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Purpose: A study was conducted to identify significant associations between affective domain (AD) features identified using the Birkman Method assessment and students' likelihood to pursue and to successfully match for postgraduate residency training (PGRT), while controlling for demographic and academic variables known to impact PGRT match rates., Methods: A retrospective analysis of 3 graduating classes of PharmD students from 2 colleges of pharmacy was performed. Data points such as PGRT match results, PGRT pursuit, student demographics, academic performance information, and AD data from the Birkman assessment were analyzed. Regression analysis was used to identify statistically significant associations between demographic, academic performance, and AD variables with both pursuit of PGRT and successful matching for PGRT., Results: Data from 503 students were evaluated, with 211 (42%) pursuing PGRT. A variety of AD variables were significantly associated with pursuing PGRT and matching for PGRT. Two groups of actionable variables emerged: (1) variables associated with a lesser likelihood of pursuing PGRT but a greater likelihood of successful matching, and (2) variables associated with a greater likelihood of pursuing PGRT and a lesser likelihood of successful matching., Conclusion: Early identification of students' AD features along with specific interventions to promote PGRT pursuit in those less likely to pursue but more likely to match, as well as interventions to promote successful matching in students most likely to pursue but less likely to match for PGRT, is a strategy for possibly optimizing PharmD student career path planning and PGRT match success that merits further evaluation., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture-positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542-9188] vs 698 [218-4060] pg/mL, respectively; P = .004) and after (3650 [1214-3888] vs 720 [551-1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Tuberculosis (TB) case finding efforts typically target symptomatic people attending health facilities. We compared the prevalence of Mycobacterium tuberculosis (Mtb) sputum culture-positivity among adult clinic attendees in rural South Africa with a concurrent, community-based estimate from the surrounding demographic surveillance area (DSA)., Methods: Clinic: Randomly selected adults (≥18 years) attending 2 primary healthcare clinics were interviewed and requested to give sputum for mycobacterial culture. Human immunodeficiency virus (HIV) and antiretroviral therapy (ART) status were based on self-report and record review. Community: All adult (≥15 years) DSA residents were invited to a mobile clinic for health screening, including serological HIV testing; those with ≥1 TB symptom (cough, weight loss, night sweats, fever) or abnormal chest radiograph were asked for sputum., Results: Clinic: 2055 patients were enrolled (76.9% female; median age, 36 years); 1479 (72.0%) were classified HIV-positive (98.9% on ART) and 131 (6.4%) reported ≥1 TB symptom. Of 20/2055 (1.0% [95% CI, .6-1.5]) with Mtb culture-positive sputum, 14 (70%) reported no symptoms. Community: 10 320 residents were enrolled (68.3% female; median age, 38 years); 3105 (30.3%) tested HIV-positive (87.4% on ART) and 1091 (10.6%) reported ≥1 TB symptom. Of 58/10 320 (0.6% [95% CI, .4-.7]) with Mtb culture-positive sputum, 45 (77.6%) reported no symptoms. In both surveys, sputum culture positivity was associated with male sex and reporting >1 TB symptom., Conclusions: In both clinic and community settings, most participants with Mtb culture-positive sputum were asymptomatic. TB screening based only on symptoms will miss many people with active disease in both settings., Competing Interests: Potential conflicts of interest. I. G. reports salary support from the UK Economic and Social Research Council (grant awarded to the London School of Hygiene and Tropical Medicine [LSHTM]). A. S. K. reports support from The Bloomsbury SET (Research England) (grant awarded to their institution, London School of Hygiene & Tropical Medicine), the National Institute for Health Research (UK), Colt Foundation (UK), ViiV Healthcare (USA), Queen Margaret University (UK), World Health Organization, Medical Research Council (UK), London School of Hygiene and Tropical Medicine (UK), and grants awarded to their employer/institution; reports consulting fees from the University of Cape Town (South Africa), South African National TB Think Tank (funded by the Bill and Melinda Gates Foundation, USA), Center for Health Policy and Studies (Republic of Moldova), Vital Strategies (Singapore; funded by Bloomberg Philanthropies, USA), The Aurum Institute (South Africa), and Edanz Group (Japan); reports travel and accommodation costs from Africa Health Research Institute (South Africa), Kyoto University (Japan), University College London (UK), Vital Strategies (Singapore), and Open Access publishing costs from the Bill and Melinda Gates Foundation (USA). K. K. reports salary support and travel expenses and support towards article-processing charges received for a role on the Umoya Omuhle project (from which the paper draws its data) from the UK Economic and Social Research Council (payments made to Queen Margaret University), grant received from the Joint Health Systems Research Initiative (Medical Research Council/Economic and Social Research Council/Department for International Development/Wellcome Trust) and a grant received from the National Institute for Health Research (NIHR; payments made to Queen Margaret University). O. K. reports salary support through grant to the institutions (Africa Health Research Institute [AHRI] and LSHTM) from Wellcome Trust (core grant 082384/Z/07/Z) and the Bill and Melinda Gates Foundation (OPP1175182). T. N. reports support from Wellcome Trust African Academy of Sciences and the South African National Research Foundation, the Bill and Melinda Gates Foundation and Max Planck Society and reports serving as member of the External Advisory Committee for HIV Vaccine Trials Network. E. B. W. reports support from Massachusetts General Hospital, the Africa Health Research Institute, University of Alabama at Birmingham, Bill and Melinda Gates Foundation, Wellcome Trust and National Institutes of Health. A. G. reports funding for other projects paid to their institution by the National Institutes of Allergy and Infectious Diseases, Bill and Melinda Gates Foundation, Research England, Wellcome Trust, and Medical Research Council and reports travel support paid to their institution by Wellcome Trust and Economic and Social Research Council. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: We assessed coverage of symptom screening and sputum testing for tuberculosis (TB) in hospital outpatient clinics in Ghana., Methods: In a cross-sectional study, we enrolled adults (≥18 years) exiting the clinics reporting ≥1 TB symptom (cough, fever, night sweats or weight loss). Participants reporting a cough ≥2 weeks or a cough of any duration plus ≥2 other TB symptoms (per national criteria) and those self-reporting HIV-positive status were asked to give sputum for testing with Xpert MTB/RIF., Results: We enrolled 581 participants (median age 33 years [IQR: 24-48], 510/581 [87.8%] female). The most common symptoms were fever (348, 59.9%), chest pain (282, 48.5%) and cough (270, 46.5%). 386/581 participants (66.4%) reported symptoms to a healthcare worker, of which 157/386 (40.7%) were eligible for a sputum test per national criteria. Only 31/157 (19.7%) had a sputum test requested. Thirty-two additional participants gave sputum among 41 eligible based on positive HIV status. In multivariable analysis, symptom duration ≥2 weeks (adjusted odds ratio [aOR] 6.99, 95% confidence interval [CI] 2.08-23.51) and previous TB treatment (aOR: 6.25, 95% CI: 2.24-17.48) were the strongest predictors of having a sputum test requested. 6/189 (3.2%) sputum samples had a positive Xpert MTB/RIF result., Conclusion: Opportunities for early identification of people with TB are being missed in health facilities in Ghana., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: WHO guidelines recommend the lateral flow urine lipoarabinomannan assay (LF-LAM) for TB diagnosis in hospitalised HIV-positive individuals. The role of LF-LAM among ambulant patients remains less well defined. We investigated the sensitivity of LF-LAM among ambulant HIV-positive adults in primary health clinics in South Africa., Methods: We enrolled adults (aged ≥18 y) with CD4 counts of ≤150 cells/mm3 who had not received TB treatment or antiretroviral therapy in the preceding 3 or 6 mo, respectively. Research nurses performed the LF-LAM test on freshly voided urine. Results were compared with a reference standard of positive mycobacterial culture (sputum or urine)., Results: Of 1505 (54.5% female; median age 37 y; median CD4 count 73 cells/mm3) participants, 973 (64.7%) had a mycobacterial culture result; 105/973 (10.8%) were positive for Mycobacterium tuberculosis. LF-LAM sensitivity was 41.9% (95% CI 32.3 to 51.9%) and 19.0% (95% CI 12.0 to 27.9%) using grade 1+ and grade 2+ cut-off points, respectively. Sensitivity increased with severe immunosuppression and in the presence of poor prognostic indicators (low haemoglobin, body mass index)., Conclusions: When used as the only TB diagnostic test, LF-LAM sensitivity is suboptimal, particularly using the grade 2+ cut-off. More sensitive tests for TB are needed that can be used in primary care settings., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13-1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To reduce the incidence of tuberculosis, it is insufficient to simply understand the dynamics of tuberculosis transmission. Rather, we must design and rigorously evaluate interventions to halt transmission, prioritizing those interventions most likely to achieve population-level impact. Synergy in reducing tuberculosis transmission may be attainable by combining interventions that shrink the reservoir of latent Mycobacterium tuberculosis infection (preventive therapy), shorten the time between disease onset and treatment initiation (case finding and diagnosis), and prevent transmission in key settings, such as the built environment (infection control). In evaluating efficacy and estimating population-level impact, cluster-randomized trials and mechanistic models play particularly prominent roles. Historical and contemporary evidence suggests that effective public health interventions can halt tuberculosis transmission, but an evidence-based approach based on knowledge of local epidemiology is necessary for success. We provide a roadmap for designing, evaluating, and modeling interventions to interrupt the process of transmission that fuels a diverse array of tuberculosis epidemics worldwide., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Adults being investigated for TB in South Africa experience high mortality, yet causes of death (CoD) are not well defined. We determined CoD in this population using verbal autopsy (VA), and compared HIV- and TB-associated CoD using physician-certified verbal autopsy (PCVA) and InterVA-4 software., Methods: All contactable consenting caregivers of participants who died during a trial comparing Xpert MTB/RIF to smear microscopy were interviewed using the WHO VA tool. CoD were assigned using PCVA and InterVA-4. Kappa statistic (K) and concordance correlation coefficient (CCC) were calculated for comparison., Results: Among 231 deaths, relatives of 137 deceased were interviewed. Of the 137 deceased 76 (55.4%) were males, median age 41 years (IQR 33-50). PCVA assigned 70 (51.1%) TB immediate CoD (44 [62.8%] pulmonary TB; 26 [37.1%] extra-pulmonary TB); 21 (15.3%) HIV/AIDS-related; and 46 (33.5%) other CoD. InterVA-4 assigned 48 (35.0%) TB deaths; 49 (35.7%) HIV/AIDS-related deaths; and 40 (29.1%) other CoD. Agreement between PCVA and InterVA-4 CoD was slight at individual level (K=0.20; 95% CI 0.10-0.30) and poor at population level (CCC 0.67; 95% CI 0.38-0.99)., Conclusions: TB and HIV are leading CoD among adults being investigated for TB. PCVA and InterVA agreement at individual level was slight and poor at population level. VA methodology needs further development where TB and HIV are common., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006-2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to trial data and explored 1) factors contributing to the lack of population-level impact, 2) the best-achievable impact if all implementation characteristics were increased to the highest level achieved during the trial ("optimized intervention"), and 3) how tuberculosis might be better controlled with additional interventions (improving diagnostics, reducing treatment delay, providing isoniazid preventive therapy continuously to human immunodeficiency virus-positive people, or scaling up antiretroviral treatment coverage) individually and in combination. We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus-positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years. Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification., Methods: Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression., Results: One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77-263) and 4.3 log10 copies/mL (IQR, 3.8-4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥ 1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL., Conclusions: Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure.

