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Since 2015 Médecins Sans Frontières (MSF) has been supporting the Ministry of Health (MoH) in Tonkolili district, Sierra Leone, with an integrated health care approach at the community, primary health centre (PHC), and hospital level. This programme is planned to be handed over to MoH. To prepare for this handover, a qualitative study exploring elements of a successful handover was undertaken in 2019. Focus group discussions (FGD) with the community members (n-48) and in-depth interviews (IDI) with MSF staff, community leaders, and MoH staff in Sierra Leone (n-15) were conducted. Data were audio-recorded, transcribed verbatim from English, Creole, and Themne, coded, and thematically analysed. Participants expressed that an optimal project handover and exit strategy should be a continuous, long-term, the staggered process included from the inception of the programme design. It requires clear communication and relationship building by all relevant stakeholders and demands efficient resources and management capacity. Associated policy implications are applicable across humanitarian settings on the handover of programmes where the government is functional and willing to accept responsibilities.

SETTING: Since 2015, Eswatini has been scaling up bedaquiline (BDQ) and delamanid (DLM) based drug-resistant TB treatment regimens under programmatic conditions.OBJECTIVE: Identification of factors associated with treatment outcomes in patients receiving BDQ and/or DLM either as a new treatment initiation or drug substitution.DESIGN: This is a retrospective cohort study of patients receiving BDQ and/or DLM in Eswatini between March 2015 and October 2018. We describe factors associated with unfavourable treatment outcomes (death, lost to follow-up, treatment failure and amplification of resistance) and culture conversion using multivariable flexible parametric survival and competing-risks regression analyses.RESULTS: Of 352 patients receiving BDQ and/or DLM, 7.8% and 21.2% had an unfavourable treatment outcome at 6 and 24 months, respectively. Predictors were age ≥ 60 years (adjusted hazard ratio aHR 4.49, 95%CI 1.61–12.57) vs. age 20–39 years, and a treatment regimen combining both drugs (aHR 4.49, 95%CI 1.61–12.57) vs. BDQ only. The probability of culture conversion was increased for two health facilities and patients with a poly resistance profile (adjusted sub-hazard ratio 2.01, 95%CI 1.13–3.59) vs. multidrug resistance.CONCLUSION: Single use of BDQ or DLM was associated with low rates of unfavourable outcomes, suggesting that these medications may be effectively adopted at scale under routine programmatic conditions. Combined use of BDQ and DLM was a risk factor for unfavourable outcomes and should prompt for collection of more data on the combined use of these medications.

To describe the effect of adaptations to a person-centred care with short oral regimens on retention in care for rifampicin-resistant TB (RR-TB) in Kandahar province, Afghanistan.The study included people with RR-TB registered in the programme between 01 October 2016 and 18 April 2021. From 19 November 2019, the programme implemented a trial investigating the safety and effectiveness of short oral RR-TB regimens. During the trial, person-centred care was adapted. We included the data from people living with RR-TB treated in the period before and after the care model was adapted and applied Kaplan-Meier statistics to compare rates of retention in care.Of 236 patients registered in the RR-TB programme, 146 (61.9%) were registered before and 90 (38.1%) after the model of care was adapted. Before adaptations enhancing person-centred care, pre-treatment attrition was 23.3% (n = 34/146), whilst under the adapted care model it was 5.6% (n = 5/90). Attrition on treatment was 22.3% (n = 25/112) before adaptations, whilst during the study period none of the participants were lost-to-follow-up on treatment and 3.3% died (n = 3/90).As person-centred care delivery and treatment regimens were adapted to better fit-specific contextual challenges and the needs of the target population, retention in care improved amongst people with RR-TB in Kandahar, Afghanistan.

Bedaquiline (BDQ) has been recommended by the World Health Organization for the treatment of multi-drug-resistant tuberculosis (MDR-TB) since 2013, but experience using the drug in high-burden, lower-income countries is limited and case studies are needed. Swaziland started using BDQ under national TB programme conditions in 2015 in four pilot sites. As of 1 December 2016, 93 patients had been initiated on BDQ, i.e., 19% of MDR-TB patients treated in the country. Swaziland has developed a systematic and efficient model for BDQ introduction in collaboration with several partners. This model is also being used to introduce other innovations and can serve as an example for other countries facing similar challenges.La bédaquiline (BDQ) a été recommandée par l'Organisation Mondiale de la Santé pour le traitement de la tuberculose multirésistante (TB-MDR) depuis 2013, mais l'expérience de son utilisation dans des pays à faible revenu et durement touchés est limitée et des études de cas sont requises. Le Swaziland a commencé à utiliser la BDQ dans des conditions de programme national TB en 2015 dans quatre sites pilotes. Au 1er décembre 2016, 93 patients avaient été mis sous BDQ, c'est-à-dire 19% des patients TB-MDR traités dans le pays. Le Swaziland a élaboré un modèle systématique et efficace d'introduction de la BDQ en collaboration avec plusieurs partenaires. Ce modèle est également utilisé pour introduire d'autres innovations et peut servir d'exemple à d'autres pays confrontés à des défis similaires.La Organización Mundial de la Salud recomienda desde el 2013 la bedaquilina (BDQ) en el tratamiento de la tuberculosis multirresistente (TB-MDR), pero la experiencia con su utilización en los países con alta carga de morbilidad es limitada y se precisan estudios de casos. En Swazilandia, se comenzó a utilizar la BDQ en el contexto del programa nacional contra la TB en cuatro centros piloto en el 2015. Al 1° de diciembre del 2016, 93 pacientes habían iniciado el tratamiento con BDQ, es decir, el 19% de los casos de TB-MDR tratados en el país. En Swazilandia se ha elaborado un modelo sistemático y eficiente de introducción de este medicamento en colaboración con diversos asociados. El modelo se utiliza también con el propósito de aplicar otras medidas innovadoras y puede servir como ejemplo a los países que afrontan dificultades semejantes.

