The American Journal of Tropical Medicine and Hygiene - Volume 94, Issue 1, January 2016

There are many successful global health research partnerships, but little information is available about what makes them successful. We asked 14 research colleagues from Uganda, Kenya, and the United States who have extensive global health research experience about what they considered the top three factors that led to or impeded successful international research collaborations. Four key factors were identified: 1) mutual respect and benefit, 2) trust, 3) good communication, and 4) clear partner roles and expectations. Initial and ongoing assessment of these factors in global health research partnerships may prevent misunderstandings and foster a collaborative environment that leads to successful research.

The development of good quality and affordable ultrasound machines has led to the establishment and implementation of numerous point-of-care ultrasound (POCUS) protocols in various medical disciplines. POCUS for major infectious diseases endemic in tropical regions has received less attention, despite its likely even more pronounced benefit for populations with limited access to imaging infrastructure. Focused assessment with sonography for HIV-associated TB (FASH) and echinococcosis (FASE) are the only two POCUS protocols for tropical infectious diseases, which have been formally investigated and which have been implemented in routine patient care today. This review collates the available evidence for FASH and FASE, and discusses sonographic experiences reported for urinary and intestinal schistosomiasis, lymphatic filariasis, viral hemorrhagic fevers, amebic liver abscess, and visceral leishmaniasis. Potential POCUS protocols are suggested and technical as well as training aspects in the context of resource-limited settings are reviewed. Using the focused approach for tropical infectious diseases will make ultrasound diagnosis available to patients who would otherwise have very limited or no access to medical imaging.

In South Korea, scrub typhus is one of the most common rickettsial diseases. The number of scrub typhus patients has increased in South Korea, a total of 69,210 cases were reported from 2001 to 2013. The seasonality and relation of scrub typhus cases to latitude were analyzed in this article using data obtained from the National Notifiable Diseases Surveillance System website of the Korea Centers for Disease Control and Prevention. The incidence of scrub typhus tended to increase in the later months of the year, especially in October–December. In general, lower latitudes were associated with a later peak incidence. Our results suggest for the first time that the monthly observed incidence tended to increase in the later months of the year as the latitude decreased, and on a yearly basis in Korea.

Spotted fever group (SFG) rickettsioses are notifiable conditions in the United States caused by the highly pathogenic Rickettsia rickettsii and less pathogenic rickettsial species such as Rickettsia parkeri and Rickettsia sp. 364D. Surveillance data from 2008 to 2012 for SFG rickettsioses are summarized. Incidence increased from 1.7 cases per million person-years (PY) in 2000 to 14.3 cases per million PY in 2012. During 2008–2012, cases of SFG rickettsiosis were more frequently reported among males, persons of white race, and non-Hispanic ethnicity. Overall, case fatality rate (CFR) was low (0.4%), however, risk of death was significantly higher for American Indian/Alaska Natives (relative risk [RR] = 5.4) and Asian/Pacific Islanders (RR = 5.7) compared with persons of white race. Children aged < 10 years continue to experience the highest CFR (1.6%). Higher incidence of SFG rickettsioses and decreased CFR likely result from increased reporting of tick-borne disease including those caused by less pathogenic species. Recently, fewer cases have been confirmed using species-specific laboratory methods (such as cell culture and DNA detection using polymerase chain reaction [PCR] assays), causing a clouded epidemiological picture. Use of PCR and improved documentation of clinical signs, such as eschars, will better differentiate risk factors, incidence, and clinical outcomes of specific rickettsioses in the future.

Spotted fever group (SFG) Rickettsia species are etiologic agents of a wide range of human infections from asymptomatic or mild infections to severe, life-threatening disease. In the United States, recent passive surveillance for SFG rickettsiosis shows an increased incidence and decreased severity of reported cases. The reasons for this are not well understood; however, we hypothesize that less pathogenic rickettsiae are causing more human infections, while the incidence of disease caused by more pathogenic rickettsiae, particularly Rickettsia rickettsii, is relatively stable. During the same period, the range of Amblyomma americanum has expanded. Amblyomma americanum is frequently infected with “Candidatus Rickettsia amblyommii”, a SFG Rickettsia of unknown pathogenicity. We tested our hypothesis by modeling incidence rates from 1993 to 2013, hospitalization rates from 1981 to 2013, and case fatality rates from 1981 to 2013 regressed against the presence of A. americanum, the decade of onset of symptoms, and the county of residence. Our results support the hypothesis, and we show that the expanding range of A. americanum is associated with changes in epidemiology reported through passive surveillance. We believe epidemiological and acarological data collected on individual cases from enhanced surveillance may further elucidate the reasons for the changing epidemiology of SFG rickettsiosis.

