The consequences of over a year of full-blown conflict on the health and wellbeing of people in Sudan are disastrous. The population has faced horrendous levels of violence, succumbing to widespread fighting and surviving repeated attacks, abuse, and exploitation by the Sudanese Armed Forces (SAF) and the Rapid Support Forces (RSF). Drawing on medical and operational data collected from April 15, 2023, to May 15, 2024, this report highlights the patterns of violence observed by our teams, the features of abuse characterising this conflict, and the ensuing health consequences for affected populations.
In active conflict areas in Khartoum and across Darfur states, MSF supports the few remaining hospitals and emergency wards functioning in Sudan. Our teams treat thousands of war-wounded patients in locations affected by crossfire, large-scale bombing, and shelling where homes, health facilities and essential infrastructure were hit, destroyed, and made inoperable. From August 15, 2023, to April 30, 2024, the Al Nao hospital in Omdurman – one of the eight facilities MSF supports in Khartoum state – admitted a total of 6,776 war wounded patients, on average 26 war wounded patients per day, for gunshot (53%), shrapnel (42%), and stabbing wounds (5%). At least 399 of them died from their injuries. Women and children have not been spared, comprising almost 30% of the 624 war-wounded treated – in March 2c024 alone. From May 2023 to April 2024, MSF teams in Bashair Teaching Hospital in Khartoum treated 4,393 patients presenting with trauma related injuries, corresponding to 42% of all Emergency department consultations across the period of analysis.
Across Sudan, people’s access to lifesaving care has been drastically affected due to critical shortages, widespread obstruction and looting of medical supplies, insecurity and attacks against patients and medical staff, breaches of medical protocols in hospitals, and structural damages to healthcare infrastructure. Al-Nao Hospital was hit by shells on three separate occasions in August, October, and June 2024, leading to a reduction in the availability of lifesaving services. In July 2023, a healthcare worker of the MSF-supported Al-Saudi Maternity Hospital was shot dead inside the maternity ward, leading to the closure of the facility. Nowhere is safe for populations trapped in Sudan’s conflict hotspots, forcing millions to flee.
In the camps and gathering sites where refugees and displaced populations seek safety, MSF patients recount horrific stories of inhuman treatment and violence perpetrated by armed groups on the civilian population. People’s accounts describe systematic cases of forced eviction, looting and arson, degrading interrogation, arbitrary arrest, abduction and torture – all against the backdrop of heightened suspicion around those attempting to flee and reach safer areas.
Sexual and gender-based violence is pervasive but critically underreported due to stigma, silence for fear of retaliation, and the void in protection services and confidential spaces conducive to disclosure. Data from MSF facilities supporting Sudanese refugees in Chad hint at the widespread use of sexual violence as a form of warfare, particularly targeting women and girls. Between July and December 2023, 135 survivors turned to our teams in Adre (Chad), disclosing cases of rape, abduction, and exploitation perpetrated in Sudan during the conflict. In 90% of cases, perpetrators were armed men.
In Western Darfur, violence has taken an ethnic dimension, targeted against the Masalit tribe, and has included forced displacement, unlawful killing, and other forms of inhuman treatment reportedly by the RSF and affiliated groups. In June 2023, MSF teams in Chad treated over 800 war-wounded patients in three days, most of them Masalit having fled El Geneina city and its surroundings. A retrospective mortality survey conducted by MSF between August and September 2023 in three Sudanese refugee camps in Chad showed excess mortality across the camps; Ourang camp observed a 20-fold increase in mortality rates from April 2023 onwards with a peak in June, compared to pre-crisis rates. Additionally, an MSF survey conducted in South Darfur in February-March 2024 indicated excess crude mortality rates and found that in north Nyala, the conflict is leading to a doubling of the crude mortality rate (CMR), especially during heavy fighting in October 2023.
More than a year of full-blown conflict has had disastrous consequences on the health and wellbeing of people in Sudan. The physical and mental wounds of violence have been exacerbated by the collapse of the health system and the paucity of the international humanitarian response. MSF teams continue to treat people dying from preventable complications because they were unable to reach any facilities earlier or afford medicine, if available. MSF mental health teams are seeing the tremendous toll of conflict and violence on people’s mental health and psychological wellbeing, with widespread trauma-related symptoms sometimes leading patients to self-harm.
