Gametocyte carriage after seasonal malaria chemoprevention in Plasmodium falciparum infected asymptomatic children.

BACKGROUND: Treatment of clinical Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) is associated with increased post-treatment gametocyte carriage. The effect of seasonal malaria chemoprevention (SMC) with SP and AQ on gametocyte carriage was assessed in asymptomatic P. falciparum infected children. METHODS: The study was carried out in eastern Gambia. Asymptomatic P. falciparum malaria infected children aged 24-59 months old who were eligible to receive SMC (SMC group) and children 5-8 years that were not eligible to receive SMC (comparison group) were recruited. Gametocytaemia was determined by molecular methods before and after SMC administration. Gametocyte carriage between the groups was compared using the chi-squared test and within-person using conditional logistic regression. RESULTS: During the 2017 and 2018 malaria transmission seasons, 65 and 75 children were recruited in the SMC and comparison groups, respectively. Before SMC administration, gametocyte prevalence was 10.7% (7/65) in the SMC group and 13.3% (10/75) in the comparison group (p = 0.64). At day 13 (IQR 12, 13) after SMC administration, this was 9.4% (5/53) in children who received at least the first dose of SMC treatment and 12.7% (9/71) for those in the comparison group (p = 0.57). Similarly, there was no difference in prevalence of gametocytes between children that adhered to all 3-day doses of SMC treatment 15.6% (5/32) and those in the comparison group (p = 0.68). In the SMC group, within-group gametocyte carriage was similar before and after SMC administration in children that received at least the first dose of SMC treatment (OR 0.6, 95% CI 0.14-2.51; p = 0.48) and in those that adhered to all 3-day doses of SMC treatment (OR 1.0, 95% CI 0.20-4.95; p = 1.0). CONCLUSION: In this study with relative low gametocyte prevalence prior to SMC treatment, no evidence was observed that SMC treatment increased gametocyte carriage in asymptomatic P. falciparum malaria infected children.

Correlates of knowledge of family planning among people living in fishing communities of Lake Victoria, Uganda.

BACKGROUND: Knowledge of family planning (FP) is a key determinant of contraceptive use which ultimately plays a role in attainment of good health and in conduct of clinical research. People living in fishing communities (FCs) have limited access to health services including FP and are targeted for future clinical research but their knowledge of FP and its correlates are scantily known. We determined correlates of knowledge of FP among people living in FCs of L. victoria in Uganda to inform future FP education programs in FCs. METHODS: We conducted a comparative cross-sectional survey among participants aged 15-49 years from Kigungu and Nsazi. Participants were asked if they were aware of any FP method. All those who responded in the affirmative were further asked to mention what FP methods they had heard of or knew. Those who reported knowledge of at least one FP method were asked a series of questions about FP methods and their side effects. Knowledge was categorized into good or poor knowledge based on their mean total score. Poor knowledge constituted a score below the mean while good knowledge constituted a score of more than or equal to the mean total score. To further explore attitudes and perceptions of FP, ten in-depth interviews and four focus group discussions were conducted. RESULTS: Of the 1410 screened participants, 94.5% were aware of at least one FP method. Pills and injectable hormonal methods were the most commonly known methods. Slightly over a third (38%) had good knowledge of FP. Correlates of knowledge of FP were; being female (aOR: 1.92 95% CI: 1.39-2.67), residing in Kigungu (aOR: 4.01 95% CI: 2.77-5.81), being married (aOR: 1.59 95% CI: 1.11-2.28) and currently being in a sexual relationship (aOR: 1.75 95% CI: 1.18-2.60). Concerns about safety and effectiveness of some modern FP methods exist. Misconceptions on effects of FP like sterility, cancers and foetal abnormalities were common. CONCLUSION: FP awareness among people living in FCs of L. Victoria in Uganda is high. However, good knowledge about specific methods tends to be low. Correlates of knowledge of FP include gender, residence, marital status and sexual engagement.

Prevalence of malaria parasitaemia in school-aged children and pregnant women in endemic settings of sub-Saharan Africa: A systematic review and meta-analysis.

