Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine and prevalence of molecular markers of anti-malarial drug resistance in children in Togo in 2021.

BACKGROUND: Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the currently recommended first- and second-line therapies for uncomplicated Plasmodium falciparum infections in Togo. This study assessed the efficacy of these combinations, the proportion of Day3-positive patients (D3 +), the proportion of molecular markers associated with P. falciparum resistance to anti-malarial drugs, and the variable performance of HRP2-based malaria rapid diagnostic tests (RDTs). METHODS: A single arm prospective study evaluating the efficacy of AL and DP was conducted at two sites (Kouvé and Anié) from September 2021 to January 2022. Eligible children were enrolled, randomly assigned to treatment at each site and followed up for 42 days after treatment initiation. The primary endpoint was polymerase chain reaction (PCR) adjusted adequate clinical and parasitological response (ACPR). At day 0, samples were analysed for mutations in the Pfkelch13, Pfcrt, Pfmdr-1, dhfr, dhps, and deletions in the hrp2/hrp3 genes. RESULTS: A total of 179 and 178 children were included in the AL and DP groups, respectively. After PCR correction, cure rates of patients treated with AL were 97.5% (91.4-99.7) at day 28 in Kouvé and 98.6% (92.4-100) in Anié, whereas 96.4% (CI 95%: 89.1-98.8) and 97.3% (CI 95%: 89.5-99.3) were observed at day 42 in Kouvé and Anié, respectively. The cure rates of patients treated with DP at day 42 were 98.9% (CI 95%: 92.1-99.8) in Kouvé and 100% in Anié. The proportion of patients with parasites on day 3 (D3 +) was 8.5% in AL and 2.6% in DP groups in Anié and 4.3% in AL and 2.1% DP groups in Kouvé. Of the 357 day 0 samples, 99.2% carried the Pfkelch13 wild-type allele. Two isolates carried nonsynonymous mutations not known to be associated with artemisinin partial resistance (ART-R) (A578S and A557S). Most samples carried the Pfcrt wild-type allele (97.2%). The most common Pfmdr-1 allele was the single mutant 184F (75.6%). Among dhfr/dhps mutations, the quintuple mutant haplotype N51I/C59R/S108N + 437G/540E, which is responsible for SP treatment failure in adults and children, was not detected. Single deletions in hrp2 and hrp3 genes were detected in 1/357 (0.3%) and 1/357 (0.3%), respectively. Dual hrp2/hrp3 deletions, which could affect the performances of HRP2-based RDTs, were not observed. CONCLUSION: The results of this study confirm that the AL and DP treatments are highly effective. The absence of the validated Pfkelch13 mutants in the study areas suggests the absence of ART -R, although a significant proportion of D3 + cases were found. The absence of dhfr/dhps quintuple or sextuple mutants (quintuple + 581G) supports the continued use of SP for IPTp during pregnancy and in combination with amodiaquine for seasonal malaria chemoprevention. TRIAL REGISTRATION: ACTRN12623000344695.

Evaluation of the performance of advantage P.f. malaria Card® and advantage malaria Pan + Pf Card®, two rapid diagnostic tests for parasitological confirmation of malaria cases in field situation in Togo.

BACKGROUND: In Togo, malaria remains a major public health problem, and the management of suspected cases requires confirmation with appropriate biological methods. Malaria diagnosis has been improved by the introduction of rapid diagnostic tests (RDTs), recommended by the World Health Organization (WHO) for areas where microscopy is not available. To be used, these RDTs must meet performance criteria defined by the WHO. This study was conducted to evaluate the diagnostic performance of two RDTs: Advantage P.f. Malaria Card® detecting HRP2 antigen and Advantage Malaria Pan + Pf Card® detecting both HRP2 and pLDH antigens. METHODS: This was a cross-sectional analytical study conducted from December 2019 to February 2020 on malaria-suspected cases received in three sentinel sites in Togo and from whom capillary blood was collected to perform the two RDTs according to the manufacturer's instructions. Sensitivity and specificity were estimated by comparing to thick/thin blood smear, the gold standard, and to PCR, which is a more sensitive. RESULTS: A total of 390 participants (54.9% female) with a median age of 18 (± 0.8) years were included in the study. The sensitivity of both Advantage P.f. Malaria Card® and Advantage Malaria Pan + Pf Card® compared to thick/thin blood smear was 91.8% and 91.3%, respectively, and for both the specificity was 94.7%. Compared to PCR, the sensitivity was 84.2% and 83.8%, respectively, and the specificity 96.5%. CONCLUSIONS: The performances of the Advantage P.f. Malaria Card® and Advantage Malaria PAN + Pf Card® compared to microscopy, considered the gold standard, were acceptable under the field conditions found in Togo. They can therefore be used for the biological diagnosis of malaria.

