Histoplasmosis diseminada y síndrome hemofagocítico en pacientes VIH: serie de casos en un hospital peruano / Disseminated histoplasmosis and haemophagocytic syndrome in HIV patients: a case series in a Peruvian hospital

ANTECEDENTES: La histoplasmosis diseminada (HD) es una infección fúngica oportunista en pacientes con infección por VIH gravemente inmunocomprometidos. El síndrome hemofagocítico (SHF), que puede presentarse en estos pacientes coinfectados cuando la respuesta inmunitaria está significativamente alterada, suele estar asociado a una elevada mortalidad. OBJETIVOS: Describir las características epidemiológicas, clínicas, analíticas y microbiológicas, así como evaluar la presencia de SHF, en pacientes con HD-VIH. MÉTODOS: Estudio retrospectivo de serie de casos, consistente en la revisión de registros clínicos de pacientes con diagnóstico de HD e infección VIH, durante los años 2014 y 2015. RESULTADOS: El 1,3% (8/597) de los pacientes VIH presentaron HD. El 100% se hallaban en estadio C3 y el 75% (6/8) no se encontraban en terapia antirretroviral combinada (TARVc). Los dos pacientes restantes habían comenzado recientemente el tratamiento con TARVc (posible síndrome de reconstitución inmunológica). El 62,5% (5/8) cumplieron con criterios diagnósticos de SHF. Las manifestaciones clínicas más frecuentes fueron el síndrome linfoproliferativo y consuntivo, el compromiso respiratorio y la citopenia. En el 75% (6/8) de los pacientes se aisló Histoplasma en ganglios, en el 25% (2/8) en muestras hemáticas y en uno adicionalmente en tejido intestinal. La terapia antifúngica fue anfotericina B desoxicolato; no se emplearon adyuvantes. La mortalidad global fue del 50%. CONCLUSIONES: En nuestra serie la coinfección HD-VIH progresó en la mayoría de los casos a SHF con elevada mortalidad. El cuadro clínico puede asemejarse al de otras enfermedades sistémicas, como la tuberculosis, o presentarse simultáneamente a ellas. Con el fin de obtener un diagnóstico precoz y poder prescribir la terapia específica oportuna es importante poseer un adecuado índice de sospecha en pacientes con síndrome linfoproliferativo y consuntivo asociado a citopenia grave

BACKGROUND: Disseminated histoplasmosis (DH) is an opportunistic fungal infection in severely immunocompromised patients with HIV infection. Haemophagocytic syndrome (HFS), which can occur in these co-infected patients when the immune response is significantly altered, is often associated with high mortality. AIMS: To describe the epidemiological, clinical, analytical and microbiological characteristics, along with studying the presence of HFS, in patients with DH-HIV. METHODS: A retrospective study was conducted on a case series using data from the clinical records of patients diagnosed with DH and HIV infection during the years 2014 and 2015. RESULTS: DH was diagnosed in 8 (1.3%) of 597 HIV patients. All patients were in stage C3, and 75% (6/8) were not receiving combined antiretroviral therapy (CART). The remaining two patients had recently begun CART (possible immune reconstitution syndrome). Five (62.5%) of the 8 patients met criteria for HFS. The most frequent clinical symptoms were lymphoproliferative and consumptive syndrome, respiratory compromise, and cytopenia. Histoplasma was isolated in lymph nodes of 75% (6/8) of the patients, in blood samples in 25% (2/8), and also in intestinal tissue in one patient. The antifungal therapy was amphotericin B deoxycholate, without adjuvants. The overall mortality was 50%. CONCLUSIONS: In this case series, DH-HIV co-infection frequently progressed to HFS with high mortality. The clinical picture may resemble that of other systemic opportunistic infections, such as tuberculosis, or can take place simultaneously with other infections. Clinical suspicion is important in patients with severe cytopenia and lymphoproliferative and consumptive syndrome in order to establish an early diagnosis and prescribing a timely specific therapy

[Disseminated histoplasmosis and haemophagocytic syndrome in HIV patients: A case series in a Peruvian hospital]. / Histoplasmosis diseminada y síndrome hemofagocítico en pacientes VIH: serie de casos en un hospital peruano.

