The American Journal of Tropical Medicine and Hygiene - Current Issue

Molecular data are required to improve our understanding of the epidemiology of leptospirosis in Africa and to identify sources of human infection. We applied molecular methods to identify the infecting Leptospira species and genotypes among patients hospitalized with fever in Tanzania and compared these with Leptospira genotypes detected among animals in Tanzania to infer potential sources of human infection. We performed lipL32 real-time PCR to detect the presence of pathogenic Leptospira in acute-phase plasma, serum, and urine samples obtained from study participants with serologically confirmed leptospirosis and participants who had died with febrile illness. Leptospira blood culture was also performed. In positive specimens, we performed species-specific PCR and compared participant Leptospira secY sequences with Leptospira reference sequences and sequences previously obtained from animals in Tanzania. We detected Leptospira DNA in four (3.6%) of 111 participant blood samples. We detected Leptospira borgpetersenii (one participant, 25.0%), Leptospira interrogans (one participant, 25.0%), and Leptospira kirschneri (one participant, 25.0%) (one [25%] undetermined). Phylogenetic comparison of secY sequence from the L. borgpetersenii and L. kirschneri genotypes detected from participants was closely related to but distinct from genotypes detected among local livestock species. Our results indicate that a diverse range of Leptospira species is causing human infection. Although our analysis suggests a close relationship between Leptospira genotypes found in people and livestock, continued efforts are needed to obtain more Leptospira genetic material from human leptospirosis cases to help prioritize Leptospira species and genotypes for control.

Acute Q fever is usually asymptomatic or is associated with a mild self-limited course and a favorable outcome. The occurrence of endocarditis during acute infection by Coxiella burnetii is an emerging clinical entity observed in adults that has been attributed to an autoimmune complication of early infection. Herein, we report the first case of a previously healthy 2-year-old child with endocarditis complicated by septic embolic stroke, in which the identified microbiological evidence was suggestive of acute rather than chronic C. burnetii infection. The development of endocarditis in this case occurred in the absence of any autoimmune reaction, but in the context of a very mild form of congenital heart disease, a small ventricular septal defect, which might serve as a predisposing factor for endocarditis. This case suggests that acute Q fever endocarditis may affect children as well and can be attributed not only to autoimmune mechanisms but also to a potential effect of the infectious agent per se on the cardiac endothelium in patients with underlying heart defects, regardless of their severity.

Leprosy is a rare, chronic granulomatous disease, and India accounts for two-thirds of the new cases reported worldwide. Hypercalcemia is a rare complication of granulomatous disease. Here, we report a case of an older adult patient with leprosy and type I lepra reaction presenting with severe hypercalcemia.

Rifampicin is a highly effective antibacterial drug and an important component of multidrug therapy used to treat leprosy. Side effects of rifampicin are rare with the once-a-month dosage regimen of anti-leprosy multidrug therapy. Here, we report a case of rifampicin-induced thrombocytopenia during anti-leprosy treatment. Although rare, this potential side effect merits attention.

We report a case of acquired fluoroquinolone (FQ) resistance under short-course multidrug-resistant tuberculosis (MDR-TB) treatment. The patient was managed at Kabutare hospital, one of the two specialized MDR-TB clinics in Rwanda. A low dose of moxifloxacin was used in the first three critical months. Acquired resistance was identified at the ninth month of treatment, 3 months after stopping kanamycin in a strain initially susceptible only to FQs, kanamycin, and clofazimine. Fluoroquinolone resistance was detected in the same month by deep sequencing as routinely used second-line line probe assay and phenotypic drug susceptibility testing. High-dose FQ, preferably gatifloxacin, should be used to maximize effectiveness.