How well do coverage surveys and programmatically reported mass drug administration coverage match? Results from 214 mass drug administration campaigns in 15 countries, 2008-2017.

INTRODUCTION: Delivering preventive chemotherapy through mass drug administration (MDA) is a central approach in controlling or eliminating several neglected tropical diseases (NTDs). Treatment coverage, a primary indicator of MDA performance, can be measured through routinely reported programmatic data or population-based coverage evaluation surveys. Reported coverage is often the easiest and least expensive way to estimate coverage; however, it is prone to inaccuracies due to errors in data compilation and imprecise denominators, and in some cases measures treatments offered as opposed to treatments swallowed. OBJECTIVE: Analyses presented here aimed to understand (1) how often coverage calculated using routinely reported data and survey data would lead programme managers to make the same programmatic decisions; (2) the magnitude and direction of the difference between these two estimates, and (3) whether there is meaningful variation by region, age group or country. METHODS: We analysed and compared reported and surveyed treatment coverage data from 214 MDAs implemented between 2008 and 2017 in 15 countries in Africa, Asia and the Caribbean. Routinely reported treatment coverage was compiled using data reported by national NTD programmes to donors, either directly or via NTD implementing partners, following the implementation of a district-level MDA campaign; coverage was calculated by dividing the number of individuals treated by a population value, which is typically based on national census projections and occasionally community registers. Surveyed treatment coverage came from post-MDA community-based coverage evaluation surveys, which were conducted as per standardised WHO recommended methodology. RESULTS: Coverage estimates using routine reporting and surveys gave the same result in terms of whether the minimum coverage threshold was reached in 72% of the MDAs surveyed in the Africa region and in 52% in the Asia region. The reported coverage value was within ±10 percentage points of the surveyed coverage value in 58/124 of the surveyed MDAs in the Africa region and 19/77 in the Asia region. Concordance between routinely reported and surveyed coverage estimates was 64% for the total population and 72% for school-age children. The study data showed variation across countries in the number of surveys conducted as well as the frequency with which there was concordance between the two coverage estimates. CONCLUSIONS: Programme managers must grapple with making decisions based on imperfect information, balancing needs for accuracy with cost and available capacity. The study shows that for many of the MDAs surveyed, based on the concordance with respect to reaching the minimum coverage thresholds, the routinely reported data were accurate enough to make programmatic decisions. Where coverage surveys do show a need to improve accuracy of routinely reported results, NTD programme managers should use various tools and approaches to strengthen data quality in order to use data for decision-making to achieve NTD control and elimination goals.

Prevalence of Malaria and Covid-19 in Febrile Patients in Lomé, Togo in 2020.

PURPOSE: The objective of this study was to estimate the prevalence of malaria and Covid-19 by PCR and serological tests in febrile patients in Lomé. METHODS: A cross-sectional study was conducted from September 1 to October 31, 2020 in febrile patients ≥ 10 years in three health facilities in Lomé. Finger stick blood was collected to detect Plasmodium spp. using thin/thick smear and venous blood on EDTA tubes to test for malaria Histidin-Rich-Protein-2 antigen using rapid diagnostic tests (RDT) and SARS-CoV-2 antibodies specific immunoglobulin (Ig) M and G. Detection of SARS-CoV-2 in nasopharyngeal samples was performed by rRT-PCR using GeneXpert. RESULTS: A total of 243 participants (61.7% of female) with median age 28 years (IQR 18-41) were included in the study. Prevalence of malaria was 25.1%, 95% CI [19.8-31.0] and 30.4%, 95% CI [24.7-36.7] for thin/thick smear and rapid malaria test, respectively. Eighteen patients (7.4%, 95% CI [4.4-11.5]) were positive for SARS-CoV-2 and forty-two (17.3%, 95% CI [12.8-22.6]) were positive for IgM and/or IgG against SARS-CoV-2. SARS-CoV-2 IgM seroprevalence was significantly higher in malaria RDT positive participants (33.8% vs. 10.1%, p < 0.001). CONCLUSION: This study confirms a possible cross-reactivity between Covid-19 and malaria in case of single use of rapid tests, suggesting a possible past contamination. In case of clinical signs related to Covid-19 in malaria-endemic areas, PCR screening should be requested in order to identify and isolate patients.

