Journal Article > ResearchFull Text
Infect Agent Cancer. 2018 January 19; Volume 13 (Issue 1); DOI:10.1186/s13027-018-0177-6
Fardhdiani V, Molfino L, Zamudio AG, Manuel R, Luciano G, et al.
Infect Agent Cancer. 2018 January 19; Volume 13 (Issue 1); DOI:10.1186/s13027-018-0177-6
Kaposi's sarcoma (KS) is a common HIV-associated malignancy associated with disability, pain and poor outcomes. The cornerstone of its treatment is antiretroviral therapy, but advanced disease necessitates the addition of chemotherapy. In high-income settings, this often consists of liposomal anthracyclines, but in Mozambique, the first line includes conventional doxorubicin, bleomycin and vincristine, which is poorly-tolerated. Médecins Sans Frontières supports the Ministry of Health (MOH) in a specialized HIV and KS treatment center at the Centro de Referencia de Alto Maé in Maputo.
Journal Article > ResearchFull Text
Confl Health. 2017 May 15; Volume 11 (Issue 1); 7.; DOI:10.1186/s13031-017-0110-4
Coldiron ME, Roederer T, Llosa AE, Bouhenia M, Madi S, et al.
Confl Health. 2017 May 15; Volume 11 (Issue 1); 7.; DOI:10.1186/s13031-017-0110-4
The Central African Republic has known long periods of instability. In 2014, following the fall of an interim government installed by the Séléka coalition, a series of violent reprisals occurred. These events were largely directed at the country's Muslim minority and led to a massive displacement of the population. In 2014, we sought to document the retrospective mortality among refugees arriving from the CAR into Chad by conducting a series of surveys.
Journal Article > ResearchFull Text
Malar J. 2022 September 9; Volume 21 (Issue 1); 261.; DOI:10.1186/s12936-022-04280-w
Lynch E, Jensen TO, Assao B, Chihana ML, Turuho T, et al.
Malar J. 2022 September 9; Volume 21 (Issue 1); 261.; DOI:10.1186/s12936-022-04280-w
BACKGROUND
Rapid diagnostic tests (RDT) for malaria are the primary tool for malaria diagnosis in sub-Saharan Africa but the utility of the most commonly used histidine-rich protein 2 (HRP2) antigen-based tests is limited in high transmission settings due to the long duration of positivity after successful malaria treatment. HRP2 tests are also threatened by the emergence of Plasmodium that do not carry pfhrp2 or pfhrp 3 genes. Plasmodium lactate dehydrogenase (pLDH)-based tests are promising alternatives, but less available. This study assessed the performances of HRP2 and pLDH(pan) tests under field conditions.
METHODS
The study performed a prospective facility-based diagnostic evaluation of two malaria RDTs in Aweil, South Sudan, during the high transmission season. Capillary blood by fingerprick was collected from 800 children under 15 years of age with fever and no signs of severity. SD Bioline HRP2 and CareStart pLDH(pan) RDTs were performed in parallel, thick and thin smears for microscopy were examined, and dried blood was used for PCR testing.
RESULTS
Using microscopy as the gold standard, the sensitivity of both tests was estimated at > 99%, but the specificity of each was lower: 55.0% for the pLDH test and 61.7% for the HRP2 test. When using PCR as the gold standard, the sensitivity of both tests was lower than the values assessed using microscopy (97.0% for pLDH and 96.5% for HRP2), but the specificity increased (65.1% for pLDH and 72.9% for HRP2). Performance was similar across different production lots, sex, and age. Specificity of both the pLDH and HRP2 tests was significantly lower in children who reported taking a therapeutic course of anti-malarials in the 2 months prior to enrollment. The prevalence of pfhrp2/3 deletions in the study population was 0.6%.
CONCLUSIONS
The low specificity of the pLDH RDT in this setting confirms previous results and suggests a problem with this specific test. The prevalence of pfhrp2/3 deletions in the study area warrants continued monitoring and underscores the relevance of assessing deletion prevalence nationally. Improved malaria RDTs for high-transmission environments are needed.
Rapid diagnostic tests (RDT) for malaria are the primary tool for malaria diagnosis in sub-Saharan Africa but the utility of the most commonly used histidine-rich protein 2 (HRP2) antigen-based tests is limited in high transmission settings due to the long duration of positivity after successful malaria treatment. HRP2 tests are also threatened by the emergence of Plasmodium that do not carry pfhrp2 or pfhrp 3 genes. Plasmodium lactate dehydrogenase (pLDH)-based tests are promising alternatives, but less available. This study assessed the performances of HRP2 and pLDH(pan) tests under field conditions.
METHODS
The study performed a prospective facility-based diagnostic evaluation of two malaria RDTs in Aweil, South Sudan, during the high transmission season. Capillary blood by fingerprick was collected from 800 children under 15 years of age with fever and no signs of severity. SD Bioline HRP2 and CareStart pLDH(pan) RDTs were performed in parallel, thick and thin smears for microscopy were examined, and dried blood was used for PCR testing.