Diagnosis of tuberculosis with GeneXpert and same-day initiation of tuberculosis treatment (SITT) has important public health and clinical benefits. GeneXpert allows for rapid diagnosis, hence presenting an opportunity for SITT. We determined the association between GeneXpert diagnosis and SITT, and the effect of SITT on treatment success rate among adult persons with bacteriologically confirmed pulmonary tuberculosis (BC-PTB) in rural eastern Uganda. We conducted a retrospective cohort study using routinely collected data at 10 health facilities, used modified Poisson regression analysis to determine the association between GeneXpert and SITT, and expressed the results as risk ratio (RR). We used propensity score-matched analysis to match SITT participants to delayed initiation of treatment (DIT) participants and then performed logistic regression analysis to determine the independent effect of SITT on treatment success rate, expressed as odds ratio (OR). Of 1,045 participants, 764 (73.1%) had SITT. The use of GeneXpert for diagnosis of tuberculosis was associated with higher likelihood of SITT (adjusted RR [aRR], 1.28; 95% CI: 1.19–1.37) and for persons with new BC-PTB diagnosis (aRR, 1.16; 95% CI: 1.02–1.32). We successfully matched 530 participants (265 in SITT and 265 in DIT) through 1:1 nearest neighbor caliper matching. Before propensity score-matched analysis, SITT was not significantly associated with treatment success rate (adjusted OR, 0.97; 95% CI: 0.70–1.33). After propensity score-matched analysis, SITT remained nonsignificantly associated with treatment success rate (OR, 0.96; 95% CI: 0.67–1.40). GeneXpert thus increases the likelihood of SITT, but SITT has no significant effect on treatment success rate.

Tuberculosis (TB) remains to be the leading cause of morbidity and mortality in the developing world. Early TB case detection (TCD) and treatment of infectious cases is vital to reduce the TB burden. The objective of this study was to identify possible barriers to TCD in East Gojjam Zone, northwest Ethiopia. The study used a descriptive phenomenological research method. The study participants included 21 TB patients, six TB control officers, and 40 health workers (HWs) selected by a heterogeneous purposive sampling technique. In-depth interviews and focus group discussions were used to collect data. Interviews were audio recorded, transcribed verbatim, translated, and thematically analyzed using NVivo 12 software (developed by QSR International Qualitative Software Developer, Melbourne, Australia). The study participants identified numerous barriers to TCD which were grouped into three major themes and 14 subthemes: 1) patient-related barriers including rural residence, low income, poor health literacy, and health-seeking delay; 2) healthcare system barriers grouped into two subthemes: HWs barriers (shortage of HWs, lack of training access, and low level of knowledge and skills) and health facility barriers (health service delay, using only passive TCD strategy, poor health education provision, and lack of regular supervision and timely feedback); 3) sociocultural and environmental barriers which included stigma and discrimination, lack of health information sources, poor transportation infrastructure, and community resistance. In conclusion, the TCD activity which is one of the pillars of the TB control program has been confronted with several patient-related, environmental, and healthcare system–related barriers. Improving community health literacy, scale-up access, and improving quality of TB diagnostic services, conducting regular supportive supervision and provision of timely feedback, arranging regular refresher training and staff motivation and recruitment schemes, and engaging local health officials and political leaders to address budgetary problems for TB and transportation infrastructure challenges are imperative interventions to enhance the TCD efforts in the study area.

In many low- and middle-income countries, tuberculosis (TB) incidence in prisons is high, exposing incarcerated populations to an elevated risk of TB infection. We conducted a randomized, double-blind, placebo-controlled trial among HIV-negative male inmates of a high TB burden prison to determine whether isoniazid given twice weekly (900 mg) for 12 months prevents TB infection. The primary outcome was QuantiFERON–TB Gold in Plus (QFT) conversion to ≥ 0.35 international units per milliliter (IU/mL) at 6 months; secondary outcomes included alternative QFT thresholds (≥ 0.7, ≥ 2.0, and ≥ 4.0 IU/mL). In total, 467 participants were randomly assigned to intervention (N = 258) or control (N = 209). In an interim analysis of participants who had completed 6 months of follow-up (N = 170), QFT conversion occurred in 20.8% (19/91) and 21.5% (17/79) of participants in intervention and control arms (efficacy: 2.9%, P = 0.91), respectively. The trial was then stopped according to the trial protocol, and the remaining participants prematurely discontinued. In an analysis of secondary outcomes, the intervention arm had significantly lower rates of conversion at a cutoff of ≥ 2.0 IU/mL (efficacy: 82.6%, P < 0.01). In conclusion, 900 mg of isoniazid, administered twice a week, did not effectively prevent QFT conversion at a cutoff point ≥ 0.35 IU/mL in a trial of QFT-negative inmates. Higher QFT cutoffs are associated with sustained conversion and greater protection. Future clinical trials that evaluate protection for latent infection should use the highest cutoff than that recommended by the manufacturer.

Phaeohyphomycosis causes a wide spectrum of systemic manifestations and can affect even the immunocompetent hosts. Involvement of the central nervous system is rare. A 48-year-old farmer presented with chronic headache, fever, and impaired vision and hearing. Serial MRIs of the brain showed enhancing exudates in the basal cisterns, and lesions in the sella and perichiasmatic and cerebellopontine angle regions along with enhancement of the cranial nerves and leptomeninges. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis with elevated protein and decreased glucose on multiple occasions. Clinical, imaging, and CSF abnormalities persisted despite treatment with antitubercular drugs and steroids for 2 years. Biopsy of the dura mater at the cervicomedullary junction revealed necrotizing granulomatous lesions, neutrophilic abscesses, and giant cells containing slender, pauci-septate, pigmented fungal hyphae. Fungal culture showed growth of Fonsecaea pedrosoi, which is classically known to cause brain abscesses. Here, we report the diagnostic odyssey in a patient with chronic meningitis from a region endemic for tuberculosis and describe the challenges in establishing the accurate diagnosis. Lack of therapeutic response to an adequate trial of empirical antitubercular therapy warrants search for alternative causes, including fungal meningitis. We highlight the uncommon manifestation of F. pedrosoi with chronic meningitis as well as the protracted clinical course despite not receiving antifungal therapy.

Chagas disease is an emerging infectious disease in Europe and other non-endemic areas, mainly owing to migration from endemic areas. We aimed at investigating the value of advanced echocardiography (ECHO) and cardiac magnetic resonance (CMR) in patients newly diagnosed with Chagas disease to compare findings with those of electrocardiogram (ECG) and conventional ECHO and thus detecting cardiac abnormalities. We included consecutive patients with newly diagnosed Chagas disease and registered cardiac test results (ECG, ECHO, and CMR). We divided ECHO parameters into three tiers: 1) left ventricular ejection fraction, regional wall motion abnormality, and left ventricular diastolic dimension (ECHO-1); 2) other common ECHO parameters (ECHO-2); and 3) global longitudinal strain (GLS) (ECHO-3). Cardiac magnetic resonance included global and segmental biventricular function, the presence of myocardial fibrosis, and edema. The study comprised 100 patients from South America. The mean age was 43.9 ± 0.9 years, and 66% were women. Mean time living in Spain was 9.7 ± 0.5 years. The ECG revealed ≥ 2 abnormal findings in 47% of patients. ECHO-1 was abnormal in 22% of patients, ECHO-2 in 52%, and GLS in 16%. Cardiac magnetic resonance was abnormal in 50% of cases, and in 3% of these, ECHO was normal. When ECG and conventional ECHO were taken together, abnormalities were detected in 83% of patients. This value increased to 86% and 92% for GLS and CMR, respectively. These findings suggest that ECG and conventional ECHO should be used routinely as standard cardiac tests for newly diagnosed cases of Chagas disease. The value of advanced ECHO techniques and CMR is low.

A collaborative investigation was initiated in rural coastal South Carolina in response to a reported triatomine bite. The eastern conenose bug, Triatoma sanguisuga, was identified and tested for Trypanosoma cruzi. The insect was negative by PCR, and no additional triatomines were found in the vicinity of the home. This is the first published report of a bite from T. sanguisuga in South Carolina despite the fact that triatomine vectors have been documented in the state since the 1850s, and specimens have been collected from homes in the past. Sylvatic T. cruzi reservoirs are common throughout the southeastern United States, and this case brings to light the possibility of human contact with infected triatomines in the state of South Carolina for public health and clinical and entomology professionals.