As MSF continues to respond to urgent medical needs and the consequences of ongoing violence, further exacerbated by lack of humanitarian access and the warring parties’ blatant disregard for human life and international humanitarian law (IHL), MSF calls for:
- Warring parties to cease attacks on residential neighborhoods, allow safe passage and routes for people seeking protection, and protect vital infrastructure from further destruction and looting;
- Warring parties to stop all targeted forms of violence and abuse against populations and ensure that ethnic violence and sexual and gender-based violence are not used as weapons of war;
- Warring parties to immediately facilitate aid; allow unhindered humanitarian access and ensure supplies and staff reach those in need; assistance must be able to reach people in need across borders and front lines.
- Vested partner states and regional bodies to increase pressure on the warring parties in Sudan to abide by their obligations regarding civilian protection and hold those violating civilian protections to account;
- The United Nations to repeat and amplify messages regarding the promotion and respect of international humanitarian and human rights laws, increase field presence of UN senior staff, and ensure that protection responses are scaled up and adequately coordinated;
- Humanitarian organisations to scale up programming and adapt the response across all sectors to the complexity of the operational context in Sudan.
كارثية هي العواقب المترتبة على أكثر من عام من النزاع الشامل على صحة الناس في السودان. حيث واجه السكان مستويات مروعة من العنف، وعانوا من قتال واسع النطاق ونجوا من الهجمات المتكررة والانتهاكات والاستغلال من قبل القوات المسلحة السودانية وقوات الدعم السريع. وبالاعتماد على البيانات الطبية والتشغيلية التي جُمِعت في الفترة الواقعة ما بين 15 أبريل/نيسان 2023 حتى 15 مايو/أيار 2024، يسلّط هذا التقرير الضوء على أنماط العنف التي لاحظتها فرقنا، وسمات الانتهاكات التي تشكل هذا النزاع، والعواقب الصحية المترتبة على السكان المتضررين.
وفي مناطق النزاع النشطة في الخرطوم وفي جميع أنحاء ولايات دارفور، تدعم أطباء بلا حدود المستشفيات وأجنحة الطوارئ القليلة المتبقية العاملة في السودان. وتعالج فرقنا الآلاف من جرحى الحرب في المواقع المتضررة من تبادل إطلاق النار والقصف واسع النطاق حيث تعرضت المنازل والمرافق الصحية والبنية التحتية الأساسية للقصف والتدمير وأصبحت غير صالحة للعمل. وفي الفترة ما بين 15 أغسطس/آب 2023 وحتى 30 أبريل/نيسان 2024، استقبل مستشفى النوّ في أم درمان - وهو أحد المرافق الثمانية التي تدعمها أطباء بلا حدود في ولاية الخرطوم - ما مجموعه 6,776 جريح حرب، أيّ بمتوسط 26 جريح حرب يوميًا، بسبب الطلقات النارية (53 في المئة)، والشظايا (42 في المئة)، وعمليات الطعن (5 في المئة). وتوفي ما لا يقل عن 399 منهم متأثرين بجراحهم. ولم يسلم النساء والأطفال، الذين يشكلون ما يقرب من 30 في المئة من جرحى الحرب البالغ عددهم 624 جريحًا في شهر مارس/آذار 2024 وحده. وفي الفترة ما بين مايو/أيار 2023 وحتى أبريل/نيسان 2024، عالجت فرق أطباء بلا حدود في مستشفى بشائر التعليمي في الخرطوم 4,393 مريضًا يعانون من الإصابات البالغة، أيّ ما يعادل 42 في المئة من جميع استشارات قسم الطوارئ خلال فترة تحليل البيانات.
