Direct Detection by the Xpert MTB/RIF Assay and Characterization of Multi and Poly Drug-Resistant Tuberculosis in Guinea-Bissau, West Africa.

BACKGROUND: This study aimed to evaluate the usefulness of the Xpert MTB/RIF assay for the rapid direct detection of M. tuberculosis complex (MTBC) strains and rifampicin resistance associated mutations in a resource-limited setting such as Guinea-Bissau and its implications in the management of tuberculosis (TB) and drug resistant tuberculosis, complementing the scarce information on resistance and genotypic diversity of MTBC strains in this West African country. METHODS AND RESULTS: This cross-sectional prospective study included 100 consecutive TB patients with positive acid-fast smears at two months of anti-tuberculosis treatment or in a re-treatment situation, between May and December 2012. Resistance to rifampicin was detected using the GeneXpert system and the Xpert MTB/RIF assay. MTBC isolates obtained with the BACTEC MGIT 960 system were tested for susceptibility to first- and second-line anti-tuberculosis drugs. Overall, the prevalence of multidrug-resistant tuberculosis (MDR-TB) was found to be 9 cases. Of these, 67% (6 patients) of confirmed MDR-TB cases had no past history of TB treatment and 33% (3 patients) were previously treated cases. Extensively drug-resistant TB was not found. Molecular typing of the MDR-TB strains revealed recent transmission patterns of imported MDR strains. CONCLUSIONS: The Xpert MTB/RIF assay was reliable for the detection of rifampicin resistant MTBC strains directly from sputum samples of patients undergoing first-line treatment for two months, being more trustworthy than the simple presence of acid-fast bacilli in the smear. Its implementation is technically simple, does not require specialized laboratory infrastructures and is suitable for resource-limited settings when a regular source of electricity and maintenance is available as well as financial and operation sustainability is guaranteed by the health authorities. A high prevalence of MDR-TB among patients at risk of MDR-TB after two months of first-line treatment was found, in support of the WHO recommendations for its use in the management of this risk group.

Short term advantages of a public-private partnership for tuberculosis in Guinea bissau: reduction of mortality and increased diagnostic capacity.

BACKGROUND: Tuberculosis (TB) is widespread in Africa, but weak health systems in developing countries, often display poor quality of care with delays in case identification, irrational therapy and drug shortage, clinical mismanagement, unnecessary expenditures for patients, reduced adherence and increased mortality. Public-private partnership has demonstrated to increase TB case detection, but less is known about its effects on quality of care, mortality and costs for hospitalized TB patients. METHODS: Clinical outcomes and costs for TB patients at the TB National Reference Center of Bissau, in Guinea Bissau, West Africa, were determined during the first 5 months of the public-private management and compared to the ones of previous years when the hospitals was under direct Government's management. RESULTS: 215 (2009-2010) and 194 (2012-2013) patients were admitted, respectively. Improvement (p<0.05) was observed in mortality reduction (21% vs 6%), cause of death determination (50% vs 85%), treatment abandonment (15 vs 1). Direct costs for patients during TB diagnostic pathway and inpatient care were significantly reduced, 475 vs. 0 USD. CONCLUSIONS: Public-private partnerships displays significant short term benefits in National TB reference centers, even in post-conflict countries. Further studies could aid in determining the overall long term benefits of this type of cooperation, and the specific characteristic of TB and concomitant hematologic and infectious diseases in TB admitted patients.

Impact of isoniazid preventive therapy on mortality among children less than 5 years old following exposure to tuberculosis at home in Guinea-Bissau: a prospective cohort study.

