Journal Article > ResearchFull Text
Int J Epidemiol. 1996 August 1
Seaman J, Mercer A, Sondorp H
Int J Epidemiol. 1996 August 1
BACKGROUND: Although endemic in parts of southern Sudan, visceral leishmaniasis (VL) had not been reported in Western Upper Nile (WUN) until an epidemic was confirmed in 1989. A combination of circumstances created conditions for transmission among a population of mainly Nuer and Dinka people who had no immunity. The civil war which restarted in 1983 has been a major contributing cause and continues to hinder provision of treatment, data collection and control measures. METHODS: Since the first of three clinics to treat VL was established in WUN in 1989, data on the epidemic and mortality have been collected in seven retrospective surveys of villages and among patients. Adults were interviewed about surviving family members and those who had died since the epidemic came. Survey death rates are used here to estimate mortality from VL and 'excess mortality' above expected levels. RESULTS: The surveys found high mortality at all ages and suggest an overall death rate of 38-57% since the epidemic started in 1984, and up to 70% in the most affected areas. Both methods of estimation suggest that around 100,000 deaths, among about 280,000 people in the epidemic area, might be attributable to VL. CONCLUSIONS: This continuing epidemic has shown that VL can cause high mortality in an outbreak with astonishingly high infection rates. Population movement has been a major factor in transmission and poor nutritional status has probably contributed to the risk of clinical infection. Although over 17,000 people have been successfully treated for VL at the clinics in WUN, the disease is likely to become endemic there.
Journal Article > ResearchFull Text
Lancet Infect Dis. 2005 December 1; Volume 5 (Issue 12); DOI:10.1016/S1473-3099(05)70296-6
Olliaro PL, Guerin PJ, Gerstl S, Haaskjold AA, Rottingen JA, et al.
Lancet Infect Dis. 2005 December 1; Volume 5 (Issue 12); DOI:10.1016/S1473-3099(05)70296-6
The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with different treatments between 1980 and 2004. Overall, 53 studies were included (all but one published), of which 15 were comparative (randomised, quasi-randomised, or non-randomised), 23 dose-finding, and 15 non-comparative. Data from comparative studies were pooled when appropriate for meta-analysis. Overall, these studies enrolled 7263 patients in 123 treatment arms. Adequacy of methods used to do the studies and report on them varied. Unresponsiveness to antimony has developed steadily in the past to such an extent that antimony must now be replaced, despite attempts to stop its progression by increasing dose and duration of therapy. The classic second-line treatments are unsuited: pentamidine is toxic and its efficacy has also declined, and amphotericin B deoxycholate is effective but requires hospitalisation for long periods and toxicity is common. Liposomal amphotericin B is very effective and safe but currently unaffordable because of its high price. Miltefosine-the first oral drug for visceral leishmaniasis-is now registered and marketed in India and is effective, but should be used under supervision to prevent misuse. Paromomycin (or aminosidine) is effective and safe, and although not yet available, a regulatory submission is due soon. To preserve the limited armamentarium of drugs to treat visceral leishmaniasis, drugs should not be deployed unprotected; combinations can make drugs last longer, improve treatment, and reduce costs to households and health systems. India, Bangladesh, and Nepal agreed recently to undertake measures towards the elimination of visceral leishmaniasis. The lessons learnt in Bihar could help inform policy decisions both regionally and elsewhere.
Journal Article > ReviewFull Text
Trans R Soc Trop Med Hyg. 2024 May 1; Online ahead of print; DOI:10.1093/trstmh/trae018
Dahal P, Singh-Phulgenda S, Wilson JM, Cota G, Ritmeijer K, et al.
Trans R Soc Trop Med Hyg. 2024 May 1; Online ahead of print; DOI:10.1093/trstmh/trae018
Blood transfusion remains an important aspect of patient management in visceral leishmaniasis (VL). However, transfusion triggers considered are poorly understood. This review summarises the transfusion practices adopted in VL efficacy studies using the Infectious Diseases Data Observatory VL clinical trials library. Of the 160 studies (1980–2021) indexed in the IDDO VL library, description of blood transfusion was presented in 16 (10.0%) (n=3459 patients) studies. Transfusion was initiated solely based on haemoglobin (Hb) measurement in nine studies, combining Hb measurement with an additional condition (epistaxis/poor health/clinical instability) in three studies and the criteria was not mentioned in four studies. The Hb threshold range for triggering transfusion was 3–8 g/dL. The number of patients receiving transfusion was explicitly reported in 10 studies (2421 patients enrolled, 217 underwent transfusion). The median proportion of patients who received transfusion in a study was 8.0% (Interquartile range: 4.7% to 47.2%; range: 0–100%; n=10 studies). Of the 217 patients requiring transfusion, 58 occurred before VL treatment initiation, 46 during the treatment/follow-up phase and the time was not mentioned in 113. This review describes the variation in clinical practice and is an important initial step in policy/guideline development, where both the patient's Hb concentration and clinical status must be considered.
