The American Journal of Tropical Medicine and Hygiene - Current Issue

Maternal rectovaginal colonization is the major risk factor for early-onset neonatal sepsis due to Group B Streptococcus (GBS), a major cause of early life morbidity and mortality. Transmission generally occurs perinatally from colonized mothers to infants. Vaccines targeting a subset of GBS serotypes are under development, but GBS epidemiology remains poorly understood in many African nations. We performed a cross-sectional study of GBS colonization among pregnant women at two sites in Botswana, a country with minimal prior GBS carriage data. We found a rectovaginal colonization rate of 19%, comparable with studies in other regions; however, we also noted a striking predominance of serotype V (> 45% of strains). Although further studies are required to delineate the burden of invasive GBS disease in Botswana and the generalizability of type V epidemiology, these data provide a useful baseline for understanding the potential local impact of GBS prevention strategies, including vaccines.

This study aimed to identify recurrent acute rheumatic fever (ARF) episodes which occurred despite adherence to prophylactic benzathine penicillin G (BPG). Data from Australia’s Northern Territory were analyzed; ARF recurrences between 2012 and 2017 diagnosed while the person was prescribed BPG were identified. Days at risk (DAR)—median and interquartile range—preceding ARF onset were calculated. The timing of BPG doses was examined for individuals with no DAR. One hundred sixty-nine ARF recurrences were analyzed; median DAR in the previous 8 weeks before ARF onset was 29. Most recurrences occurred following > 7 DAR (87%). Eight recurrences (5%) occurred despite no DAR; all were aged less than 16 years at the time of their recurrence/s. Recurrent ARF most commonly occurs after delayed BPG doses, but in some cases, receiving every prescribed BPG dose on time did not prevent recurrent ARF. A method to identify high-risk individuals before recurrent ARF is needed.

Understanding antibiotic use may help predict emergence of antimicrobial resistance. We evaluated antibiotic prescription trends in rural Burkina Faso, where little is known about antibiotic consumption. Antibiotic prescription data for 20 communities were extracted through record review in six primary health-care facilities serving the communities. The number of antibiotic prescriptions per child-year was calculated using population-based census data from the communities. A total of 1,444 antibiotic prescriptions were made from March to June 2017 among 3,401 children in the communities. The frequency of antibiotic prescription was 1.70 prescriptions per child-year (95% CI: 1.61–1.79). Penicillins were the most common (1.04 prescriptions per child-year, 95% CI: 1.01–1.06), followed by sulfonamides (0.69 prescriptions per child-year, 95% CI: 0.67–0.71) and macrolides (0.38 prescriptions per child-year, 95% CI: 0.37–0.40). Continued monitoring of antibiotic consumption in diverse settings will be important to understand the potential for emergence of antibiotic resistance.

Clinical syndromes associated with Bartonella quintana infection can be insidious and difficult to diagnose for multiple reasons. Clinically, B. quintana can manifest as asymptomatic bacteremia or with subtle subacute constitutional symptoms. Second, it is a fastidious organism that is difficult to identify using traditional culture methods. Last, the body lice vector of B. quintana transmission is likely not uncommon in most patients affected, who are homeless and of low socioeconomic status. Therefore, barriers in seeking medical care and financial constraints for medications are important considerations. The mainstay of literature surrounding B. quintana endocarditis is from Europe and the developing nations. Herein, we describe a case of native valve endocarditis secondary to B. quintana in a homeless male with preexisting valvular disease and undertake a comprehensive literature review of documented B. quintana endocarditis in North America.

A 56-year-old female goat herder had scrub typhus that persisted after receiving doxycycline for 5 days. Her symptoms continued, prompting us to perform further examinations that revealed coinfection of Q fever and scrub typhus via molecular and serological testing. We also isolated Orientia tsutsugamushi using BALB/c mice and L929 cells.

