Positioning Africa's public health doctoral students to lead societal transformation and development.

The public health context is becoming increasingly more complex requiring highly trained professionals equipped with knowledge, competencies and tools to address or transform current and future challenges. Doctoral degree training offers an opportunity to build the capacity to detect and respond to such dynamic health challenges. In this paper, we discuss how Africa's public health doctoral students can be better positioned for the different career pathways to provide leadership on complex health and development challenges. Public health PhD graduates can take up careers in academia, civil service, private sector and civil society, among others. To thrive in these pathways, PhD training should equip them with knowledge, skills and competencies in leadership, creativity and social competence among others. To produce career-ready PhD graduates, there is need to rethink training curricula to build critical skills for diverse career pathways, introduce students to entrepreneurship, and enhance linkages between universities and industry. Experiential learning, exposure to networks and partnerships, postdoctoral programmes and mentorship and exchange programmes can further equip PhD students with key knowledge, skills and competencies. For students to position themselves for the different careers, they ought to plan their careers early, albeit with flexibility. Students should build their soft skills and embrace technology among other transferable competencies. By identifying potential career pathways and being positioned for these early, Africa can produce transformative PhD students on a path for success not just for themselves but for society at large, including in new environments such as that created by COVID-19.

Needs-driven talent and competency development for the next generation of regulatory scientists in Africa.

Capacity building programmes for African regulators should link education, training and research with career development in an approach that combines an academic base and experiential learning aligned within a competency framework. A regulatory ecosystem that engages with a broad range of stakeholders will mean that expertise in the ever-expanding field of regulatory science filters into teaching and research in a symbiotic way. In this way capacity development interventions will be a collaborative approach between the learning context (academic and training institutions) and the performance context (regulatory agencies and industry), which will ultimately best serve the patients. Monitoring and evaluation of capacity development interventions will be essential to show value of investments and ultimately guide continued funding and sustainability. This paper reviews the skills and human capacity gaps, reports on regulatory assessment pathways used in Ghana, South Africa and Zimbabwe and outlines a staged tactical approach for Africa that builds on previous efforts to strengthen African regulatory ecosystems.

Effectiveness of peer-supervision on pediatric fever illness treatment among registered private drug sellers in East-Central Uganda: An interrupted time series analysis.

RATIONALE AIMS AND OBJECTIVES: Appropriate treatment of pediatric fever in rural areas remains a challenge and maybe partly due to inadequate supervision of licensed drug sellers. This study assessed the effectiveness of peer-supervision among drug sellers on the appropriate treatment of pneumonia symptoms, uncomplicated malaria, and non-bloody diarrhea among children less than 5 years of age in the intervention (Luuka) and comparison (Buyende) districts, in East-Central Uganda. METHODS: Data on pneumonia symptoms, uncomplicated malaria, and non-bloody diarrhea among children less than 5 years of age was abstracted from drug shop sick child registers over a 12-month period; 6 months before and 6 months after the introduction of peer-supervision. Interrupted time series were applied to determine the effectiveness of the peer-supervision intervention on the appropriate treatment of pneumonia, uncomplicated malaria, and non-bloody diarrhea among children less than 5 years of age attending drug shops in East Central Uganda. RESULTS: The proportion of children treated appropriately for pneumonia symptoms was 10.84% (P < .05, CI = [1.75, 19.9]) higher, for uncomplicated malaria was 1.46% (P = .79, CI = [-10.43, 13.36]) higher, and for non-bloody diarrhea was 4.00% (P < .05, CI = [-7.95, -0.13]) lower in the intervention district than the comparison district, respectively.Post-intervention trend results showed an increase of 1.21% (P = .008, CI = [0.36, 2.05]) in the proportion appropriately treated for pneumonia symptoms, no difference in appropriate treatment for uncomplicated malaria, and a reduction of 1% (P < .06, CI = [-1.95, 0.02]) in the proportion of children appropriately treated for non-bloody diarrhea, respectively. CONCLUSIONS: Peer-supervision increased the proportion of children less than 5 years of age that received appropriate treatment for pneumonia symptoms but not for uncomplicated malaria and non-bloody diarrhea. Implementation of community-level interventions to improve pediatric fever management should consider including peer-supervision among drug sellers.

