Journal Article > ResearchFull Text
Am J Trop Med Hyg. 25 September 2023; Online ahead of print; tpmd230382.; DOI:10.4269/ajtmh.23-0382
Molina-de la Fuente I, Sagrado Benito MJ, Ousley J, Gisbert FdB, García L, et al.
Am J Trop Med Hyg. 25 September 2023; Online ahead of print; tpmd230382.; DOI:10.4269/ajtmh.23-0382
Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.
Journal Article > CommentaryFull Text
Am J Trop Med Hyg. 6 September 2023; Volume 109 (Issue 3); 511-514.; DOI:10.4269/ajtmh.22-0606
Kabore Y, Vatrinet R, Guindo O, Moussa SH, Schilling WHK, et al.
Am J Trop Med Hyg. 6 September 2023; Volume 109 (Issue 3); 511-514.; DOI:10.4269/ajtmh.22-0606
In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a rapidly emerging virus causing the coronavirus disease 2019 (COVID-19) pandemic, had no known effective prophylaxis and no widely available proven effective antiviral treatment. Hydroxychloroquine/Chloroquine was identified as an early potential therapeutic candidate drawing on evidence from reports of both in vitro and in vivo testing. A multicountry placebo-controlled randomized trial was set to evaluate the use of hydroxychloroquine/chloroquine to prevent infection in healthcare workers and staff working in a health facility involved in COVID-19 management. One of the sites of this trial was in Niger. In Niger, of the 240 persons who were provided information about the study and with whom participation was discussed, only five participants provided their informed consent. In this article, we describe the key difficulties encountered in the conduct of this trial from the perspective of the site study team. Among the difficulties, we recognize that the epidemic context, controversy surrounding hydroxychloroquine, vaccine rollout, participants’ perspectives, and trial design had a major impact on participation.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 18 April 2022; Volume Online version ahead of print; 1-5.; DOI:10.4269/ajtmh.21-1045
Chandna A, Richard-Greenblatt M, Tustin R, Lee SJ, Kain KC, et al.
Am J Trop Med Hyg. 18 April 2022; Volume Online version ahead of print; 1-5.; DOI:10.4269/ajtmh.21-1045
Host biomarker testing can be used as an adjunct to the clinical assessment of patients with infections and might be particularly impactful in resource-constrained settings. Research on the merits of this approach at peripheral levels of low- and middle-income country health systems is limited. In part, this is due to resource-intense requirements for sample collection, processing, and storage. We evaluated the stability of 16 endothelial and immune activation biomarkers implicated in the host response to infection stored in venous plasma and dried blood spot specimens at different temperatures for 6 months. We found that –80°C storage offered no clear advantage over –20°C for plasma aliquots, and most biomarkers studied could safely be stored as dried blood spots at refrigeration temperatures (4°C) for up to 3 months. These results identify more practical methods for host biomarker testing in resource-limited environments, which could help facilitate research in rural and remote environments.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 11 November 2013; Volume 90 (Issue 1); DOI:10.4269/ajtmh.13-0150
Mueller YK, Kolaczinski JH, Koech T, Lokwang P, Riongoita M, et al.
Am J Trop Med Hyg. 11 November 2013; Volume 90 (Issue 1); DOI:10.4269/ajtmh.13-0150
Between 2000 and 2010, Médecins Sans Frontières diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An Rk39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 7 October 2019; Volume 101 (Issue 6); DOI:10.4269/ajtmh.19-0430
Kamink SS, Abdi AM, Kamau C, Ashraf S, Ansari MA, et al.