In this diagnostic accuracy study, we evaluated data from 135 febrile patients from Chiang Rai, to determine the optimal optical density (OD) cutoffs for an in-house scrub typhus IgM ELISA. Receiver operating characteristic curves were generated using a panel of reference assays, including an IgM immunofluorescence assay (IFA), PCR, in vitro isolation, presence of an eschar, or a combination of these. Altogether, 33 patients (24.4%) were diagnosed as having scrub typhus. Correlation between positivity by IFA and increasing OD values peaked at a cutoff of 2.0, whereas there was little association between positivity by culture or eschar with increasing ELISA cutoffs—cutoffs of 3.0 and 4.0 were demonstrated to be optimal for the total absorbance of the OD at dilutions 1:100, 1:400, 1:1,600, and 1:6,400, for admission and convalescent samples, respectively. The optimal cutoff at a 1:100 dilution was found to be between 1.85 and 2.22 for admission samples and convalescent-phase samples, respectively. Sensitivities for the cutoffs varied from 57.1% to 90.0% depending on the reference test and sample timing, whereas specificities ranged from 85.2% to 99.0%. We therefore recommend a cutoff of around 2.0, depending on the sensitivity and specificity desired in clinical or epidemiological settings. The results demonstrate the ELISA to be a valuable diagnostic tool, suitable for use in resource-limited endemic regions, especially when used in combination with other diagnostic modalities such as the presence of an eschar.

Latent tuberculosis infection (LTBI) remains the main source of new active tuberculosis (TB) cases worldwide. Household close contacts (HCCs) are at high risk of acquiring LTBI and subsequent development of TB. In this study, we aim to identify risk factors associated with LTBI in HCCs of TB patients living in a low TB-incidence setting. Our results revealed that HCCs who are aged more than 50 years (OR = 4.05) and overweight (OR = 15.3) are at higher risk of acquiring LTBI. None of these LTBI household contacts progressed to active TB. These findings suggest that HCCs who are young adults and children with normal and low body mass index are less likely to acquire LTBI after exposure to TB patients, even in low TB-incidence settings.

Type 1 reactions, characterized by increasing lesion erythema, pain, and nerve damage, commonly complicate leprosy. Dapsone hypersensitivity syndrome (DHS) is a potentially fatal reaction occurring 6–8 weeks into dapsone therapy. We present a case of intercurrent Type 1 reaction and DHS in a multibacillary leprosy patient recently started on multidrug treatment.

Substandard and falsified medicines pose significant risks to global health, including increased deaths, prolonged treatments, and growing drug resistance. Antimalarials are one of the most common medications to be of poor quality in low- and middle-income countries. We assessed the health and economic impact of substandard and falsified antimalarials for children less than 5 years of age in the Democratic Republic of the Congo, which has one of the world’s highest malaria mortality rates. We developed an agent-based model to simulate patient care-seeking behavior and medicine supply chain processes to examine the impact of antimalarial quality in Kinshasa province and Katanga region. We simulated the impact of potential interventions to improve medicinal quality, reduce stockouts, or educate caregivers. We estimated that substandard and falsified antimalarials are responsible for $20.9 million (35% of $59.6 million; 95% CI: $20.7–$21.2 million) in malaria costs in Kinshasa province and $130 million (43% of $301 million; $129–$131 million) in malaria costs in the Katanga region annually. If drug resistance to artemisinin were to develop, total annual costs of malaria could increase by $17.9 million (30%; $17.7–$18.0 million) and $73 million (24%; $72.2–$72.8 million) in Kinshasa and Katanga, respectively. Replacing substandard and falsified antimalarials with good quality medicines had a larger impact than interventions that prevented stockouts or educated caregivers. The results highlight the importance of improving access to good quality antimalarials to reduce the burden of malaria and mitigate the development of antimalarial resistance.

Despite recent large-scale investments, malaria remains a major public health concern. Few studies have examined congenital malaria, defined as the presence of malaria parasitemia within the first 7 days of life, in endemic areas. This study aimed to determine the prevalence, to describe the clinical presentation, and to examine factors associated with congenital malaria in newborns aged up to 7 days attending Tororo General Hospital in Uganda. A total of 261 mother/baby pairs were recruited in this cross-sectional study. Giemsa-stained thick blood smears for malaria parasites and rapid malaria diagnostic tests were performed on capillary blood samples from all newborns and mothers, as well as on placental and cord samples from newborns delivered in the hospital. The prevalence of congenital malaria in the newborns was 16/261 (6.1%). No single clinical feature was associated with congenital malaria. However, there were associations between congenital malaria and maternal parasitemia (P < 0.001), gravidity of one (P = 0.03), maternal age < 19 years (P = 0.01), cord blood parasitemia (P = 0.01), and placental malaria (P = 0.02). In conclusion, congenital malaria is not rare in Uganda and there are no obvious clinical features associated with it in the newborn. Based on these findings, we recommend strengthening malaria prevention during pregnancy to reduce the occurrence of congenital malaria in newborns.