BACKGROUND: Disseminated histoplasmosis (DH) is an opportunistic fungal infection in severely immunocompromised patients with HIV infection. Haemophagocytic syndrome (HFS), which can occur in these co-infected patients when the immune response is significantly altered, is often associated with high mortality. AIMS: To describe the epidemiological, clinical, analytical and microbiological characteristics, along with studying the presence of HFS, in patients with DH-HIV. METHODS: A retrospective study was conducted on a case series using data from the clinical records of patients diagnosed with DH and HIV infection during the years 2014 and 2015. RESULTS: DH was diagnosed in 8 (1.3%) of 597 HIV patients. All patients were in stage C3, and 75% (6/8) were not receiving combined antiretroviral therapy (CART). The remaining two patients had recently begun CART (possible immune reconstitution syndrome). Five (62.5%) of the 8 patients met criteria for HFS. The most frequent clinical symptoms were lymphoproliferative and consumptive syndrome, respiratory compromise, and cytopenia. Histoplasma was isolated in lymph nodes of 75% (6/8) of the patients, in blood samples in 25% (2/8), and also in intestinal tissue in one patient. The antifungal therapy was amphotericin B deoxycholate, without adjuvants. The overall mortality was 50%. CONCLUSIONS: In this case series, DH-HIV co-infection frequently progressed to HFS with high mortality. The clinical picture may resemble that of other systemic opportunistic infections, such as tuberculosis, or can take place simultaneously with other infections. Clinical suspicion is important in patients with severe cytopenia and lymphoproliferative and consumptive syndrome in order to establish an early diagnosis and prescribing a timely specific therapy.

Obstrucción intestinal por Ascaris lumbricoides en un adulto mayor / Intestinal obstruction due to Ascaris lumbricoides infection in a geriatric patient

Ascaris lumbricoides is considered the largest intestinal nematode with a higher incidence in the childhood, representing a truly medical and public health problem, principally in undeveloped countries. We present the case of an 83 year old man, born and coming from the amazon region, without any relevant previous history of disease, admitted in the emergency department of our hospital for presenting intestinal obstruction and also presumptive biliary obstruction due to multiple balls of parasites, requiring immediate surgical intervention. We emphasize the need of consider this etiologic possibility in the differential diagnosis, that in this particular case, wasn't suspected in the first place.

Ascaris lumbricoides es considerado el nemátodo intestinal de mayor tamaño. Se presenta con mayor frecuencia en la infancia, representando un verdadero problema médico y de salud pública, especialmente en países en vías de desarrollo. Presentamos el caso de un varón de 83 años, natural y procedente de la región amazónica del Perú, sin antecedentes médicos de relevancia, que ingresa a Servicio de urgencias de nuestro hospital por un cuadro de obstrucción intestinal y presunta obstrucción biliar, requiriendo una intervención quirúrgica inmediata. El diagnóstico final de obstrucción intestinal por la presencia de múltiples ovillos de Ascaris lumbricoides, no fue considerado dentro de los diagnósticos diferenciales previo al acto quirúrgico.

[Intestinal obstruction due to Ascaris lumbricoides infection in a geriatric patient]. / Obstrucción intestinal por Ascaris lumbricoides en un adulto mayor.

Ascaris lumbricoides is considered the largest intestinal nematode with a higher incidence in the childhood, representing a truly medical and public health problem, principally in undeveloped countries. We present the case of an 83 year old man, born and coming from the amazon region, without any relevant previous history of disease, admitted in the emergency department of our hospital for presenting intestinal obstruction and also presumptive biliary obstruction due to multiple balls of parasites, requiring immediate surgical intervention. We emphasize the need of consider this etiologic possibility in the differential diagnosis, that in this particular case, wasn't suspected in the first place.

[Recurrent diarrhea due to Cystoisopora belli in HIV/AIDS patients receiving HAART]. / Diarrea recurrente por Cystoisopora belli en pacientes con infección por VIH con TARGA.

The Cystoisospora belli, before denominated as Isospora belli, is the etiologic agent of cystoisosoporiasis, an opportunistic infection affecting immunocompromised patients, characterized by chronic diarrhea and weight loss. The incidence of chronic diarrhea for this agent, in HIV patients, has decreased considerably. This thanks to the advent of highly active antiretroviral therapy (HAART), which has improved the patient's immune response and decrease viral load. We present six cases of cystoisosoporiasis recurrent and refractory to treatment in HIV patients, who was being treated with with trimethoprim / sulfamethoxazole (TMP / SMX) orally as a prophylaxis. Five of these patients passed away due to the infection, despite of the fact that they had a good response to HAART (adequate increase in CD4 and viral load undetectable) and they had been treated with second line drugs.