RESULTS
Using microscopy as the gold standard, the sensitivity of both tests was estimated at > 99%, but the specificity of each was lower: 55.0% for the pLDH test and 61.7% for the HRP2 test. When using PCR as the gold standard, the sensitivity of both tests was lower than the values assessed using microscopy (97.0% for pLDH and 96.5% for HRP2), but the specificity increased (65.1% for pLDH and 72.9% for HRP2). Performance was similar across different production lots, sex, and age. Specificity of both the pLDH and HRP2 tests was significantly lower in children who reported taking a therapeutic course of anti-malarials in the 2 months prior to enrollment. The prevalence of pfhrp2/3 deletions in the study population was 0.6%.
CONCLUSIONS
The low specificity of the pLDH RDT in this setting confirms previous results and suggests a problem with this specific test. The prevalence of pfhrp2/3 deletions in the study area warrants continued monitoring and underscores the relevance of assessing deletion prevalence nationally. Improved malaria RDTs for high-transmission environments are needed.
Conference Material > Video
Coldiron ME
MSF Scientific Days International 2020: Research. 2020 May 13
Conference Material > Video
Coldiron ME
Epicentre Scientific Day Paris 2022. 2022 June 21
Journal Article > ResearchFull Text
Epidemics. 2015 September 3; Volume 14; 1-10.; DOI:10.1016/j.epidem.2015.08.001
Allan M, Grandesso F, Pierre R, Magloire R, Coldiron ME, et al.
Epidemics. 2015 September 3; Volume 14; 1-10.; DOI:10.1016/j.epidem.2015.08.001
BACKGROUND
Cholera is caused by Vibrio cholerae, and is transmitted through fecal-oral contact. Infection occurs after the ingestion of the bacteria and is usually asymptomatic. In a minority of cases, it causes acute diarrhea and vomiting, which can lead to potentially fatal severe dehydration, especially in the absence of appropriate medical care. Immunity occurs after infection and typically lasts 6-36 months. Cholera is responsible for outbreaks in many African and Asian developing countries, and caused localised and episodic epidemics in South America until the early 1990s. Haiti, despite its low socioeconomic status and poor sanitation, had never reported cholera before the recent outbreak that started in October 2010, with over 720,000 cases and over 8700 deaths (Case fatality rate: 1.2%) through 8 December 2014. So far, this outbreak has seen 3 epidemic peaks, and it is expected that cholera will remain in Haiti for some time.
METHODOLOGY/FINDINGS
To trace the path of the early epidemic and to identify hot spots and potential transmission hubs during peaks, we examined the spatial distribution of cholera patients during the first two peaks in Artibonite, the second-most populous department of Haiti. We extracted the geographic origin of 84,000 patients treated in local health facilities between October 2010 and December 2011 and mapped these addresses to 63 rural communal sections and 9 urban cities. Spatial and cluster analysis showed that during the first peak, cholera spread along the Artibonite River and the main roads, and sub-communal attack rates ranged from 0.1% to 10.7%. During the second peak, remote mountain areas were most affected, although sometimes to very different degrees even in closely neighboring locations. Sub-communal attack rates during the second peak ranged from 0.2% to 13.7%. The relative risks at the sub-communal level during the second phase showed an inverse pattern compared to the first phase.
CONCLUSION/SIGNIFICANCE
These findings demonstrate the value of high-resolution mapping for pinpointing locations most affected by cholera, and in the future could help prioritize the places in need of interventions such as improvement of sanitation and vaccination. The findings also describe spatio-temporal transmission patterns of the epidemic in a cholera-naïve country such as Haiti. By identifying transmission hubs, it is possible to target prevention strategies that, over time, could reduce transmission of the disease and eventually eliminate cholera in Haiti.
Cholera is caused by Vibrio cholerae, and is transmitted through fecal-oral contact. Infection occurs after the ingestion of the bacteria and is usually asymptomatic. In a minority of cases, it causes acute diarrhea and vomiting, which can lead to potentially fatal severe dehydration, especially in the absence of appropriate medical care. Immunity occurs after infection and typically lasts 6-36 months. Cholera is responsible for outbreaks in many African and Asian developing countries, and caused localised and episodic epidemics in South America until the early 1990s. Haiti, despite its low socioeconomic status and poor sanitation, had never reported cholera before the recent outbreak that started in October 2010, with over 720,000 cases and over 8700 deaths (Case fatality rate: 1.2%) through 8 December 2014. So far, this outbreak has seen 3 epidemic peaks, and it is expected that cholera will remain in Haiti for some time.