Plasmodium malariae is a neglected malaria parasite. It has wide geographic distribution and, although often associated with mild malaria, is linked to a high burden of anemia and nephrotic syndromes. Here, we report a cohort study conducted in the Kanchanaburi Province of Thailand during May 2013–June 2014 in which P. malariae infection was detected. Of the 812 study participants, two were found to be infected with P. malariae. One had an infection that led to acute malaria, but the other was positive for P. malariae at multiple visits during the study and apparently had chronic asymptomatic infection. Such persistent infection may explain how P. malariae has been able to thrive at very low prevalence and represents a challenge for malaria elimination.

Multidrug-resistant Plasmodium falciparum malaria on the Cambodia–Thailand border is associated with working in forested areas. Beyond broad recognition of “forest-going” as a risk factor for malaria, little is known about different forest-going populations in this region. In Oddar Meanchey Province in northwestern Cambodia, qualitative ethnographic research was conducted to gain an in-depth understanding of how different populations, mobility and livelihood patterns, and activities within the forest intersect with potentiate malaria risk and impact on the effectiveness of malaria control and elimination strategies. We found that most forest-going in this area is associated with obtaining precious woods, particularly Siamese rosewood. In the past, at-risk populations included large groups of temporary migrants. As timber supplies have declined, so have these large migrant groups. However, groups of local residents continue to go to the forest and are staying for longer. Most forest-goers had experienced multiple episodes of malaria and were well informed about malaria risk. However, economic realities mean that local residents continue to pursue forest-based livelihoods. Severe constraints of available vector control methods mean that forest-goers have limited capacity to prevent vector exposure. As forest-goers access the forest using many different entry and exit points, border screening and treatment interventions will not be feasible. Once in the forest, groups often converge in the same areas; therefore, interventions targeting the mosquito population may have a potential role. Ultimately, a multisectoral approach as well as innovative and flexible malaria control strategies will be required if malaria elimination efforts are to be successful.

Prevalence of and risk factors associated with polymerase chain reaction (PCR)-determined Plasmodium falciparum positivity were assessed on day 3 after initiation of treatment, pre-implementation and up to 8 years post-deployment of artemether–lumefantrine as first-line treatment for uncomplicated malaria in Bagamoyo district, Tanzania. Samples originated from previously reported trials conducted between 2006 and 2014. Cytochrome b-nested PCR was used to detect malaria parasites from blood samples collected on a filter paper on day 3. Chi-square and McNemar chi-squared tests, logistic regression models, and analysis of variance were used as appropriate. Primary outcome was based on the proportion of patients with day 3 PCR-determined P. falciparum positivity. Overall, 256/584 (43.8%) of screened patients had day 3 PCR-determined positivity, whereas only 2/584 (0.3%) had microscopy-determined asexual parasitemia. Day 3 PCR-determined positivity increased from 28.0% (14/50) in 2006 to 74.2% (132/178) in 2007–2008 and declined, thereafter, to 36.0% (50/139) in 2012–2013 and 27.6% (60/217) in 2014. When data were pooled, pretreatment microscopy-determined asexual parasitemia ≥ 100,000/µL, hemoglobin < 10 g/dL, age < 5 years, temperature ≥ 37.5°C, and year of study 2007–2008 and 2012–2013 were significantly associated with PCR-determined positivity on day 3. Significant increases in P. falciparum multidrug resistance gene 1 N86 and P. falciparum chloroquine resistant transporter K76 across years were not associated with PCR-determined positivity on day 3. No statistically significant association was observed between day 3 PCR-determined positivity and PCR-adjusted recrudescence. Day 3 PCR-determined P. falciparum positivity remained common in patients treated before and after implementation of artemether–lumefantrine in Bagamoyo district, Tanzania. However, its presence was associated with pretreatment characteristics. Trials registration numbers: NCT00336375, ISRCTN69189899, NCT01998295, and NCT02090036.

