Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.

This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 µg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 µg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).

'Cough-triggered' tuberculosis screening among adults with diabetes in Tanzania.

AIMS: Diabetes increases the risk of tuberculosis and the prevalence of diabetes is rising in tuberculosis-endemic regions such as sub-Saharan Africa. Resource-appropriate strategies for tuberculosis case finding among African adults with diabetes are needed. The aims of this study were to determine prevalence of tuberculosis and evaluate one screening strategy among adult Tanzanians with diabetes. METHODS: In this prospective cohort study, we evaluated a 'cough-triggered' strategy for tuberculosis case finding among adults with diabetes at our zonal hospital in Tanzania. All adults with diabetes and cough underwent further tuberculosis symptom assessment, and those with productive cough had sputum collected for microscopy and Mycobacterium tuberculosis culture. RESULTS: Between September 2011 and March 2012, 700 adults with diabetes attended our hospital. A total of 693 were enrolled, 121/693 (17.5%) had cough and 32/693 (4.6%) had at least two of the classic symptoms of tuberculosis. Of note, 87/121 (71.9%) of patients with cough could not produce sputum spontaneously. Nine patients were diagnosed with tuberculosis for a prevalence of 1299/100 000 (1.3%), sevenfold greater than the national average. CONCLUSIONS: Tuberculosis is common among Tanzanian adults with diabetes, but tuberculosis case finding is challenging because of the high prevalence of non-productive cough. This low-cost, 'cough-triggered' tuberculosis case-finding strategy may serve as a reasonable first step for improving tuberculosis screening among adults with diabetes in sub-Saharan Africa.

An Ad5-vectored HIV-1 vaccine elicits cell-mediated immunity but does not affect disease progression in HIV-1-infected male subjects: results from a randomized placebo-controlled trial (the Step study).

BACKGROUND: The Step study was a randomized trial to determine whether an adenovirus type 5 (Ad5) vector vaccine, which elicits T cell immunity, can lead to control of human immunodeficiency virus (HIV) replication in participants who became HIV-infected after vaccination. METHODS: We evaluated the effect of the vaccine on trends in HIV viral load, CD4+ T cell counts, time to initiation of antiretroviral therapy (ART), and AIDS-free survival in 87 male participants who became infected with HIV during the Step study and who had a median of 24 months of post-infection follow-up. RESULTS: There was no overall effect of vaccine on mean log(10) viral load (estimated difference between groups, -0.11; P = .47). In a subset of subjects with protective HLA types (B27, B57, B58), mean HIV-1 RNA level over time was lower among vaccine recipients. There was no significant difference in CD4+ T cell counts, time to ART initiation, or in AIDS-free survival between HIV-1-infected subjects who received vaccine versus those who received placebo. CONCLUSIONS: HIV RNA levels, CD4+ T cell counts, time to initiation of ART, and AIDS-free survival were similar in vaccine and placebo recipients. There may have been a favorable effect of vaccine on HIV-1 RNA levels in participants with HLA types associated with better control of HIV-1.

Diagnostic yield of active case finding for tuberculosis at human immunodeficiency virus testing in Haiti.

SETTING: The Groupe Haïtien d'étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) Centres, Port-au-Prince, Haiti, facilitate "test and treat" strategies by screening all patients for tuberculosis (TB) at human immunodeficiency virus (HIV) testing.OBJECTIVE: 1) To determine the proportion of patients with chronic cough at HIV testing diagnosed with TB, stratified by HIV test results; and 2) to evaluate the additional diagnostic yield of Xpert® MTB/RIF vs. sputum microscopy.DESIGN: We conducted a retrospective cohort analysis including all adults tested for HIV at GHESKIO from August 2014 to July 2015.RESULTS: Of 29 233 adult patients tested for HIV, 2953 (10%) were diagnosed as HIV-positive. Chronic cough lasting ≥2 weeks was reported by 1116 (38%) HIV-positive patients; 984 (88%) were tested and 265 (27%) were diagnosed with TB. Chronic cough was reported by 5985 (23%) HIV-negative patients; 5654 (94%) were tested and 1179 (21%) were diagnosed with TB. Of all bacteriologically confirmed cases, 27% were smear-negative and Xpert-positive. Among all TB patients, 81% were HIV-negative.CONCLUSIONS: Screening for TB at HIV testing was high-yield, among both HIV-infected and HIV-negative individuals. Testing for both diseases should be conducted among patients who present with chronic cough at HIV testing.