Despite increased malaria control efforts, school-aged children (5-14 years) have higher a malaria prevalence compared to children under-five. In high-transmission settings, up to 70% of school-aged children harbour malaria parasitaemia and therefore contribute significantly to the reservoir for transmission. A systematic review was performed to explore the correlation between the malaria parasite carriage in pregnant women and school-aged children living in similar endemic settings of sub Saharan Africa to inform strategies to improve targeted malaria control. In order to obtain data on malaria prevalence in pregnant women and school-aged children living in the same endemic setting, we searched the Malaria in Pregnancy Library, PubMed, Cochrane library and Web of Science in December 2018. We fit a fixed effect model to obtain a pooled risk ratio (PRR) of malaria in school-aged children versus pregnant women and used Poisson regression to estimate risk ratios in school-aged children for every increase in prevalence in pregnant women. We used data from six (out of 1096) sources that included 10 data points. There was a strong linear relation between the prevalence of malaria infection in pregnant women and school-aged children (r = 0·93, p < 0·0001). School-aged children were nearly twice at risk to carry parasites compared to pregnant women (RR = 1.95, 95% CI: 1·69-2.25, p < 0.01). Poisson regression showed that a 1% increase in prevalence of malaria infection in pregnant women was significantly associated with increase in risk in school-aged children by 4%. Malaria infection prevalence in school-aged children is strongly correlated with the prevalence in pregnant women living in the same community, and may be considered as alternative indicators to track temporal and spatial trends in malaria transmission intensity. Chemoprevention strategies targeting school-aged children should be explored to reduce malaria burden and transmission in school-aged children and its potential impact on communities.

Development and implementation of a strategy for intensified screening for gambiense human African trypanosomiasis in Kongo Central province, DRC.

BACKGROUND: The Democratic Republic of the Congo (DRC) accounts for the majority of the reported gambiense human African trypanosomiasis (HAT) cases. Kongo Central province in the DRC reports a relatively low, yet steady number of cases, and forms a transboundary focus with Angola and the Republic of Congo. This paper describes an intervention aimed at reducing the case burden in Kongo Central by improving passive case detection, complemented with reactive screening. METHODOLOGY/PRINCIPAL FINDINGS: At the initiation of this programme in August 2015, 620 health facilities were identified and equipped with Rapid Diagnostic Tests (RDTs) for HAT screening. Of these, 603 (97%) reported use of RDTs, and 584 (94%) that continued to use RDTs to the last quarter of 2016 were used in the analysis going forward. Among all health facilities involved, 23 were equipped to confirm HAT by microscopy, and 4 of the latter were equipped to perform molecular testing with loop-mediated isothermal amplification (LAMP). Patients clinically suspected of HAT were tested with an RDT and those with a positive RDT result were referred to the nearest microscopy facility for confirmatory testing. If RDT positive patients were negative by microscopy, they were tested by LAMP, either on fresh blood or blood that was dried on filter paper and transported to a facility performing LAMP. This network of diagnostic facilities reduced the median distance for a patient to travel to a screening facility from 13.7km when the classical card agglutination test for trypanosomiasis (CATT) was used as a screening test in the past, to 3.4km. As a consequence, passive case detection was improved by between 30% and 130% compared to the period before. Furthermore, the proportion of HAT cases detected in early stage disease by passive screening increased from 27% to 64%. Reactive screening took place in 20 villages where cases were reported by passive screening, and in 45 villages in the neighbourhood of these villages. Reactive screening was responsible for detection of 40% of cases, of which, 90% were in first stage of the disease. CONCLUSIONS: This programme has demonstrated that it is possible to deploy passive screening for HAT at sub-country or country levels in the DRC, and this is made more effective when supplemented with reactive screening. Results and achievements showed an increase in the number of HAT cases detected, the majority of them in early disease, demonstrating that this strategy enables better population coverage and early detection of cases, which is critical in removing the HAT reservoir and interrupting transmission, and could contribute to HAT elimination in regions where it is implemented.

Can direct smear results that are routinely collected at health centre level be used for monitoring the impact of mass drug administration with praziquantel on schistosomiasis in Burundi? A preliminary assessment.

BACKGROUND: Intestinal schistosomiasis is still a public health problem in Burundi. Since 2008, annual mass drug administration with praziquantel has been rolled out in 11 endemic districts. The national programme relies on school-based surveys with kato-katz to monitor the impact of mass drug administration. We explored whether routine data on intestinal schistosomiasis as determined by direct fecal smears at health centre level could be used. METHODS: From the Burundian National Health Information System, we collected routine incidence data on intestinal schistosomiasis as determined by direct smear examination in all 45 sanitary districts during 2011-2015. A temporal trends analysis was performed using a mixed negative binomial regression. Sanitary districts with mass drug administration campaigns with praziquantel (n = 11) were compared with those without (n = 34). In addition, prevalence data on intestinal schistosomiasis based on kato-katz results from a school-based national mapping in 2014 were compared with the incidence data in health centres based on direct smear results, in the same 45 sanitary districts. RESULTS: In the 11 sanitary districts applying mass drug administration with praziquantel, the incidence rate decreased significantly for the years 2014 (ß2014 = - 0.826, P = 0.010) and 2015 (ß2015 = - 1.294, P < 0.001) and for the five-year period (ß = - 0.286, P < 0.001), whereas in the 34 districts where mass drug administration was not delivered, there was no significant decrease over time (ß = - 0.087, P = 0.219). In most of the 45 sanitary districts, the low prevalence based on kato-katz in school children was confirmed by low incidence rates based on direct smears in the health centres. CONCLUSIONS: National Health Information System surveillance data, based on routinely collected direct smear results at health centre level, may be able to monitor the impact of mass drug administration with praziquantel on intestinal schistosomiasis in Burundi. Control and elimination of intestinal schistosomiasis call for integration of adequate diagnosis and treatment into routine activities of primary health care facilities, as recommended by the World Health Organization since more than 20 years. When moving towards elimination, more sensitive tests, such as the point-of-care circulating cathodic antigen assay are desirable.

Performance of OncoE6TM Cervical Test in detecting cervical precancer lesions in HIV-positive women attending an HIV clinic in Bujumbura, Burundi: a cross-sectional study.

OBJECTIVE: New rapid and low-cost molecular tests for cervical cancer screening, such as the OncoE6 Cervical Test, are emerging and could be alternatives for low-income and middle-income countries. To this end, we evaluated the clinical performance of the OncoE6 Cervical Test in detecting cervical intraepithelial neoplasia (CIN) among HIV-infected women in Bujumbura, Burundi. METHODS: From June to December 2017, a cross-sectional study was conducted in 680 HIV-positive women at the University Hospital. Women aged 25-65 years who declared having had vaginal intercourse were consecutively recruited, and cervical specimens for OncoE6, liquid-based cytology and human papillomavirus (HPV) genotyping were obtained and visual inspection with acetic acid performed. Thereafter, participants underwent a colposcopic examination. The sensitivity, specificity, and positive and negative predictive values of the different tests were calculated with reference to 'colposcopic-histological' diagnoses, and areas under the receiver operating curves of OncoE6 and cytology tests were compared. RESULTS: The prevalence of CIN was 4.9%, and OncoE6 positivity was 3.1%. OncoE6 sensitivity varied from poor to low with increasing disease severity (42.1%, 95% CI 19.9% to 64.3% at CIN2+ threshold; and 58.3%, 95% CI 30.4% to 86.2% at CIN3+ threshold). OncoE6 had the highest specificity compared with all other tests used together. The performance of the OncoE6 test was significantly lower compared with cytology at atypical squamous cell of undetermined significance (ASCUS+) cut-off (AUC=0.68 vs 0.85, p=0.03) and low-grade squamous intraepithelial lesion (LSIL+) cut-off (AUC=0.68 vs 0.83, p=0.04) for CIN2+ diagnoses. However, the performance of the OncoE6 test was similar to that of cytology at high-grade squamous intraepithelial lesion (HSIL+) cut-off (AUC=0.68 vs 0.76; p=0.30) for CIN2+ diagnoses and was also similar to that of cytology at all cut-offs (ASCUS+, LSIL+ and HSIL+) for CIN3+ diagnoses (p1=0.76, p2=0.95 and p3=0.50, respectively). CONCLUSION: The current OncoE6 test proved to be a point-of-care test. However, given its poor performance for CIN2+ diagnoses, we do not recommend it for primary screening. We recommend to enrich it with more oncogenic HPV types, which may improve the performance of the test akin to that of cytology.

Prevalence and Distribution of Human Papillomavirus Genotypes Among Women in Kinshasa, The Democratic Republic of the Congo.

PURPOSE: Cervical cancer is the leading cause of mortality by cancer in sub-Saharan Africa. The human papillomavirus (HPV) infection is recognized as a necessary and sufficient cause for cervical cancer. Population-specific estimates of HPV prevalence in the Democratic Republic of the Congo (DRC) are unknown. This study aims to estimate the prevalence of HPV and identify predominant genotypes circulating in Kinshasa, DRC. METHODS: Between July 2015 and July 2017, women were invited to attend a screening program at Mont-Amba Health Centre in Kinshasa. Cervical specimens were collected using the Preservcyt medium. HPV DNA testing was performed for all specimens using real-time polymerase chain reaction. RESULTS: During the 2-year period, a total of 1,870 women age 25 to 82 years were screened. The mean age was 46 years (± 11.4 years). The overall HPV prevalence was 28.2% (95% CI, 26.1% to 30.3%). High-risk HPV prevalence was 24.8% (95% CI, 22.8% to 26.8%). Women younger than 30 years had the highest overall HPV prevalence (42.2%; 95% CI, 34.7% to 49.9%). A second peak of prevalence was observed in women age 60 years and older. HPV68 (5.5%; 95% CI, 4.5% to 6.6%) was the most prevalent HPV type. CONCLUSION: The distribution of HPV genotypes among women in our population was different compared with other world regions. A key finding was that HPV68 was the most prevalent high-risk HPV genotype. These findings highlight the need for the determination in our population of the etiologic fraction of different HPV types in invasive cervical cancers.

Impact of antiviral AV2 in the topical treatment of HPV-associated lesions of the cervix: Results of a phase III randomized placebo-controlled trial.

BACKGROUND: Non-surgical topical therapies have been assessed in the treatment of precancerous lesions of the cervix. Their use can offer logistical and feasibility advantages in low-resource settings. Antiviral AV2® is a mixture of natural essential oils (eugenol, carvone, nerolidol, geraniol) in olive oil, and has a broad spectrum anti-viral activity. In a phase II randomized controlled trial (RCT), AV2® proved effective in reducing the size of cervical lesions associated with human papillomavirus (HPV). The purpose of the present study was to further evaluate the efficacy of AV2 over placebo in the topical treatment of HPV-associated cervical lesions. METHODS: Women aged 25 years and older were included in this phase 3 RCT. Cytology screening, HPV testing and visual inspection of the cervix with 5% acetic acid (VIA) were performed on all participants. VIA-positive women were randomized to one of two groups to receive treatment by either AV2® or placebo. The treatment consisted of 2 puffs of spray of the investigational drug directed to the cervix. Participants were subjected to repeat examinations two months and six months later for assessment of outcomes. The primary outcome was the change of lesions on VIA at 2 months after application of the investigational drug. Secondary outcomes were: HPV clearance and cytologic regression at 2 months and 6 months, and number of participants with AEs. RESULTS: A total 327 VIA positive women were randomized in two groups (168 in AV2 group and 159 in placebo group). Women in the 2 groups were similar with respect to baseline demographics and clinical characteristics. At 2 months, regression of lesions on VIA was observed in 127 (89.4%) out of 142 women in AV2 group compared to 120 (91.6%) out of 131 women in placebo group (P = 0.7). On cytology, regression of lesions occurred in 14 (56%) out of 25 women in the AV2 arm and in 13 (48.1) out of 27 women in the placebo arm (p = 0.7), and HPV clearance rates were 34.1% and 35% in AV2 group and placebo group respectively (p = 0.8). At 6 months cytologic regression was observed in 64.7% of women in AV2 group and 45.8% in placebo group (p = 0.2), while HPV clearance occurred in 11 (51.9%) out of 17 women in AV2 arm versus 11 (34.4%) in placebo arm (p = 0.3).Some local side effects (burning, itching, irritation) were similarly noted in the 2 groups (p-values = 0.169, 0.623 and 0.172 respectively) but they were mild and transitory. CONCLUSION: A topical application of AV2 onto the cervix can induce the regression of cervical precancerous lesions, but its efficacy does not significantly differ with that of placebo. The discrepancy between the expected and the recorded sample size as well as the huge number of lost to follow-up probably impeded the power of analyses, which could be one of the reasons for the lack of difference seen between AV2 and placebo. Further evaluation of the effects of AV2 with different diagnostic methods and treatment regimen and arms is warranted. CLINICAL TRIAL REGISTRATION: NCT02346227 registered on November 8, 2014.

Prevalence and genotype-specific distribution of human papillomavirus in Burundi according to HIV status and urban or rural residence and its implications for control.