Diarrea recurrente por Cystoisopora belli en pacientes con infección por VIH con TARGA / Recurrent diarrhea due to Cystoisopora belli in HIV/AIDS patients receiving HAART

La Cystoisospora belli, antes denominada Isospora belli, es el agente etiológico de la cystoisosporiasis, una infección oportunista que afecta a pacientes inmunodeprimidos, caracterizada por diarrea crónica y pérdida ponderal. La incidencia de diarrea crónica por este agente, en pacientes infectados por el VIH, ha disminuido considerablemente. Ello gracias al advenimiento de la terapia antirretroviral de gran actividad (TARGA), con la que se ha logrado mejorar la respuesta inmunológica del paciente y disminuir su carga viral. Se presentan seis casos de cystoisosporiasis recurrente y refractaria en pacientes con infección por VIH, en quienes se diagnosticó cystoisosporiasis pese a que previamente se encontraban recibiendo profilaxis con trimetropin/sulfametoxazol (TMP/SMX). Cinco de ellos evolucionaron de manera tórpida y fallecieron, a pesar de una buena respuesta al TARGA (adecuado incremento de CD4 y disminución de la carga viral hasta rangos indetectables), y de tratamiento con TMP/SMX por vía oral y otros medicamentos de segunda línea.

The Cystoisospora belli, before denominated as Isospora belli, is the etiologic agent of cystoisosoporiasis, an opportunistic infection affecting immunocompromised patients, characterized by chronic diarrhea and weight loss. The incidence of chronic diarrhea for this agent, in HIV patients, has decreased considerably. This thanks to the advent of highly active antiretroviral therapy (HAART), which has improved the patient’s immune response and decrease viral load. We present six cases of cystoisosoporiasis recurrent and refractory to treatment in HIV patients, who was being treated with with trimethoprim / sulfamethoxazole (TMP / SMX) orally as a prophylaxis. Five of these patients passed away due to the infection, despite of the fact that they had a good response to HAART (adequate increase in CD4 and viral load undetectable) and they had been treated with second line drugs.

[Guillain Barré syndrome in association with Brucellosis]. / Síndrome de Guillain Barré asociado a Brucelosis.

We describe a case of a 47 years old male, with a history of 2 days of progressive, ascendant, symmetrical weakness in the lower extremities; a lumbar puncture was performed after the brain CT scan, as well as an electromyography, evidencing pure motor polyradiculopathy with axonal pattern, compatible with Guillain Barre syndrome. Afterwards, he received four plasmapheresis sessions, with clinical improvement from the second session. Due to his epidemiological background, Brucella set testing was done. Rose Bengal was positive, antibiotic treatment with rifampin and doxicicline was initiated, as well as rehabilitation. Three months later the patient recovered completely. The relevance of early treatment with plasmapheresis and the definition of the etiologic diagnosis determine that the prognosis of the Guillain Barre syndrome is favorable.

Cryptococcus gattii meningoencephalitis in an HIV-negative patient from the Peruvian Andes.

We report a case of an immunocompetent Peruvian patient from the Andes with a one-month history of meningoencephalitis. Cryptococcus gattii was identified from a cerebrospinal fluid culture through assimilation of D-proline and D-tryptophan as the single nitrogen source. Initially, the patient received intravenous antifungal therapy with amphotericin B. The patient was discharged 29 days after hospitalization and continued with oral fluconazole treatment for ten weeks. During this period, the patient showed clinical improvement with slight right-side residual weakness. Through this case report, we confirm the existence of this microorganism as an infectious agent in Peru.

Cryptococcus gattii meningoencephalitis in an HIV-negative patient from the Peruvian Andes / Meningoencefalite causada por Cryptococcus gattii em um paciente HIV-negativo procedente dos Andes Peruanos

We report a case of an immunocompetent Peruvian patient from the Andes with a one-month history of meningoencephalitis. Cryptococcus gattii was identified from a cerebrospinal fluid culture through assimilation of D-proline and D-tryptophan as the single nitrogen source. Initially, the patient received intravenous antifungal therapy with amphotericin B. The patient was discharged 29 days after hospitalization and continued with oral fluconazole treatment for ten weeks. During this period, the patient showed clinical improvement with slight right-side residual weakness. Through this case report, we confirm the existence of this microorganism as an infectious agent in Peru.