Introduction Since 2011 Medecins sans Frontieres together with the eSwatini Ministry of Health have been managing patients with multi-drug resistant tuberculosis (MDR-TB) at Matsapha and Mankayane in Manzini region. This analysis describes the model of care and outcomes of patients receiving a 20 months MDR-TB treatment regimen between 2011 and 2013. Method We conducted a retrospective observational cohort study of MDR-TB patients enrolled for treatment between May 2011 and December 2013. An extensive package of psychological care and socio-economic incentives were provided including psychological support, paid treatment supporters, transport fees and a monthly food package. Baseline demographic details and treatment outcomes were recorded and for HIV positive patient’s univariate analysis as well as a cox regression hazard model were undertaken to assess risk factors for unfavorable outcomes. Results From the 174 patients enrolled, 156 (89.7%) were HIV co-infected, 102 (58.6%) were female, median age 33 years old (IQR: 28–42), 55 (31.6%) had a BMI less than 18 and 86 (49.4%) had not been previously treated for any form of TB. Overall cohort outcomes revealed a 75.3% treatment success rate, 21.3% mortality rate, 0.6% failure and 0.6% lost to follow-up rate. In the adjusted multivariate analysis, low BMI and low CD4 count at treatment initiation were associated with an increased risk of unfavorable outcome. Conclusions A model of care that included psychosocial support and patient’s enablers led to a high level of treatment success with a very low lost to follow up rate. Limiting the overall treatment success was a high mortality rate which was associated with advanced HIV and a low BMI at presentation. These factors will need to be addressed in order to improve upon the overall treatment success rate in future.

Both northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine-pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south). In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use should be rapidly discontinued in this region. SP resistance may propagate rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is limited to the combination.

An atypical outbreak of West Nile virus (WNV) occurred in Ngorban County, South Kordophan, Sudan, from May to August 2002. We investigated the epidemic and conducted a case-control study in the village of Limon. Blood samples were obtained for cases and controls. Patients with obvious sequelae underwent cerebrospinal fluid (CSF) sampling as well. We used enzyme-linked immunosorbent assay (ELISA) and neutralization tests for laboratory diagnosis and identified 31 cases with encephalitis, four of whom died. Median age was 36 months. Bivariate analysis did not reveal any significant association with the risk factors investigated. Laboratory analysis confirmed presence of IgM antibodies caused by WNV in eight of 13 cases, indicative of recent viral infection. The unique aspects of the WNW outbreak in Sudan, i.e. disease occurrence solely among children and the clinical domination of encephalitis, involving severe neurological sequelae, demonstrate the continuing evolution of WNV virulence. The spread of such a virus to other countries or continents cannot be excluded.

We analyzed data obtained from 3365 patients with kala-azar (KA) or post-KA dermal leishmaniasis (PKDL) treated by Medecins Sans Frontieres-Holland in south Sudan from October 1998-May 2002. Patients were malnourished (median body mass index [BMI], 15.5; median weight for height [WFH], 75.5%) and anemic (median hemoglobin (Hb) level, 8.5 g/dL). The proportion of patients with primary KA who were children5 years old increased from 2.5%, in 1998, to 19.8%, in 2002 (P.0001). Therapy with sodium stibogluconate cured 91.9% of patients with primary KA, and dosages of850 mg per day did not decrease the chances of survival. Risk factors for death among adults were ageor =45 years (odds ratio [OR], 4.6), malnutrition (BMI,13; OR, 11.0), anemia (Hb level,8 g/dL; OR, 4.0), and duration of illness (duration,or =5 months; OR, 2.3). Risk factors for death among children and adolescents were age2 years (OR, 5.4,), malnutrition (WFH,60%; OR, 5.0), anemia (Hb level,6 g/dL; OR, 3.7), and splenomegaly (OR, 2.9). A higher risk of death was associated with episodes of diarrhea (OR, 1.4), vomiting (OR, 2.7), and bleeding (OR, 2.9). Relapse and PKDL occurred in 3.9% and 10.0% of cases, respectively.