BACKGROUND: Human papillomaviruses are the most important causative agents for invasive cervical cancer development. HPV type-specific vaccination and HPV cervical cancer screening methods are being widely recommended to control the disease but the epidemiology of the circulating HPV types may vary locally. The circulating HPV-strains have never been assessed in Burundi. This study determined the prevalence and genotype-specific distribution of HPV in four different strata in Burundi: HIV-infected or non-infected and women living in rural or urban areas. Implications for HPV diagnosis and vaccine implementation was discussed. METHODS: Four cross-sectional surveys were conducted in Burundi (2013 in a rural area and 2016 in urban area) among HIV-infected and uninfected women living in rural and urban areas. Liquid-Based Cytology (LBC) and HPV genotyping were performed and risk factors for HPV infection and cervical pre-cancer lesions were determined using logistic regression model. RESULTS: HPV prevalence was very high in urban area with significant differences between HIV-positive and negative women (p<0.0001). In fact, 45.7% of HIV-positive participants were infected with any HPV type and all were infected with at least one HR/pHR-HPV type. Among the HIV-negative participants, 13.4% were HPV-infected, of whom, only four women (2.7%) were infected with HR/pHR-HPV types. In rural area, HPV infection did not significantly differ between HIV-positive and negative women (30.0% and 31.3% respectively; p = 0.80). In urban area, multiple infections with HR/pHR-HPV types were detected in 13.9% and 2.7% among HIV-positive and negative women respectively (p<0.0001), whereas in rural area, multiple infections with HR/pHR-HPV types were detected in 4.7% and 3.3% of HIV-positive and negative women respectively (p = 0.56). The most prevalent HR/pHR-HPV types in HIV-positive women living in urban area were HPV 52, 51, 56, 18 and 16 types. In HIV-negative women living in urban area, the most prevalent HR/pHR-HPV types were HPV 66, 67, 18, 45 and 39 types. In HIV-positive women living in rural area, the most prevalent HR/pHR-HPV types were HPV 66, 16, 18 and 33 types. In HIV-negative women living in rural area, the most prevalent HR/pHR-HPV types were HPV 16, 66, 18, 35 and 45 types. Independent risk factors associated with cervical lesions were HPV and HIV infections. CONCLUSIONS: There is a high burden of HR and pHR-HPV infections, in particular among HIV-infected women living in urban area. The study points out the need to introduce a comprehensive cervical cancer control programme adapted to the context. This study shows that the nonavalent vaccine covers most of the HR/pHR-HPV infections in rural and urban areas among HIV-infected and uninfected women.

Efficacy of commercially available biological agents for the topical treatment of cervical intraepithelial neoplasia: a systematic review.

BACKGROUND: Cervical cancer is a major public health issue in the world, especially in developing countries. It can be prevented through vaccination against HPV (primary prevention) and through screening and treatment of cervical intraepithelial neoplasia (CIN) (secondary prevention). Surgical methods for treatment of CIN are linked to complications such as bleeding and adverse pregnancy outcomes. Furthermore, these methods are not generally available in resource-poor settings. Therefore, topical agents for local application on the cervix have been used since decades to overpass complications and limitations of the surgical methods. AIMS: Review of the literature on the efficacy of commercially available biological agents used for topical treatment of cervical intraepithelial neoplasia (CIN). METHODS: A systematic search through PubMed and the Cochrane database was performed up to December 2017, using the medical subheadings (MesH) for topical agent, treatment, and cervical intraepithelial neoplasia. Appropriate inclusion/exclusion criteria have been used for the selection of eligible clinical studies. Clinical studies containing a minimum of 20 women, aged 18-50 with a diagnosis of CIN 1-3, and at least a 4 weeks follow-up after the end of the topical treatment were included. RESULTS: The initial electronic database search resulted in a total of 849 articles. After screening titles and abstracts, 62 articles were selected as potential studies. Of these, six articles were included in the review after reading the full text: two were on 5-FluoroUracil, two on trans retinoic acid, one on Imiquimod, and one on Cidofovir. The reported regression/remission rates for CIN differed among studies. In CIN2 patients, the overall remission rate ranged between 43 and 93% for the active agents. CONCLUSION: Among the topical agents studied, 5-FluoroUracil showed good remission rates above 80%. Varying results seen in this review is due to the differences in quality of the design between studies. Large-scale and less biaised studies are needed to elucidate the true efficacy and safety of topical agents in the treatment of CIN.

Capacity gaps in health facilities for case management of intestinal schistosomiasis and soil-transmitted helminthiasis in Burundi.