Background: Episodes of viremia are common in African antiretroviral therapy (ART) programs. We sought to describe viremia, resuppression, and accumulation of resistance during first-line combination ART (cART) in South Africa., Methods: Retrospective analysis of a cohort receiving zidovudine, lamivudine, and either efavirenz or nevirapine with human immunodeficiency virus (HIV) RNA monitoring every 6 months. We assessed viremia (HIV RNA >1000 copies/mL after initial HIV RNA response) and resuppression (HIV RNA <400 copies/mL after viremia). Genotypic resistance testing was performed using stored plasma on a subset of patients at first detection of viremia and subsequently among patients with persistent viremia., Results: Between 2002 and 2006, 3727 patients initiated cART (median CD4, 147 cells/mm(3)). Of 1007 patients who developed viremia, 815 had subsequent HIV RNA assays, and 331 (41%) of these resuppressed without regimen switch. At identification of viremia, 45 (66%) of 68 patients had HIV-1 drug resistance, 42 (62%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistance, 25 (37%) had M184V/I, and 4 (6%) had multi-nucleoside analogue drug mutations. By 12 months of persistent viremia among a subset of 14 patients with resistance testing to 12 months, 11 (78%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistance, 8 (57%) had M184V/I, and 2 (14%) had multi-nucleoside analogue drug mutations. Resistance was associated with a reduced probability of resuppression; however, 50% of patients with NNRTI resistance resuppressed while receiving an NNRTI., Conclusions: The majority of patients had NNRTI resistance mutations at detection of viremia. However, 41% resuppressed without regimen switch. Our findings support maximizing first-line use while minimizing risk of significant cross-resistance by implementing intensive adherence support and repeat HIV RNA testing 3-6 months after detecting viremia, with regimen switch only if viremia persists.

