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

An outbreak of acute haemorrhagic conjunctivitis associated with coxsackievirus A24 variant in The Gambia, West Africa.

OBJECTIVE: An outbreak of acute haemorrhagic conjunctivitis occurred in The Gambia, West Africa in 2011. Affected individuals presented with conjunctival haemorrhages, swelling and ocular discharge. In an effort to identify a causative agent of the disease, ocular swabs were taken from patients during the acute and convalescent phases. Total RNA was extracted from all samples and reverse-transcriptase PCR performed using primers specific for all enteroviruses. Resulting amplicons were sequenced and data compared to known sequences using the BLAST algorithm. RESULTS: Forty-eight swabs were included in the analysis. Of these, 21 acute and 9 convalescent swabs (65% of the total) gave positive PCR results. Sequence analysis of the resulting amplicons indicated 99% sequence identity with coxsackievirus A24 variant identified during independent outbreaks of acute haemorrhagic conjunctivitis around the world and suggest the Gambian outbreak was due to this virus

Use of Lumbar Perforator Recipient Vessels for Salvage Chest Wall Reconstruction: A Case Report

Summary: Abdominal-based free flaps are commonly used for breast reconstruction, and the internal mammary or thoracodorsal vessels are typically used as recipient sites. Conversely, free tissue transfer is less commonly used for chest wall reconstruction in the setting of chest wall recurrence, in part, because of a paucity of recipient vessels. Here, we describe a case of a 68-year-old female smoker with metastatic breast cancer, who presented with a chest wall recurrence. There was a large area of chronic ulceration with foul smelling drainage, in addition to radiation-induced tissue injury, and palliative resection was performed. The area was reconstructed with a free transverse rectus abdominis myocutaneous flap using lumbar perforators as recipient vessels, because conventional recipient sites were unavailable because of scarring from radiation and residual tumor. This case demonstrates that uncommon recipient vessels such as lumbar perforators may allow for successful palliative chest wall reconstruction. We hypothesize that the tumor burden, previous surgeries, and radiation may have rendered the recipient field relatively ischemic, thereby inducing hypertrophy of the lumbar perforators, similar to a delay phenomenon

Impact of the Mass Drug Administration for malaria in response to the Ebola outbreak in Sierra Leone

Background: As emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate–amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014–January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres. Methods: The coverage of the two rounds of MDA with ASAQ was estimated by relating the number anti-malarial medicines distributed to the estimated resident population. Segmented time-series analysis was applied to weekly data collected from 49 primary health units (PHUs) and 11 hospitals performing malaria parasitological testing during the study period, to evaluate trends of malaria cases and Ebola alerts during the post-MDA weeks compared to the pre-MDA weeks in MDA- and non-MDA-cheifdoms. Results: After two rounds of the MDA, the number of suspected cases tested with rapid diagnostic test (RDT) decreased significantly by 43 % (95 % CI 38–48 %) at week 1 and remained low at week 2 and 3 post-first MDA and at week 1 and 3 post-second MDA; RDT positive cases decreased significantly by 47 % (41–52 %) at week 1 post-first and remained lower throughout all post-MDA weeks; and the RDT test positivity rate (TPR) declined by 35 % (32–38 %) at week 2 and stayed low throughout all post-MDA weeks. The total malaria (clinical + confirmed) cases decreased significantly by 45 % (39–52 %) at week 1 and were lower at week 2 and 3 post-first MDA; and week 1 post-second MDA. The proportion of confirmed malaria cases (out of all-outpatients) fell by 33 % (29–38 %) at week 1 post-first MDA and were lower during all post-MDA weeks. On the contrary, the non-malaria outpatient cases (cases due to other health conditions) either remained unchanged or fluctuated insignificantly. The Ebola alerts decreased by 30 % (13–46 %) at week 1 post-first MDA and much lower during all the weeks post–second MDA. Conclusions: The MDA achieved its goals of reducing malaria morbidity and febrile cases that would have been potentially diagnosed as suspected Ebola cases with increased risk of nosocomial infections. The intervention also helped reduce patient case-load to the severely strained health services at the peak of the Ebola outbreak and malaria transmission. As expected, the effect of the MDA waned in a matter of few weeks and malaria intensity returned to the pre-MDA levels. Nevertheless, the approach was an appropriate public health intervention in the context of the Ebola epidemic even in high malaria transmission areas of Sierra Leone

Non-participation during azithromycin mass treatment for trachoma in The Gambia: heterogeneity and risk factors.

BACKGROUND: There is concern that untreated individuals in mass drug administration (MDA) programs for neglected tropical diseases can reduce the impact of elimination efforts by maintaining a source of transmission and re-infection. METHODOLOGY/PRINCIPAL FINDINGS: Treatment receipt was recorded against the community census during three MDAs with azithromycin for trachoma in The Gambia, a hypo-endemic setting. Predictors of non-participation were investigated in 1-9 year olds using random effects logistic regression of cross-sectional data for each MDA. Two types of non-participators were identified: present during MDA but not treated (PNT) and eligible for treatment but absent during MDA (EBA). PNT and EBA children were compared to treated children separately. Multivariable models were developed using baseline data and validated using year one and two data, with a priori adjustment for previous treatment status. Analyses included approximately 10000 children at baseline and 5000 children subsequently. There was strong evidence of spatial heterogeneity, and persistent non-participation within households and individuals. By year two, non-participation increased significantly to 10.4% overall from 6.2% at baseline, with more, smaller geographical clusters of non-participating households. Multivariable models suggested household level predictors of non-participation (increased time to water and household head non-participation for both PNT and EBA; increased household size for PNT status only; non-inclusion in a previous trachoma examination survey and younger age for EBA only). Enhanced coverage efforts did not decrease non-participation. Few infected children were detected at year three and only one infected child was EBA previously. Infected children were in communities close to untreated endemic areas with higher rates of EBA non-participation during MDA. CONCLUSIONS/SIGNIFICANCE: In hypo-endemic settings, with good coverage and no association between non-participation and infection, efforts to improve participation during MDA may not be required. Further research could investigate spatial hotspots of infection and non-participation in other low and medium prevalence settings before allocating resources to increase participation