Blood transcriptomic markers of Mycobacterium tuberculosis load in sputum.

BACKGROUND: Peripheral blood transcriptome signatures that distinguish active pulmonary tuberculosis (TB) from control groups have been reported, but correlations of these signatures with sputum mycobacterial load are incompletely defined. METHODS: We assessed the performance of published TB transcriptomic signatures in Haiti, and identified transcriptomic biomarkers of TB bacterial load in sputum as measured by Xpert® MTB/RIF molecular testing. People in Port au Prince, Haiti, with untreated pulmonary TB (n = 51) formed the study cohort: 19 people with low and 32 with high sputum Mycobacterium tuberculosis load. Peripheral whole blood transcriptomes were generated using RNA sequencing. RESULTS: Twenty of the differentially expressed transcripts in TB vs. no TB were differentially expressed in people with low vs. high sputum mycobacterial loads. The difference between low and high bacterial load groups was independent of radiographic severity. In a published data set of transcriptomic response to anti-tuberculosis treatment, this 20-gene subset was more treatment-responsive at 6 months than the full active TB signature. CONCLUSION: We identified genes whose transcript levels in the blood distinguish active TB with high vs. low M. tuberculosis loads in the sputum. These transcripts may reveal mechanisms of mycobacterial control of M. tuberculosis during active infection, as well as identifying potential biomarkers for bacterial response to anti-tuberculosis treatment.

Outcomes across the tuberculosis care continuum among adolescents in Haiti.

Setting: GHESKIO (Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes) clinic, Port-au-Prince, Haiti. Objective: To evaluate tuberculosis (TB) care continuum outcomes among adolescents. Design: Among a retrospective cohort of 10-24 year olds diagnosed with active TB, we report completion of the following steps of the TB care continuum stratified by human immunodeficiency virus (HIV) status: diagnosis of microbiologically confirmed TB, initiation of anti-tuberculosis treatment, retention in care at 2 months on anti-tuberculosis treatment, and TB treatment success. Factors associated with attrition at each step were identified using multivariable regression. Results: A total of 1005 adolescents were diagnosed with active TB; 74 (7%) were HIV-positive at the time of TB diagnosis. HIV-positive patients had poorer outcomes than non-HIV-infected patients: 73% vs. 85% initiated anti-tuberculosis treatment (P < 0.01), 46% vs. 74% were retained in care at 2 months (P < 0.01), and 41% vs. 68% achieved TB treatment success (P < 0.01). Among those who initiated treatment, same-day initiation resulted in less treatment failure. Attrition before treatment initiation was associated with female sex and HIV coinfection. Attrition after treatment initiation was associated with age ⩾16 years and HIV coinfection. Conclusion: Outcomes across the TB care continuum are suboptimal among adolescents, with only two thirds of patients achieving treatment success. Interventions tailored to adolescents are needed to improve retention in care, particularly for those who are co-infected with HIV.

Contexte : Centre de santé, Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes, Port-au-Prince, Haïti.Objectif : Evaluer les résultats tout au long de la prise en charge de la tuberculose (TB) parmi les adolescents.Schéma : Parmi une cohorte rétrospective d'adolescents âgés de 10­24 ans ayant eu un diagnostic de TB active, nous rapportons le déroulement des étapes suivantes des soins de la TB stratifiés par statut virus de l'immunodéficience humaine (VIH) : diagnostic de TB confirmée par microbiologie ; mise en route du traitement de la TB ; rétention en soins à 2 mois sous traitement de TB ; et succès du traitement de TB. Les facteurs associés à l'attrition à chaque étape ont été identifiés grâce à une régression logistique multivariée.Résultats: Des 1005 adolescents qui ont eu un diagnostic de TB active, 74 (7%) ont été positifs au VIH au moment du diagnostic de TB. Les patients VIH positifs ont eu des résultats plus médiocres comparés aux patients non infectés par le VIH : 73% contre 85% ont mis en route le traitement de TB (P < 0,01), 46% contre 74% sont restés sous traitement à 2 mois (P < 0,01) et 41% contre 68% ont achevé le traitement avec succès (P < 0,01). Parmi ceux qui ont mis en route le traitement, une prise dès le premier jour a abouti à moins d'échec du traitement. L'attrition avant le début du traitement a été associée au sexe féminin et à la coinfection à VIH. L'attrition après mise en route du traitement a été associée à un âge ⩾16 ans et à la coinfection à VIH.Conclusion : Les résultats au niveau de la continuité des soins de TB sont sousoptimaux parmi les adolescents, dont seulement deux tiers achèvent le traitement avec succès. Des interventions adaptées aux adolescents sont requises pour améliorer la rétention en soins, particulièrement pour ceux qui sont coinfectés par le VIH.