Conference Material > Slide Presentation
Solomos A, Musa AM, Mbui J, Mohammed R, Olobo J, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/81jj-tz57
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 2008 February 7
Marlet MVL, Wuillaume F, Jacquet D, Quispe KW, Dujardin JC, et al.
Trans R Soc Trop Med Hyg. 2008 February 7
Visceral leishmaniasis (VL) was observed in children in Bakool region, Somalia, an area where VL has not been reported before. We describe the extent of the problem in this war- and famine-stricken area. A retrospective analysis was done of all cases admitted to a VL treatment centre between July 2000 and August 2001. Patients with longstanding fever, splenomegaly and a positive direct agglutination test (DAT; titre > 1:3200) were treated as suspected VL cases. A rapid epidemiological and entomological assessment was performed in the area. Species identification was attempted from blood samples by polymerase chain reaction-restriction fragment length polymorphism analysis of cysteine proteinase B genes. In 1 year, 230 serologically-positive cases were diagnosed as VL, and response to therapy was good in 91.6% of the 225 treated with sodium stibogluconate. Parasitological confirmation was attempted and obtained in 2 cases. Parasites were found to be most similar to Sudanese and Ethiopian reference strains of the Leishmania donovani complex. In a serological survey of 161 healthy displaced persons, 15% were positive by the leishmanin skin test and 3 (2%) were positive by the DAT. The sandfly captures showed Phlebotomus martini and P. vansomerenae. VL seems to be a longstanding and serious health problem in Bakool region. Food insecurity might have contributed to the emergence and detection of VL in this area.
Protocol > Research Study
Diro EGJ, Griensven JV, Woldegebreal T, Belew Z, Taye M, et al.
2018 July 1
2.1 OBJECTIVES
2.1.1 General objective:
To document the effectiveness, safety and feasibility of monthly PM secondary prophylaxis (PSP) in VL/HIV co-infected patients that have documented parasite clearance after VL treatment when used for prevention of VL relapse.
2.1.2 Specific objectives of the primary study period
2.1.2.1 Primary objectives
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the effectiveness of PSP in terms of preventing relapse and death;
- to assess the safety of PSP in terms of drug-related serious adverse events or permanent drug discontinuations due to adverse events;
- to assess the feasibility of PSP in terms of number of patients compliant to therapy
during the first year of monthly PM secondary prophylaxis.
2.1.2.2 Secondary objectives;
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the safety of PSP in terms of:
- drug-related non-serious adverse events
- serious adverse events (drug-related or not)
- to assess the feasibility of PSP in terms of:
- number of treatment interruptions/discontinuations,
- number of therapeutic interventions needed to treat adverse drug reactions
2.1.1 General objective:
To document the effectiveness, safety and feasibility of monthly PM secondary prophylaxis (PSP) in VL/HIV co-infected patients that have documented parasite clearance after VL treatment when used for prevention of VL relapse.
2.1.2 Specific objectives of the primary study period
2.1.2.1 Primary objectives
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the effectiveness of PSP in terms of preventing relapse and death;
- to assess the safety of PSP in terms of drug-related serious adverse events or permanent drug discontinuations due to adverse events;
- to assess the feasibility of PSP in terms of number of patients compliant to therapy
during the first year of monthly PM secondary prophylaxis.
2.1.2.2 Secondary objectives;
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the safety of PSP in terms of:
- drug-related non-serious adverse events
- serious adverse events (drug-related or not)
- to assess the feasibility of PSP in terms of:
- number of treatment interruptions/discontinuations,
- number of therapeutic interventions needed to treat adverse drug reactions
Journal Article > EditorialFull Text
Pathogens. 2023 October 19; Volume 12 (Issue 10); 1263.; DOI:10.3390/pathogens12101263
Santos ALS, Rodrigues IA, d’Avila-Levy CM, Sodré CL, Ritmeijer KKD, et al.
Pathogens. 2023 October 19; Volume 12 (Issue 10); 1263.; DOI:10.3390/pathogens12101263
Human African trypanosomiasis (also known as sleeping sickness, with Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense as etiological agents), American trypanosomiasis (also known as Chagas disease, with Trypanosoma cruzi as the etiological agent), and leishmaniasis (including cutaneous, mucocutaneous, and visceral forms, with multiple species belonging to the Leishmania genus as etiological agents) are recognized as neglected tropical diseases (NTDs). These diseases affect marginalized populations and pose a high-impact health problem, primarily in low- or low-to-middle-income countries in Africa, Asia, Latin America, and the Caribbean. Leishmania and Trypanosoma not only infect humans, but they also infect wild and domesticated animals, which serve as reservoirs for these diseases. Relevantly, the movement of people and animals across borders and within countries has become increasingly common in our interconnected world, and this mobility can both facilitate the transmission of diseases and challenge efforts to control outbreaks. Furthermore, climate changes can contribute to the spread of NTDs to areas that were previously unaffected.