Eight years of the East African Community Medicines Regulatory Harmonization initiative: Implementation, progress, and lessons learned.

Jane H. Mashingia and colleagues reveal the progress made to date for the East African Community Medicines Regulatory Harmonization initiative.

Coming together to improve access to medicines: The genesis of the East African Community's Medicines Regulatory Harmonization initiative.

Hiiti Sillo and colleagues reveal how the East African Community's Medicines Regulatory Harmonization initiative improves access to important medicines in Africa.

Peer supervision experiences of drug sellers in a rural district in East-Central Uganda: a qualitative study.

BACKGROUND: Support supervision improves performance outcomes among health workers. However, the national professional guidelines for new licenses and renewal for Class C drug shops in Uganda prescribe self-supervision of licensed private drug sellers. Without support supervision, inappropriate treatment of malaria, pneumonia and diarrhoea among children under 5 years of age continues unabated. This study assessed experiences of drug sellers and peer supervisors at the end of a peer supervision intervention in Luuka District in East Central Uganda. METHODS: Eight in-depth interviews (IDIs) were held with peer supervisors while five focus group discussions (FGDs) were conducted among registered drug sellers at the end of the peer supervision intervention. The study assessed experiences and challenges of peer supervisors and drug sellers regarding peer supervision. Transcripts were imported into Atlas.ti 7 qualitative data management software where they were analysed using thematic content analysis. RESULTS: Initially, peer supervisors were disliked and regarded by drug sellers as another extension of drug inspectors. However, with time a good relationship was established between drug sellers and peer supervisors leading to regular, predictable and supportive peer supervision. This increased confidence of drug sellers in using respiratory timers and rapid diagnostic tests in diagnosing pneumonia symptoms and uncomplicated malaria, respectively, among children under 5 years. There was also an improvement in completing the sick child register which was used for self-assessment by drug sellers. The drug shop association was mentioned as a place where peer supervision should be anchored since it was a one-stop centre for sharing experiences and continuous professional development. Drug sellers proposed including community health workers in monthly drug shop association meetings so that they may also gain from the associated benefits. Untimely completion of the sick child registers by drug sellers and inadequate financial resources were the main peer supervision challenges mentioned. CONCLUSION: Drug sellers benefitted from peer supervision by developing a good relationship with peer supervisors. This relationship guaranteed reliable and predictable supervision ultimately leading to improved treatment practices. There is need to explore the minimum resources needed for peer supervision of drug sellers to further inform practice and policy.

Scientific considerations for global drug development.

Requiring regional or in-country confirmatory clinical trials before approval of drugs already approved elsewhere delays access to medicines in low- and middle-income countries and raises drug costs. Here, we discuss the scientific and technological advances that may reduce the need for in-country or in-region clinical trials for drugs approved in other countries and limitations of these advances that could necessitate in-region clinical studies.

Non-treatment of children with community health worker-diagnosed fast-breathing pneumonia in rural Malawi: exploratory subanalysis of a prospective cohort study.

BACKGROUND: Despite recent progress, pneumonia remains the largest infectious killer of children globally. This paper describes outcomes of not treating community-diagnosed fast-breathing pneumonia on patient recovery. METHODS: We conducted an exploratory subanalysis of an observational prospective cohort study in Malawi. We recruited children (2-59 months) diagnosed by community health workers with fast-breathing pneumonia using WHO integrated community case management (iCCM) guidelines. Children were followed at days 5 and 14 with a clinical assessment of recovery. We conducted bivariate and multivariable logistic regression for the association between treatment of fast-breathing pneumonia and recovery, adjusting for potential confounders. RESULTS: We followed up 847 children, of whom 78 (9%) had not been given antibiotics (non-treatment). Non-treatment cases had higher baseline rates of diarrhoea, non-severe hypoxaemia and fever. Non-recovery (persistence or worsening of symptoms) was 13% and 23% at day 5 in those who did receive and those who did not receive co-trimoxazole. Non-recovery, when defined as worsening of symptoms only, at day 5 was 7% in treatment and 10% in non-treatment cases. For both definitions, combined co-trimoxazole and lumefantrine-artemether (LA) treatment trended towards protection (adjusted OR (aOR) 0.28; 95% CI 0.12 to 0.68/aOR 0.29; 95% CI 0.08 to 1.01). CONCLUSION: We found that children who did not receive co-trimoxazole treatment had worse clinical outcomes; malaria co-diagnosis and treatment also play a significant role in non-recovery. Further research into non-treatment of fast-breathing pneumonia, using a pragmatic approach with consideration for malaria co-diagnosis and HIV status is needed to guide refinement of community treatment algorithms in this region.