Nós reportamos o caso de um paciente peruano immunocompetente proveniente dos Andes com história de um mês com meningoencefalite. Foi identificado o Cryptococcus gattii na cultura de liquido cerebrospinal através da assimilação de D-prolina e D-tryptofano como fonte única de nitrogênio. Inicialmente, o paciente recebeu tratamento antifúngico intravenoso com amfotericina B. O paciente foi liberado 29 dias depois da hospitalização, seguindo tratamento oral durante 10 semanas com fluconazol. Durante este período, o paciente apresentou melhoria clinica e uma leve fraqueza residual direita. Com o reporte do caso, nós confirmamos a existência desse microorganismo como agente infeccioso em nosso país.

Síndrome de Guillain Barré asociado a Brucelosis / Guillain Barré Syndrome in association with Brucellosis

Se describe el caso de un varón de 47 años, con tiempo de enfermedad de dos días, caracterizado por pérdida de fuerza progresiva, simétrica y ascendente de miembros inferiores, se realizó punción lumbar luego de la tomografía cerebral y electromiografía lo cual evidenció polirradiculopatía motora pura con patrón axonal, compatible con el síndrome de Guillain Barré. Posteriormente, recibió cuatro sesiones de plasmaféresis, con mejoría clínica significativa desde la segunda sesión. Debido al antecedente epidemiológico se solicitó set para Brucellas, con rosa de Bengala positivo, se inició tratamiento antibiótico con rifampicina y doxiciclina, además de rehabilitación. Tres meses después el paciente mejoró completamente. La importancia del tratamiento temprano con plasmaféresis y determinar su diagnóstico etiológico hacen que el pronóstico del síndrome de Guillain Barré sea favorable.

We describe a case of a 47 years old male, with a history of 2 days of progressive, ascendant, symmetrical weakness in the lower extremities; a lumbar puncture was performed after the brain CT scan, as well as an electromyography, evidencing pure motor polyradiculopathy with axonal pattern, compatible with Guillain Barre syndrome. Afterwards, he received four plasmapheresis sessions, with clinical improvement from the second session. Due to his epidemiological background, Brucella set testing was done. Rose Bengal was positive, antibiotic treatment with rifampin and doxicicline was initiated, as well as rehabilitation. Three months later the patient recovered completely. The relevance of early treatment with plasmapheresis and the definition of the etiologic diagnosis determine that the prognosis of the Guillain Barre syndrome is favorable.

Microscopic observation drug susceptibility assay for tuberculosis screening before isoniazid preventive therapy in HIV-infected persons.

BACKGROUND: Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons. METHODS: A total of 471 HIV-infected IPT candidates at 3 hospitals in Lima, Peru, were enrolled in a prospective comparison of TB screening strategies, including laboratory, clinical, and radiographic assessments. RESULTS: Of 435 patients who provided 2 sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS culture, 22 (5.1%) by Lowenstein-Jensen culture, and 7 (1.6%) by smear. Of patients with any positive microbiological test result, a MODS culture was positive in 96% by 14 days and 100% by 21 days. The MODS culture simultaneously detected multidrug-resistant TB in 2 patients. Screening strategies involving combinations of clinical assessment, chest radiograph, and sputum smear were less effective than 2 liquid TB cultures in accurately diagnosing and excluding TB (P<.01). Screening strategies that included nonculture tests had poor sensitivity and specificity. CONCLUSIONS: MODS culture identified and reliably excluded cases of pulmonary TB more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. Streamlining of the ruling out of TB through the use of liquid culture-based strategies could help facilitate the massive up-scaling of IPT required to reduce HIV and TB morbidity and mortality.

Upper-room ultraviolet light and negative air ionization to prevent tuberculosis transmission.

BACKGROUND: Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. METHODS AND FINDINGS: For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. CONCLUSIONS: Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings.

Cutaneous acanthamebiasis infection in immunocompetent and immunocompromised patients.