Human visceral leishmaniasis (HVL) is a parasitic disease infecting children in the Mediterranean region. Here, we portray a case of a 2-year-old child with an epidemiological description of the situation surrounding the case. The patient was suffering from recurrent fever, weakness, and abdominal discomfort associated with loss of appetite. Routine blood investigations showed pancytopenia, whereas examination revealed hepatomegaly. A diagnosis of HVL was made by demonstrating amastigotes in a Giemsa-stained smear from a bone marrow aspirate followed by genotyping by PCR and sequencing. In conclusion, early detection of VL infection followed by appropriate treatment protocols is essential to saving the patient.

Mucosal leishmaniasis (ML) affects predominantly the nose and occurs usually weeks or months after the cure of the primary cutaneous lesion. The pathology of ML is characterized by an exaggerated inflammatory reaction with infiltration of lymphocytes, macrophages, and plasma cells. There is also a paucity of parasites and a strong delayed-type hypersensitivity reaction. Herein, we report a case of a young man who had a large ulcer in his left leg and complained of dysphagia. In nasofibrolaryngoscopy, there were nodular lesions in the oropharynx and rhinopharynx. The skin lesion biopsy showed a chronic inflammation with amastigotes inside macrophages, and DNA of Leishmania braziliensis confirmed the diagnosis of ML in tissue biopsied from the pharynx. The leishmaniasis skin test was negative. Cytokine evaluation showed lack of production of interferon (IFN)-γ, interleukin (IL)-1β, and IL-17 with enhancement of these cytokine levels after cure.

In the United States, phlebotomine sand flies carrying Leishmania (Leishmania) mexicana are endemic along the southern border. However, relatively little is known about the enzootic and zoonotic transmission of L. (L.) mexicana within the United States, and autochthonous cases of the consequent disease are rarely reported. We investigated an atypical case of cutaneous leishmaniasis (CL) caused by L. (L.) mexicana in a patient from central Texas which did not respond to a typical antileishmanial chemotherapy. We also investigated sand fly vectors around the patient’s residence. PCR followed by DNA sequencing was used for determination of Leishmania spp., sand fly species, and host blood meal source. The L. (L.) mexicana genotype from the patient was identical to one found in a positive sand fly. Moreover, this genotype presented the same single-nucleotide polymorphisms as other historical CL cases acquired in Texas over the last 10 years, but distinct from those originating in Mexico and Central America. Three sand fly species were identified among the samples analyzed (n = 194), the majority of which were Lutzomyia (Dampfomyia) anthophora (n = 190), of which four specimens tested positive for Leishmania and two blood-fed specimens showed the presence of a human blood meal. This study highlights the complexity of clinical management of CL in a setting where the disease is infrequently encountered. The detection of human blood in Lu. (D.) anthophora is the first documentation of anthropophagy in this species. This is the first report of wild-caught, naturally infected sand flies found in association with an autochthonous case of human leishmaniasis and the specific strain of Leishmania (Leishmania) mexicana in the United States.

There are two main species of Leishmania reported in Thailand, that is, Leishmania siamensis and Leishmania martiniquensis. Moreover, leishmaniasis cases caused by Leishmania donovani complex were also reported. There is still a lack of information concerning risk factors of Leishmania infection in Thailand. This study aimed to identify the risk factors of Leishmania infection caused by these three species among HIV-infected patients. A cross-sectional study was conducted in HIV clinic at Trang Hospital, Thailand. Nested PCR and sequencing were performed to detect Leishmania DNA in blood and saliva samples and identify Leishmania species. A standardized questionnaire was used to interview individuals. A total of 526 patients were recruited in this study. Sixty-three (12.0%) were positive for L. siamensis, 24 (4.6%) were positive for L. martiniquensis, and 23 (4.4%) were positive for L. donovani complex. Risk factors of L. siamensis infection included using intravenous drug (adjusted odds ratio [AOR] 2.01, 95% CI: 1.01–4.02). Risk factors of L. martiniquensis infection included female gender (AOR 4.23, 95% CI: 1.52–11.75), using recreational drug (AOR 3.43, 95% CI: 1.00–11.74), and having comorbidities (AOR 4.94, 95% CI: 2.00–12.21). Risk factors of L. donovani complex infection included having opportunistic infection (AOR 4.22, 95% CI: 1.00–17.79), CD4 count 200–500 cells/mm3 (AOR 3.64, 95% CI: 1.14–6.86), and not using insect repellent (AOR 3.04, 95% CI: 1.08–8.58). This study identified the risk factors of Leishmania infection caused by three Leishmania species in Thailand. The data could be useful for disease prevention and control. Further studies on trends of Leishmania infection and preventive measures are recommended.