Health worker and policy-maker perspectives on use of intramuscular artesunate for pre-referral and definitive treatment of severe malaria at health posts in Ethiopia.

BACKGROUND: The World Health Organization (WHO) recommends injectable artesunate given either intravenously or by the intramuscular route for definitive treatment for severe malaria and recommends a single intramuscular dose of intramuscular artesunate or intramuscular artemether or intramuscular quinine, in that order of preference as pre-referral treatment when definitive treatment is not possible. Where intramuscular injections are not available, children under 6 years may be administered a single dose of rectal artesunate. Although the current malaria treatment guidelines in Ethiopia recommend intra-rectal artesunate or alternatively intramuscular artemether or intramuscular quinine as pre-referral treatment for severe malaria at the health posts, there are currently no WHO prequalified suppliers of intra-rectal artesunate and when available, its use is limited to children under 6 years of age leaving a gap for the older age groups. Intramuscular artesunate is not part of the drugs recommended for pre-referral treatment in Ethiopia. This study assessed the perspectives of health workers, and policy-makers on the use of intramuscular artesunate as a pre-referral and definitive treatment for severe malaria at the health post level. METHODS: In-depth interviews were held with 101 individuals including health workers, malaria focal persons, and Regional Health Bureaus from Oromia and southern nations, nationalities, and peoples' region, as well as participants from the Federal Ministry of Health and development partners. An interview guide was used in the data collection and thematic content analysis was employed for analysis. RESULTS: Key findings from this study are: (1) provision of intramuscular artesunate as pre-referral and definitive treatment for severe malaria at health posts could be lifesaving; (2) with adequate training, and provision of facilities including beds, health posts can provide definitive treatment for severe malaria using intramuscular artesunate where referral is delayed or not possible; (3) health workers at health centres and hospitals frequently use the intravenous route because it allows for co-administration of other drugs, but they find the intramuscular route easier to use at the health post level; (4) the reasons commonly cited against the management of severe malaria using intramuscular artesunate at health post level were: lack of capacity to manage complications and fear of irrational drug use; (5) use of intramuscular artesunate at health post level will require evidence on safety and feasibility before policy shift. CONCLUSION: From the perspective of health workers, use of intramuscular artesunate as pre-referral treatment of severe malaria cases at the health post is possible but dependent on training and availability of skilled workers. Use of intramuscular artesunate as definitive treatment at health posts was not supported, however, operational research to establish its feasibility, safety and efficacy was recommended to guide any implementation of such an intervention.

Non-adherence to community oral-antibiotic treatment in children with fast-breathing pneumonia in Malawi- secondary analysis of a prospective cohort study.

BACKGROUND: Despite significant progress, pneumonia is still the leading cause of infectious deaths in children under five years of age. Poor adherence to antibiotics has been associated with treatment failure in World Health Organisation (WHO) defined clinical pneumonia; therefore, improving adherence could improve outcomes in children with fast-breathing pneumonia. We examined clinical factors that may affect adherence to oral antibiotics in children in the community setting in Malawi. METHODS: We conducted a sub-analysis of a prospective cohort of children aged 2-59 months diagnosed by community health workers (CHW) in rural Malawi with WHO fast-breathing pneumonia. Clinical factors identified during CHW diagnosis were investigated using multivariate logistic regression for association with non-adherence, including concurrent diagnoses and treatments. Adherence was measured at both 80% and 100% completion of prescribed oral antibiotics. RESULTS: Eight hundred thirty-four children were included in our analysis, of which 9.5% and 20.0% were non-adherent at 80% and 100% of treatment completion, respectively. A concurrent infectious diagnosis (OR: 1.76, 95% CI: 0.84-2.96/OR: 1.81, 95% CI: 1.21-2.71) and an illness duration of >24 h prior to diagnosis (OR: 2.14, 95% CI: 1.27-3.60/OR: 1.88, 95% CI: 1.29-2.73) had higher odds of non-adherence when measured at both 80% and 100%. Older age was associated with lower odds of non-adherence when measured at 80% (OR: 0.41, 95% CI: 0.21-0.78). CONCLUSION: Non-adherence to oral antibiotics was not uncommon in this rural sub-Saharan African setting. As multiple diagnoses by the CHW and longer illness were important factors, this provides an opportunity for further investigation into targeted interventions and refinement of referral guidelines at the community level. Further research into the behavioural drivers of non-adherence within this setting is needed.

