Biomedical subjects

Alison D Grant

Publications and source records attributed to Alison D Grant.

12 recordsLinked to original sources

PubMed2006

Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control.

BACKGROUND: Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program. METHODS: Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire. Survey findings were correlated with notification data extracted from the TB treatment register. RESULTS: Of those surveyed, 174 (23%) tested HIV positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear-negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among HIV-positive and -negative individuals, prevalence of notified smear-positive PTB was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was 2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%, respectively. Estimated duration of infectiousness was similar for HIV-positive and HIV-negative individuals. However, 87% of total person-years of undiagnosed smear-positive TB in the community were among HIV-infected individuals. CONCLUSIONS: PTB was identified in 9% of HIV-infected individuals, with 5% being previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low case-finding rates. DOTS strategy based on passive case finding should be supplemented by active case finding targeting HIV-infected individuals.

Adolescent↗

PubMed2006

Early risk assessment for viral haemorrhagic fever: experience at the Hospital for Tropical Diseases, London, UK.

OBJECTIVES: To implement a policy of systematic screening for viral haemorrhagic fever (VHF) among travellers returning from African countries with fever, commencing at initial clinical contact. METHODS: A protocol based on UK Advisory Committee on Dangerous Pathogens guidance was developed collaboratively by medical, nursing and laboratory staff. Audit was carried out to quantify resource demands and effects on time to diagnose malaria, the main differential diagnosis. RESULTS: A protocol is now implemented for all patients presenting to HTD with fever, with clear guidelines for interaction with clinical and laboratory staff at each stage. The protocol required moderate amounts of clinical and laboratory staff time and resulted in some additional hospital admissions. The time to a diagnosis of malaria increased from a median of 90 (range 50-125) min in patients without VHF risk to a median of 140 (range 101-225) min (p=0.0025) in those assessed as at risk. CONCLUSIONS: Although all acute medical services need to have robust procedures for early detection of patients with serious transmissible conditions, few implement such a policy. Our protocol requires increased human and other resources but has no important impact on the rapidity of diagnosis of malaria, and is now embedded in local practice.

Africa↗

PubMed2006

Isoniazid preventive therapy and risk for resistant tuberculosis.

In the context of tuberculosis (TB) resurgence, isoniazid preventive therapy (IPT) is increasingly promoted, but concerns about the risk for development of isoniazid-resistant tuberculosis may hinder its widespread implementation. We conducted a systematic review of data published since 1951 to assess the effect of primary IPT on the risk for isoniazid-resistant TB. Different definitions of isoniazid resistance were used, which affected summary effect estimates; we report the most consistent results. When all 13 studies (N = 18,095 persons in isoniazid groups and N = 17,985 persons in control groups) were combined, the summary relative risk for resistance was 1.45 (95% confidence interval 0.85-2.47). Results were similar when studies of HIV-uninfected and HIV-infected persons were considered separately. Analyses were limited by small numbers and incomplete testing of isolates, but findings do not exclude an increased risk for isoniazid-resistant TB after IPT. The diagnosis of active TB should be excluded before IPT. Continued surveillance for isoniazid resistance is essential.

Antitubercular Agents↗

PubMed2005

Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infected men in South Africa: a novel randomized incremental recruitment study.