Am J Trop Med Hyg. 7 October 2019; Volume 101 (Issue 6); DOI:10.4269/ajtmh.19-0430
Cutaneous leishmaniasis (CL), a neglected parasitic skin disease, is endemic in Pakistan, where Leishmania tropica and Leishmania major are the causative protozoan species. Standard treatment with antimonial injections is long, painful, and costly; has toxic side effects; and is not always available in public hospitals. Small pilot studies have previously evaluated a low-cost and noninvasive hand-held exothermic crystallization thermotherapy (HECT-CL) device. We aimed to further establish the effectiveness, safety, and feasibility of HECT-CL in L. tropica. In a prospective observational study, patients with parasitological confirmation of CL were treated using the HECT-CL heat pack for 3 minutes with an initial temperature of 52-53°C for 7 consecutive days. Dried blood spot samples were taken for species identification by PCR. Effectiveness was assessed by using medical photographs and measurements of the lesion size at baseline and subsequent follow-up visits, for up to 180 days. We intended to enroll 317 patients. The HECT-CL treatment was easy to apply and well tolerated. Species identification demonstrated the presence of L. tropica. Interim analysis of 56 patients showed a failure rate of 91% at follow-up (median 45 days after treatment, interquartile range 30-60 days). Enrollment of patients was prematurely suspended because of futility. This study showed a high failure rate for HECT-CL thermotherapy in this setting. Leishmania tropica is known to be less sensitive to antileishmanial drugs, more temperature-resistant, and spontaneous healing is slower than that in L. major. More research is needed to identify low-cost, effective, and more patient-friendly treatment for L. tropica.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 1 April 2004; Volume 70 (Issue 4); 390-394.
Hutin Y, Legros D, Owini V, Brown V, Lee EC, et al.
Am J Trop Med Hyg. 1 April 2004; Volume 70 (Issue 4); 390-394.
We estimated the pre-intervention prevalence of Trypanosoma brucei gambiense (Tbg) trypanosomiasis using the lot quality assurance sampling (LQAS) methods in 14 parishes of Terego County in northern Uganda. A total of 826 participants were included in the survey sample in 1996. The prevalence of laboratory confirmed Tbg trypanosomiasis adjusted for parish population sizes was 2.2% (95% confidence interval =1.1-3.2). This estimate was consistent with the 1.1% period prevalence calculated on the basis of cases identified through passive and active screening in 1996-1999. Ranking of parishes in four categories according to LQAS analysis of the 1996 survey predicted the prevalences observed during the first round of active screening in the population in 1997-1998 (P < 0.0001, by chi-square test). Overall prevalence and ranking of parishes obtained with LQAS were validated by the results of the population screening, suggesting that these survey methods may be useful in the pre-intervention phase of sleeping sickness control programs.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 22 February 2018; Volume 98 (Issue 4); 1091–1101.; DOI:10.4269/ajtmh.17-0872
Sunyoto T, Adam GK, Atia AM, Hamid Y, Babiker RA, et al.
Am J Trop Med Hyg. 22 February 2018; Volume 98 (Issue 4); 1091–1101.; DOI:10.4269/ajtmh.17-0872
Early diagnosis and treatment is the principal strategy to control visceral leishmaniasis (VL), or kala-azar in East Africa. As VL strikes remote rural, sparsely populated areas, kala-azar care might not be accessed optimally or timely. We conducted a qualitative study to explore access barriers in a longstanding kala-azar endemic area in southern Gadarif, Sudan. Former kala-azar patients or caretakers, community leaders, and health-care providers were purposively sampled and thematic data analysis was used. Our study participants revealed the multitude of difficulties faced when seeking care. The disease is well known in the area, yet misconceptions about causes and transmission persist. The care-seeking itineraries were not always straightforward: "shopping around" for treatments are common, partly linked to difficulties in diagnosing kala-azar. Kala-azar is perceived to be "hiding," requiring multiple tests and other diseases must be treated first. Negative perceptions on quality of care in the public hospitals prevail, with the unavailability of drugs or staff as the main concern. Delay to seek care remains predominantly linked to economic constraint: albeit treatment is for free, patients have to pay out of pocket for everything else, pushing families further into poverty. Despite increased efforts to tackle the disease over the years, access to quality kala-azar care in this rural Sudanese context remains problematic. The barriers explored in this study are a compelling reminder of the need to boost efforts to address these barriers.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 1 June 2009; Volume 80 (Issue 6); 929-34.
ter Horst R, Tefera T, Assefa G, Ebrahim AZ, Davidson RN, et al.
Am J Trop Med Hyg. 1 June 2009; Volume 80 (Issue 6); 929-34.