Marco de Referencia: El centro du Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes de Port-au-Prince, en Haití.Objetivo: Evaluar los resultados del proceso asistencial continuo de la tuberculosis (TB) en los adolescentes.Método: En una cohorte retrospectiva de jóvenes de 10­24 años de edad con diagnóstico de TB activa, se comunican los resultados logrados en las siguientes etapas del proceso asistencial continuo de la TB, estratificados según la situación frente al virus de la inmunodeficiencia humana (VIH): diagnóstico de TB confirmada microbiológicamente; inicio del tratamiento antituberculoso; retención en la atención a los 2 meses del tratamiento; y el éxito del tratamiento antituberculoso. Se determinaron los factores asociados con el abandono en cada etapa mediante un modelo de regresión multivariante.Resultados: Se diagnosticó TB activa en 1005 adolescentes; 74 de ellos (7%) eran positivos frente al VIH en el momento del diagnóstico de TB. Los pacientes positivos frente al VIH presentaron desenlaces más desfavorables que los pacientes sin infección por el VIH (73% contra 85% inició el tratamiento antituberculoso, P < 0,01; 46% contra 74% continuaba en la atención a los 2 meses, P < 0,01; y 41% contra 68% alcanzó un tratamiento antituberculoso exitoso, P < 0,01). Los jóvenes que iniciaron tratamiento el mismo día de la consulta presentaron menos fracasos terapéuticos. El abandono antes de iniciar el tratamiento se asoció con el sexo femenino y la coinfección por el VIH. El abandono después de haber iniciado el tratamiento se asoció con la edad ⩾16 años y la coinfección por el VIH.Conclusión: Los resultados a lo largo de la continuidad asistencial de la TB son deficientes en los adolescentes, pues solo dos tercios de ellos alcanzan el éxito terapéutico. Se precisan intervenciones adaptadas a los adolescentes que mejoren la retención en los servicios de atención, sobre todo en los pacientes coinfectados por el VIH.

The ripple effect: why promoting female leadership in global health matters.

Leadership positions in global health are greatly skewed toward men; the imbalance is more pronounced in low- and middle-income countries (LMICs). The under-representation of women in leadership is a threat to gender equality, and also impacts the improvement of women's health outcomes globally. In this perspectives piece, we assert that the promotion and retention of women in global health leadership has a ripple effect that can achieve improvement in global health outcomes. We present pragmatic, actionable solutions to promote and retain female global health leaders in this field.

Les positions de dirigeant dans la santé du monde sont largement orientées vers les hommes et ce déséquilibre est encore plus prononcé dans les pays à revenu faible et moyen. La sous-représentation des femmes en termes de dirigeant menace l'égalité des genres et a également un impact sur l'amélioration de l'état de santé des femmes dans le monde. Dans cette perspective, nous affirmons que la promotion et la rétention des femmes au sein du leadership de la santé dans le monde a un effet d'entraînement qui peut aboutir à une amélioration de l'état de santé dans le monde. Nous présentons des solutions pragmatiques et réalisables pour promouvoir et retenir des leaders féminins en matière de santé dans le monde.

