Therapeutic efficacy of chloroquine and sulfadoxine/pyrimethamine against Plasmodium falciparum infection in Somalia

Study on the therapeutic efficacy of treatments based on chloroquine and sulfadoxine/pyrimethamine in cases of malaria (Plasmodium falciparum) in Merka and Gabiley, Somalia.Daraasaad ku saabsan waxtarka ku daaweynta chloroquine iyo sulfadoxine/pyrimethamine cudurka duumada, degaannada soomaaliyeed ee Marka iyo Gabiley.Studio sull'efficacia terapeutica di trattamenti a base di clorochina e sulfadossina/pirimetamina nei casi di malaria (Plasmodium falciparum) a Merka e Gabiley, Somalia

Assessment of the Therapeutic Efficacy of Two Artemisinin-Based Combinations in the Treatment of Uncomplicated Falciparum Malaria among Children Under 5 Years in Four District Hospitals in Sierra Leone

Plasmodium falciparum has developed resistance to almost every class of antimalarial compounds. As a result of this, the World Health Organization has recommended artemisinin-based combination therapy as first line treatment for P. falciparum malaria. There is however need for the continuous monitoring of the efficacy of these antimalarials in order to provide timely information on trends of the emergence of resistant strains. We assessed the therapeutic efficacy of oral artesunate – amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated P. falciparum malaria in four District Hospitals in Sierra Leone. A total of 320 children under five years partiiccipated in the study sites (Kenema, Rokupa, Bo and Makeni). Oral Artesunate-amodiaquine combination was administered to participants in Kenema and Rokupa whilst Artemetherlumefantrine combination was administered to participants in Bo and Makeni. The new WHO Protocol for recruitment of participants in therapeutic efficacy trials in high transmission zones was adopted for the study with filter paper blood samples taken from each participant on days 0 and 28 to distinguish between treatment failure and new infection. When uncorrected for PCR analysis, 96% (95% CI: 902 – 989) and 100% (95% CI:63.1 – 100) responses were obtained in Kenema and Bo respectively with Artesunate-amodiaquine combination whilst 94.3% (CI 95 : 88.1 – 979) and 100% (95% CI: 96.5 – 100) were obtained with Artemether-lumefantrine combination in Bo and Makeni respectively. When corrected for PCR on the other hand, a 100% (95% CI) Adequate Clinical and Parasitological Response was obtained for the two drugs in all four study sites. Results from this study indicate that both Artesunate-amodiaquine and Artemether-lumefantrine combinations remain highly efficacious in Sierra Leone with presently no observed emergence of resistant strains to both drugs.Keywords: Artemisinin-based combination, uncomplicated falciparum malaria, children, Sierra Leon

Patterns of resistance and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania prior to the adoption of sulfadoxine-pyrimethamine as first-line treatment.

A study was carried out to assess the patterns of resistance and occurrence of DHFR/DHPS genotypes of Plasmodium falciparum prior to the adoption of sulfadoxine-pyrimethamine (SP) as first-line treatment for uncomplicated malaria in Tanzania. Children under five years (n = 117) with clinical, uncomplicated malaria were randomly allocated to standard treatments of either chloroquine (CQ) (25 mg/kg) or SP (25 mg sulfadoxine and 1.25 mg pyrimethamine/kg). Patients were monitored for 28 days. Clinical recovery was achieved in 98% (n = 58) and 90% (n = 59) of the patients in the SP and CQ groups, respectively. Parasitologically, 14% of the patients in the SP group and 51% in the CQ group exhibited RII/RIII resistance. When relating pre-treatment blood drug levels to treatment outcome and the degree of parasite resistance to the number of mutations, no relationships could be detected. There was an overall significant increase in haemoglobin levels from day 0 to day 28 in both patient groups. Sulfadoxine-pyrimethamine produced an acceptable clinical response but the high degree of parasitological resistance (RII/RIII) observed two years prior to the introduction of the drug as first-line treatment is of concern, especially considering the long half-lives of sulfadoxine and pyrimethamine

Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients

Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18â question Center for Epidemiologic Studiesâ Depression Scale (CESâ D). Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CESâ D score > 14) and frailty were associated with KT length of stay (LOS), deathâ censored graft failure (DCGF), and mortality. At KT admission, 10.0% of patients exhibited depressive symptoms, 16.3% were frail, and 3.6% had both. Recipients with depressive symptoms were more likely to be frail (aOR = 3.97, 95% CI: 2.28â 6.91, P < 0.001). Recipients with both depressive symptoms and frailty had a 1.88 times (95% CI: 1.70â 2.08, P < 0.001) longer LOS, 6.20â fold (95% CI:1.67â 22.95, P < 0.01) increased risk of DCGF, and 2.62â fold (95% CI:1.03â 6.70, P = 0.04) increased risk of mortality, compared to those who were nonfrail and without depressive symptoms. There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction < 0.001). Interventions aimed at reducing preâ KT depressive symptoms and frailty should be explored for their impact on postâ KT outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146305/1/ctr13391_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146305/2/ctr13391.pd

Impact of laboratory diagnosis for improving the management of uncomplicated malaria at peripheral health care settings in Coast region, Tanzania

Malaria is a disease caused by parasites of the genus Plasmodium. Five species cause human disease, but the most common in tropical areas, and the cause of severe disease is Plasmodium falciparum. Control of morbidity and mortality is mainly achieved through appropriate malaria case management, which includes prompt diagnosis and treatment with effective antimalarial drugs. While definitive diagnosis of malaria is made by demonstration of parasites in the patient blood through microscopic examination of giemsa stained blood smears, in most clinical settings in Africa, diagnosis is limited by lack of facilities and personnel. The availability of malaria rapid diagnostic tests (RDTs) offers an opportunity to extend diagnostic services to areas previously not covered by conventional microscopy services. Two intervention trials were conducted, one at primary health care (PHC) facilities using microscopy, and the other at community level, through community health workers (CHWs), using rapid diagnostic tests (RDTs) for malaria diagnosis, and the impact of the interventions on antimalarial drugs prescription practices, antibiotic prescriptions and health outcome was investigated (Study I and II). A descriptive, cross sectional study was conducted to assess health workers diagnostic and prescription practices following introduction of RDTs for universal testing of malaria at PHC level in Tanzania (Study III). An exploratory study was also carried out to assess the usefulness of Histidine rich protein 2 (HRP2) and lactate dehydrogenase (LDH) based RDTs for treatment monitoring and detection of recurrent infection following artemisinin-based combination therapy (ACT) during a 42 day follow up period (Study IV). The use of parasite-based diagnostics significantly reduced antimalarial prescriptions at health facility and community level without affecting the health outcome of patients not treated with antimalarials (study I and II). The prescriptions of antimalarial drugs were 61% at intervention health facilities, whereas in the clinical and control arms the prescription rates remained high, 95% and 99%, respectively (study I). Similarly, 53% of patients tested with RDT at community level were provided antimalarial drugs compared to 96% among patients treated based on clinical diagnosis only (Study II). The availability of parasite-based diagnostics and antimalarial drugs within the community allowed early access to treatment as 67% of patients consulted CHWs within 24 hours of onset of fever (Study II). The rate of non adherence to test results was low in both study I and II. Study III observed low use of parasite-based diagnostics among fever patients (63%), low non adherence to test results (14%), substantial prescription of antimalarial drugs to non-tested patients (28%) and high prescriptions of antibiotics among patients with negative RDT results (81%), as well as frequent stock outs of both RDTs and ACTs. HRP2 based tests performed poorly when compared to LDH based tests for treatment monitoring, with median clearance times of 28 (7-42) and 7 (2-14) days respectively (Study IV). HRP2 based tests were unable to detect 8/10 recurrent infections during follow up compared to only two recurrent infections missed by LDH based tests. These studies lead to a conclusion that the availability of parasite-based diagnostics helps to restrict treatment with antimalarial drugs to patients with malaria. However, non adherence to malaria test results could undermine the potential of RDTs, and in-depth studies should be conducted to identify its causes. As the relative contribution of malaria as a cause of fever is declining in Tanzania, there is need to improve the overall management of non-malarial fevers. The longer the persistence of HRP2 antigen in blood makes HRP2 based tests not suitable for treatment monitoring and detection of recurrent infection calling for alternative diagnostic strategies for this purpose

