Clinical trials, evaluating 9-month/7-drug and 6-month/4-drug all-oral rifampicin-resistant tuberculosis (RR-TB) treatment regimens showed that these are at least as effective and safer than previously used longer and injectable-containing regimens [1–4]. Findings directly informed World Health Organization (WHO) guidelines for the treatment of adults with RR-TB, including pre-extensively drug-resistant TB (pre-XDR-TB; RR-TB with resistance to fluoroquinolones, FQ) [5]. However, children were not included in these trials. Especially for children with pre-XDR-TB, severe TB disease, or extrapulmonary TB (other than peripheral lymphadenitis) this has dire consequences. They are still treated with individualized 18-month regimens, which are not only longer, but also more toxic, less effective and with a higher pill burden than regimens for adults with a similar condition [5, 6]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of Interest: All authors have nothing to disclose.

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.

Objectives 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. Methods 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. Results 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). Conclusions 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.

BACKGROUND: Risk factors associated with L. donovani visceral leishmaniasis (VL; kala azar) relapse are poorly characterized. METHODS: We investigated patient characteristics and drug regimens associated with VL relapse using data from Médecins Sans Frontières - Holland (MSF) treatment centres in Southern Sudan. We used MSF operational data to investigate trends in VL relapse and associated risk factors. RESULTS: We obtained data for 8,800 primary VL and 621 relapse VL patients treated between 1999 and 2007. Records of previous treatment for 166 VL relapse patients (26.7%) were compared with 7,924 primary VL patients who had no record of subsequent relapse. Primary VL patients who relapsed had larger spleens on admission (Hackett grade >or=3 vs 0, odds ratio (OR) for relapse = 3.62 (95% CI 1.08, 12.12)) and on discharge (Hackett grade >or=3 vs 0, OR = 5.50 (1.84, 16.49)). Age, sex, malnutrition, mobility, and complications of treatment were not associated with risk of relapse, nor was there any trend over time. Treatment with 17-day sodium stibogluconate/paromomycin (SSG/PM) combination therapy vs 30-day SSG monotherapy was associated with increased risk of relapse (OR = 2.08 (1.21, 3.58)) but reduced risk of death (OR = 0.27 (0.20, 0.37)), although these estimates are likely to be residually confounded. MSF operational data showed a crude upward trend in the proportion of VL relapse patients (annual percentage change (APC) = 11.4% (-3.4%, 28.5%)) and a downward trend in deaths (APC = -18.1% (-22.5%, -13.4%)). CONCLUSIONS: Splenomegaly and 17-day SSG/PM vs 30-day SSG were associated with increased risk of VL relapse. The crude upward trend in VL relapses in Southern Sudan may be attributable to improved access to treatment and reduced mortality due to SSG/PM combination therapy.

Médecins sans Frontières-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.

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.

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 aged < 15 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.

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 aged <5 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 and >80% 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.