Barbara J. Marston

Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS.

Objective:Cryptococcal meningitis is one of the most important HIV-related opportunistic infections, especially in the developing world. In order to help develop global strategies and priorities for prevention and treatment, it is important to estimate the burden of cryptococcal meningitis. Design:Global burden of disease estimation using published studies. Methods:We used the median incidence rate of available studies in a geographic region to estimate the region-specific cryptococcal meningitis incidence; this was multiplied by the 2007 United Nations Programme on HIV/AIDS HIV population estimate for each region to estimate cryptococcal meningitis cases. To estimate deaths, we assumed a 9% 3-month case-fatality rate among high-income regions, a 55% rate among low-income and middle-income regions, and a 70% rate in sub-Saharan Africa, based on studies published in these areas and expert opinion. Results:Published incidence ranged from 0.04 to 12% per year among persons with HIV. Sub-Saharan Africa had the highest yearly burden estimate (median incidence 3.2%, 720 000 cases; range, 144 000–1.3 million). Median incidence was lowest in Western and Central Europe and Oceania (≤0.1% each). Globally, approximately 957 900 cases (range, 371 700–1 544 000) of cryptococcal meningitis occur each year, resulting in 624 700 deaths (range, 125 000–1 124 900) by 3 months after infection. Conclusion:This study, the first attempt to estimate the global burden of cryptococcal meningitis, finds the number of cases and deaths to be very high, with most occurring in sub-Saharan Africa. Further work is needed to better define the scope of the problem and track the epidemiology of this infection, in order to prioritize prevention, diagnosis, and treatment strategies.

Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment

Rapid scale-up of antiretroviral treatment programmes is happening in Africa, driven by international advocacy and policy directives and supported by unprecedented donor funding and technical assistance. This welcome development offers hope to millions of HIV-infected Africans, among whom tuberculosis is the major cause of serious illness and death. Little in the way of HIV diagnosis or care was previously offered to patients with tuberculosis, by either national tuberculosis or AIDS control programmes, with tuberculosis services focused exclusively on diagnosis and treatment of rising numbers of patients. Tuberculosis control in Africa has yet to adapt to the new climate of antiretroviral availability. Many barriers exist, from drug interactions to historic differences in the way that tuberculosis and HIV are perceived, but failure to successfully integrate HIV and tuberculosis control will threaten the viability of both programmes. Here, we review tuberculosis epidemiology in Africa and policy implications of HIV/AIDS treatment scale-up.

Parainfluenza Virus Infection Among Adults Hospitalized for Lower Respiratory Tract Infection

To better define the contribution of human parainfluenza viruses (HPIVs) to lower respiratory tract infection in adults, we tested acute- and convalescent-phase serum specimens from hospitalized adults participating in a population-based prospective study of lower respiratory tract infection during 1991-1992. We tested all available specimens from the epidemic seasons for each virus and approximately 300 randomly selected specimens from the corresponding off-seasons for antibodies to HPIV-1, HPIV-2, or HPIV-3. During the respective epidemic season, HPIV-1 infection was detected in 18 (2.5%) of 721 and HPIV-3 infection in 22 (3.1%) of 705 patients with lower respiratory tract infection. Only 2 (0.2%) of 1,057 patients tested positive for HPIV-2 infection. No HPIV-1 infections and only 2 (0.7% of 281 patients tested) HPIV-3 infections were detected during the off-seasons. HPIV-1 and HPIV-3 were among the four most frequently identified infections associated with lower respiratory tract infection during their respective outbreak seasons.

Serotonin syndrome in Hiv-infected individuals receiving antiretroviral therapy and fluoxetine

ObjectiveTo describe HIV-infected individuals taking antidepressants who developed the serotonin syndrome due to drug–drug or drug–food interactions. Design and settingCase studies carried out at the HIV Outpatient Clinic, Atlanta Veterans Affairs Medical Center. Participants and interventionsHIV-positive patients who were receiving antiretroviral and antidepressant therapies and presented with symptoms consistent with the serotonin syndrome. Their antidepressants were discontinued or the doses reduced in order to resolve the symptoms. ResultsFive cases of serotonin syndrome developed after patients who were taking antidepressants ingested P450 inhibitors. ConclusionsSerotonin syndrome should be suspected in patients on serotonergic medications who present with mental status change, autonomic dysfunction, and neuromuscular abnormalities. Suspicion should be heightened in those who are ingesting substances known to inhibit P450 enzymes, such as protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and grapefruit juice.

HIV and malaria: interactions and implications.