Los puestos directivos en materia de salud mundial se asignan de manera desproporcionada a los hombres; este desequilibrio es aun más notorio en los países de ingresos bajos y medianos. La subrepresentación de las mujeres en los cargos de responsabilidad pone en peligro la equidad entre los hombres y las mujeres y tiene además repercusiones en los resultados de salud de las mujeres en el mundo. En el presente artículo de opinión, se sostiene que promover a las mujeres a las funciones directivas relacionadas con la salud mundial y facilitar su permanencia en ellas genera una reacción en cadena que puede dar lugar a mejores resultados de salud a escala mundial. Se proponen soluciones viables y prácticas encaminadas a estimular la presencia de las mujeres en los cargos de responsabilidad en materia de salud mundial y a respaldar su permanencia en esta actividad.

CD4 deficit and tuberculosis risk persist with delayed antiretroviral therapy: 5-year data from CIPRA HT-001.

SETTING: Port-au-Prince, Haiti. OBJECTIVE: To determine long-term effects of early vs. delayed initiation of antiretroviral therapy (ART) on immune recovery and tuberculosis (TB) risk in human immunodeficiency virus (HIV) infected individuals. DESIGN: Open-label randomized controlled trial of immediate ART in HIV-infected adults with CD4 counts between 200 and 350 cells/mm(3) vs. deferring ART until the CD4 count was <200 cells/mm(3). The primary comparisons were CD4 counts over time and risk for incident TB, with 5 years of follow-up. RESULTS: A total of 816 participants were enrolled, with 408 in each treatment arm. The early treatment group started ART within 2 weeks, while the deferred treatment group started ART a median of 1.3 years after enrollment. After 5 years, the mean CD4 count in the early treatment group was significantly higher than in the deferred treatment group (496 cells/mm(3), 95% confidence interval [CI] 477-515 vs. 373 cells/mm(3), 95%CI 357-389; P < 0.0001). TB risk was higher in the deferred treatment group (unadjusted HR 2.41, 95%CI 1.56-3.74; P < 0.0001) and strongly correlated with lower CD4 counts in time-dependent multivariate analysis. CONCLUSION: Delays in ART initiation for HIV-infected adults with CD4 counts of 200-350 cells/mm(3) can result in long-term immune dysfunction and persistent increased risk for TB.

HIV infection in Haiti: natural history and disease progression.

OBJECTIVE: A study was conducted to define the natural history and disease progression of HIV infection in a developing country. DESIGN: A prospective longitudinal cohort study. METHODS: Forty-two patients with documented dates of HIV seroconversion were followed in Port-au-Prince, Haiti. Patients were seen at 3 month intervals or when ill. Patients were treated for bacterial, mycobacterial, parasitic, and fungal infections, but antiretroviral therapy was not available. Patients were followed until death or until 1 January 2000; median follow-up was 66 months. RESULTS: By Kaplan-Meier analyses, the median time to symptomatic HIV disease (CDC category B or C) was 3.0 years [95% confidence interval (CI) 2.3-5.0 years]. The median time to AIDS (CDC category C) was 5.2 years (95% CI 4.7-6.5 years), and the median time to death was 7.4 years (95% CI 6.2-10.2 years). Community-acquired infections, including respiratory tract infections, acute diarrhea, and skin infections were common in the pre-AIDS period. AIDS-defining illnesses included tuberculosis, wasting syndrome, cryptosporidiosis, cyclosporiasis, candida esophagitis, toxoplasmosis, and cryptococcal meningitis. Rapid progression to death was associated with anemia at the time of seroconversion hazards ratio (HR) 4.1 (95% CI 1.1-15.0), age greater than 35 years at seroconversion HR 4.4 (95% CI 1.1-16.6), and lymphopenia at seroconversion HR 11.0 (95% CI 2.3-53.0). CONCLUSION: This report documents rapid disease progression from HIV seroconversion until death among patients living in a developing country. Interventions, including nutritional support and prophylaxis of common community-acquired infections during the pre-AIDS period may slow disease progression and prolong life for HIV-infected individuals in less-developed countries.

Integration of tuberculosis screening at an HIV voluntary counselling and testing centre in Haiti.