Diseases of zoonotic origin contribute to the burden of febrile illnesses in developing countries. We evaluated serologic evidence of exposure to Bacillus anthracis, Brucella spp., spotted fever group rickettsioses (SFGR), and typhus group rickettsioses (TGR) from samples of persons aged 15–64 years collected during a nationwide human immunodeficiency virus (HIV) serosurvey conducted in 2007 in Kenya. The seropositivity observed for pathogens was B. anthracis 11.3%, Brucella spp. 3.0%, SFGR 23.3%, and TGR 0.6%. On univariate analysis, seropositivity for each pathogen was significantly associated with the following risk factors: B. anthracis with province of residence; Brucella spp. with sex, education level, and wealth; SFGR with age, education level, wealth, and province of residence; and TGR with province of residence. On multivariate analysis, seropositivity remained significantly associated with wealth and province for B. anthracis; with sex and age for Brucella spp; and with sex, education level, and province of residence for SFGR whereas TGR had no significance. High IgG seropositivity to these zoonotic pathogens (especially, B. anthracis and SFGR) suggests substantial exposure. These pathogens should be considered in the differential diagnosis of febrile illness in Kenya.

Human ehrlichiosis is a potentially fatal disease caused by Ehrlichia chaffeensis and Ehrlichia ewingii. Cases of ehrlichiosis are reported to Centers for Disease Control and Prevention through two national surveillance systems: Nationally Notifiable Diseases Surveillance System (NNDSS) and Case Report Forms. During 2008–2012, 4,613 cases of E. chaffeensis infections were reported through NNDSS. The incidence rate (IR) was 3.2 cases per million person-years (PYs). The hospitalization rate (HR) was 57% and the case fatality rate (CFR) was 1%. Children aged < 5 years had the highest CFR of 4%. During 2008–2012, 55 cases of E. ewingii infection were reported through NNDSS. The national IR was 0.04 cases per million PY. The HR was 77%; no deaths were reported. Immunosuppressive conditions were reported by 26% of cases. The overall rate for ehrlichiosis has increased 4-fold since 2000. Although previous literature suggests E. ewingii primarily affects those who are immunocompromised, this report shows most cases occurred among immunocompetent patients. This is the first report to show children aged < 5 years with ehrlichiosis have an increased CFR, relative to older patients. Ongoing surveillance and reporting of tick-borne diseases are critical to inform public health practice and guide disease treatment and prevention efforts.

Relapsing fever borreliae, produced by ectoparasite-borne Borrelia species, cause mild to deadly bacteremia and miscarriage. In the perspective of developing inexpensive assays for the rapid detection of relapsing fever borreliae, we produced 12 monoclonal antibodies (MAbs) against Borrelia crocidurae and characterized the two exhibiting the highest titers. P3A10 MAb reacts with the 35.6-kDa flagellin B (flaB) of B. crocidurae while P6D9 MAb recognizes a 35.1-kDa variable-like protein (Vlp) in B. crocidurae and a 35.2-kDa Vlp in Borrelia duttonii. Indirect immunofluorescence assay incorporating relapsing fever and Lyme group borreliae and 11 blood-borne organisms responsible for fever in West Africa confirmed the reactivity of these two MAbs. Combining these two MAbs in indirect immunofluorescence assays detected relapsing fever borreliae including B. crocidurae in ticks and the blood of febrile Senegalese patients. Both antibodies could be incorporated into inexpensive and stable formats suited for the rapid point-of-care diagnosis of relapsing fever. These first-ever MAbs directed against African relapsing fever borreliae are available for the scientific community to promote research in this neglected field.

