Septicaemia in a population-based HIV clinical cohort in rural Uganda, 1996-2007: incidence, aetiology, antimicrobial drug resistance and impact of antiretroviral therapy.

OBJECTIVES: To describe the incidence and aetiology of septicaemia, and antimicrobial drug resistance in HIV-infected and uninfected individuals, and the impact of antiretroviral therapy (ART) on septicaemia. METHODS: Between 1996 and 2007, we followed up a rural population-based cohort of HIV-infected and uninfected participants. The aetiology and incidence of septicaemia, and antimicrobial drug resistances were determined. ART became available in 2004, and its impact on the incidence of septicaemia was examined. RESULTS: The overall septicaemia incidence (per 1000 pyrs) was 32.4 (95% CI 26.2-40.6) but was only 2.6 (95% CI 1.3-6.2) in HIV-negative patients and 67.1 (95% CI 53.4-85.4) in HIV-positive patients not on ART. Among those on ART, the overall incidence was 71.5 (95% CI 47.1-114.3), although it was 121.4 (95%CI 77.9-200.4) in the first year on ART and 37.4 (95%CI 18.9-85.2) in the subsequent period. Septicaemia incidence was significantly associated with lower CD4 counts. The commonest isolates were Streptococcus pneumoniae (SPN, n = 68) and Non-typhi salmonellae (NTS, n = 42). Most SPN isolates were susceptible to ceftriaxone and erythromycin, while resistance to cotrimoxazole and penicillin was common. All NTS isolates were susceptible to ciprofloxacin, but resistance to cotrimoxazole and chloramphenicol was common. CONCLUSIONS: Septicaemia incidence was higher in HIV-infected than in HIV-uninfected participants, and it remained high for some time among those who started ART. Starting ART earlier at higher CD4 counts is likely to lead to lower septicaemia incidence. Both SPN and NTS, the commonest isolates, were resistant to most commonly available antimicrobials. Blood culture laboratory surveillance systems to monitor antibiotic susceptibility and inform treatment guidelines are needed in Africa.

Tat-specific binding IgG and disease progression in HIV type 1-infected Ugandans.

There are data to suggest that both the humoral and cellular immune responses directed against Tat are beneficial in delaying HIV disease progression. We examined the association between the occurrence of Tat-specific binding antibodies (Abs) and different parameters of HIV-1 disease progression. We generated eight Tat proteins, derived from HIV-1 subtypes A, B, C, and D, and circulating recombinant form CRF01_AE. These proteins were used to screen for Tat-specific binding Abs by an ELISA. Using five Tat proteins, we investigated whether the occurrence of Tat-specific Abs within 2 years after seroconversion for the majority, affected disease progression over time among 126 participants using survival analysis and rate of CD4 decline. Of these, 52 participants with a sample at 1.5 and 4.5 years after seroconversion were further examined to study the effect of Tat-specific Ab loss or maintenance on disease progression. Finally, using all the eight Tat proteins, we also investigated whether specific Abs to these Tat proteins among 48 participants, grouped as rapid progressors (RP, n = 26) and long-term survivors (LTS, n = 22) according to their CD4 decline over time, affected disease progression. Survival analysis did not reveal any evidence of protection from progression by Tat-specific Abs. Comparison of rate of CD4 declines between individuals with and without Abs to any Tat protein showed only a small and borderline significant advantage of having Tat-specific Abs (p = 0.043). There was no correlation between either loss or maintenance of Tat-specific Abs and disease progression. Comparison of LTS with RP showed no evidence that Tat-specific Abs slows participants' disease progression. This study showed no evidence of a protective effect of having Tat-specific Abs among these Ugandan subjects.

Association between active GB virus-C (hepatitis G) infection and HIV-1 disease in Uganda.

Although not linked to a disease, GB virus-C viraemia has been associated with an improved prognosis in HIV-1-co-infected individuals. Most studies have been conducted on men (men who have sex with men or injection drug users) infected with HIV-1 subtype B, whereas here we report on both male and female subjects from rural Uganda, predominantly infected via the heterosexual route with HIV-1 subtypes A and D. In a longitudinal study of 272 participants, 47 were GBV-C positive and 181 negative, as determined by reverse transcription-polymerase chain reaction, in both of two plasma samples taken a median of 5.0 years apart. The remainder either acquired (25) or cleared (19) infection. Multilevel regression analyses and Cox survival analyses revealed that participants chronically infected with GBV-C had a slower decline in CD4(+) T cells (P<0.001) and increased survival time (P=0.041) compared with GBV-C RNA-negative, HIV-positive adults. We show that the association between active GBV-C co-infection and improved survival of HIV-1-infected adults is not restricted to HIV subtype B, but is also observed in both males and females infected with HIV subtypes A and D.

Aetiology of sexually transmitted infections and response to syndromic treatment in southwest Uganda.

OBJECTIVE: To determine the aetiology of genital ulcers and discharges in rural south western Uganda and to assess response to syndromic treatment. METHOD: A longitudinal, prospective study using laboratory testing and questionnaires to evaluate 561 adult men and women presenting with clinically verified genital ulcers, urethral, or vaginal discharge at a general outpatient clinic and two health centres between December 1999 and July 2001. RESULTS: One third of patients had genital ulcers and two thirds discharges. There was good response to treatment in 461/508 patients (90.7%). Herpes simplex virus type 2 was found in 95/217 (43.8%) genital ulcers. In 24.1% of ulcer cases there was also a genital discharge. HIV seropositivity was high in ulcer cases (63.2%), with significantly more HSV2 and secondary bacterial infection than in seronegative cases. Neisseria gonorrhoeae was found in 135/204 (66.2%) male genital discharges. Female genital discharges were mostly associated with bacterial vaginosis (36.1%), Trichomonas vaginalis (18.9%), and candidiasis (18.6%). CONCLUSIONS: The aetiological pattern of STI syndromes reported will help inform revision of national STI guidelines. The importance of herpes simplex virus type 2, the variation in causes of genital ulcers according to HIV serostatus, the high frequency of multiple infections and secondary bacterial contamination of genital ulcers are notable. These results help explain the lack of effect of an STI intervention on HIV incidence in a recent trial in this area.

Perinatal mortality attributable to complications of childbirth in Matlab, Bangladesh.

Very few population-based studies of perinatal mortality in developing countries have examined the role of intrapartum risk factors. In the present study, the proportion of perinatal deaths that are attributable to complications during childbirth in Matlab, Bangladesh, was assessed using community-based data from a home-based programme led by professional midwives between 1987 and 1993. Complications during labour and delivery--such as prolonged or obstructed labour, abnormal fetal position, and hypertensive diseases of pregnancy--increased the risk of perinatal mortality fivefold and accounted for 30% of perinatal deaths. Premature labour, which occurred in 20% of pregnancies, accounted for 27% of perinatal mortality. Better care by qualified staff during delivery and improved care of newborns should substantially reduce perinatal mortality in this study population.

Efficacy of an unsupervised ambulatory treatment regimen for smear-negative pulmonary tuberculosis and tuberculous pleural effusion in Malawi.

SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To evaluate treatment outcome of unsupervised ambulatory treatment (2R3H3Z3/2TH[EH]/4H) in Blantyre and 'standard' treatment (1STH[SEH]/11TH[EH]) in Zomba in human immunodeficiency virus (HIV) seropositive and seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB. DESIGN: All patients with smear-negative and pleural TB registered between 1 April and 31 December 1995 were assessed for enrolment in the study. Study patients were followed up and 12-month treatment outcomes were recorded. RESULTS: A total of 434 patients, 296 with smear-negative PTB and 138 with pleural TB, were enrolled: 366 (84%) of patients were HIV-positive; 220 (51%) completed treatment, and 144 (33%) died by 12 months. In patients from Blantyre and Zomba, baseline characteristics were similar, apart from older age in those from Zomba, and the proportion of patients who completed treatment and who died were similar. In both sites, significantly higher case fatality rates were found in older patients, HIV-positive patients and patients with pulmonary parenchymal lung disease. CONCLUSION: Unsupervised ambulatory treatment evaluated in this study had an efficacy similar to that of 'standard' treatment. For operational reasons, however, it will not be recommended for widespread use in Malawi's National Tuberculosis Control Programme.