Johannes Mischlinger

Demography, maternal health and the epidemiology of malaria and other major infectious diseases in the rural department Tsamba-Magotsi, Ngounie Province, in central African Gabon

BackgroundSub-Saharan Africa is undergoing an epidemiological transition from a predominance of infectious diseases to non-communicable and lifestyle related conditions. However, the pace of this transition and the pattern of disease epidemiology are uneven between affluent urban and rural poor populations. To address this question for a remote rural region located in the central African rainforest region of Gabon, this study was conducted to assess reasons for health care attendance and to characterize the epidemiology of malaria and other major infectious diseases for the department of Tsamba Magotsi.MethodsMajor causes for health care attendance were collected from local hospital records. Cross sectional population based surveys were performed for the assessment of local malaria epidemiology. Pregnant women attending antenatal care services were surveyed as a sentinel population for the characterization of chronic viral and parasitic infections in the community.ResultsInfectious diseases were responsible for 71% (7469) of a total of 10,580 consultations at the formal health care sector in 2010. Overall, malaria – defined by clinical syndrome – remained the most frequent cause for health care attendance. A cross sectional malaria survey in 840 asymptomatic individuals residing in Tsamba Magotsi resulted in a Plasmodium spp. infection prevalence of 37%. The infection rate in 2–10 year old asymptomatic children – a standard measure for malaria endemicity – was 46% (100 of 217) with P. falciparum as predominant species (79%). Infection with other plasmodial species (P. ovale and P. malariae) presented most commonly as coinfections (23.2%). Prevalence of HIV, HBV, and syphilis were 6.2, 7.3, and 2.5%, respectively, in cross-sectional assessments of antenatal care visits of pregnant women. Urogenital schistosomiasis and the filarial pathogens Loa loa and Mansonella perstans are highly prevalent chronic parasitic infections affecting the local population.ConclusionsDespite major improvements in the accessibility of Tsamba Magotsi over the past decade the epidemiological transition does not appear to have majorly changed on the spectrum of diseases in this rural Gabonese population. The high prevalence of Plasmodium infection indicates a high burden of malaria related morbidity. Infectious diseases remain one of the most important health issues and further research activities in the field of tropical medicine and infectious diseases could help improve health care for the local population.

Single dose treatment of malaria - current status and perspectives.

ABSTRACT Introduction: Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Areas covered: Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

Seroprevalence of Toxocara spp. in a rural population in Central African Gabon

Toxocara spp. are zoonotic parasites with global distribution infecting humans by incidental ingestions of eggs shed in feces of dogs or cats. High seroprevalences have been reported from several regions of Africa, however data from the Central African region remain limited. Although several clinical entities caused by larvae of Toxocara spp. have been described, the public heath impact of this infection has so far often been neglected. This study was conducted to estimate the prevalence in a rural central African population. The population based study was performed in volunteers in a rural region of Gabon. A two-step testing approach was applied using an ELISA as screening test and a Western Blot (immunoblot) as confirmatory assay. Basic demographic data and risk factors were collected and compared between seropositive and negative participants. In total, 199 out of 332 serum samples were tested positive for Toxocara spp. antibodies (59.9%). After standardization for age to the overall Gabonese population seroprevalence was 53.6% (95% CI 48.2-59.0%). There was a trend towards higher seroprevalence in participants with agricultural activity. Seroprevalence of antibodies against Toxocara spp. is high in this rural population in Gabon. These results are comparable with previous reports from other sub-regions of Africa and add to our understanding of the epidemiology of toxocariasis in Africa. Given the high prevalence of toxocariasis in tropical regions, it may be speculated that clinically relevant presentations (e.g. visceral or ocular larva migrans syndrome) may occur in considerable numbers. A formal assessment of the burden of disease and the public health impact of human toxocariasis is therefore warranted.

Use of Capillary Blood Samples Leads to Higher Parasitemia Estimates and Higher Diagnostic Sensitivity of Microscopic and Molecular Diagnostics of Malaria Than Venous Blood Samples

Background Diagnosis of malaria is usually based on samples of peripheral blood. However, it is unclear whether capillary (CAP) or venous (VEN) blood samples provide better diagnostic performance. Quantitative differences of parasitemia between CAP and VEN blood and diagnostic performance characteristics were investigated. Methods Patients were recruited between September 2015 and February 2016 in Gabon. Light microscopy and quantitative polymerase chain reaction (qPCR) measured parasitemia of paired CAP and VEN samples. CAP and VEN performance characteristics using microscopy were evaluated against a qPCR gold standard. Results Microscopy revealed a median parasitemia of 495/μL in CAP and 429/μL in VEN samples, manifesting in a 16.6% (P = .04) higher CAP parasitemia compared with VEN parasitemia. Concordantly, in qPCR -0.278 (P = .006) cycles were required for signal detection in CAP samples. CAP sensitivity of microscopy relative to the gold standard was 81.5% vs VEN sensitivity of 73.4%, while specificities were 91%. CAP and VEN sensitivities dropped to 63.3% and 45.9%, respectively, for a subpopulation of low-level parasitemias, whereas specificities were 92%. Conclusions CAP sampling leads to higher parasitemias compared to VEN sampling and improves diagnostic sensitivity. These findings may have important implications for routine diagnostics, research, and elimination campaigns of malaria.

Efficacy and Safety of Fosmidomycin–Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria: A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon

Fosmidomycin–piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval.