CONTEXT: Tuberculosis preventive therapy reduces tuberculosis incidence among human immunodeficiency virus (HIV)-infected individuals in clinical trials, but implementation has been limited and there are no data on effectiveness under routine conditions. OBJECTIVE: To determine the effect on tuberculosis incidence of a clinic providing isoniazid preventive therapy to HIV-infected adults under routine conditions. DESIGN, SETTING, AND PARTICIPANTS: Randomized intervention study with a novel incremental recruitment design. Between 1999 and 2001 (before antiretroviral therapy was available), 1655 HIV-infected male employees of a South African gold-mining company (median age, 37 years) were enrolled in the study. Median follow-up was 22.1 months. INTERVENTION: Employees were invited in random sequence to attend a workplace HIV clinic. Isoniazid, 300 mg/d, was self-administered for 6 months among attendees with no evidence of active tuberculosis. MAIN OUTCOME MEASURE: Incidence of tuberculosis (including both first and recurrent episodes) during the periods before and after clinic enrollment. RESULTS: A total of 1016 of 1655 men included in the analysis attended the clinic at least once. Six hundred seventy-nine (97%) of 702 men eligible to start primary isoniazid preventive therapy did so. The tuberculosis incidence rate before vs after clinic enrollment was 11.9 vs 9.0 per 100 person-years, respectively (incidence rate ratio [IRR] after adjustment for calendar period, 0.68; 95% confidence interval [CI], 0.48-0.96). In a multivariable analysis adjusting for calendar period, age, and silicosis grade, the tuberculosis IRR for clinic enrollment was 0.62 (95% CI, 0.43-0.89). In a further analysis excluding individuals with a history of tuberculosis (and, hence, ineligible for isoniazid preventive therapy), the adjusted IRR for clinic enrollment was 0.54 (95% CI, 0.35-0.83). CONCLUSIONS: Enrollment in a clinic offering primary isoniazid preventive therapy to HIV-infected adults reduced tuberculosis incidence by 38% overall and by 46% among individuals with no history of tuberculosis prior to the study. Tuberculosis incidence remained high despite isoniazid preventive therapy, and further work is needed to determine how to use additional interventions most effectively to reduce morbidity and mortality due to tuberculosis in HIV-infected persons.

AIDS-Related Opportunistic Infections↗

PubMed2004

Does tuberculosis increase HIV load?

BACKGROUND: The effect that tuberculosis (TB) has on human immunodeficiency virus (HIV) disease progression is not clearly understood. METHODS: In an observational cohort study of HIV-infected adults in South Africa, baseline and final HIV load were compared between individuals who experienced an episode of TB (n=30) during follow-up and control subjects (n=56) matched by baseline CD4 cell count and follow-up time; linear regression modeling was used to control for confounding. RESULTS: Mean HIV load was higher in the TB group than in the non-TB control group for both baseline (4.73 vs. 4.24 log(10) copies/mL; P=.003) and final values (5.02 vs. 4.34 log(10) copies/mL; P<.001). After adjustment for baseline HIV load and World Health Organization HIV stage, the difference in final HIV load was 0.24 log(10) copies/mL (95% confidence interval, -0.01 to 0.50 log(10) copies/mL; P=.06). CONCLUSIONS: Poor prognosis for HIV-infected individuals after TB may be due to preexisting high HIV load rather than to the TB event itself. An episode of TB was associated with a small adjusted increase in HIV load at the end of the study--an increase that would not be regarded as clinically significant in an individual but could have some effect on HIV disease progression or HIV transmission at the population level. Prevention of TB is important for the reduction of HIV-related morbidity and mortality; however, antiretroviral therapy is required to have a major effect on survival in individuals with HIV disease.

AIDS-Related Opportunistic Infections↗

PubMed2004

Human immunodeficiency virus and the prevalence of undiagnosed tuberculosis in African gold miners.

We hypothesized that rapid presentation may be a general feature of tuberculosis (TB) associated with human immunodeficiency virus (HIV) that limits the impact of HIV on the point prevalence of TB. To investigate this, we performed a cross-sectional HIV and TB disease survey with retrospective and prospective follow-up. HIV prevalence among 1,773 systematically recruited miners was 27%. TB incidence was much more strongly HIV associated (incidence rate ratio, 5.5; 95% confidence interval [CI], 3.5-8.6) than the point prevalence of undiagnosed TB disease (odds ratio, 1.7; 95% CI, 0.9-3.3). For smear-positive TB, 7 of 9 (78%) prevalent cases were HIV negative, and point prevalence was nonsignificantly lower in miners who were HIV positive (odds ratio, 0.8; 95% CI, 0.1-4.2). The calculated mean duration of smear positivity before diagnosis (point prevalence/incidence) was substantially shorter for HIV-positive than HIV-negative TB patients (0.17 and 1.15 years, respectively; ratio, 0.15; 95% CI, 0.00-0.73). HIV has considerably less impact on the point prevalence of TB disease than on TB incidence, probably because rapid disease progression increases presentation and case-finding rates. The difference in mean duration of smear positivity was particularly marked and, if generalizable, will have major implications for TB control prospects in high HIV prevalence areas.