Evaluating the impact of pulse oximetry on childhood pneumonia mortality in resource-poor settings.

It is estimated that pneumonia is responsible for 15% of childhood deaths worldwide. Recent research has shown that hypoxia and malnutrition are strong predictors of mortality in children hospitalized for pneumonia. It is estimated that 15% of children under 5 who are hospitalized for pneumonia have hypoxaemia and that around 1.5 million children with severe pneumonia require oxygen treatment each year. We developed a deterministic compartmental model that links the care pathway to disease progression to assess the impact of introducing pulse oximetry as a prognostic tool to distinguish severe from non-severe pneumonia in under-5 year olds across 15 countries with the highest burden worldwide. We estimate that, assuming access to supplemental oxygen, pulse oximetry has the potential to avert up to 148,000 deaths if implemented across the 15 countries. By contrast, integrated management of childhood illness alone has a relatively small impact on mortality owing to its low sensitivity. Pulse oximetry can significantly increase the incidence of correctly treated severe cases as well as reduce the incidence of incorrect treatment with antibiotics. We also found that the combination of pulse oximetry with integrated management of childhood illness is highly cost-effective, with median estimates ranging from US$2.97 to $52.92 per disability-adjusted life year averted in the 15 countries analysed. This combination of substantial burden reduction and favourable cost-effectiveness makes pulse oximetry a promising candidate for improving the prognosis for children with pneumonia in resource-poor settings.

Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.

BACKGROUND: Pneumonia is the leading cause of infectious death amongst children globally, with the highest burden in Africa. Early identification of children at risk of treatment failure in the community and prompt referral could lower mortality. A number of clinical markers have been independently associated with oral antibiotic failure in childhood pneumonia. This study aimed to develop a prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan Africa. METHOD: We prospectively followed a cohort of children (2-59 months), diagnosed by community health workers with fast-breathing pneumonia using World Health Organisation (WHO) integrated community case management guidelines. Cases were followed at days 5 and 14 by study data collectors, who assessed a range of pre-determined clinical features for treatment outcome. We built the prognostic model using eight pre-defined parameters, using multivariable logistic regression, validated through bootstrapping. RESULTS: We assessed 1,542 cases of which 769 were included (32% ineligible; 19% defaulted). The treatment failure rate was 15% at day 5 and relapse was 4% at day 14. Concurrent malaria diagnosis (OR: 1.62; 95% CI: 1.06, 2.47) and moderate malnutrition (OR: 1.88; 95% CI: 1.09, 3.26) were associated with treatment failure. The model demonstrated poor calibration and discrimination (c-statistic: 0.56). CONCLUSION: This study suggests that it may be difficult to create a pragmatic community-level prognostic child pneumonia tool based solely on clinical markers and pulse oximetry in an HIV and malaria endemic setting. Further work is needed to identify more accurate and reliable referral algorithms that remain feasible for use by community health workers.

Predictors of treatment failure for non-severe childhood pneumonia in developing countries--systematic literature review and expert survey--the first step towards a community focused mHealth risk-assessment tool?

BACKGROUND: Improved referral algorithms for children with non-severe pneumonia at the community level are desirable. We sought to identify predictors of oral antibiotic failure in children who fulfill the case definition of World Health Organization (WHO) non-severe pneumonia. Predictors of greatest interest were those not currently utilized in referral algorithms and feasible to obtain at the community level. METHODS: We systematically reviewed prospective studies reporting independent predictors of oral antibiotic failure for children 2-59 months of age in resource-limited settings with WHO non-severe pneumonia (either fast breathing for age and/or lower chest wall indrawing without danger signs), with an emphasis on predictors not currently utilized for referral and reasonable for community health workers. We searched PubMed, Cochrane, and Embase and qualitatively analyzed publications from 1997-2014. To supplement the limited published evidence in this subject area we also surveyed respiratory experts. RESULTS: Nine studies met criteria, seven of which were performed in south Asia. One eligible study occurred exclusively at the community level. Overall, oral antibiotic failure rates ranged between 7.8-22.9%. Six studies found excess age-adjusted respiratory rate (either WHO-defined very fast breathing for age or 10-15 breaths/min faster than normal WHO age-adjusted thresholds) and four reported young age as predictive for oral antibiotic failure. Of the seven predictors identified by the expert panel, abnormal oxygen saturation and malnutrition were most highly favored per the panel's rankings and comments. CONCLUSIONS: This review identified several candidate predictors of oral antibiotic failure not currently utilized in childhood pneumonia referral algorithms; excess age-specific respiratory rate, young age, abnormal oxygen saturation, and moderate malnutrition. However, the data was limited and there are clear evidence gaps; research in rural, low-resource settings with community health workers is needed.

Assessing the impact of integrated community case management (iCCM) programs on child mortality: Review of early results and lessons learned in sub-Saharan Africa.

AIM: To accelerate progress in reducing child mortality, many countries in sub-Saharan Africa have adopted and scaled-up integrated community case management (iCCM) programs targeting the three major infectious killers of children under-five. The programs train lay community health workers to assess, classify and treat uncomplicated cases of pneumonia with antibiotics, malaria with antimalarial drugs and diarrhea with Oral Rehydration Salts (ORS) and zinc. Although management of these conditions with the respective appropriate drugs has proven efficacious in randomized trials, the effectiveness of large iCCM scale-up programs in reducing child mortality is yet to be demonstrated. This paper reviews recent experience in documenting and attributing changes in under-five mortality to the specific interventions of a variety of iCCM programs. METHODS: Eight recent studies have been identified and assessed in terms of design, mortality measurement and results. Impact of the iCCM program on mortality among children age 2-59 months was assessed through a difference in differences approach using random effect Poisson regression. RESULTS: Designs used by these studies include cluster randomized trials, randomized stepped-wedge and quasi-experimental trials. Child mortality is measured through demographic surveillance or household survey with full birth history conducted at the end of program implementation. Six of the eight studies showed a higher decline in mortality among children 2-59 months in program areas compared to comparison areas, although this acceleration was statistically significant in only one study with a decline of 76% larger in intervention than in comparison areas. CONCLUSION: Studies that evaluate large scale iCCM programs and include assessment of mortality impact must ensure an appropriate design. This includes required sample sizes and sufficient number of program and comparison districts that allow adequate inference and attribution of impact. In addition, large-scale program utilization, and a significant increase in coverage of care seeking and treatment of targeted childhood illnesses are preconditions to measurable mortality impact. Those issues need to be addressed before large investments in assessing changes in child mortality is undertaken, or the results of mortality impact evaluation will most likely be inconclusive.

Training and service in public health, Nigeria Field Epidemiology and Laboratory Training, 2008 - 2014.

The health workforce is one of the key building blocks for strengthening health systems. There is an alarming shortage of curative and preventive health care workers in developing countries many of which are in Africa. Africa resultantly records appalling health indices as a consequence of endemic and emerging health issues that are exacerbated by a lack of a public health workforce. In low-income countries, efforts to build public health surveillance and response systems have stalled, due in part, to the lack of epidemiologists and well-trained laboratorians. To strengthen public health systems in Africa, especially for disease surveillance and response, a number of countries have adopted a competency-based approach of training - Field Epidemiology and Laboratory Training Program (FELTP). The Nigeria FELTP was established in October 2008 as an inservice training program in field epidemiology, veterinary epidemiology and public health laboratory epidemiology and management. The first cohort of NFELTP residents began their training on 20th October 2008 and completed their training in December 2010. The program was scaled up in 2011 and it admitted 39 residents in its third cohort. The program has admitted residents in six annual cohorts since its inception admitting a total of 207 residents as of 2014 covering all the States. In addition the program has trained 595 health care workers in short courses. Since its inception, the program has responded to 133 suspected outbreaks ranging from environmental related outbreaks, vaccine preventable diseases, water and food borne, zoonoses, (including suspected viral hemorrhagic fevers) as well as neglected tropical diseases. With its emphasis on one health approach of solving public health issues the program has recruited physicians, veterinarians and laboratorians to work jointly on human, animal and environmental health issues. Residents have worked to identify risk factors of disease at the human animal interface for influenza, brucellosis, tick-borne relapsing fever, rabies, leptospirosis and zoonotic helminthic infections. The program has been involved in polio eradication efforts through its National Stop Transmission of Polio (NSTOP). The commencement of NFELTP was a novel approach to building sustainable epidemiological capacity to strengthen public health systems especially surveillance and response systems in Nigeria. Training and capacity building efforts should be tied to specific system strengthening and not viewed as an end to them. The approach of linking training and service provision may be an innovative approach towards addressing the numerous health challenges.

