Increased CD4 counts, pain and depression are correlates of lower sleep quality in treated HIV positive patients with low baseline CD4 counts.

Poor sleep quality leads to increased immune activation and immune activation leads to worse sleep quality. South African HIV positive patients typically have delayed start of treatment, which has been associated with CD4+ effector T cells being more spontaneously activated in chronically treated patients. This cross-sectional study investigated whether subjective sleep quality was associated with CD4+ T lymphocyte reconstitution in treated South African HIV+ patients. One hundred and thirty-nine treated HIV+ patients (109 F, age average (SD) = 43 (9)) were recruited from Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, South Africa. Participants completed questionnaires evaluating their subjective sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth sleepiness scale), pain, and depression severity (Beck Depression Inventory). Univariate and multivariate analyses were run to determine the correlates of sleep quality in this population. Patients had been on antiretroviral treatment for about 4 years and had increased their CD4 counts from a median at baseline of 82 to 467 cells/µL. They had overall poor sleep quality (average (SD) PSQI = 7.7 (±5), 61% reporting PSQI > 5, a marker of lower sleep quality), 41% had clinical depression (average (SD) BDI = 17 (±12)) and 55% reported pain. In two separate multivariate analyses, both the overall CD4 count increase from baseline (p = 0.0006) and higher current CD4 counts (p = 0.0007) were associated with worse sleep quality, when adjusting for depression severity (p < 0.001), daytime sleepiness (p = 0.01) and the presence of pain (p < 0.01). In this cohort of treated South African HIV positive patients, poor sleep quality was associated with higher current CD4 counts, when adjusting for depression severity, daytime sleepiness and pain. Further studies should investigate the temporal relationship between HIV-related poor sleep quality and underlying immune activation.

Evaluation of screening and treatment of cryptococcal antigenaemia among HIV-infected persons in Soweto, South Africa.

OBJECTIVES: We retrospectively evaluated clinic-based screening to determine the prevalence of cryptococcal antigenaemia and management and outcome of patients with antigenaemia. METHODS: Cryptococcal antigen (CrAg) screening of HIV-infected adults who attended the HIV clinic at Chris Hani Baragwanath Hospital was conducted over 19 months. Data collected from CrAg-positive patients included CD4 T-lymphocyte count at screening, prior or subsequent cryptococcal meningitis (CM), antifungal and antiretroviral treatment and outcome after at least 8 months. RESULTS: Of 1460 patients with no prior CM, 30 (2.1%) had a positive CrAg test. The prevalence of antigenaemia among patients with a CD4 count < 100 cells/µl and no prior CM was 2.8% (20 of 708). Of 29 evaluable CrAg-positive patients with no prior CM, 14 (48%) did not return for post-screening follow-up. Of these 14, five developed CM and one (7%) was known to be alive at follow-up. Of 15 patients who returned for follow-up, two already had evidence of nonmeningeal cryptococcosis. Overall, 11 received fluconazole, one did not and fluconazole treatment was unknown for three. Among these 15, one developed CM and 10 (67%) were known to be alive at follow-up. Overall, 18 (62%) of 29 CrAg-positive patients died or were lost to follow-up. Seven (0.5%) of 1430 CrAg-negative patients developed CM a median of 83 days post-screening (range 34 to 219 days). CONCLUSIONS: Loss to follow-up is the major operational issue relevant to scale-up of screen-and-treat. Patient outcomes may be improved by rapid access to CrAg results and focus on linkage to and retention in HIV care.

Use of a rapid test of pneumococcal colonization density to diagnose pneumococcal pneumonia.