BACKGROUND: Schistosomiasis and soil-transmitted helminthiasis (STH) are endemic diseases in Burundi. STH control is integrated into health facilities (HF) across the country, but schistosomiasis control is not. The present study aimed to assess the capacity of HF for integrating intestinal schistosomiasis case management into their routine activities. In addition, the current capacity for HF-based STH case management was evaluated. METHODS: A random cluster survey was carried out in July 2014, in 65 HF located in Schistosoma mansoni and STH endemic areas. Data were collected by semi-quantitative questionnaires. Staff with different functions at the HF were interviewed (managers, care providers, heads of laboratory and pharmacy and data clerks). Data pertaining to knowledge of intestinal schistosomiasis and STH symptoms, human and material resources and availability and costs of diagnostic tests and treatment were collected. FINDINGS: Less than half of the 65 care providers mentioned one or more major symptoms of intestinal schistosomiasis (abdominal pain 43.1%, bloody diarrhoea 13.9% and bloody stool 7.7%). Few staff members (15.7%) received higher education, and less than 10% were trained in-job on intestinal schistosomiasis case management. Clinical guidelines and laboratory protocols for intestinal schistosomiasis diagnosis and treatment were available in one third of the HF. Diagnosis was performed by direct smear only. Praziquantel was not available in any of the HF. The results for STH were similar, except that major symptoms were more known and cited (abdominal pain 69.2% and diarrhoea 60%). Clinical guidelines were available in 61.5% of HF, and albendazole or mebendazole was available in all HF. CONCLUSIONS: The current capacity of HF for intestinal schistosomiasis and STH detection and management is inadequate. Treatment was not available for schistosomiasis. These issues need to be addressed to create an enabling environment for successful integration of intestinal schistosomiasis and STH case management into HF routine activities in Burundi for better control of these diseases.

Knowledge and practices of general practitioners at district hospitals towards cervical cancer prevention in Burundi, 2015: a cross-sectional study.

BACKGROUND: Well-organized screening and treatment programmes are effective to prevent Invasive Cervical Cancer (ICC) in LMICs. To achieve this, the World Health Organization (WHO) recommends the involvement of existing health personnel in casu doctors, nurses, midwives in ICC prevention. A necessary precondition is that health personnel have appropriate knowledge about ICC. Therefore, to inform policy makers and training institutions in Burundi, we documented the knowledge and practices of general practitioners (GPs) at district hospital level towards ICC control. METHODS: A descriptive cross-sectional survey was conducted from February to April, 2015 among all GPs working in government district hospitals. A structured questionnaire and a scoring system were used to assess knowledge and practices of GPs. RESULTS: The participation rate was 58.2%. Majority of GPs (76.3%) had appropriate knowledge (score > 70%) on cervical cancer disease; but some risk factors were less well known as smoking and the 2 most important oncogenic HPV. Only 8.4% of the participants had appropriate knowledge on ICC prevention: 55% of the participants were aware that HPV vaccination exists and 48.1% knew cryotherapy as a treatment method for CIN. Further, 15.3% was aware of VIA as a screening method. The majority of the participants (87%) never or rarely propose screening tests to their clients. Only 2 participants (1.5%) have already performed VIA/VILI. Wrong thoughts were also reported: 39.7% thought that CIN could be treated with radiotherapy; 3.1% thought that X-ray is a screening method. CONCLUSION: In this comprehensive assessment, we observed that Burundian GPs have a very low knowledge level about ICC prevention, screening and treatment. Suboptimal practices and wrong thoughts related to ICC screening and treatments have also been documented. We therefore recommend an adequate pre- and in-service training of GPs and most probably nurses on ICC control before setting up any public health intervention on ICC control.

Different origin and dispersal of sulfadoxine-resistant Plasmodium falciparum haplotypes between Eastern Africa and Democratic Republic of Congo.

Sulfadoxine/pyrimethamine (SP) is still used for malaria control in sub-Saharan Africa; however, widespread resistance is a major concern. This study aimed to determine the dispersal and origin of sulfadoxine resistance lineages in the Democratic Republic of the Congo compared with East African Plasmodium falciparum dihydropteroate synthetase (Pfdhps) haplotypes. The analysis involved 264 isolates collected from patients with uncomplicated malaria from Tanzania, Uganda and DR Congo. Isolates were genotyped for Pfdhps mutations at codons 436, 437, 540, 581 and 613. Three microsatellite loci (0.8, 4.3 and 7.7 kb) flanking the Pfdhps gene were assayed. Evolutionary analysis revealed a shared origin of Pfdhps haplotypes in East Africa, with a distinct population clustering in DR Congo. Furthermore, in Tanzania there was an independent distinct origin of Pfdhps SGEGA resistant haplotype. In Uganda and Tanzania, gene flow patterns contribute to the dispersal and shared origin of parasites carrying double- and triple-mutant Pfdhps haplotypes associated with poor outcomes of intermittent preventive treatment during pregnancy using SP (IPTp-SP). However, the origins of the Pfdhps haplotypes in DR Congo and Eastern Africa sites are different. The genetic structure demonstrated a divergent and distinct population cluster predominated by single-mutant Pfdhps haplotypes at the DR Congo site. This reflects the limited dispersal of double- and triple-mutant Pfdhps haplotypes in DR Congo. This study highlights the current genetic structure and dispersal of high-grade Pfdhps resistant haplotypes, which is important to guide implementation of SP in malaria chemoprevention strategies in the region.