BACKGROUND: Cutaneous acanthamebiasis is a rare infection and few patients have been reported worldwide. METHODS: Observational and descriptive study carried out from March 1996 to February 2006 in patients with diagnosis of cutaneous free-living amebic infection caused by Acanthamoeba spp. The patients were diagnosed at the Dos de Mayo National Hospital (Lima-Peru) where skin biopsies, histopathologic studies and cultures were performed. The clinical and epidemiologic characteristics, diagnosis, treatment and evolution were recorded in a survey. RESULTS: Five patients with cutaneous free-living amebic infection caused by Acanthamoeba spp. were identified. Skin lesions were ulceronecrotic (four patients), an infiltrative bluish plaque (one patient), and a periorbital tumor (one patient). Three patients were positive for human immunodeficiency virus (HIV), had only cutaneous involvement, and died of opportunistic infections. The two immunocompetent patients developed Acanthamoeba granulomatous encephalitis and meningoencephalitis that progressed to intracranial hypertension and death. CONCLUSION: The clinical manifestations of cutaneous free-living amebic infection caused by Acanthamoeba spp. appear to vary according to the underlying immunologic status.

The infectiousness of tuberculosis patients coinfected with HIV.

BACKGROUND: The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB. METHODS AND FINDINGS: All air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour. CONCLUSIONS: A small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.

The detection of airborne transmission of tuberculosis from HIV-infected patients, using an in vivo air sampling model.

BACKGROUND: Nosocomial transmission of tuberculosis remains an important public health problem. We created an in vivo air sampling model to study airborne transmission of tuberculosis from patients coinfected with human immunodeficiency virus (HIV) and to evaluate environmental control measures. METHODS: An animal facility was built above a mechanically ventilated HIV-tuberculosis ward in Lima, Peru. A mean of 92 guinea pigs were continuously exposed to all ward exhaust air for 16 months. Animals had tuberculin skin tests performed at monthly intervals, and those with positive reactions were removed for autopsy and culture for tuberculosis. RESULTS: Over 505 consecutive days, there were 118 ward admissions by 97 patients with pulmonary tuberculosis, with a median duration of hospitalization of 11 days. All patients were infected with HIV and constituted a heterogeneous group with both new and existing diagnoses of tuberculosis. There was a wide variation in monthly rates of guinea pigs developing positive tuberculin test results (0%-53%). Of 292 animals exposed to ward air, 159 developed positive tuberculin skin test results, of which 129 had laboratory confirmation of tuberculosis. The HIV-positive patients with pulmonary tuberculosis produced a mean of 8.2 infectious quanta per hour, compared with 1.25 for HIV-negative patients with tuberculosis in similar studies from the 1950s. The mean monthly patient infectiousness varied greatly, from production of 0-44 infectious quanta per hour, as did the theoretical risk for a health care worker to acquire tuberculosis by breathing ward air. CONCLUSIONS: HIV-positive patients with tuberculosis varied greatly in their infectiousness, and some were highly infectious. Use of environmental control strategies for nosocomial tuberculosis is therefore a priority, especially in areas with a high prevalence of both tuberculosis and HIV infection.

Natural ventilation for the prevention of airborne contagion.

BACKGROUND: Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings. METHODS AND FINDINGS: The study was carried out in eight hospitals in Lima, Peru; five were hospitals of "old-fashioned" design built pre-1950, and three of "modern" design, built 1970-1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open. CONCLUSIONS: Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion.

Diagnosis of sputum-scarce HIV-associated pulmonary tuberculosis in Lima, Peru.

Sputum induction, bronchoalveolar lavage, or gastric aspiration are often needed to produce adequate diagnostic respiratory samples from people with HIV in whom tuberculosis is suspected. Since these procedures are rarely appropriate in less-developed countries, we compared the performances of a simple string test and the gold-standard sputum induction. 160 HIV-positive adults under investigation for tuberculosis, and 52 asymptomatic HIV-positive control patients underwent the string test followed by sputum induction. The string test detected tuberculosis in 14 patients in whom this disease was suspected; sputum induction detected only eight of them (McNemar's test, p=0.03). These preliminary data suggest that the string test is safe and effective for retrieval of useful clinical specimens for diagnosis of pulmonary tuberculosis, and is at least as sensitive as sputum induction.