A common trap of diagnostic tests

rapid disease ascertainment has become routine in everyday clinical practice and large-scale screening programs [1, 2]. It is therefore of increasing importance to adequately take into account the performance characteristics of the various test methods [3, 4]. Sensitivity and specificity are two of these characteristics. They are usually taught in medical school and are therefore widely known to physicians. Physicians are less familiar with predictive values, although these test properties contain relevant information for diagnostic and therapeutic decision-making. Simply put, predictive values can be expressed as the probability with which one can trust the correctness of the test result. For positive test results, this information is expressed by the positive predictive value (PPV), whereas for negative test results, this is expressed by the negative predictive value (NPV). Both of them, particularly the positive predictive value, are affected by the specificity of a given diagnostic method and—even more significantly—by the prevalence of the disease being tested. The positive predictive value may formally be denoted as PPV = (sensitivity × prevalence) / (sensitivity × prevalence) + (1 – specificity) × (1 – prevalence) [5]. Prevalence is

Validity and reliability of methods to microscopically detect and quantify malaria parasitaemia

The recommended microscopy method by WHO to quantify malaria parasitaemia yields inaccurate results when individual leucocyte (WBC) counts deviate from 8000 leucocytes/μl. A method avoiding WBC count assumptions is the Lambaréné method (LAMBA). Thus, this study compared validity and reliability of the LAMBA and the WHO method.

Detection of the Malaria causing Plasmodium Parasite in Saliva from Infected Patients using Topoisomerase I Activity as a Biomarker

Malaria is among the major threats to global health with the main burden of disease being in rural areas of developing countries where accurate diagnosis based on non-invasive samples is in high demand. We here present a novel molecular assay for detection of malaria parasites based on technology that may be adapted for low-resource settings. Moreover, we demonstrate the exploitation of this assay for detection of malaria in saliva. The setup relies on pump-free microfluidics enabled extraction combined with a DNA sensor substrate that is converted to a single-stranded DNA circle specifically by topoisomerase I expressed by the malaria causing Plasmodium parasite. Subsequent rolling circle amplification of the generated DNA circle in the presence of biotin conjugated deoxynucleotides resulted in long tandem repeat products that was visualized colorimetrically upon binding of horse radish peroxidase (HRP) and addition of 3,3′,5,5′-Tetramethylbenzidine that was converted to a blue colored product by HRP. The assay was directly quantitative, specific for Plasmodium parasites, and allowed detection of Plasmodium infection in a single drop of saliva from 35 out of 35 infected individuals tested. The results could be determined directly by the naked eye and documented by quantifying the color intensity using a standard paper scanner.

Behavioural and clinical predictors for Loiasis

Background Loiasis is a vector-borne disease in Central and West Africa. While there is still uncertainty to what extent loiasis is responsible for population morbidity, individuals having both loiasis and onchocerciasis have a high risk of fatal encephalopathy when treatment (ie, ivermectin) for onchocerciasis is given. Therefore it is current policy that communities of high loiasis-burden are excluded from mass drug administration programmes of ivermectin. To address this treatment gap we present diagnostic scores, based on clinical and behavioural predictors that may help to rapidly identify sub-groups with loiasis within high-burden communities. Methods A cross-sectional survey was performed in the province of la Ngounie, Gabon between December 2015 and Februrary 2016 and 947 participants of all ages were recruited. Clinical parameters and behavioural exposure factors were ascertained by questionnaire-based interviews. Parasitological analysis of blood samples was performed for L. loa detection. Diagnostic scores consisting of clinical and behavioural factors were modelled to predict loiasis in sub-groups residing in endemic regions. Results Increasing sylvan exposure was identified as important risk factor for loiasis with adjusted odds ratios of 5.1 (95% confidence interval CI 2.6-9.9) for occasional forest exposure, 11.1 (95% CI 5.4-22.6) for frequent forest exposure and 25.7 (95% CI 12.5-52.9) for intensive forest exposure. Individuals with loiasis were 7.7 (95% CI 5.4-11.0) times more likely to report recurrent pruritus than those without loiasis. Reporting of regular daily exposure to the deep rain forest and recurrent pruritus was 9-fold (positive likelihood ratio 9.18; 95% CI: 6.39-13.18) more prevalent in individuals with loiasis than in controls. Concordantly, the absence of regular weekly forest exposure was associated with extremely low disease-likelihood (negative likelihood ratio 0.09; 95% CI 0.05-0.16). Conclusions These composite scores may serve as a simple tool to rapidly identify both those most and those least at risk of disease and may simplify loiasis control activities as well as screening procedures for studies on loiasis. Further, they may aid policy-makers to tailor the delivery of ivermectin mass drug administration for onchocerciasis control programmes more effectively and safely in regions of high loiasis-burden.

Leishmaniasis in Northern Syria during Civil War

Since the onset of the ongoing civil war in Syria, the governmental surveillance system for leishmaniasis has lost access to provinces of northern Syria. The MENTOR Initiative, an international not-for-profit organization, was commissioned to implement an integrated leishmaniasis control program, providing an opportunity to reassess the epidemiology of leishmaniasis in northern Syria. Epidemiologic data and biologic samples for molecular species diagnostics were collected from collaborating local health centers. Incidence peaked in March 2015 at 7,743 estimated monthly cases. High levels of transmission were observed in traditional endemic regions but extended to previously hypoendemic regions, such as Al-Raqqa and Al-Hasakah. Incidence decreased to 3,209 in July 2015. Data indicate that the prewar trend of increasing incidence of cutaneous leishmaniasis accelerated during the beginning of armed conflict but declined after implementation of the comprehensive control program by the MENTOR Initiative. Molecular analysis revealed a spectrum of Leishmania species and sporadic cases of visceral leishmaniasis.