BACKGROUND: There is major need for a more sensitive assay for the diagnosis of pneumococcal community-acquired pneumonia (CAP). We hypothesized that pneumococcal nasopharyngeal (NP) proliferation may lead to microaspiration followed by pneumonia. We therefore tested a quantitative lytA real-time polymerase chain reaction (rtPCR) on NP swab samples from patients with pneumonia and controls. METHODS: In the absence of a sensitive reference standard, a composite diagnostic standard for pneumococcal pneumonia was considered positive in South African human immunodeficiency virus (HIV)-infected adults hospitalized with radiographically confirmed CAP, if blood culture, induced good-quality sputum culture, Gram stain, or urinary Binax demonstrated pneumococci. Results of quantitative lytA rtPCR in NP swab samples were compared with quantitative colony counts in patients with CAP and 300 HIV-infected asymptomatic controls. RESULTS: Pneumococci were the leading pathogen identified in 76 of 280 patients with CAP (27.1%) using the composite diagnostic standard. NP colonization density measured by lytA rtPCR correlated with quantitative cultures (r = 0.67; P < .001). The mean lytA rtPCR copy number in patients with pneumococcal pneumonia was 6.0 log(10) copies/mL, compared with patients with CAP outside the composite standard (2.7 log(10) copies/mL; P < .001) and asymptomatic controls (0.8 log(10) copies/mL; P < .001). A lytA rtPCR density ≥8000 copies/mL had a sensitivity of 82.2% and a specificity of 92.0% for distinguishing pneumococcal CAP from asymptomatic colonization. The proportion of CAP cases attributable to pneumococcus increased from 27.1% to 52.5% using that cutoff. CONCLUSIONS: A rapid molecular assay of NP pneumococcal density performed on an easily available specimen may significantly increase pneumococcal pneumonia diagnoses in adults.

Clinical aspects and outcomes of patients with malaria at Chris Hani Baragwanath Academic Hospital,Johannesburg, South Africa.

BACKGROUND: South Africa (SA) is currently experiencing a significant increase in malaria cases despite having shifted focus from malaria control towards malaria elimination. The clinical features of malaria are nonspecific, but their relative frequency on presentation are not well described. HIV and malaria are both independently associated with high mortality in sub-Saharan Africa. There are important interactions between HIV and malaria. OBJECTIVES: To describe the population characteristics of patients with malaria at Chris Hani Baragwanath Academic Hospital, Johannesburg, SA, clinical and biochemical features of severity, the proportion of patients with HIV infection, management and outcomes. METHODS: A prospective observational study was conducted whereby patients with a confirmed laboratory diagnosis of malaria were identified, approached and consented for study inclusion over the time period January 2017 - January 2018. Clinical and biochemical data were collected at the time of consent and later analysed. RESULTS: The mean (standard deviation) age was 35.7 (12.98) years, and 72 (70.6%) of the 102 patients were male. Peak admissions for malaria were in January, with 58 patients (56.9%) admitted during January 2017 and 2018. All malaria cases were imported, with 74.5% associated with travel to Mozambique. The majority of the patients (61.8%) were expatriates living in SA. The most common presenting symptoms were chills (95.1%), weakness (94.1%), fever (91.2%), headache (90.2%) and lethargy (88.2%). The most common clinical signs were dehydration (31.4%), prostration (19.6%) and jaundice (13.7%). Among the 40 patients (39.2%) who had severe malaria, prostration was the most common feature of severity (19.6%), 8 (7.8%) were admitted to an intensive care unit, and 6 (5.9%) required haemodialysis. The median (interquartile range) duration of hospital stay was 5 (3 -6) (range 2 - 35) days. HIV status was known in 83 patients (81.4%), of whom 32 (38.6%) were HIV-positive. Malaria prophylaxis had been taken by only 8 patients. The all-cause mortality rate was 4.9%, and mortality attributable to malaria 3.9%. CONCLUSIONS: There was a high proportion of complicated malaria cases, particularly in January. The majority of patients were young expatriate males with a history of travel to southern Mozambique or Limpopo Province, with very few taking malaria prophylaxis. Most clinical signs and symptoms were constitutional and nonspecific. A large number of patients were found to be HIV-positive, and most were newly diagnosed. Mortality was high, at around five times the national average, and may have been an underestimate.