Prevalence and factors associated with trichomonas vaginalis infection among female sex workers in Togo, 2017.

BACKGROUND: The aim of this study was to estimate the prevalence and factors associated with Trichomonas vaginalis (T. vaginalis) among female sex workers (FSW) in Togo in 2017. A cross-sectional bio-behavioral study was conducted from August to October 2017 using a respondent-driven sampling method in four cities in Togo. METHOD: A standardized questionnaire was used to record socio-demographic data and sexual behavior patterns. T. vaginalis detection by molecular biology tests was performed using Allplex STI Essential Assay which detect also 6 others micro-organisms. A blood sample was drawn and serological test using SD Bioline Duo VIH/Syphilis rapid test was performed for Human immunodeficiency virus (HIV) and syphilis testing. RESULTS: A total of 310 FSW with median age 25 years, interquartile range (IQR) [21-32 years] were included. The prevalence of T. vaginalis was 6.5% (95%CI = [4.1-9.9]) and, overall, prevalence of other STI ranged from 4.2% (95%CI = [2.3-7.2]) for N. gonorrhoeae to 10.6% (95% CI = [7.5-14.7]) for HIV. Binary logistic regression was conducted to assess factors associated with T. vaginalis infection. Living in Lomé (aOR = 3.19; 95%CI = [1.11-11.49]), having had sexual intercourse before the age of 18 (aOR = 5.72; 95%CI = [1.13-10.89]), and being infected with C. trachomatis (aOR = 3.74; 95%CI = [2.95-12.25]) were factors associated with T. vaginalis among FSW. CONCLUSION: The prevalence of T. vaginalis infection using molecular test was low among FSW in Togo. Extensive studies are needed to confirm and to better understand the epidemiology of T. vaginalis among this population and in other populations in Togo.

Assessment of the usefulness of anti-Wb123 antibody for post-elimination surveillance of lymphatic filariasis.

BACKGROUND: The World Health Organization has targeted lymphatic filariasis (LF) for elimination as a public health problem and recommends, among other measures, post-elimination surveillance of LF. The identification of sensitive and specific surveillance tools is therefore a research priority. The Wuchereria bancrofti-specific antigen Wb123-based enzyme-linked immunosorbent assay (Wb123 ELISA) detects antibodies to the recombinant Wb123 antigen of W. bancrofti and may be useful as a surveillance tool for LF. Six years after stopping mass drug administration to eliminate LF and recording successful results on two post-treatment transmission assessment surveys, a study was conducted in Togo aimed at helping to identify the role of the Wb123 ELISA in post-validation surveillance of LF. METHODS: This was a cross-sectional study in eight previously LF-endemic districts and one non-endemic district in Togo. In each sub-district of these nine districts, two schools were selected and 15 children aged 6 to 9 years old at each school provided finger-stick blood for testing for antibodies to Wb123 using the Filaria Detect™ IgG4 ELISA kit® (InBios, International, Inc., Seattle, WA, USA). RESULTS: A total of 2654 children aged 6 to 9 years old were tested in 134 schools in the nine districts. Overall, 4.7% (126/2654) children tested positive for antibodies to the Wb123 antigen of W. bancrofti. The prevalence of Wb123 antibodies varied across the eight previously endemic LF districts, from 1.56 to 6.62%. The highest prevalence, 6.99%, was found in the non-endemic district, but this was not significantly different from the average of all the LF districts (4.49%, P = 0.062). CONCLUSIONS: The Wb123 ELISA was positive in 4.7% of Togolese school-age children who were almost certainly unexposed to LF. This apparent lack of specificity in the Togo context makes it difficult to establish a seroprevalence threshold that could serve to signal LF resurgence in the country, precluding the use of this test for post-validation surveillance in Togo. There remains a need to develop a useful and reliable test for post-elimination surveillance for LF in humans.

Prevalence of SARS-CoV-2 among high-risk populations in Lomé (Togo) in 2020.

