Analysis of Immunity to Febrile Malaria in Children That Distinguishes Immunity from Lack of Exposure

In studies of immunity to malaria, the absence of febrile malaria is commonly considered evidence of “protection.” However, apparent “protection” may be due to a lack of exposure to infective mosquito bites or due to immunity. We studied a cohort that was given curative antimalarials before monitoring began and documented newly acquired asymptomatic parasitemia and febrile malaria episodes during 3 months of surveillance. With increasing age, there was a shift away from febrile malaria to acquiring asymptomatic parasitemia, with no change in the overall incidence of infection. Antibodies to the infected red cell surface were associated with acquiring asymptomatic infection rather than febrile malaria or remaining uninfected. Bed net use was associated with remaining uninfected rather than acquiring asymptomatic infection or febrile malaria. These observations suggest that most uninfected children were unexposed rather than “immune.” Had they been immune, we would have expected the proportion of uninfected children to rise with age and that the uninfected children would have been distinguished from children with febrile malaria by the protective antibody response. We show that removing the less exposed children from conventional analyses clarifies the effects of immunity, transmission intensity, bed nets, and age. Observational studies and vaccine trials will have increased power if they differentiate between unexposed and immune children.Malaria is a pressing global health problem (36). The correlates of immunity in observational field-based studies are often used to guide vaccine design (22), in which the chosen definition of immunity to malaria is usually the absence of febrile malaria. However, the findings obtained with this approach are often inconsistent, and responses to a specific antigen are associated with protection in some studies but not in others (4, 6, 7, 9-12, 23, 29). This may be because of parasite polymorphism (38), because of a confounding association between protective and nonprotective responses, because the endpoint of mild febrile malaria is not specific (26), or because rapidly waning antibody responses are not a stable predictive measure for the follow-up period (15).In studies in Kilifi, Kenya, associations between specific antibody responses and protection were stronger in children who had asymptomatic parasitemia at the start of monitoring (5, 16, 20, 28, 30, 31). This might imply that there is premunition, where a chronic low-level infection is required to provide immunity against further infection (35), and that antibody responses are more long lived in the presence of asymptomatic parasitemia (1). Alternatively, antibody responses measured in the presence of a challenge with asymptomatic parasitemia may be more informative than antibody responses measured without current exposure. For instance, protection against hepatitis B is predicted by the antibody titer shortly after vaccination, even when antibody titers subsequently become undetectable (32). However, it may simply be that parasitemia reflects greater exposure to malaria and hence a greater power to detect associations.In this study, we cleared asymptomatic parasitemia with highly effective antimalarials in order to identify newly acquired parasitemia during follow-up. We compared children who acquired asymptomatic parasitemia with children who developed febrile malaria by examining the associations with known markers of exposure and immunity. We then examined what impact excluding “unexposed” children had on conventional survival analyses in order to determine whether such analyses should be more widely used to study outcomes in observational studies or clinical trials.     

Isolation of Leishmania donovani from Phlebotomus martini in Baringo district, Kenya

An 18-month sandfly survey was conducted at 4 locations in Baringo District, Rift Valley Province, Kenya. 3 collection techniques were used: aspiration, sticky paper trap, and light trap in sites selected because of their proximity to homes of visceral leishmaniasis patients diagnosed and treated within 6 months before the survey. Over 2000 female Phlebotomus martini were collected of which 6 females were found to have flagellate protozoan infections. 3 of these infections were cultured successfully and cryopreserved. 2 isolates were identified as Leishmania donovani by cellulose acetate electrophoresis. The zymogram of the third isolate was different from all Old World Leishmania reference strains examined, and it is still unidentified. The finding of 2 P. martini naturally infected with L. donovani strongly supports the hypothesis that this species is a vector of visceral leishmaniasis in this area.     

Cutaneous leishmaniasis in Kenya: transmission of Leishmania major to man by the bite of a naturally infected Phlebotomus duboscqi

One leishmanial stock was isolated from a Phlebotomus duboscqi female captured in Baringo District, Kenya, and others from papular lesions that developed at sites where this sandfly had fed on a man. When characterized by cellulose acetate electrophoresis (eight enzymes examined), these isolates proved to be identical to known Leishmania major strains from man and a rodent (Arvicanthis sp.) and different from L. donovani and L. adleri, which also occur in Baringo. This is the first case of human cutaneous leishmaniasis caused by L. major reported from Kenya.     

Characteristics and treatment outcomes of HIV infected elderly patients enrolled in Kisii Teaching and Referral Hospital,Kenya

BackgroundA better understanding of the baseline characteristics of elderly people living with HIV/AIDS (PLWHA) is relevant because the world''s HIV population is ageing.ObjectivesThis study aimed to evaluate the baseline characteristics of PLWHA aged ≥ 50years at recruitment to HIV/AIDS clinic compared against the viral load (VL) and CD4 count among patients attending Kisii Teaching and Referral Hospital (KTRH), Kenya.MethodsWe retrospectively evaluated temporal inclinations of CD4 levels, viral load change and baseline demographic characteristics in the electronic records at the hospital using a mixed error-component model for 1329 PLWHA attending clinic between January 2008 and December 2019.ResultsFindings showed a significant difference in the comparison between baseline VL and WHO AIDS staging (p=0.026). Overall VL levels decreased over the period significantly by WHO AIDS staging (p<0.0001). Significant difference was observed by gender (p<0.0001), across age groups (p<0.0001) and baseline CD4 counts (p=0.003). There were significant differences in WHO staging by CD4 count >200cell/mm3 (p=0.048) and residence (p=0.001).ConclusionAge, WHO AIDS staging, gender and residence are relevant parameters associated with viral load decline and CD4 count in elderly PLWHA. A noticeable VL suppression was attained confirming possible attainment of VL suppression among PLWHA under clinical care.     