OBJECTIVE: To describe the integration of tuberculosis screening into the activities of an HIV voluntary counselling and testing (VCT) centre in a country with endemic tuberculosis. SETTING: An HIV VCT centre in Port au Prince, Haiti. DESIGN: All patients presenting for HIV VCT who reported cough received same-day evaluation for active tuberculosis. Of the 1327 adults presenting to the centre for the first time between January and April 1997, 263 (20%) reported cough and of these 241 (92%) were evaluated. RESULTS: Of the 241 patients evaluated for cough, 76 (32%) were diagnosed with pulmonary tuberculosis. Of the 76 patients diagnosed with pulmonary tuberculosis, 28 (37%) had a positive smear for acid-fast bacilli (AFB), 14 (18%) had a negative AFB smear but a positive sputum culture for Mycobacterium tuberculosis, and 34 (45%) had culture-negative tuberculosis. Also, 31 out of 241 (13%) VCT clients evaluated for cough were diagnosed with bacterial pneumonia. CONCLUSION: This report confirms that in areas with a high HIV and tuberculosis prevalence, a high proportion of VCT clients have active pulmonary tuberculosis. The integration of tuberculosis screening offers several benefits, including the diagnosis and treatment of large numbers of individuals with tuberculosis, a decreased risk of nosocomial tuberculosis transmission, and the opportunity to provide tuberculosis prophylaxis to HIV-positive patients in whom tuberculosis has been excluded. Future studies are needed to determine the cost-effectiveness of integrated tuberculosis and HIV VCT services, and whether integration should be recommended in all countries with high HIV and tuberculosis rates.

Economic hardship and sexually transmitted diseases in Haiti's rural Artibonite Valley.

A study was conducted to determine the prevalence rate and risk factors for sexually transmitted diseases (STDs) in Haiti's rural Artibonite Valley. Women attending antenatal services at Hospital Albert Schweitzer from October to December 1996 were tested for gonorrhea, chlamydia, trichomonas, syphilis, and human immunodeficiency virus (HIV). Of the 476 women tested, 121 (25.4%) had trichomonas, 11/475 (2.3%) had gonorrhea, 51/475 (10.7%) had chlamydia, 32/474 (6.8%) were seropositive for syphilis, 20/469 (4.3%) were seropositive for HIV, and 191 (40.1%) had at least one STD. Nearly 30% of the women reported having entered a sexual relationship out of economic necessity and had increased odds of HIV infection, Odds Ratio (OR) 6.3 (P < 0.001). We postulate that due to recent economic hardship in rural Haiti, women are entering into sexual relationships out of economic necessity and that this trend is contributing to the growing HIV epidemic. We recommend STD prevention and development programs that target young people and economically disadvantaged women.

Prevalence, burden, and control of syphilis in Haiti's rural Artibonite region.

OBJECTIVES: A study was conducted to determine the prevalence and health consequences of syphilis and to evaluate existing control measures in a Haitian rural district of 200,000 people served by 12 community dispensaries and Hospital Albert Schweitzer. METHODS: Syphilis seroprevalence among consecutive women receiving antenatal services was assessed using rapid plasma reagin (RPR) screening and fluorescent treponemal antibody absorption (FTA-ABS) confirmatory testing. Hospital and dispensary records were used to review genital ulcer disease and syphilis cases seen during 1995. RESULTS: Of 811 pregnant women attending prenatal clinics during a 3-month period in 1996, 46 (5.7%) were RPR reactive. Syphilis seroreactivity was confirmed in 45 (97.8%) of 46 samples by FTA-ABS. Of 649 women attending dispensaries in the valley 41 (6.3%) were syphilis seroreactive compared with 4 (2.5%) of 162 women attending dispensaries in the mountains (OR = 2.66; P = 0.056). In 1995, 620 cases of genital ulcer disease were seen at the community dispensaries. At the central hospital, 257 new diagnoses of syphilis were made in 1995, including 30 cases of primary and secondary syphilis, 168 cases of latent disease, 17 cases of recurrent infection, 9 cases of tertiary disease, and 33 cases of congenital syphilis. CONCLUSIONS: The 33 cases of congenital syphilis, a rate of 550 cases for 100,000 live births, clearly demonstrated a failure of local control measures. Decentralized prenatal screening for syphilis, same-day treatment of seroreactors, and strengthened partner treatment were initiated. Further studies to improve primary prevention of syphilis in rural populations have been started. Other strategies, including mass treatment of high-risk groups, should be investigated.