Immune reconstitution inflammatory syndrome involving the skin.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) occurs in 10-25% of unselected patients starting highly active antiretroviral therapy (HAART). About 52-78% of these cases involve cutaneous features. AIM: To describe the prevalence and incidence of new dermatological conditions within 6 months of patients starting HAART, and to specify the clinical and immunological features and time of onset in patients responding to HAART. METHODS: A retrospective cohort analysis was performed of 59 treatment-naive patients started on HAART and followed up for 6 months by a clinician trained in dermatology. Medical records were reviewed for new dermatological conditions diagnosed clinically. RESULTS: In all, 30 patients (50.8%) developed 45 new skin conditions at a median of 8 weeks (range 3-24 weeks) after starting HAART. The incidence rate was 104.5 cases per 100 patient-years. Diagnoses included seborrhoeic dermatitis (nine patients), anogenital herpes (seven patients), acne, tinea and folliculitis (six patients each), Kaposi's sarcoma, herpes zoster, genital warts and eczema (two patients each), and molluscum contagiosum, planar warts and pityriasis versicolor (one patient each). Significantly more women (23/38; 60.5%) than men (7/21; 33.3%) (P < 0.05) developed new skin lesions after starting HAART. Baseline median CD4 counts in those with and without IRIS were 60/microL and 62/microL, respectively, and in both groups, the counts increased to > 90/microL by week 12. Baseline median viral load was > 100,000 copies/mL and was < or = 32 copies/mL by week 12. In both groups, the majority of patients were in World Health Organization stages 3 and 4. CONCLUSIONS: New skin lesions were very common in this cohort, with the majority being women and patients with very low baseline CD4 counts.

What causes symptoms suggestive of tuberculosis in HIV-positive people with negative initial investigations?

OBJECTIVE: To identify the causes of symptoms suggestive of tuberculosis (TB) among people living with the human immunodeficiency virus (PLHIV) in South Africa. METHODS: A consecutive sample of HIV clinic attendees with symptoms suggestive of TB (1 of cough, weight loss, fever or night sweats) at enrolment and at 3 months, and negative initial TB investigations, were systematically evaluated with standard protocols and diagnoses assigned using standard criteria. TB was 'confirmed' if Mycobacterium tuberculosis was identified within 6 months of enrolment, and 'clinical' if treatment started without microbiological confirmation. RESULTS: Among 103 participants, 50/103 were pre-antiretroviral therapy (ART) and 53/103 were on ART; respectively 68% vs. 79% were female; the median age was 35 vs. 45 years; the median CD4 count was 311 vs. 508 cells/mm³. Seventy-two (70%) had 5% measured weight loss and 50 (49%) had cough. The most common final diagnoses were weight loss due to severe food insecurity (n = 20, 19%), TB (n = 14, 14%: confirmed n = 7; clinical n = 7), other respiratory tract infection (n = 14, 14%) and post-TB lung disease (n = 9, 9%). The basis for TB diagnosis was imaging (n = 7), bacteriological confirmation from sputum (n = 4), histology, lumbar puncture and other (n = 1 each). CONCLUSION: PLHIV with persistent TB symptoms require further evaluation for TB using all available modalities, and for food insecurity in those with weight loss.

Treatment outcomes of pre- and extensively drug-resistant tuberculosis in Johannesburg, South Africa.

BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB) has a poor treatment success rate and high mortality. Multidrug-resistant TB (MDR-TB) has worse outcomes when there is added resistance to second-line injectable drugs (pre-XDR-TBSLID) or fluoroquinolones (pre-XDR-TBFQ). OBJECTIVES: Treatment outcomes in patients with pre-XDR-TB and XDR-TB in a high HIV prevalence area were compared. METHODS: A retrospective medical record review was conducted of patients with pulmonary pre-XDR-TB and XDR-TB managed from 2008 to 2010 at Sizwe Tropical Disease Hospital, Johannesburg, South Africa. Standardised MDR-TB treatment was instituted and was subsequently individualised when further second-line susceptibility results became available. RESULTS: Of 86 patients studied, 95% were sputum smear-positive at baseline, 73% had sputum culture conversion, and 65% were human immunodeficiency virus (HIV) infected, with a median CD4 count of 201 cells/mm³. Of 53 patients with XDR-TB, 26 with pre-XDR-TBFQ and 7 with pre-XDR-TBSLID, respectively 13%, 12% and 29% were cured, 21%, 23% and 57% had a favourable outcome, and 26%, 23% and 14% died. Clofazimine (P < 0.001) and linezolid (P = 0.044) impacted on favourable outcomes. CONCLUSION: Patients with pre-XDR-TBFQ did not have better outcomes than those with XDR-TB. In countries with standardised regimens for resistant TB, patients with pre-XDR-TBFQ may need to receive XDR-TB treatment.

