bluuebunny/crossref_metadata_2025 huggingface dataset:
WATER SUPPLY AND SANITATION CONDITIONS IN RURAL SOUTHERN MOZAMBIQUE AND ITS ASSOCIATION WITH MORBIDITY AND MORTALITY INDICATORS, 2012–2015
Authors: Grau-Pujol Berta , Sacoor Charfudin , Nhabomba Augusto , Casellas Aina , Quintó Llorenç , Subirà Carme , Giné Ricard , Valentín Antònia , Muñoz Jose
Published: February 2017

Background

Water, sanitation and hygiene (WASH) are major health determinants, responsible for an estimated world-wide disease burden of 5.7%. However, the debate about the effect of water quality, hygiene and sanitation in preventing diarrhoea is still ongoing. The aim of this study is to describe access to improved water supply and sanitation infrastructure, as defined by the Joint Monitoring Programme, in the Manhiça Health Research Centre (CISM) study area and evaluate its association with morbidity and mortality indicators.

Methods

We conducted a retrospective cohort study. All children under 15 living in the study area during the period 2012–2015 were included (N=61900). Children were followed up until they moved from the study area, turned 15 or until 2015. Water and sanitation household data were obtained from the CISM demographic surveillance system (DSS) in the Manhiça district, an area of around 2380 km2. Clinical data were obtained from CISM's round-the-clock morbidity surveillance system covering outpatient and hospital admissions at the Manhiça District Hospital (MDH) and rural health posts. A negative binomial regression model using Wald test was performed to assess the minimum community-based incidence rates (MCBIR) for every morbidity-mortality indicator.ResultsPreliminary data showed that 86% of the children lived at least once in a household with unimproved sanitation facilities, 27% with an unimproved water source. Spatial distribution of unimproved water and sanitation facilities showed to be clustered. Access to unimproved sanitation and water facilities was associated to higher rates of diarrhoea, a significant 30% of diarrhoea rate increase was observed for rivers, lakes and ponds as water sources. Other morbidity indicators (malnutrition, parasitaemia, anaemia) also showed a rate increase with the use of unimproved water and sanitation facilities.

Conclusions

Obtained results are useful to inform sector-related decision-making processes and ultimately improve access to safe drinking water and sanitation in rural southern Mozambique.
URGENT NEED TO EDUCATE NIGERIANS ABOUT THE EBOLA VACCINE TRIAL PROGRAM
Authors: Oluremi Adeolu , Opaleye Oluyinka
Published: February 2017

Background

With the effort of the World Health Organization to start distributing an experimental Ebola vaccine in West Africa, there is need to assess knowledge and willingness to participate in Ebola virus vaccine trials (EBVT) and possible barriers to participation.

Methods

From June to November 2015, a structured questionnaire was used to measure the participants' knowledge and attitudes about Ebola virus vaccine in Nigeria. Data were analysed with packages within SPSS software and p< 0.05 considered significant.

Results

A total of 5000 participants aged 18–49 years were involved; mean age was 37 years; 3218 (64.4%) were female and 1782 (35.6%) male. Willingness to participate in Ebola virus vaccine trials was found in 803 (16.1%) in this population. It was higher in men than women (p=0.001), increased with education levels (p=0.003), higher among employed than unemployed (p=0.005) and higher among single than married (p=0.01). Those who wanted to participate were primarily youth and reasons for readiness to participate include: free health care, monetary gain, international connection and employment opportunity. Decreased willingness was associated with concerns about: fear of reverting back, side effect, refusal of spouses, physical harm, use of parenteral route for vaccine administration, multiple doses of vaccines and societal stigmatisation.

Conclusions

This study showed reduced willingness to participate in EBVT. It also revealed limited knowledge about EBVT in Nigeria. Therefore, there is a need for proper education on the potential role of preventive Ebola virus vaccines in the control of epidemics and the importance of vaccination among the populace of Nigeria. Incentives for would-be subjects should also be part of the planning to encourage greater participation in these trials.
EFFECT OF ONCHOCERCIASIS TREATMENT ON THE FREQUENCY OF SEIZURES IN PATIENTS WITH EPILEPSY AND ONCHOCERCIASIS
Authors: Michel Mandro
Published: February 2017

Background

A high prevalence of epilepsy is mainly observed inOnchocerca volvulus(OV) hyperendemic areas with no or low ivermectin coverage. There is anecdotal evidence that ivermectin may reduce seizure frequency in patients with onchocerciasis associated epilepsy (OAE).

Methods

Between 2008 and 2012, Rethy in Ituri Province, Democratic Republic of Congo, was a study site for a phase III trial comparing moxidectin versus ivermectin as treatment for subjects infested with OV. Participants received a single oral dose of OV drug and were followed for 18 months. Parasitological efficacy was assessed by skin snip exams. In July 2016, the randomisation code has not been broken yet. In 2015 we traced 7 families of patients with epilepsy who had been enrolled in the trial. We interviewed them and reviewed the trial case report forms.

Results

Of 472 trial participants, 13(2.7%) had a medical history of active convulsive epilepsy. After OV treatment, 6 (80%) of 7 male patients with epilepsy became seizure free during the following 18 months. Seizures continued in this period in only 1 person with a decrease in frequency; in the latter microfilariae remained detectable in the skin. In all subjects who became seizure free, the skin snips too became microfilaria free for at least 6 months. None of the patients received any anti-epileptic drug nor an additional dose of moxidectin or ivermectin during or after the trial. In all subjects the frequency of seizures increased again after the 18 months and 2 patients died in 2015, because of drowning in the river during seizures.