تأثرت إمكانية حصول الناس على الرعاية المنقذة للحياة بشكل كبيرفي جميع أنحاء السودان بسبب النقص الحاد في التزويدات الطبية، وعرقلة إيصال الإمدادات الطبية على نطاق واسع بالإضافة إلى نهبها، وانعدام الأمن والهجمات ضد المرضى والطاقم الطبي، وانتهاكات البروتوكولات الطبية في المستشفيات، والأضرار الهيكلية التي لحقت بالبنية التحتية للرعاية الصحية. وقد تعرّض مستشفى النّو للقصف في ثلاث حوادث منفصلة في أغسطس/آب وأكتوبر/تشرين الأوّل 2023 ويونيو/حزيران 2024، ممّا أدى إلى نقص في إمكانية توفير الخدمات المنقذة للحياة. وفي يوليو/تموز 2023، قُتل أحد العاملين في الرعاية الصحية في المستشفى السعودي للتوليد الذي تدعمه أطباء بلا حدود بالرصاص داخل جناح الولادة، ممّا أدى إلى إغلاق المرفق. وهكذا فلا يوجد أيّ مكان آمن للسكان المحاصرين في مناطق النزاع الساخنة في السودان، ممّا أجبر الملايين على الفرار.
وفي المخيمات ومواقع التجمّع التي يبحث فيها اللاجئون والنازحون عن الأمان، يروي مرضى أطباء بلا حدود قصصًا مروعة عن المعاملة اللاإنسانية والعنف الذي ترتكبه الجماعات المسلحة ضد السكان المدنيين. وتصف روايات الناس حالات ممنهجة من الإخلاء القسري، والنهب والحرق العمد، والاستجواب المهين، والاعتقال التعسفي، والاختطاف والتعذيب - كل ذلك على خلفية الشكوك المتزايدة حول أولئك الذين يحاولون الفرار والوصول إلى مناطق أكثر أمانًا.
ينتشر العنف الجنسي والعنف القائم على النوع الاجتماعي،ولكن لا يُبلَّغ عنهما بشكل كبير بسبب الوصمة والصمت خوفًا من الانتقام وغياب خدمات الحماية والمساحات السرية التي تساعد على الإفصاح. وتشير البيانات الواردة من مرافق أطباء بلا حدود التي تدعم اللاجئين السودانيين في تشاد إلى انتشار استخدام العنف الجنسي كشكل من أشكال الحرب، ولا سيما ضد النساء والفتيات. وفي الفترة ما بين يوليو/تموز وديسمبر/كانون الأول 2023، لجأ 135 ناجية وناجيًا إلى فرقنا في أدري (تشاد)، وكشفوا عن حالات اغتصاب واختطاف واستغلال ارتكبت في السودان أثناء النزاع. وفي 90 في المئة من الحالات، كان الجناة رجالاً مسلحين.
وحسبما أفادت التقارير، اتخذ العنف بعدًا عرقيًا في غرب دارفور، واستهدف قبيلة المساليت، وشمل التهجير القسري، والقتل غير القانوني، وأشكالًا أخرى من المعاملة اللاإنسانية على يد قوات الدعم السريع والجماعات التابعة لها. وفي يونيو/حزيران 2023، عالجت فرق منظمة أطباء بلا حدود في تشاد أكثر من 800 جريح حرب في ثلاثة أيام، معظمهم من المساليت الذين فروا من مدينة الجنينة والمناطق المحيطة بها. وأظهرت دراسة مسحية للوفيات بأثر رجعي أجرتها أطباء بلا حدود بين أغسطس/آب وسبتمبر/أيلول 2023 في ثلاثة مخيمات للاجئين السودانيين في تشاد زيادة في الوفيات في جميع أنحاء المخيمات؛ وشهد مخيم أورانغ زيادة بمقدار 20 ضعفًا في معدلات الوفيات منذ أبريل/نيسان 2023 فصاعدًا وبلوغ ذروتها في يونيو/حزيران، مقارنة بمعدلات ما قبل الأزمة. بالإضافة إلى ذلك، أشارت دراسة مسحية أجرتها أطباء بلا حدود في جنوب دارفور في فبراير/شباط ومارس/آذار 2024 إلى زيادة معدلات الوفيات ، وتوصلت أيضًا إلى أنّ النزاع في شمال نيالا أدى إلى مضاعفة معدل الوفيات الخام، خاصة أثناء القتال العنيف في أكتوبر/تشرين الأول 2023.