A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa.

BACKGROUND: Lactic acidosis and symptomatic hyperlactatemia may complicate nucleoside reverse-transcriptase inhibitor use. Females may be at increased risk for such complications. Our study evaluated the incidence of lactic acidosis and symptomatic hyperlactatemia by sex, analyzed clinical features, and described the safety of reintroducing highly active antiretroviral therapy (HAART) with zidovudine replacing stavudine. METHODS: A retrospective cohort analysis was performed for 1735 adults (63% of whom were female) who initiated HAART from April 2004 through August 2005 in Soweto, South Africa, with follow-up until February 2006. Patients with lactate levels > or =4.5 mmol/L and no potential cause of elevated lactic acidosis other than receipt of HAART were included in the study. RESULTS: A total of 23 patients (22 of whom were female) experienced lactic acidosis. The overall incidence was 10.6 cases per 1000 patient-years; the incidence was 16.1 cases per 1000 patient-years in female patients and 1.2 cases per 1000 patient-years in male patients. Seven (30.4%) of the patients died. Eight (34.8%) of the patients were obese (body mass index [calculated as weight in kilograms divided by the square of height in meters], >30) at HAART initiation. Forty-four patients (37 of whom were female) had symptomatic hyperlactatemia. The overall incidence was 20.2 cases per 1000 patient-years, with an incidence of 27.0 cases per 1000 patient-years in female patients and 8.7 cases per 1000 patient-years in male patients. None of the patients died. Nine (20.4%) of the patients were obese at HAART initiation. Sixty-six of 67 patients were receiving stavudine, and 5 patients were receiving didanosine. Among 56 patients who restarted HAART with zidovudine for a cumulative nucleoside reverse-transcriptase inhibitor reexposure of 44.6 patient-years--including 41 patients who received treatment for > or =9 months--there were no relapses. CONCLUSION: Women in Soweto, South Africa, have a higher frequency of symptomatic hyperlactatemia and lactic acidosis than has been reported for patients in other study groups. In cases associated with stavudine use, restarting HAART with zidovudine seemed to be safe and effective for patients with limited nucleoside reverse-transcriptase inhibitor alternatives.

Prevalence and clinical manifestations of disseminated Mycobacterium avium complex infection in South Africans with acquired immunodeficiency syndrome.

In a sample of 100 hospitalized human immunodeficiency virus-seropositive black South African patients with CD4 cell counts of <100 cells/mm(3), the point prevalence of disseminated Mycobacterium avium complex infection was 10%, in contrast with other African studies that report that the infection is uncommon. The point prevalence of Mycobacterium tuberculosis was 54%. The clinical and laboratory features of these patients were largely unhelpful in detecting M. avium complex; the BACTEC blood culture (Becton Dickinson) was the only reliable method.

Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa.