Conclusions

This study suggests that moxidectin and/or ivermectin may be able to decrease the frequency of seizures in OV-infested people with epilepsy. A clinical trial will be needed to support this hypothesis.
ASSESSMENT OF THE ENDEMICITY STATUS OF SCHISTOSOMIASIS AND SOIL-TRANSMITTED HELMINTHIASIS IN THE GAMBIA
Authors: Camara Yaya , Sanneh Bakary
Published: February 2017

Background

The Ministry of Health and Social Welfare, The Gambia with support from WHO and Task Force for Global Health (TFGH), conducted a national endemicity mapping survey for schistosomiasis (SCH) and soil-transmitted helminths (STH) to establish their endemicity status. The survey was meant to provide baseline information on endemicity in order to plan and implement strategic interventions. This is a critical step towards NTD elimination by 2020.

Methods

A cross-section of fifty school-aged children (SAC, 25 boys and 25 girls) per school was sampled in 209 schools countrywide. Eligible SAC of 7 to 14 years old were randomly selected using formula (n/50) where n=total eligible pupils per school. Stool, urine and finger prick samples provided, were examined for SCH and STH using Kato-Katz, urine filtration, dip-stick and CCA techniques.

Results

National prevalence of schistosomiasis and soil-transmitted helminthiasis were 4.3% and 2.5%, respectively. At district level, Niani had the highest prevalence of SCH, recording 22%. Whereas for STH, Banjul, the capital city, had the highest prevalence, recording 55%, followed by 22% prevalence in Kombo South.Schistosoma haematobiumis the most dominant parasitic infection in The Gambia. Fourteen (38%) districts in the country are co-endemic for both STH and SCH. Generally, male pupils are more infected with urinary schistosomiasis than females.

Conclusions

It was established that 19 (45%) of districts mapped are endemic for schistosomiasis; thus the need for treatment with praziquantel. Twenty (47%) of districts mapped are endemic for soil-transmitted helminthiasis at varying rates. However, only two STH endemic districts, Banjul (55%), and Kombo South (22%), within the high and very high prevalence rates of endemicity, are eligible for treatment with albendazole.
THE INTERNATIONAL GOOD CLINICAL PRACTICES GUIDELINES: TIME FOR A REVISION?
Authors: Ravinetto Raffaella , Tinto Halidou , Diro Ermias , Okebe Joseph , Mahendradhata Yodi , Rijal Suman , Gotuzzo Eduardo , Lutumba Pascal , Nahum Alain , Nys Kateljine De , Casteels Minnes , Boelaert Marleen
Published: February 2017

Background

The Good Clinical Practices (GCP) codes of the World Health Organization and the International Conference of Harmonization set international standards for clinical research. But critics argue that they were written without considering the challenges faced by clinical researchers in low- and middle-income countries (LMIC).

Methods

We analysed the challenges met when conducting clinical trials in LMIC, including in several locations in sub-Saharan Africa and in EDCTP-funded trials. We compared these challenges to GCP guidance, in order to (a) verify if there are gaps between the international GCP codes and the field reality in LMIC, and (b) formulate recommendations for GCP improvement if needed.

Results

We identified shortcomings in the GCP guidance concerning three broad domains: ethical, legal and operational. We identified also eleven specific issues: the double ethical review of ‘externally sponsored’ trials; the informed consent in children; the informed consent in illiterate people; the informed consent comprehension; the definition of vulnerability; the post-trial access to communities; the role of communities as key stakeholders in research; the definition of sponsor; the guidance for contractual agreements; the clinical monitoring; the laboratory quality management systems; and the quality assurance of investigational products. For each specific issue, we formulated a recommendation for the improvement of GCP.

Conclusions

Clinical trials are increasingly conducted in LMICs, thus a comprehensive revision of GCP guidelines is needed, to ensure adequate guidance for researchers operating in these contexts, and to maximise protection of research participants. The revised GCP code should be strongly rooted in ethics, sensitive to different socio-cultural perspectives, and allow consideration of trial- and context-specific challenges. This can be only achieved if researchers, sponsors, regulators and ethical reviewers from LMIC are transparently involved in the revision process, as well as non-commercial researchers and sponsors, and major agencies that fund international collaborative clinical research.
ETHICAL AND SCIENTIFIC CONSIDERATIONS FOR THE DESIGN AND IMPLEMENTATION OF THE PREP DEMONSTRATION PROJECT IN NIGERIA
Authors: Ukpong Morenike , Sagay Atiene , Khamofu Hadiza , Torpey Kwasi , Afiadigwe Evaristus , Anenih James , Ezechi Oliver , Nweneka Chidi , Idoko John
Published: February 2017

Background

This abstract highlights the ethical and scientific considerations that informed the development and review of the Nigeria PrEP demonstration study protocol.

Methods

A desk review was conducted on all the meeting reports that led to the choice of the study design and the decisions made to modify the protocol for the PrEP demonstration project in Nigeria. The study focused on the ethical and scientific rationales for modifying the Partners' PrEP Sero-discordant protocol for this study as well as for the first and second protocol amendments of this study.

Results

The decision to conduct a PrEP study was based on the outcome of a modelling study that suggested that sero-discordant couples will benefit from access to condom, TasP, and PrEP. Next, the decisions on the target population for the PrEP demonstration study, the models for evaluation at specific project site, and the design of the community engagement programme were reached through a formative research which engaged 611 individuals using multiple media. The study did not exclude study participants based on Hepatitis status and HIV risk profile since Truvada was an effective hepatitis treatment and the prevalence of hepatitis infection is high in Nigeria. Participants' interest in PrEP use was considered enough reason to prescribe PrEP in a country where uptake of ARV is slow and stigma associated with ARV use is high. Also, HIV-negative partners could assess when the viral load of the HIV-positive partner was 400 copies/ml. Since adherence was a challenge for PrEP use, adherence was enhanced through the use of the MEMS Cap.