Efficacy and safety of intermittent preventive treatment in schoolchildren with sulfadoxine/pyrimethamine (SP) and SP plus piperaquine in Democratic Republic of the Congo: a randomised controlled trial.

In endemic areas, malaria and its adverse effects in schoolchildren may be prevented by intermittent preventive treatment (IPTsc). However, the most appropriate drug regimen for IPTsc remains to be identified. A randomised controlled trial was conducted in Kinshasa, DRC. Enrolled schoolchildren were assigned to a passive control arm (n = 212), sulfadoxine/pyrimethamine (SP) (n = 202) or SP plus piperaquine (SP/PQ) (n = 202). The primary endpoint was haemoglobin (Hb) change. Secondary endpoints were anaemia, parasitaemia prevalence and clinical malaria incidence. Data were analysed by modified intention-to-treat (mITT) and per-protocol. A linear mixed mode was used due to repeated measurements. Of 616 enrolled children, 410 (66.6%) were eligible for mITT analysis. The control arm was used as reference. After 12 months, the Hb level increased by 0.20 g/dL (95% CI -0.61 to 0.47; P = 0.168) and 0.39 g/dL (0.12-0.66; P <0.01) in the SP and SP/PQ arms, respectively. SP treatment reduced anaemia, malaria parasitaemia and clinical malaria by 10% (0-20%; P = 0.06), 19% (2-33%; P = 0.042) and 25% (-32 to 57%; P = 0.37), respectively. The corresponding values for SP/PQ were 28% (19-37%; P <0.001), 40% (26-52%; P <0.001) and 58% (17-79%; P <0.01). No deaths or severe adverse events (SAEs) were observed. SP/PQ offered substantial protection against anaemia, malaria parasitaemia and clinical malaria and showed no SAEs. SP/PQ, a combination of two long-acting non-artemisinin-based antimalarials, may be a valuable option for IPTsc in Africa.

The perception of parents and teachers about intermittent preventive treatment for malaria in school children in a semi-rural area of Kinshasa, in the Democratic Republic of Congo.

BACKGROUND: Intermittent preventive treatment (IPT) is likely to be the most promising therapeutic strategy to prevent malaria and its related adverse outcomes in schoolchildren. However, its successful implementation will depend on acceptability to key stakeholders such as parents and teachers. METHODS: A qualitative research was conducted, following a clinical trial assessing the effectiveness of IPT in schoolchildren (IPTsc), to understand the perceptions and experiences of parents and teachers with IPTsc, in two schools of Mokali, in Kinshasa, Democratic Republic of the Congo. Eighty parents participated in 8 focus group discussions and 6 school staff were involved in 6 semi-structured interviews. RESULTS: Parents experiences with IPTsc divided them into two groups (owning positive experiences and owning negative experiences with IPTsc). Three major themes emerged as key factors associated with reluctance of parents to IPT use in schoolchildren. These included wrong malaria-related knowledge, bad experience with IPTsc administered during the trial and misunderstanding of IPTsc. The school staff were generally willing to be trained to give medicine to schoolchildren within the scope of IPT. However, most parents were more comfortable with the use of health workers than teachers for drug administration. More importantly, all parents accepting IPT suggested to diagnose malaria infection before any administration of IPT, which is not in line with IPT principal. CONCLUSION: These results suggest that more efforts are needed to improve overall malaria-related knowledge in the community, specifically chemo-prevention strategies and the safety of the drugs used, to ensure the success of health interventions.

Efficacy of antiviral drug AV2 in the treatment of human papillomavirus-associated precancerous lesions of the uterine cervix: A randomized placebo-controlled clinical trial in Kinshasa, DR Congo. (KINVAV study).