Purpose of review This review summarizes accumulating evidence of interactions between HIV and malaria and implications related to prevention and treatment of coinfection. Recent findings HIV-infected persons are at increased risk for clinical malaria; the risk is greatest when immune suppression is advanced. Adults with advanced HIV may be at risk for failure of malaria treatment, especially with sulfa-based therapies. Malaria is associated with increases in HIV viral load that, while modest, may impact HIV progression or the risk of HIV transmission. Cotrimoxazole prophylaxis greatly reduces the risk of malaria in people with HIV; the risk can be further reduced with antiretroviral treatment and the use of insecticide treated mosquito nets. Increased numbers of doses of intermittent preventive treatment during pregnancy can reduce the risk of placental malaria in women with HIV. Summary Interactions between malaria and HIV have important public health implications. People with HIV should use cotrimoxazole and insecticide treated mosquito nets. Malaria prevention is particularly important for pregnant women with HIV, although more information is needed about the best combination of strategies for prevention. In people with HIV, malaria diagnoses should be confirmed, highly effective drugs should be used for treatment, and possible drug interactions should be considered.

High Prevalence of Pulmonary Tuberculosis and Inadequate Case Finding in Rural Western Kenya

RATIONALE Limited information exists on the prevalence of tuberculosis and adequacy of case finding in African populations with high rates of HIV. OBJECTIVES To estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) and the fraction attributable to HIV, and to evaluate case detection. METHODS Residents aged 15 years and older, from 40 randomly sampled clusters, provided two sputum samples for microscopy; those with chest radiograph abnormalities or symptoms suggestive of PTB provided one additional sputum sample for culture. MEASUREMENTS AND MAIN RESULTS PTB was defined by a culture positive for Mycobacterium tuberculosis or two positive smears. Persons with PTB were offered HIV testing and interviewed on care-seeking behavior. We estimated the population-attributable fraction of HIV on prevalent and notified PTB, the patient diagnostic rate, and case detection rate using provincial TB notification data. Among 20,566 participants, 123 had PTB. TB prevalence was 6.0/1,000 (95% confidence interval, 4.6-7.4) for all PTB and 2.5/1,000 (1.6-3.4) for smear-positive PTB. Of 101 prevalent TB cases tested, 52 (51%) were HIV infected, and 58 (64%) of 91 cases who were not on treatment and were interviewed had not sought care. Forty-eight percent of prevalent and 65% of notified PTB cases were attributable to HIV. For smear-positive and smear-negative PTB combined, the patient diagnostic rate was 1.4 cases detected per person-year among HIV-infected persons having PTB and 0.6 for those who were HIV uninfected, corresponding to case detection rates of 56 and 65%, respectively. CONCLUSIONS Undiagnosed PTB is common in this community. TB case finding needs improvement, for instance through intensified case finding with mobile smear microscopy services, rigorous HIV testing, and improved diagnosis of smear-negative TB.

Care seeking and attitudes towards treatment compliance by newly enrolled tuberculosis patients in the district treatment programme in rural western Kenya: a qualitative study

BackgroundThe two issues mostly affecting the success of tuberculosis (TB) control programmes are delay in presentation and non-adherence to treatment. It is important to understand the factors that contribute to these issues, particularly in resource limited settings, where rates of tuberculosis are high. The objective of this study is to assess health-seeking behaviour and health care experiences among persons with pulmonary tuberculosis, and identify the reasons patients might not complete their treatment.MethodsWe performed qualitative one-on-one in-depth interviews with pulmonary tuberculosis patients in nine health facilities in rural western Kenya. Thirty-one patients, 18 women and 13 men, participated in the study. All reside in an area of western Kenya with a Health and Demographic Surveillance System (HDSS). They had attended treatment for up to 4 weeks on scheduled TB clinic days in September and October 2005.The nine sites all provide diagnostic and treatment services. Eight of the facilities were public (3 hospitals and 5 health centres) and one was a mission health centre.ResultsMost patients initially self-treated with herbal remedies or drugs purchased from kiosks or pharmacies before seeking professional care. The reported time from initial symptoms to TB diagnosis ranged from 3 weeks to 9 years. Misinterpretation of early symptoms and financial constraints were the most common reasons reported for the delay.We also explored potential reasons that patients might discontinue their treatment before completing it. Reasons included being unaware of the duration of TB treatment, stopping treatment once symptoms subsided, and lack of family support.ConclusionsThis qualitative study highlighted important challenges to TB control in rural western Kenya, and provided useful information that was further validated in a quantitative study in the same area.

Screening Strategies for Tuberculosis Prevalence Surveys: The Value of Chest Radiography and Symptoms

Background We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding. Methods All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR) and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture. Results Presence of any abnormality on CXR had 94% (95%CI 88–98) sensitivity (92% in HIV-infected and 100% in HIV-uninfected) and 73% (95%CI 68–77) specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for ‘any TB symptom’ which had 90% (95%CI 84–95) sensitivity (96% in HIV-infected and 82% in HIV-uninfected) and 32% (95%CI 30–34) specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97–100) sensitivity. Specificity was 65% (95%CI 61–68). Sequential application of first a symptom screen for ‘any symptom’, followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%. Conclusion CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not feasible.

Cost-effectiveness analysis of diagnostic options for pneumocystis pneumonia (PCP).

Background Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented. Methods and Findings We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77–90% of patients at

The adult population impact of HIV care and antiretroviral therapy in a resource poor setting 2003-2008.

26–51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68–90% of patients at costs of