وأسفر النزاع الشامل الذي بدأ منذ أكثر من عام عن عواقب وخيمة على صحة الناس في السودان وسلامتهم. وقد تفاقمت الجروح الجسدية والنفسية الناجمة عن العنف بسبب انهيار النظام الصحي وندرة الاستجابة الإنسانية الدولية. وفي هذا السياق، تواصل فرق أطباء بلا حدود علاج الأشخاص ممن يفقدون حياتهم بسبب مضاعفات يمكن الوقاية منها لأنهم لم يتمكنوا من الوصول إلى المرافق في وقت مبكر أو شراء الأدوية، إذا كانت متوفرة. وتشهد فرق الصحة النفسية التابعة لأطباء بلا حدود الخسائر الهائلة الناجمة عن النزاع والعنف على الصحة النفسية للأشخاص وسلامتهم النفسية، حيث تؤدي الأعراض المرتبطة بالصدمة المنتشرة على نطاق واسع أحيانًا إلى إيذاء المرضى لأنفسهم.
مع استمرار أطباء بلا حدود في الاستجابة للاحتياجات الطبية العاجلة وعواقب العنف المستمر، والتي تفاقمت بسبب عدم وصول المساعدات الإنسانية وتجاهل الأطراف المتحاربة الصارخ للحياة البشرية والقانون الدولي الإنساني، تدعو أطباء بلا حدود إلى:
• وقف الأطراف المتحاربة الهجمات على الأحياء السكنية، والسماح بالمرور الآمن وضمان الطرق الآمنة للأشخاص الذين يبحثون عن الحماية، وحماية البنية التحتية الحيوية من تعرضها لمزيد من التدمير والنهب؛
• وقف الأطراف المتحاربة جميع أشكال العنف والإساءة الموجهة ضد السكان وضمان عدم استخدام العنف العرقي والعنف الجنسي والعنف القائم على النوع الاجتماعي كأسلحة حرب.
• تسهيل الأطراف المتحاربة إتاحة المساعدات على الفور؛ والسماح بوصول المساعدات الإنسانية من دون عوائق وضمان وصول الإمدادات والموظفين إلى المحتاجين؛ ويجب إتاحة وصول المساعدات إلى المحتاجين عبر الحدود وخطوط المواجهة.
• زيادة الدول الشريكة والهيئات الإقليمية الضغط على الأطراف المتحاربة في السودان لاحترام التزاماتها في ما يتعلّق بحماية المدنيين ومحاسبة من ينتهكون حقوق الإنسان ومبادئ حماية المدنيين.
• تكرار الأمم المتحدة الرسائل المتعلقة بتعزيز واحترام القانون الدولي الإنساني وقانون حقوق الإنسان وتضخيمها، وزيادة الحضور الميداني لكبار مسؤولي الأمم المتحدة، وضمان رفع مستوى استجابات الحماية وتنسيقها بشكل مناسب؛
• توسيع المنظمات الإنسانية نطاق البرامج وتكييف الاستجابة في جميع القطاعات مع درجة تعقيد السياق التشغيلي
Background
People with human immunodeficiency virus (PWH) with recurrent visceral leishmaniasis (VL) could potentially drive Leishmania transmission in areas with anthroponotic transmission such as East Africa, but studies are lacking. Leishmania parasitemia has been used as proxy for infectiousness.
Methods
This study is nested within the Predicting Visceral Leishmaniasis in HIV-InfectedPatients (PreLeisH) prospective cohort study, following 490 PWH free of VL at enrollment for up to 24–37 months in northwest Ethiopia. Blood Leishmania polymerase chain reaction (PCR) was done systematically. This case series reports on 10 PWH with chronic VL (≥3 VL episodes during follow-up) for up to 37 months, and 3 individuals with asymptomatic Leishmania infection for up to 24 months.