Background: Coinfection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common in Africa; however, the impact of HBV infection on the outcomes of antiretroviral therapy programs is unclear. We evaluated the impact of chronic hepatitis B on HIV virologic response, changes in CD4 cell count, hepatotoxicity, and mortality among Africans receiving highly active antiretroviral therapy (HAART)., Methods: We conducted a retrospective cohort study involving a workplace HAART program in South Africa. Participants received HAART according to a protocol and were followed up for up to 72 weeks. On the basis of pre-HAART serum assays, patients were classified as being hepatitis B surface antigen (HBsAg) negative, HBsAg positive with a low HBV DNA level ( 1 x 10(4) copies/mL). The relationships between HBV status and HIV RNA suppression, change in CD4 cell count, mortality, and hepatotoxicity were assessed with use of regression techniques., Results: Five hundred thirty-seven individuals fulfilled the inclusion criteria; 431 (80.3%) of these patients were HBsAg negative, 60 (11.2%) were HBsAg positive with a low HBV DNA level, and 46 (8.6%) were HBsAg positive with a high HBV DNA level. All groups had similar rates of HIV RNA suppression (P = .61), CD4 cell count increases (P =.75), and mortality (17 total deaths; P=.11) for up to 72 weeks after the initiation of HAART. Baseline transaminase levels were highest in the group with high HBV DNA levels (P=.004). Hepatotoxicity was similar between the HBsAg-negative group and the group with low HBV DNA levels but was higher in the group with high HBV DNA levels (incidence rate ratio, 4.4)., Conclusions: We revealed that HBV status does not affect HIV RNA suppression, CD4 cell count response, or mortality during the first 72 weeks of HAART in an African setting. The risk of HBV-associated hepatotoxicity, however, is associated with the baseline HBV DNA level.