Conclusions

A PrEP demonstration study that mimics real life scenarios for PrEP provision within public health care institutions and is designed on the basis of community consultations, ethical and scientific considerations, will enhance the success of PrEP roll-out in resource-limited settings like Nigeria.
DETERMINING THE ENVIRONMENTAL, SOCIAL AND CULTURAL CONTEXTS OF A PROPOSED SCHISTOSOMIASIS HEALTH EDUCATION INTERVENTION IN EGGUA, YEWA NORTH LOCAL GOVERNMENT AREA, OGUN STATE NIGERIA
Authors: Anumudu Chiaka , Onile Olugbenga , Oladele Victoria , Adebayo Adewale , Awobode Henrietta
Published: February 2017

Background

The role of health education in the control of schistosomiasis cannot be over-emphasised. Central to its utility is an understanding of the way a community perceives, understands and can explain how schistosomiasis occurs among them.

Methods

In order to study the environmental, social and cultural determinants of continued schistosomiasis prevalence in Eggua, we administered a semi-structured questionnaire to 371 adults and 265 children between November 2012 and December 2015. We asked questions about their occupation, present and previous water contact pattern, knowledge of schistosomiasis, sanitation, smoking and alcohol behaviour and length of residence in the village.

Results

The respondents ranged in age from 35 to above 60 years; 45% had no schooling and 30% had a least a primary education. Most were farmers (48%) and traders (30%) with a small number (2%) of fisher-folk and had been at this work for more than 15 years. The majority (93%) were Christian, of a denomination in which members spend long periods in the river praying. The rivers are the main source of water for a large number of respondents (63%). Water contact is frequent: 90% go at least daily to the rivers. All the respondents worked at non-itinerant jobs. Despite the research surveys were taking place in Yewa since 2009, 90% of respondents did not know the cause of blood in urine and self-reported haematuria was low (4.6%). Many homes did not have a latrine. Children respondents also didn't have knowledge of the cause of schistosomiasis (60%); those who had heard about it were not well educated on ways to avoid being infected; and 83% did not know they could be re-infected after treatment.

Conclusions

Formal health education initiatives for the control of schistosomiasis in Eggua are imperative and these findings should be taken into account in designing them.
FROM LABORATORY RESEARCH TO THE PUBLIC: SCIENCE COMMUNICATION FOR POLICY, RESEARCH COMMUNITY AND PUBLIC
Authors: Kabuye Emily , Lutalo Tom , Kaleebu Pontiano , Mbidde Edward
Published: February 2017

Background

The Government of Uganda uses empirical evidence for policy formulation. The Uganda Virus Research Institute (UVRI) and the International Association of National Public Health Institutions (IANPHI) trained journalists and scientists to communicate research processes and findings to the public. This improved the capacity to communicate important information during outbreaks and to disseminate research findings as part of policy formulation.

Methods

Through training workshops, 30 research scientists including study coordinators, research officers and principal investigators interacted with 12 health reporters from various media houses. Training covered writing policy briefs and press releases. Attendees were taken through the ‘dos and don'ts’ when being interviewed by television/radio journalist while journalists were trained in basic epidemiology terms and research processes. They analysed research papers to find different story angles. They conducted mock media talk shows for television and radio and these sessions were reviewed by all those in attendance, identifying areas for improvement.

Results

Key findings revealed that journalists do not ably write about research findings because they do not understand the scientific research procedure. Training journalists on health research communication, ethical issues and research procedure enabled them to appreciate the scientific research process. Continued interaction was found to be of help to articulate research findings for health journalist before they are presented in print and audio media for the wider audience/public. This method built capacity of participating scientists to communicate to the lay audiences. It also helped the scientists plan for the media and policy makers during future dissemination of their research findings.

Conclusions

Meaningful engagement of journalists and the public by scientists results in proper understanding of the ethical and scientific research procedure. This calls for systematic investment by research organisations and, during proposal development, budgeting for communication and knowledge translation of research findings to benefit policy makers and the wider research community.
PREVALENCE AND CLINICAL SIGNIFICANCE OF SCHISTOSOMIASIS-CHRONIC HEPATITIS B VIRUS CO-INFECTION IN ZAMBIA
Authors: Chisenga Caroline , Sinkala Edford , Chilengi Roma , Chitundu Hellen , Zyambo Zude , Wandeler Gilles , Vinikoor Michael
Published: February 2017

Background

Hepatosplenic schistosomiasis (HSS) and hepatitis B virus (HBV) are both endemic in sub-Saharan Africa but the clinical epidemiology of co-infection is not well-characterised. Within a current HIV cohort study, we assessed the prevalence of HSS and its impact on markers of liver fibrosis in HIV-HBV co-infected individuals.

Methods

At two urban HIV care facilities in Zambia's capital Lusaka, we screened for HBV co-infection using a hepatitis B surface antigen (HBsAg) test and for lifetime infection withSchistosoma mansoniusing an IgG enzyme-linked immunoassay (Abcam, Cambridge, UK). Among HIV-HBV patients, we also performed abdominal ultrasonography. We defined HSS as evidence of periportal hepatic fibrosis on ultrasound regardless of IgG result. Patient characteristics, including liver fibrosis markers (ALT and transient elastography) were measured and stratified by HSS. We used Wilcoxon rank sum test for continuous and chi-square test for categorical comparisons between groups.