The prevalence of malaria in India is decreasing, but it remains a major concern for public health administration. The role of submicroscopic malaria and asymptomatic malaria parasitemia and their persistence is being explored. A cross-sectional survey was conducted in the Kandhamal district of Odisha (India) during May–June 2017. Blood samples were collected from 1897 individuals for screening of asymptomatic parasitemia. Samples were screened using rapid diagnostic tests (RDTs) and examined microscopically for Plasmodium species. Approximately 30% of randomly selected samples (n = 586) were analyzed using real-time PCR (qPCR), and the genetic diversity of Plasmodium falciparum was analyzed. The prevalence of Plasmodium species among asymptomatic individuals detected using qPCR was 18%, which was significantly higher than that detected by microscopy examination (5.5%) or RDT (7.3%). Of these, 37% had submicroscopic malaria. The species-specific prevalence among asymptomatic malaria-positive cases for P. falciparum, Plasmodium vivax, and mixed infection (P. falciparum and P. vivax) by qPCR was 57%, 29%, and 14%, respectively. The multiplicity of infection was 1.6 and 1.2 for the merozoite surface protein-1 gene (msp1) and (msp2), respectively. Expected heterozygosity was 0.64 and 0.47 for msp1 and msp2, respectively. A significant proportion of the study population, 105/586 (18%), was found to be a reservoir for malaria infection, and identification of this group will help in the development of elimination strategies.

Malaria is frequently diagnosed in urban Kampala, despite low transmission intensity. To evaluate the association between recent travel out of Kampala and malaria, we conducted a matched case–control study. Cases were febrile outpatients with a positive malaria test; controls were febrile outpatients with a negative test. For every two cases, five controls were selected, matching on age. Data were collected on recent overnight travel out of Kampala (past 60 days), destination and duration of travel, and behavioral factors, including sleeping under an insecticide-treated net (ITN) during travel. From July to August 2019, 162 cases and 405 controls were enrolled. The locations of residence of cases and controls were similar. More controls were female (62.7% versus 46.3%, P < 0.001). Overall, 158 (27.9%) participants reported recent overnight travel. Travelers were far more likely to be diagnosed with malaria than those who did not travel (80.4% versus 8.6%, OR 58.9, 95% CI: 23.1–150.1, P < 0.001). Among travelers, traveling to a district not receiving indoor residual spraying of insecticide (OR 35.0, 95% CI: 4.80–254.9, P < 0.001), no ITN use (OR 30.1, 95% CI: 6.37–142.7, P < 0.001), engaging in outdoor activities (OR 22.0, 95% CI: 3.42–141.8, P = 0.001), and age < 16 years (OR 8.36, 95% CI: 2.22–56.2, P = 0.03) were associated with increased odds of malaria. Kampala residents who traveled overnight out of the city were at substantially higher risk of malaria than those who did not travel. For these travelers, personal protection measures, including sleeping under an ITN when traveling, should be advocated.