Results
All 10 chronic VL cases were male, on antiretroviral treatment, with 0–11 relapses before enrollment. Median baseline CD4 count was 82 cells/µL. They displayed 3–6 VL treatment episodes over a period up to 37 months. Leishmania blood PCR levels were strongly positive for almost the entire follow-up (median cycle threshold value, 26 [interquartile range, 23–30]), including during periods between VL treatment. Additionally, we describe 3 PWH with asymptomatic Leishmania infection and without VL history, with equally strong Leishmania parasitemia over a period of up to 24 months without developing VL. All were on antiretroviral treatment at enrollment, with baseline CD4 counts ranging from 78 to 350 cells/µL.
Conclusions
These are the first data on chronic parasitemia in PWH from Leishmania donovani–endemic areas. PWH with asymptomatic and symptomatic Leishmania infection could potentially be highly infectious and constitute Leishmania superspreaders. Xenodiagnosis studies are required to confirm infectiousness.
Background
Every year, 60% of deaths from diarrhoeal disease occur in low and middle-income countries due to inadequate water, sanitation, and hygiene. In these countries, diarrhoeal diseases are the second leading cause of death in children under five, excluding neonatal deaths. The approximately 100,000 people residing in the Bentiu Internally Displaced Population (IDP) camp in South Sudan have previously experienced water, sanitation, and hygiene outbreaks, including an ongoing Hepatitis E outbreak in 2021. This study aimed to assess the gaps in Water, Sanitation, and Hygiene (WASH), prioritise areas for intervention, and advocate for the improvement of WASH services based on the findings.
Methods
A cross-sectional lot quality assurance sampling (LQAS) survey was conducted in ninety-five households to collect data on water, sanitation, and hygiene (WASH) coverage performance across five sectors. Nineteen households were allocated to each sector, referred to as supervision areas in LQAS surveys. Probability proportional to size sampling was used to determine the number of households to sample in each sector block selected using a geographic positioning system. One adult respondent, familiar with the household, was chosen to answer WASH-related questions, and one child under the age of five was selected through a lottery method to assess the prevalence of WASH-related disease morbidities in the previous two weeks. The data were collected using the KoBoCollect mobile application. Data analysis was conducted using R statistical software and a generic LQAS Excel analyser. Crude values, weighted averages, and 95% confidence intervals were calculated for each indicator. Target coverage benchmarks set by program managers and WASH guidelines were used to classify the performance of each indicator.
Results
The LQAS survey revealed that five out of 13 clean water supply indicators, eight out of 10 hygiene and sanitation indicators, and two out of four health indicators did not meet the target coverage. Regarding the clean water supply indicators, 68.9% (95% CI 60.8%-77.1%) of households reported having water available six days a week, while 37% (95% CI 27%-46%) had water containers in adequate condition. For the hygiene and sanitation indicators, 17.9% (95% CI 10.9%-24.8%) of households had handwashing points in their living area, 66.8% (95% CI 49%-84.6%) had their own jug for cleansing after defaecation, and 26.4% (95% CI 17.4%-35.3%) of households had one piece of soap. More than 40% of households wash dead bodies at funerals and wash their hands in a shared bowl. Households with sanitary facilities at an acceptable level were 22.8% (95% CI 15.6%-30.1%), while 13.2% (95% CI 6.6%-19.9%) of households had functioning handwashing points at the latrines. Over the previous two weeks, 57.9% (95% CI 49.6–69.7%) of households reported no diarrhoea, and 71.3% (95% CI 62.1%-80.6%) reported no eye infections among children under five.
Conclusion
The camp’s hygiene and sanitation situation necessitated immediate intervention to halt the hepatitis E outbreak and prevent further WASH-related outbreaks and health issues. The LQAS findings were employed to advocate for interventions addressing the WASH gaps, resulting in WASH and health actors stepping in.
Schizophrenia is often a severe and disabling psychiatric disorder. Antipsychotics remain the mainstay of psychotropic treatment for people with psychosis. In limited resource and humanitarian contexts, it is key to have several options for beneficial, low-cost antipsychotics, which require minimal monitoring. We wanted to compare oral haloperidol, as one of the most available antipsychotics in these settings, with a second-generation antipsychotic, olanzapine.
OBJECTIVES
To assess the clinical benefits and harms of haloperidol compared to olanzapine for people with schizophrenia and schizophrenia-spectrum disorders.