OBJECTIVE: In a cohort of children less than 5 years old exposed to adult intrathoracic tuberculosis (TB) in 1996-1998, we found 66% increased mortality compared with community controls. In 2005, we implemented isoniazid preventive therapy (IPT) for children exposed to TB at home, and the present study evaluates the effect of this intervention on mortality. SETTING: This prospective cohort study was conducted in six suburban areas included in the demographic surveillance system of the Bandim Health Project in Bissau, the capital city of Guinea-Bissau. PARTICIPANTS: All children less than 5 years of age and living in the same house as an adult with intrathoracic TB registered for treatment in the study area between 2005 and 2007 were evaluated for inclusion in the IPT programme. MAIN OUTCOME MEASURES (END POINTS): The all-cause mortality rate ratio (MRR) between exposed children on IPT, exposed without IPT and unexposed community control children. RESULTS: A total of 1396 children were identified as living in the same houses as 416 adult TB cases; of those, 691 were enrolled in the IPT programme. Compared with community controls, the IPT children had an MRR of 0.30 (95%CI 0.1 to 1.2). The MRR comparing exposed children with and without IPT was 0.21 (0.0 to 1.1). The relative mortality in IPT children compared with community controls in 2005-2008 differed significantly from the relative mortality of exposed untreated children compared with the community controls in 1996-1998 (test of interaction, p=0.01). CONCLUSIONS: In 2005-2008, exposed children on IPT had 70% lower mortality than the community control children, though not significantly. Relative to the community control children, the mortality among TB-exposed children on IPT in 2005-2008 was significantly lower than the mortality among TB-exposed children not on IPT in 1996-1998.

Malaria prevention reduces in-hospital mortality among severely ill tuberculosis patients: a three-step intervention in Bissau, Guinea-Bissau.

BACKGROUND: Malaria and Tuberculosis (TB) are important causes of morbidity and mortality in Africa. Malaria prevention reduces mortality among HIV patients, pregnant women and children, but its role in TB patients is not clear. In the TB National Reference Center in Guinea-Bissau, admitted patients are in severe clinical conditions and mortality during the rainy season is high. We performed a three-step malaria prevention program to reduce mortality in TB patients during the rainy season. METHODS: Since 2005 Permethrin treated bed nets were given to every patient. Since 2006 environmental prevention with permethrin derivates was performed both indoor and outdoor during the rainy season. In 2007 cotrimoxazole prophylaxis was added during the rainy season. Care was without charge; health education on malaria prevention was performed weekly. Primary outcomes were death, discharge, drop-out. RESULTS: 427, 346, 549 patients were admitted in 2005, 2006, 2007, respectively. Mortality dropped from 26.46% in 2005 to 18.76% in 2007 (p-value 0.003), due to the significant reduction in rainy season mortality (death/discharge ratio: 0.79, 0.55 and 0.26 in 2005, 2006 and 2007 respectively; p-value 0.001) while dry season mortality remained constant (0.39, 0.37 and 0.32; p-value 0.647). Costs of malaria prevention were limited: 2€/person. No drop-outs were observed. Health education attendance was 96-99%. CONCLUSIONS: Malaria prevention in African tertiary care hospitals seems feasible with limited costs. Vector control, personal protection and cotrimoxazole prophylaxis seem to reduce mortality in severely ill TB patients. Prospective randomized trials are needed to confirm our findings in similar settings.

Impact of tuberculosis exposure at home on mortality in children under 5 years of age in Guinea-Bissau.

OBJECTIVE: To assess mortality related to exposure to tuberculosis (TB) at home among children in urban areas of Guinea-Bissau. METHODS: In four suburban areas included in the demographic surveillance system of the Bandim Health Project in Bissau, the mortality of children aged <5 years living with an adult with TB was compared with the mortality of children in the general population. RESULTS: Children <5 years of age exposed to an adult with intrathoracic TB had 66% higher mortality than unexposed children (HR 1.66, 95% CI 1.2 to 2.3). The risk was higher for children living in the same family as a TB case (HR 2.15, 95% CI 1.3 to 3.7) than for children living in the same house but not belonging to the same family as the TB case (HR 1.51, 95% CI 1.0 to 2.2). For children whose mother had TB, mortality was increased eightfold (HR 7.82, 95% CI 2.1 to 30). The risk of death was particularly increased from 6 months following exposure (HR 2.16, 95% CI 1.5 to 3.2) and the highest rate of excess mortality was found in children aged 3­4 years. Excess mortality was highest among children with close contact with an adult with sputum-positive pulmonary TB (HR 1.90, 95% CI 1.1 to 3.2), but contact with a sputum-negative case was also associated with increased mortality (HR 1.55, 95% CI 1.0 to 2.3). Adjusting for potential confounding factors did not change these results. The mortality among children living in the same houses 3 years earlier was not increased (HR 0.90, 95% CI 0.6 to 1.3). CONCLUSION: Intimate family contact with a TB case represents a significant risk factor for child mortality in a low-income country.