BACKGROUND: In December 2019, the COVID-19 outbreak began in China and quickly spread throughout the world and was reclassified as a pandemic in March 2020. The first case of COVID-19 was declared in Togo on March 5. Two months later, few data were available to describe the circulation of the new coronavirus in the country. OBJECTIVE: This survey aimed to estimate the prevalence of SARS-CoV-2 in high-risk populations in Lomé. MATERIALS AND METHODS: From April 23, 2020, to May 8, 2020, we recruited a sample of participants from five sectors: health care, air transport, police, road transport and informal. We collected oropharyngeal swabs for direct detection through real-time reverse transcription polymerase chain reaction (rRT-PCR) and blood for antibody detection by serological tests. The overall prevalence (current and past) of infection was defined by positivity for both tests. RESULTS: A total of 955 participants with a median age of 36 (IQR 32-43) were included, and 71.6% (n = 684) were men. Approximately 22.1% (n = 212) were from the air transport sector, 20.5% (n = 196) were from the police sector, and 38.7% (n = 370) were from the health sector. Seven participants (0.7%, 95% CI: 0.3-1.6%) had a positive rRT-PCR test result at the time of recruitment, and nine (0.9%, 95% CI: 0.4-1.8%) were seropositive for IgM or IgG against SARS-CoV-2. We found an overall prevalence of 1.6% (n = 15), 95% CI: 0.9-2.6%. CONCLUSION: The prevalence of SARS-CoV-2 infection among high-risk populations in Lomé was relatively low and could be explained by the various measures taken by the Togolese government. Therefore, we recommend targeted screening.

African histoplasmosis of the penis.

African Histoplasmosis is deep mycosis caused by Histoplasma duboisii and genitourinary involvement is extremely rare. We report a case of African histoplasmosis in a 27-year-old subject with painful penis ulcer. Ulcer edge biopsy had revealed inflammatory granulomas made of epithelioid cells, lymphoplasmocytes, polynuclear eosinophils and giant multinucleated cells, with ovoid yeasts surrounded by a clear halo. PAS and Grocott stains revealed numerous fungal structures with a morphology measuring 7 to 15 nm. The diagnosis Histoplasma capsulatum var. duboisii was placed and the patient put on itraconazole (400 mg/day) for six months with a good course. African histoplasmosis of the subject penis is an extremely rare entity. The diagnosis of certainty often makes use of histology and mycological examination, and makes it possible to eliminate differential diagnoses such as cryptoccocosis, tuberculosis or cancer.

Mycetoma in the Togolese: An Update from a Single-Center Experience.

BACKGROUND: Mycetoma is a chronic inflammatory process caused either by fungi (eumycetoma) or bacteria (actinomycetoma). In this retrospective study, we report epidemiologic and histopathological data of mycetoma observed in the Lome Hospital, Togo in a 25-year period (1992-2016). METHODOLOGY: This is a retrospective study, over a period of 25 years, to analyze epidemiological and etiological findings of mycetomas seen in the single laboratory of pathological anatomy of the Lomé, Togo. RESULTS: A total of 61 cases were retrieved from which only 33 cases were included which where clinically and microbiologically confirmed. The mean age of the patients was 29.7 ± 1.34 and a sex ratio (M/F) of 1.5. The majority of patients were farmers (n = 23 cases; 69.7%). Diagnosed etiologic agents were fungal in 24 cases (72.7%) and actinomycotic cases in 9 cases (27.3%). The fungal mycetomas consisted of Madurella mycetomatis (black grains) and Falcifomispora senegaliensis (black grains). The actinomycotic agents were represented by Actinomadura madurae (white grains), Actinomadurae pelletieri (red grains) and Nocardia sp. (yellow grains). CONCLUSION: This report represents a single-center study which provides epidemiologic and histopathological data of mycetoma cases in Togo.

Histoplasmosis by Histoplasma capsulatum var. duboisii Observed at the Laboratory of Pathological Anatomy of Lomé in Togo.

Our study aimed to describe the epidemiological, clinical, and diagnostic aspects of African histoplasmosis in Togo through a descriptive and cross-sectional study on histological diagnosed African histoplasmosis in Pathology Department of Lomé from 2002 to 2016 (15 years). A total of 17 cases of African histoplasmosis were diagnosed. The sex ratio (M/F) was 1.8. The annual incidence was 1.1 cases. The mean age of the patients was 27.2 ± 0.4 years. All our patients were of social categories with a low socioeconomic level. HIV infection was known in 3 patients and one patient contracted tuberculosis. The clinical manifestations were cutaneous in 7 cases, cutaneous and mucous in 3 cases, cutaneous and lymph node in 3 cases, cutaneous and bone in 2 cases, and disseminated in 2 cases. The samples examined consisted of 14 cutaneous biopsies measuring 2-3 cm and 3 ganglionic biopsies each measuring 4 cm of major axis. Histologically, all cases were of chronic form made of granulomatous reaction with ovoid yeasts measuring between 1 and 2 microns. Despite the low frequency of this disease in our country, it should be kept constantly in mind before any granulomatous lesions, especially in the context of the HIV pandemic.