Hyperreactive malarial splenomegaly syndrome (HMSS) is a rare cause of splenomegaly in the Western world. Hyperreactive malarial splenomegaly syndrome is caused by an aberrant immunological response to chronic malaria exposure in endemic areas. Revised Fakunle’s criteria may be helpful for diagnosis: persistent splenomegaly (> 10 cm below the costal margin), increased anti-Plasmodium antibodies, increased IgM levels, exclusion of other causes of splenomegaly or malignancy, and a favorable response to antimalarial treatment. We describe the case of a 16-year-old patient, who recently arrived in Belgium from Guinea with a history of splenomegaly and B symptoms in whom HMSS diagnosis was achieved, thanks to the loop-mediated isothermal amplification method. To our knowledge, this is also the first described case treated by dihydroartemisinin/piperaquine.

Plasmodium falciparum infection causes febrile illness and severe disease with multiple organ failure and death when treatment is delayed. Antipyretic treatment is standard, and inducing hypothermia has been proposed to protect the brain in cerebral malaria. Here, we investigated the temperature dependence of asexual-stage parasite development and parasite multiplication in vitro. Plasmodium falciparum laboratory strain TM267 was incubated for 2 hours (short exposure) or 48 hours (continuous exposure) at different temperatures (32°C, 34°C, 35°C, 38°C, 39°C, and 40°C). The starting parasite developmental stage (ring, trophozoite, or schizont) varied between experiments. The parasite multiplication rate (PMR) was reduced under both hyper- and hypothermic conditions; after continuous exposure, the mean PMR ± SD was 9.1 ± 1.2 at 37°C compared with 2.4 ± 1.8 at 32°C, 2.3 ± 0.4 at 34°C, and 0.4 ± 0.1 at 40°C (P < 0.01). Changes in PMR were not significant after 2-hour exposure at temperatures ranging from 32°C to 40°C. Morphological changes in parasite cytoplasm and nucleus could be observed after long exposure to low or high temperature. After 48-hour incubation, rosette formation (≥ 2 uninfected red blood cells bound to infected red blood cells) was decreased at 34°C or 39°C compared with that at 37°C. In conclusion, both hyper- and hypothermia reduce PMR and delay erythrocytic stage development of P. falciparum, subsequently reducing rosette formation.

Current malaria rapid diagnostic tests (RDTs) contain antibodies against Plasmodium falciparum–specific histidine-rich protein 2 (PfHRP2), Plasmodium lactate dehydrogenase (pLDH), and aldolase in various combinations. Low or high parasite densities/target antigen concentrations may influence the accuracy and sensitivity of PfHRP2-detecting RDTs. We analyzed the SD Bioline Malaria Ag P.f/Pan RDT performance in relation to P. falciparum parasitemia in Madagascar, where clinical Plasmodium vivax malaria exists alongside P. falciparum. Nine hundred sixty-three samples from patients seeking care for suspected malaria infection were analyzed by RDT, microscopy, and Plasmodium species–specific, ligase detection reaction-fluorescent microsphere assay (LDR-FMA). Plasmodium infection positivity by these diagnostics was 47.9%, 46.9%, and 58%, respectively. Plasmodium falciparum–only infections were predominant (microscopy, 45.7%; LDR-FMA, 52.3%). In all, 16.3% of P. falciparum, 70% of P. vivax, and all of Plasmodium malariae, Plasmodium ovale, and mixed-species infections were submicroscopic. In 423 P. falciparum mono-infections, confirmed by microscopy and LDR-FMA, the parasitemia in those who were positive for both the PfHRP2 and pan-pLDH test bands was significantly higher than that in those who were positive only for the PfHRP2 band (P < 0.0001). Plasmodium falciparum parasitemia in those that were detected as P. falciparum–only infections by microscopy but P. falciparum mixed infections by LDR-FMA also showed similar outcome by the RDT band positivity. In addition, we used varying parasitemia (3–0.0001%) of the laboratory-maintained 3D7 strain to validate this observation. A positive pLDH band in high P. falciparum–parasitemic individuals may complicate diagnosis and treatment, particularly when the microscopy is inconclusive for P. vivax, and the two infections require different treatments.

Low-density malaria infections are a source of human morbidity in endemic settings and potentially contribute to ongoing malaria transmission. Conventional rapid diagnostic tests (RDTs) were designed to detect clinically relevant parasite and antigen levels, but it is largely unknown what proportion of parasite (and antigen positive) infections are missed by conventional RDTs. Furthermore, RDTs can also provide false positives from lingering histidine-rich protein 2 (HRP2) antigenemia from a past infection. We analyzed 207 samples from Angolan outpatients with a bead-based HRP2 antigen assay and by qRT-PCR for the presence of parasite nucleic acids. Among patients HRP2 positive but negative by conventional RDT, the rate of quantitative reverse transcription-PCR (qRT-PCR) positivity was 45% (95% CI: 35–56%), with a median parasitemia of 3.4 parasites/µL (interquartile range: 0.14–4.8). Only 15% (7–26%) of HRP2-negative samples were found to have parasite nucleic acids. A substantial proportion of persons with blood HRP2 antigen concentrations not detected by the conventional RDT were found to have evidence of active infection, but at low parasite density levels.