Accuracy of an rK39 rapid diagnostic test (DiaMed-IT-Leish ) for visceral leishmaniasis (VL) was compared with splenic aspiration and the direct agglutination test (DAT) in a population with a high prevalence of infection with human immunodeficiency virus (HIV) in Ethiopia. There were 699 patients clinically suspected of having VL (153 parasitologically confirmed, 482 DAT confirmed, and 130 DAT negative), and 97 DAT-negative controls. A total of 84% were tested for HIV and 34% were HIV positive. Sensitivity of the rK39 test in parasitologically confirmed VL patients was 84% (77% in HIV positive and 87% in HIV negative; P = 0.25). Sensitivity of the DAT was higher (94%; P = 0.01), 89% in HIV-positive patients and 95% in HIV-negative patients; P = 0.27). Specificity of the rK39 test was 99% in DAT-negative controls and 92% in DAT-negative patients clinically suspected of having VL. A diagnostic algorithm combining DAT and the rK39 test had a sensitivity of 98% in HIV-positive VL patients and 99% in HIV-negative VL patients. Despite the lower sensitivity in a population with a high prevalence of HIV, the DiaMed-IT-Leish rK39 test enables decentralization of diagnosis. Patients clinically suspected of having VL who show negative results on the rK39 antigen test should undergo follow-up DAT testing, especially if they are HIV positive.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 3 October 2016; Volume 95 (Issue 6); 1389–1397 .; DOI:10.4269/ajtmh.16-0376
Tiffany A, Moundekeno FP, Traore A, Haile M, Sterk E, et al.
Am J Trop Med Hyg. 3 October 2016; Volume 95 (Issue 6); 1389–1397 .; DOI:10.4269/ajtmh.16-0376
Multiple community-based approaches can aid in quantifying mortality in the absence of reliable health facility data. Community-based sentinel site surveillance that was used to document mortality and the systems utility for outbreak detection was evaluated. We retrospectively analyzed data from 46 sentinel sites in three sous-préfectures with a reinforced malaria control program and one sous-préfecture without (Koundou) in Guinea. Deaths were recorded by key informants and classified as due to malaria or another cause. Malaria deaths were those reported as due to malaria or fever in the 3 days before death with no other known cause. Suspect Ebola virus disease (sEVD) deaths were those due to select symptoms in the EVD case definition. Deaths were aggregated by sous-préfecture and analyzed by a 6-month period. A total of 43,000 individuals were monitored by the surveillance system; 1,242 deaths were reported from July 2011-June 2014, of which 55.2% (N = 686) were reported as due to malaria. Malaria-attributable proportional mortality decreased by 26.5% (95% confidence interval [CI] = 13.9-33.1, P < 0.001) in the program area and by 6.6% (95% CI = -17.3-30.5, P = 0.589) in Koundou. Sixty-eight deaths were classified as sEVD and increased by 6.1% (95% CI = 1.3-10.8, P = 0.021). Seventeen sEVD deaths were reported from November 2013 to March 2014 including the first two laboratory-confirmed EVD deaths. Community surveillance can capture information on mortality in areas where data collection is weak, but determining causes of death remains challenging. It can also be useful for outbreak detection if timeliness of data collection and reporting facilitate real-time data analysis.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 1 June 2015; Volume 92 (Issue 6_Suppl); 39-50.; DOI:10.4269/ajtmh.14-0391
Yeung S, Lawford H, Tabernero P, Nguon C, van Wyk A, et al.
Am J Trop Med Hyg. 1 June 2015; Volume 92 (Issue 6_Suppl); 39-50.; DOI:10.4269/ajtmh.14-0391
Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open surveyors and mystery clients (MCs). Few oral artemisinin-based monotherapies and no suspected falsified medicines were found. All 291 samples contained the stated active pharmaceutical ingredient (API) of which 69% were considered good quality by chemical analysis. Overall, medicine quality did not differ by collection method, although open surveyors were less likely to obtain oral artemisinin-based monotherapies than MCs. The results are an encouraging indication of the positive impact of the country's efforts to tackle falsified antimalarials and artemisinin-based monotherapies. However, poor-quality medicines remain an ongoing challenge that demands sustained political will and investment of human and financial resources.