Melioidosis is a tropical disease of high mortality caused by the environmental bacterium, Burkholderia pseudomallei. We have collected clinical isolates from the highly endemic Northern Territory of Australia routinely since 1989, and animal and environmental B. pseudomallei isolates since 1991. Here we provide a complete record of all B. pseudomallei multilocus sequence types (STs) found in the Northern Territory to date, and distribution maps of the eight most common environmental STs. We observed surprisingly restricted geographic distributions of STs, which is contrary to previous reports suggesting widespread environmental dissemination of this bacterium. Our data suggest that B. pseudomallei from soil and water does not frequently disperse long distances following severe weather events or by migration of infected animals.

Brucellosis, a zoonosis that is common worldwide, is endemic in many countries, primarily those of the Mediterranean region (including Turkey). Human brucellosis is a systemic infection with a wide clinical spectrum. Although hepatic involvement is very common during the course of chronic brucellosis, hepatic abscess is a very rare complication of Brucella spp. infection. We present a case of hepatic abscess caused by Brucella melitensis, which resembled the clinical presentation of surgical acute abdomen.

In 1998, a cholera epidemic in east Africa reached the Comoros Islands, an archipelago in the Mozambique Channel that had not reported a cholera case for more than 20 years. In just a little over 1 year (between January 1998 and March 1999), Grande Comore, the largest island in the Union of the Comoros, reported 7,851 cases of cholera, about 3% of the population. Using case reports and field observations during the medical response, we describe the epidemiology of the 1998–1999 cholera epidemic in Grande Comore. Outbreaks of infectious diseases on islands provide a unique opportunity to study transmission dynamics in a nearly closed population, and they may serve as stepping-stones for human pathogens to cross unpopulated expanses of ocean.

Helicobacter pylori infection is among the most prevalent infections in the world and a key cause of gastric diseases; however, its route of transmission remains unclear. This study aimed to assess the potential for fecal–oral transmission of H. pylori by leveraging its association with a disease with known etiology. Utilizing serology data from the National Health and Nutrition Examination Survey (NHANES 1999; N = 6,347), the association between H. pylori and hepatitis A virus (HAV), a sensitive indicator for fecal–oral exposure, was assessed. Survey-weighted kappa and multiple logistic regression were used to quantify the association between H. pylori and HAV after controlling for age, sex, race, poverty, birthplace, crowding, smoking, and alcohol use. Concordant serological results were found among 69.8% of participants (survey-weighted κ = 0.30, 95% confidence interval [CI] = 0.26, 0.35). The adjusted odds of H. pylori seropositivity were over two times higher after adjusting for confounders (odds ratio = 2.27, 95% CI = 1.79, 2.87). Results from this study suggest H. pylori and HAV infections are strongly associated. Since HAV is primarily transmitted through the fecal–oral route, fecal–oral transmission may be an important pathway for H. pylori spread.

The reservoir of Mycobacterium ulcerans causing Buruli ulcer (BU) remains unknown. Here, sterilized watery soil was mixed with 2 × 106 colony-forming units (CFU)/g of M. ulcerans Agy99 or M. ulcerans ATCC 33728 and incubated in a microaerophilic atmosphere in the presence of negative controls. Both M. ulcerans strains survived in soil for 4 months with a final inoculum of 300–440 CFU/g. Further, three groups of five mice with and without footpad scarification were exposed to control soil or M. ulcerans-inoculated soil. Although no specific clinical and histopathological lesions were observed in control animals, red spots observed on 8/20 scarified feet in 8/10 challenged mice yielded inflammatory infiltrates and positive real-time polymerase chain reaction detection of M. ulcerans DNA in five mice. BU can be acquired as an inoculation infection with watery soil as a transient source of infection. These experimental observations warrant additional field observations.