Journal Article > ReviewFull Text
Lancet. 2018 September 1; Volume 392 (Issue 10151); 951-970.; DOI:10.1016/S0140-6736(18)31204-2
Burza S, Croft SL, Boelaert M
Lancet. 2018 September 1; Volume 392 (Issue 10151); 951-970.; DOI:10.1016/S0140-6736(18)31204-2
Leishmaniasis is a poverty-related disease with two main clinical forms: visceral leishmaniasis and cutaneous leishmaniasis. An estimated 0·7-1 million new cases of leishmaniasis per year are reported from nearly 100 endemic countries. The number of reported visceral leishmaniasis cases has decreased substantially in the past decade as a result of better access to diagnosis and treatment and more intense vector control within an elimination initiative in Asia, although natural cycles in transmission intensity might play a role. In east Africa however, the case numbers of this fatal disease continue to be sustained. Increased conflict in endemic areas of cutaneous leishmaniasis and forced displacement has resulted in a surge in these endemic areas as well as clinics across the world. WHO lists leishmaniasis as one of the neglected tropical diseases for which the development of new treatments is a priority. Major evidence gaps remain, and new tools are needed before leishmaniasis can be definitively controlled.
Journal Article > ResearchFull Text
J Infect Dev Ctries. 2020 June 30; Volume 14 (Issue 06.1); DOI:10.3855/jidc.11731
Tekalign S, Adera C, den Boer ML, Miecha H, Zewde A, et al.
J Infect Dev Ctries. 2020 June 30; Volume 14 (Issue 06.1); DOI:10.3855/jidc.11731
Introduction: In three health care facilities in the Oromia region, the aim of this study is to report on 1) the number of VL cases registered over time (2013-2018) and 2) the clinical profile, type of treatment used and response to treatment.
Methodology: A retrospective cohort study was conducted among all VL cases admitted with a diagnosis of VL.
Results: A total of 434 VL cases were registered at the three health facilities, but patient files were available for only 188. Most (51.6%) were children and only three presented with VL relapse. 78 (41.5%) of the 188 patients presented within one month of symptom onset. Concurrent severe acute malnutrition (27.1%), tuberculosis (6.4%) and malaria (6.4%) were common. There were only two cases with HIV coinfection. Fourty-three percent were treated with antimonials, 34% with antimonials combined with paromomycin and 23% with AmBisome. Amongst the 188 patients with patient files there were no deaths and one treatment failure. Six months outcome data were however missing for all. Aggregated data from the 434 VL cases reported three deaths, two treatment failures and one relapse.
Conclusions: Children were most commonly affected, suggesting long-term endemicity. While short-term outcomes are encouraging, long-term follow-up data are required.
Methodology: A retrospective cohort study was conducted among all VL cases admitted with a diagnosis of VL.
Results: A total of 434 VL cases were registered at the three health facilities, but patient files were available for only 188. Most (51.6%) were children and only three presented with VL relapse. 78 (41.5%) of the 188 patients presented within one month of symptom onset. Concurrent severe acute malnutrition (27.1%), tuberculosis (6.4%) and malaria (6.4%) were common. There were only two cases with HIV coinfection. Fourty-three percent were treated with antimonials, 34% with antimonials combined with paromomycin and 23% with AmBisome. Amongst the 188 patients with patient files there were no deaths and one treatment failure. Six months outcome data were however missing for all. Aggregated data from the 434 VL cases reported three deaths, two treatment failures and one relapse.
Conclusions: Children were most commonly affected, suggesting long-term endemicity. While short-term outcomes are encouraging, long-term follow-up data are required.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 2006 January 1; Volume 74 (Issue 1); 76-80.
Ritmeijer KKD, Melaku Y, Mueller M, Kipngetich S, O'keeffe C, et al.
Am J Trop Med Hyg. 2006 January 1; Volume 74 (Issue 1); 76-80.
A new rK39 rapid diagnostic dipstick test (DiaMed-IT-Leish) was compared with aspiration and a direct agglutination test (DAT) for diagnosis of visceral leishmaniasis (VL) in 201 parasitologically confirmed cases, 133 endemic controls, and in 356 clinical suspects in disease-endemic and -epidemic areas in Sudan. The sensitivity of the rK39 test in parasitologically confirmed VL cases was 90%, whereas the specificity in disease-endemic controls was 99%. The sensitivity of the DAT was 98%. In clinically suspected cases, the sensitivity of the rK39 test was 81% and the specificity was 97%. When compared with the diagnostic protocol based on the DAT and aspiration used by Médecins sans Frontières in epidemic situations, the positive predictive value was 98%, and the negative predictive value was 71%. This rK39 rapid diagnostic test is suitable for screening as well as diagnosis of VL. Further diagnostic work-up of dipstick-negative patients with clinically suspected VL is important. The ease and convenience of the dipstick test will allow decentralization and improved access to care in disease-endemic areas in Sudan.