The American Journal of Tropical Medicine and Hygiene - Volume 103, Issue 2, August 2020

As of June 11, 2020, the Democratic Republic of the Congo (DRC) has reported 4,258 COVID-19 cases with 90 deaths. With other African countries, the DRC faces the challenge of striking a balance between easing public health lockdown measures to curtail the spread of SARS-CoV-2 and minimizing both economic hardships for large sectors of the population and negative impacts on health services for other infectious and noninfectious diseases. The DRC recently controlled its tenth Ebola virus disease (EVD) outbreak, but COVID-19 and a new EVD outbreak beginning on June 1, 2020 in the northwest Équateur Province have added an additional burden to health services. Although the epidemiology and transmission of EVD and COVID-19 differ, leveraging the public health infrastructures and experiences from coordinating the EVD response to guide the public health response to COVID-19 is critical. Building on the DRC’s 40 years of experience with 10 previous EVD outbreaks, we highlight the DRC’s multi-sectoral public health approach to COVID-19, which includes community-based screening, testing, contact-tracing, risk communication, community engagement, and case management. We also highlight remaining challenges and discuss the way forward for achieving control of both COVID-19 and EVD in the DRC.

Immediately after declaring COVID-19 as a pandemic, numerous wild conspiracy theories sprouted through social media. Pakistan is quite vulnerable to such conspiracy narratives and has experienced failures of polio vaccination programs because of such claims. Recently, two well-known political figures raised conspiracy theories against COVID-19 vaccines in Pakistan, stating that COVID-19 is a grand illusion and a conspiracy against Muslim countries. This theory is much discussed in the local community, supporting COVID-19 vaccine hesitancy. We urge healthcare authorities in Pakistan to take necessary measures against such claims before they penetrate to the general community. Anti-vaccine movements could undermine efforts to end the COVID-19 pandemic. We believe that ethical and responsible behavior of mass media, a careful advisory from the Pakistan Electronic Media Regulatory Authority, stern measures from healthcare authorities, effective maneuvers to increase public awareness on COVID-19, vigorous analysis of information by data or communications scientists, and publication of counter opinions from health professionals against such theories will go a long way in neutralizing such misleading claims. Because Pakistan is experiencing a large burden of disease, with a sharp rise in confirmed cases, immediate action is of paramount importance to eradicate any potential barriers to a future COVID-19 vaccination program.

As COVID-19 cases continue to increase globally, fragile health systems already facing challenges with health system infrastructure, SARS-CoV-2 diagnostic capacity, and patient isolation capabilities may be left with few options to effectively care for acutely ill patients. Haiti—with only two laboratories that can perform reverse transcriptase PCR for SARS-CoV-2, a paucity of hospital beds, and an exponential increase in cases—provides an example that underpins the need for immediate infrastructure solutions for the crisis. We present two COVID-19 treatment center designs that leverage lessons learned from previous outbreaks of communicable infectious diseases and provide potential solutions when caseload exceeds existing capacity, with and without access to SARS-CoV-2 testing. These designs are intended for settings in which health facilities and testing resources for COVID-19 are surpassed during the pandemic, are adaptable to local conditions and constraints, and mitigate the likelihood of nosocomial transmission while offering an option to care for hospitalized patients.

The newly discovered SARS-CoV-2 is the cause of COVID-19, including severe respiratory symptoms with an important lethality rate and high dissemination capacity. Considering the indigenous people of Brazil, it is feared that COVID-19 will spread to these communities, causing another stage of decimation. Despite advances in indigenous health care in the country, there are still many challenges due to the social vulnerability of this population, whose lands continue to be illegally exploited. Based on these considerations, this article discusses challenges in caring for the indigenous population in the context of the COVID-19 pandemic in Brazil.

Noma affects the most marginalized communities in the world, beginning as oral ulceration and rapidly progressing to orofacial gangrene. With a mortality rate estimated to be as high as 90% and with very few able to access treatment in its active phase, very little is understood about the disease. This retrospective review of patients treated by Facing Africa for deformity and functional impairment secondary to noma between May 2015 and 2019 highlights some of the difficulties encountered by those afflicted. Eighty new patients with historical noma defects were identified and were seen over the course of nine surgical missions, with notes providing valuable geographical, socioeconomic, and psychosocial information. The mean self-reported age of onset was 5 years and 8 months, with a median time of 18 years from onset to accessing treatment. Before intervention, 65% covered their face in public, 59% reported difficulty eating, 81% were unhappy with their appearance, and 71% experienced bullying. We aimed at emphasizing the significant burden, both psychologically and physically of noma, demonstrating the disparity between recent decades of progress in the well-being of Ethiopians in general and the access to health care and mental health support for some of those most in need.