METHODS
We searched the Cochrane Schizophrenia study-based register of trials, which is based on monthly searches of CENTRAL, CINAHL, ClinicalTrials.gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed and WHO ICTRP. We screened the references of all included studies. We contacted relevant authors of trials for additional information where clarification was required or where data were incomplete. The register was last searched on 14 January 2023.
SELECTION CRITERIA
Randomised clinical trials comparing haloperidol with olanzapine for people with schizophrenia and schizophrenia-spectrum disorders. Our main outcomes of interest were clinically important change in global state, relapse, clinically important change in mental state, extrapyramidal side effects, weight increase, clinically important change in quality of life and leaving the study early due to adverse effects.
DATA COLLECTION AND ANALYSIS
We independently evaluated and extracted data. For dichotomous outcomes, we calculated risk ratios (RR) and their 95% confidence intervals (CI) and the number needed to treat for an additional beneficial or harmful outcome (NNTB or NNTH) with 95% CI. For continuous data, we estimated mean differences (MD) or standardised mean differences (SMD) with 95% CIs. For all included studies, we assessed risk of bias (RoB 1) and we used the GRADE approach to create a summary of findings table.
RESULTS
We included 68 studies randomising 9132 participants. We are very uncertain whether there is a difference between haloperidol and olanzapine in clinically important change in global state (RR 0.84, 95% CI 0.69 to 1.02; 6 studies, 3078 participants; very low-certainty evidence). We are very uncertain whether there is a difference between haloperidol and olanzapine in relapse (RR 1.42, 95% CI 1.00 to 2.02; 7 studies, 1499 participants; very low-certainty evidence). Haloperidol may reduce the incidence of clinically important change in overall mental state compared to olanzapine (RR 0.70, 95% CI 0.60 to 0.81; 13 studies, 1210 participants; low-certainty evidence). For every eight people treated with haloperidol instead of olanzapine, one fewer person would experience this improvement. The evidence suggests that haloperidol may result in a large increase in extrapyramidal side effects compared to olanzapine (RR 3.38, 95% CI 2.28 to 5.02; 14 studies, 3290 participants; low-certainty evidence). For every three people treated with haloperidol instead of olanzapine, one additional person would experience extrapyramidal side effects. For weight gain, the evidence suggests that there may be a large reduction in the risk with haloperidol compared to olanzapine (RR 0.47, 95% CI 0.35 to 0.61; 18 studies, 4302 participants; low-certainty evidence). For every 10 people treated with haloperidol instead of olanzapine, one fewer person would experience weight increase. A single study suggests that haloperidol may reduce the incidence of clinically important change in quality of life compared to olanzapine (RR 0.72, 95% CI 0.57 to 0.91; 828 participants; low-certainty evidence). For every nine people treated with haloperidol instead of olanzapine, one fewer person would experience clinically important improvement in quality of life. Haloperidol may result in an increase in the incidence of leaving the study early due to adverse effects compared to olanzapine (RR 1.99, 95% CI 1.60 to 2.47; 21 studies, 5047 participants; low-certainty evidence). For every 22 people treated with haloperidol instead of olanzapine, one fewer person would experience this outcome. Thirty otherwise relevant studies and several endpoints from 14 included studies could not be evaluated due to inconsistencies and poor transparency of several parameters. Furthermore, even within studies that were included, it was often not possible to use data for the same reasons. Risk of bias differed substantially for different outcomes and the certainty of the evidence ranged from very low to low. The most common risks of bias leading to downgrading of the evidence were blinding (performance bias) and selective reporting (reporting bias).
CONCLUSIONS
Overall, the certainty of the evidence was low to very low for the main outcomes in this review, making it difficult to draw reliable conclusions. We are very uncertain whether there is a difference between haloperidol and olanzapine in terms of clinically important global state and relapse. Olanzapine may result in a slightly greater overall clinically important change in mental state and in a clinically important change in quality of life. Different side effect profiles were noted: haloperidol may result in a large increase in extrapyramidal side effects and olanzapine in a large increase in weight gain. The drug of choice needs to take into account side effect profiles and the preferences of the individual. These findings and the recent inclusion of olanzapine alongside haloperidol in the WHO Model List of Essential Medicines should increase the likelihood of it becoming more easily available in low- and middle- income countries, thereby improving choice and providing a greater ability to respond to side effects for people with lived experience of schizophrenia. There is a need for additional research using appropriate and equivalent dosages of these drugs. Some of this research needs to be done in low- and middle-income settings and should actively seek to account for factors relevant to these. Research on antipsychotics needs to be person-centred and prioritise factors that are of interest to people with lived experience of schizophrenia.