Little is known about achievable levels of antiretroviral treatment (ART) adherence in resource-limited settings. We conducted a cross-sectional study of adherence among patients at Chris Hani Baragwanath Hospital's Adult HIV Clinic in Soweto, South Africa. Adherence was assessed using a 1-month, self-report questionnaire and was calculated as a ratio of doses taken to doses prescribed. The 66 patients studied had a mean age of 36.1 years, a median duration of ART use of 18 months, and an overall baseline median CD4(+) cell count of 200/mm(3) (IQR: 114-364). The adherence reported by these patients for the previous month was >95% for 58 patients (88%), 90-95% for 6 (9%) and, < 90% for 2 (3%). The main reasons given for missing doses were being away from home (30%), difficulty with the dosing schedules (23%), and running out of pills (12%). Adherence decreased considerably with fear of being stigmatized by the sexual partner (OR = 0.13 95%, CI 0.02-0.70). Plasma HIV RNA levels were <400 copies/ml in the majority of patients (73% of those with adherence >95% and 88% of patients with < or =95% adherence) and the overall median CD4(+) cell count rose to 324/mm(3) (IQR: 193-510). High adherence and viral suppression are achievable for a significant proportion of HIV-infected patients taking ART in a resource-limited area such as Soweto, South Africa. Strategies to maximize adherence in this setting should emphasize ready access to affordable and simple ART regimens, as well as HIV education programs to help increase awareness and decrease disease stigmatization.

Pneumococcal bacteremia during a decade in children in Soweto, South Africa.

OBJECTIVES: To monitor for a decade the incidence and the clinical and microbiologic characteristics of pneumococcal bacteremia in children in Soweto and to assess the influence of HIV infection on any changes. METHODS: Case records of children with pneumococcal bacteremia at Chris Hani Baragwanath Hospital from July, 1986, to June, 1987 (1986/ 1987), and from July, 1996, to June, 1997 (1996/ 1997), were retrospectively reviewed. RESULTS: There were 194 episodes, 62 in 19861 1987 and 132 in 1996/1997. The minimum annual incidence for children younger than 5 years of age increased from 61 per 100000 (179 per 100000 for those <12 months old) in 1986/1987 to 130 per 100000 (349 per 100000 for those <12 months old) in 1996/1997. Sixty-seven (60%) of 111 patients tested in 1996/1997 were HIV-seropositive; none were tested in 1986/1987. The HIV-infected compared with HIV-noninfected were more likely to be malnourished (61% vs. 36%, P = 0.02), less likely to have other underlying disease (12% vs. 50%, P = 0.00001) and more frequently used antibiotics recently (69% vs. 43%, P = 0.008). Penicillin-nonsusceptible isolates were found in 22 (35%) patients in 1986/1987 and 52 (39%) in 1996/1997. There was no significant change in antimicrobial susceptibility during the decade or by HIV serostatus. CONCLUSIONS: Children in Soweto had a high incidence of pneumococcal bacteremia which doubled during the decade mainly as a result of the impact of the HIV epidemic. There has been no significant change in antimicrobial susceptibility for the decade.

The spectrum of meningitis in a population with high prevalence of HIV disease.

We studied the spectrum of meningitis and impact of HIV infection retrospectively (8 months) and prospectively (4 months) in 284 adult patients with meningitis hospitalized in Soweto, South Africa. Tuberculous meningitis (TBM) was the most common cause of meningitis (25.4%) followed by acute bacterial meningitis (ABM; 22.5%), acute viral meningitis (14.1%) and cryptococcal meningitis (13%). The in-hospital mortality was > 40% in TBM, ABM, cryptococcal meningitis, the neurosurgery and the parameningeal/parenchymal groups. At least 37.3% of all patients were HIV-seropositive (only 67.9% of patients were tested). In at least 27% of the study group the meningitis was an AIDS-defining illness (TBM, cryptococcal meningitis). Only 56.2% of patients with ABM had positive cultures (CSF or blood), of which Streptococcus pneumoniae was by far the most frequently found organism (35.8%). The spectrum of meningitis in HIV-affected communities in Africa can be expected to change towards a predominance of TBM and cryptococcal meningitis.

