cases yet published. METHODS: Cases from 1 practice over 8 years were evaluated with a consistent protocol, including skin testing, serum chemistries and serologies, and surgical specimen analysis. RESULTS: All patients were atopic (100 %) and had nasal polyposis (100%). They tended to be young (33.3+/-13.1 years, mean +/-SEM), immunocompetent (92 %; remaining 8 % with low quantitative immunoglobulin but normal function), have slight female preponderance (58%), have a history of hypertrophic rhinosinusitis (100%), report nasal cast production (75%), and have developed their disease in the southwestern United States. Bipolaris spicifera was the most prevalent fungus involved (67%). Total serum IgE (mean 668 IU/mL) and fungal-specific IgG were generally elevated, whereas fungal-specific precipitins and specific IgE were generally negative despite positive fungal-specific immediate hypersensitivity skin tests. CONCLUSIONS: Patients with allergic fungal sinusitis tend to have elevated total serum IgE and fungal-specific IgG at diagnosis but not fungal-specific IgE or precipitins. Histopathologic criteria for allergic fungal sinusitis diagnosis are discussed. The southwestern United States appears to be a "hot spot" for the disease, particularly caused by B spicifera.     

False-positive results in premature infants with the Platelia Aspergillus sandwich enzyme-linked immunosorbent assay

The sensitivity of a sandwich enzyme-linked immunosorbent assay (ELISA) for detecting Aspergillus galactomannan was tested using 783 serum samples obtained from 247 patients (1-15 sera per patient) with severe underlying diseases (haematological malignancies or intensive care unit stay). We selected 146 serum samples from 50 patients for retesting. Serum samples were frozen after routine testing at -18 degrees C until retesting. All patients charts were checked for signs of Aspergillus infection, such as pneumonia or sinusitis. Adult patients were divided into four groups: proven (5), probable (6), suspected (8) or unlikely (25) Aspergillus infection. The results of Platelia ELISA were 100% in proven, 33% in probable and 50% in suspected Aspergillus infection. Patients with unlikely infection had no positive results with Platelia ELISA. Group 5 consists of six paediatric patients with prolonged ICU stay and a birth weight of 400-1320 g. In five out of six infants we found positive results with Platelia ELISA. All positive results in this group of patients are considered as false positive (83.3%).     

Invasive pulmonary aspergillosis in AIDS: radiographic, CT, and pathologic findings

PURPOSE: To review the radiographic and computed tomographic (CT) manifestations of invasive pulmonary aspergillosis and to correlate the imaging and pathologic findings in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Chest radiographs, CT scans, and pathologic specimens were reviewed retrospectively in 10 AIDS patients with proved invasive pulmonary aspergillosis. RESULTS: The most common radiographic finding was the presence of thick-walled cavitary lesions. Less common findings included nodules, consolidation, and pleural effusion. CT depicted more nodules and cavities than did radiography. The predominant pathologic abnormalities consisted of tissue invasion and abscess formation and angioinvasion with or without infarction. All patients had infection with Aspergillus fumigatus as well as other pathogens, the most common being cytomegalovirus and Pseudomonas aeruginosa. CONCLUSION: Thick-walled cavitary lesions are the most common radiologic manifestation of invasive pulmonary aspergillosis in AIDS. The findings are more numerous and better defined on CT scans. The radiologic findings reflect a spectrum of pathologic abnormalities.     

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

BACKGROUND: 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% CI 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/microL(SD 191) and was 171/microL (105) for recurrent episodes. During acute Strep pneumoniae infection the CD4 cell count was reversibly suppressed (mean fall in sixteen episodes, 105/microL [123]). The neutrophil response to acute infection was blunted and was correlated with CD4 count (r=0.50, 95% CI 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.