Telling the stories of people with AIDS in rural Haiti.

For 20 years, Hospital Albert Schweitzer (HAS) in Haiti's Artibonite Valley has struggled with the evolving acquired immune deficiency syndrome (AIDS) epidemic. Initial efforts to confront the disease met numerous obstacles including denial, stigmatization, powerlessness, and mistrust. Over time, HAS and local community organizations developed a new approach to the AIDS problem. The first step in this approach flowed from the founding principle of HAS: Reverence for Life; hospital staff and community leaders provided hospice care to people dying of AIDS. Caring for people with AIDS and hearing the stories of people with AIDS quickly generated sympathy and a personal sense of vulnerability among community leaders and created a desire for community human immunodeficiency virus (HIV) education and prevention. Using the stories of people with AIDS as a basis, a community education program was launched. More than 1,000 church leaders, voodoo priests, and schoolteachers were trained. The majority of these leaders returned to their communities and started creative and unexpected initiatives to confront the AIDS problem.

Predictors of tuberculosis in first 6 months after initiation of antiretroviral therapy: a case-control study.

SETTING: In Africa, 10% of human immunodeficiency virus (HIV) infected adults starting antiretroviral therapy (ART) die within the first year, and tuberculosis (TB) is the leading cause of death. OBJECTIVE: To investigate the predictors of ART-associated TB at an adult HIV clinic in Tanzania. DESIGN: In this nested case-control study, adults starting ART were screened for TB according to the World Health Organization protocol. Those not diagnosed with TB were observed for 6 months. Patients diagnosed with TB were defined as cases, and controls were selected from among the patients who did not develop TB using incidence density matching. RESULTS: Among the 2514 HIV-positive adults in our cohort, 72 (3%) were diagnosed with TB during the first 6 months of ART. By multivariate analysis, baseline characteristics predictive of TB were cough, fever and night sweats; 76% (55/72) of the cases had at least one of these symptoms at the time of starting ART. CONCLUSION: Overall, 75% of the patients who developed TB during the first 6 months of ART had TB symptoms at the time of starting ART. Improved TB diagnostics and/or better strategies for empirical anti-tuberculosis treatment are needed for patients with symptoms of TB at ART initiation.

Outcomes of HIV-infected patients treated for recurrent tuberculosis with the standard retreatment regimen.

SETTING: The Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (the GHESKIO AIDS and TB Center) in Port-au-Prince, Haiti. OBJECTIVE: To measure the effectiveness of the standard TB retreatment regimen (2HRZES/1HRZE/5HRE) in human immunodeficiency virus (HIV) infected adults. DESIGN: Cohort study. RESULTS: Of 1318 HIV-infected patients with access to antiretroviral therapy following World Health Organization guidelines, 56 were diagnosed with recurrent pulmonary TB and retreated with the standard retreatment regimen: 10 patients (18%) died during retreatment, 3 (5%) defaulted, and 2 (4%) failed treatment. Forty-one patients (73%) achieved retreatment 'success' (cure, treatment completed). Of these, 8 (20%) died during follow-up, 5 (12%) were lost, and 5 (12%) had a second recurrence of TB. Only 26 (46%) of the 56 patients remained alive, in care, and TB-free after a median of 36 months of follow-up. CONCLUSION: HIV-infected patients treated for recurrent TB with the standard retreatment regimen have high mortality and poor long-term outcomes.

A multi-centre evaluation of nine rapid, point-of-care syphilis tests using archived sera.

OBJECTIVES: To evaluate nine rapid syphilis tests at eight geographically diverse laboratory sites for their performance and operational characteristics. METHODS: Tests were compared "head to head" using locally assembled panels of 100 archived (50 positive and 50 negative) sera at each site using as reference standards the Treponema pallidum haemagglutination or the T pallidum particle agglutination test. In addition inter-site variation, result stability, test reproducibility and test operational characteristics were assessed. RESULTS: All nine tests gave good performance relative to the reference standard with sensitivities ranging from 84.5-97.7% and specificities from 84.5-98%. Result stability was variable if result reading was delayed past the recommended period. All the tests were found to be easy to use, especially the lateral flow tests. CONCLUSIONS: All the tests evaluated have acceptable performance characteristics and could make an impact on the control of syphilis. Tests that can use whole blood and do not require refrigeration were selected for further evaluation in field settings.