Cystic echinococcosis (CE) is a common, chronic, and endemic zoonotic disease usually localized in a single organ; multivisceral cases are rare, especially outside the liver or lung. Here, we describe an unusual case of a 43-year-old Tibetan man with echinococcosis of the infratemporal fossa, heart, liver, pancreas, abdomen, and pelvic cavity. He only presented with diminished vision of the left eye, especially when chewing. Computed tomography and magnetic resonance imaging revealed multivisceral CE. The patient underwent surgery for the excision of a cyst in the infratemporal fossa, as well as chemotherapy, and the diagnosis was confirmed by histopathological examination. The diagnosis, clinical features, treatment, and follow-up in this case are discussed. In areas with high echinococcosis prevalence, examination by full imaging is necessary for an accurate diagnosis, especially in cases of atypical localization. Chemotherapy for treatment, as well as prophylaxis against recurrence, can be effective when surgery is not possible.

Mass drug administration (MDA) with ivermectin must reach a high treatment coverage (90% of the eligible population) if onchocerciasis is to be eliminated. Questions have been raised as to whether reported treatment figures reaching such high coverage are reliable. Sample surveys are proposed as the method of choice for “validating” reported coverage figures. The purpose of this study was to compare the district-level MDA coverage reported by programs with contemporaneous surveys of randomly selected respondents living in those same districts. Over an 8-year period, 19,219 households were selected using multistage random sampling; 38,433 adult male and female heads of those households were asked about their recent ivermectin MDA treatment experience. District coverage reports were considered “accurate” if they fell within the 95% CIs determined by the corresponding district’s survey. Ninety-eight treatment rounds were evaluated over an 8-year period. Overall, the reported coverage of 96.5% (range: 68–100%) was significantly higher than the 92.5% surveyed coverage (range: 62.1–99.6%, 95% CI: 91.9–93.2%). However, only 20% of districts reported significantly higher coverage than surveys, 68% of district program reports were judged as accurate, and 12% of districts reported significantly lower coverage figures than their corresponding surveys. Eighty-eight percent of districts reported coverage ≥ 90% threshold for success, compared with 97% of surveys that included 90% in their 95% CIs. We conclude that when analyzed statistically at the district level, most surveys verified the reported coverage.

Many parasitic infections have different presenting features in endemic individuals (ENDs) and immunologically naive temporary residents (TRs). Temporary residents with loiasis often display acute symptoms and hypereosinophilia, in contrast to a parasite-induced subclinical state in chronically infected ENDs. Few studies have examined differences in ENDs and TRs infected with the related filarial parasite Onchocerca volvulus. We identified 40 TRs and 36 ENDs with imported onchocerciasis at the National Institutes of Health between 1976 and 2016. All study subjects received an extensive pretreatment medical history, physical examination, and laboratory investigations. We performed additional parasite-specific serologic testing on stored patient sera. Asymptomatic infection occurred in 12.5% of TRs and no ENDs (P = 0.06). Papular dermatitis was more common in TRs (47.5% versus 2.7%, P < 0.001), whereas more pigmentation changes occurred in ENDs (41.7% versus 15%, P = 0.01). Only endemic patients reported visual disturbance (13% versus 0%, P = 0.03). One TR (3.3%) had onchocercal eye disease, compared with 22.6% of ENDs (P = 0.053). Absolute eosinophil counts (AECs) were similar in ENDs and TRs (P = 0.5), and one-third of subjects had a normal AEC. Endemic individuals had higher filarial-specific IgG4 and were more likely to be positive for IgG4 antibodies to Ov-16. Temporary residents and ENDs with imported O. volvulus infection presented with different dermatologic manifestations; ocular involvement occurred almost exclusively in ENDs. Unlike Loa loa, clinical differences appear not to be eosinophil-mediated and may reflect chronicity, intensity of infection, or the presence of Wolbachia in O. volvulus.