Results

Among 895 HIV-infected adults, lifetime exposure toS. mansoniwas observed in 23.3%. Within the cohort 92 HBsAg-positives underwent assessment for HSS. Median age among these was 34.7 years (interquartile range [IQR], 28.9–39.9), 48% were men, CD4 count was 247 cells/mm3 (IQR, 145–335), HBV viral load was 2.87 (IQR, 1.00–5.18) log10 IU/mL, and liver stiffness was 5.5 kilopascals (IQR, 4.7–6.9).

On ultrasound, 1 patient had cirrhosis and 36 (39.1%) had evidence of HSS. HBV-HSS patients had a non-significant trend toward higher portal vein diameter (8.5 versus 10.2; p=0.15) compared to those without HSS but ALT (18.5vs20 U/L), and liver stiffness (5.3vs5.0 kPa) were similar between groups (both p >0.05).

Conclusions

LifetimeS. mansoniexposure and current HSS were common among HIV-infected patients with HBV co-infection in Zambia. Mild HSS did not appear to alter non-invasive markers of liver fibrosis. Further research on the impact of more advanced HSS on HBV co-infection is needed.
RUBELLA SEROPREVALENCE AMONG HIV-INFECTED AND UNINFECTED ZAMBIAN CHILDREN AND ADOLESCENTS
Authors: Matakala Kalumbu , Sutcliffe Catherine , Searle Kelly , Greenman Michelle , Rainwater-Lovett Kaitlin , Thuma Philip , Moss William
Published: February 2017

Background

Congenital rubella syndrome remains a significant cause of morbidity and mortality among children in sub-Saharan Africa. A safe and effective vaccine is available and many countries, including Zambia, plan to introduce the measles-rubella vaccine by 2020. HIV-infected youths may be an important group to consider as they may remain susceptible to rubella virus due to waning immunity. More information is needed in this age group to guide policy on catch-up rubella vaccination campaigns after introduction.

Methods

This cross-sectional study was nested within ongoing studies of HIV and malaria in Southern Province, Zambia. Dried blood spot cards from children and youths 5–15 years of age enrolled in these studies from 2009–2013 were selected and tested for IgG antibodies to rubella virus. Antibody levels among HIV-uninfected youth, HIV-infected treatment-naïve youth, and HIV-infected youth receiving antiretroviral therapy (ART) were compared.

Results

617 HIV-uninfected, 144 HIV-infected treatment-naïve, and 128 HIV-infected youth receiving ART were included in the study. The proportion seropositive for rubella virus was significantly higher among HIV-uninfected youth (54.7%) compared to HIV-infected treatment-naïve youth (41.7%) and HIV-infected youth receiving ART (49.6%). The proportion of youth with equivocal results was significantly higher for the two groups of HIV-infected youth (treatment-naïve=11.8%; receiving ART=7.9%) compared to HIV-uninfected youth (1.1%). Within groups, the proportion seropositive increased with age. Other than age, no demographic or clinical characteristics were associated with susceptibility among HIV-infected youth.

Conclusions

Our results suggest that HIV-infected youth would benefit from vaccination against rubella virus. Half of all youth in rural Zambia were susceptible to Rubella virus. When rubella vaccine is introduced, failure to target older girls in immunisation campaigns could lead to an increase in congenital rubella cases.
PREVALENCE AND RISK FACTORS OF VIROLOGICAL FAILURE AMONG CHILDREN ON ANTIRETROVIRAL THERAPY
Authors: Owusu Michael , Mensah Eric , Enimil Anthony , Mutocheluh Mohamed
Published: February 2017

Background

An unprecedented global effort at scaling up universal access to antiretroviral therapy has decreased the progression of HIV. However, due to challenges with supplies and adherence to intermittent antiretroviral therapy (ART) for mothers, infants continue to be infected, some with resistant viruses. Exposure to these resistant strains leads to non-responsiveness to therapy resulting in virological failure. Children are more vulnerable to HIV drug resistance because of their life long treatment, the possible selection of resistant strains as a result of prophylaxis for mothers with HIV enrolled in PMTCT. The objective of the study was to determine the prevalence and risk factors of virological resistance among HIV-1-positive children on antiretroviral therapy.

Methods

This was a longitudinal study that was performed at the HIV paediatric clinic of the Komfo Anokye Teaching Hospital, Kumasi, Ghana. Blood samples of children below the age of 18 years who had been on therapy for at least 3 months were analysed for virological load using real-time COBAS AmpliPrep/COBAS Taqman PCR. The samples were analysed at two consecutive time points when they came for their ART refill. Socio-demographic and clinical information was collected from their folders and also from the mother.

Results

A total of 188 subjects were enrolled into the study from September 2015 to June 2016. The average duration on ART was 36 months (IQR=12–72 months). Of all subjects recruited, 134 (71.3%) were found to be on regular drug ART. Of these, 21 (15.7%) had virological failure and 102 (76.1%) had virological suppression. A regression analysis showed that subjects whose parents were unemployed had 5.4 (1.4–20.9) chances of virological failure compared to those with parents employed.

Conclusions

The risk of virological failure among HIV-positive children is still high. Efforts must be made to further identify the potential causes of virological failure among these children.
VIROLOGICAL RESPONSE TO EARLY COMBINED ANTIRETROVIRAL THERAPY IN HIV-INFECTED INFANTS: EVALUATION AFTER TWO YEARS OF TREATMENT IN THE PEDIACAM STUDY
Authors: Ndongo Francis Ateba , Tejiokem Mathurin Cyrille , Texier Gaetan , Penda Calixte , Ndiang Suzie , Ndongo Jean-Audrey , Guemkam Georgette , Sofeu Casimir Ledoux , Afumbom Kfutwa , Faye Albert , Msellati Philippe , Warszawski Josiane
Published: February 2017

Background

Little is known about virological responses to early combined antiretroviral therapy (cART) in HIV-infected infants in limited-resource settings. We estimated the probability of achieving viral suppression within two years of cART initiation, and investigated the factors associated with success.