Tororo, a district in Uganda with historically high malaria transmission intensity, has recently scaled up control interventions, including universal long-lasting insecticidal net distribution in 2013 and 2017, and sustained indoor residual spraying (IRS) of insecticide since December 2014. We describe the burden of malaria in Tororo 5 years following the initiation of IRS. We followed a cohort of 531 participants from 80 randomly selected households in Nagongera subcounty, Tororo district, from October 2017 to October 2019. Mosquitoes were collected every 2 weeks using CDC light traps in all rooms where participants slept, symptomatic malaria was identified by passive surveillance, and microscopic and submicroscopic parasitemia were measured every 4 weeks using active surveillance. Over the 2 years of follow-up, 15,780 female anopheline mosquitos were collected, the majority (98.0%) of which were Anopheles arabiensis. The daily human biting rate was 2.07, and the annual entomological inoculation rate was 0.43 infective bites/person/year. Only 38 episodes of malaria were diagnosed (incidence 0.04 episodes/person/year), and there were no cases of severe malaria or malarial deaths. The prevalence of microscopic parasitemia was 1.9%, and the combined prevalence of microscopic and submicroscopic parasitemia was 10.4%, each highest in children aged 5–15 years (3.3% and 14.0%, respectively). After 5 years of intensive vector control measures in Tororo, the burden of malaria was reduced to very low transmission levels. However, a significant proportion of the population remained parasitemic, primarily school-aged children with submicroscopic parasitemia, providing a potential reservoir for malaria transmission.

This study aimed to describe the epidemiology of Plasmodium falciparum malaria and identify risk factors for severe disease in Hubei Province, China, using a case-based survey of retrospective data from 2013 to 2018. From 2013 to 2018, a total of 763 imported malaria cases were reported in Hubei Province; 69.2% (528/763) cases were caused by P. falciparum species. The proportion of malaria caused by P. falciparum increased from 66.7% in 2013 to 74.0% in 2018 (χ2 = 21.378, P < 0.05). Plasmodium falciparum malaria was reported in 77 counties of Hubei Province. The majority of imported P. falciparum cases originated from Africa (98.9%, 522/528); 9.7% (51/528) of patients infected with P. falciparum developed severe malaria. Three deaths (case fatality rate: 0.6%) were related to imported P. falciparum malaria. Risk factors for severe malaria were being female (odds ratio [OR] = 3.593, 95% CI: 1.003–12.874), age ≥ 50 years (OR = 2.674, 95% CI: 1.269–5.634), > 3 days between symptom onset and diagnosis (OR = 2.383, 95% CI: 1.210–4.693), and the first-visit medical institution at the township level or lower (OR = 2.568, 95% CI: 1.344–4.908). Malaria prevention should be undertaken among high-risk groups, infection with P. falciparum should be detected early to prevent severe disease and death, and healthcare providers in health facilities at the township level should be trained on early recognition of malaria.

Malaria in Vietnam has become focal to a few provinces, including Phu Yen. This study aimed to assess correlations between intervention (population proportion protected by insecticide-treated nets and indoor residual spraying) and climatic variables with malaria incidence in Phu Yen Province. The Vietnam National Institute of Malariology, Parasitology, and Entomology provided incidence data for Plasmodium falciparum and Plasmodium vivax for 104 communes of Phu Yen Province from January 2005 to December 2016. A multivariable, zero-inflated Poisson regression model was developed with a conditional autoregressive prior structure to identify the underlying spatial structure of the data and quantify associations with covariates. There were a total of 2,778 P. falciparum and 1,770 P. vivax cases during the study period. Plasmodium falciparum and P. vivax incidence increased by 5.4% (95% credible interval [CrI] 5.1%, 5.7%) and 3.2% (95% CrI 2.9%, 3.5%) for a 10-mm increase in precipitation without lag, respectively. Plasmodium falciparum and P. vivax incidence decreased by 7.7% (95% CrI 5.6%, 9.7%) and 10.5% (95% CrI 8.3%, 12.6%) for a 1°C increase in minimum temperature without lag, respectively. There was a > 95% probability of a higher than provincial average trend of P. falciparum and P. vivax in Song Cau and Song Hoa districts. There was a > 95% probability of a lower than provincial average trend in Tuy Dong Xuan and Hoa districts for both species. Targeted distribution of resources, including intensified interventions, in this part of the province will be required for local malaria elimination.