The green shoots of a novel training programme: progress and identified key actions to providing services to MSM at Kenyan health facilities

Introduction

Although men who have sex with men (MSM) in sub-Saharan Africa are at high risk for HIV acquisition, access to and quality of health and HIV services within this population are negatively affected by stigma and capacity within the health sector. A recently developed online MSM training programme (www.marps-africa.org) was shown to contribute to reductions in MSM prejudice among healthcare providers (HCPs) in coastal Kenya. In this study, we used qualitative methods to explore the provision of MSM healthcare services two years post-training in coastal Kenya.

Methods

From February to July 2014, we held 10 focus group discussions (FGD) with 63 participants, including HCP from 25 facilities, county AIDS coordinators and MSM from local support groups. Participants discussed availability, acceptability and accessibility of HIV healthcare for MSM. HCP also discussed changes in their health service practices after completing the training. FGD were recorded, transcribed verbatim and analyzed using Ritchie and Spencer''s “framework approach” for qualitative data.

Results

HCPs described continued improvements in their ability to provide service in a non-stigmatizing way to MSM patients since completing the training programme and expressed comfort engaging MSM patients in care. Four additional recommendations for improving MSM healthcare services were identified: 1) expanding the reach of MSM sensitivity training across the medical education continuum; 2) establishing guidelines to manage sexually transmitted anal infections; 3) promoting legal and policy reforms to support integration of MSM-appropriate services into healthcare; and 4) including MSM information in national reporting tools for HIV services.

Conclusions

Positive impacts of this sensitivity and skills training programme were reflected in HCP attitudes two years post-intervention. Scaling-up of efforts will rely on continued policies to include MSM in healthcare programmes to reduce stigma in health settings and guidelines for MSM STI service delivery.     

Phlebotomus guggisbergi (Diptera: Psychodidae), a vector of Leishmania tropica in Kenya

Sand flies were collected in light traps and on oiled papers at four active case sites of human cutaneous leishmaniasis due to Leishmania tropica at Muruku Sublocation, Laikipia District, Kenya. Nearly 5,200 females of five species, including Phlebotomus guggisbergi, were dissected and examined for flagellates. Of 3,867 P. guggisbergi females collected at a multiple case site, 168 (4.3%) harbored mature infections (to include metacyclic promastigotes) of flagellates morphologically identical to Leishmania, while all other flies were negative. Of the infected flies, 164 were collected in a cave near the patients' home, three from crevices on an escarpment immediately behind the house, and one from the bedroom of one of the patients. One hundred sixty-four of the isolates were successfully grown in Schneider's Drosophila medium and harvested for typing by cellulose-acetate electrophoresis. Isoenzyme profiles of the first 22 of these were compared with those of WHO reference strains and well characterized local strains using 12 enzyme loci. The isolates yielded isoenzyme migration patterns that were indistinguishable from those of two L. tropica reference strains and of six L. tropica patient isolates from the same locality. This is the first reported isolation of L. tropica from a sand fly in Kenya, the first reported isolation of Leishmania parasites from P. guggisbergi, and the first confirmed isolation of this Leishmania from a sand fly other than P. sergenti. The finding of such a large number of P. guggisbergi naturally harboring mature infections of L. tropica at an active case site of cutaneous leishmaniasis due to this agent strongly implicates this fly as a vector.     

Cytological physiognomies and genotype distribution of human papillomaviruses among HPV/HIV co-infected and HPV mono-infected women

BackgroundCo-infection of High Risk Human Papillomavirus (HR-HPV) and HIV is thought to favour initiation of intraepithelial squamous cell lesion and subsequent progression to cervical carcinoma.ObjectivesEvaluation of cytological physiognomies in relation to possible age influence and the genotype distribution of human papillomaviruses among HPV/HIV co-infected and HPV monoinfected women in Kisii, Kenya.MethodsThe case-control study enrolled 42 HPV/HIV co-infected and 42 HPV monoinfected women. Cervical swabs were collected in ThinPrep vials for HPV tying and cytological analysis. HPV subtypes were assayed by Xpert® HPV system (GXHPV-CE-10).ResultsMono-infected women aged 30–39 years had the highest proportion of low grade squamous intraepithelial lesion (LSIL) at 14 (16.67%) while the co-infected aged 50–59 years had the highest proportion of high grade squamous intraepithelial lesion (HSIL) at 9 (10.71%). HPV-16 genotype was the most predominant and it increased with age rise. Older coinfected and mono-infected women (>40 years) had HSIL and LSIL as the most predominant cytological grade respectively.ConclusionThe predominance of HPV-16 and HPV-18/45 genotypes in the study setting is a consideration that would benefit targeted prophylactic vaccination programs. HPV testing and cervical cancer screening for young and older women on a regular basis ought to be reinforced.