Background
Isoniazid (INH, H) resistance is the most common drug-resistant TB pattern, with treatment success rates lower than those in drug-susceptible TB. The WHO recommends a 6-month regimen of rifampicin (RIF, R), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (Lfx) (6REZLfx) for INH-resistant, RIF-susceptible TB (HRRS-TB). Uzbekistan has a high burden of TB (62/100,000 population) and multidrug-resistant TB (12/100,000 population).
Methods
We conducted a retrospective, descriptive study of microbiologically confirmed HRRS-TB using routinely collected programmatic data from 2009 to 2020.
Results
We included 854 HRRS-TB cases. Treatment success was 80.2% overall. For REZLfx, the treatment success rate was 92.0% over a short treatment duration, with no amplifications to RIF or second-line anti-TB drug resistance. We documented 46 regimens with REZLfx plus linezolid (success 87.0%) and 539 regimens using kanamycin or capreomycin (success 76.6%). We identified 37 treatment failures (4.3%), 30 deaths (3.5%), 25 resistance amplifications (2.9%), including eight to RIF (0.9%), and 99 lost to follow-up (LTFU) cases (11.6%). Unsuccessful outcomes were more common with older age, diabetes, chest X-ray cavities, smear positivity, smear-positive persistence, and male sex. LTFU was more common with injection-containing regimens.
Conclusions
REZLfx is a safe and effective first-line treatment for INH-resistant, RIF-susceptible TB. Treatment success was lower and LTFU was higher for injection-containing regimens.
Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of “prolonged fevers” (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments.
METHODS
We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias.
RESULTS
196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles.
CONCLUSIONS
Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.
In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred.
CONCLUSIONS/SIGNIFICANCE
Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia.
The burden of advanced HIV disease remains a significant concern in sub-Saharan Africa. In 2015, the World Health Organization released recommendations to treat all people living with HIV (PLHIV) regardless of CD4 (“treat all”) and in 2017 guidelines for managing advanced HIV disease. We assessed changes over time in the proportion of PLHIV with advanced HIV and their care cascade in two community settings in sub-Saharan Africa.
METHODS
Cross-sectional population-based surveys were conducted in Ndhiwa (Kenya) in 2012 and 2018 and in Eshowe (South Africa) in 2013 and 2018. We recruited individuals aged 15-59 years. Consenting participants were interviewed and tested for HIV at home. All participants with HIV had CD4 count measured. Advanced HIV was defined as CD4 < 200 cells/µL.
RESULTS
Overall, 6076 and 6001 individuals were included in 2012 and 2018 (Ndhiwa) and 5646 and 3270 individuals in 2013 and 2018 (Eshowe), respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 2012 (159/1376 (11.8%; 95% CI: 9.8-14.2)) to 2018 (53/1000 (5.0%; 3.8-6.6)). The proportion of individuals with advanced HIV on antiretroviral therapy (ART) was 9.1% (6.9-11.8) in 2012 and 4.2% (3.0-5.8) in 2018. In Eshowe, the proportion with advanced HIV was 130/1400 (9.8%; 8.0-11.9) in 2013 and 38/834 (4.5%; 3.3-6.1) in 2018. The proportion with advanced HIV among those on ART was 6.9% (5.5-8.8) in 2013 and 2.8% (1.8-4.3) in 2018. There was a significant increase in coverage for all steps of the care cascade among people with advanced HIV between the two Ndhiwa surveys, with all the changes occurring among men and not women. No significant changes were observed in Eshowe between the surveys overall and by sex.
CONCLUSION
The proportion with advanced HIV disease decreased between the first and second surveys where all guidelines have been implemented between the two HIV surveys.