Journal Article > ResearchFull Text
BMJ Open. 2023 January 30; Volume 13 (Issue 1); e059134.; DOI:10.1136/bmjopen-2021-059134
Mashe T, Chaibva BV, Nair P, Sani KA, Jallow M, et al.
BMJ Open. 2023 January 30; Volume 13 (Issue 1); e059134.; DOI:10.1136/bmjopen-2021-059134
OBJECTIVES
This study was conducted to explore the epidemiology and microbiological pattern of the cholera outbreaks that occurred in Zimbabwe from 2018 to 2019.
STUDY SETTING AND DESIGN
This descriptive study used secondary data of 9971 out of 10 730 suspected cases from the Zimbabwean National Diseases Surveillance system and microbiology data of 241 out of 371 patients from the National Microbiology Reference Laboratory in Harare, for the period 5 September 2018 and 3 January 2019. Descriptive analysis was performed to describe the characteristics of the outbreak in terms of person, place and time.
RESULTS
A cumulative total of 10 730 suspected, 371 laboratory-confirmed cholera cases and 68 deaths were reported in Zimbabwe through the situation analysis report (sitrep). The attack rate during the outbreak was 174.6 per 100 000 with a case fatality rate of 0.63%. Most cases seen were among adults from Harare province. Antimicrobial sensitivity testing results showed that a multidrug resistant strain of Vibrio cholerae O1, Ogawa serotype was responsible for the outbreak. The treatment of cases was changed from the standard recommended medicine ciprofloxacin to azithromycin as confirmed by the antimicrobial sensitivity test results. Strategies employed to contain the outbreak included mass oral cholera vaccination in the hotspot areas of Harare, provision of improved and appropriate sanitation measures, provision of safe and adequate water, chlorination of water and improved waste management practice.
CONCLUSIONS
The recurrence of a cholera outbreak is a global concern, especially with the emergence of multi-drug resistant strains of the causal organism. Improving water, sanitation, hygiene infrastructure, health system strengthening measures and inter-sectoral collaboration in responding to the cholera outbreak was key to controlling the outbreak.
This study was conducted to explore the epidemiology and microbiological pattern of the cholera outbreaks that occurred in Zimbabwe from 2018 to 2019.
STUDY SETTING AND DESIGN
This descriptive study used secondary data of 9971 out of 10 730 suspected cases from the Zimbabwean National Diseases Surveillance system and microbiology data of 241 out of 371 patients from the National Microbiology Reference Laboratory in Harare, for the period 5 September 2018 and 3 January 2019. Descriptive analysis was performed to describe the characteristics of the outbreak in terms of person, place and time.
RESULTS
A cumulative total of 10 730 suspected, 371 laboratory-confirmed cholera cases and 68 deaths were reported in Zimbabwe through the situation analysis report (sitrep). The attack rate during the outbreak was 174.6 per 100 000 with a case fatality rate of 0.63%. Most cases seen were among adults from Harare province. Antimicrobial sensitivity testing results showed that a multidrug resistant strain of Vibrio cholerae O1, Ogawa serotype was responsible for the outbreak. The treatment of cases was changed from the standard recommended medicine ciprofloxacin to azithromycin as confirmed by the antimicrobial sensitivity test results. Strategies employed to contain the outbreak included mass oral cholera vaccination in the hotspot areas of Harare, provision of improved and appropriate sanitation measures, provision of safe and adequate water, chlorination of water and improved waste management practice.
CONCLUSIONS
The recurrence of a cholera outbreak is a global concern, especially with the emergence of multi-drug resistant strains of the causal organism. Improving water, sanitation, hygiene infrastructure, health system strengthening measures and inter-sectoral collaboration in responding to the cholera outbreak was key to controlling the outbreak.
Journal Article > ResearchFull Text
Am J Respir Crit Care Med. 2020 July 24; Volume 203 (Issue 1); 111-119.; DOI:10.1164/rccm.202001-0135OC
Franke MF, Khan PY, Hewison CCH, Khan UT, Huerga H, et al.
Am J Respir Crit Care Med. 2020 July 24; Volume 203 (Issue 1); 111-119.; DOI:10.1164/rccm.202001-0135OC
BACKGROUND
Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid- and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion.
METHODS
We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.
FINDINGS
1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0·73 [95% CI: 0·62, 0·84]) than patients without HIV (0·84 [95% CI: 0·79, 0·90]; p=0·03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0·68 [95% CI: 0·57, 0·79]) relative to patients without either (0·89; 95% CI: 0·84, 0·95; p=0·0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion.
INTERPRETATION
Frequent sputum conversion in patients with rifampin-resistant/MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.
Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid- and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion.
METHODS
We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.
FINDINGS
1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0·73 [95% CI: 0·62, 0·84]) than patients without HIV (0·84 [95% CI: 0·79, 0·90]; p=0·03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0·68 [95% CI: 0·57, 0·79]) relative to patients without either (0·89; 95% CI: 0·84, 0·95; p=0·0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion.
INTERPRETATION
Frequent sputum conversion in patients with rifampin-resistant/MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2020 October 1; Volume 24 (Issue 10); 1087-1094.; DOI:10.5588/ijtld.20.0115
Lachenal N, Hewison CCH, Mitnick CD, Lomtadze N, Coutisson S, et al.
Int J Tuberc Lung Dis. 2020 October 1; Volume 24 (Issue 10); 1087-1094.; DOI:10.5588/ijtld.20.0115
SETTING
Active pharmacovigilance (PV) is recommended for TB programmes, notably for multidrug-resistant TB (MDR-TB) patients treated with new drugs. Launched with the support of UNITAID in April 2015, endTB (Expand New Drug markets for TB) facilitated treatment with bedaquiline (BDQ) and/or delamanid of >2600 patients in 17 countries, and contributed to the creation of a central PV unit (PVU).