Background: Pneumocystis jirovecii pneumonia (PCP) remains the leading cause of opportunistic infection among human immunodeficiency virus (HIV)-infected persons. Previous studies of PCP that identified case-fatality risk factors involved small numbers of patients, were performed over few years, and often focused on patients who were admitted to the intensive care unit., Objective: The objective of this study was to identify case-fatality risk factors present at or soon after hospitalization among adult HIV-infected patients admitted to University College London Hospitals (London, United Kingdom) from June 1985 through June 2006., Patients and Methods: We performed a review of case notes for 494 consecutive patients with 547 episodes of laboratory-confirmed PCP., Results: Overall mortality was 13.5%. Mortality was 10.1% for the period from 1985 through 1989, 16.9% for the period from 1990 through June 1996, and 9.7% for the period from July 1996 through 2006 (P = .142). Multivariate analysis identified factors associated with risk of death, including increasing patient age (adjusted odds ratio [AOR], 1.54; 95% confidence interval [CI], 1.11-2.23; P = .011), subsequent episode of PCP (AOR, 2.27; 95% CI, 1.14-4.52; P = .019), low hemoglobin level at hospital admission (AOR, 0.70; 95% CI, 0.60-0.83; P < .001), low partial pressure of oxygen breathing room air at hospital admission (AOR, 0.70; 95% CI, 0.60-0.81; P < .001), presence of medical comorbidity (AOR, 3.93; 95% CI, 1.77-8.72; P = .001), and pulmonary Kaposi sarcoma (AOR, 6.95; 95% CI, 2.26-21.37; P = .001). Patients with a first episode of PCP were sicker (mean partial pressure of oxygen at admission +/- standard deviation, 9.3+/-2.0 kPa) than those with a second or third episode of PCP (mean partial pressure of oxygen at admission +/- standard deviation, 9.9+/-1.9 kPa; P = .008), but mortality among patients with a first episode of PCP (12.5%) was lower than mortality among patients with subsequent episodes of PCP (22.5%) (P = .019). No patient was receiving highly active antiretroviral therapy before presentation with PCP, and none began highly active antiretroviral therapy during treatment of PCP., Conclusions: Mortality risk factors for PCP were identifiable at or soon after hospitalization. The trend towards improved outcome after June 1996 occurred in the absence of highly active antiretroviral therapy.