Pre-referral Rectal Artesunate Treatment by Community-Based Treatment Providers in Ghana, Guinea-Bissau, Tanzania, and Uganda (Study 18): A Cluster-Randomized Trial

BACKGROUND:  If malaria patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate prior to hospital referral can prevent death and disability. The goal is to reduce death from malaria by having rectal artesunate treatment available and used. How best to do this remains unknown. METHODS:  Villages remote from a health facility were randomized to different community-based treatment providers trained to provide rectal artesunate in Ghana, Guinea-Bissau, Tanzania, and Uganda. Prereferral rectal artesunate treatment was provided in 272 villages: 109 through community-based health workers (CHWs), 112 via trained mothers (MUMs), 25 via trained traditional healers (THs), and 26 through trained community-chosen personnel (COMs); episodes eligible for rectal artesunate were established through regular household surveys of febrile illnesses recording symptoms eligible for prereferral treatment. Differences in treatment coverage with rectal artesunate in children aged <5 years in MUM vs CHW (standard-of-care) villages were assessed using the odds ratio (OR); the predictive probability of treatment was derived from a logistic regression analysis, adjusting for heterogeneity between clusters (villages) using random effects. RESULTS:  Over 19 months, 54 013 children had 102 504 febrile episodes, of which 32% (31 817 episodes) had symptoms eligible for prereferral therapy; 14% (4460) children received treatment. Episodes with altered consciousness, coma, or convulsions constituted 36.6% of all episodes in treated children. The overall OR of treatment between MUM vs CHW villages, adjusting for country, was 1.84 (95% confidence interval [CI], 1.20-2.83; P = .005). Adjusting for heterogeneity, this translated into a 1.67 higher average probability of a child being treated in MUM vs CHW villages. Referral compliance was 81% and significantly higher with CHWs vs MUMs: 87% vs 82% (risk ratio [RR], 1.1 [95% CI, 1.0-1.1]; P < .0001). There were more deaths in the TH cluster than elsewhere (RR, 2.7 [95% CI, 1.4-5.6]; P = .0040). CONCLUSIONS:  Prereferral episodes were almost one-third of all febrile episodes. More than one-third of patients treated had convulsions, altered consciousness, or coma. Mothers were effective in treating patients, and achieved higher coverage than other providers. Treatment access was low. CLINICAL TRIALS REGISTRATION:  ISRCTN58046240

Date of introduction and epidemiologic patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Mogadishu, Somalia: estimates from transmission modelling of satellite-based excess mortality data in 2020