OBJECTIVE
To explain the endTB PVU process by describing the serious adverse events (SAEs) experienced by patients who received BDQ-containing regimens.
DESIGN
The overall PV strategy was in line with the ‘advanced´ WHO active TB drug safety monitoring and management (aDSM) system. All adverse events (AEs) of clinical significance were followed up; the PVU focused on signal detection from SAEs.
RESULTS AND CONCLUSION
Between 1 April 2015 and 31 March 2019, the PVU received and assessed 626 SAEs experienced by 417 BDQ patients. A board of MDR-TB/PV experts reviewed unexpected and possibly drug-related SAEs to detect safety signals. The experts communicated on clusters of risks factors, notably polypharmacy and off-label drug use, encouraging a patient-centred approach of care. Organising advanced PV in routine care is possible but demanding. It is reasonable to expect local/national programmes to focus on clinical management, and to limit reporting to aDSM systems to key data, such as the SAEs.
Active pharmacovigilance (PV) is recommended for TB programmes, notably for multidrug-resistant TB (MDR-TB) patients treated with new drugs. Launched with the support of UNITAID in April 2015, endTB (Expand New Drug markets for TB) facilitated treatment with bedaquiline (BDQ) and/or delamanid of >2600 patients in 17 countries, and contributed to the creation of a central PV unit (PVU).
OBJECTIVE
To explain the endTB PVU process by describing the serious adverse events (SAEs) experienced by patients who received BDQ-containing regimens.
DESIGN
The overall PV strategy was in line with the ‘advanced´ WHO active TB drug safety monitoring and management (aDSM) system. All adverse events (AEs) of clinical significance were followed up; the PVU focused on signal detection from SAEs.
RESULTS AND CONCLUSION
Between 1 April 2015 and 31 March 2019, the PVU received and assessed 626 SAEs experienced by 417 BDQ patients. A board of MDR-TB/PV experts reviewed unexpected and possibly drug-related SAEs to detect safety signals. The experts communicated on clusters of risks factors, notably polypharmacy and off-label drug use, encouraging a patient-centred approach of care. Organising advanced PV in routine care is possible but demanding. It is reasonable to expect local/national programmes to focus on clinical management, and to limit reporting to aDSM systems to key data, such as the SAEs.
Conference Material > Video
Janssens B, King C, Nair P, Teck R
MSF Scientific Days International 2021: Innovation. 2021 May 20
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2022 July 1; Volume 26 (Issue 7); 658-663.; DOI:10.5588/ijtld.21.0631
Nair P, Hasan T, Zaw KK, Allamuratova S, Ismailov A, et al.
Int J Tuberc Lung Dis. 2022 July 1; Volume 26 (Issue 7); 658-663.; DOI:10.5588/ijtld.21.0631
BACKGROUND
The WHO recommends the use of bedaquiline (BDQ) in longer, as well as shorter, multidrug-resistant TB (MDR-TB) treatment regimens. However, resistance to this new drug is now emerging. We aimed to describe the characteristics of patients in Karakalpakstan, Uzbekistan, who were treated for MDR-TB and acquired BDQ resistance during treatment.
METHODS
We performed a retrospective study of routinely collected data for patients treated for MDR-TB in Karakalpakstan between January 2015 and December 2020. We included patients on BDQ-containing regimens with baseline susceptibility to BDQ who developed BDQ resistance at any point after treatment initiation. Patients resistant to BDQ at baseline or with no confirmed susceptibility to BDQ at baseline were excluded.
RESULTS:
Of the 523 patients who received BDQ-containing regimens during the study period, BDQ resistance was detected in 31 patients (5.9%); 20 patients were excluded-16 with no prior confirmation of BDQ susceptibility and 4 who were resistant at baseline. Eleven patients with acquired BDQ resistance were identified. We discuss demographic variables, resistance profiles, treatment-related variables and risk factors for unfavourable outcomes for these patients.
CONCLUSION
Our programmatic data demonstrated the acquisition of BDQ resistance during or subsequent to receiving a BDQ-containing regimen in a patient cohort from Uzbekistan. We highlight the need for individualised treatment regimens with optimised clinical and laboratory follow up to prevent resistance acquisition.
The WHO recommends the use of bedaquiline (BDQ) in longer, as well as shorter, multidrug-resistant TB (MDR-TB) treatment regimens. However, resistance to this new drug is now emerging. We aimed to describe the characteristics of patients in Karakalpakstan, Uzbekistan, who were treated for MDR-TB and acquired BDQ resistance during treatment.
METHODS
We performed a retrospective study of routinely collected data for patients treated for MDR-TB in Karakalpakstan between January 2015 and December 2020. We included patients on BDQ-containing regimens with baseline susceptibility to BDQ who developed BDQ resistance at any point after treatment initiation. Patients resistant to BDQ at baseline or with no confirmed susceptibility to BDQ at baseline were excluded.
RESULTS:
Of the 523 patients who received BDQ-containing regimens during the study period, BDQ resistance was detected in 31 patients (5.9%); 20 patients were excluded-16 with no prior confirmation of BDQ susceptibility and 4 who were resistant at baseline. Eleven patients with acquired BDQ resistance were identified. We discuss demographic variables, resistance profiles, treatment-related variables and risk factors for unfavourable outcomes for these patients.
CONCLUSION
Our programmatic data demonstrated the acquisition of BDQ resistance during or subsequent to receiving a BDQ-containing regimen in a patient cohort from Uzbekistan. We highlight the need for individualised treatment regimens with optimised clinical and laboratory follow up to prevent resistance acquisition.