Bed bugs (Cimex spp.) are common ectoparasites of humans. Their ubiquity across diverse human environments combined with their blood-feeding behavior creates an ideal interface for the transmission of pathogenic microbes. Despite this potential, the current dogma is that bed bugs are not vectors of any known infectious agents. However, this conclusion is based largely on the results of studies conducted before the advent of modern molecular biology and the resurgence of bed bugs on a global scale. More importantly, a small but compelling body of modern research suggesting that bed bugs can potentially vector some human pathogens exists but is often overlooked. This article critically examines the current classification of the bed bug as an insect that does not transmit disease agents. In doing so, it highlights key knowledge gaps that still exist in understanding the potential of bed bugs as pathogen vectors and outlines several arguments for why new research on the topic is necessary.

Our understanding of SARS-CoV-2, the virus responsible for coronavirus disease 2019 (COVID-19), its clinical manifestations, and treatment options continues to evolve at an unparalleled pace. This review sought to summarize the key literature regarding transmission, case definitions, clinical management, and the burden of COVID-19. Our review of the literature showed that SARS-CoV-2 was mainly transmitted via inhalation of respiratory droplets containing the virus and had a mean incubation period of 4–6 days. The commonly reported symptoms were fever (75.3% ± 18.7%) and cough (62.6% ± 17.7%) across the spectrum of clinical disease—mild, moderate, severe, and critical, but with the disease phenotype varying with severity. Categorization of these cases for home care or hospital management needs to be defined, with risk stratification accounting for the age of the patient and the presence of underlying comorbidities. The case definitions varied among countries, which could have contributed to the differences in the case fatality rates among affected countries. The severity and risk of death due to COVID-19 was associated with age and underlying comorbidities. Asymptomatic cases, which constitute 40–80% of COVID-19 cases are a considerable threat to control efforts. The presence of fever and cough may be sufficient to warrant COVID-19 testing, but using these symptoms in isolation will miss a proportion of cases. A clear definition of a COVID-19 case is essential for the management, treatment, and tracking of clinical illness, and to inform the quarantine measures and social distancing that can help control the spread of SARS-CoV-2.

The parasitic helminth infection neurocysticercosis (NCC) is the most common cause of adult-acquired epilepsy in the world. Despite the serious consequences of epilepsy due to this infection, an in-depth review of the distinct characteristics of epilepsy due to neurocysticercosis has never been conducted. In this review, we evaluate the relationship between NCC and epilepsy and the unique characteristics of epilepsy caused by NCC. We also discuss recent advances in our understanding of NCC-related epilepsy, including the importance of anti-inflammatory therapies, the association between NCC and temporal lobe epilepsy, and the recent discovery of biomarkers of severe epilepsy development in individuals with NCC and seizures.

On October 6, 2017, the Zambia Ministry of Health declared a cholera outbreak in Lusaka. By December, 1,462 cases and 38 deaths had occurred (case fatality rate, 2.6%). We conducted a case–control study to identify risk factors and inform interventions. A case was any person with acute watery diarrhea (≥ 3 loose stools in 24 hours) admitted to a cholera treatment center in Lusaka from December 16 to 21, 2017. Controls were neighbors without diarrhea during the same time period. Up to two controls were matched to each case by age-group (1–4, 5–17, and ≥ 18 years) and neighborhood. Surveyors interviewed cases and controls, tested free chlorine residual (FCR) in stored water, and observed the presence of soap in the home. Conditional logistic regression was used to generate matched odds ratios (mORs) based on subdistricts and age-groups with 95% CIs. We enrolled 82 cases and 132 controls. Stored water in 71% of case homes had an FCR > 0.2 mg/L. In multivariable analyses, those who drank borehole water (mOR = 2.4, CI: 1.1–5.6), had close contact with a cholera case (mOR = 6.2, CI: 2.5–15), and were male (mOR = 2.5, CI: 1.4–5.0) had higher odds of being a cholera case than their matched controls. Based on these findings, we recommended health education about household water chlorination and hygiene in the home. Emergency responses included providing chlorinated water through emergency tanks and maintaining adequate FCR levels through close monitoring of water sources.