Methods

We analysed all 190 infants from the Cameroon PediaCAM study who began free cART before the age of 12 months. The main outcome measure was viral suppression (<1000 cp/mL) on at least one occasion. The other outcome measures considered were viral suppression (<400 copies/ mL) on at least one occasion and confirmed viral suppression (both thresholds) on two consecutive occasions. We used competing-risks regression for a time-to-event analysis to estimate the cumulative incidence of outcomes, and univariate and multivariate models to identify risk factors.

Results

During the first 24 months of cART, 20.0% (38) of the infants died, giving a mortality rate of 11.9 deaths per 100 infant-years [95% CI: 8.1–15.7]. The probability of achieving a viral load below 1000 or 400 copies/mL was 80.0% [69.0–81.0] and 78.0% [66.0–79.0], respectively. The probability of virological suppression (with these two thresholds) on two consecutive occasions was 67.0% [56.0–70.0] and 60.0% [49.0–64.0], respectively. Virological success was associated with not having missed any doses of treatment before the visit, but not with socioeconomic and living conditions.

Conclusions

The long-term daily administration of drugs to babies seems to be difficult. Mortality remained high despite early cART initiation. Future studies should focus on longer-term treatment outcomes in children still alive after two years of treatment.
PHYLOGENETIC AND DEMOGRAPHIC CHARACTERISATION OF HIV-1 TRANSMISSION NETWORKS IN A GENERAL POPULATION COHORT IN UGANDA
Authors: Ssemwanga Deogratius , Lyagoba Frederick , Magambo Brian , Kapaata Anne , Kirangwa Joseph , Nannyonjo Maria , Nassolo Faridah , Nsubuga Rebecca , Yebra Gonzalo , Brown Andrew , Kaleebu Pontiano
Published: February 2017

Background

The General Population Cohort (GPC) in Southwestern Uganda is a low-risk population with low HIV incidence rates (<1%). Despite several interventions for close to 30 years, new cases of HIV continue to emerge. We set out to use phylogenetics and patients' demographic data to understand the HIV transmission dynamics in this population to inform prevention.

Methods

A total of 2049 pol sequences of participants diagnosed from 2003–2015 were included in this analysis; pol sequences were from GPC (n=1049), Central Uganda (n=800) and Eastern Uganda (n=200). Phylogenetic analysis was used to identify transmission networks. The demographic and clinical characteristics of the transmission clusters were analysed.

Results

The overall subtype distribution was: A (45%), C (3%), D (40%) and others (12%). The subtype distribution by region was for GPC: A (41%), C (2%), D (45%) and others (12%). For Central: A (49%), C (4%), D (35%) and others (12%). Eastern: A (60%), C (3%), D (24%) and others (13%). We identified 233 transmission clusters (cluster size variation 2–10) that comprised of 559 (27%) of the 2049 participants.

The majority of clusters comprised transmission pairs (n=186) and triplets (n=30). The majority (∼60%) of the 233 clusters was from the GPC and all 13 large clusters (≥5) were also from the GPC. A significant number of clusters (n=25, 11%) was formed between individuals from different geographic locations. Participants in transmission networks were associated with high-risk sexual behaviour: low condom use, high alcohol use, and partner change even with known HIV-positives.

Conclusions

The transmission networks identified among individuals from the GPC and other populations or geographic regions may imply HIV introductions from outside communities. This suggests that HIV introductions into communities are common and account for a substantial number of new infections in the GPC. HIV prevention efforts should therefore target the broader communities beyond the GPC.
PREVALENCE AND RISK FACTORS FOR EFAVIRENZ-BASED ANTIRETROVIRAL TREATMENT-ASSOCIATED SEVERE VITAMIN D DEFICIENCY: A PROSPECTIVE COHORT STUDY
Authors: Nylén Hanna , Habtewold Abiy , Makonnen Eyasu , Yimer Getnet , Burhenne Jürgen , Diczfalusy Ulf , Aklillu Eleni
Published: February 2017

Background

Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) co-treatment is not explored well.

Methods

Treatment-naïve HIV patients with (n=102) or without (n=89) tuberculosis co-infection were enrolled prospectively and received efavirenz-based cART. In TB-HIV co-infected patients, rifampicin-based TB treatment was initiated. Plasma 25-hydroxyvitamin D (25(OH)D), cholesterol and 4-beta hydroxycholesterol concentrations were measured at baseline, and weeks 4, 16 and 48 of cART. Plasma efavirenz concentrations were determined at week 4 and 16 of cART. Genotyping for CYP2B6, CYP3A5, ABCB1, SLCO1B1, and UGT2B7 were done.

Results

TB-HIV patients had significantly lower plasma 25(OH)D3 levels than HIV-only patients at baseline. TB co-infection, low Karnofsky score, high viral load and high CYP3A activity as measured by plasma 4-beta hydroxycholesterol/ cholesterol ratios were significant predictors of low 25(OH) D3 levels at baseline. In HIV-only patients, initiation of efavirenz-based cART increased the prevalence of SVVD from 27% at baseline to 76%, 79% and 43% at weeks 4, 16 and 48 of cART, respectively. The median 25(OH)D3 levels declined from baseline by –40%, –50% and –14% at weeks 4, 16 and 48 of cART, respectively. In TB-HIV patients, prior TB therapy had no influence on 25(OH)D3 levels, but the initiation of efavirenz-based cART increased the prevalence of SVDD from 57% at baseline to 70% and 72% at weeks 4 and 16 of cART, respectively. Whereas the median plasma 25(OH)D3 declined from baseline by –17% and –21% at week 4 and 16 of cART, respectively. None of the genotypes were significantly associated with SVDD.