PIP: To evaluate the spectrum of meningitis and its impact on human immunodeficiency virus (HIV) infection, 284 adults hospitalized with meningitis in Soweto, South Africa, were studied. Tuberculosis meningitis (TBM) was the most common cause of meningitis (25.4%), followed by acute bacterial meningitis (ABM; 22.5%), acute viral meningitis (AVM; 14.1%), and cryptococcal meningitis (13%). The in-hospital mortality rate exceeded 40% in TBM, ABM, cryptococcal meningitis, the neurosurgery group, and the parameningeal/parenchymal group. Only 56.2% of patients with ABM had positive blood or cerebrospinal fluid cultures. 37.3% of the 193 patients tested for HIV were seropositive. All patients with cryptococcal meningitis and at least 54% of those with TBM were HIV-infected. Moreover, at least 27% of the study population presented with an acquired immunodeficiency syndrome (AIDS)-defining illness such as cryptococcal meningitis or TBM. The high mortality rates observed among meningitis patients in this series reflect immunosuppression associated with HIV infection or malnutrition, late presentation at a hospital, lack of access to medical care, and failure on the part of some primary care providers to consider a diagnosis of meningitis. Underlying HIV infection in increasing numbers of meningitis patients can be expected to produce a need for more hospital beds and increased medical expenditures in South Africa.

Tuberculous meningitis in South African urban adults.

We retrospectively reviewed 56 adults with culture-proven tuberculous meningitis (TBM), investigating clinical signs, cerebrospinal fluid (CSF) findings and outcome. There were 50 patients, aged 18-59 years, 39 with and 11 without human immunodeficiency virus (HIV) infection. Six were aged 60 years or older. Neurological signs of TBM in 18-59-year-olds were unaffected by HIV serostatus while, compared to those > or = 60 years of age, there were more patients with meningism (86.0% vs. 33.3%; p = 0.011) and fewer with seizures (12.0% vs. 50.0%; p = 0.046). The HIV-infected 18-59-year-olds had significantly more extrameningeal tuberculosis compared to the non-HIV-infected (76.9% vs. 9.1%; p = 0.0001) and 23.1% had 'breakthrough' TBM. CSF analysis revealed 12 patients (21.4%) with acellular fluid (more common in those > or = 60 years of age, p = 0.016), of whom three had completely normal CSF. A neutrophil predominance was found in 22 patients (39.3%). Only three patients (5.4%) had a positive CSF smear for acid-fast bacilli. In-hospital mortality occurred in 39 patients (69.1%), was similar in all study groups, and was not related to neurological stage. The diagnosis of TBM can be masked by lack of meningism in the elderly and by atypical CSF findings.

The utility of bone-marrow examination in HIV-infected adults in South Africa.

We retrospectively reviewed a consecutive case series of 257 adults with HIV infection who had undergone a bone-marrow examination with trephine bone biopsy, to assess the diagnostic usefulness of bone-marrow examination and evaluate possible predictors of a diagnostic examination. Bone-marrow examination was positive in 97 (38%) patients and gave a unique diagnosis in 61 (24%). The diseases were tuberculosis (83 patients), Mycobacterium avium complex infection and cryptococcosis (four patients each), and haematological malignancies (eight patients). The yield of the examination was significantly increased, by univariate analysis, in patients with wasting, oral thrush, leukopenia, CD4< or =100/mm3, and granuloma formation on histopathology. Granulomata were present in 113 (44%) patients, of whom 28 (25%) had no specific cause identified. Granulomata occurred in 22 (25%) of 89 patients with CD4 >100/mm3 compared to 36 (51%) of 70 patients with CD4< or =100/mm3 (OR 0.3; 95%CI 0.15-0.62). Of 48 patients with CD4 <50/mm3, 25 had granulomata, including 15 with caseation necrosis. The yield of bone-marrow examination was considerable in our setting. Expanding access to modern blood culture techniques for mycobacteria to primary care level could limit the number of bone-marrow examinations required.

The bacteriology of pulmonary tuberculosis in a population with high human immunodeficiency virus seroprevalence.