Background: In countries with weak surveillance systems, confirmed coronavirus disease 2019 (COVID-19) deaths are likely to underestimate the pandemic’s death toll. Many countries also have incomplete vital registration systems, hampering excess mortality estimation. Here, we fitted a dynamic transmission model to satellite imagery data of cemeteries in Mogadishu, Somalia during 2020 to estimate the date of introduction and other epidemiologic parameters of the early spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this low-income, crisis-affected setting. Methods: We performed Markov chain Monte Carlo (MCMC) fitting with an age-structured compartmental COVID-19 model to provide median estimates and credible intervals for the date of introduction, the basic reproduction number (R0) and the effect of non-pharmaceutical interventions (NPIs) up to August 2020. Results: Under the assumption that excess deaths in Mogadishu March-August 2020 were attributable to SARS-CoV-2 infections, we arrived at median estimates of November-December 2019 for the date of introduction and low R0 estimates (1.4-1.7) reflecting the slow and early rise and long plateau of excess deaths. The date of introduction, the amount of external seeding, the infection fatality rate (IFR) and the effectiveness of NPIs are correlated parameters and not separately identifiable in a narrow range from deaths data. Nevertheless, to obtain introduction dates no earlier than November 2019 a higher population-wide IFR (≥0.7%) had to be assumed than obtained by applying age-specific IFRs from high-income countries to Somalia’s age structure. Conclusions: Model fitting of excess mortality data across a range of plausible values of the IFR and the amount of external seeding suggests an early SARS-CoV-2 introduction event may have occurred in Somalia in November-December 2019. Transmissibility in the first epidemic wave was estimated to be lower than in European settings. Alternatively, there was another, unidentified source of sustained excess mortality in Mogadishu from March to August 2020

Assessment of B Cell Repertoire in Humans

The B cell receptor (BCR) repertoire is highly diverse. Repertoire diversity is achieved centrally by somatic recombination of immunoglobulin (Ig) genes and peripherally by somatic hypermutation and Ig heavy chain class-switching. Throughout these processes, there is selection for functional gene rearrangements, selection against gene combinations resulting in self-reactive BCRs, and selection for BCRs with high affinity for exogenous antigens after challenge. Hence, investigation of BCR repertoires from different groups of B cells can provide information on stages of B cell development and shed light on the etiology of B cell pathologies. In most instances, the third complementarity determining region of the Ig heavy chain (CDR-H3) contributes the majority of amino acids to the antibody/antigen binding interface. Although CDR-H3 spectratype analysis provides information on the overall diversity of BCR repertoires, this fairly simple technique analyzes the relative quantities of CDR-H3 regions of each size, within a range of approximately 10–80 bp, without sequence detail and thus is limited in scope. High-throughput sequencing (HTS) techniques on the Roche 454 GS FLX Titanium system, however, can generate a wide coverage of Ig sequences to provide more qualitative data such as V, D, and J usage as well as detailed CDR3 sequence information. Here we present protocols in detail for CDR-H3 spectratype analysis and HTS of human BCR repertoires

Social sciences research in neglected tropical diseases 2: A bibliographic analysis

The official published version of the article can be found at the link below.Background There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. Methods A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. Results There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. Conclusion There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises

Do health systems delay the treatment of poor children? A qualitative study of child deaths in rural Tanzania.

Child mortality remains one of the major public-health problems in Tanzania. Delays in receiving and accessing adequate care contribute to these high rates. The literature on public health often focuses on the role of mothers in delaying treatment, suggesting that they contact the health system too late and that they prefer to treat their children at home, a perspective often echoed by health workers. Using the three-delay methodology, this study focus on the third phase of the model, exploring the delays experienced in receiving adequate care when mothers with a sick child contact a health-care facility. The overall objective is to analyse specific structural factors embedded in everyday practices at health facilities in a district in Tanzania which cause delays in the treatment of poor children and to discuss possible changes to institutions and social technologies. The study is based on qualitative fieldwork, including in-depth interviews with sixteen mothers who have lost a child, case studies in which patients were followed through the health system, and observations of more than a hundred consultations at all three levels of the health-care system. Data analysis took the form of thematic analysis. Focusing on the third phase of the three-delay model, four main obstacles have been identified: confusions over payment, inadequate referral systems, the inefficient organization of health services and the culture of communication. These impediments strike the poorest segment of the mothers particularly hard. It is argued that these delaying factors function as 'technologies of social exclusion', as they are embedded in the everyday practices of the health facilities in systematic ways. The interviews, case studies and observations show that it is especially families with low social and cultural capital that experience delays after having contacted the health-care system. Reductions of the various types of uncertainty concerning payment, improved referral practices and improved communication between health staff and patients would reduce some of the delays within health facilities, which might feedback positively into the other two phases of delay