Conclusions

Low plasma cholesterol, high CYP3A activity, and high plasma efavirenz concentrations are significant predictors of early efavirenz-based cART-induced SVDD. Low plasma 25(OH)D3 level at baseline is associated with TB co-infection and HIV diseases progression.
THE BURDEN AND FUTURE SCOPE FOR IMPORTANT VIRAL ENTERIC PATHOGENS IN AFRICA
Authors: Steele Duncan
Published: February 2017

Background

The burden of viral enteric infections in Africa is enormous, although poorly described. Some, such as rotavirus, are well recognized, whereas others including norovirus or enteric adenovirus (EAd), show high burden which is only now being described. Hepatitis E virus (HEV) is a neglected enteric viral infection although is on WHO's radar screen as an important pathogen which needs further evaluation in Africa and Asia. This presentation will focus on these four enteric viral pathogens describing our current understanding of disease burden and the potential for vaccines as potential interventions.

Many

countries in Africa have documented the high burden of rotavirus. Almost 30 countries have introduced rotavirus vaccines with or without Gavi support, and recent studies document dramatic reductions in diarrhoeal hospitalizations and diarrhoeal deaths post introduction.

Norovirus

is a ubiquitous virus causing diarrhoeal disease in all age ranges, although the incidence is highest in young children. Although a common cause of diarrhoea, norovirus is often associated with asymptomatic shedding making it difficult to ascertain the true burden of the disease. Nevertheless, advances towards understanding the epidemiology and diversity of norovirus in Africa are important to inform future vaccine efforts.

EAds

have recently been described as one of the top 5 pathogens associated with acute severe diarrhoea in young children <5 years in Africa and Asia. Coupled with the high prevalence of EAds in HIV-infected children requires more focused research, although there is very limited vaccine development currently.

HEV

is associated with water-borne and zoonotic infections, and is reported in large outbreaks. It has high mortality in pregnant women and is associated with high rates of stillbirths. Little is known of the extent of HEV infection in Africa. A Chinese vaccine against HEV has been licensed and WHO has identified gaps in research that are required for future immunization opportunities.
IMPACT OF TARGETED INTERVENTIONS AGAINST DIARRHOEA IN ZAMBIA
Authors: Chilengi Roma , Simuyandi Michelo , Beres Laura , Bosomprah Samuel
Published: February 2017

Background

Diarrhoea is a leading cause of morbidity and mortality with the brunt of diarrhoea felt most in developing countries like Zambia where 13% of all deaths of children between 1–59 months are attributable to the disease. The Ministry of Health, in partnership with the Centre for Infectious Disease Research in Zambia (CIDRZ) and other stakeholders, implemented the Programme for the Awareness and Elimination of Diarrhoea (PAED) in 2012 to reduce all-cause under-five mortality by 15% in Lusaka Province.

Methods

Baseline data were collected in 2012 and endline data were collected 3 years following PAED implementation. The primary outcome of interest was all-cause under-five mortality rate. Additionally, a case-control study to estimate rotavirus vaccine effectiveness (VE) was undertaken.

Results

The percentage of children under age 5 who had diarrhoea in the last 2 weeks preceding the survey declined from 15.8% (95% CI: 15.2–16.4%) in 2012 to 12.7% (95% CI:

12.3–13.%) in 2015. Post-neonatal mortality declined by 34%, from an estimated rate of 29 (95% CI: 26–32) to 19 (95% CI: 16–21) deaths per 1000 live births. The adjusted 2-dose VE was 26% (95% CI: 30%–58%) among children ≥6 months of age. VE against hospitalised children ≥6 months of age was 56% (95% CI, – 34%–86%).

Conclusions

Well-packaged preventive and treatment interventions against diarrhoea could reduce probability of death among children aged 1–59 months. VE results from Zambia were consistent with others in the region, and while we observed a higher point estimate for VE against increased severity of illness compared with milder disease, the study was not powered to detect a low level of VE against milder disease.
EVIDENCE-INFORMED POLICY MAKING: CHALLENGES AND OPPORTUNITIES
Authors: Volmink Jimmy
Published: February 2017

Evidence-informed health policy making depends on the availability of the results of studies that have assessed what works, what does not work, and what may be harmful. However, even where such evidence exists it will not always be embraced by policy makers or other decision makers.

This presentation begins by discussing the environment in which policy making takes place and identifying the role of players involved, drawing attention to the complexity of the policy making process. It shows how competing forces, such as beliefs, vested interests, values, habits and financial considerations can lead to important evidence being rejected or ignored by national and international policy makers, sometimes with serious consequences.