SETTING: A public sector urban university hospital in Soweto, South Africa. OBJECTIVE: To describe the utility of sputum smear microscopy and the prevalence of Mycobacterium tuberculosis resistance to antituberculosis drugs according to human immunodeficiency virus (HIV) serostatus in adults. DESIGN: A retrospective descriptive study of consecutive cases using a record review. RESULTS: We studied 412 adults with culture-proven pulmonary tuberculosis, of whom 185 (44.9%) were HIV-seropositive and had a significantly lower sputum smear positivity than HIV seronegatives (68% versus 79%, P < 0.05). Smear positivity was significantly higher in HIV-infected patients with CD4 counts < or = 50/mm3 compared to those with CD4 counts of 201-300/mm3 (P < 0.05). In patients with and those without a history of previous treatment for tuberculosis, resistance to one or more antituberculosis drugs was found in 32.2% and 13.6% of cases, respectively, while resistance to both isoniazid and rifampicin (multidrug-resistant tuberculosis [MDR]) was found in 15.3% and 4.5% of patients, respectively. There was no significant difference in resistance between HIV-positive and seronegative patients. CONCLUSION: A strong tuberculosis control programme and good surveillance will be required to prevent the further spread of MDR tuberculosis. Surveys such as these are useful for monitoring control programmes.

Sisters of women with premature ovarian failure may not be ideal ovum donors.

OBJECTIVES: To determine whether the sisters of women with premature ovarian failure (POF) showed a response to gonadotropin stimulation comparable to that of anonymous ovum donors. DESIGN: Historical cohort study. SETTING: Records of 228 consecutive ovum recipients in an academic assisted reproductive technology program. PATIENT(S): Criteria for inclusion were oocyte recipients age < or = 40 years, FSH > 18 mIU/mL (conversion factor to SI unit, 1.00), and/or failure to respond appropriately to controlled ovarian hyperstimulation (COH). Seventy-nine recipients were classified on the basis of whether they received oocytes from anonymous donors (group I, n = 66) or sister donors (group II, n = 13). MAIN OUTCOME MEASURE(S): Controlled ovarian hyperstimulation response, pregnancy rates (PRs), and implantation rates. RESULT(S): The ages of the donors to groups I and II were comparable (31.1 +/- 16.7 versus 29.8 +/- 7.2 years), but those in group II exhibited a higher baseline FSH level (12.8 +/- 2.1 versus 8.6 +/- 5.8 mIU/mL). Group II versus I had a relative risk of 5.1 for cancellation (4 of 13 [30.8%] versus 4 of 66 [6.1%], respectively). In completed cycles of groups I and II, respectively, there was no difference in serum E2 on the day of hCG administration (2,356 +/- 826 versus 1,847 +/- 843 pg/mL; conversion factor to SI unit, 3,671), number of oocytes retrieved (25 +/- 14 versus 22 +/- 13), number of embryos transferred (4.4 +/- 2.1 versus 4.0 +/- 1.0), spontaneous abortion rate (22.7% versus 25.0%), PR (35.5% versus 36.4%), and implantation rate (16.2% versus 16.4%). CONCLUSION(S): There is an increased cancellation rate and, consequently, an overall trend toward decreased ovarian response to gonadotropin stimulation in the sisters of patients with POF. Despite these factors, the implantation rates and PRs of embryos derived from patients reaching retrieval were similar to those from anonymous donors. We recommend counseling women with POF that their sisters may not be ideal ovum donors.

Age-related decline in female fertility is not due to diminished capacity of the uterus to sustain embryo implantation.