Physicochemical properties of cloned nucleocapsid protein from HIV. Interactions with metal ions.

The nucleocapsid (NC) protein (p15) of the human immunodeficiency virus (HIV) has been cloned and overproduced (under the control of a phage T7 promoter) in soluble form in an Escherichia coli host. The soluble NC protein is a fusion protein containing 15 amino acids from the T7 gene 10 and 7 amino acids from the HIV p24 protein at the N-terminus to make a protein of 171 amino acids. The plasmid containing the fusion gene is designated p15DF. A homogeneous product has been isolated from the induced cells and, when isolated under aerobic conditions, contains 0.3-0.5 mol of Zn/mol of protein and has only 2 titratable SH groups. Reduction and refolding in the presence of Zn(II) yields a protein containing 2.0 mol of Zn/mol of protein and 6 titratable SH groups. On the other hand, if the cells are sonicated in 2 mM CdCl2 and purified at pH 5.0, an unoxidized protein containing 2 mol of Cd/mol of protein is obtained. The Cd(II) ions can be exchanged with Zn(II), Co(II), or 113Cd(II). The Co(II)2 NC protein shows d-d electronic transitions at 695 nm [epsilon = 675 M-1 cm-1 per Co(II)] and 640 nm [epsilon = 825 M-1 cm-1 per Co(II)] compatible with regular tetrahedral geometry around both Co(II) ions. The Co(II)2 and Cd(II)2 NC proteins show intense charge-transfer bands in the near-UV, at 355 nm (epsilon = approximately 4000 M-1 cm-1) and 310 nm (epsilon = approximately 8000 M-1 cm-1) for the Co(II) protein and 255 nm (epsilon = approximately 10(4) M-1 cm-1) for the Cd(II)2 NC protein, compatible with -S- coordination. 113Cd NMR of the 113Cd(II)2 NC protein shows two 113Cd NMR signals at 659 and 640 ppm, respectively, each integrating to approximately 1 Cd(II) ion. The downfield chemical shifts suggest coordination of each 113Cd(II) ion to 3 sulfur donor atoms. The spectroscopic data fully support the prediction that the NC protein binds metal ions to each of the tandem repeats of the -Cys-X2-Cys-X4-His-X4-Cys- sequence contained in the N-terminal half of the molecule. 113Cd NMR shows, however, that the sites are not identical. Isolation of the NC protein under standard aerobic conditions results in oxidation of the sulfhydryl groups and loss of the coordinated Zn(II) ions, while preparation of the NC protein as the Cd(II) derivative at low pH protects the sulfhydryl groups from oxidation.

Trimethoprim-sulfamethoxazole compared with ciprofloxacin for treatment and prophylaxis of Isospora belli and Cyclospora cayetanensis infection in HIV-infected patients. A randomized, controlled trial.

BACKGROUND: In developing countries, Isospora belli and Cyclospora cayetanensis frequently cause chronic diarrhea in HIV-infected patients. OBJECTIVE: To compare 1 week of trimethoprim-sulfamethoxazole treatment and 1 week of ciprofloxacin treatment in HIV-infected patients with chronic diarrhea caused by I. belli and C. cayetanensis. DESIGN: Randomized, controlled trial. SETTING: HIV clinic in Port-au-Prince, Haiti. PATIENTS: 42 HIV-infected patients with chronic diarrhea due to I. belli (n = 22) or C cayetanensis (n = 20). INTERVENTIONS: Patients were randomly assigned to receive oral trimethoprim-sulfamethoxazole (160 mg or 800 mg) or ciprofloxacin (500 mg) twice daily for 7 days. Patients who responded clinically and microbiologically received prophylaxis for 10 weeks (1 tablet orally, three times per week). MEASUREMENTS: Treatment success was measured by cessation of diarrhea and negative stool examination at day 7. Prophylaxis success was measured by recurrent disease rate. RESULTS: Diarrhea ceased in all 19 patients treated with trimethoprim-sulfamethoxazole. Eighteen of 19 patients had negative results on stool examination at day 7 (95%). Among the 23 patients who received ciprofloxacin, diarrhea ceased in 20 (87% [CI; 66% to 97%]) and 16 had negative results on stool examination at day 7 (70%). By survival analysis, diarrhea from isosporiasis and cyclosporiasis ceased more rapidly with trimethoprim-sulfamethoxazole than with ciprofloxacin. All patients receiving secondary prophylaxis with trimethoprim-sulfamethoxazole remained disease-free, and 15 of 16 patients receiving secondary prophylaxis with ciprofloxacin remained disease-free. CONCLUSIONS: A 1-week course of trimethoprim-sulfamethoxazole is effective in HIV-infected patients with cyclosporiasis or isosporiasis. Although ciprofloxacin is not as effective, it is acceptable for patients who cannot tolerate trimethoprim-sulfamethoxazole.