The talk also explores the role researchers can play in promoting the flow of evidence from research to policy to implementation by focussing on 5 key issues: generating primary research, conducting systematic reviews of evidence, improving access to relevant evidence, enhancing the use of evidence in policy making, and providing information on how best to scale up programmes. Case studies from LMIC settings, relevant to the EDCTP's remit, will be employed to illustrate the various concepts covered in the presentation.
ONE-YEAR SAFETY OF THE RVSV∆G-ZEBOV-GP VACCINE IN ADOLESCENTS AND CHILDREN IN LAMBARENE, GABON
Authors: Bache Bache Emmanuel , Fernandes José F. , Mba Régis M Obiang , Kabwende Anita L. , Grobusch Martin P. , Krishna Sanjeev , Kremsner Peter G. , Todagbe Agnandji Selidji
Published: February 2017

Background

The rVSV∆G-ZEBOV-GP vaccine was safe and immunogenic in American, European and African adults. Few cases of transient, self-limiting arthritis have been reported in some adult participants in Geneva. We describe one-year safety of a single dose (2×107plaque forming unit (PFU)) of the vaccine administered to adolescents and children living in Lambaréné.

Methods

A phase I, open label randomized trial conducted in Lambaréné, Gabon, to assess the clinical safety (adverse events (local/systemic symptoms, and laboratory anomalies)) for 365 days' post injection. The primary objective was to assess the nature, frequency, and severity of adverse events (AEs) and/or serious adverse events (SAEs) associated with the administration of the vaccine.

Results

From 08-May 2015 to 07-Jul-2015, a total of 20 adolescents and 20 children aged 13–17 and 6–12 years respectively, were vaccinated with a single intramuscular dose of 2×107PFU rVSV∆G-ZEBOV-GP vaccine. Two serious adverse events (SAE) were reported over one year of follow-up. Two adolescents were hospitalized forPlasmodium falcipariummalaria and pneumonia infection. Up to 12 months' (6 months of extended follow-up) of both active and passive reporting, the most frequently reported symptoms by vaccinees are classified under the following system organ classes (SOC): Gastrointestinal disorders 30%(6/20) and 40%(8/20), respiratory-thoracic and mediasternal disorders 5%(1/20) and 45%(9/20), and infections/infestations 20%(4/20) and 20%(4/20) for adolescents and children respectively. No case of arthritis was observed, few cases 13%(5/40) of mild to moderate arthralgia, unrelated to the vaccine were reported. No delayed reactogenicity symptoms were reported beyond the already mild to moderate intensity symptoms reported during the first 28 days' post injection. No severe (grade 3) adverse event was reported. Median haematology and biochemistry values were within site normal ranges at month 12.

Conclusion

The vaccine dose of 2×107PFU showed an acceptable safety and tolerability profile in our volunteers' age 6–17 years, living in a setting endemic for Ebola virus transmission. This acceptable safety profile seen in adolescents and children is similar to that previously reported in adults.
THE ROLE OF CLINICAL TRIALS FOR ELIMINATION OF NEGLECTED INFECTIOUS DISEASES AMENABLE TO MASS DRUG ADMINISTRATION
Authors: Bockarie Moses
Published: February 2017

Background

In 2012, WHO published a roadmap, for ‘Accelerating Work to Overcome the Global Impact of Neglected Tropical Diseases (NTD)’, which set out control and elimination targets for five NTDs that were considered tools-ready. Lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil-transmitted helminthiasis are amenable to the preventive chemotherapy (PC) strategy and manageable through the implementation of available diagnostic products, and safe and effective medicines. The optimism for achieving the WHO 2020 targets for control and elimination for these PC NTDs was crystallised by the London Declaration of 2012 – a pledge by leaders of several major global health and development organizations, together with industry partners to unite efforts to achieve the targets by 2020. Clinical research involving human subjects is driven primarily by the need for novel products, devices or interventions. The question remains whether clinical trials have a role in the fight against NTDs that are tools-ready. Can an investment case be made for vaccines or new drugs for the five PC NTDs? Four of the five PC NTDs are vector-borne diseases, but clinical trials are not normally designed to measure vector outcomes and there is little information available for the conduct of clinical trials involving entomological tools and products. Moreover, human and laboratory capabilities for conducting clinical trials in the countries most affected by NTDs in sub-Saharan Africa are limited. Nonetheless, alternative intervention strategies based on new drugs, vaccines and novel devices have been proposed as additional tools that could fast-track the fight against the PC NTDs. The role of clinical trials in defining these new strategies will be discussed.
PATTERNS OF MOLECULAR MARKERS OF RESISTANCE IN ‘REAL LIFE’ REPETITIVE DIHYDROARTEMISININ-PIPERAQUINE MALARIA TREATMENT: A MOLECULAR ANALYSIS OF THE WANECAM CLINICAL TRIAL PLATFORM OUTPUT
Authors: Kone Aminatou , Sagara Issaka , Björkman Anders , Djimde Abdoulaye , Gil Jose Pedro
Published: February 2017

Background

The pharmacologic characteristic of piperaquine (PPQ), namely its very long half-life, raises concerns on the possibility of relatively rapid rise of resistance. Recent unequivocal reports from SE Asia support this worry. Due to its long half-life, conventional follow-up of up to 63 days in efficacy trials misses the low concentrations of PPQ, prone to select less sensitive parasite sub-populations. The WANECAM clinical trials included a follow-up of two years of the same patients, allowing for the first time the analysis of both, the patterns of selection upon an expected large range of PPQ concentrations and the potential effect of residual levels upon repetitive treatments.

Methods

We have successfully determined a random sample of E1 (D0) 151 and 405 (E2-E10) pfcrt K76T genotypes, as well as 151 E1 (D0) and 389 (E2-E10) genotypes for the pfmdr1 E2-E10 episodes. Pfmdr1 N86Y analysis was limited by a large (>90%) prevalence of the 86N allele. Established PCR-RFLP methods were applied, with high precision band analysis being performed through image analysis software (GelEval®). Qui Square and Kruskal Wallis tests were used as applicable.