The efficacy of commonly used antibiotics for treating severe cholera has been compromised over time because of the reduced antibiotic susceptibility. This study aimed to describe the rate of detection of Vibrio cholerae O1 from fecal samples and antimicrobial susceptibility profiles of V. cholerae O1 serotypes to commonly used antibiotics. During January 2000–December 2018, V. cholerae O1 was detected in fecal samples of 7,472 patients. Vibrio cholerae O1 Inaba serotype was predominant, ranging from 60% to 86% during the period 2000–2006 except for 2003 and 2005 when the Ogawa serotype was predominant. Later on, the Ogawa serotype became predominant from 2007 to 2015, fluctuating between 52% and 100%. However, in 2016 and 2017, isolation rates declined to 2% and 1%, respectively, but surged again to 75% in 2018. Nearly 100% of V. cholerae O1 strains were sensitive to tetracycline during 2000–2004. Thereafter, a declining trend of sensitivity was observed to be continued and dropped down to < 6% during 2012–2017 and again increased to 76% in 2018. Susceptibility to azithromycin and ciprofloxacin was nearly 100%, and susceptibility to cotrimoxazole and furazolidone was 01% throughout the study period. We also found the emergence of resistance to erythromycin in 2005 and sensitivity to cotrimoxazole in 2018. Thus, the rapid decline of the sensitivity of V. cholerae O1 to tetracycline and a reversed peak after 6 years need continued monitoring and reporting.

There is a paucity of data on Francisella tularensis in the Middle East and North Africa. This is the first countrywide study to determine the seroprevalence, spatial distribution, and risk factors for F. tularensis in Jordan. A total of 828 Jordanians were serologically tested for F. tularensis by ELISA. These individuals filled out a self-administered questionnaire to collect demographic and risk factor information. Bivariate and multivariate logistic regressions were performed to determine which variables are associated with seropositivity. The overall seroprevalence of F. tularensis was 7.7% (95% CI: 6.10–9.75). The bivariate analyses showed that age, region of residence, small ruminant ownership, and practicing horticulture were significantly associated with seropositivity, and these variables were controlled for in the multivariate analysis. The multivariate analysis showed an increased odds of seropositivity among individuals living in northern desert, middle, and northern highland areas, compared with individuals living in the drier southern area, as 7.27 (95% CI: 2.49–21.19), 3.79 (95% CI: 1.53–9.39), and 3.52 (95% CI: 1.45–388.55), respectively. Individuals owning a small ruminant had 1.86 (95% CI: 1.02–3.40) greater odds for seropositivity than individuals who do not own a small ruminant. Individuals practicing horticulture had 2.10 (95% CI: 1.20–3.66) greater odds for seropositivity than individuals who do not practice horticulture. This is the first study to address the seroprevalence of F. tularensis in Jordan and the Middle East. Further research is needed to identify clinical cases of tularemia in Jordan and to determine the circulating F. tularensis subspecies.

Blood cultures (BCs) detect an estimated 50% of typhoid fever cases. There is need for validated clinical criteria to define cases that are BC negative, both to help direct empiric antibiotic treatment and to better evaluate the magnitude of protection conferred by typhoid vaccines. To derive and validate a clinical rule for defining BC-negative typhoid fever, we assessed, in a cluster-randomized effectiveness trial of Vi-polysaccharide (ViPS) typhoid vaccine in Kolkata, India, 14,797 episodes of fever lasting at least 3 days during 4 years of comprehensive, BC-based surveillance of 70,865 persons. A recursive partitioning algorithm was used to develop a decision rule to predict BC-proven typhoid cases with a diagnostic specificity of 97–98%. To validate this rule as a definition for BC-negative typhoid fever, we assessed whether the rule defined culture-negative syndromes prevented by ViPS vaccine. In a training subset of individuals, we identified the following two rules: rule 1: patients aged < 15 years with prolonged fever accompanied by a measured body temperature ≥ 100°F, headache, and nausea; rule 2: patients aged ≥ 15 years with prolonged fever accompanied by nausea and palpable liver but without constipation. The adjusted protective efficacy of ViPS against clinical typhoid defined by these rules in persons aged ≥ 2 years in a separate validation subset was 33% (95% CI: 4–53%). We have defined and validated a clinical rule for predicting BC-negative typhoid fever using a novel vaccine probe approach. If validated in other settings, this rule may be useful to guide clinical care and to enhance typhoid vaccine evaluations.