Active tuberculosis in individuals infected with human immunodeficiency virus after isoniazid prophylaxis.

A review was conducted in Haiti to determine the timing and outcome of active tuberculosis (TB) in human immunodeficiency virus (HIV)-positive patients who had previously received isoniazid (INH) prophylaxis. Of 1005 HIV-seropositive patients who completed INH prophylaxis, 14 (1.4%) subsequently had active TB diagnosed. The median interval between discontinuation of INH prophylaxis and TB diagnosis was 8 months for 6 patients receiving 6 months of INH, 22 months for 5 patients receiving 12-24 months of INH, and 40 months for 3 patients receiving 24-36 months of INH (P = .026). There is a postprophylaxis effect on INH that is dependent upon the duration of therapy.

Effect of post-treatment isoniazid on prevention of recurrent tuberculosis in HIV-1-infected individuals: a randomised trial.

BACKGROUND: Patients with HIV-1 infection respond well to treatment for active tuberculosis, but whether such patients are at increased risk of disease recurrence after complete cure is uncertain. We did a randomised trial in Port au Prince, Haiti, to determine whether recurrent tuberculosis after curative tuberculosis treatment is more common in HIV-1-infected individuals than HIV-1-uninfected individuals, and to determine whether post-treatment isoniazid prophylaxis decreases the risk of recurrent tuberculosis. METHODS: Patients older than 18 years who were diagnosed with a first episode of tuberculosis at the national HIV testing centre in Haiti, and who successfully completed a 6-month rifampicin-containing regimen for active pulmonary tuberculosis, were randomly assigned 1 year of post-treatment isoniazid prophylaxis or placebo. The primary outcome measure was rate of recurrent tuberculosis after at least 24 months. An intention-to-treat analysis was used. FINDINGS: Of 354 patients with active pulmonary tuberculosis, 274 successfully completed treatment, and 233 were randomised. Of 142 HIV-1-positive patients, 68 were assigned isoniazid and 74 placebo. Of 91 HIV-1-negative individuals, 51 were assigned isoniazid and 40 placebo. The rate of recurrent tuberculosis was 4.8 per 100 person-years in HIV-1-infected individuals and 0.4 per 100 person-years in uninfected individuals (relative risk 10.7 [95% CI 1.4-81.6]). Among HIV-1-positive patients receiving isoniazid, the tuberculosis recurrence rate was 1.4 per 100 person-years, and among HIV-1-positive patients receiving placebo, it was 7.8 per 100 person-years (0.18 [0.04-0.83]). Among HIV-1-positive individuals, all cases of recurrent tuberculosis occurred in individuals with a history of HIV-1-related symptoms before initial tuberculosis diagnosis. INTERPRETATION: The rate of recurrent tuberculosis is higher in HIV-1-positive individuals than in HIV-1-negative individuals, and is strongly associated with a history of symptomatic HIV-1 disease before initial tuberculosis diagnosis. Post-treatment isoniazid prophylaxis decreases the risk of recurrence in HIV-1-positive individuals, and should be considered for HIV-1-positive individuals with a history of HIV-1-related symptoms at the time of tuberculosis diagnosis.