Results

The present data analysis was limited to episodes with an intervening period of<180 days. Preliminary conclusions point to recurrences of pfmdr1 carrying 184Y parasites to emerge earlier as compared with 184F (D78vsD89, Kruskal Wallis test, p< 0.01), corresponding to an expected difference of ca. 20 to 10 nM on PPQ blood levels. No significant differences were detected concerning pfcrt K76T.

Conclusions

Long-term analysis of molecular markers throughout repetitive treatments is expected to unveil informative patterns concerning early steps of PPQ resistance development. The complete set of data will be presented and analysed in the context of the recent findings of PPQ resistance in SE Asia. Its relevance for the East African settings will be discussed.
THE RESULTS OF THE EV06 DNA-PROTEIN COMBINATION TRIAL AND PLANS FOR GREAT, AN EDCTP2-FUNDED CONSERVED-MOSAIC EPITOPE HIV VACCINE TRIAL
Authors: Kaleebu Pontiano , Levin Jonathan , Nanvubya Annet , Kibengo Freddie , Jaoko Walter , Pala Pietro , Perreau Matthieu , Namuniina Annemarie , Kitandwe Paul , Tapia Gonzalo , Serwanga Jennifer , Yates Nicole , Fast Pat , Mayer Bryan , Montefiori David , Tomaras Georgia , Robb Merlin , Lee Carter , Wagner Ralf , Sanders Edward , Kilembe William , Kiwanuka Noah , Gilmour Jill , Kuipers Hester , Vooij Dani , Chinyenze Kundai , Priddy Frances , Ding Song , Hanke Tom , Pantaleo Giuseppe ,   EV06 study team GREAT study team
Published: February 2017

Background

These two trials under Europe-Africa collaborations aim at addressing two factors relevant for Africa i.e helminth infections and HIV-1 diversity. EV06 used a novel combination of DNA expressing clade C Env, Gag and Pol-nef co-administered with AIDSVAX®B/E Env protein to study the effect ofS. mansonion vaccine responses. GREAT is a recently awarded trial using a 2nd generation improved conserved tHIVConsvX T-cell vaccine candidate combined with bivalent mosaic design to increase breadth and protective epitopes.

Methods

EV06 enrolled 72 males and females aged 18–45, half infected withS. mansoni(SM+). In each arm 30 received vaccine and 6 placebo at week 0, 4 and 24. Responses were evaluated at week 0, 6, 26 and 36. Humoral responses were measured as binding IgG against a panel of HIV-1 envelope glycoproteins and as neutralizing antibodies (Nabs), using TZM/ bl cells and tier 1 pseudoviruses. Cellular responses were measured as HIV-specific CD4+ and CD8+ T-cell by IFN-γ ELIS-pot and multi-cytokine intracellular staining flow cytometry. GREAT will be a phase IIa trial and preparation for efficacy trials in Kenya, Uganda and Zambia testing ChAdOx1.tHIVconsv5 and ChAdOx1.tHIVconsv6 followed by MVA.tHIVconsv3 and MVA.tHIVconsv4 on week 2 (Arm 1) or week 8 (Arm 2).

Progress

Differences in binding IgG response rates were observed in vaccinated participants against the vaccine matched clade C V1V2 (gp70–96ZM651.02 V1V2) at week 6: 56% among SM+ versus 86% among SM – (p=0.039). At week 36, response magnitudes were statistically lower in the SM+ against gp120 and gp140 proteins (p=0.04 for both). SM+ also had lower Nabs and ELISpot responses at various time points. Still blinded data on the first 20 volunteers show 80% responders for CD4 T cell at w26 and 70% CD8 responders at w36. These trials will provide more data on challenges facing HIV vaccine development in Africa.
REVIEW OF HIV IN SUB-SAHARAN AFRICA: CURRENT SITUATION, OPPORTUNITIES AND CHALLENGES
Authors: Hankins Catherine
Published: February 2017

UNAIDS estimates that in 2015, 19 million (17.7–20.5 million) and 6.5 million (5.3–7.8 million) people were living with HIV in Eastern and Southern Africa (ESA) and Western and Central Africa (WCA), respectively. Between 2010 and 2015, new HIV infections declined by 14% in ESA and 8% in WCA, while AIDS-related deaths fell by 38% and 10%, respectively. In ESA, 10.3 million people or 54% (50–58%) of all people living with HIV were accessing antiretroviral therapy (ART), compared to 1.8 million people or 28% (23–34%) of all people living with HIV in WCA. Since 2010, there has been a 66% decline in new HIV infections among children in ESA compared to a 31% decline in WCA.

These striking regional differences mask large discrepancies in country progress, sex differences in ART uptake, and a diversity of micro-epidemics across sub-Saharan Africa. The goal to end AIDS as a public health threat by 2030, the UN-AIDS 90–90–90 treatment cascade goal for 2020, and the WHO recommendation to offer ART when HIV is diagnosed regardless of CD4 count are galvanizing public health and community-based responses in Africa. Despite improvements in ART and new prevention tools, including voluntary medical male circumcision and oral pre-exposure prophylaxis, the goals will not be achieved without new tools, including an HIV vaccine and a cure.

EDCTP has funded high-impact HIV research that has resulted in, among others, policy change; prequalification of new products; improved treatment strategies, including for children; and strategies to prevent mother-to-child transmission, while building research capacity and clinical trial infrastructures. Promoting African country membership and increased financial contributions from African countries, EDCTP2 aims to leverage co-funding from public/private sources for calls for proposals that address important gaps in HIV prevention and treatment science that can be answered through phase I-IV clinical trials in sub-Saharan Africa.