We report a patient with risk factors for both microbial keratitis and endophthalmitis, which were initially challenging to distinguish. Cultures of corneal scrapings yielded several organisms, including an uncultivable Gram-negative rod, eventually identified as Kingella negevensis. Kingella negevensis is so named because most strains have been isolated in the Negev, a desert region of southern Israel. The epidemiology of K. negevensis remains incompletely understood. We found no other reports in the literature of this organism causing microbial keratitis.

Melioidosis is endemic in many rural areas in Southeast Asia where facilities for culture and identification of Burkholderia pseudomallei are often limited. We performed a prospective observational study in patients presenting with fever to Mahosot Hospital, the primary referral hospital in Laos, to establish whether the detection of abscesses on ultrasound could support a presumptive diagnosis of melioidosis. All patients underwent ultrasound examination to detect abscesses in the liver, spleen, prostate, or, if indicated, subcutaneous tissue. We enrolled 153 patients, including 18 patients with melioidosis. Of these, 11 (61%) had an abscess at one or more sites, including five (28%) with splenic and/or liver abscesses. Absence of abscesses cannot rule out melioidosis, but the positive predictive value of abscesses for melioidosis was high at 93% (88–96%). Therefore, in endemic areas, the presence of abscesses in febrile patients should prompt empiric antibiotic therapy for melioidosis even in the absence of culture confirmation.

Mass drug administration (MDA) with azithromycin (AZ) has been used successfully to control trachoma. However, several studies have shown that MDA with AZ has led to the emergence of resistance to AZ in Streptococcus pneumoniae. The emergence of resistance to AZ has also been observed when this antibiotic was combined with the antimalarials used for seasonal malaria chemoprevention (SMC). The development of antibiotic resistance, including resistance to AZ, is sometimes associated with the emergence of a bacterial clone that belongs to a specific serotype. We hypothesize that the increase in resistance of S. pneumoniae observed after 3 years of SMC with AZ might be associated with a change in the distribution of pneumococcal serotypes. Therefore, 698 randomly selected isolates from among the 1,468 isolates of S. pneumoniae obtained during carriage studies undertaken during an SMC plus AZ trial were serotyped. A polymerase chain reaction (PCR) multiplex assay using an algorithm adapted to the detection of the pneumococcal serotypes most prevalent in African countries was used for initial serotyping, and the Quellung technique was used to complement the PCR technique when necessary. Fifty-six serotypes were detected among the 698 isolates of S. pneumoniae. A swift appearance and disappearance of many serotypes was observed, but some serotypes including 6A, 19F, 19A, 23F, and 35B were persistent. The distribution of serotypes between isolates obtained from children who had received AZ or placebo was similar. An increase in AZ resistance was seen in several serotypes following exposure to AZ. Mass drug administration with AZ led to the emergence of resistance in pneumococci of several different serotypes and did not appear to be linked to the emergence of a single serotype.

Increasing antibiotic consumption has been shown to lead to increased antibiotic resistance selection. We evaluated the prevalence of antibiotic resistance in Streptococcus pneumoniae to commonly used antibiotic classes as well as correlations between resistance and antibiotic consumption at the individual and community levels in children aged 0–59 months in Nouna district, Burkina Faso. A population-based sample of 300 children aged 0–59 months was randomly selected from the most recent census in 18 communities in the Nouna Health and Demographic Surveillance Site. Caregivers were interviewed about children’s recent antibiotic use, and a nasopharyngeal swab was collected from each child. Nasopharyngeal swabs were processed using standard microbiological methods to determine pneumococcal carriage and resistance. Community-level antibiotic consumption was determined by record review from primary healthcare facilities, which routinely collect prescription data for children aged 0–59 months. Streptococcus pneumoniae was isolated from 101 (35.7%) nasopharyngeal samples. Among positive isolates, co-trimoxazole (75.6%) and tetracycline (69.3%) resistance was the most common, followed by oxacillin (26.7%) and azithromycin (9.9%). Recent antibiotic use was associated with decreased pneumococcal carriage (odds ratio 0.56, 95% CI: 0.33–0.93) at the individual level. There was no statistically significant relationship between antibiotic use and antibiotic resistance at the individual or community levels, although CIs were generally wide. The prevalence of antibiotic resistance to commonly used antibiotics was high in the study area. Expanding antimicrobial resistance surveillance in areas with little population-based data will be important for informing policy related to antibiotic use.