India bears the burden of about half of global visceral leishmaniasis (VL) cases with emerging problems of stibanate resistance. Liposomal preparations have improved treatment outcome through shorter duration of therapy and lower toxicity compared with conventional amphotericin B. We report the efficacy of two short-course regimens of an Indian preparation of liposomal amphotericin B (Fungisome™) for VL caused by Leishmania donovani in India. An open-label, randomized, single-center comparative study was undertaken from 2008 to 2011, involving 120 treatment naive non–human immunodeficiency virus VL patients randomly allocated to two groups. Fungisome™ was given, in groups A (N = 60), 5 mg/kg daily for 2 days and B (N = 60), 7.5 mg/kg daily for 2 days, as intravenous infusion. Initial cure rate was 100% in both the groups after 1 month posttreatment. At 6 months after completion of treatment, definitive cure rate was group A 90% (54/60, 95% confidence interval (CI): 80.55–95.72%); group B: 100% (95% CI: 95.92–100%); (P = 0.027). No serious adverse events occurred in either group. The short-course, 2-day regimen of 15 mg/kg Fungisome™ infusion is easy to administer, effective, and safe for treatment of VL caused by L. donovani in India.

This report presents two cases of visceral leishmaniasis (VL) recurrence where the microscopy of the splenic smear failed in diagnosis. However, a strong clinical suspicion compelled further evaluation by polymerase chain reaction (PCR), which validated the etiology. This short report highlights the usefulness of PCR in diagnosing cases of suspected smear-negative VL recurrence.

In South America, the presence of the Leishmania RNA virus type 1 (LRV1) was described in Leishmania guyanensis and Leishmania braziliensis strains. The aim of this study was to determine the prevalence distribution of LRV1 in Leishmania isolates in French Guiana given that, in this French overseas department, most Leishmania infections are due to these parasite species. The presence of the virus was observed in 74% of Leishmania spp. isolates, with a highest presence in the internal areas of the country.

Mucosal leishmaniasis (ML) is a disfiguring manifestation of Leishmania (Viannia) infection. We evaluated parasite load (PL) over time as a potential biomarker of treatment outcome in ML. PL was assessed with kinetoplast DNA quantitative real-time polymerase chain reaction (kDNA-qPCR) at enrollment, days 14 and 21–28 of therapy and 3, 6, 12–18, and 18–24 months after treatment of ML and correlated to demographic, clinical, and parasitologic factors. Forty-four patients were enrolled: 30 men and 14 women. Enrollment PL differed significantly by causative species (P < 0.001), and was higher in patients with severe ML (nasal and laryngeal involvement) compared with those with only isolated nasal involvement (median = 1,285 versus 51.5 parasites/μg tissue DNA; P = 0.005). Two patterns of PL emerged: pattern 1 (N = 23) was characterized by a sequential decline in PL during and after therapy until kDNA was undetectable. Pattern 2 (N = 18) was characterized by clearance of detectable kDNA during treatment, followed by an increased PL thereafter. All patients who failed treatment (N = 4) demonstrated pattern 1. Leishmania (Viannia) braziliensis was overrepresented among those with pattern 2 (P = 0.019). PL can be quantified by cytology brush qPCR during and after treatment in ML. We demonstrate that treatment failure was associated with undetectable PL, and L. (V.) braziliensis infection was overrepresented in those with rebounding PL.

Trypanosoma cruzi causes life-long disease after infection and leads to cardiac disease in 30% of infected individuals. After infection, the parasites are readily detectable in the blood during the first few days before disseminating to infect numerous cell types. Preliminary data suggested that the Tc24 protein that localizes to the T. cruzi membrane during all life stages possesses B-cell superantigenic properties. These antigens facilitate immune escape by interfering with antibody-mediated responses, particularly the avoidance of catalytic antibodies. These antibodies are an innate host defense mechanism present in the naive repertoire, and catalytic antibody–antigen binding results in hydrolysis of the target. We tested the B-cell superantigenic properties of Tc24 by comparing the degree of Tc24 hydrolysis by IgM purified from either Tc24 unexposed or exposed mice and humans. Respective samples were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, silver stained, and the degree of hydrolysis was measured. Data presented in this report suggest that the T. cruzi Tc24 is a B-cell superantigen based on the observations that 1) Tc24 was hydrolyzed by IgM present in serum of unexposed mice and humans and 2) exposure to Tc24 eliminated catalytic activity as early as 4 days after T. cruzi infection.