METHODOLOGY/FINDINGS
To trace the path of the early epidemic and to identify hot spots and potential transmission hubs during peaks, we examined the spatial distribution of cholera patients during the first two peaks in Artibonite, the second-most populous department of Haiti. We extracted the geographic origin of 84,000 patients treated in local health facilities between October 2010 and December 2011 and mapped these addresses to 63 rural communal sections and 9 urban cities. Spatial and cluster analysis showed that during the first peak, cholera spread along the Artibonite River and the main roads, and sub-communal attack rates ranged from 0.1% to 10.7%. During the second peak, remote mountain areas were most affected, although sometimes to very different degrees even in closely neighboring locations. Sub-communal attack rates during the second peak ranged from 0.2% to 13.7%. The relative risks at the sub-communal level during the second phase showed an inverse pattern compared to the first phase.
CONCLUSION/SIGNIFICANCE
These findings demonstrate the value of high-resolution mapping for pinpointing locations most affected by cholera, and in the future could help prioritize the places in need of interventions such as improvement of sanitation and vaccination. The findings also describe spatio-temporal transmission patterns of the epidemic in a cholera-naïve country such as Haiti. By identifying transmission hubs, it is possible to target prevention strategies that, over time, could reduce transmission of the disease and eventually eliminate cholera in Haiti.
Journal Article > ResearchFull Text
Infect Agent Cancer. 2021 January 7; Volume 16 (Issue 1); DOI:10.1186/s13027-020-00341-4
Coldiron ME, Gutierrez Zamudio AG, Manuel R, Luciano G, Rusch B, et al.
Infect Agent Cancer. 2021 January 7; Volume 16 (Issue 1); DOI:10.1186/s13027-020-00341-4
BACKGROUND
Kaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique.
METHODS
We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment.
RESULTS
At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2–6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD.
DISCUSSION
PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.
Kaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique.
METHODS
We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment.
RESULTS
At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2–6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD.
DISCUSSION
PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.
Conference Material > Poster
Mamaty AA, Atti S, Sani KA, Tonamou G, Ciglenecki I, et al.
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/QLiHOZ
Conference Material > Abstract
Coldiron ME
Epicentre Scientific Day Paris 2022. 2022 June 1
The early 2000s saw great advances in malaria control worldwide, in part due to scale-up of proven preventive strategies such as insecticide-treated bednets and a variety of chemoprevention measures. In 2015, that progress began to stall, and in 2020, according to WHO, there was a marked increase in the number of malaria cases and deaths, larger than any seen in the last two decades: over 241 million cases of malaria and 626 000 deaths, including 479 000 deaths among African children under 5 years old. In this troubling context, there have been many recent advances and changes regarding malaria prevention, which will be detailed in the introduction to this roundtable.
• The largest headline came in 2021, with a recommendation to use the RTS,S vaccine, the first malaria vaccine to be approved for broad use in African contexts. This modestly effective vaccine will be expensive but could have a major impact if access issues could be overcome and the vaccine used effectively at scale.
• New WHO guidelines for a variety of chemoprevention strategies are expected soon. Strategies like Seasonal Malaria Chemoprevention (SMC) may see their eligibility criteria broadened, and Mass Drug Administration may be given a more prominent place in the malaria toolbox. Older proven strategies, like Intermittent Preventive Treatment (IPT) among pregnant women and IPT among infants may be re-branded, and re-emphasized in an effort to improve uptake.
• Pyrethroid insecticides are standard in impregnated bednets. Mosquito resistance to pyrethroid insecticides is increasing, which might eventually warrant the roll-out of next-generation pyrethroid-PBO bednets, which are more expensive and less durable.
Malaria prevention is at a critical juncture. We will discuss these scientific, public health, and strategic considerations in-depth with an expert panel.
This abstract is not to be quoted for publication
• The largest headline came in 2021, with a recommendation to use the RTS,S vaccine, the first malaria vaccine to be approved for broad use in African contexts. This modestly effective vaccine will be expensive but could have a major impact if access issues could be overcome and the vaccine used effectively at scale.
• New WHO guidelines for a variety of chemoprevention strategies are expected soon. Strategies like Seasonal Malaria Chemoprevention (SMC) may see their eligibility criteria broadened, and Mass Drug Administration may be given a more prominent place in the malaria toolbox. Older proven strategies, like Intermittent Preventive Treatment (IPT) among pregnant women and IPT among infants may be re-branded, and re-emphasized in an effort to improve uptake.
• Pyrethroid insecticides are standard in impregnated bednets. Mosquito resistance to pyrethroid insecticides is increasing, which might eventually warrant the roll-out of next-generation pyrethroid-PBO bednets, which are more expensive and less durable.
Malaria prevention is at a critical juncture. We will discuss these scientific, public health, and strategic considerations in-depth with an expert panel.
This abstract is not to be quoted for publication
Conference Material > Abstract
Idrissa AA, Atti S, Wasaulua RK, Kazadi S, Guindo O, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/wg9g-dq47
INTRODUCTION
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared