Raph L Hamers

• MD PhD
• Senior Clinician Scientist Associate Professor at Oxford University Clinical Research Unit

Antibodies play a crucial role in protection against SARS-CoV-2. Understanding the correlation between binding and functional antibodies is essential to determine whether binding antibody levels can reliably predict neutralizing activity. We assessed antibody responses in 111 individuals vaccinated with the inactivated vaccine CoronaVac and 111 COV...

International guidelines are available for the assessment and improvement of antimicrobial stewardship (AMS) programmes: an important strategy to address the escalating global antimicrobial resistance problem. However, existing AMS assessment tools lack contextual specificity for resource-limited settings, leading to limited applicability in Asia....

Introduction Indonesia has an escalated HIV epidemic concentrated among key populations. To strengthen the care cascade, we implemented a care pathway for the screening of individuals for acute HIV infection (AHI), to achieve prompt diagnosis and antiretroviral treatment (ART) initiation, at three non‐governmental sexual health clinics in Jakarta a...

An increasing number of people living with HIV (PLHIV) are failing treatment without HIV drug resistance in the drug target region. While sub-optimal adherence is likely the cause of treatment failure in many PLHIV, resistance emerging at non-canonical (HIV drug resistance mutations occurring outside the drug target site) drug target site sites is...

Leprosy is effectively treated with multi-drug therapy (MDT), a regimen containing three antibiotic drugs, including dapsone - a sulfone drug associated with potentially life-threatening adverse drug reactions. Specifically, dapsone hypersensitivity syndrome (DHS), linked to HLA-B∗13:01 polymorphism, and hemolytic anemia associated with glucose-6-p...

Background Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-anal...

Background: Low dose corticosteroids have been shown to reduce mortality for hypoxic COVID-19 patients. We have previously reported that higher dose corticosteroids cause harm in patients with hypoxia but not receiving ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation),...

BACKGROUND Health research requires high-quality data, and population-based health research comes with specific opportunities and challenges. Electronic data collection can mitigate some of the challenges of working with large populations in multiple, sometimes difficult to reach, locations. OBJECTIVE To discuss the opportunities, challenges, and...

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire p...

Background Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI)...

By September 2022, more than 600 million cases of SARS-CoV-2 infection have been reported globally, resulting in over 6.5 million deaths. COVID-19 mortality risk estimators are often, however, developed with small unrepresentative samples and with methodological limitations. It is highly important to develop predictive tools for pulmonary embolism...

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first...

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria...

Background To reduce the high HIV incidence among key populations in Indonesia, we implemented a clinical pathway for screening, diagnosis and treatment of acute HIV infection (AHI) in sexual health clinics in Jakarta and Bali. This paper presents a cohort profile and analysis of baseline data on the study uptake, diagnostic yield, and estimated AH...

Background: Molnupiravir and nirmatrelvir-ritonavir (Paxlovid) are oral antivirals that have been proposed as treatments for patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, adaptive platform trial, several potential treatments for patients hospitalised with COVID-19 pneumonia were evaluated. Molnupi...

Background The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens, but data remain limited in many low and middle-income countries including Indonesia. Methods We systematically searched Embase, PubMed and Global Health Database and three...

Background The clinical management of leprosy is complicated by leprosy reactions (LR) causing irreversible nerve damage and disabilities. LR often require long-term use of corticosteroids causing serious side effects. Adjunct host-directed therapy (HDT) is a potentially attractive strategy in leprosy to prevent LR and associated immunopathology, m...

Indonesia has the third highest number of tuberculosis (TB) patients infected with Mycobacterium tuberculosis ( MTB ) Lineage 1 (L1). Most of these MTB L1 cases can be found in Indonesia’s remote easternmost province of Papua, one of Indonesia’s most underdeveloped provinces with a particularly high burden for TB. In this study, we sequenced and de...

Background COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory sy...

A strong and effective COVID-19 and future pandemic responses rely on global efforts to carry out surveillance of infections and emerging SARS-CoV-2 variants and to act accordingly in real time. Many countries in Southeast Asia lack capacity to determine the potential threat of new variants, or other emerging infections. Funded by Wellcome, the Sou...

Antimicrobial Surveillance

Background Little is known about diagnostic and antibiotic use practices in low and middle-income countries (LMICs) before and during COVID-19 pandemic. This information is crucial for monitoring and evaluation of diagnostic and antimicrobial stewardships in healthcare facilities. Methods We linked and analyzed routine databases of hospital admiss...

Background Limited data exist from southeast Asia on the impact of SARS-CoV-2 variants and inactivated vaccines on disease severity and death among patients hospitalised with COVID-19. Methods A multicentre hospital-based prospective cohort was enrolled from September 2020 through January 2023, spanning pre-delta, delta, and omicron periods. The p...

Background Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV. Methods We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort...

Objective This study investigated the association of plasma microRNAs before and during antiretroviral therapy (ART) with poor CD4 ⁺ T-cell recovery during the first year of ART. Design MicroRNAs were retrospectively measured in stored plasma samples from people with HIV (PWH) in sub-Saharan Africa who were enrolled in a longitudinal multicountry...

Existing literature has portrayed numerous challenges that healthcare workers (HCWs) faced during the COVID-19 pandemic, such as heightened risks of transmission against the scarcity of protective equipment, burgeoning workload, and emotional distress, to name a few. However, most studies explored HCWs' experiences at the individual level rather th...

Objective Blood culture (BC) sampling is recommended for all suspected sepsis patients prior to antibiotic administration. We examine barriers and enablers to BC sampling in three Southeast Asian countries. Design A Theoretical Domains Framework (TDF)-based survey, comprising a case scenario of a patient presenting with community-acquired sepsis a...

Skin diseases are a major public health concern in Indonesia, although access to specialized care in remote areas is limited. We initiated a low-cost teledermatology service in Sumba, a remote island in eastern Indonesia. Eighteen healthcare workers (HCWs) at five primary healthcare centers received training to manage common skin diseases and submi...

Importance Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. Objectives To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary obj...

Introduction Delays in diagnosis and treatment contribute to high mortality of tuberculous meningitis (TBM). We studied TBM patient pathways including delays to diagnosis, and their alignment with available diagnostic services in Indonesia. Methods We recruited patients admitted to two tertiary hospitals who started TBM treatment. Participants or...

Background Adjunctive corticosteroids are widely used to treat HIV-associated tuberculous meningitis despite limited data supporting their safety and efficacy. Methods We conducted a randomized double-blind placebo-controlled trial in HIV-positive adults (≥18 years) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomized...

Background: The impact of the COVID-19 pandemic on tuberculosis control in high-burden countries has not been adequately assessed. We aimed to estimate the impact of the COVID-19 pandemic on the national tuberculosis programme in Indonesia, in association with indicators of human development and health-system capacity across all 514 districts in 3...

Background Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. Methods Here, w...

Introduction During the COVID-19 pandemic, healthcare workers (HCWs) faced unprecedented challenges, increased workload, and often struggled to provide healthcare services. We explored the experiences faced by HCWs working at primary healthcare centers (PHCs) and hospitals across urban and rural settings in Indonesia. Methods As part of a larger m...

Objective: To identify and summarize existing global knowledge gaps on antimicrobial resistance (AMR) in human health, focusing on the WHO bacterial priority pathogens, M. tuberculosis and selected fungi. Methods: We conducted a scoping review of grey and peer-reviewed literature, published in English from January 2012 through December 2021, tha...

Background: Cellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusi...

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these co...

Background: Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic and haemodynamic effects. Methods: In this randomised, controlled, open-label trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly al...

Background There are limited measures of the impact of the COVID-19 pandemic on tuberculosis (TB) control in high-burden countries like Indonesia. Methods We analysed district-level data of reported TB cases, treatment and deaths, COVID-19 incidence and mortality, health care capacity, economic status, education level, and public health development...

Background Cellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusin...

Background: Case-based surveillance of antimicrobial resistance (AMR) provides more actionable data than isolate- or sample-based surveillance. We developed A Clinically Oriented antimicrobial Resistance surveillance Network (ACORN) as a lightweight but comprehensive platform, in which we combine clinical data collection with diagnostic stewardship...

Background Low-dose corticosteroids have been shown to reduce mortality for hypoxic COVID-19 patients requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. Methods This ra...

Real-world data on heterologous boosting with messenger RNA (mRNA)-1273 (Moderna) after inactivated COVID-19 vaccination are limited. We report mRNA-1273 boosting in heavily SARS-CoV-2–exposed Indonesian health-care workers who received a two-dose CoronaVac 6 months prior. Between August and November 2021, we measured SARS-CoV-2 spike-specific IgG...

Background Blood culture (BC) sampling is recommended for all suspected sepsis patients prior to antibiotic administration. Here, we aimed to identify barriers and enablers to BC sampling in three Southeast Asian countries. Methods We conducted a systematic review of studies evaluating barriers/enablers to BC sampling from 1900 to 2020 globally (PR...

Introduction Antimicrobial stewardship (AMS) is an important strategy to control antimicrobial resistance. Resources are available to provide guidance for design and implementation of AMS programmes, however these may have limited applicability in resource-limited settings including those in Asia. This scoping review aims to identify context-specif...

Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised wit...

The burden of antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs) is largely unknown. Here, we evaluate attributable mortality of AMR infections in Indonesia. We used routine databases of the microbiology laboratory and hospital admission at Dr. Wahidin Sudirohusodo Hospital, a tertiary-care hospital in South Sulawes...

Standard diagnosis of SARS-CoV-2 by nasopharyngeal swab (NPS) and real-time reverse transcriptase-polymerase chain reaction (PCR) requires a sophisticated laboratory, skilled staff, and expensive reagents that are difficult to establish and maintain in isolated, low-resource settings. In the remote setting of tropical Sumba Island, eastern Indonesi...

Background We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with...

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World...

Background Antimicrobial resistance (AMR) is one of the leading global public health threats of the 21st Century. Antimicrobial stewardship (AMS) programmes have been shown to improve antibiotic use and clinical outcomes in high-income settings, but context-specific evidence is lacking on the value and effectiveness of current AMS programmes in low...

Chikungunya virus (CHIKV) is recognized but rarely considered as a cause of central nervous system infection in endemic areas. A total of 244 patients with acute meningoencephalitis in Indonesia were retrospectively tested to identify whether any CHIKV infection was associated with neurological manifestations, especially in provinces known for CHIK...

Introduction To accelerate the response to the public health threat by antimicrobial resistance (AMR), the WHO is developing a Global Research Agenda for AMR in the human health sector that aims to provide a global and transparent assessment of priority knowledge gaps related to critical bacteria—including Mycobacterium tuberculosis— and fungi that...

Introduction: Worldwide, the 33 recognised megacities comprise approximately 7% of the global population, yet account for 20% COVID-19 deaths. The specific inequities and other factors within megacities that affect vulnerability to COVID-19 mortality remain poorly defined. We assessed individual, community-level and healthcare factors associated w...

Objective: In a multicountry prospective cohort of persons with HIV from six countries between 2007 and 2015, we evaluated long-term outcomes of first-line non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART), and risk factors for loss-to-follow-up, mortality, virological failure, and incomplete CD4+ T-cell recovery....

Background: There is a paucity of data regarding blood culture utilization and antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs). In addition, there has been a concern for increasing AMR infections among COVID-19 cases in LMICs. Here, we investigated epidemiology of AMR bloodstream infections (BSI) before and duri...

Objectives Antibiotic overuse is one of the main drivers of antimicrobial resistance (AMR), especially in low-income and middle-income countries. This study aimed to understand the perceptions and views towards AMR, antibiotic prescribing practice and antimicrobial stewardship (AMS) among hospital physicians in Jakarta, Indonesia. Design Cross-sec...

Background A major driver of antimicrobial resistance (AMR) and poor clinical outcomes is suboptimal antibiotic use, although data are lacking in low-resource settings. We reviewed studies on systemic antibiotic use (WHO ATC/DDD category J01) for human health in Indonesia, and synthesized available evidence to identify opportunities for interventio...

Objectives To describe the use of bacterial cultures, and the etiology and antibiotic susceptibility of common high-priority bacteria isolated from hospitalized patients in Jakarta, Indonesia. Methods We conducted a hospital-wide cross-sectional study of all inpatients receiving systemic antibiotic treatment (WHO ATC J01) in six hospitals in 2019,...

Introduction A major driver of antimicrobial resistance (AMR) and poor clinical outcomes is suboptimal antibiotic use, although data are lacking in low-resource settings. We reviewed studies on systemic antibiotic use (WHO ATC/DDD category J01) for human health in Indonesia, and synthesized available evidence to identify opportunities for intervent...

p>Background: Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hosp...

Background Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospit...

Background: The inactivated whole-virus vaccine CoronaVac (SinoVac) is the COVID-19 vaccine most administered worldwide. However, data on its immunogenicity and reactogenicity to heterologous boosting with mRNA vaccines are lacking. Methods: In a cohort of hospital staff in Jakarta, Indonesia, who received two-dose CoronaVac six months prior (media...

Background: When the novel coronavirus – SARS-CoV-2 – started to spread globally, there was a call for social and behavioral scientists to conduct research to explore the wider socio-cultural contexts of coronavirus disease 2019 (COVID-19), to understand vulnerabilities, as well as to increase engagement within communities to facilitate adoption of...

PIIS14733099210056 5X.pdf

Background The 33 recognized megacities comprise approximately 7% of the global population, yet account for 20% COVID-19 deaths. The specific inequities and other factors within megacities that affect vulnerability to COVID-19 mortality remain poorly defined. We assessed individual, community-level and health care factors associated with COVID-19-r...

Background Aspirin has been proposed as a treatment for COVID-19 on the basis of its anti-thrombotic properties. We aimed to evaluate the efficacy and safety of aspirin in patients admitted to hospital with COVID-19. Methods In this randomised, controlled, open-label, platform trial, several possible treatments were compared with usual care in pa...

The World Health Organization (WHO) living guideline on drugs to prevent COVID-19 has recently advised that ongoing trials evaluating hydroxychloroquine in chemoprophylaxis should stop. The WHO guideline cites “high certainty” evidence from randomised controlled trials (RCTs) that hydroxychloroquine prophylaxis does not reduce mortality and does no...

Background The public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of SARS-CoV-2 transmission, COVID-19 dise...

Objectives: Antibiotic overuse is one of the main drivers of antimicrobial resistance (AMR), especially in low and middle-income countries. This study aimed to gain an understanding of perceptions, views, and practices regarding AMR, antibiotic prescribing, and stewardship (AMS) among hospital physicians in Jakarta, Indonesia. Design: cross-section...

Objectives: To investigate the safety and pharmacokinetic profiles of long-acting injectable pre-exposure prophylaxis (LAI PrEP), notably cabotegravir (CAB-LA) and rilpivirine (RPV-LA), for the prevention of human immunodeficiency virus-1 (HIV-1) infection. Methods: Eligible randomized trials of LAI PrEP in HIV-uninfected and/or healthy patients we...

Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings We develop a mathematical model of SARS-Co...

Background: Aspirin has been proposed as a treatment for COVID-19 on the basis of its antithrombotic properties. Methods: In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either...

Background Routine microbiology results are a valuable source of antimicrobial resistance (AMR) surveillance data in low- and middle-income countries (LMICs) as well as in high-income countries. Different approaches and strategies are used to generate AMR surveillance data. Objectives We aimed to review strategies for AMR surveillance using routin...

Background: Colchicine has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory actions. Methods: In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to eith...

There is a clear need to improve host-directed therapy for tuberculous meningitis (TBM), the most severe and deadly manifestation of tuberculosis. Corticosteroids represent the only host-directed therapy of proven benefit in TBM, yet their effect is modest, the mechanism by which they reduce mortality is unknown, and there is evidence for heterogen...