BACKGROUND: Cervical Cancer (CC) is a major public health problem in DR Congo; the high incidence of CC is due to the inexistence of effective screening programs based on cytology and/or HPV detection followed by appropriate treatments. This situation highlights the need to implement efficacious and inexpensive treatment methods. This study aims at evaluating the efficacy of a topical antiviral drug named AV2® as a treatment for HPV-associated lesions of the cervix. METHODS: Women will undergo cytology sampling, HPV testing and Visual inspection of the cervix after application of 5% acetic acid (VIA). VIA-positive women will be randomized to one of two groups to receive treatment by either AV2®or placebo. They will undergo control examinations after two months and after six months. In case of persistent lesions on VIA, treatment by cryotherapy will be done. The primary outcomes will be the change of lesions, the clearance of HPV DNA, and the correlation of the two 2 months after treatment with AV2®. CONCLUSION: This study is the first large-scale study in Africa to evaluate systematically the efficacy and safety of a topical antiviral drug for the treatment of HPV- associated lesions of the cervix. Its findings will direct the planning of suitable algorithms for CC screening and treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov - Unique identifier: NCT02346227, registered on November 8, 2014.

Weight status and associated factors among HIV infected people on antiretroviral therapy in rural Dikgale, Limpopo, South Africa.

BACKGROUND: Underweight in human immunodeficiency virus (HIV)-infected people on antiretroviral therapy (ART) complicates the management of HIV infection and contributes to mortality, whereas overweight increases the risk of cardiovascular disease (CVD). AIM: The study determined weight status and associated factors in people with HIV infection receiving ART. SETTING: Rural primary health care clinics in Dikgale, Limpopo province, South Africa. METHODS: A cross-sectional study in which data were collected using the World Health Organization (WHO) stepwise approach to surveillance (STEPS) questionnaire and calculated using WHO analysis programmes guide. Weight and height were measured using standard WHO procedures, and body mass index was calculated as weight (kg)/height (m2). Data on ART duration were extracted from patients' files. CD4 lymphocyte counts and viral load were determined using standard laboratory techniques. RESULTS: Of the 214 participants, 8.9%, 54.7% and 36.4% were underweight, normal weight and overweight, respectively. Physical activity (OR: 0.99, p = 0.001) and male gender (OR: 0.29, p = 0.04) were negatively associated with overweight. Men who used tobacco were more likely to be underweight than non-tobacco users (OR: 10.87, p = 0.02). Neither ART duration nor viral load or CD4 count was independently associated with underweight or overweight in multivariate analysis. CONCLUSION: A high proportion of people on ART were overweight and a smaller proportion underweight. There is a need to simultaneously address the two extreme weight problems in this vulnerable population through educating them on benefits of avoiding tobacco, engaging in physical activity and raising awareness of CVD risk.

Efficacy and safety of intermittent preventive treatment for malaria in schoolchildren: a systematic review.

BACKGROUND: Intermittent preventive treatment (IPT) is a proven malaria control strategy in infants and pregnancy. School-aged children represent 26 % of the African population, and an increasing percentage of them are scholarized. Malaria is causing 50 % of deaths in this age group and malaria control efforts may shift the malaria burden to older age groups. Schools have been suggested as a platform for health interventions delivery (deworming, iron-folic acid, nutrients supplementation, (boost-)immunization) and as a possible delivery system for IPT in schoolchildren (IPTsc). However, the current evidence on the efficacy and safety of IPTsc is limited and the optimal therapeutic regimen remains controversial. METHODS: A systematic search for studies reporting efficacy and safety of IPT in schoolchildren was conducted using PubMed, Web of Science, Clinicaltrials and WHO/ICTRP database, and abstracts from congresses with the following key words: intermittent, preventive treatment AND malaria OR Plasmodium falciparum AND schoolchildren NOT infant NOT pregnancy. RESULTS: Five studies were identified. Most IPTsc regimes demonstrated substantial protection against malaria parasitaemia, with dihydroartemisinin-piperaquine (DP) given monthly having the highest protective effect (PE) (94 %; 95 % CI 93-96). Contrarily, SP did not provide any PE against parasitaemia. However, no IPT regimen provided a PE above 50 % in regard to anaemia, and highest protection was provided by SP+ amodiaquine (AQ) given four-monthly (50 %; 95 % CI 41-53). The best protection against clinical malaria was observed in children monthly treated with DP (97 %; 95 % CI 87-98). However, there was no protection when the drug was given three-monthly. No severe adverse events were associated with the drugs used for IPTsc. CONCLUSION: IPTsc may reduce the malaria-related burden in schoolchildren. However, more studies assessing efficacy of IPT in particular against malaria-related anaemia and clinical malaria in schoolchildren must be conducted.