The recognition of tuberculosis (TB) as a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected persons has led to renewed interest in TB preventive therapy and its incorporation into the essential package of health care for these individuals. Despite convincing data regarding its efficacy, TB preventive therapy has not been widely implemented. Further work is needed to determine how to overcome the barriers to the implementation of such therapy, including how best to exclude the presence of active TB before providing preventive therapy. Such issues as the optimal duration of preventive therapy for and the role of TB preventive therapy in the treatment of individuals receiving antiretroviral therapy remain to be defined. Ongoing research will help to determine how best to use this intervention in the care of HIV-infected persons and in the control of TB on a wider basis.

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.

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.

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.

We describe 3 returned travellers who developed profuse watery diarrhoea associated with marked blood eosinophilia. Delayed appearance of ova in stool samples caused difficulty in establishing diagnoses of acute hookworm infection. Low activity of ivermectin against hookworm resulted in failure of empiric treatment with this agent prior to parasitological diagnosis.

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.

The burden of HIV infection and disease continues to increase in many developing countries. An emerging theme is of an HIV pandemic composed of mini-epidemics, each with its own characteristics in terms of the trends in HIV prevalence, those affected, and the HIV-related opportunistic diseases observed. A number of explanations for the observed differences in the spread of HIV infection have been proposed but since the factors concerned, such as sexual behaviour and the prevalence of other sexually transmitted diseases, are closely interrelated, it is difficult to tease out which are the most important. Among HIV-related opportunistic diseases, tuberculosis stands out as the most important cause of morbidity and mortality in most developing countries, but the relative prevalence of other diseases shows considerable regional variation. Thus, there is a need for local approaches to the global problem of managing HIV disease. The most pressing public health challenges are to use existing knowledge of strategies to reduce HIV transmission, and to apply them in ways appropriate to the local situation, and to develop, evaluate and implement interventions to prolong healthy life in those already infected.