This is a descriptive report of a pilot project of tuberculosis (TB) treatment in a conflict zone. A TB programme was implemented by Medecins Sans Frontieres (MSF)-Holland in a semi-nomadic population in a very insecure and underdeveloped area of Upper Nile Province in South Sudan. Outcome measures were operational feasibility, default rate, and sputum smear conversion at 4 months. A cohort of TB patients was admitted over a 10-week period (July-September 2001). Adherence strategy, project implementation, and contingency planning were adapted to local conditions. The treatment regimen (4 HRZE [4-month daily supervised regimen] followed by 3EH or 3TH [3-month unsupervised regimen] isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E), and thiacetazone (T)) was a variant on the Manyatta regimen developed for semi-nomads in Kenya. Of 163 patients, 84 (52%) were children aged

Amodiaquine, a 4-aminoquinoline compound, is being considered as an alternative to chloroquine and pyrimethamine/sulfadoxine where resistance in Plasmodium falciparum to both drugs has been selected. Although amodiaquine is more potent than chloroquine, its effectiveness is reduced in areas where chloroquine resistance is high. We report an association of the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multiple drug resistance 1 (pfmdr1) gene, two chloroquine resistance markers, with chloroquine and amodiaquine efficacy in vivo in southern Sudan. The data show that the allele of the pfcrt gene with a lysine to threonine change at codon 76 is strongly associated with both chloroquine and amodiaquine resistance. No such association was observed with the pfmdr1 gene.

The current first-line and second-line drugs for Plasmodium falciparum malaria in South Sudan, chloroquine and sulfadoxine-pyrimethamine (SP), were evaluated and compared with amodiaquine, in an MSF-Holland-run clinic in eastern Upper Nile, South Sudan from June to December 2001. Patients with uncomplicated malaria and fever were stratified by age group and randomly allocated to one of 3 treatment regimes. A total of 342 patients was admitted and followed for 14 d after treatment. The dropout rate was 10.2%. Of those who completed the study, 104 were treated with chloroquine (25 mg/kg, 3 d), 102 with SP (25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine, single dose) and 101 with amodiaquine (25 mg/kg, 3 d). Adequate clinical response was observed in 88.5% of patients treated with chloroquine, 100% of patients treated with SP and 94.1% of patients treated with amodiaquine. In children aged5 years, the success rate was lower: 83.3% for chloroquine and 93.0% for amodiaquine. In adults no treatment failures were found, but children aged 5-15 years showed intermediate levels. In addition, we determined the initial genotypes of dhfr and dhps of 44 isolates from the SP-treated group and80% were found to be wild type for dhfr and 100% for dhps. Two percent of isolates had a single mutation and 16% had double mutations of dhfr. These data are in full agreement with the clinical effectiveness of SP. A change in malaria treatment protocols for South Sudan is recommended.

This is a descriptive report of a pilot project of tuberculosis (TB) treatment in a conflict zone. A TB programme was implemented by Médecins Sans Frontières(MSF)-Holland in a semi-nomadic population in a very insecure and underdeveloped area of Upper Nile province in Southern Sudan. Outcome measures were operational feasibility, default rate, and sputum smear conversion at 4 months. A cohort of TB patients was admitted over a 10-week period (July-September 2001). Adherence strategy, project implementation, and and contingency planning were adapted to local conditions. The treatment regimen (4 HRZE [4-month daily supervised regimen] followed by 3EH or 3TH [3-month unsupervised regimen]: isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E) and thiacetazone (T)) was a variant on the Manyatta regimen developed for semi-nomads in Kenya. Of 163 patients, 84 (52%) were children aged15 years. Lymph node TB comprised 34% and spinal TB 15% of all patients. Among adults, 41% had smear-positive pulmonary disease. Only 1 patient (0.6%) defaulted. All sputum smear-positive patients who completed 4 months of therapy converted to smear-negative, although 2 were subsequently found to have relapsed. TB in complex emergency situations is an underrecognized priority. Using an approach adapted especially to this setting, TB treatment was successfully implemented with minimal risk of promoting drug resistance, in an unstable setting.

Medecins sans Frontieres-Holland has treated > 67,000 patients with kala-azar (KA) in southern Sudan since 1989. In 2002, we replaced the standard regimen of 30 days of daily sodium stibogluconate (SSG) with a 17-day regimen of daily SSG combined with paromomycin (PM). We analyzed data for 4,263 primary KA patients treated between 2002 and 2005 in southern Sudan to determine the relative efficacy of the combination therapy regimen (PM/SSG). The initial cure rate among patients treated with PM/SSG was 97.0% compared with 92.4% among patients treated with SSG monotherapy. Relative efficacy of PM/SSG compared with SSG increased over the study period: odds of death in the PM/SSG group were 44% lower (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.37-0.84) in 2002, 78% lower (OR = 0.22, 95% CI = 0.10-0.50) in 2003, and 86% lower (OR = 0.14, 95% CI = 0.07-0.27) in 2004-2005. In remote field settings, 17 days of SSG combined with PM gives better survival and initial cure rates than 30 days of SSG monotherapy.