Cholera surveillance in Uganda: an analysis of notifications for the years 2007-2011.

INTRODUCTION: Cholera outbreaks have occurred periodically in Uganda since 1971. The country has experienced intervals of sporadic cases and localized outbreaks, occasionally resulting in prolonged widespread epidemics. METHODS: Cholera surveillance data reported to the Uganda Ministry of Health from 2007 through 2011 were reviewed to determine trends in annual incidence and case fatality rate. Demographic characteristics of cholera cases were analyzed from the national line list for 2011. Cases were analyzed by district and month of report to understand the geographic distribution and identify any seasonal patterns of disease occurrence. RESULTS: From 2007 through 2011, Uganda registered a total of 7615 cholera cases with 181 deaths (case fatality rate = 2.4%). The absolute number of cases and incidence per 100 000 varied from year to year with the highest incidence occurring in 2008 following heavy rainfall and flooding in eastern Uganda. For 2011, cholera cases occurred in 1.6 times more males than females. The geographical areas affected by the outbreaks shifted each year, with the exception of a few endemic districts. No clear seasonal trends in cholera occurrence were identified for this time period. CONCLUSIONS: We observed an overall decline in cases reported during the 5 years under review. During this period, concerted efforts were made by the Ugandan government and development partners to educate communities on proper sanitation and hygiene and provide safe water and timely treatment. Mechanisms to ensure timely and complete cholera surveillance data are reported to the national level should continue to be strengthened.

Over-the-counter suboptimal dispensing of antibiotics in Uganda.

BACKGROUND: Overuse and misuse of antibiotics is a serious global problem. While resistance to older antibiotics is increasing, development of newer molecules has stalled. Resistance to the existing antibiotics that is largely driven by their high-volume use is a global public health problem. Uganda is one of the countries where prescription-only drugs, including antibiotics, can be obtained over the counter. We determined the rate of antibiotic dispensing and use in Uganda. METHODS: The study utilized a descriptive cross-sectional study design to determine the number of antibiotic "prescribed" daily doses per 1,000 clients. Data were collected from one health center II, eight general/district hospitals, one national referral hospital, and 62 registered community pharmacies. From each study site, data were collected for five consecutive days over the months of November 2011 to January 2012. RESULTS: The overall antibiotic issue rate was 43.2%. Amoxicillin, metronidazole, ciprofloxacin, sulfamethoxazole-trimethoprim, cloxacillin, and ampicillin, belonging to the WHO anatomical therapeutic chemical classifications of penicillin with extended spectra, imidazole derivatives, fluoroquinolones, and sulfonamide-trimethoprim combinations, constituted 70% of the issued antibiotics. About 41% of antibiotics were issued over the counter. At community pharmacies, where 30% of antibiotic dispensing occurred, the number of prescribed daily doses/1,000 antibiotic clients was 4,169 compared to 6,220, 7,350 and 7,500 at general/district hospitals, the national referral hospital, and the health center, respectively. CONCLUSION: In Uganda, at least four in every ten individuals that visit a health-care facility are treated with an antibiotic. Antibiotics are largely given as over-the-counter drugs at community pharmacies. The number of antibiotic prescribed daily doses/1,000 antibiotic clients does not significantly differ between categories of health-care facilities except at community pharmacies, where lower doses are dispensed compared to other health-care facilities.