Patients with tuberculous meningitis (TBM) in any stage of the British Medical Research Council (BMRC) scale, if requiring mechanical ventilation (MV), are likely to have a poor outcome. We report the usefulness of BMRC, BMRC-MV, and BMRC-hydrocephalus (BMRC-HC) staging, and Haydarpasa Meningitis Severity Index (HAMSI) scoring in predicting the outcome of TBM. One hundred ninety-seven TBM patients were analyzed from a prospectively maintained TBM registry. The severity of meningitis was categorized using BMRC (stages I–III), BMRC-MV (I–IV [MV patients were grouped as stage IV]), and BMRC-HC (I–IV [BMRC stage III patients with hydrocephalus were grouped as stage IV]). Haydarpasa Meningitis Severity Index scoring was categorized as < 6 and ≥ 6. The outcome was defined at 6 months using the modified Rankin Scale (mRS) as death, poor (mRS score > 2), or good (mRS score ≤ 2). Forty-nine (25%) patients died. BMRC-mechanical ventilation stage IV had the highest predictive value for defining death, with a sensitivity of 88% and a specificity of 86%. About 81.7% of surviving patients had a good outcome at 6 months. BMRC-mechanical ventilation stages I–III had the highest predictive value for defining good outcome, with a sensitivity of 93% and a specificity of 61%. In TBM, BMRC-MV staging has the best predictive value for defining death and disability.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Transformation of Fonsecaea pedrosoi into muriform cells enhances the resistance against phagocytosis and elimination by host immune cells, and links to the chronicity of chromoblastomycosis. Here, we aim to determine whether the muriform cells can reproduce in tissue without reverse transformation into hyphal form by using an experimental nu/nu-BALB/c mouse model of chromoblastomycosis due to F. pedrosoi. During the whole 81-day observation period, most of the hyphal inocula had transformed into muriform cells at 75 days postinoculation and maintained as this parasitic morphology till 81 days postinoculation simultaneously with increased fungal loads in tissue and the worsening of footpad lesion. Scanning and transmitting electronic microscope examinations showed that the muriform cells obtained in tissue or induced in vitro can reproduce daughter cells by dividing, and, meanwhile, the daughter cells had the potential to produce buds and grow into hyphae reversely. Furthermore, exoenzyme examination suggested that the profile of exoenzymes constituted by muriform cells was quite different from that constituted by hyphae although the assay showed both of them had obvious metabolic activity. By contrast, most muriform cells in the footpad gradually transformed into the elongated hyphae without obvious infiltration of inflammatory cells during repeated intraperitoneal administration of cyclophosphamide (50 mg/kg, per every other day) from 50 to 80 days postinoculation. Therefore, we infer that F. pedrosoi can reproduce by dividing as muriform cells in mouse tissue, and the morphological transformation between hyphal form and muriform cells is possibly associated with the host immune status.

Clinical worsening or new manifestation of cryptococcal disease following initiation of anti-retroviral therapy (ART) in an HIV patient is a hallmark of cryptococcal immune reconstitution inflammatory syndrome (C-IRIS). However, it can be difficult to distinguish IRIS from worsening or new infection. Here, we present a case of severe C-IRIS involving multiple cerebellar, spinal, and intradural abscesses and spinal arachnoiditis 7 months after ART initiation in an AIDS patient with uncertain prior ART compliance. He had multiple prior episodes of cryptococcal meningitis with complications necessitating ventriculoperitoneal shunt placement and was on suppressive fluconazole when he developed worsening brain manifestations. He received empiric anti-cryptococcal re-induction without improvement. All cerebrospinal fluid cultures remained sterile, with negative Cryptococcus PCR testing, and his condition continued to worsen prior to corticosteroid initiation. Ultimately, C-IRIS was diagnosed by brain biopsy. This case demonstrates an extreme in severity of C-IRIS and in the timeline of presentation after ART initiation.