OBJECTIVE: To evaluate the contribution of the uterus to age-related reproductive failure in women. PATIENTS: Thirty-eight ovum donors (30.2 +/- 4.9 years [mean +/- SD]) donating oocytes throughout 102 ovum donations. Fifty-one cycles were documented in "younger" recipients (35.8 +/- 3.1 years) and 51 in "older" recipients (44.0 +/- 3.1 years). The study was prospectively designed; same-cohort oocytes obtained from one young donor during a specific cycle were evenly distributed between "young" and "old" ovum recipients. Use of oocytes from a single source and a unique ovulatory cohort provides strict control over oocyte quality. Uterine age is varied by design, according to the age of the recipient at the time of ET. The role of the aging uterus in the decline of female fertility can be thus isolated and scrutinized. RESULTS: No significant (NS) difference in the number of ova received (7.9 +/- 3.4 versus 7.0 +/- 3.5), ova fertilized (4.4 +/- 1.5 versus 4.5 +/- 2.3), or embryos transferred (4.1 +/- 1.5 versus 4.1 +/- 1.6) was observed between the < 40 and > or = 40 recipient age groups. A total of 23 pregnancies occurred among the 102 ETs (22.6%). Eleven clinical pregnancies (21.6%) resulting in 10 deliveries were observed in the < 40 recipient age group, and 12 clinical pregnancies (23.5%) leading to 10 deliveries occurred in the > or = 40 recipient age group (NS). The pregnancy loss rates were 9.1% (1 of 11) and 16.7% (2 of 12) for the two recipient age groups, respectively, (NS). CONCLUSION: The capacity to conceive and to gestate a conception to term when oocyte quality is controlled appears to be independent of uterine aging through the fifth decade of life.

Nocardial infection as a complication of HIV in South Africa.

OBJECTIVES: To assess the occurrence, clinical and microbiological features of nocardial infections complicating HIV in Soweto, South Africa. METHODS: A prospective study was carried out over a 2-year period. Patients were identified after isolation of Nocardia spp. from a clinical specimen. Clinical details were recorded. The nocardial isolates were identified to species level and susceptibility tests performed. RESULTS: Ten patients were identified as having nocardial disease complicating HIV. Clinical presentations were pulmonary (five patients), pulmonary and cerebral (one patient), cerebral (one patient) and skin and soft tissue infection of the lower limb (three patients). Three infections were fatal. The isolates were Nocardia asteroides (seven patients), N. farcinica (two patients) and Nocardia spp. (one). Isolates of N. farcinica demonstrated opacification of Middlebrook agar. All isolates were sensitive to amikacin and minocycline. Most nocardial isolates were susceptible to cefotaxime, imipenem and coamoxiclav. In vitro resistance to cotrimoxazole was present in five. CONCLUSIONS: Nocardial infection occurs as a complication of HIV infection in the Republic of South Africa. Pulmonary cases may be difficult to distinguish from tuberculosis. Nocardia asteroides is the most common species isolated. Nocardia farcinica has resistance to multiple antibacterial agents and demonstrates opacification of Middlebrook agar, a useful screening test for this species. Agents with good in vitro antinocardial activity were amikacin, minocycline, cefotaxime, imipenem and coamoxiclav. There was a high level of resistance in vitro to cotrimoxazole.

Tick bite fever in black South Africans--a rare disease?

Tick bite fever (Rickettsia conorii) is a disease which occurs commonly in South Africa. Clinical illness in the black African patient is however rare, despite high seroprevalence rates of antibodies against R. conorii reported from other areas of Southern Africa. We present two case reports of clinically apparent tick bite fever occurring in black South Africans, the first to be documented in sub-Saharan Africa, and examine possible explanations for the marked discrepancy between clinical illness and seroprevalence rates.

Bone marrow cryptococcal infection in the acquired immunodeficiency syndrome.

OBJECTIVES: To describe the bone marrow lesions in eight cases of Cryptococcus neoformans infection involving the bone marrow in HIV-infected patients. METHODS: Archival bone marrow biopsies from patients with HIV-related cryptococcosis of the bone marrow were retrospectively reviewed. Cryptocococcal organisms were identified on haematoxylin- and eosin-stained slides and confirmed using mucicarmine staining. RESULTS: Yeast cells stimulated a granulomatous response in all cases despite immunosuppression. The number of cryptococcal organisms appeared to be inversely proportional to the adequacy of the granulomatous response. All patients had a cytopenia. CONCLUSIONS: The ability to mount a tissue response in order to localize organisms is retained in patients with AIDS. Infection of the bone marrow with cryptococci may act in synergy with HIV to cause cytopenia.