Adolescent↗

PubMed2004

Malaria in camps for internally-displaced persons in Uganda: evaluation of an insecticide-treated bednet distribution programme.

Malaria is a key health problem among displaced populations in malaria-endemic areas. Mass distribution of insecticide-treated bednets (ITN) to prevent malaria is often carried out in complex emergencies, but there are few data on the outcome or operational effectiveness of such programmes. In June 2001, Medecins Sans Frontieres completed a mass distribution of ITNs (Permanet) to internally displaced persons in Bundibugyo, southwest Uganda, distributing one to four nets per household, and aiming to provide coverage for all residents. In July 2002, we did a cross-sectional survey using three-stage cluster sampling to evaluate the programme. A total of 1245 individuals from 835 households were interviewed. An ITN was present in 75.6% (95% CI 72.7-78.5) of the households, but only 56.5% (95% CI 52.3-60.4) of individuals were sleeping under an ITN, and nets were often damaged. The prevalence of malarial parasitaemia was 11.2% (95% CI 9.4-13.0), and was significantly lower in ITN users compared to non-users (9.2% vs. 13.8%, relative risk [RR] 0.63, 95% CI 0.46-0.87); ITNs with severe damage remained effective (RR for severely damaged net 0.58, 95% CI 0.35-0.98). There was no significant difference in haemoglobin concentration between ITN users and non-users.

Adult↗

PubMed2004

Risk factors for malaria in UK travellers.

After observing an apparent increase in severe falciparum malaria among travellers returning from The Gambia to the United Kingdom (UK) in the last quarter of 2000, we conducted a case-control study to investigate risk factors for malaria. The study participants had visited The Gambia between 1 September and 31 December 2000, travelling with the largest UK tour operator serving this destination. The main outcome measures were risk factors associated with malaria. Forty-six cases and 557 controls were studied. Eighty-seven percent of all participants reported antimalarial use (41% chloroquine/proguanil, 31% mefloquine). On univariate analysis the strongest risk factors for disease were: early calendar period of visit, longer duration of stay, non-use of antimalarial prophylaxis, non-use of mefloquine, lack of room air-conditioning, less use of insect repellent, prior visit to another malarial area and accommodation in 'hotel X'. After adjustment in multivariate analysis, use of mefloquine remained strongly protective (odds ratios, OR 0.13 [95% confidence intervals, 95% CI 0.04-0.40]), and the strongest independent risk factors for malaria were early calendar period (OR 5.19 [2.35-11.45] for 1 September to 9 November 2000 versus 10 November to 31 December 2000), prior visit to another malarial area (OR 3.27 [1.41-7.56]), main accommodation in 'hotel X' (OR 3.24 [1.51-6.97]) and duration of stay (OR 2.05 per extra week [1.42-2.95]). Neither any use, nor > 90% adherence to chloroquine/proguanil were protective (adjusted OR for any use 0.57 [0.27-1.21], P = 0.14). We concluded mefloquine use was strongly protective against malaria (87% protective efficacy), whereas chloroquine/proguanil, which is no longer recommended but remains widely used, was less than half as effective (43% protective efficacy). Waning efficacy of chloroquine/proguanil may have contributed to the observed increase in malaria among travellers to The Gambia in 2000. Local factors may also influence the risk of malaria. Malaria could be prevented among travellers to West Africa if current national guidelines on antimalarial prophylaxis were better implemented.

Adult↗

PubMed2004

The natural history of HIV-1 and HIV-2 infections in adults in Africa: a literature review.