Mass drug administration with azithromycin for trachoma elimination and the population structure of Streptococcus pneumoniae in the nasopharynx

ABSTRACTBackgroundMass drug administration (MDA) with azithromycin for trachoma elimination reduces nasopharyngeal carriage of Streptococcus pneumoniae in the short term. We evaluated S. pneumoniae carried in the nasopharynx before and after a round of azithromycin MDA to determine whether MDA was associated with changes in pneumococcal population structure.MethodsWe analysed 514 pneumococcal isolates cultured from nasopharyngeal samples collected in Gambian villages that received MDA for trachoma elimination. The samples were collected during three cross-sectional surveys conducted before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. Whole genome sequencing was conducted on randomly selected isolates. Bayesian Analysis of Population Structure (BAPS) was used to cluster related isolates by capturing variation in the core genome. Serotype and multi-locus sequence type were inferred from the genotype. The Antimicrobial Resistance Identification by Assembly (ARIBA) tool was used to identify macrolide resistance genes.ResultsTwenty-seven BAPS clusters were assigned. These consisted of 81 sequence types (STs), 15 of which were novel additions to pubMLST. Two BAPS clusters, BAPS20 (p-value&lt;=0.016) and BAPS22 (p-value&lt;=0.032) showed an increase in frequency at CSS-3 not associated with antimicrobial resistance. Macrolide resistance within BASP17 increased after treatment (p&lt;0.05) and was carried on a mobile transposable element that also conferred resistance to tetracycline.ConclusionsLimited changes in pneumococcal population structure were observed after the third round of MDA suggesting treatment had little effect on the circulating lineages. An increase in macrolide resistance within one BAPS highlights the need for antimicrobial resistance surveillance in treated villages.</jats:sec

Mass administration of azithromycin and Streptococcus pneumoniae carriage: cross-sectional surveys in the Gambia.

OBJECTIVE: To evaluate the effect of repeated mass drug administration (MDA) of azithromycin in the Gambia on the nasopharyngeal carriage of Streptococcus pneumoniae and on the emergence of antibiotic-resistant strains. METHODS: This study involved villages that participated in a cluster randomized trial comparing the effect of one versus three azithromycin MDA rounds on the prevalence of trachoma. Only villages in which most children received 7-valent pneumococcal conjugate vaccine were included. Three cross-sectional surveys were performed in two villages that received three annual MDA rounds: the first immediately before the third MDA round and the second and third, 1 and 6 months, respectively, after the third MDA round. The third survey also covered six villages that had received one MDA round 30 months previously. Pneumococcal carriage was assessed using nasopharyngeal swabs and azithromycin resistance was detected using the Etest. FINDINGS: The prevalence of pneumococcal carriage decreased from 43.4% to 19.2% between the first and second surveys (P < 0.001) but rebounded by the third survey (45.8%; P = 0.591). Being a carrier at the first survey was a risk factor for being a carrier at the second (odds ratio: 3.71; P <  0.001). At the third survey, the prevalence of carriage was similar after one and three MDA rounds (50.3% versus 45.8%, respectively; P = 0.170), as was the prevalence of azithromycin resistance (0.3% versus 0.9%, respectively; P = 0.340). CONCLUSION: Three azithromycin MDA rounds did not increase the prevalence of nasopharyngeal carriage of azithromycin-resistant S. pneumoniae strains compared with one round

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study.

Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10(-6) > P > 5 × 10(-8)). The most strongly associated SNP (rs111513399, P = 5.38 × 10(-7)) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling

Assessment of trace elements (Cu, Fe, and Zn) in Limnothrissa miodon from Lake Kariba, Zambia: implications for ecological and human health

This study examined Copper (Cu), Iron (Fe), and Zinc (Zn) levels in Limnothrissa miodon fish from Lake Kariba in Zambia and their potential impact on human health. Two-gram samples from each stratum underwent a 12-hour digestion, and concentrations were determined using Microwave Plasma Atomic Emission Spectrometer. Results indicated that Cu, Fe, and Zn concentrations fell within Food and Agricultural Organization and World Health Organization safety limits. Estimated Daily Intake (EDI) and Hazard Quotient (THQ) values for males and females remained under recommended thresholds, suggesting minimal health risks from consumption. Element concentrations followed the order Fe > Zn > Cu, all below Recommended Daily Allowances (RDAs). THQ values, with Zn posing the highest potential risk followed by Fe and Cu, were under one. Overall, the Hazard Index (HI) was 0.02, signifying a low non-carcinogenic risk from fish consumption. Despite safety, ongoing monitoring of heavy metal accumulation in the ecosystem is advisable for long-term safety. In conclusion, trace element levels in Limnothrissa miodon from Lake Kariba are safe for human consumption with low associated health risks. Nonetheless, continued monitoring of heavy metal levels is vital