About 30 million people in Africa are estimated to be living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), yet data about the natural history of infection on the continent are sparse. We reviewed the literature on the natural history of HIV-1 and HIV-2 infections among African adults. Only one study, conducted in rural Uganda, has reported on survival from the time of HIV-1 seroconversion: the median was 9.8 years, which is similar to that reported in developed countries in the early stages of the epidemic and consistent with the findings from the follow-up of individuals identified by serological testing during community-based prevalence studies from Africa. Progression to symptomatic disease was faster in Uganda than in developed countries, due largely to the high background level of morbidity. Various studies suggest that people infected with HIV-2 survive longer and the course of the disease is possibly more variable than in people infected with HIV-1. However no studies have investigated survival from time of seroconversion among people infected with HIV-2. The majority of patients in hospital in Africa with either HIV-1 or HIV-2 have the clinical features of AIDS just before they die, and many are severely immunosuppressed. This is similar to the situation in developed countries before the introduction of highly active antiretroviral therapy (HAART). Potentially preventable infections are the leading causes of death among individuals infected with HIV-1. Prophylactic regimens and better treatments could have some effect on survival, but major improvements in life expectancy will require HAART.

Adult↗

PubMed2003

Efficacy of secondary isoniazid preventive therapy among HIV-infected Southern Africans: time to change policy?

OBJECTIVE: To determine the efficacy of secondary preventive therapy against tuberculosis (TB) among gold miners working in South Africa. DESIGN: An observational study. SETTING: Health service providing comprehensive care for gold miners. METHODS: The incidence of recurrent TB was compared between two cohorts of HIV-infected miners: one cohort (n = 338) had received secondary preventive therapy with isoniazid (IPT) and the other had not (n = 221). RESULTS: The overall incidence of recurrent TB was reduced by 55% among men who received IPT compared with those who did not (incidence rates 8.6 and 19.1 per 100 person-years, respectively; incidence rate ratio, 0.45; 95% confidence interval 0.26-0.78). The efficacy of isoniazid preventive therapy was unchanged after controlling for CD4 cell count and age. The number of person-years of IPT required to prevent one case of recurrent TB among individuals with a CD4 cell count < 200 x 106 cells/l, and > or = 200 x 106 cells/l was 5 and 19, respectively. CONCLUSION: Secondary preventive therapy reduces TB recurrence: the absolute impact appears to be greatest among individuals with low CD4 cell counts. International TB preventive therapy guidelines for HIV-infected individuals need to be expanded to include recommendations for secondary preventive therapy in settings where TB prevalence is high.

Adult↗

PubMed2002

HIV/AIDS treatment and HIV vaccines for Africa.

Increased support from the global HIV/AIDS community is driving advances in HIV treatment and vaccine development in the developing world. Care of patients with AIDS includes many biomedical, nutritional, psychosocial, and behavioural interventions. In resource-poor settings, antiretroviral drugs should be given with use of standardised treatment regimens and streamlined algorithms for monitoring use. A safe and effective HIV vaccine will supplement prevention efforts to protect uninfected people against infection, or might possibly be able to modify the course of HIV infection. Advances have been made in understanding the immune response and immunisation to HIV, and new ideas for candidate vaccines have been developed, including several based on HIV-1 strains prevalent in Africa. HIV vaccine efficacy trials are needed in Africa to determine whether these advances can be translated into clinical and public health benefits. In this review, we discuss the prospects for use of treatment and vaccines in resource-poor settings.

AIDS Vaccines↗

PubMed2002

Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus.

A cohort of 1792 human immunodeficiency virus (HIV)-positive and 2970 HIV-negative South African miners was observed for 12 months starting in February 1998. All-cause hospitalizations and deaths were significantly associated with HIV infection (respective unadjusted incidence rate ratios, 2.9 and 9.2; respective 95% confidence intervals, 2.5-3.4 and 5.5-16.0). Tuberculosis (TB), bacterial pneumonia, cryptococcosis, and trauma were the major causes of admission for HIV-positive patients, whereas Pneumocystis carinii pneumonia was an uncommon cause (respective admission rates, 8.5, 6.9, 2.2, 6.0, and 0.53 admissions per 100 person-years). Enteritis, bronchitis, urinary tract infections, and soft-tissue infections were also significantly associated with HIV infection. Cryptococcosis caused 44% of deaths among HIV-positive patients. Trauma was the main hazard for HIV-negative men, causing 42% of admissions and 60% of deaths. A broad range of infectious conditions is significantly associated with HIV infection in South African miners. Identification and implementation of effective prophylactic regimens are urgently needed.

Adult↗